Abnormalities in the connectivity of white-matter (WM) tracts in schizophrenia are supported by evidence from post-mortem investigations, functional and structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). The aims of this study were to explore the microstructural changes in first-episode schizophrenia in a Han Chinese population and to investigate whether a family history of psychiatric disorder is related to the severity of WM tract integrity abnormalities in these patients.

T1-weighted MR and DT images were collected in 68 patients with first-episode schizophrenia [22 with a positive family history (PFH) and 46 with a negative family history (NFH)] and 100 healthy controls. Voxel-based analysis was performed and WM integrity was quantified by fractional anisotropy (FA). Cluster- and voxel-level analyses were performed by using two-sample t tests between patients and controls and/or using a full factorial model with one factor and three levels among the three sample groups (patients with PFH or NFH, and controls), as appropriate.

FA deficits were observed in the patient group, especially in the left temporal lobe and right corpus callosum. This effect was more severe in the non-familial schizophrenia than in the familial schizophrenia subgroup.

Overall, these findings support the hypothesis that loss of WM integrity may be an important pathophysiological feature of schizophrenia, with particular implications for brain dysmaturation in non-familial and familial schizophrenia.

This study prospectively examined the natural clinical course of six anxiety disorders over 7 years of follow-up in individuals with personality disorders (PDs) and/or major depressive disorder. Rates of remission, relapse, new episode onset and chronicity of anxiety disorders were examined for specific associations with PDs.

Participants were 499 patients with anxiety disorders in the Collaborative Longitudinal Personality Disorders Study, who were assessed with structured interviews for psychiatric disorders at yearly intervals throughout 7 years of follow-up. These data were used to determine probabilities of changes in disorder status for social phobia (SP), generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), panic disorder and panic disorder with agoraphobia.

Estimated remission rates for anxiety disorders in this study group ranged from 73% to 94%. For those patients who remitted from an anxiety disorder, relapse rates ranged from 34% to 67%. Rates for new episode onsets of anxiety disorders ranged from 3% to 17%. Specific PDs demonstrated associations with remission, relapse, new episode onsets and chronicity of anxiety disorders. Associations were identified between schizotypal PD with course of SP, PTSD and GAD; avoidant PD with course of SP and OCD; obsessive-compulsive PD with course of GAD, OCD, and agoraphobia; and borderline PD with course of OCD, GAD and panic with agoraphobia.

Findings suggest that specific PD diagnoses have negative prognostic significance for the course of anxiety disorders underscoring the importance of assessing and considering PD diagnoses in patients with anxiety disorders.

One third of referrals from primary to secondary care are for medically unexplained symptoms (MUS). We aimed to determine the association of depression and anxiety disorders with high use of specialist services by patients with MUS. We did this by comparing their prevalence in patients who had been repeatedly referred with symptoms for which they had received repeated specialist diagnoses of MUS with that in two control groups. We also determined the adequacy of treatment received.

A case-control study in five general practices in Edinburgh, UK. Data collection was by case note review and questionnaire. Cases were 193 adults with three or more referrals over 5 years, at least two of which resulted in a diagnosis of MUS. Controls were: (a) patients referred only once over 5 years (n=152); (b) patients with three or more referrals for symptoms always diagnosed as medically explained (n=162).

In total, 93 (48%) of the cases met our criteria for current depression, anxiety or panic disorders. This compared with 38 (25%) and 52 (35.2%) of the control groups; odds ratios (95% confidence intervals) of 2.6 (1.6–4.1) and 1.6 (1.01–2.4), respectively. Almost half (44%) of the cases with current depression or anxiety had not received recent minimum effective therapy.

Depression, anxiety and panic disorders are common in patients repeatedly referred to hospital with MUS. Improving the recognition and treatment of these disorders in these patients has the potential to provide better, more appropriate and more cost-effective medical care.

