Abstract: Frontostriatal circuit mediated cognitive dysfunction has been implicated in frontotemporal lobar degeneration (FTLD) and may differ across subtypes of FTLD. We manually segmented the neostriatum (caudate nucleus and putamen) in FTLD subtypes: behavioral variant frontotemporal dementia, FTD, n=12; semantic dementia, SD, n=13; and progressive non-fluent aphasia, PNFA, n=9); in comparison with controls (n=27). Diagnoses were based on international consensus criteria. Manual bilateral segmentation of the caudate nucleus and putamen was conducted blind to diagnosis by a single analyst, on MRI scans using a standardized protocol. Intracranial volume was calculated via a stereological point counting technique and was used for normalizing the shape analysis. Segmented binaries were analyzed using the Spherical Harmonic (SPHARM) Shape Analysis tools (University of North Carolina) to perform comparisons between FTLD subtypes and controls for global shape difference, local significance maps and mean magnitude maps of shape displacement. Shape analysis revealed that there was significant shape difference between FTLD subtypes and controls, consistent with the predicted frontostriatal dysfunction and of significant magnitude, as measured by displacement maps. These differences were not significant for SD compared to controls; lesser for PNFA compared to controls; whilst FTD showed a more specific pattern in regions relaying fronto- and corticostriatal circuits. Shape analysis shows regional specificity of atrophy, manifest as shape deflation, with a differential between FTLD subtypes, compared to controls.
Abstract: The neuroacanthocytoses are a group of disorders characterised by peripheral blood acanthocytes, central nervous system as well as neuromuscular symptoms. These disorders uniformly result in pathology in the basal ganglia, which account for the characteristic motor symptoms such as chorea or dystonia, but may also account for the apparent elevated rates of major mental disorders in these syndromes. Elevated rates of dysexecutive syndromes, obsessive-compulsive disorder, depression and schizophrenia-like psychosis appear to occur in chorea-acanthocytosis, McLeod's syndrome, pantothenate kinase-associated neurodegeneration, and Huntington's disease-like 2. Disruptions to key frontostriatal loops secondary to pathology in the striatum and pallidum appear to predispose individuals to major neuropsychiatric syndromes; however, treatment can be instituted for a number of these manifestations, which lessens the overall burden of disease in neuroacanthocytosis patients and their families.
Abstract: Background and purpose:  Niemann-Pick disease type C (NPC) is a progressive neurovisceral disorder associated with dystonia, ataxia and a characteristic gaze palsy. Neuropathological studies have demonstrated brainstem atrophy associated with neuronal inclusions and loss, and neurofibrillary tangles, although it is not known whether this pathology can be detected in vivo or how these changes relate to illness variables, particularly ocular-motor changes. Our aim was to utilize a method for brainstem atrophy, validated in progressive supranuclear palsy (PSP), in a group of adult patients with NPC, and explore its relationship to illness variables and ocular-motor functioning. Methods:  We calculated the midbrain and pontine area, and pontine-to-midbrain ratio (PMR) from midsagittal images of 10 adult patients with NPC and 27 age- and gender-matched controls. Measures were correlated with illness variables, and measures of horizontal saccadic functioning. Results:  Pontine-to-midbrain ratio was 14% higher in the NPC group, but this difference was not significant. However, PMR showed a significant positive correlation with duration of illness and a measure of illness severity. Furthermore, PMR was significantly negatively correlated with saccadic peak velocity and gain, and self-paced saccadic performance. Conclusions:  Pontine-to-midbrain ratio was increased in adult patients with NPC compared to controls, although not to the same degree as previously described in PSP, which also presents with significant gaze palsy. These changes were driven predominantly by progressive midbrain atrophy. The strong correlation with illness and ocular-motor variables suggests that it may be a useful marker for illness progression in NPC.
Abstract: Chorea-acanthocytosis (ChAc) is an uncommon autosomal recessive disorder due to mutations of the VPS13A gene, which encodes for the membrane protein chorein. ChAc presents with progressive limb and orobuccal chorea, but there is often a marked dysexecutive syndrome. ChAc may first present with neuropsychiatric disturbance such as obsessive-compulsive disorder (OCD), suggesting a particular role for disruption to striatal structures involved in non-motor frontostriatal loops, such as the head of the caudate nucleus. Two previous studies have suggested a marked reduction in volume in the caudate nucleus and putamen, but did not examine morphometric change. We investigated morphometric change in 13 patients with genetically or biochemically confirmed ChAc and 26 age- and gender-matched controls. Subjects underwent magnetic resonance imaging and manual segmentation of the caudate nucleus and putamen, and shape analysis using a non-parametric spherical harmonic technique. Both structures showed significant and marked reductions in volume compared with controls, with reduction greatest in the caudate nucleus. Both structures showed significant shape differences, particularly in the head of the caudate nucleus. No significant correlation was shown between duration of illness and striatal volume or shape, suggesting that much structural change may have already taken place at the time of symptom onset. Our results suggest that striatal neuron loss may occur early in the disease process, and follows a dorsal-ventral gradient that may correlate with early neuropsychiatric and cognitive presentations of the disease.
