Abstract: BACKGROUND: Although schizotypal traits, such as anhedonia and aberrant perceptions, may increase the risk for schizophrenia-spectrum disorders, little is known about early-life characteristics that predict more pronounced schizotypal traits. AIMS: To examine whether birth size or several other early-life factors that have been previously linked with schizophrenia predict schizotypal traits in adulthood. METHOD: Participants of the Northern Finland 1966 Birth Cohort Study (n = 4976) completed a questionnaire on positive and negative schizotypal traits at the age of 31 years. RESULTS: Lower placental weight, lower birth weight and smaller head circumference at 12 months predicted elevated positive schizotypal traits in women after adjusting for several confounders (P<0.02). Moreover, higher gestational age, lower childhood family socioeconomic status, undesirability of pregnancy, winter/autumn birth, higher birth order and maternal smoking during pregnancy predicted some augmented schizotypal traits in women, some in men and some in both genders. CONCLUSIONS: The results point to similarities in the aetiology of schitzotypal traits and schizophrenia-spectrum disorders.

Abstract: CONTEXT: There is an abundance of data from human genetic studies and animal models that implies a role for the disrupted in schizophrenia 1 gene (DISC1) in the etiology of schizophrenia and other major mental illnesses. OBJECTIVE: To study the effect of previously identified risk alleles of DISC1 on quantitative intermediate phenotypes for psychosis in an unselected population. DESIGN: We examined 41 single-nucleotide polymorphisms within DISC1 and performed tests of association with 4 quantitative phenotypes. SETTING: Academic research. PARTICIPANTS: Individuals from an unselected birth cohort in Finland. Originally, everyone born in the catchment area in 1966 (N = 12 058) was included in the study. Of these, 4651 (38.6%) attended the 31-year follow-up and could be included in the study. MAIN OUTCOME MEASURES: Scores on 4 psychometric instruments selected to function as proxies for positive and negative aspects of psychotic disorders, including the Perceptual Aberration Scale, Revised Social Anhedonia Scale, Revised Physical Anhedonia Scale, and Schizoidia Scale by Golden and Meehl. RESULTS: Carriers of the minor allele of marker rs821577 had significantly higher scores on social anhedonia (P < .001). The minor allele of marker rs821633 was strongly associated with lower scores on social anhedonia when analyzed dependent on the absence of the minor alleles of markers rs1538979 and rs821577 (P < .001). CONCLUSIONS: Variants in DISC1 affect the level of social anhedonia, a cardinal symptom of schizophrenia in the general population. DISC1 might be more central to human psychological functioning than previously thought, as it seems to affect the degree to which people enjoy social interactions.

Abstract: Social reward dependence (RD) in humans is a stable pattern of attitudes and behaviour hypothesized to represent a favourable disposition towards social relationships and attachment as a personality dimension. It has been theorized that this long-term disposition to openness is linked to the capacity to process primary reward. Using brain structure measures from magnetic resonance imaging, and a measure of RD from Cloninger's temperament and character inventory, a self-reported questionnaire, in 41 male subjects sampled from a general population birth cohort, we investigated the neuro-anatomical basis of social RD. We found that higher social RD in men was significantly associated with increased gray matter density in the orbitofrontal cortex, basal ganglia and temporal lobes, regions that have been previously shown to be involved in processing of primary rewards. These findings provide evidence for a brain structural disposition to social interaction, and that sensitivity to social reward shares a common neural basis with systems for processing primary reward information.

Abstract: Baseline activity of resting state brain networks (RSN) in a resting subject has become one of the fastest growing research topics in neuroimaging. It has been shown that up to 12 RSNs can be differentiated using an independent component analysis (ICA) of the blood oxygen level dependent (BOLD) resting state data. In this study, we investigate how many RSN signal sources can be separated from the entire brain cortex using high dimension ICA analysis from a group dataset. Group data from 55 subjects was analyzed using temporal concatenation and a probabilistic independent component analysis algorithm. ICA repeatability testing verified that 60 of the 70 computed components were robustly detectable. Forty-two independent signal sources were identifiable as RSN, and 28 were related to artifacts or other noninterest sources (non-RSN). The depicted RSNs bore a closer match to functional neuroanatomy than the previously reported RSN components. The non-RSN sources have significantly lower temporal intersource connectivity than the RSN (P < 0.0003). We conclude that the high model order ICA of the group BOLD data enables functional segmentation of the brain cortex. The method enables new approaches to causality and connectivity analysis with more specific anatomical details. Hum Brain Mapp, 2009. (c) 2009 Wiley-Liss, Inc.

Abstract: AIMS: Higher rates of psychiatric morbidity among non-participants may lead to biased estimates of prevalence and incidence in epidemiological studies of psychiatric disorders. We had a unique opportunity to explore psychiatric morbidity and non-participation in a large epidemiological survey including questionnaires and a clinical examination. METHODS: Members of the Northern Finland 1966 Birth Cohort were included in the study. In phase I, a postal questionnaire was mailed to all those with a known address in 1997 (N=11,540). In phase II, all subjects living in northern Finland or the Helsinki area (N=8,463) were invited to a clinical examination. In phase III, clinical examination participants were given a questionnaire with psychological subscales to be filled in at home and returned by mail. The data on hospital-treated psychiatric disorders were obtained from the Finnish Hospital Discharge Register. Educational level was obtained from Statistics Finland. RESULTS: The participation rates were 76%, 71% and 61% in phases I, II and III, respectively. Subjects with any psychiatric disorder participated less actively than those without any psychiatric disorder in all phases, in both genders and at all educational levels. Participation was not found to vary across specific disorders. Gender or education did not explain the association of psychiatric disorders with participation. CONCLUSIONS: Owing to non-participation, the true prevalence of psychiatric disorders may be higher than the prevalence estimated from epidemiological field surveys.