A cross-sectional study was conducted in participants with schizophrenia to explore a potential association between the patients' remission status and neurocognitive functioning and to examine whether these factors have an impact on functional outcome.

Psychopathological symptoms were rated by means of the Positive and Negative Syndrome Scale with symptom remission being assessed by applying the severity component of the recently proposed remission criteria. Tests for the cognitive battery were selected to cover domains known to be impaired in patients with schizophrenia. Next to pre-morbid intelligence, attention performance, executive functioning, verbal fluency, verbal learning and memory, working memory and visual memory were assessed. The joint effect of remission status and neurocognitive functioning on treatment outcome was investigated by logistic regression analysis.

Out of 140 patients included in the study, 62 were symptomatically remitted. Mean age, education and sex distribution were comparable in remitted and non-remitted patients. Remitted patients showed significantly higher values on tests of verbal fluency, alertness and optical vigilance. Both symptomatic remission as well as performance on tests of working memory and verbal memory had a significant effect on the patients' employment status.

In the present study neuropsychological measures of frontal lobe functioning were associated with symptomatic remission from schizophrenia. In addition, both symptomatic remission and performance on tests of working memory and verbal memory had a significant effect on the patients' employment status. Longitudinal follow-up data are needed to determine how the associations of these determinants of functional outcome interact and change over time.

Etiological theory and prior research with small or selected samples suggest that interpersonal violence clusters in families. However, the strength and pattern of this aggregation remains mostly unknown.

We investigated all convictions for violent crime in Sweden 1973–2004 among more than 12.5 million individuals in the nationwide Multi-Generation Register, and compared rates of violent convictions among relatives of violent individuals with relatives of matched, non-violent controls, using a nested case–control design.

We found strong familial aggregation of interpersonal violence among first-degree relatives [e.g. odds ratio (OR)sibling 4.3, 95% confidence interval (CI) 4.2–4.3], lower for more distant relatives (e.g. ORcousin 1.9, 95% CI 1.9–1.9). Risk patterns across biological and adoptive relations provided evidence for both genetic and environmental influences on the development of violent behavior. Familial risks were stronger among women, in higher socio-economic strata, and for early onset interpersonal violence. There were crime-specific effects (e.g. ORsibling for arson 22.4, 95% CI 12.2–41.2), suggesting both general and subtype-specific familial risk factors for violent behavior.

The observed familiality should be accounted for in criminological research, applied violence risk assessment, and prevention efforts.

The cerebellum is rich in cannabinoid receptors and implicated in the neuropathology of schizophrenia. Long-term cannabis use is associated with functional and structural brain changes similar to those evident in schizophrenia, yet its impact on cerebellar structure has not been determined. We examined cerebellar grey and white matter in cannabis users with and without schizophrenia.

Seventeen patients with schizophrenia and 31 healthy controls were recruited; 48% of the healthy group and 47% of the patients were long-term heavy cannabis users (mean 19.7 and 17.9 years near daily use respectively). Cerebellar measures were extracted from structural 3-T magnetic resonance imaging (MRI) scans using semi-automated methods, and examined using analysis of covariance (ANCOVA) and correlational analyses.

Cerebellar white-matter volume was reduced in cannabis users with and without schizophrenia compared to healthy non-users, by 29.7% and 23.9% respectively, and by 17.7% in patients without cannabis use. Healthy cannabis users did not differ in white-matter volume from either of the schizophrenia groups. There were no group differences in cerebellar grey matter or total volumes. Total cerebellar volume decreased as a function of duration of cannabis use in the healthy users. Psychotic symptoms and illness duration correlated with cerebellar measures differentially between patients with and without cannabis use.

Long-term heavy cannabis use in healthy individuals is associated with smaller cerebellar white-matter volume similar to that observed in schizophrenia. Reduced volumes were even more pronounced in patients with schizophrenia who use cannabis. Cannabis use may alter the course of brain maturational processes associated with schizophrenia.