Abstract: Despite an increasing number of published voxel based morphometry studies of schizophrenia, there has been no adequate attempt to examine gray (GM) and white matter (WM) abnormalities and the heterogeneity of published findings. In the current article, we used a coordinate based meta-analysis technique to simultaneously examine GM and WM abnormalities in schizophrenia and to assess the effects of gender, chronicity, negative symptoms and other clinical variables. 79 studies meeting our inclusion criteria were included in the meta-analysis. Schizophrenia was associated with GM reductions in the bilateral insula/inferior frontal cortex, superior temporal gyrus, anterior cingulate gyrus/medial frontal cortex, thalamus and left amygdala. In WM analyses of volumetric and diffusion-weighted images, schizophrenia was associated with decreased FA and/or WM in interhemispheric fibers, anterior thalamic radiation, inferior longitudinal fasciculi, inferior frontal occipital fasciculi, cingulum and fornix. Male gender, chronic illness and negative symptoms were associated with more severe GM abnormalities and illness chronicity was associated with more severe WM deficits. The meta-analyses revealed overlapping GM and WM structural findings in schizophrenia, characterized by bilateral anterior cortical, limbic and subcortical GM abnormalities, and WM changes in regions including tracts that connect these structures within and between hemispheres. However, the available findings are biased towards characteristics of schizophrenia samples with poor prognosis.
Abstract: Progressive supranuclear palsy (PSP) is a neurodegenerative disease characterized by gait and postural disturbance, gaze palsy, apathy, decreased verbal fluency and dysexecutive symptoms, with some of these clinical features potentially having origins in degeneration of frontostriatal circuits and the mesencephalon. This hypothesis was investigated by manual segmentation of the caudate and putamen on MRI scans, using previously published protocols, in 15 subjects with PSP and 15 healthy age-matched controls. Midbrain atrophy was assessed by measurement of mid-sagittal area of the midbrain and pons. Shape analysis of the caudate and putamen was performed using spherical harmonics (SPHARM-PDM, University of North Carolina). The sagittal pons area/midbrain area ratio (P/M ratio) was significantly higher in the PSP group, consistent with previous findings. Significantly smaller striatal volumes were found in the PSP group - putamina were 10% smaller and caudate volumes were 17% smaller than in controls after controlling for age and intracranial volume. Shape analysis revealed significant shape deflation in PSP in the striatum, compared to controls; with regionally significant change relevant to frontostriatal and corticostriatal circuits in the caudate. Thus, in a clinically diagnosed and biomarker-confirmed cohort with early PSP, we demonstrate that neostriatal volume and shape are significantly reduced in vivo. The findings suggest a neostriatal and mesencephalic structural basis for the clinical features of PSP leading to frontostriatal and mesocortical-striatal circuit disruption.
Abstract: Cognitive impairment is not uncommon in patients with epilepsy, and may relate to the underlying pathophysiology of epilepsy, the effects of seizures, or epilepsy treatment. Formal neuropsychological testing is not available in many centers, and few cognitive screening tools have been validated in an epilepsy population. We aimed to ascertain the reliability and validity of a multidimensional cognitive screening instrument, the Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG), in a mixed epilepsy population.
Abstract: Although historically gray matter changes have been the focus of neuropathological and neuroradiological studies in schizophrenia, in recent years an increasing body of research has implicated white matter structures and its constituent components (axons, their myelin sheaths and supporting oligodendrocytes). This article summarizes this body of literature, examining neuropathological, neurogenetic and neuroradiological evidence for white matter pathology in schizophrenia. We then look at the possible role that antipsychotic medication may play in these studies, examining both its role as a potential confounder in studies examining neuronal density and brain volume, but also the possible role that these medications may play in promoting myelination through their effects on oligodendrocytes. Finally, the role of potential novel therapies is discussed.
