Abstract: Introduction: The aim of the present study was to explore the relationship between subthreshold mood symptoms and suicidality in patients with complicated grief (CG). Methods: Fifty patients with CG were included in the study and evaluated by the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis-I disorders, the Inventory of Complicated Grief, and the Mood Spectrum Self Report (MOODS-SR) lifetime version, to evaluate the subthreshold mood symptoms. Results: Twenty-eight patients (56%) reported lifetime suicidal ideation and 11 patients (22%) reported suicide attempts. Subthreshold depressive and rhythmicity/vegetative functions items of the MOODS-SR were significantly associated with increased suicidal ideation and attempts, while subthreshold manic items were associated with suicidal ideation only. Relationships were confirmed after controlling for Axis-I disorders comorbidity. Conclusion: The results of the present study suggest the usefulness of exploring lifetime subthreshold mood symptoms in CG patients, in order to promptly identify those who may be more prone to suicidality.
Abstract: Although there are studies describing the prevalence of patients with drug addiction and dual diagnosis, there is a paucity of data regarding the progression from psychiatric disorders to drug addiction or vice versa. A total of 1,090 patients dependent on heroin were interviewed to examine the presence of dual diagnosis and the progression from psychiatric disorders to drug dependence or vice versa. A total of 574 patients met the criteria for a dual diagnosis. A total of 362 patients progressed from substance abuse disorders to psychiatric disorders (SUD-PR) and 144 patients progressed from psychiatric disorders to drug addiction (PSY-PR). SUD-PR patients are more frequently affected by mood disorders. PSY-PR patients were more frequently diagnosed as psychotic or affected by anxiety disorders. The authors' findings suggest that the self-medication theory of dual diagnosis was relevant only for those with existing diagnoses of schizophrenia or anxiety disorders. When treating patients with a dual diagnosis, clinicians should ensure that the same attention is given to the treatment of drug dependence as it is to the treatment of comorbid psychiatric conditions.
Abstract: The temperament evaluation of the Memphis, Pisa, Paris and San Diego questionnaire (TEMPS), in its rater-wise and its self-evaluation forms, has been designed to evaluate temperamental characteristics in clinical and non-clinical populations. The validation process is currently in progress in various countries. In order to improve this validation process we have extended the area of correlations of its self-evaluation form (TEMPS-A[P]) to MMPI, and to a special RS that allows assessment of the emotional-affective state following a stressful situation.
Abstract: Self-injurious behavior (SIB) associated with Tourette's syndrome (TS) is a severe neuropsychiatric condition that causes significant distress and can impair social functioning. The current treatment options for the condition include pharmacological, physical and psychosocial interventions. However, given the need for more effective interventions, especially for those patients who are unresponsive and/or intolerant to standard medications, further exploration of novel treatments is imperative. In this report, we present a case of SIB-TS that was successfully treated with pregabalin. The patient received 1-year of follow-up and was noted to have considerable improvement in symptoms. Although rigorous controlled studies are required, based on our case study, pregabalin may be a potential treatment option in some cases of SIB with TS.
Abstract: Earthquakes are one of the most frequently occurring natural disasters and extensive research has been conducted on mental disorders on exposed populations, particularly on post-traumatic stress disorder (PTSD). On April 6th 2009, the town of L'Aquila (Abruzzo), in central Italy, was struck by an earthquake with a strength of 5.9 on the Richter scale. In the town of L'Aquila many buildings collapsed and large parts of the town were destroyed. Overall, 309 people were killed, 1600 injured among which 200 severely injured and hospitalized, more than 65,000 people were displaced.
Abstract: Over the past fifty years in the Western world the professions and activities that were once practised only by males, are now available to females, too. Affective temperaments, in line with their adaptive function, influence career choices. In general, males and females have proved to have different temperamental profiles. In this study we inquire into the question whether gender differences in temperament have continued unchanged in a field, such as the military career, that has been historically characterized by a male identity.
Abstract: While psychiatric comorbidity has been shown to produce a negative impact on the outcome of opioid use disorders, longitudinal studies carried out in the context of methadone maintenance treatment programs (MMTP) to evaluate outcomes strictly linked to methadone efficacy have not demonstrated a similar negative influence. To verify whether results obtained considering psychopathology in terms of formal psychiatric diagnoses were replicated when assessing psychopathology in terms of global psychiatric severity, a retrospective cohort study was designed. 259 patients commencing methadone maintenance treatment were divided into two groups on the basis of SCL-90 severity score and compared for retention in treatment, toxicological urine test results and psychological/psychiatric status throughout a one year period of observation. The results of the study suggest that patients in MMTP with high psychiatric severity are not characterized by a lower retention in treatment or higher substance use than those with low psychiatric severity. Moreover, during treatment high severe psychiatric patient status appears to improve significantly for all psychological/psychiatric dimensions explored by SCL-90. These results are consistent with those obtained in previous studies on the efficacy of MMTP, comprehensive of psychiatric care, irrespective of the severity of psychopathology exhibited by patients at the beginning of treatment.
Abstract: A structural and functional interaction between A(2A) adenosine receptors and D(2) dopamine receptors has been implicated in the pathophysiology of impulse control disorders. The aim of this study was to use platelet membranes to assess A(2A) adenosine receptor affinity and density in patients affected by pathological gambling (PG; which is classified as a specific impulse control disorder) with respect to those of control subjects.
Abstract: Abstract Objectives. The cyclic adenosine monophosphate responsive element binding (CREB) protein is a transcription factor involved in different neural processes, such as learning, neuroplasticity and the modulation of stress response. Alterations in the CREB pathway have been observed in the brains and lymphocytes of patients affected by depression and alcohol abuse. Given the lack of information, our study aimed at investigating the levels of total and activated CREB protein in lympho-monocytes of 20 drug-free patients suffering from post-traumatic stress disorders (PTSD), as compared with 20 healthy control subjects. Methods. Blood samples were collected from patients and healthy control subjects on the same time and lympho-monocytes were isolated according to standardized methods. CREB protein levels and activation were measured by means of immunoenzymatic techniques. Results. The results showed that PTSD patients had statistically lower levels of total CREB protein in lympho-monocytes than healthy control subjects. On the contrary, no difference in the activated CREB protein was detected. Conclusions. These findings, albeit preliminary, would suggest that the CREB pathway might be involved in the pathophysiology of PTSD. Future studies should clarify if specific PTSD symptom clusters might be related to the CREB pathway.
Abstract: The relationship between anxiety and impulsivity is controversial and not well explored. In a previous study we compared impulsivity, measured by different rating tools, in patients with anxiety disorders vs. healthy controls. In the same sample we now explore the influence of comorbid soft bipolar spectrum disorders on the relationship between anxiety disorders and impulsivity.
Abstract: On April 6th 2009, the town of L'Aquila, Italy, was struck by an earthquake (6.3 on the Richter scale) that lead large parts of the town to be destroyed and the death of 309 people. Significant losses in the framework of earthquakes have been reported as a major risk factor for PTSD development. Aim of this study was to investigate post-traumatic spectrum symptoms in a sample of adolescents exposed to the L'Aquila 2009 earthquake 21 months earlier, with particular attention to the impact of loss.
Abstract: ABSTRACT: BACKGROUND: Around 9% to 20% of bereaved individuals experience symptoms of complicated grief (CG) that are associated with significant distress and impairment. A major issue is whether CG represents a distinctive nosographic entity, independent from other mental disorders, particularly major depression (MD), and the role of symptoms of adult separation anxiety. The purpose of this study was to compare the clinical features of patients with CG versus a sample of healthy control subjects, with particular focus on adult separation anxiety and lifetime mood spectrum symptoms. METHODS: A total of 53 patients with CG and 50 healthy control subjects were consecutively recruited and assessed by means of the Structured Clinical Interview for DSM-IV Axis-I disorders (SCID-I/P), Inventory of Complicated Grief (ICG), Adult Separation Anxiety Questionnaire (ASA-27), Work and Social Adjustment Scale (WSAS) and Mood Spectrum-Self Report (MOODS-SR) lifetime version. RESULTS: Patients with CG reported significantly higher scores on the MOODS-SR, ASA-27, and WSAS with respect to healthy control subjects. The scores on the ASA-27 were significantly associated with the MOODS-SR depressive and manic components amongst both patients and healthy control subjects, with a stronger association in the latter. CONCLUSIONS: A major limitation of the present study is the small sample size that may reduce the generalizability of the results. Moreover, lifetime MOODS-SR does not provide information about the temporal sequence of the manic or depressive symptoms and the loss. The frequent comorbidity with MD and the association with both depressive and manic lifetime symptoms do not support the independence of CG from mood disorders. In our patients, CG is associated with high levels of separation anxiety in adulthood. However, the presence of lifetime mood instability, as measured by the frequent presence of depressive and hypomanic lifetime symptoms, suggests that cyclothymia might represent the common underlying feature characterizing the vulnerability to both adult separation anxiety and CG.
Abstract: Introduction: Despite the clinical and social relevance of depression, and the availability of numerous antidepressants and non-pharmacological interventions, response rates remain unsatisfactory and novel therapeutic targets are being explored. Areas covered: This review starts with a brief overview of the evolution of the current antidepressant drug scenario and ends with a focus on the potential influence of the underestimation of bipolarity on the exploration of novel antidepressant drugs. Expert opinion: The field of antidepressant drug development has suffered from a relative decline recently and, with the exception of agomelatine, innovative non-monoaminergic antidepressants have yet to be developed. The need for more effective compounds is evident. Clinicians and researchers should pay greater attention to the impact of bipolarity in depression. The ultimate goal of this review is not to discourage the use of antidepressants but rather to encourage judicious prescriptions, and also to solicit a better collaboration between clinicians and preclinical researchers so that more reliable diagnostic criteria can be adopted.
Abstract: OBJECTIVES: Although several findings have highlighted the prevalence of Axis I psychiatric disorders in fibromyalgia (FM) and rheumatoid arthritis (RA), very little information is available on the prevalence of subthreshold mood symptoms in these conditions. Therefore, we aimed at comparing the prevalence of subthreshold mood symptoms in rheumatic patients suffering from FM and RA. The hypothesis is that subthreshold mood symptoms are more represented in FM, given the evidence of higher rates of Axis I psychopathology in FM than in RA. METHODS: Sixty patients suffering from FM and 50 from RA, assessed according to the American College of Rheumatology (ACR) criteria, selected in a Rheumatology Department, were included in the study. The subthreshold affective symptoms were assessed by means of the Mood Spectrum-Self Report (MOODS-SR). RESULTS: The results showed that FM patients presented significantly higher scores than RA patients in 'mood depressive', 'cognition depressive' domains and in total depressive component. CONCLUSIONS: The present study demonstrates that subthreshold depressive symptoms are more represented in FM than in RA patients. This fact could play a role in the worse quality of life and in the major perception of pain which characterises FM.
Abstract: BACKGROUND: This study investigated the rate of suicidal intention and its relationship with the features of religious involvement in a non-clinical sample of the adult population exposed to the L'Aquila earthquake. METHODS: The study population was composed of 426 people who had experienced the earthquake (188 males and 238 females). For comparison, 522 people were recruited from nearby unaffected areas. The sample was investigated for suicidal intention screening, distinguishing Suicidal Screen-Negative (SSN) subjects from Positive (SSP) subjects. Brief Multidimensional Measure of Religiousness/Spirituality (BMMRS) and Impact of Event Scale (IES) assessments were administered. RESULTS: More SSP subjects were observed in the population exposed to the earthquake (Odds Ratio 3.54). A higher proportion of females showed suicidal ideation. Multivariate analysis showed overall significance for the between-subject factor. Univariate F tests for each BMMRS variable that contributed to significant overall effect showed that negative spiritual coping was significantly different. No differences were observed for IES scores between the two groups, but correlations with negative spiritual coping were found. LIMITATIONS: The samples are relatively small and data are based on self-reports. CONCLUSIONS: Negative religious coping such as expression of conflict and doubt regarding matters of faith, as well as a feeling of being punished or abandoned by God, can prevail in response to prolonged stress without relief, as was experienced by the population exposed to the earthquake. These features are more associated with suicide ideation. Degree of religious affiliation and commitment examination by mental health practitioners can be useful when suicidal ideation is investigated.
Abstract: BACKGROUND: The prevalence of bipolar spectrum disorders in the community is under debate and the prescription of antidepressant drugs (ADs) in bipolar depression appears to be an underestimated problem. OBJECTIVES: To evaluate the prevalence of bipolar disorders by means of a screening instrument in seven communities within six regions of Italy and evaluate the appropriateness and number of prescriptions for ADs in bipolar depression. METHODS: Study design: community survey. Study population: samples randomly drawn, after stratification from the adult population of municipal records. Sample size: 4999 people from seven communities within six regions of Italy. Tools: questionnaire on psychotropic drug consumption, prescription, health services utilization; Structured Clinical Interview NP for DSM-IV modified (ANTAS); Mood Disorder Questionnaire (MDQ). Training: interviewers were trained psychologists or medical doctors. Study limitations: the population studied did not represent a nationally representative multistage clustered area probability sample of households. RESULTS: 3398 subjects were interviewed (68% of recruited sample). Positivity at MDQ (MDQ+) was higher in males (3.4% vs. 2.8%) but the difference was not significant (OR=1.2, P=0.37). The association between MDQ+ and Major Depressive Disorder (MDD) was statistically significant for both males (OR=14.9, P<0.0001) and females (OR=8.3, P<0.001); 30% of subjects with MDQ+ and MDD lifetime diagnosis were taking ADs. CONCLUSIONS: These overall rates of being MDQ+ are similar to community surveys conducted within USA and the use of ADs in people with MDQ+ and MDD diagnoses are.