The anxiety disorders are robust correlates/predictors of suicidal ideation, but it is unclear whether (a) the anxiety disorders are specifically associated with suicidal ideation or (b) the association is due to co-morbidity with depression and other disorders. One means of modeling co-morbidity is through the personality traits neuroticism/negative emotionality (N/NE) and extraversion/positive emotionality (E/PE), which account for substantial shared variance among the internalizing disorders. The current study examines the association between the internalizing disorders and suicidal ideation, after controlling for co-morbidity via N/NE and E/PE.

The sample consisted of 327 psychiatric out-patients. Multiple self-report and interview measures were collected for internalizing disorders [depression, generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD), social anxiety, panic and specific phobia] and suicidal ideation, as well as self-report measures for N/NE and E/PE. A model was hypothesized in which each disorder and suicidal ideation was regressed on N/NE, and depression and social anxiety were regressed on E/PE. Structural equation modeling (SEM) was used to examine the unique association of suicidality with each disorder, beyond shared variance with N/NE and E/PE.

The hypothesized model was an acceptable fit to the data. Although zero-order analyses indicated that suicidal ideation was moderately to strongly correlated with all of the disorders, only depression and PTSD remained significantly associated with suicidal ideation in the SEM analyses.

In a latent variable model that accounts for measurement error and a broad source of co-morbidity, only depression and PTSD were uniquely associated with suicidal ideation; panic, GAD, social anxiety and specific phobia were not.

Recent neurodevelopmental models of schizophrenia, together with substantial evidence of neurocognitive dysfunction among people with schizophrenia, have led to a widespread view that general cognitive deficits are a central aspect of schizophrenic pathology. However, the temporal relationships between intellectual functioning and schizophrenia-spectrum illness remain unclear.

Longitudinal data from the Copenhagen High-Risk Project (CHRP) were used to evaluate the importance of intellectual functioning in the prediction of diagnostic and functional outcomes associated with the schizophrenia spectrum. The effect of spectrum illness on intellectual and educational performance was also evaluated. The sample consisted of 311 Danish participants: 99 at low risk, 155 at high risk, and 57 at super-high risk for schizophrenia. Participants were given intellectual [Weschler's Intelligence Scale for Children (WISC)/Weschler's Adult Intelligence Scale (WAIS)] assessments at mean ages of 15 and 24 years, and diagnostic and functional assessments at mean ages 24 and 42 years.

Intellectual functioning was found to have no predictive relationship to later psychosis or spectrum personality, and minimal to no direct relationship to later measures of work/independent living, psychiatric treatment, and overall severity. No decline in intellectual functioning was associated with either psychosis or spectrum personality.

These largely negative findings are discussed in the light of strong predictive relationships existing between genetic risk, diagnosis and functional outcomes. The pattern of predictive relationships suggests that overall cognitive functioning may play less of a role in schizophrenia-spectrum pathology than is widely believed, at least among populations with an evident family history of schizophrenia.

We present the incidence and risk factors for major depressive disorder (MDD) among community-dwelling elderly Nigerians.

A cohort study of persons aged ⩾65 years residing in eight contiguous Yoruba-speaking states in south-west and north-central Nigeria was conducted between November 2003 and December 2007. Of the 2149 baseline sample, 1408 (66%) were successfully followed up after approximately 39 months. Face-to-face in-home assessments were conducted with the World Health Organization (WHO) Composite International Diagnostic Interview, version 3 (CIDI.3) and diagnosis was based on the DSM-IV. Incident MDD was determined in the group with no prior lifetime history of MDD at baseline and who were free of dementia at follow-up (n=892).

During the follow-up period, 308 persons had developed incident MDD, representing a rate of 104.3 [95% confidence interval (CI) 93.3–116.6] per 1000 person-years. Compared to males, the age-adjusted hazard for females was 1.63 (95% CI 1.30–2.06). Lifetime or current subsyndromal symptoms of depression at baseline did not increase the risk of incident MDD. Among females, but not males, rural residence and poor social network were risk factors for incident MDD. Physical health status at baseline did not predict new onset of MDD.