Abstract: Inhalants, frequently abused during adolescence, are neurotoxic to white matter. We investigated the impact of inhalant misuse on the morphology of the corpus callosum (CC), the largest white matter bundle in the brain, in an adolescent sample of inhalant users [n = 14; mean age = 17.3; standard deviation (SD) = 1.7], cannabis users (n = 11; mean age = 19.7; SD = 1.7) and community controls (n = 9; mean age = 19.5; SD = 2.6). We identified significant morphological differences in the CC among inhalant users compared with community controls. There were no morphological differences between inhalant and cannabis users. Our findings may represent the early stages of neurobiological damage associated with chronic inhalant misuse.
Abstract: Variable alterations to the structure of the corpus callosum have been described in adults with NPC, a neurometabolic disorder known to result in both white and gray matter pathology. This study sought to examine the structure of the callosum in a group of adult patients with NPC and compared callosal structure with a group of matched controls, and to relate callosal structure with state and trait illness variables.
Abstract: Hypothalamic-pituitary-adrenal (HPA) axis dysregulation has been reported in bipolar disorder (BD), but previous magnetic resonance imaging (MRI) studies of pituitary gland volume in BD have yielded inconsistent findings. In addition, the contribution of genetic factors to the pituitary changes in BD remains largely unknown.
Abstract: We describe the presentation of an adolescent with juvenile-onset Niemann-Pick disease type C (NPC) who presented with post-ictal psychosis in the context of a developing seizure disorder. After demonstrating mild gait disturbance beginning at the age of 4 years, he was diagnosed with NPC at age 12 on the basis of 95% of cultured fibroblasts staining positive for filipin and a reduced fibroblast cholesterol esterification rate. He then developed a seizure disorder at age 15, where clusters of seizures produced typical psychotic symptoms, including hallucinations and delusions. His seizure disorder responded to valproate, which resulted in a settling of his psychotic symptoms. Whilst post-ictal psychosis is rarely reported prior to the age of 16, NPC in adolescents and adults is particularly psychotogenic and may increase the risk for post-ictal psychosis in the pediatric population.
Abstract: The superior temporal gyrus (STG), especially its lateral portion, and temporal pole (TP) both play a central role in emotional processing, but it remains largely unknown whether patients with major depressive disorder (MDD) exhibit morphologic changes in these regions. We delineated the STG subregions [planum polare (PP), Heschl gyrus (HG), planum temporale (PT), rostral STG, and caudal STG] and TP using magnetic resonance imaging in 29 currently depressed patients (mean age=32.5 years, 7 males), 27 remitted depressed patients (mean age=35.1 years, 9 males), and 33 age- and gender-matched healthy control subjects (mean age=34.0 years, 12 males). Both current and remitted MDD patients showed a significant volume reduction of the left PT and bilateral caudal STG as compared with healthy controls. The TP volume did not differ between the groups. The right PT volume was negatively correlated with total score on the Beck Depression Inventory in the MDD patients as a whole. Medication, presence of melancholia, and comorbidity with anxiety disorders did not affect the TP and STG volumes. These findings suggest that the volume reduction of the STG, but not the TP, may represent enduring brain changes in MDD even after recovery from depression, but right STG volume may also be related to the severity of depressive symptoms.
Abstract: Morphologic changes of cortico-limbic regions have been reported in bipolar disorder, but it remains unclear whether midline brain abnormalities relevant to cortico-limbic connectivity are also present.
Abstract: Functional abnormalities of the superior temporal gyrus (STG) have been implicated in the pathophysiology of bipolar disorder, but magnetic resonance imaging (MRI) studies of this region have yielded inconsistent findings.
Abstract: Frontostriatal circuit mediated cognitive dysfunction has been implicated in frontotemporal lobar degeneration (FTLD), but not Alzheimer's disease, or healthy aging. We measured the neostriatum (caudate nucleus and putamen) volume in FTLD (n=34), in comparison with controls (n=27) and Alzheimer's disease (AD, n=19) subjects.
Abstract: Niemann-Pick disease type C (NPC) is a progressive neurovisceral disorder with disrupted intracellular cholesterol metabolism that results in significant alterations to neuronal and axonal structure. Adult patients present with ataxia, gaze palsy, impaired cognition, and neuropsychiatric illness, but the neural substrate has not been well-characterized in vivo. Our aim was to investigate a well-characterized sample of adults with confirmed NPC for gray and white matter abnormalities.
Abstract: Morphological abnormalities of the superior temporal gyrus have been consistently reported in schizophrenia, but the timing of their occurrence remains unclear.
Abstract: Although several studies have been conducted in an attempt to characterize the phenotype and underlying pathophysiology of individuals with early-onset obsessive-compulsive disorder (OCD), the literature on patients who develop OCD later in life remains sparse.