Abstract: In this study we evaluated, by means of the "cocaine rush visual analog scale," the impact of ropinirole on the expected rush induced by cocaine in a group of heroin addicts abusing cocaine; the self-reported reaction to the rush blockade (if any) on cocaine consumption, and the correlations between this self-reported reaction and individual, clinical, and therapeutic parameters. Nineteen cocaine abuser heroin-dependent patients entered the study. Their experienced cocaine rush was 61.31 ± 32.1% of the maximum effect previously experienced. Compared with their previous rush intensity 16 patients experienced significantly lower intensity, 3 the same intensity, and none a higher intensity. In particular, two patients experienced a complete blockade of rush and reported a reduced use of cocaine. Fourteen patients experienced a partial blockade of cocaine rush; of these, nine reported they had reduced their use of cocaine. Ropinirole does diminish the subjective intensity of an expected cocaine rush, so interfering with the dynamics of reward, while supporting its possible use in the treatment of cocaine dependence.
Abstract: Orthorexia, from the Greek words orthos (straight, proper) and orexis (appetite), is a newly conceptualized disorder characterized by distorted eating habits and cognitions concerning supposedly healthy nutrition. In this article we present preliminary results of a wider research aimed to investigate the diffusion of Orthorexia in the general population and to highlight its characteristics and particularly the relationship with Eating Disorder and Obsessive-Compulsive Disorder.
Abstract: Leading Italian studies support the use of γ-hydroxybutyric acid (GHB), not only in the treatment of the alcohol withdrawal syndrome, but also in maintaining alcohol abstinence. GHB gives a better result than naltrexone and disulfiram in maintaining abstinence, and it has a better effect on craving than placebo or disulfiram. The problem is that about 30-40% of alcoholics are non-responders to GHB therapy. In our clinical practice, we speculate that by combining disulfiram with GHB treatment we may be able to achieve a kind of 'antagonist' effect by using the 'psychological threat' of disulfiram (adversative effect) while taking advantage of the anticraving effect of GHB, despite the limitation of its 'non-blockade' effect on alcohol. In this context, to improve the outcome in GHB long-term treated alcoholics, we added disulfiram to GHB in the management of GHB treatment-resistant alcoholics. In this study we compared retention in treatment of 52 patients who were treated with the GHB-disulfiram combination for up to six months, with retention for the same subjects considering their most recent unsuccessful outpatient long-term treatment with GHB only. An additional comparison was carried out on the days of complete abstention from alcohol. Thirty four patients (65.4%) successfully completed the protocol and were considered to be responders; 18 (34.6%) left the programme, and were considered to be non-responders. Considering the days of complete abstinence from alcohol, 36 patients stayed in treatment longer with the GHB-Disulfiram combination, 12 stayed for a shorter time and four for the same time. The results of this study seem to indicate a higher efficacy of the GHB-disulfiram association compared with GHB alone. Randomized controlled trials are now needed to verify this hypothesis.
Abstract: This study attempts to analyse potential gender differences among a group of heroin addicts seeking treatment at a university-based medical centre. The central modality of treatment at this centre is the use of methadone maintenance. Among those patients entering this program there seems to be an emerging pattern of males who tend to use heroin as their opiate of choice, and are more likely to combine it with cannabis, while females are more likely to use to street methadone, with adjunctive use of ketamine, benzodiazepines, hypnotic drugs and/or amphetamines. Women are at higher risk of abusing opioids through a pathway of initial prescription painkiller use, and later to resort to street methadone to cope with prescription pain killer addiction. This latter pattern seems to result in an increased risk for fatal accidental overdoses. The use of these longer-acting agents in women may be influenced by psychosocial and hormonal factors.
Abstract: Initially explored in military settings, post-traumatic stress disorder (PTSD) has shown increasing prevalence in the general population. The high comorbidity rates between bipolar disorder (BD) and PTSD have raised the issue of whether some characteristics of BD could represent risk factors for PTSD. In combat-related PTSD, the 18 kDa mitochondrial translocator protein (TSPO), essential for steroid synthesis, was found to be decreased. Aims of the present study were: 1) the assessment of the TSPO mitochondrial density in lymphomonocytes from civilian patients with non-combat-related PTSD, without current or lifetime Axis I mood comorbidity, versus controls; 2) the exploration of the correlations between TSPO density and the presence of comorbid manic/hypomanic lifetime spectrum symptoms. Assessments included the Structured Clinical Interview for DSM-IV (SCID), the Impact of Event Scale (IES), and the lifetime Mood Spectrum Self-Report (MOODS-SR). Blood samples were processed to assess TSPO binding parameters in lymphomonocyte mitochondrial membranes. PTSD patients showed a significant decrease in TSPO density, without changes in mitochondrial citrate synthase activity. Further, TSPO density correlated with the number of lifetime manic/hypomanic spectrum symptoms. For the first time, TSPO density was found to be decreased in non-war-related PTSD and such decreases correlated with comorbid manic/hypomanic spectrum symptoms, indicating a possible role of sub-threshold bipolar comorbidity in PTSD-related neurobiological dysregulation.
Abstract: Addiction is a relapsing chronic condition in which psychiatric phenomena play a crucial role. Psychopathological symptoms in patients with heroin addiction are generally considered to be part of the drug addict's personality, or else to be related to the presence of psychiatric comorbidity, raising doubts about whether patients with long-term abuse of opioids actually possess specific psychopathological dimensions.
Abstract: Temperaments have been described with respect to their adaptive roles. Thus, depressive traits seem to increase sensitivity to suffering, cyclothymic traits appear relevant to creativity, and hyperthymic traits have been implicated in territoriality and leadership and more generally in active pursuits.
Abstract: There is increasing evidence that the brain-derived neurotrophic factor (BDNF) is involved in the pathophysiology of mood disorders and that its peripheral levels represent a reliable mirror of its concentration in the brain. The aim of the present study was to measure BDNF plasma levels in patients affected by major depression and to explore the possible relationship between the biological parameter and characteristics of the illness.
Abstract: The increased use of antidepressant drugs (ADs) improved the response to the needs of care although some community surveys have shown that subjects without lifetime psychiatric diagnosis (anxiety/depression) used ADs.
Abstract: The aim of the present study was to explore and compare the caffeine intake, intoxication, withdrawal and dependence prevalence in Italian psychiatric patients and healthy subjects.
Abstract: Impulsivity, describing action without foresight, is an important feature of several psychiatric diseases, suicidality and violent behaviour. The complex origins of impulsivity hinder identification of the genes influencing it and the diseases with which it is associated. Here we perform exon-focused sequencing of impulsive individuals in a founder population, targeting fourteen genes belonging to the serotonin and dopamine domain. A stop codon in HTR2B was identified that is common (minor allele frequency > 1%) but exclusive to Finnish people. Expression of the gene in the human brain was assessed, as well as the molecular functionality of the stop codon, which was associated with psychiatric diseases marked by impulsivity in both population and family-based analyses. Knockout of Htr2b increased impulsive behaviours in mice, indicative of predictive validity. Our study shows the potential for identifying and tracing effects of rare alleles in complex behavioural phenotypes using founder populations, and indicates a role for HTR2B in impulsivity.
Abstract: Seven patients with a diagnosis of Parkinson's disease (PD) and pathological gambling (PG) and 7 PD patients without PG were investigated by functional MRI and a block-design experiment with gambling-related visual cues alternating with neutral stimuli and rest periods. Compared with PD/non-PG, in PD/PG patients, several areas of increased cue-related blood oxygen level dependent (BOLD)-response were observed including bilateral anterior cingulate cortex, medial and superior frontal gyri, and precuneus, right inferior parietal lobule, and ventral striatum. The over activation of cingulate cortex and ventral striatum in PD/PG patients after the craving task is similar to that reported in addicted patients, whereas the activation of the parietal structures is probably related to the attentional network.
Abstract: In both animals and humans, stress has been demonstrated to reduce the expression of the Brain-Derived Neurotrophic Factor (BDNF), a neurotrophin (NT) which promotes the proliferation, survival and differentiation of neurons. Although traumatic events have been found to be associated with lower BDNF plasma levels in affective disorders, no study has explored this parameter in patients with post-traumatic stress disorder (PTSD). We, therefore, measured BDNF plasma level in 18 patients with PTSD and in 18 healthy control subjects. Diagnoses were assessed by the Structured Clinical Interview for DSM-IV, while the specific symptoms were examined in the patients by means of the Impact of Event Scale for PTSD and the traumas experienced were assessed by using the Life Events Checklist. BDNF plasma levels were evaluated by means of a standardized Elisa method. The results, while showing significantly lower BDNF levels in PTSD patients, as compared with those of healthy subjects (p=0.001), although obtained in a small sample size, would suggest that this NT may be involved in the pathophysiology of PTSD.
Abstract: Although the association between mood disorders, and particularly bipolar disorders, comorbidity and suicidality in posttraumatic (PTSD) patients is well established, less information is available on the impact of subsyndromal mood symptoms. The aim of the present study was, thus, to explore the frequency and relationship between subthreshold mood symptoms, assessed by a specific and validated questionnaire, and suicidality in PTSD patients.
Abstract: Recent data have shown the presence of immunological alterations in adult patients suffering from obsessive-compulsive disorder (OCD). The objective of this study was to examine the possible effects of 12 months of treatment with different serotonergic drugs, such as clomipramine and selective serotonin reuptake inhibitors (SSRIs) on peripheral immunological cells of 18 OCD patients. Both the absolute number and percent of CD4+, CD8+, CD3+, CD19+ and CD56+ cells were measured in peripheral blood before and after treatment by means of a Facstar Flow Sorter apparatus. At baseline, all patients showed a significant increase of CD8+ and decrease of CD4+ lymphocytes when compared with a similar group of healthy control subjects; after the treatment, CD8+ and CD4+ cells, respectively, decreased and increased significantly, and the CD4+/CD8+ ratio increased, when compared with baseline values, in parallel with the clinical improvement. These data suggest that the alterations of immune cells reported in patients with OCD at baseline may be reverted by treatment with SRIs and should be considered a state-dependent marker, perhaps related to a condition of stress.
Abstract: There is an increasing evidence that the Brain-Derived Neurotrophic Factor (BDNF) could be involved in the mode of action of antidepressants and, perhaps, of ECT. This study aimed to investigate whether the clinical course of medication-resistant depressed patients following a course of ECT might be associated with changes of plasma BDNF concentrations. Our findings showed that at T0 (baseline) plasma BDNF levels of patients were significantly lower than those of control subjects, and that at T2 (after ECT) were significantly increased in parallel with the decrease of the Hamilton Rating Scale for Depression (HRSD) total score. However, only remitter patients who showed higher baseline BDNF levels than non-remitters reached normalized BDNF levels after ECT. These findings would suggest the potential usefulness of baseline plasma BDNF levels as predictors of response to ECT in treatment-resistant depressed patients.
Abstract: ABCB1 is a transmembrane transporter that is expressed in excretory organs (kidneys and liver), in intestine mucosa and on the blood-brain barrier. Because of the particular distribution of the protein, the activity of ABCB1 may significantly affect drug pharmacokinetics during absorption and distribution. Of note, several SNPs of ABCB1 are known and many of them affect transporter activity and/or expression. In this view, changes in the pharmacokinetics of drugs that are ABCB1 substrates could be clinically relevant and the evaluation of ABCB1 SNPs should deserve particular attention. Therefore, the aim of the present study was to investigate the possible association between ABCB1 polymorphisms and clozapine plasma levels in psychotic patients.
Abstract: We aimed at investigating the impact of lifetime manic spectrum symptoms on the severity of pain and the health-related quality of life (HRQoL) in patients with fibromyalgia (FM).
Abstract: Aim of the study was to investigate caffeine use in different types of eating disorders (ED) patients either using a categorical approach [Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition - Text Revision (DSM-IV-TR) diagnostic criteria] or a dimensional perspective.
Abstract: Impairment in sexual function is frequent and underestimated in patients with mental disorders, particularly in those with mood disorders. Few studies have examined the relationship between sexual dysfunctions and the clinical characteristics of mood disorders.
Abstract: Dimensional approaches to psychiatric disorders have shown an increased relevance in the ongoing debate for the forthcoming Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. In line with previously validated instruments for the assessment of different mood, anxiety, eating and psychotic spectra, we tested the validity and reliability of a newly developed Structured Clinical Interview for Trauma and Loss Spectrum (SCI-TALS). The instrument is based on a multidimensional approach to post-traumatic stress spectrum that includes a range of threatening or frightening experiences, as well as a variety of potentially significant losses, to which an individual can be exposed. Furthermore, it explores the spectrum of the peritraumatic reactions and post-traumatic symptoms that may ensue from either type of life events, targeting soft signs and subthreshold conditions, as well as temperamental and personality traits that may constitute risk factors for the development of the disorder. The aim of the present study is to describe the reliability of the self-report version of the SCI-TALS: the TALS-SR. Thirty patients with PTSD and thirty healthy control subjects were assessed with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Half of the patients and controls received the TALS-SR first and the SCI-TALS after 15 days; for the other half of the sample, the order of administration was reversed. Agreement between the self-report and the interview formats was substantial. Intraclass correlation coefficients ranged from 0.934 to 0.994, always exceeding the threshold of 0.90. Our findings provide substantial support for the reliability of the TALS-SR questionnaire.