The finding of a high incidence of MDD among elderly Nigerians complements earlier reports of a high prevalence of the disorder in this understudied population. Social factors, in particular those relating to social isolation, constitute a risk for incident MDD.

The Met allele of the catechol-O-methyltransferase (COMT) valine-to-methionine (Val158Met) polymorphism is known to affect dopamine-dependent affective regulation within amygdala–prefrontal cortical (PFC) networks. It is also thought to increase the risk of a number of disorders characterized by affective morbidity including bipolar disorder (BD), major depressive disorder (MDD) and anxiety disorders. The disease risk conferred is small, suggesting that this polymorphism represents a modifier locus. Therefore our aim was to investigate how the COMT Val158Met may contribute to phenotypic variation in clinical diagnosis using sad facial affect processing as a probe for its neural action.

We employed functional magnetic resonance imaging to measure activation in the amygdala, ventromedial PFC (vmPFC) and ventrolateral PFC (vlPFC) during sad facial affect processing in family members with BD (n=40), MDD and anxiety disorders (n=22) or no psychiatric diagnosis (n=25) and 50 healthy controls.

Irrespective of clinical phenotype, the Val158 allele was associated with greater amygdala activation and the Met158 allele with greater signal change in the vmPFC and vlPFC. Signal changes in the amygdala and vmPFC were not associated with disease expression. However, in the right vlPFC the Met158 allele was associated with greater activation in all family members with affective morbidity compared with relatives without a psychiatric diagnosis and healthy controls.

Our results suggest that the COMT Val158Met polymorphism has a pleiotropic effect within the neural networks subserving emotional processing. Furthermore the Met158 allele further reduces cortical efficiency in the vlPFC in individuals with affective morbidity.

The aim of this study was to investigate the distribution of the regional cerebral blood flow (rCBF) in occupational-related post-traumatic stress disorder (PTSD) subjects and to seek possible correlations between brain perfusion and self-rating scales (SRS) in order to cross-check their diagnostic value and to look for their neural correlates.

A total of 13 traumatized underground and long-distance train drivers developing (S) and 17 not developing (NS) PTSD who had experienced a ‘person under train’ accident or who had been assaulted at work underwent clinical assessment and 99mTc-HMPAO SPECT imaging during autobiographical trauma scripts. Statistical parametric mapping was applied to analyse rCBF changes in S as compared with NS and to search for correlations between rCBF and the administered SRS scores, modelling age, months to SPECT and the ratio ‘grey matter/intra-cranial volume’ as nuisance variables.

Significantly higher activity was observed during trauma script in left posterior and anterior insula, posterior cingulate, inferior parietal lobule, precuneus, caudate and putamen in PTSD subjects as compared with the trauma-exposed control group. Impact of Event Scale and World Health Organisation (10) Well-Being Index scores highly correlated with tracer uptake to a great extent in the same regions in which rCBF differences between S and NS were found.

These findings support the involvement of insular, cingulate and parietal cortices (as well as the basal ganglia) in the pathogenesis of PTSD and in the processing of related subjective well-being and distress.

Elevated levels of circulating C-reactive protein (CRP) have been associated with coronary heart disease and, in some studies, depression. Most studies have been of populations selected by age and/or gender. We investigate these associations with depression, myocardial infarction (MI), or both, in a large general population sample.

A cross-sectional population study of 9258 women and men aged ⩾20 years. The study included clinical examination, self-report of MI and depression and factors known to confound their associations. The Hospital Anxiety and Depression Scale was used to assess severity of depressive symptoms. Elevated high sensitive-CRP was defined as values >2.2 mg/l.