Abstract: Only a limited number of cognitive screening tools are available for the Persian-speaking population, and we sought to translate and validate the Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG), a multidimensional cognitive screening tool.
Abstract: Previous studies have demonstrated alterations to fronto-limbic circuitry and callosal structure in borderline personality disorder (BPD). We predicted that a first-presentation BPD cohort who demonstrated orbitofrontal cortex (OFC) reductions would show regional reductions in the anterior corpus callosum.
Abstract: Functional neuroimaging studies have implicated the insular cortex in emotional processing, including the evaluation of one's own emotion, as well as in the neurobiology of major depressive disorder (MDD). Nevertheless, it remains largely unknown whether MDD patients exhibit morphologic changes of the insular cortex, and whether such changes reflect state or trait markers of the disorder.
Abstract: This structural magnetic resonance imaging study investigated insular cortex volume in 26 patients with bipolar I disorder and 24 matched controls. While insular volume did not differ between these groups, exploratory analyses demonstrated that the number of depressive episodes correlated negatively with the anterior insular volume in the patients, suggesting it may have a role in the pathophysiology of bipolar disorder.
Abstract: Brain morphologic changes of limbic-cortical regions have been reported in major depressive disorder (MDD). However, it remains largely unknown whether MDD is associated with abnormalities in midline brain structures, which play a critical role in limbic-cortical connectivity, and whether such changes reflect state or trait markers of the disorder. We used magnetic resonance imaging to investigate the length of the adhesio interthalamica (AI) and cavum septum pellucidum (CSP) in 29 currently depressed patients, 27 remitted depressed patients, and 33 age- and gender-matched healthy control subjects. The currently depressed patients had a significantly shorter AI compared with controls, but there was no difference in the AI length between the remitted patients and controls. The AI length in the overall patient group was negatively correlated with the severity of symptoms of "loss of interest" at the time of scanning. Furthermore, the patients with co-morbid anxiety disorders tended to have a shorter AI compared with those without. The CSP length and prevalence of a large CSP (>or=6 mm) did not differ between the groups. Although a comprehensive investigation of medication effects was not possible due to incomplete medication data, these findings suggest that a shorter length of the AI may be associated with state-related brain changes in major depression rather than a stable marker of illness vulnerability. Whether the AI length exhibits ongoing changes across the course of the illness remains to be determined in longitudinal studies.
Abstract: Reductions in the size of the anterior callosum have been described for both first-episode and established schizophrenia and bipolar affective disorder, but never in individuals with psychotic bipolar disorder. We recruited 110 first-episode psychosis subjects (74 schizophrenia spectrum and 36 affective psychosis) and 36 age- and gender-matched controls. The callosum was extracted from a mid-sagittal slice from T1-weighted magnetic resonance images, and total area, length and curvature of the callosum were compared. The schizophrenia-spectrum group showed reductions in thickness of the genu across schizophreniform and schizoaffective disorder and schizophrenia, and the schizoaffective disorder group also showed an increase in thickness in the splenium and isthmus. None of these changes were seen in the affective disorder group, although a non-significant increase in the region of the isthmus and splenium was seen, particularly in the depressed group. Psychotic affective disorders do not show the anterior callosal reductions that are seen in the schizophrenia-spectrum group at first episode. The schizoaffective patients show additional posterior callosal expansions that may be a marker of an affective diathesis. This suggests that schizoaffective disorder may represent two interacting illness processes or be mid-way along a continuum of these two broad categories of illness at first psychosis.
Abstract: The corpus callosum enables the efficient linking of the two cerebral hemispheres. Reductions in the size of the anterior callosum have been described in geriatric depression, although findings in young adults have been much more equivocal.
Abstract: The autosomal recessive disorder Niemannn-Pick type C (NPC) presents in adulthood with psychosis or cognitive deficits associated with supranuclear gaze palsies. While saccadic innervation to the extraocular muscles is generated in the brainstem, the frontal lobes play an integral role in the initiation of volitional saccades and the suppression of unwanted reflexive saccades. No study has examined the frontally driven volitional control of saccadic eye movements in NPC.
Abstract: Brain morphologic changes have been reported in borderline personality disorder (BPD), but it remains largely unknown whether BPD is associated with midline brain abnormalities. We used magnetic resonance imaging to investigate the length of the adhesio interthalamica (AI) and cavum septum pellucidum (CSP) as well as third ventricular volume in 20 teenagers with first-presentation BPD and 20 healthy controls. While the CSP length did not differ between the groups, the AI was significantly shorter in BPD patients than in controls. Furthermore, the BPD patients had a significantly larger third ventricle than controls. These preliminary findings suggest that ongoing neuroimaging studies should further evaluate a potential involvement of midline brain structures in the pathogenesis of BPD.