Abstract: Brain-Derived Neurotrophic Factor (BDNF) has a central role in neuronal survival, differentiation, and plasticity. The brain level of BDNF is changed by several mood stabilizers and antidepressant drugs acting on neurotransmitters such as noradrenaline and serotonin. We investigated the effects of acute and chronic treatment with Duloxetine, a new drug blocking the re-uptake of serotonin and noradrenaline (SNRI), on BDNF level in the prefrontal cortex, cerebrospinal fluid, plasma, and serum.
Abstract: A functional VNTR polymorphism in the promoter of the monoamine oxidase A gene (MAOA-LPR) has previously been shown to be an important predictor of antisocial behavior in men. Testosterone analogues are known to interact with the MAOA promoter in vitro to influence gene transcription as well as in vivo to influence CSF levels of the MAO metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) in human males. We examined the possible joint effects of testosterone (measured in CSF) and MAOA-LPR genotype on antisocial personality disorder and scores on the Brown-Goodwin Aggression scale in 95 unrelated male criminal alcoholics and 45 controls. The results confirm that MAOA genotype and CSF testosterone interact to predict antisocial behaviors. The MAOA/testosterone interaction also predicted low levels of CSF MHPG, which tentatively suggests the possibility that the interaction may be mediated by a direct effect on gene transcription. If replicated these findings offer plausible explanations for previous inconsistencies in studies of the relationship between testosterone and male human aggression, as well as for how MAOA genotype may influence aggressive behavior in human males.
Abstract: To investigate obese people with/without binge-eating Disorder (BED) in terms of shared psychopathological features pertaining to spectrum of eating disorders.
Abstract: Brain-derived neurotrophic factor (BDNF) has been hypothesized to be involved in the neurobiology of major depression. The aim of this study was to assess the possible relationships between depressive symptoms and serum and/or plasma BDNF levels during 1 year of antidepressant treatment.
Abstract: The aim of this study was to investigate the serotonin transporter (SERT), by means of the 3H-paroxetine ([3H]-Par) binding to platelet membranes, in patients affected by pathological gambling (PG), as compared with a similar group of healthy control subjects.
Abstract: Scant information is available on the diurnal variation of peripheral neurotrophic factors, including brain-derived neurotrophic factor (BDNF), in human beings. We explored plasma and serum BDNF levels at three different clock times in a study of 28 healthy subjects of both sexes. Statistically significant diurnal variation in plasma BDNF level was detected in men, with the peak at 08:00 h and nadir at 22:00 h. At this time, the plasma BDNF concentration of men was significantly lower than that of women (p=.02). However, no diurnal variation was found either in plasma BDNF of women, in either the follicular or luteal phases of the menstrual cycle, or in serum BDNF level in both men and women. These findings support the concept of rhythmic variation in plasma BDNF regulation that seems to be sex-related.
Abstract: Our objectives were to investigate thyroid abnormalities and autoimmunity in 120 patients affected by fibromyalgia (FM) and to study their relationships with clinical data and symptoms. Thyroid assessment by means of antithyroglobulin antibodies, antithyroid peroxidase antibodies, free triiodo-thyronine, free thyroxine, and thyroid stimulating hormone analyses was carried out. The clinical parameters "Fibromyalgia Impact Questionnaire", pain, tender points, fatigue, and other symptoms, and the presence of depression or anxiety disorders were evaluated. The basal thyroid hormone levels of FM patients were in the normal range, while 41% of the patients had at least one thyroid antibody. Patients with thyroid autoimmunity showed a higher percentage of dry eyes, burning, or pain with urination, allodynia, blurred vision, and sore throat. Correlations found between thyroid autoimmunity and age or with the presence of depression or anxiety disorders were not significant. However, in the cohort of post-menopausal patients, the frequency of thyroid autoimmunity was higher with respect to pre-menopausal patients. In conclusion, autoimmune thyroiditis is present in an elevated percentage of FM patients, and it has been associated with the presence of typical symptoms of the disease.
Abstract: Controversies exist regarding the impact of psychological stress on the functioning of the immune system in humans. The aim of the present study, therefore, was to evaluate whether the condition of a pre-exam stress may or not modify resting lymphocyte subsets, as well as blood pressure and heart rate. About 22 medical residents of both sexes not suffering from any medical or psychiatric disorder were included in the study. Anxiety levels were measured by means of the Hamilton rating scale for anxiety (HRSA) and anxiety traits by means of the panic-agoraphobic spectrum self-report (PAS-SR) version and the obsessive-compulsive spectrum self-report (OBS-SR) version. The results showed that systolic blood pressure and heart rate increased significantly just before sitting an examination (t(1)) in all subjects, as compared with a calm situation (t(2)), in parallel with the increase in the HRSA total score, while no significant difference was observed in lymphocyte subsets at the two assessment times. However, men had a higher number of CD4+ cells than women at t(1) and t(2), while women showed a higher heart rate at t(1). In addition, significant correlations between CD4+ lymphocyte count and heart rate at t(1) or HRSA at t(2) were detected. These findings indicate that the acute stress determined by sitting for examination provokes changes in autonomic nervous system parameters, such as blood pressure and heart rate, as well as in the subjective feeling of anxiety, as shown by the increased HRSA total scores, which were not paralleled by modifications of lymphocyte subsets. However, individual differences, related to both sex and personality traits yet to be identified, seem to have an impact in shaping the stress response.
Abstract: To examine the possible role of the soluble factor in fibromyalgia (FM) by studying the correlation of cytokine levels with the patients' clinical and psychiatric profile.
Abstract: This cross-sectional study examined the reasons for substance use and the presence of vulnerability factors such as substance sensitivity, sensation seeking, and symptoms related to the attention deficit hyperactivity disorder (ADHD) in patients with substance use disorder (SUD) and comorbid mood and anxiety disorders by using the Structured Clinical Interview for the Spectrum of Substance Use (SCI-SUBS), a novel instrument designed to explore the spectrum of substance use and its clinical correlates. Study participants included 61 patients with SUD and mood or anxiety disorder, and two comparison groups including 35 patients with SUD only and 50 controls not in treatment for mental disorders or SUD. We found that patients with co-morbid mood or anxiety disorder had significantly higher scores on the SCI-SUBS domains 'substance sensitivity' and 'self-medication' as compared to those with SUD only. Scores on 'sensation seeking' and 'ADHD' domains were similar between both groups of patients and higher than in controls. Patients with comorbid mood or anxiety disorders showed a higher sensitivity to substances and were more prone to self-medication than those with SUD only. These characteristics should be taken into account in the diagnostic assessment and in long-term treatment to decrease the risk of relapse.
Abstract: Depression is considered the most frequent interferon (IFN)-alpha-induced psychiatric disorder. However, other neuropsychiatric side effects of IFN treatment, such as irritability, anxiety, and manic episodes, are reported as well. We analyzed the impact of lifetime manic-hypomanic symptoms and anxiety on the development of depression in hepatitis-C-virus-infected subjects treated with two different types of IFN-alpha.
Abstract: To examine the spectrum of alcohol and substance abuse, including reasons for use, in patients with bipolar I disorder, compared with patients with substance use disorder and healthy controls, with a specific focus on the relationship between substance use, substance sensitivity, other comorbid psychiatric symptoms and traits related to sensation seeking.
Abstract: The aim of this study was to characterize the health-related quality of life (HR-QOL) and functioning in 90 bipolar I remitted outpatients. According to Diagnostic and Statistical Manual of Mental Disorders IV remission specifiers, patients were categorized into 4 groups: group 1, fully remitted; group 2, less than 2 months remitted; group 3, with persisting manic symptoms; group 4, with persisting depressive symptoms. The severity of psychopathology was evaluated by using the Bech-Rafaelsen Mania-Melancholia Scale. The HR-QOL, functioning, and insight were assessed via the medical outcomes study 36-item short form, the global assessment of functioning scale, and the scale to assess unawareness of mental disorder, respectively. Fully remitted patients reported the highest scores in almost all domains of medical outcomes study 36-item short form, and had significantly higher scores on physical functioning, general health, social functioning, and mental health compared to patients with persisting depressive symptoms. Furthermore, patients with persisting manic symptoms reported significantly higher scores on general health, vitality and mental health than the group with persisting depressive symptoms. In contrast, the global assessment of functioning scale score differed among the 4 groups, with fully remitted patients reporting higher, although not statistically significant, scores than the other groups. Our data suggest that the persistence of depressive or manic symptoms seem to affect self-report measures of HR-QOL. An affectively biased cognition may explain the gap between patient's perception of functioning and estimated functional adjustment, as assessed by clinicians.
Abstract: Existing trials investigated the impact of medical treatment of thyroid disorders on health-related quality of life (QOL) and psychiatric symptoms. The aim of this prospective study is to analyze the impact of thyroid surgery on QOL and severity of psychiatric symptoms.
Abstract: Romantic attachment is the establishment of a relationship with a partner and is strongly influenced by the individual's attachment style. While several studies have shown that attachment style may contribute to the development of psychopathology, less information is available for romantic attachment. The aim of the present study was to compare romantic attachment styles among patients with different mood and anxiety disorders and control subjects.
Abstract: Most of the studies on the duration of untreated illness (DUI) as a possible predictor of the clinical outcome and the course have focused on the psychotic disorders. The present naturalistic study was aimed to evaluate the possible relationship between the DUI and some clinical characteristics of a sample of patients with major depressive disorder (MDD).
Abstract: The aim of our study was to explore the presence and the distribution of D4 dopamine receptors in postmortem human prefrontal cortex, by means of the binding of [3H]YM-09151-2, an antagonist that has equal affinity for D2, D3 and D4 receptors. It was therefore necessary to devise a unique assay method in order to distinguish and detect the D4 component.
Abstract: The authors investigated frequency, clinical correlates and onset temporal relationship of social anxiety disorder (SAD) in adult patients with a diagnosis of bipolar I disorder.
Abstract: Antipsychotic drugs, potent dopamine receptor antagonists, are commonly used in the treatment of psychotic and affective illness. The discovery of antagonistic interactions between A2A adenosine receptors (ARs) and D2 dopamine receptors (DRs) in the central nervous system suggests that the adenosine system may be involved in the pathogenesis of psychiatric and neurological disorders. In the present study, we demonstrated for the first time that human platelets co-express A2A ARs and D2 DRs assembled into an heteromeric complexes. We also investigated the effects of chronic treatment with either typical or atypical antipsychotics on A2A AR binding parameters and receptors responsiveness in human platelets from patients affected by bipolar disorder. Chronic administration of typical antipsychotics induced a significant upregulation of A2A AR binding sites. Since no effects on A2A AR were obtained following "in vitro" platelet treatment with a typical antipsychotic (haloperidol), we could exclude a direct effect of the drug on A2A AR at the peripheral level. Moreover, typical antipsychotics induced a significant increase in the agonist potency to mediate A2A AR-G protein coupling. On the contrary, chronic treatment with atypical antipsychotics did not induce any significant alterations in A2A AR equilibrium binding parameters and receptor responsiveness suggesting that typical but not atypical antipsychotic drugs induced a selective modification of A2A AR binding parameters in human platelets. These results are in accordance with the literature data describing the selective A2A AR upregulation induced by typical antipsychotics in human striatum suggesting platelets as a peripheral model of the interactions between adenosine and dopamine system occurring in the central nervous system.
Abstract: Previous studies suggested that rheumatoid arthritis (RA) is associated with depressive and anxiety symptomatology. The well-being and functioning of patients with RA may be significantly influenced by subthreshold psychiatric comorbidity. Health-related quality of life (HRQoL) of patients with RA, compared with the Italian norms and patients with diabetes, was assessed by the influence of lifetime mood and panic-agoraphobic spectrum symptoms and demographic and clinical variables.
Abstract: The aim of this study was to compare the level of insight in patients with body dysmorphic disorder (BDD) with and without comorbid obsessive-compulsive disorder (OCD), and to measure its possible relationships with clinical features.
Abstract: The aim of this study is to establish to what degree variation in lifetime experience of rhythmicity and manic-hypomanic features correlates with suicidality in individuals with mood disorders and other major psychiatric diagnoses and in a comparison group of controls.
Abstract: The formation of social bonding is fundamental for several animals, including humans, for its relevant and obvious impact upon reproduction and, thus, survival of the species. Recent data would suggest that oxytocin might be one of the mediators of this process. Given the paucity of data on the possible involvement of oxytocin in human attachment, the present study was aimed to explore the possible relationships between the plasma levels of this neuropeptide and romantic attachment in healthy subjects. Forty-five healthy subjects who volunteered for the study, were included in the study. The romantic attachment was assessed using the Italian version of the so-called "Experiences in Close Relationships" (ECR), a self-report questionnaire for measuring this parameter in adults. The results showed that attachment anxiety and oxytocin are positively linked in romantic attachment to a statistically significant degree (r = 0.30, p = 0.04), that is, the higher the oxytocin levels the higher the score on the anxiety scale of the ECR. The authors suggest the hypothesis that this link represents one of the biological processes resulting in those rewarding emotions related to romantic attachment.