The association of elevated CRP with depression was attenuated towards the null [from odds ratio (OR) 1.28, p=0.001 to OR 1.08, p=0.388] following extensive adjustment, while associations with MI (adjusted OR 1.42, p=0.032) and co-morbid MI and depression (adjusted OR 2.66, p=0.003) persisted. Confounders associated with elevated CRP levels were smoking (OR 1.66; p<0.001), chronic physical illness (OR 1.34, p<0.001), BMI ⩾30 (OR 1.13, p<0.001), employment (OR 0.70, p<0.001) and high coffee consumption (OR 0.83, p=0.017). Interaction tests indicated a lower effect of old age (OR 0.54, p<0.001) and smoking (OR 0.63, p<0.001) on elevated CRP levels in women compared with men.

CRP levels were raised in those with MI and co-morbid MI and depression; the positive association with depression was explained by confounding factors. We found new evidence that might help understand gender-specific patterns. Future studies should explore the neurobiological mechanisms underpinning these interrelations and their relevance for treatment of these conditions.

Certain aspects of sleep co-occur with externalizing behaviours in youth, yet little is known about these associations in adults. The present study: (1) examines the associations between diurnal preference (morningness versus eveningness), sleep quality and externalizing behaviours; (2) explores the extent to which genetic and environmental influences are shared between or are unique to these phenotypes; (3) examines the extent to which genetic and environmental influences account for these associations.

Questionnaires assessing diurnal preference, sleep quality and externalizing behaviours were completed by 1556 young adult twins and siblings.

A preference for eveningness and poor sleep quality were associated with greater externalizing symptoms [r=0.28 (95% CI 0.23–0.33) and 0.34 (95% CI 0.28–0.39), respectively]. A total of 18% of the genetic influences on externalizing behaviours were shared with diurnal preference and sleep quality and an additional 14% were shared with sleep quality alone. Non-shared environmental influences common to the phenotypes were small (2%). The association between diurnal preference and externalizing behaviours was mostly explained by genetic influences [additive genetic influence (A)=80% (95% CI 0.56–1.01)], as was the association between sleep quality and externalizing behaviours [A=81% (95% CI 0.62–0.99)]. Non-shared environmental (E) influences accounted for the remaining variance for both associations [E=20% (95% CI −0.01 to 0.44) and 19% (95% CI 0.01–0.38), respectively].

A preference for eveningness and poor sleep quality are moderately associated with externalizing behaviours in young adults. There is a moderate amount of shared genetic influences between the phenotypes and genetic influences account for a large proportion of the association between sleep and externalizing behaviours. Further research could focus on identifying specific genetic polymorphisms common to both sleep and externalizing behaviours.

Neuroimaging research has demonstrated medial prefrontal cortex (mPFC) hyporesponsivity and amygdala hyperresponsivity to trauma-related or emotional stimuli in post-traumatic stress disorder (PTSD). Relatively few studies have examined brain responses to the recollection of stressful, but trauma-unrelated, personal events in PTSD. In the current study, we sought to determine whether regional cerebral blood flow (rCBF) abnormalities in mPFC and amygdala in PTSD could be observed during the recollection of trauma-unrelated stressful personal events.

Participants were 35 right-handed male combat veterans (MCVs) and female nurse veterans (FNVs) who served in Vietnam: 17 (seven male, 10 female) with current military-related PTSD and 18 (nine male, nine female) with no current or lifetime PTSD. We used positron emission tomography (PET) and script-driven imagery to study rCBF during the recollection of trauma-unrelated stressful versus neutral and traumatic events.

Voxelwise tests revealed significant between-group differences for the trauma-unrelated stressful versus neutral comparison in mPFC, specifically in the anterior cingulate cortex (ACC). Functional region of interest (ROI) analyses demonstrated that this interaction in mPFC represented greater rCBF decreases in the PTSD group during trauma-unrelated stressful imagery relative to neutral imagery compared to the non-PTSD group. No differential amygdala activation was observed between groups or in either group separately.