Abstract: Reductions in the size of the corpus callosum (CC) have been described in patients with bipolar disorder (BD), although the contribution of genetic factors to these changes is unclear. We previously showed a global thinning of the CC in BD patients, and found those with a family history of affective disorders had a larger CC than those without. In this study, we compared callosal size and shape in 180 individuals: 70 with BD, 45 of their first-degree relatives, and 75 healthy controls. The callosum was extracted from a mid-sagittal slice from T1-weighted magnetic resonance images, and its total area, length and curvature were compared across groups. A non-parametric permutation method was used to examine for alterations in width of the callosum along 39 points. Validating our previous findings, a significant global reduction in callosal thickness was seen in BD patients, with a disproportionate thinning in the anterior body. First-degree relatives did not differ in callosal size or shape from controls. In BD patients, duration of illness and age were associated with thinning in the anterior body; BD patients on lithium treatment showed a thicker anterior mid-body than those on other psychotropics. Global and regional thinning of the callosum is seen in BD but not in their first-degree relatives. This suggests that CC abnormalities are linked to disease expression in BD and may not represent a marker of familial predisposition.
Abstract: Spatial working memory (SWM) dysfunction has been suggested as a trait marker of schizophrenia and implicates a diffuse network involving prefrontal, temporal and parietal cortices. However, structural abnormalities in both grey and white matter in relation to SWM deficits are largely unexplored. The current magnetic resonance imaging (MRI) study examined this relationship in a sample of young first-episode schizophrenia (FES) patients using a whole-brain voxel-based method. SWM ability of 21 FES patients and 41 comparable controls was assessed by the CANTAB SWM task. Using an automated morphometric analysis of brain MRI scans, we assessed the relationship between SWM abilities and both grey matter volume and white matter density in both groups. Our findings demonstrated the different directionality of the association between SWM errors and grey matter volume in left frontal regions and white matter tracts connecting these regions with temporal and occipital areas between FES patients and controls. This suggests that the substrate underpinning the normal variability in SWM function in healthy individuals may be abnormal in FES, and that the normal neurodevelopmental processes that drive the development of SWM networks are disrupted in schizophrenia.
Abstract: We describe the differential presentation of schizophrenia-like psychosis in two siblings with the 'variant' biochemical presentation of adult Niemann-Pick disease type C. The male sibling presented with psychosis at age 16 years and cognitive and motor disturbance at age 25 years, whereas his elder sister, sharing the same mutation but showing less severe biochemical, neuroimaging and ocular motor parameters, presented with a similar schizophrenia-like illness with associated cognitive and motor disturbance at age 31 years. Their illness onset, course and response to treatment mirrors the sex dimorphism seen in schizophrenia, and is suggestive of an interaction between the neurobiology of their metabolic disorder and sex differences in neurodevelopment.
Abstract: Callosal structural and functional alterations have been demonstrated in a range of neuropsychiatric illnesses, including bipolar disorder, but no study has examined regional callosal thickness in this phenotype. The aim of the present study was therefore to examine callosal size and shape in a well-defined group of bipolar affective disorder patients and controls.
Abstract: 'Pseudoneurotic schizophrenia' was a diagnostic term coined in the 1940s by Hoch and Polatin. It described a subgroup of patients who presented with prominent anxiety symptoms, which masked a latent psychotic disorder. Pseudoneurotic schizophrenia as a diagnostic entity has fallen out of clinical use.
Abstract: Miglustat has been shown to stabilize disease progression in children, juveniles and adults with Niemann-Pick disease type C (NP-C), a rare genetic disorder characterized by progressive neurological deterioration. We report findings from a retrospective observational cohort study assessing the effects of miglustat on neurological disease progression in patients treated in the clinical practice setting. Data from all NP-C patients prescribed miglustat at 25 expert centers were evaluated using a disease disability scale. The scale analyzed four key parameters of neurological disease progression in NP-C (ambulation, manipulation, language, swallowing). Mean individual parameter scores and a composite score were calculated at baseline (time of diagnosis) and up to 4 follow-up visits. Overall, 66 patients were included (mean [SD] age at diagnosis, 9.7 [7.6] years, and at treatment start, 12.8 [9.5] years). The median (range) miglustat exposure was 1.46 (0.05-4.51) years. Mean annual progression was +0.11 score units/year from diagnosis to treatment start, indicating disease progression prior to therapy, and decreasing to -0.01 score units/year from treatment start to last clinic visit, indicating stabilization. Stabilization of neurological disease on miglustat was observed in all age groups, but the magnitude of the effect was greater in patients diagnosed in late childhood and in juveniles and adults. Stabilization of neurological disease was also observed in a subset of 19 patients with extended pre-treatment information. Overall, these data support previous clinical trial findings indicating clinically relevant beneficial effects of miglustat on neurological disease progression in patients with NP-C.