Abstract: In this study we describe the frequency of eating disorders (EDs) in a group of bipolar (BP) patients. We evaluated a sample of 51 outpatients, diagnosed as having BP I disorder on the basis of the Structured Clinical Interview for DSM-IV (SCID). Each of these subjects was administered the Binge Eating Disorder Clinical Interview (BEDCI) to determine the presence of binge eating disorder (BED) or bulimia nervosa (BN). Of the 51 BP patients, 14 (9 BED, 5 BN) met criteria for an ED. Most patients developed binge eating coincident with the first episode of BP disorder or after the onset of it. This was true for those who developed BED as well as BN, and involved both manic and depressive phases. All BN patients were women (5/5), and family history of binge eating was present in 80% of BN subjects, but only in 22.2% of BED and 29.7% of non-ED BP patients. We found a high frequency of concordance between BP illness and binge eating problems in our sample of BP patients. Given the temporal sequence of the mood disorder, which generally preceded the ED, we suggest a model in which the ED evolves due to modulation of emotions with food, as well as use of medications to treat BP disorder that disrupt hunger and satiety mechanisms. Given differences in gender distribution and family history, cultural and familial influences may also be significant in the minority of BP binge-eating patients who develop BN.
Abstract: This study evaluates the validity and the reliability of a new instrument developed to assess the psychotic spectrum: the Structured Clinical Interview for the Psychotic Spectrum (SCI-PSY). The instrument is based on a spectrum model that emphasizes soft signs, low-grade symptoms, subthreshold syndromes, as well as temperamental and personality traits comprising the clinical and subsyndromal psychotic manifestations. The items of the interview include, in addition to a subset of the DSM-IV criteria for psychotic syndromes, a number of features derived from clinical experience and from a review of the phenomenological descriptions of psychoses. Study participants were enrolled at 11 Italian Departments of Psychiatry located at 9 sites and included 77 consecutive patients with schizophrenia or schizoaffective disorder, 66 with borderline personality disorder, 59 with psychotic mood disorders, 98 with non-psychotic mood disorders and 57 with panic disorder. A comparison group of 102 unselected controls was enrolled at the same sites. The SCI-PSY significantly discriminated subjects with any psychiatric diagnosis from controls and subjects with from those without psychotic disorders. The hypothesized structure of the instrument was confirmed empirically.
Abstract: This study evaluates the prevalence of threshold and subthreshold use of substances among patients with psychiatric disorders and 2 comparison groups. Participants were outpatients and inpatients with mood and anxiety disorders, subjects with opiate dependence, and a comparison group of individuals not undergoing treatment for psychiatric disorders. Assessments included the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition , Axis I Disorders, an interview exploring the spectrum of substance use (Structured Clinical Interview for the Spectrum of Substance Use), and a self-report instrument exploring the spectrum of 5 psychiatric disorders (General 5-Spectrum Measure). The overall frequency of substance use disorder (SUD) and that of subthreshold use were 46% and 8% in patients with bipolar disorder, 4% and 26% in those with panic disorder, 8% and 26% in those with obsessive-compulsive disorder, and 6% and 10% in the control group, respectively ( Idouble dagger 2 = 51.6, P < .001). Inspection of standardized residuals indicated that alcohol use disorder and SUD were significantly ( P < .05) more frequent in subjects with bipolar disorder than among those with obsessive-compulsive disorder or panic disorder. The latter showed a significantly higher subthreshold use of substances than control subjects. The pattern of motivations for use varied according to the psychiatric disorder. Our results suggest that the well-established relationship between SUDs and psychiatric disorders might be the end point of a process that starts from increased proneness to substance use, which first leads to self-medication and then may eventually develop into substance abuse or dependence, among subjects with psychiatric symptoms.
Abstract: Evidence that high levels of aircraft noise lead to psychiatric disorders in the community is contradictory. The aim of the present study was to investigate the frequency of mental disorders in a sample living in the immediate surroundings of an airport compared with those from a sample of residents from the same region who had not been exposed to the risk of aircraft noise.
Abstract: To further investigate the differentiation between non-purging bulimia nervosa (BN-NP) and binge eating disorder (BED), particularly as concerns weight-shape overconcern affecting self-esteem, a core belief to both anorexia and bulimia nervosa.
Abstract: Peripheral benzodiazepine (BDZ) receptors were investigated by means of the binding of the specific ligand (3)H-PK 11195 to platelet membranes in patients suffering from bipolar disorder and in healthy controls. The results showed that the density (Bmax) of peripheral BDZ receptors was significantly higher in patients than in control subjects, with no change in the dissociation constant. No correlation with demographic or clinical features was observed. These findings would suggest that alterations of peripheral BDZ receptors are present in patients suffering from bipolar disorder, but it is premature to conclude whether they may be related to the pathophysiology of the disorder, or are secondary to changes occurring in other systems, such as those regulating the stress response.
Abstract: The present study reports the results of an open-label trial on the use of the combination of olanzapine (an atypical antipsychotic) serotonin reuptake inhibitors (SRIs) in 26 resistant outpatients affected by resistant obsessive-compulsive disorder (OCD). All patients had been suffering from OCD, according to DSM IV criteria, for at least 2 years and had different comorbid disorders; they had been treated with an SRI at adequate dosages for at least 6 months, or had tried different augmentation strategies with no or poor response. As a result, olanzapine was added and continued for 1 year. After 12 weeks of this regimen, most of the patients (17) had shown a reduction in OC symptoms, as assessed by a decrease in the Yale-Brown Obsessive Compulsive Scale total score, which continued throughout subsequent months. Only mild side-effects were recorded and no patient halted the treatment. The addition of olanzapine would appear to be a useful short- and long-term strategy for augmenting SRI effectiveness in resistant OCD patients, especially in those presenting comorbidity with bipolar disorders.
Abstract: The aim of this study was to investigate the impact of disability and lifetime subthreshold depressive symptoms on Health-Related Quality of Life (HRQoL) among patients with rheumatoid arthritis (RA).
Abstract: To investigate the relationship between lifetime mood and psychotic spectrum features in patients with borderline personality disorder (BPD). Method: The study sample consisted of BPD patients with (n=39, BPD-M) or without (n=21, BPD-no M) lifetime mood disorders. The diagnostic assessment was conducted with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I). The diagnosis of BPD was made clinically and then confirmed by Gunderson's diagnostic interview for borderlines. Subjects were also administered the Structured Clinical Interview for Psychotic Spectrum (SCI-PSY) and the Mood Spectrum self-report questionnaire (MOODS-SR).
Abstract: Behavioural disturbances are frequently observed in Parkinson's disease (PD), including mood and anxiety disorders. The existence of a comorbidity between such psychiatric disorders in PD patients has been suggested only in a few studies. To assess the prevalence of mood and anxiety disturbances, and the rate of comorbidity of such disorders in PD. Secondary aim was to correlate the prevalence of psychiatric disorders in PD with age, sex, laterality of motor symptomatology, clinical features, severity of disease, age of onset and PD duration, and anti-parkinsonian therapy. Ninety consecutive PD outpatients, and 90 age- and sex-matched controls were included. All PD patients enrolled were non-fluctuating (21 de novo, 69 treated with levodopa or dopamine agonists). PD patients and controls with Mini Mental State Examination score <23 were excluded. Psychiatric diagnosis was performed by semistructured interview according with DSM-IV criteria and the severity of depressive and anxious symptoms was rated with clinical rating scales. Major depression was found in 21.1% PD patients vs. 3.3% controls (P < 0.01, chi-square analysis), dystimia in 18.8% PD patients vs. 4.4% controls (P < 0.05), panic disorders in 30% PD patients vs. 5.5% controls (P < 0.01). No difference in the prevalence of other anxiety disorders was observed between the two groups. The comorbidity of mood and anxiety disorders was found in 19.3% PD patients vs. 8.6% controls (P < 0.01). No correlation was reported between the prevalence of behavioural disturbances and any of the demographic, clinical or pharmacological data taken into account. Our findings might suggest the existence of a wide spectrum of psychiatric disorders in PD ranging from pure depressive disorders, comorbid depressive and anxiety disorders, and pure anxiety disorders, presumably linked to the same neurobiological substrate.
Abstract: Cyclic adenosine monophosphate (cAMP) pathway abnormalities have been suggested to be involved in anxiety disorders including panic (PD). The present study sought at investigating the downstream inhibitory adenylyl cyclase (AC) pathway activated by 5-HT in platelets obtained from 22 patients with a diagnosis of PD versus 22 healthy volunteers. In PD patients, a significant impairment of 5-HT potency to inhibit AC was observed. One month of treatment with paroxetine induced a significant increase of 5-HT potency in T1 patients close to the control values. [(35)S]GTPgammaS binding studies showed that in PD patients, a reduction of 5-HT receptor-G protein coupling occurred without any significant changes in G protein levels. These findings demonstrated that (1) a reduction of the inhibitory AC pathway activated by 5-HT occurred in platelets from PD patients; (2) the reduced 5-HT responsiveness in PD was related to an impairment of 5-HT receptor-G protein coupling, and (3) after 1 month of treatment with paroxetine, such a dysfunction significantly reversed together with a significant improvement of clinical symptoms.
Abstract: This study examined the extent to which individuals with a lifetime diagnosis of recurrent unipolar disorder endorse experiencing manic/hypomanic symptoms over their lifetimes and compared their reports with those of patients with bipolar I disorder.
Abstract: Phosphorylation of extracellular signal-regulated kinases (ERK 1/2) represents a converging intracellular signalling pathway which is involved in the modulation of gene transcription and may contribute to the feed-back regulation of neurotransmitter receptor functioning. The purpose of the current study was to investigate the serotonin-mediated phosphorylation of ERK 1/2 in platelets from patients (n = 17) with panic disorder, with respect to healthy volunteers (n = 17). Patients presented a severe symptomatology as assessed by the self-report rating scales for panic-agoraphobic (PAS-SR) and mood (MOOD-SR) spectrum, and by Clinical Global Impression Severity Scale (CGI-S). In platelets from healthy volunteers, serotonin induced a rapid increase of ERK 1/2 phosphorylation with a transient monophasic kinetic. The dose-response curves showed this effect was concentration dependent with an average of the EC(50) value of 22.8 +/- 2.4 microM. Platelet pre-incubation with 5HT(1A) and 5HT(2A) antagonists, pindobind and ritanserin, significantly inhibited serotonin-mediated kinase activation with an EC(50) of 3.2 +/- 0.2 and 1.99 +/- 0.08 nM, respectively, suggesting an involvement of these specific receptor subtypes in serotonin-mediated response. Furthermore, the 5HT(1A) and 5HT(2A) agonists, 8-hydroxy-N,N-dipropyl-aminotetralin (8OH-DPAT) and 1-(2,5-dimethoxy)-4-iodophenyl-2-aminopropane (DOI), were able to modulate ERK 1/2 phosphorylation in a concentration-dependent manner with an EC(50) value of 3.1 +/- 0.2 and 76 +/- 4.5 nM, respectively. ERK 1/2 phosphorylation was not observed after serotonin treatment of platelets from drug-free panic disorder patients, suggesting an alteration in intracellular phosphorylative pathways. Since ERK 1/2 responsiveness to other stimulus, such as collagen and thrombin, was comparable in platelets from healthy volunteers and patients, our results suggested that a specific alteration of serotonergic system occurred in panic disorder. Further studies to investigate 5HT(1A) and 5HT(2A) receptor expression and threonine phosphorylation levels showed that, nevertheless no significant differences in the receptor expression levels were detected, an increase of both 5HT receptor phosphorylation, on threonine residues, occurred in platelet from panic patients with respect to controls, suggesting that a reduction of serotonin receptor functioning was involved in the loss of serotonin responsiveness in panic.
Abstract: The cross-sectional clinical differentiation of schizophrenia or schizoaffective disorder from mood-incongruent psychotic mania or mixed mania is difficult, since pathognomonic symptoms are lacking in these conditions.
Abstract: The aim of this preliminary open-label trial was to evaluate the efficacy and safety of oxcarbazepine (OXC) as adjunctive therapy in 18 patients with bipolar disorder who did not respond satisfactorily to lithium.
Abstract: The Judgment of Line Orientation Test, a visuospatial processing task, was administered to normal subjects, to schizophrenic patients and to patients with delusional disorder. Significantly better performance was seen in the normal subjects than in the schizophrenic and delusional patients. Delusional patients, in turn, showed better performance than the schizophrenic patients.
Abstract: This study aims at identifying potential predictors of clinical response and functional outcome in 101 neuroleptic-refractory patients with a DSM-III-R diagnosis of schizophrenia (N = 34), schizoaffective disorder (N = 30) or bipolar disorder with psychotic features (N = 37), naturalistically treated with clozapine over a 48-month period. The "clinical response" and "functional outcome" criteria were respectively defined a priori as: a reduction of at least 50 % in the Brief Psychiatric Rating Scale total score in one evaluation with respect to baseline; and a Global Assessment of Functioning Scale score of at least 50. Several clinical and socio-demographic variables were assessed at baseline and only the diagnosis of bipolar disorder was significantly related with the clinical response. Variables significantly related with the functional outcome were female gender, university education and early age at onset.