Veterans with PTSD, compared to those without PTSD, exhibited decreased rCBF in mPFC during mental imagery of trauma-unrelated stressful personal experiences. Functional neuroanatomical models of PTSD must account for diminished mPFC responses that extend to emotional stimuli, including stressful personal experiences that are not directly related to PTSD.

An intrinsic cerebral network comprising the anterior cingulate and anterior insula (the salience network) is considered to play an important role in salience detection in healthy volunteers. Aberrant salience has been proposed as an important mechanism in the production of psychotic symptoms such as delusions and hallucinations (reality distortion). We investigated whether structural deficits in the salience network are associated with the reality distortion seen in schizophrenia.

A sample of 57 patients in a clinically stable state of schizophrenia and 41 controls were studied with high-resolution magnetic resonance imaging.

Bilateral volume reduction was seen in the anterior cingulate and anterior insula in patients with schizophrenia. Reduced volume in the two left-sided regions of the salience network was significantly correlated with the severity of reality distortion.

These findings suggest that a deficit of grey matter in the salience network leads to an impaired attribution of salience to stimuli that is associated with delusions and hallucinations in schizophrenia.

Genetic and environmental factors are important in the etiology of substance use. However, little is known about the stability of these factors across development. We aimed to answer three crucial questions about this etiology that have never been addressed in a single study: (1) Is there a general vulnerability to substance consumption from early adolescence to young adulthood? (2) If so, do the genetic and environmental influences on this vulnerability change across development? (3) Do these developmental processes differ in males and females?

Subjects included 1480 twin pairs from the Swedish Twin Study of Child and Adolescent Development who have been followed since 1994. Prospective, self-reported regular smoking, alcohol intoxication and illicit drug use were assessed at ages 13–14, 16–17 and 19–20 years. Structural modeling was performed with the program Mx.

An underlying common factor accounted for the association between smoking, alcohol and illicit drug consumption for the three age groups. Common genetic and shared environmental effects showed substantial continuity. In general, as participants aged, the influence of the shared environment decreased, and genetic effects became more substance specific in their effect.

The current report answers three important questions in the etiology of substance use. The genetic and environmental risk for substance consumption is partly mediated through a common factor and is partly substance specific. Developmentally, evidence was strongest for stability of common genetic effects, with less evidence for genetic innovation. These processes seem to be the same in males and females.

Relatives of schizophrenia patients demonstrate abnormalities in prefrontal cortical activation during executive processing as measured by functional neuroimaging, albeit not consistently. A meta-analysis was conducted to determine whether reliable patterns of brain hypo- and hyperactivity, especially in the middle frontal region, were present in the relatives of patients.

Seventeen studies, containing 18 samples of relatives and controls, were included in this meta-analysis. Studies were included if relatives of schizophrenia patients were compared to controls, an executive processing task was used, and standard space coordinates were reported for the functional activations. Activation likelihood estimation (ALE) was implemented to find convergence across functional neuroimaging experiment coordinates. A separate analysis was conducted to assess the potential impact of a priori hypothesis testing used in region-of-interest (ROI) approaches on the meta-analysis results.

Relatives demonstrated hypo- and hyperactivity in statistically overlapping right middle frontal regions [Brodmann area (BA) 9/10]. Use of an ROI analysis that a priori focused on prefrontal regions resulted in more findings of reduced activity in the middle frontal region.

The cortical regions identified by this meta-analysis could potentially serve as intermediate biological markers in the search for candidate genes for schizophrenia. As neurocognitive deficits are related to functional impairments in patients, a better understanding of neural and genetic vulnerabilities would be beneficial in our efforts to remediate these important deficits.

Understanding how common mental disorders such as anxiety and depression vary with socio-economic circumstances as people age can help to identify key intervention points. However, much research treats these conditions as a single disorder when they differ significantly in terms of their disease burden. This paper examines the socio-economic pattern of anxiety and depression separately and longitudinally to develop a better understanding of their disease burden for key social groups at different ages.