Abstract: Young patients with frontotemporal dementia (FTD) may present with schizophrenia-like psychosis. Few studies have investigated whether FTD-like neuropathological changes are present in schizophrenia. The purpose of the present study was therefore to determine whether FTD-like abnormalities in TARDNA binding protein (TDP-43) and ubiquitin are detectable in hippocampal dentate gyrus of patients with schizophrenia and bipolar disorder. A secondary objective was to identify clinicopathological relationships of any such abnormalities.
Abstract: Hypothalamic-pituitary-adrenal (HPA) axis dysfunction has been demonstrated in bipolar disorder (BD), but previous magnetic resonance imaging (MRI) studies of pituitary gland volume in BD have reported variable findings. In this MRI study we investigated pituitary volume in 26 patients with established bipolar I disorder (8 males and 18 females, mean age=38.4 years) and 24 matched controls (7 males and 17 females, mean age=38.7 years). The BD patients had a significantly larger pituitary volume as compared with controls, but there was no association between pituitary volume and illness duration, number of manic/depressive episodes, daily medication dosage, family history, or clinical subtype (i.e., psychotic and nonpsychotic). Pituitary volume was larger in females than in males for both groups. These results support previous neuroendocrine findings that implicate HPA axis dysfunction in the core pathophysiological process of BD.
Abstract: Organic solvent abuse is associated with increased risk for serious medical, neurological, and neuropsychological impairments. While animal research suggests that exposure to organic solvents (especially toluene) may be neurotoxic, much less is known about the consequences of long-term exposure in humans. We reviewed neuroimaging and neuropsychological studies examining chronic toluene misuse in humans. Thirty empirical studies fulfilled the inclusion and exclusion criteria, including case studies (n=9) as well as group studies with (n=11) and without a control group (n=10). Our review indicates that toluene preferentially affects white matter (relative to gray matter) structures and periventricular/subcortical (relative to cortical) regions. The lipid-dependent distribution and pharmacokinetic properties of toluene appears to explain the pattern of MRI abnormalities, as well as the common symptoms and signs of toluene encephalopathy. The commonly observed neuropsychological deficits such as impairments in processing speed, sustained attention, memory retrieval, executive function and language, are also consistent with white matter pathology. We discuss the implications of these findings in the context of a neurodevelopmental framework, as well as the neuropathology and pathophysiology of toluene abuse. We also propose a set of recommendations to guide future research in this area.
Abstract: Diffusion Tensor Imaging (DTI) investigations in schizophrenia have provided evidence of impairment in white matter as indicated by reduced fractional anisotropy (FA). However, the neuropathological implications of these findings remain unclear. In the current study, we conducted a voxelwise analysis of the constituent parameters of FA, Axial (lambda(||)) and Radial Diffusivity (lambda( upper left and right quadrants)), in 14 male participants with schizophrenia and 14 age, gender, education, and premorbid intelligence matched healthy controls. Significantly reduced FA and higher Radial Diffusivity were concurrently observed in several major white matter tracts in the schizophrenia group. This finding suggests that the loss of white matter integrity in schizophrenia is the result of demyelination and/or changes to the axonal cytoskeleton rather than gross axonal damage.
Abstract: We describe one male and one female patient who each developed childhood/adolescent obsessive-compulsive disorder as a prelude to the development of a typical picture of chorea-acanthocytosis (ChAc). In each patient, the caudate nucleus showed dramatic atrophy. The role of the caudate in compulsive phenomena, and the predilection for neurological disorders with onset in adolescence to present as major mental illness, is discussed. On the basis of the current evidence and previous findings, we suggest that ChAc can be understood as a disorder whose clinical presentation reflects an interaction between the disease process and the individual's neurodevelopmental stage with both initial interrupted neurodevelopment, and supervening neurodegeneration.