Abstract: Psychological factors play an important role in the aetiopathogenesis of temporomandibular disorders (TMD), as demonstrated by an increase in stress, anxiety, depression and somatization in TMD patients. The aim of this work was to investigate the presence of mood and panic-agoraphobic symptoms in different groups of TMD patients by means of a spectrum approach to psychopathology. A total of 131 subjects were included in this study and TMD signs and symptoms were investigated by means of a standardized clinical examination. Two self-report questionnaires were used to evaluate mood (MOODS-SR) and panic-agoraphobic (PAS-SR) spectrum. anova and Bonferroni's post hoc test for multiple comparisons were used to compare mean scores of all TMD groups for MOODS-SR, PAS-SR and all their domains. Results revealed a significantly higher prevalence of both mood (P < 0.001) and panic-agoraphobic (P < 0.01) symptoms in myofascial pain patients than in all other diagnostic groups (TMD-free, disc displacement and joint disorders). With regard to mood spectrum, strong differences emerged for all domains evaluating depressive symptoms. As for the panic-agoraphobic spectrum, myofascial pain patients differed from the other groups for the presence of stress sensitivity, panic, separation anxiety, hypochondriac and agoraphobic symptoms. It was concluded that myofascial pain patients differed from those with disc displacement, joint disorders and no TMD in relation to some psychopathological symptoms, while the last three groups presented very similar profiles.
Abstract: The lifetime prevalence of Social Phobia (SP) in European countries other than Italy has been estimated to range from 3.5% to 16.0%. The aim of this study was to assess the frequency of SP in Sardinia (Italy) in order to verify the evidence of a lower frequency of SP in Italy observed in previous studies (from 1.0% to 3.1%).
Abstract: Tardive Dyskinesia (TD) is an adverse effect of several psychotropic drugs for long-term therapy for schizophrenia and other psychoses. TD is considered an important issue for public health for its invalidating characteristics. An extensive review of the literature on studies concerning efficacious treatments for TD has been carried out.
Abstract: The purpose of this study was to investigate for difference in the prevalence of mood disorders between patients with different painful temporomandibular disorders (TMD). After a sample size necessary for the study was calculated, 60 patients with a painful TMD were selected and divided into the following groups: myofascial pain (n=20), temporomandibular joint (TMJ) pain (n=18), combined myofascial and TMJ pain (n=22). Two distinct comparison groups were selected: subjects with a nonpainful TMD (n=25) and TMD-free subjects (n=29). All participants filled out a self-report validated instrument (MOODS-SR) to evaluate psychopathological symptoms related to mood disturbances. A one-way analysis of variance (ANOVA) with Bonferroni's post hoc test for multiple comparisons was performed to investigate for significant differences among the groups. The three groups of patients with painful TMD scored significantly higher than comparison groups in all MOODS-SR domains investigating depression, but no difference was shown between subjects with myofascial pain and those with TMJ pain. No significant differences among the groups emerged for the presence of manic symptoms, indicating that depressive disorders associated with TMD are not an expression of a more complex manic depressive illness. The study concluded that the presence of depressive symptoms in TMD patients seems to be related to the presence of a painful condition and seems to be unrelated to the location of pain. Furthermore, depressive disturbances in painful TMD patients affect the whole spectrum of depressive psychopathology.
Abstract: To evaluate the association between mood and anxiety disorders and thyroid autoimmunity in a community sample. Methods: A community based sample of 222 subjects was examined. Psychiatric diagnoses were formulated using the International Composite Diagnostic Interview Simplified (CIDIS), according to DSM-IV criteria. All subjects underwent a complete thyroid evaluation including physical examination, thyroid echography and measure of serum free T4 (FT4), free T3 (FT3), thyroid-stimulating hormone (TSH) and anti-thyroid peroxidase autoantibodies (anti-TPO).
Abstract: Obsessive-compulsive disorder (OCD) is a common psychiatric condition during childhood and adolescence, which continues to be underestimated and undertreated. For these reasons, it constitutes a primary cause of major disabilities in those ages and, sometimes, of permanent impairments later on. In these last few years, childhood and adolescence OCD has attracted an increasing focus which has promoted a deeper awareness of this illness, a better recognition with earlier interventions, as well as the set-up of more tailored and specific strategies, including psychotropic drugs. The aim of this paper is to present a critical review of paediatric OCD, with a special attention towards the most compelling reports available up to now and towards the most interesting areas for future research.
Abstract: This paper reports on the acceptability, reliability and validity of the Structured Clinical Interview for the Spectrum of Substance Use (SCI-SUBS), a new instrument exploring the interactive pathway between substance abuse and psychiatric disorders. Psychiatric outpatients with (n = 21) and without (n = 32) substance abuse comorbidity according to the DSM-IV, non-psychiatric subjects with opioid dependence (OD, n = 14) and normal controls (n = 33) were assessed with the SCI-SUBS. The presence or absence of psychiatric disorders was determined with the Structured Clinical Interview for DSM IV (SCID). The SCI-SUBS was well accepted by participants. The internal consistency of the domains was satisfactory (between 0.64 and 0.93). Domain scores of OD subjects were significantly higher than those of controls and of psychiatric patients without substance abuse. The cut-off point on the SCI-SUBS total score at which there was optimal discrimination between the presence and the absence of a DSM-IV diagnosis of substance abuse was 45. The pilot version of the SCI-SUBS has satisfactory internal consistency and construct validity.
Abstract: Most of the evidence from pharmacological studies supports the hypothesis of a serotonergic (5-HT) dysregulation in eating disorders (ED), though a specific alteration related to the major ED subtypes, anorexia (AN) and bulimia nervosa (BN), has not been identified yet, possibly because of changes over time in ED nosology. The aim of the present study was to verify whether differences in serotonergic activity, measured by platelet [3H]paroxetine binding, would validate current ED classification. Platelet [3H]paroxetine binding was investigated in 26 patients with eating disorders diagnosed in accord with DSM-IV criteria (AN, n=11; BN, n=15) and 26 normal weight controls of comparable age; ED symptomatology was assessed by the Diagnostic Schedule for Eating Disorders. ED patients had significantly lower B(max) values than controls (288.5+/-109.2 vs. 1396.8+/-251.3 fmol/mg), whereas the K(d) was not significantly altered (0.12+/-0.13 and 0.12+/-0.05 nM, respectively). Among patients, differences in B(max) were related neither to DSM-IV subtypes nor to clinical variables such as presence of binge-eating, purging, impulsive behaviors, or symptoms of depression. Although ED patients share a dysregulation in serotonergic activity, DSM-IV subtype classification was not validated by [3H]paroxetine binding, and hence does not correspond to a specific 5-HT profile.
Abstract: The present study examined whether specific types of comorbid anxiety disorders, namely panic disorder (PD), social phobia (SP) and obsessive-compulsive disorder (OCD) are differentially associated with course variables and insight into bipolar illness.
Abstract: Approximately 50% of patients with schizophrenia or schizoaffective disorder attempt suicide, and approximately 10% die of suicide. Study results suggest that clozapine therapy significantly reduces suicidal behavior in these patients.
Abstract: Recent researches on temporomandibular disorders (TMD) have been focused on the interaction between physical and psychological factors. In this work, studies on the role of the latter have been critically reviewed and analysed. A number of works proved the existence of an association between TMD and anxiety, depression and stress, but none demonstrated causality of that relation. In consideration of that, debates are still open to discuss the possible predisposing, triggering and/or worsening role played by some psychic disorders in TMD subjects. Nevertheless, considering the usefulness of recent taxonomic proposals, it seems logical to adopt a broad therapeutic approach, directed both to the physical and psychic component of TMD symptoms. Besides, from this review it is underlined the need for controlled trials which, regardless of the causality of TMD-psychic disorders associations, definitively evaluate the efficacy of the various psychotherapy modalities proposed.
Abstract: To compare the efficacy and tolerability of moclobemide versus paroxetine for the treatment of depression with comorbid anxiety disorders. Outpatients fulfilling DSM-III-R criteria for major depression or dysthymia and for a co-occurring comorbid anxiety disorder (panic disorder, generalized anxiety disorder or obsessive-compulsive disorder) after a 1-week run-in phase were randomly assigned to open-label moclobemide (300-600 mg/day) or paroxetine (20-40 mg/day) for 4 months. Primary criterion for response was a 50% score reduction from baseline on Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale scores. Mean changes in Clinical Global Impressions Severity of Illness and Improvement Scales (CGI-I) were also used to evaluate treatment response. Of the 123 patients included in the study, 65 were randomly assigned to moclobemide and 58 to paroxetine. At study end, the two treatment groups did not differ significantly in terms of proportion of responders. Treatment group differences emerged when comorbid anxiety diagnoses were considered. In patients with comorbid panic disorder, paroxetine was superior to moclobemide in improving both anxiety and depression (five patients out of 18 in the moclobemide group and nine out of 14 in the paroxetine group were rated as responders according to CGI-I, P = 0.04). Neither medication was superior in treating comorbid generalized anxiety disorder. These findings indicate that both moclobemide and paroxetine are effective for treatment of depression with comorbid anxiety disorders. However, in the subgroup with comorbid panic disorder, paroxetine is more effective than moclobemide in reducing both depressive and anxiety symptoms.
Abstract: The aim of this study was to evaluate the long-term efficacy and safety of clozapine in patients with treatment-resistant schizophrenia, schizoaffective disorder, or bipolar disorder with psychotic features.
Abstract: Mortality in anorexic patients is mainly due to suicide or cardiac failure. The aim of this study was to investigate structural and functional cardiovascular alterations further by means of echocardiography in a sample of 15 medication-free patients with DSM-IV anorexia nervosa (AN) (BMI < 17.5 kg/m2) and without any known cardiovascular disease and/or a family history of deafness or sudden death, and correlate the findings with clinical variables. The controls consisted of a sample of 10 constitutionally thin women (BMI < 19 kg/m2), of comparable age, height and degree of physical activity. All of the subjects underwent Doppler echocardiography (ECHO), and the patients were also administered the Diagnostic Schedule for Eating Disorders (DSED) in order to assess the features and course of the eating disorder. ECHO revealed silent pericardial effusion in 71.4% of the patients vs. 10% of the controls (p < 0.05); among the patients, the separation of pericardial leaflets was more frequent in those with a shorter duration of illness (p < 0.05). Mitral valve motion abnormalities were more frequent among the patients than the controls (69.2% vs. 10%, p < 0.005), and the left ventricular mass/body surface area was lower (54.8% vs. 59%, p < 0.001). Isovolumetric relaxation time was longer in the patients (98.4 vs. 65 msec, p < 0.01), but there were no significant differences in left ventricular ejection fraction (53.8% vs. 59%) or early diastolic deceleration time (146 vs. 155 msec). The results of this study support the association between AN and demonstrable anatomic and functional cardiac abnormalities, such as a reduced ventricular mass and mitral valve abnormalities. The ECHO findings provide evidence for clinically silent pericardial effusion in AN, which may be an early sign of cardiovascular involvement.
Abstract: The aim of this paper is to provide the prevalence rates of mild, moderate and severe symptoms of social anxiety in a sample of high school students and to analyze gender differences and associated impairment levels within these three levels of severity. Five hundred and twenty students were assessed with the Social Anxiety Spectrum Self-Report (SHY-SR), a questionnaire that explores social anxiety spectrum. By applying two cut-off scores determined on a separate sample by using ROC analysis, the large majority (73.3 %) of subjects were classified as low scorers, 9% as medium scorers and 17.7% as high scorers. Fears related to social situations were reported both by high and medium scorers. Functional impairment defined by avoidance and school difficulties was more common among high scorers, but it was also reported to a significant extent by medium scorers. Compared to low and medium scorers, high scorers showed a higher F/M ratio (about 4:1) and a more homogeneous symptomatological profile in the two genders. In conclusion, our report confirms, in line with the literature, that even moderate levels of social anxiety are associated with significant functional impairment and distress for the individuals.
Abstract: Temporomandibular disorders (TMD) are a number of conditions which are frequently associated with depressive symptoms, but the possible existence of some form of manic-depressive illness in TMD patients has never been investigated. The aims of this work were to evaluate the reliability of a newly adopted spectrum model of psychopathology to detect depressive symptoms in TMD patients, and to produce pilot data on the presence of manic symptoms in TMD patients.
Abstract: The aim of the present study was to assess the general population from two Sardinian areas to ascertain the direct health care costs involved in a diagnosis of major depression, and to verify the hypothesis of an increased expenditure for untreated depressed subjects.
Abstract: The Collaborative Spectrum Project has developed structured interviews and self-report instruments to assess the spectrum of symptomatology related to panic-agoraphobia, mood, social phobia, and obsessive-compulsive and eating disorders. In order to obtain a rapid pre-test on all five of these spectrum conditions, the authors sought to develop a brief instrument that would tap these conditions. This paper reports on 1) the procedures to derive this composite instrument, the General 5-Spectrum Measure (GSM-V), by selecting items from five existing spectrum instruments, and 2) preliminary testing of the internal consistency and test-retest reliability of the GSM-V. The GSM-V consists of 54 items grouped into scales that explore the five spectra described above. It was derived from existing data on five Structured Clinical Interviews that were designed to assess spectrum features by using multiple regression models. The GSM-V was administered as a stand-alone instrument along with the self-report versions of the spectrum interviews to a sample of 56 psychiatric patients in order to determine the internal consistency of its scales and the correlation with the parent spectrum measures. Moreover, to determine whether subjects would respond consistently to the same items on two different occasions (test-retest reliability), the GSM-V was re-administered within 1 month from the baseline. From each of the five spectrum interviews, items were selected that accounted for a significant proportion of variance of the total score of the parent instrument. The five sets of items so selected constitute separate scales. The scales of the GSM-V had a good to excellent internal consistency, excellent test-retest reliability, and proved to reproduce adequately the long-form measures. The GSM-V appears to provide a reliable alternative to the five longer spectrum interviews. It is envisaged that the instrument will be most useful as a pre-test to identify subjects with spectrum features that should be explored in greater detail. Additionally, it could provide a better characterization of patients with a syndromal level Axis-I disorder, who might require specific treatment strategies targeted to co-occurring subsyndromal conditions.