Abstract: The aim of the study was to explore whether there is an association between body size at birth measured by birth weight and ponderal index and later depression at the age of 31 years. The analyses were based on 4,007 males and 4,332 females born in 1966 in the two northernmost provinces of Finland with data on current depression measured by the Hopkins Symptom Checklist-25 questionnaire (HSCL-25) and self-reported physician-diagnosed lifetime depression at 31 years and childhood characteristics. The associations between birth measures and later depression were analysed with several confounding factors including maternal depression during pregnancy. Low birth measures did not associate with adult depression in men or women. Women with high birth weight (>or=4,500 g) had a higher risk for current depression compared to women with birth weight 3,000 g-3,499 g. Women with high ponderal index (the highest 90-95 percentiles and >or=95 percentiles) had a 1.53-1.55 higher likelihood for current depression compared with women with normal ponderal index. Based on this study, large body size at birth may be a risk factor for later depression.

Abstract: Although the genetic determinants of personality have been intensively investigated especially since Cloninger proposed his psychobiological model of temperament and character, findings to date remain inconclusive and very few studies have addressed the topic in large population cohorts. In the current study we investigated one gene family in its entirety by addressing the role of all known dopamine receptor genes, DRD1-DRD5, on Cloninger's temperament traits in a Finnish population-based birth cohort. The study sample (n = 1,434) was ascertained from the Northern Finland Birth Cohort 1966 with over 5,000 study individuals tested at the age of 31 years. We utilized the genetic homogeneity and genealogical structure of this population to uncover putative effects of these genes on temperament traits at the population level. Our strategy utilizing a large birth cohort and its well established genealogical structure represents an optimal design for studying normally distributed traits. We also wished to provide a comprehensive view to one biologically relevant gene family instead of testing single candidate genes. We report evidence of association of several SNPs at the 5' end of dopamine receptor D2 (DRD2) with Novelty seeking (low) and Harm avoidance (high), and at the 3' end of DRD2 with Persistence. The strongest evidence of association emerged from females. Our study supports the involvement of the dopamine pathway in temperament traits, in particular underlining the role of DRD2 in Novelty seeking, Harm avoidance and Persistence. (c) 2008 Wiley-Liss, Inc.

Abstract: Biased recruitment and sample selection may cause variability in neuroimaging studies. Epidemiologically principled population-based magnetic resonance imaging (MRI) studies of schizophrenia are very rare. We gathered structural MRI data on 154 subjects from the Northern Finland 1966 Birth Cohort, aged 33-35 (100 controls, 54 schizophrenia patients). Regional differences in density of gray matter, white matter, and cerebrospinal fluid (CSF) were identified between groups using nonparametric statistical analysis, and the relationship of the regional differences to duration of illness was explored. Gray matter reductions were found bilaterally in the cerebellum, thalamus, basal ganglia, middle frontal gyrus, inferior frontal gyrus, precentral gyrus, insula, superior temporal gyrus, fusiform gyrus, parahippocampal gyrus, cuneus, and lingual gyrus; in the left posterior cingulate, superior frontal gyrus, transverse temporal gyrus, and precuneus; and in the right postcentral gyrus. Gray matter excesses were observed bilaterally in the basal ganglia, anterior cingulate, and medial orbitofrontal cortices. There were white matter deficits in an extensive network including inter- and intrahemispheric tracts bilaterally in the frontal, temporal, parietal, and occipital lobes, subcortical structures, cerebellum, and brain stem. CSF excesses were found bilaterally in the lateral ventricles, third ventricle, interhemispheric, and left Sylvian fissure. We replicated the previous findings of structural brain abnormalities in schizophrenia on a general population level. Gray and white matter deficits were associated with duration of illness suggesting either that developmental brain deficits relate to an earlier age of onset or that brain abnormalities in schizophrenia are progressive in nature.

Abstract: The objective of this study was to describe the temperament dimension profiles assessed by the Temperament and Character Inventory (TCI) among young adults with the DSM-III-R personality disorder (PD). Our hypothesis was that PD clusters and separate PDs can be distinguished from one another by their specific temperament profiles. As a part of the 31-year follow-up survey of the prospective Northern Finland 1966 Birth Cohort, the cohort members living in the city of Oulu at the age of 31 years (n=1609) were invited to participate in a two-phase field study. The Structured Clinical Interview for DSM-III-R for PDs (SCID-II) was used as diagnostic instrument. The final study sample consisted of the 1311 subjects who had completed the Hopkins Symptom Check List-25 questionnaire for screening and had given a written informed consent. Of the 321 SCID interviewed subjects, 74 met the criteria for at least one PD and had completed the TCI. The mean TCI scores of subjects with PD and control subjects without PD (n=910) were compared. Low Novelty Seeking, high Harm Avoidance and low Reward Dependence characterized cluster A and C PDs. Subjects with a cluster B PD did not differ from controls, except for Novelty Seeking, which was high. The temperament dimensions could not distinguish different PDs very well, with the only exception of persons with obsessive-compulsive PD. PD clusters were associated with different profiles of temperament, lending some support for Cloninger's typology.