Abstract: Reductions in the size of the anterior callosum have been described for both first-episode schizophrenia-spectrum psychosis and established schizophrenia, but have not been examined in individuals at ultra-high risk for psychosis (UHR). We compared 100 UHR individuals (27 of whom later developed psychosis) with 38 age-matched control subjects on measures of size and shape of the corpus callosum to determine if changes previously demonstrated in first-episode and established schizophrenia are present in the pre-psychotic phase. Each individual's callosum was extracted from the mid-sagittal slice from T1-weighted magnetic resonance images, and total area, length and curvature of the callosum was compared using one-way ANOVA, and 39 regional thicknesses via a non-parametric permutation method to account for non-independence of adjacent measures. Total area, length and curvature did not differ between the groups. Compared to both the UHR-NP group and controls, the UHR-P group showed significant regional reductions in the region of the anterior genu of the callosum. The UHR-NP group did not differ from controls. Positive and negative symptoms did not affect regional thickness in either of the patient groups. Cox regression showed that mean anterior genu thickness was highly predictive of a transition to psychosis. Reductions in the thickness of the anterior callosum differentiate between high-risk individuals who transition to psychosis and those who do not, and is highly predictive of transition. These changes may reflect primary pathology of orbitofrontal and medial frontal cortex, or deficits in anterior interhemispheric myelination.
Abstract: We describe the case of a 23-year-old Caucasian woman who presented with alien hand syndrome and a first episode of the coenesthetic subtype of schizophrenia. 'Alienness' of her non-dominant hand was intimately phenomenologically associated with the onset of first-psychosis. Cerebral MRI revealed a partial agenesis of the corpus callosum with a complete absence of the rostrum, hypoplastic anterior and inferior genu, and a hypoplastic splenium. This case suggests that this syndrome can occur with the development of a functional disconnection syndrome involving the anterior callosum, and in this case the 'second hit' proposed to occur in early adulthood in schizophrenia may have interacted with her earlier neurodevelopmental lesion to result in a combination of psychosis and alien hand syndrome.
Abstract: Grey matter changes have been described in individuals who are pre- and peri-psychotic, but it is unclear if these changes are accompanied by changes in white matter structures.
Abstract: Depressive symptoms occur in approximately one-third of stroke patients. We sought to evaluate whether an integrated model of stroke care and secondary prevention reduced depressive symptomatology in stroke survivors.
Abstract: We sought to identify neurobiological correlates of Melbourne-Sydney rivalry through neuroimaging measures of a key brain region involved in cognitive and emotional regulation.
Abstract: The carer history is an integral part of the assessment of patients with cognitive impairment. We aimed to develop a comprehensive yet concise carer questionnaire, the CogRisk, which captures actuarial risk variables for cognitive impairment in addition to key symptoms suggestive of cognitive decline in a number of cognitive domains, and to then assess its validity and reliability in a neuropsychiatric population.
Abstract: While the adult form of adrenoleukodystrophy (ALD) has been associated with an elevated rate of affective disturbance, the myeloneuropathic form of the disease known as adrenomyeloneuropathy (AMN) has been associated with only occasional cases of major mental illness. Given that cerebral involvement occurs in up to half of AMN sufferers, we hypothesized that rates of mental illness may match those with adult ALD.
Abstract: Patients with mental health disorders frequently have difficulties with their cognitive functioning. Assessment of cognition in this population can be complicated by psychiatric symptomatology, making standard written and verbal assessment methods difficult. In these situations, observations by nursing and allied staff of patients' routine activities provide an important source of information about cognitive ability. The Behavioural Assessment Tool for Cognition and Higher Function (BATCH) was developed to record observations of patients' daily functioning under subheadings that reflect cognitive domains. Its capacity to provide a measure of cognitive function through observational means was assessed in a neuropsychiatric unit.