Abstract: The InterSePT Scale for Suicidal Thinking (ISST) is a 12-item instrument for the assessment of current suicidal ideation in patients with schizophrenia and schizoaffective disorders. We report the psychometric characteristics of this new scale based on two studies.
Abstract: The clinical relevance of Recurrent Brief Depression (RBD) has not received sufficient attention to date and continues to represent a controversial issue. The present study was carried out in a community sample to evaluate the lifetime prevalence of RDB, the degree of comorbidity, as well as possible risk factors. Subjects from a community survey in Sardinia (Italy) were randomly selected from registers of a rural, an urban and a mining area (n=1040, 461 males, 579 females). Interviews were carried out by physicians using the Italian version of the Composite International Diagnostic Interview Simplified which had been modified for the purpose of this study. Lifetime prevalence of RBD was 7.6%; 5.8% in males, 9% in females. Subjects aged 18 to 24 years presented higher frequencies (13.8%, OR 2.2) than those aged 25 or over. Comorbidity with Major Depression was particularly frequent. RBD was furthermore associated with suicide attempts and substance abuse, thereby constituting an effective health problem. Further epidemiological and clinical studies of RBD are warranted in order to develop specific treatments and prevention strategies.
Abstract: Enhanced ability to reliably identify risk factors for suicidal behavior permits more focused decisions concerning treatment interventions and support services, with potential reduction in lives lost to suicide.
Abstract: Gender differences in the social anxiety spectrum and their correlation with other psychopathological features were analyzed in 520 students by using two questionnaires: the Social Anxiety Spectrum Self-Report (SHY-SR), which explores social anxiety spectrum, and the General Spectrum Measure (GSM), which explores panic-agoraphobia, mood, obsessive-compulsive, and eating-behavior features. Mean SHY-SR total score was significantly higher in women than in men, and gender differences were particularly pronounced for interpersonal sensitivity domain. Likewise, GSM scores were higher in women, except for the manic section. The SHY-SR domains correlated significantly with all GSM sections, except for the manic section. In conclusion, women reported more symptoms than men (who belonged to different psychopathologic dimensions) and displayed a profile of social anxiety spectrum that differs quantitatively but not qualitatively from the men's profile. The correlation between social anxiety spectrum and other psychopathological features mirrors previous findings concerning the high comorbidity of axis-I social anxiety disorder.
Abstract: Steady-state plasma concentrations of clozapine and norclozapine, its major metabolite, as well as their sum and ratio (norclozapine/clozapine), were evaluated in 50 in- and outpatients taking clozapine and naturalistically recruited. Drug plasma concentrations were measured by means of a reversed-phase high-performance liquid chromatography (RPLC) method with an ultraviolet detection. Daily doses (milligrams per kilogram of body weight) of clozapine correlated positively with clozapine plasma parameters, except with the norclozapine/clozapine ratio, in all patients. When the patients were divided in subgroups with respect to gender, the corresponding plasma concentrations were no longer dose-related in men. A lack of significant correlation was observed also in patients (n=23) co-treated with typical neuroleptics. Conversely, dose-concentration correlations were significant in either smoker or nonsmoker patients. No significant relationship between body weight and clozapine plasma parameters was reported. Further, we observed (1) a trend towards higher medians of clozapine or total analytes in women than those reported in men (P=.09 and .07); (2) no significant difference in plasma levels obtained in subjects younger than 34 years and subjects 34 years old or older; (3) a trend towards higher norclozapine and clozapine plus norclozapine levels (P=.05 and .08) in nonsmoker than smoker patients; (4) no significant difference between clozapine plasma parameters measured in patients co-medicated with typical neuroleptics and in patients receiving clozapine alone.
Abstract: The present report analyzes the agreement between the interview and the self-report formats of the instruments Structured Clinical Interview for Social Anxiety Spectrum (SCI-SHY) and Structured Clinical Interview for Obsessive Compulsive Spectrum (SCI-OBS), already validated, in three psychiatric patient samples and controls. Thirty patients (10 with obsessive-compulsive disorder [OCD], 10 with social anxiety disorder [SAD], 10 with recurrent unipolar depression in remission) and 20 control subjects (10 university students, 10 ophthalmologic patients) were assessed using the SCI-SHY, the SCI-OBS, and the self report version of the two instruments. Agreement between the two versions was very good for the seven SCI-OBS domains (with intraclass correlation coefficients [ICCs] ranging from 0.80 to 0.96) and the four SCI-SHY domains (ICCs from 0.74 to 0.90). When items were analyzed individually, subjects tended to under-report some phobia-related problems in the interview. The total number of items endorsed in the SCI-SHY, but not in the SCI-OBS, was affected by the order of administration: when the SCI-SHY interview was administered first, subjects reported a median of five more symptoms; when the self-report was administered first, there was no significant difference in the number of symptoms endorsed in the two formats. However, this difference is not clinically important, given the large number of items comprising the instruments, and might be explained by the fact that subjects are likely to overemphasize occasional symptoms or behaviors when they are asked by the interviewer to answer a long series of "new" questions as accurately as possible. Given the high agreement between domain scores in the two formats of the instruments and the fact that scores are virtually identical when the self-report is administered first, we recommend the use of the self-report versions in clinical and research settings.
Abstract: Spectrum phenomena include, in addition to the typical DSM core symptoms, isolated or atypical symptoms, often of low severity, as well as trait-like behavioral features that arise as a result of coping with the psychopathology. We have demonstrated the psychometric properties of five Structured Clinical Interviews for the assessment of specific mood and anxiety spectrum conditions, including the Structured Clinical Interview for Mood Spectrum (SCI-MOODS). The present report describes the reliability of the self-report version (MOODS-SR) of the SCI-MOODS in a sample of 21 patients with a mood disorder and 20 control subjects. Agreement between the self-report and the interview formats was substantial. Intraclass correlation coefficients (ICC) ranged from 0.88 to 0.97. Our findings provide support for the reliability of the MOODS-SR questionnaire.
Abstract: This multicenter study aimed to verify whether the historical and psychopathological characteristics of a large group of patients with deficit schizophrenia were consistent with those reported in previous studies. The authors also tested the hypothesis that neurological and neuropsychological indices sensitive to frontoparietal dysfunction, but not those sensitive to temporal lobe dysfunction, are more impaired in patients with deficit schizophrenia than in those with non-deficit schizophrenia.
Abstract: Kleptomania, listed in DSM-IV as an impulse control disorder not elsewhere classified, is a psychiatric condition still poorly understood and subject of only a few systematic studies. The aim of this research was, therefore, to evaluate the clinical features and comorbidity of Italian patients with a DSM-IV diagnosis of kleptomania. Twenty outpatients with a lifetime diagnosis of kleptomania by DSM-IV criteria, were included in the study and underwent a specially designed semistructured interview and the Family History Research Diagnostic Criteria. The majority of patients reported an early and abrupt onset and an episodic course of the disorder, with no gender preponderance. Lifetime comorbidity for other axis I disorders was high, in particular for mood, anxiety, and impulse control disorders. Family history also showed a high prevalence of psychiatric disorders. Our study indicates clear connections between kleptomania and different psychiatric disorders, the exact nature of which has yet to be clarified.
Abstract: Genetic epidemiologic and clinical data suggest that comorbid panic disorder may define a subtype of bipolar disorder. Comorbid panic disorder might thereby influence the strength of association between bipolar disorder and genes that have been implicated in bipolar disorder on the basis of their function in monoamine neurotransmission and previously reported linkage results. Polymorphic markers at catechol O-methyltransferase (COMT), serotonin transporter (5-HTT), and tryptophan hydroxylase (TPH) genes were analyzed in a case-control association study of bipolar disorder patients with or without lifetime panic disorder.
Abstract: The aim of this study was to investigate two samples of patients affected by anorexia nervosa (AN) or bulimia nervosa (BN), respectively, with and without the diagnostic feature of drive for thinness (DT).
Abstract: We investigated 5-HT reuptake and protein kinase of type C (PKC) activation in platelets of 14 OCD patients at baseline and after six months of treatment with different serotonin (5-HT) reuptake inhibitors (SRIs). The results showed that all SRIs provoked a significant increase in both the maximal velocity (V(max)) and the Michaelis-Menten constant (K(m)) of 5-HT reuptake, as compared with baseline values. The activation of PKC by means of 4-beta-12-tetradecanoylphorbol 13-acetate provoked a significant decrease in V(max) values, but the effect was not as evident as at baseline. These findings could indicate that, in OCD patients, SRIs increase the rate of reuptake and decrease the inhibitory effect of PKC and that the two phenomena may be linked, the first perhaps depending upon the second.
Abstract: Poor insight into illness is a common feature of bipolar disorder and one that is associated with poor clinical outcome. Empirical studies of illness awareness in this population are relatively scarce with the majority of studies being published over the previous decade. The study reported here sought to replicate previous report findings that bipolar patients frequently show high levels of poor insight into having an illness. We also wanted to examine whether group differences in insight exist among bipolar manic, mixed and unipolar depressed patients with psychotic features.
Abstract: Insight is a complex phenomenon that can be interpreted according to a dimensional model. Given the controversial data of insight in obsessive-compulsive disorder (OCD), our study aimed to investigate insight in an Italian sample of patients with OCD by means of the specific item on the Yale-Brown obsessive-compulsive scale (Y-BOCS) and to explore the possible correlations between it and clinical features. One hundred and seventeen out-patients with a DSM-IV diagnosis of OCD and different comorbid psychiatric disorders were included in the study and assessed by means of the Y-BOCS, Hamilton rating scale for depression (HRSD) and the global clinical impression. The results showed that almost 50% of the patients had an excellent level of insight and 15% had a little or no insight. No correlation between levels of insight and clinical features was observed, except for a negative trend with the presence of somatic obsessions. In addition, a trend towards a lower level of insight was observed in those bipolar patients with a positive history of repeated manic or hypomanic episodes. Further studies seem to be necessary in order to establish whether or not OCD patients with poor insight represent a distinct sub-group of patients.
Abstract: To assess the antidepressant efficacy and tolerability of adjunctive pramipexole, a D2-D3 dopamine agonist, in patients with drug-resistant depression.
Abstract: Deficits in insight have been found in one study to be more common and severe in patients with schizophrenia than in patients with schizoaffective and major depression with and without psychosis but not more severe than they are in patients with bipolar disorder. The goals of this study were to replicate this finding independently and to clarify whether patients with schizophrenia differ from patients with bipolar disorder in a larger study group.
Abstract: 1. The authors present here a sensitive and rapid reversed-phase liquid chromatographic method which enables the simultaneous analysis in plasma of two different drugs and their metabolites: the atypical neuroleptic clozapine and the tricyclic antidepressant clomipramine. 2. Samples and the internal standard (dibenzepine) were extracted through automated solid-phase procedure, evaporated dryness and injected into the chromatograph. Mobile phase was a mixture of water and acetonitrile (63:37, v:v) containing TEMED and triethylamine. The total chromatographic time was of 14 min and analyte peaks were detected by means of an ultraviolet spectrophotometer preset at 254 nm. 3. Results revealed an assay sensitivity of 5 microg/L for clozapine or norclozapine and of 10 microg/L for clomipramine and desmethylclomipramine. Recoveries for these drugs and their metabolites were more than 60% and their coefficient of variation (within day and day-to-day) ranged from 1.3 % to 2.5 %. In spiked plasma, within day and day-to-day coefficients of variability (CV) were less than 5%. The simultaneous evaluation of these two drugs with adequate sensitivity and precision makes it particularly useful for therapeutic drug monitoring during mono- or polypharmacotherapy.
Abstract: Different findings suggest that the serotonin (5-HT) system may be involved in both the regulation of aggression and the pathophysiology of obsessive-compulsive disorder (OCD). Our study aimed to evaluate the aggressive features of a group of OCD patients and to explore possible correlations with a serotonergic marker, namely platelet 5-HT transporter. Psychopathological and biological patterns were compared with those of a group of healthy controls and those of patients with major depression. Twenty-one patients affected by OCD, 21 by depression and 21 healthy controls were included in the study. Aggressive features were measured by means of the Buss and Durkee Hostility Inventory (BDHI). The platelet 5-HT transporter was evaluated by means of the (3)H-paroxetine binding parameters (maximum binding capacity, B(max) and dissociation constant, K(d)). The OCD patients showed a total score on the BDHI not significantly different from that of healthy controls and lower than that of depressed patients. The factor profile was similar in the 3 groups, but higher in the depressed patients. The irritability, resentment, guilt, negativism and suspiciousness factors were significantly more pronounced in depressed patients. Some sex-related difference in single factors were also observed. The B(max) of (3)H-paroxetine binding was lower in OCD patients than in depressives or healthy controls. OCD patients were more similar to healthy controls than to depressed patients with regard to aggressive features measured by means of the BDHI. This suggests that aggression in OCD is a complex phenomenon that probably requires specific instruments of evaluation.