The Twenty-07 Study has followed 4510 respondents from three cohorts in the West of Scotland for 20 years and 3846 respondents had valid data for these analyses. Hierarchical repeated-measures models were used to investigate the relationship between age, social class and the prevalence of anxiety and depression over time measured as scores of 8 or more out of 21 on the relevant subscale of the Hospital Anxiety and Depression Scale (HADS).

Social class differences in anxiety and depression widened with age. For anxiety there was a nonlinear decrease in prevalence with age, decreasing more slowly for those from manual classes compared to non-manual, whereas for depression there was a non-linear increase in prevalence with age, increasing more quickly for those from manual classes compared to non-manual. This relationship is robust to cohort, period and attrition effects.

The more burdensome disorder of depression occurs more frequently at ages where socio-economic inequalities in mental health are greatest, representing a ‘double jeopardy’ for older people from a manual class.

Movement disorders and schizotypy are both prevalent in unaffected siblings of patients with schizophrenia and both are associated with the risk of developing psychosis or schizophrenia. However, to date there has been no research into the association between these two vulnerability factors in persons with an increased genetic risk profile. We hypothesized that unaffected siblings of patients with non-affective psychosis have more movement disorders and schizotypy than healthy controls and that these co-occur.

In a cross-sectional design we assessed the prevalence and inter-relationship of movement disorders and schizotypy in 115 unaffected siblings (mean age 27 years, 44% males) and 100 healthy controls (mean age 26 years, 51% males). Movement disorders were measured with the Abnormal Involuntary Movement Scale (AIMS), the Unified Parkinson Disease Rating Scale (UPDRS), the Barnes Akathisia Rating Scale (BARS), and one separate item for dystonia. Schizotypy was assessed with the Structured Interview for Schizotypy – Revised (SIS-R).

There were significant differences in the prevalence of movement disorders in unaffected siblings versus healthy controls (10% v. 1%, p<0.01) but not in the prevalence of schizotypy. Unaffected siblings with a movement disorder displayed significantly more positive and total schizotypy (p=0.02 and 0.03 respectively) than those without. In addition, dyskinesia correlated with positive schizotypy (r=0.51, p=0.02).

The association between movement disorders (dyskinesia in particular) with positive and total schizotypy in unaffected siblings suggests that certain vulnerability factors for psychosis or schizophrenia cluster in a subgroup of subjects with an increased genetic risk of developing the disease.

The thickness of the cortical mantle is a sensitive measure for identifying alterations in cortical structure. We aimed to explore whether first episode schizophrenia patients already show a significant cortical thinning and whether cortical thickness anomalies may significantly influence clinical and cognitive features.

We investigated regional changes in cortical thickness in a large and heterogeneous sample of schizophrenia spectrum patients (n=142) at their first break of the illness and healthy controls (n=83). Magnetic resonance imaging brain scans (1.5 T) were obtained and images were analyzed by using brains2. The contribution of sociodemographic, cognitive and clinical characterictics was investigated.

Patients showed a significant total cortical thinning (F=17.55, d=−0.62, p<0.001) and there was a diffuse pattern of reduced thickness (encompassing frontal, temporal and parietal cortices) (all p's<0.001, d's>0.53). No significant group×gender interactions were observed (all p's>0.15). There were no significant associations between the clinical and pre-morbid variables and cortical thickness measurements (all r's<0.12). A weak significant negative correlation between attention and total (r=−0.24, p=0.021) and parietal cortical thickness (r=−0.27, p=0.009) was found in patients (thicker cortex was associated with lower attention). Our data revealed a similar pattern of cortical thickness changes related to age in patients and controls.

Cortical thinning is independent of gender, age, age of onset and duration of the illness and does not seem to significantly influence clinical and functional symptomatology. These findings support a primary neurodevelopment disorder affecting the normal cerebral cortex development in schizophrenia.