Abstract: Hashimoto's encephalopathy is a term used to describe an encephalopathy of presumed autoimmune origin characterised by high titres of antithyroid peroxidase antibodies. In a similar fashion to autoimmune thyroid disease, Hashimoto's encephalopathy is more common in women than in men. It has been reported in paediatric, adult and elderly populations throughout the world. The clinical presentation may involve a relapsing and remitting course and include seizures, stroke-like episodes, cognitive decline, neuropsychiatric symptoms and myoclonus. Thyroid function is usually clinically and biochemically normal.Hashimoto's encephalopathy appears to be a rare disorder, but, as it is responsive to treatment with corticosteroids, it must be considered in cases of 'investigation negative encephalopathies'. Diagnosis is made in the first instance by excluding other toxic, metabolic and infectious causes of encephalopathy with neuroimaging and CSF examination. Neuroimaging findings are often not helpful in clarifying the diagnosis. Common differential diagnoses when these conditions are excluded are Creutzfeldt-Jakob disease, rapidly progressive dementias, and paraneoplastic and nonparaneoplastic limbic encephalitis. In the context of the typical clinical picture, high titres of antithyroid antibodies, in particular antithyroid peroxidase antibodies, are diagnostic. These antibodies, however, can be detected in elevated titres in the healthy general population. Treatment with corticosteroids is almost always successful, although relapse may occur if this treatment is ceased abruptly. Other forms of immunomodulation, such as intravenous immune-globulin and plasma exchange, may also be effective. Despite the link to autoimmune thyroid disease, the aetiology of Hashimoto's encephalopathy is unknown. It is likely that antithyroid antibodies are not pathogenic, but titres can be a marker of treatment response. Pathological findings can suggest an inflammatory process, but features of a severe vasculitis are often absent. The links between the clinical pictures, thyroid disease, auto-antibody pattern and brain pathology await further clarification through research. It may be that Hashimoto's encephalopathy will be subsumed into a group of nonvasculitic autoimmune inflammatory meningoencephalopathies. This group may include disorders such as limbic encephalitis associated with voltage-gated potassium channel antibodies. Some authors have suggested abandoning any link to Hashimoto and renaming the condition 'steroid responsive encephalopathy associated with autoimmune thyroiditis' to better reflect current, if limited, understanding of this condition.
Abstract: A wide range of neuropathological abnormalities have been detected in schizophrenia sufferers, and emerging evidence points to neural substrates of connectivity as having a key role in the development of disease. This article reviews the available evidence for white matter pathology in schizophrenia, and examines its possible role as a substrate of impaired connectivity. Neuropathological data is suggestive of abnormalities in glial structure and function, and myelinated structures have also been implicated. A number of studies, particularly using gene array technology, are pointing towards significant disruption in expression of myelination genes. Magnetic resonance imaging has tended to focus on, and detect, more grey than white matter abnormalities, although non-volumetric techniques are suggestive of changes in the microstructure of white matter in schizophrenia. Myelinated structures are an attractive candidate for an anatomical substrate for disconnectivity, and may act synergistically with synaptic changes to result in functional disconnectivity although the relationship between white and grey matter changes in the illness remains unclear.
Abstract: Psychotic symptoms occur in a variety of medical and neurological conditions. The authors describe three young men with a variant form of Niemann-Pick type C disease, a neurodegenerative disorder related to abnormal intracellular cholesterol metabolism, who presented with psychosis in early adulthood. Two patients were treated for schizophrenia for many years prior to a diagnosis of Niemann-Pick type C. The cases presented in this article illustrate the role of changes in both white and gray matter structures in psychosis, and, like the assessments of other neurodevelopmental disorders that predispose toward psychotic presentations, shed light on the underlying pathophysiology of major mental disorders.
Abstract: Schizophrenia-like illnesses occur in a variety of medical and neurological conditions but to date have not been described in association with aceruloplasminemia. Aceruloplasminemia is an autosomal recessive disorder of iron metabolism which leads to iron deposition in the basal ganglia, thalamus, cerebellum and hippocampus and which usually presents in middle age with extrapyramidal symptoms and dementia. We describe a 21-year-old woman on treatment for aceruloplasminemia who presented with schizophrenia-like psychosis and declining function in the absence of neurological signs. Neuropsychological testing showed significant dominant hemisphere deficits. Magnetic resonance imaging showed bilateral iron deposition in the cerebellar dentate nuclei and thalami, frontal atrophy, and periventricular white matter hyperintensities. Functional imaging suggested global hypoperfusion. The clinical, cognitive and imaging findings were not typical for either aceruloplasminemia or schizophrenia alone and the possible relationship between the two disorders is discussed with particular reference to implications for our understanding of schizophrenia.
Abstract: To describe the phenomenology and pathophysiology of complex visual hallucinations (CVH) in various organic states, in particular Charles Bonnet syndrome and peduncular hallucinosis.
Abstract: To examine the validity and reliability of a brief cognitive screen instrument, the Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG), in patients with dementia, major psychiatric disorders and neurological disorders, and to compare its performance with the Mini-Mental State Examination (MMSE).
Abstract: Langerhan's cell histiocytosis (LCH) has been described as a progressive neurological disorder marked by neurological and cognitive decline. The authors here report a case of a childhood LCH sufferer who made a significant recovery of neuropsychological function in the absence of motor recovery in late adolescence. This differential recovery of motor and cognitive functioning may relate to the interaction between LCH and childhood and adolescent neurodevelopmental processes.