Abstract: This study aimed to evaluate the effect of citalopram in patients with refractory obsessive-compulsive disorder (OCD) which had not responded to previous antiobsessional treatments. Eighteen patients were selected for this study: they had been suffering from OCD, according to DSM-IV criteria, for at least 2 years and had various comorbid disorders. All had been treated with serotonin reuptake inhibitors at adequate dosages for at least 6 months, but had failed to respond. Consequently, they were shifted to citalopram, titrated up to the dose of 40 mg, within 2 weeks. After 4 months of this regimen, 14 out of the total of 18 patients had shown a reduction in OC symptoms, as assessed by the decrease in the Yale-Brown Obsessive Compulsive Scale total score; no relevant side-effects were reported, except for a mild nausea in four patients within the first few days of treatment, which quickly disappeared. The use of citalopram would appear to be an useful strategy in refractory OCD cases.
Abstract: Selective serotonin reuptake inhibitors (SSRIs) have been reported to be useful in the treatment of depression in patients with Parkinson's disease (PD). However, a few reports have suggested that SSRIs may worsen parkinsonian motor symptomatology and extrapyramidal side effects have been reported in depressed patients treated with SSRIs. So far, no prospective trial comparing the effects of different SSRIs in depressed patients with PD has been performed. The aim of the present study was to assess the effects of four SSRIs (citalopram, fluoxetine, fluvoxamine, and sertraline) on motor performance and their efficacy on depression in a group of patients with PD. Sixty-two consecutive nondemented, nonfluctuating, depressed patients with PD were included in four treatment groups (15 patiens received citalopram, 16 fluoxetine, 16 fluvoxamine, and 15 sertraline). The evaluation of extrapyramidal and depressive symptomatology was performed with use of the Unified Parkinson's Disease Rating Scale (UPDRS), Beck Depression Inventory, and Hamilton Depression Rating Scale at baseline and after 1, 3, and 6 months. Fifty-two patients completed the study. UPDRS scores were not significantly modified by the add-on therapy with each of the SSRIs studied. A significant improvement in depressive symptoms from baseline to the end of the trial was obtained with all SSRIs (Beck and Hamilton scores improving; p < 0.05 according to an analysis of variance). Our findings suggest that SSRIs do not significantly worsen extrapyramidal symptomatology and may ameliorate depression in patients with PD.
Abstract: Research to date would suggest the possible involvement of the serotonin (5-HT) system in the pathophysiology of suicide. With this study, we aimed to investigate the platelet 5-HT transporter, by means of the specific binding of tritiated paroxetine ([3H]Par), in a sample of 20 suicide attempters recruited at a first-aid service, as compared with healthy control subjects and psychiatric patients with no current or previous history of suicide attempt. The results, showing a decreased number of [3H]Par binding sites in suicide attempters, would suggest the involvement of the presynaptic 5-HT transporter in self-aggressive behavior.
Abstract: The aim of this study was to investigate the effectiveness of electroconvulsive therapy (ECT) in medication-nonresponsive patients with mixed mania and bipolar depression.
Abstract: The aim of this study was to evaluate the 24-month response to clozapine in patients with schizophrenia, schizoaffective disorder, or psychotic bipolar disorder.
Abstract: Different observations show a reduced functionality of the serotonin (5-HT) transporter in obsessive-compulsive disorder (OCD) that might be due to a disturbance of its regulation at intracellular level. Protein kinase C (PKC) has been reported to provoke a decrease in the number of the 5-HT transporter proteins. Therefore, we investigated whether OCD patients differed from control subjects in the effect of PKC upon the 5-HT transporter, after stimulation of this enzyme with 4beta-12-tetradecanoylphorbol 13-acetate (beta-TPA). Fifteen patients affected by OCD, according to DSM-IV criteria, were compared with a similar group of healthy subjects. The determination of 5-HT uptake was carried out according to the method of Arora and Meltzer with slight modifications. At baseline, OCD patients showed a significant decrease in the maximal velocity (V(max)) of 5-HT uptake, as compared with control subjects, with no change in the Michaelis-Menten constant (K(m)). The activation of PKC with beta-TPA provoked a significant decrease in V(max) values in both groups, but the effect was significantly more robust in OCD patients who, in turn, also showed also an increase in K(m) values. These findings could indicate the presence of hyperactivity of PKC in OCD that could be the result of increased activity of the phosphatidylinositol pathway. In addition, this suggests new potential therapeutic targets in OCD.
Abstract: A simple reversed-phase liquid chromatographic method enabling the simultaneous analysis in plasma of the tricyclic antidepressant clomipramine, its demethylated metabolite, and the selective serotonin reuptake inhibitor fluvoxamine, was developed. The drugs and dibenzepine, the internal standard, were extracted from 1 mL plasma through an automated solid-phase procedure, eluted in a total chromatographic time of approximately 14 min and detected by means of an ultraviolet spectrophotometer preset at 254 nm. An assay sensitivity of 10 microg/L was observed for all analytes. Recoveries for these drugs and their metabolites ranged between 65% and 98% and their coefficient of variation (within-day and day-to-day) between 1.9% and 2.9%. In spiked plasma, within-day and day-to-day imprecision data were less than 5%. The simultaneous determination of clomipramine, N-desmethylclomipramine, and fluvoxamine with adequate sensitivity and accuracy may be useful for the monitoring of drug treatment in depression and obsessive-compulsive disorder, where combinations of such drugs are employed.
Abstract: In 10 normal human subjects, we studied the accuracy of memory-guided saccades made to the remembered locations of visual targets and sounds. During the time of stimulus presentation, subjects were smoothly tracking a projected laser spot that was moving horizontally across a tangent screen, sinusoidally +/-15 degrees at 0.25 Hz. In one set of experiments, the laser spot moved across a 40 degrees x 28 degrees random dot display that moved synchronously in the vertical plane; this induced a strong illusion that the trajectory of the laser spot was diagonal (variant of Duncker illusion). In control experiments, the laser spot moved across the same display, which was stationary. The visual targets and speakers were at six locations (range +/-15 degrees ) in the horizontal plane. Saccades made to the remembered locations of targets presented during background motion (illusion) were significantly (P < 0.05) more inaccurate than with the background stationary (control) in 9 of 10 subjects for lights and in 6 of 10 subjects for sounds. As a group, the median change in errors due to the Duncker illusion was approximately 2.5 times greater for visual compared with acoustic targets (P < 0.001). These findings are consistent with electrophysiological studies which have shown that neurons in the primate lateral intraparietal area (LIP) may respond to both visual and auditory targets and these neurons are also influenced by the Duncker illusion during programming of memory-guided saccades.
Abstract: Binge eating disorder (BED) is a recently conceptualized eating disturbance, and its clinical features and prevalence are still a matter of debate. This study uses interview methodology to estimate the prevalence of BED in Italy in a sample of 66 obese people presenting for treatment, and examines potential related features typical of patients with anorexia and bulimia nervosa. The lifetime and the 6-month prevalences of BED were 18.1 and 12.1%, respectively. Breaking the group down on the basis of the current as well as lifetime presence of BED, we found that the weight and shape primary to self-esteem, and the interpersonal distress related to body image, were associated with lifetime BED (P<0.05). All-or-none thinking about food and dieting was typical of BED patients as a whole, either current (P<0.01) or remitted (P<0.05). We discuss two important findings from our study: (a) the key role of self-esteem depending upon weight and shape in discriminating the eating-disordered obese from non-eating-disordered individuals; and (b) the need to explore the whole lifespan when screening for BED, so pointing to the state-trait issue.
Abstract: Risperidone, an atypical neuroleptic, has been proposed for augmentation strategies in resistant obsessive-compulsive disorder (OCD). We report the results of an open-label trial on the use of the combination of serotonin reuptake inhibitors (SRIs) with risperidone in 20 refractory OCD outpatients. All patients had been suffering from OCD, according to DSM-IV criteria, for at least 2 years and had various comorbid disorders. All had been treated with a SRI at adequate dosages for at least 6 months, but had failed to respond. Therefore, risperidone was added and the dosage titrated up to the mean dose of 3 mg/day over 8 weeks. After 2 months of this regimen, all patients had shown a reduction in obsessive-compulsive symptoms, as assessed by the decrease in the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) total score, particularly those with a lifetime comorbidity with bipolar disorder; only three patients reported mild sedation and postural hypotension, two mild extrapyramidal side-effects (tremors and akatysia) and two an increased appetite. All these effects were well tolerated and no patient halted the treatment. The addition of risperidone would appear to be a useful strategy for augmenting SRI effectiveness in refractory OCD patients.
Abstract: This study investigated a series of clinical characteristics, including the level of insight into illness and axis I comorbidity, in 125 patients with bipolar disorder with psychotic features categorized in three groups: 62 patients with mania, 28 patients with mixed mania, and 35 patients with depression. All patients were hospitalized and were assessed in the week preceding discharge. The three groups did not differ in the severity of psychopathology as assessed by the Brief Psychiatric Rating Scale (BPRS). The mania group had a lower level of insight into the social consequences of illness than the other two groups, and compared with the group with depression, they had a lower level of insight of poor attention and of poor social judgment. As to axis I comorbidity, obsessive-compulsive disorder was found to be significantly more frequent in depression than in mania. Patients with depression more frequently reported a history of suicidality than those with mania, whereas they did not significantly differ from patients with mixed mania. Our results suggest that mixed mania as assessed at the time of the patient's discharge differs from mania and from depression with respect to a limited number of features among those examined. However, the overall level of insight into illness significantly discriminated mixed mania from mania, but not from depression.
Abstract: Various data have shown the involvement of serotonin (5-HT) in autism. The presence of the 5-HT transporter in platelets, similar to the same structure located in presynaptic serotonergic neurons, has produced a series of studies aimed at assessing its functionality in this disorder, but the ensuing findings are quite controversial. For this reason, we investigated the 5-HT transporter by means of the specific binding of [3H]-Paroxetine ([3H]-Par), which is currently considered the first-choice ligand for labeling it, in platelets of 20 autistic children and adolescents, as compared with healthy control subjects.
Abstract: Selective serotonin reuptake inhibitors have been used in the treatment of depression in patients with PD. Conflicting data as to whether selective serotonin reuptake inhibitors worsen parkinsonian motor symptomatology have been reported. In this study, the additional 6 months therapy with paroxetine 20 mg/d in a group of depressed patients with PD did not modify parkinsonian motor function (Unified Parkinson's Disease Rating Scale scores); however, in one patient, fully reversible worsening of tremor was observed. Depression, as evaluated by Beck Depression Inventory and Hamilton Depression Rating Scale, improved from baseline to final visit (p < 0.05 by analysis of variance).
Abstract: Different findings support the involvement of the serotonin (5-HT) system in panic disorder. The presence of the 5-HT transporter in blood platelets similar to that in presynaptic serotonergic neurons, permits the investigation of this structure in periphery. We therefore evaluated the binding of 3H-paroxetine, a selective 5-HT reuptake inhibitor which is considered the ligand of choice for labelling the 5-HT transporter, in platelets of 20 drug-free patients with panic disorder. The same measurement was repeated after one year's treatment with different drugs. The results showed patients to have a lower number of 3H-paroxetine sites than a group of age- and sex-matched controls, thus suggesting the involvement of the 5-HT transporter in panic disorder. This abnormality reverted after one year of treatment with specific drugs that provoked the symptom remission in all cases, which would suggest a link with the clinical improvement.
Abstract: The authors investigated frequencies and clinical correlates of multiple associations of panic disorder, obsessive-compulsive disorder (OCD), and social phobia in patients with severe mood disorders.
Abstract: The authors' goal was to investigate the awareness of illness and subjective cognitive complaints of patients with either bipolar I disorder or bipolar II disorder during a phase of clinical stabilization.
Abstract: Much interest is currently being directed towards serotonin (5-HT) receptors of type 2C (5-HT2C) because of their possible involvement in the control of different activities, such as the composition of the cerebrospinal fluid, locomotion, feeding, neuronal excitability and anxiety. The limited information regarding their distribution in the human brain prompted us to investigate, and to characterize the binding of [3H]mesulergine, a HT2C antagonist, in autopsy samples from 24 subjects. The results showed that the [3H]mesulergine binding represented 95% of the total binding and equilibrium saturation binding experiments resulted in a single straight line, consistent with the presence of one site only. The area with the highest density of [3H]mesulergine binding was the choroid plexus, followed at a significantly lower level by the hippocampus, substantia nigra, basal ganglia, amygdala, hypothalamus and prefrontal cortex. The pharmacological profile of the [3H]mesulergine binding was consistent with that of 5-HT2C receptors, since the most effective displacers were ritanserin, mesulergine and mianserine, followed by clozapine, ketanserine and m-CPP, while other compounds had a negligible or no effect. These findings, showing a wide distribution of [3H]mesulergine binding sites in the human brain, could provide anatomical bases for the different functions attributable to 5-HT2C receptors in humans.
Abstract: Failure to recognize subthreshold expressions of mania contributes to the frequent under-diagnosis of bipolar disorder. There are several reasons for the lower rate of recognition of subthreshold manic symptoms, when compared to the analogous pure depressive ones. These include the lack of subjective suffering, enhanced productivity, ego-syntonicity, and diurnal and seasonal rhythmicity associated with many of the manic and hypomanic symptoms, and the psychiatrists' tendency to subsume persistent or even alternating symptoms among personality disorders. Furthermore, the central diagnostic importance placed on alterations in mood distracts clinicians from paying attention to other more subtle but clinically meaningful symptoms, such as changes in energy, neurovegetative symptoms and distorted cognitions. Although officially accepted in both ICD-10 and DSM-IV, we believe bipolar II disorder is underdiagnosed because of inattention to symptoms of hypomania. Moreover, by requiring the presence of both full-blown hypomanic and major depressive episodes, current nosology fails to include symptoms or signs which are mild and do not meet threshold criteria. There is already agreement in the field that such symptoms are important for depression. We now propose that attention should also be devoted to mild symptomatic manifestations of a manic diathesis, even if such manifestations may sometimes enhance quality of life. The term 'spectrum' is used to refer to the broad range of such manifestations of a disorder from core symptoms to temperamental traits. Spectrum manifestations may be present during, between, or even in the absence of, an episode of full-blown disorder. We have developed a structured clinical interview to assess the mood spectrum (SCI-MOODS) to evaluate the whole range of depressive and manic symptoms. This instrument is currently undergoing psychometric testing procedures. Similar to the SCID interview, the SCI-MOODS interview provides a separate rating for each of the major DSM-IV symptoms, but the latter also identifies and rates subthreshold and atypical manifestations. This paper presents the concept of a subthreshold bipolar disorder and discusses the potential epidemiological, diagnostic and therapeutic relevance of such a spectrum conditions. We also describe the SCI-MOODS interview used reliably to identify the occurrence of a bipolar spectrum condition. Obviously a great deal of systematic research needs to be conducted to ascertain the reliability and validity of subthreshold bipolarity as summarized in this paper and embodied in our instrument.
Abstract: The recently introduced notion of clinical conditions being related one to another, the spectrum concept, permits the testing of the involvement of serotonergic systems in a broad range of disorders tentatively linked to obsessive-compulsive disorder (OCD) for which no pathophysiological hypotheses yet exist. We therefore compared the binding of [3H]paroxetine ([3H]Par), a ligand that specifically labels the serotonin (5-HT) transporter, in platelets of drug-free outpatients suffering from various OCD-related disorders with binding in platelets of OCD patients and healthy subjects. Diagnoses were made according to DSM-IV criteria. The most frequent diagnosis was that of body dysmorphic disorder, followed by impulse control disorder, kleptomania, Tourette's syndrome and trichotillomania. Platelet membranes and [3H]Par binding were studied according to standardized protocols. The results, showing a similarly decreased density of [3H]Par binding sites in both patient groups as compared with healthy subjects, suggest the presence of a shared abnormality at the level of the presynaptic 5-HT transporter, probably linked to a common dimension yet to be identified.
Abstract: Based on previous evidence that trazodone may have antiobsessional properties, the authors assessed trazodone augmentation of selective serotonin reuptake inhibitor (SSRI) therapy in five cases of obsessive-compulsive disorder. All patients showed symptomatic improvement after trazodone was added to treatment with various SSRIs, and in many cases, trazodone also improved the tolerability of SSRI therapy.
Abstract: Axis I comorbidities are prevalent among patients with severe bipolar disorder but the clinical and psychopathological implications are not clear.
Abstract: The aim of this study was to explore patterns and clinical correlates of psychiatric comorbidity in patients with schizophrenia spectrum disorders and mood spectrum disorders with psychotic features.
Abstract: Aim of the study was to investigate the presence of underlying abnormalities affecting the hypothalamus-pituitary-gonadal axis in 13 normal weight eumenhorreic bulimics as expressed by a different gonadotropin response to gonadotropin releasing hormone (GnRH), comparing patients with (n = 6) and without (n = 7) purging behaviours to controls (n = 5).
Abstract: The aim of our study was to measure and compare platelet phenolsulfotransferase (PST) activity in patients affected by different psychiatric disorders and in healthy volunteers. The results showed that the activity of both of the two forms of PST was significantly higher in 30 patients with obsessive-compulsive disorder and in 25 manic patients than in 20 healthy volunteers. On the contrary, normal values were found in 11 dysthymic patients, 12 bipolar depressives, and 14 patients with panic disorder, whereas lower values were found in 12 unipolar depressives and 30 patients with migraine. It would therefore seem that different neuropsychiatric disorders are associated with different levels of PST activity.
Abstract: The authors investigated the presence of a serum activity inhibiting the specific binding of 3H-flunitrazepam (which labels the central benzodiazepine receptors) (BBIA) in patients with different psychiatric disorders and analyzed it by means of high performance liquid chromatography (HPLC) analysis. The results showed that the lowest activity was present in healthy controls who were not different from patients with schizophrenia and obsessive-compulsive disorder. On the contrary, the BBIA values of these 3 groups of patients were significantly lower than those found in patients with bipolar disorder in various phases (depressive, mixed or manic), in unipolar depressives and in patients with panic and delusional disorders. The HPLC analysis of the serum extracts revealed the presence of 3 peaks of activity which were differently distributed in the patients and in the healthy controls, peak 3 being totally absent in the last group and mainly represented in bipolar depressives. The GABA ratio values showed that peaks 1 and 2 behave as agonists while peak 3 behaves as an inverse agonist. The mass fragmentography of the different peaks is in progress.
Abstract: We studied 259 female inpatients with bipolar spectrum disorders, of whom 26 (10%) were schizoaffective. Of the remaining 233, 61 (27%) met our conservatively set criteria for index mixed episodes (simultaneous presence of depressive and manic syndromes). These patients with rigorously defined mixed states were, in turn, about equally divided between psychotic and non-psychotic subgroups. The psychotic mixed patients (n = 32) were closer to the bipolar I pattern, and more often seem to come from a familial background of psychotic mood disorders; the nonpsychotic mixed patients (n = 29) conformed more closely to the bipolar II pattern, and more often had a hyperthymic and cyclothymic temperament and a family background of non-psychotic disorders and substance abuse. A three-way comparison between psychotic manic (n = 24), psychotic mixed (n = 32), and schizoaffective (n = 26) patients revealed few significant differences in temperamental, familial and course patterns. As expected, psychotic manic patients more often arose from a hyperthymic base and pursued a predominantly manic course; psychotic mixed patients were less likely to arise from such a base and more likely to pursue a mixed course. Finally, schizoaffective had earlier age at onset and longer duration of illness, suggesting that these patients had a more severe illness. Otherwise, interepisodic social adaptation was comparable in the three psychotic groups. The findings overall suggest that the presence of psychosis had relatively little impact on mixed states, which appear more based on temperamental characteristics.
Abstract: Data on 108 hospitalized bipolar I women were analyzed to characterize those whose course was marked with at least one mixed episode (i.e. an episode with concomitant manic and depressed features) on the basis of various anamnestic and cross-sectional clinical features in comparison with those without mixed episodes. Our data revealed a later age of appearance of the first mixed episode in the course of bipolar illness with a tendency to recur true to type; greater prevalence of mood incongruent psychotic features; lower frequency of hyperthymic temperament; and familial depressive, rather than bipolar, disorders. These characteristics tend to identify the mixed state as a distinct longitudinal pattern of manic-depressive illness.
Abstract: TSH secretion, with particular regard to the nocturnal surge of the hormone, was evaluated in 15 women (age range, 35-66 yr; mean, 50 yr) with untreated major endogenous depression and 15 healthy women (age range, 32-67 yr; mean, 53 yr) using an ultrasensitive assay. Mean morning (0830 h) TSH values did not differ in the 2 groups (1.3 +/- 02 mU/L in depressives and 1.4 +/- 0.1 mU/L in controls), whereas mean nighttime (2400-0200 h) values were significantly reduced in depressives (1.5 +/- 0.3 vs. 3.1 +/- 0.3 mU/L; P less than 0.0005). At variance with the control group, morning and nighttime TSH values did not differ in the depressives. The nocturnal serum TSH surge was abolished in 14 of 15 depressed patients. The mean peak TSH value after TRH was slightly yet significantly lower in the depressives. Patients with subnormal (less than 0.4 mU/L) TSH values in the morning had a serum TSH increase after TRH less than 2 mU/L in 5 of 6 cases and a lack of the nocturnal TSH surge in 6 of 6. Among the 9 patients with normal TSH values in the morning, the nocturnal serum TSH surge was lost in 8 of 9, whereas the response to TRH was normal in all. The depressives, at variance with other reports, showed significantly lower values of total and free thyroid hormones. Mean serum sex hormone-binding globulin (SHBG) and ferritin were also significantly reduced. In conclusion, major endogenous depression is associated with a major impairment of TSH secretion, which baseline TSH measurements in the morning and the evaluation of the TSH response to TRH may not reveal. In this regard, the loss of the nocturnal serum TSH rise would appear to be a more sensitive indicator of hypothalamus-pituitary-thyroid axis alterations in depressives than the TRH test, which is commonly used in the evaluation of these patients. The lack of the nocturnal TSH surge may be responsible for the reduced thyroid hormone secretion and supports the case for some degree of central hypothyroidism in endogenous depression.
Abstract: The problem of whether rapid-cycling (RC) bipolar disorder is more frequently associated than non-rapid-cycling (NRC) bipolar disorders with thyroid dysfunction was investigated in two groups of 11 women matched for age and therapy. Seven patients in each group were under chronic lithium therapy. Both RC and NRC patients, as compared to euthyroid controls, showed a reduction in mean total and free thyroid hormone concentrations, subnormal values of free thyroxine being found in four RC and three NRC patients. No patient had supranormal baseline thyroid stimulating hormone (TSH) values, but an exaggerated TSH response to thyrotropin releasing hormone was found in three RC and two NRC patients: all these patients had been receiving lithium therapy for more than one year. No differences in the prevalence of goiter and thyroid-directed autoantibodies were observed in the two groups. These data confirm that bipolar disorder, especially during treatment with lithium, is associated with at least subclinical hypothyroidism, and suggest that RC patients do not differ from NRC patients in the prevalence of spontaneous or lithium-induced thyroid hypofunction. Lithium-induced hypothyroidism is likely to be related to the length of treatment.
Abstract: Skin penetration of coenzyme Q10 (CoQ10) was investigated after topical treatment in the rat. The drug was suspended in olive oil and administered at two different concentrations. Coenzyme levels were found to be directly related to the concentrations employed and the contact time. CoQ10 topical treatment might therefore be proposed as a good pharmacological tool in dermatology and cosmetology.
Abstract: Thirty-one female inpatient depressives underwent a systematic open trial with rubidium chloride, 180 to 720 mg/day. By week 2, at least two-thirds had improved significantly (p less than 0.01) as measured by standard rating instruments such as the Brief Psychiatric Rating Scale and the Hamilton Depression Scale. Regression analysis suggested that the retarded endogenous pattern was most predictive of positive response. Treatment-emergent symptomatology, such as diarrhea, polyuria, and excitement, was generally mild and rarely necessitated interruption of the trial. The authors conclude that this salt has shown sufficient clinical promise to warrant more extensive trials under double-blind conditions.
Abstract: Rat kidney was perfused using Krebs solution containing 3 or 6 mEq/l lithium or 3 or 6 mEq/l rubidium; the histological lesions thus induced were compared. Rubidium-induced lesions, irrespective of concentrations, consisted of tubular dilations, degeneration and necrosis very similar to those induced by lower concentrations of lithium; moreover, Bowman space alterations were observed. In contrast, lithium-induced damage was dose-dependent: 6 mEq/l solution induced severe tubular damage with necrosis, endoluminal cellular debris and hyaline substance.
Abstract: Mercury and its derivatives have long been known to be toxic for the brain and other organs in both animals and man. The distribution of inhaled radioactive mercury (203Hg) in body tissues of rats and mice was investigated by means of a micro-autoradiographic technique. Animals were exposed to 203Hg vapours 6 h daily for 10 days, and then sacrificed at different times after the last exposure. Whole-body autoradiograms showed significant uptake of labelled mercury by the kidney, brain, myocardium, intestine and liver, in decreasing order. Micro-autoradiography demonstrated selective localization of 203Hg in the cytoplasm and processes of neurons, whereas little radioactivity was found in the glial cells of the gray and white matter. High levels of 203Hg were detected in nuclei of the cerebellum, midbrain, pons and medulla, in the Purkinje cells of the cerebellar cortex, and in the epithelium of the ependyma and choroid plexus. In the lung, radioactivity appeared to be confined to the erythrocytes of small blood vessels, which may be the carriers of this metal to the brain. In the liver, ingested but not inhaled radioactivity was concentrated in the reticulo-endothelium. In the kidney, proximal and distal convoluted tubules, but not the medulla or the glomeruli, took up large amounts of inhaled 203Hg. Mercury is distributed to many organs in addition to the brain. It may be transported by circulating red blood cells and it concentrates in the cytoplasm of parenchymal cells.
Abstract: Concentrations of unchanged metergoline and its main metabolite, 1-demethylmetergoline, were measured by HPLC and fluorescence detector in the plasma of 13 healthy male volunteers. The subjects received on various occasions the following single-dose metergoline treatments: 4 mg by i.v. infusion (n = 7), 8 mg orally as aqueous solution (n = 7) and 8 mg orally as two different formulations of film-coated tablets (Formulation A, n = 12; Formulation B, n = 12). The mean plasma t 1/2 of metergoline and of 1-demethylmetergoline were about 50 min and 100 min, respectively, independent of the route of administration. A considerable first-pass effect was evident from the data, with about 75% of metergoline being metabolized by the liver before reaching the systemic circulation. However, the availability of the drug in terms of 1-demethylmetergoline was similar for the i.v. and oral routes of administration indicating a complete absorption of the solution from the gastrointestinal tract. Very low plasma levels of another metabolite (12-hydroxymetergoline) were detected in some patients. The bioavailability of film-coated tablets in Formulation B was slightly better than for Formulation A with regard to both relative absorption (A vs B = 82%) and lower interpatient variation. Compared with oral solution, the absorption of Formulation B was slightly slower but practically complete.
