Natural language processing for defining linguistic features in schizophrenia: A sample from Turkish speakers.

Natural language processing (NLP) provides fast and accurate extraction of features related to the language of schizophrenia. We utilized NLP methods to test the hypothesis that schizophrenia is associated with altered linguistic features in Turkish, a non-Indo-European language, compared to controls. We also explored whether these possible altered linguistic features were language-dependent or -independent. We extracted and compared speech in schizophrenia (SZ, N = 38) and healthy well-matched control (HC, N = 38) participants using NLP. The analysis was conducted in two parts. In the first one, mean sentence length, total completed words, moving average type-token ratio to measure the lexical diversity, and first-person singular pronoun usage were calculated. In the second one, we used parts-of-speech tagging (POS) and Word2Vec in schizophrenia and control. We found that SZ had lower mean sentence length and moving average type-token ratio but higher use of first-person singular pronoun. All these significant results were correlated with the Thought and Language Disorder Scale score. The POS approach demonstrated that SZ used fewer coordinating conjunctions. Our methodology using Word2Vec detected that SZ had higher semantic similarity than HC and K-Means could differentiate between SZ and HC into two distinct groups with high accuracy, 86.84 %. Our findings showed that altered linguistic features in SZ are mostly language-independent. They are promising to describe language patterns in schizophrenia which proposes that NLP measurements may allow for rapid and objective measurements of linguistic features.

The effect of SARS-CoV-2 virus on resting-state functional connectivity during adolescence: Investigating brain correlates of psychotic-like experiences and SARS-CoV-2 related inflammation response.

We first aimed to investigate resting-state functional connectivity (rs-FC) differences between adolescents exposed to SARS-CoV-2 and healthy controls. Secondly, the moderator effect of PLEs on group differences in rs-FC was examined. Thirdly, brain correlates of inflammation response during acute SARS-CoV-2 infection were investigated. Eighty-two participants aged between 14 and 24 years (SARS-CoV-2 (n = 35), controls (n = 47)) were examined using rs-fMRI. Seed-based rs-FC analysis was performed. The positive subscale of Community Assessment of Psychotic Experiences-42 (CAPE-Pos) was used to measure PLEs. The SARS-CoV-2 group had a lesser rs-FC within sensorimotor network (SMN), central executive network (CEN) and language network (LN), but an increased rs-FC within visual network (VN) compared to controls. No significant differences were detected between the groups regarding CAPE-Pos-score. However, including CAPE-Pos as a covariate, we found increased rs-FC within CEN and SN in SARS-CoV-2 compared to controls. Among the SARS-CoV-2 group, neutrophil/lymphocyte and thrombocyte*neutrophil/lymphocyte ratio was correlated with decreased/increased FC within DMN and SN, and increased FC within CEN. Our results showed rs-FC alterations within the SMN, CEN, LN, and VN among adolescents exposed to SARS-CoV-2. Moreover, changes in rs-FC associated with PLEs existed in these adolescents despite the absence of clinical changes. Furthermore, inflammation response was correlated with alterations in FC within the triple network system.

Psychosis Endophenotypes: A Gene-Set-Specific Polygenic Risk Score Analysis.

BACKGROUND AND HYPOTHESIS: Endophenotypes can help to bridge the gap between psychosis and its genetic predispositions, but their underlying mechanisms remain largely unknown. This study aims to identify biological mechanisms that are relevant to the endophenotypes for psychosis, by partitioning polygenic risk scores into specific gene sets and testing their associations with endophenotypes. STUDY DESIGN: We computed polygenic risk scores for schizophrenia and bipolar disorder restricted to brain-related gene sets retrieved from public databases and previous publications. Three hundred and seventy-eight gene-set-specific polygenic risk scores were generated for 4506 participants. Seven endophenotypes were also measured in the sample. Linear mixed-effects models were fitted to test associations between each endophenotype and each gene-set-specific polygenic risk score. STUDY RESULTS: After correction for multiple testing, we found that a reduced P300 amplitude was associated with a higher schizophrenia polygenic risk score of the forebrain regionalization gene set (mean difference per SD increase in the polygenic risk score: -1.15 µV; 95% CI: -1.70 to -0.59 µV; P = 6 × 10-5). The schizophrenia polygenic risk score of forebrain regionalization also explained more variance of the P300 amplitude (R2 = 0.032) than other polygenic risk scores, including the genome-wide polygenic risk scores. CONCLUSIONS: Our finding on reduced P300 amplitudes suggests that certain genetic variants alter early brain development thereby increasing schizophrenia risk years later. Gene-set-specific polygenic risk scores are a useful tool to elucidate biological mechanisms of psychosis and endophenotypes, offering leads for experimental validation in cellular and animal models.

Pathways linking school bullying and psychotic experiences: Multiple mediation analysis in Chinese adolescents and young adults.

It is found that people with psychotic experiences have a 4-fold increased risk of developing a psychotic disorder later in life. Indeed, accumulating evidence has suggested that the association between school bullying and psychotic experiences works linearly. Previous studies are mainly carried out in a Western context, and only seldomly do studies address whether the association exists in the Chinese population and the related psychological and cognitive mechanisms. Therefore, we carried out the current study to address this gap in the literature focusing on the lifelong school bullying experiences of Chinese adolescents and young adults. We examined them in relation to psychotic experiences while assessing the mediating role of self-esteem, the personality trait of neuroticism, and a cognitive bias in thinking called interpretation bias. We found that multiple victimizations were quite common in Hong Kong secondary schools. In addition to a significant association between school bullying and psychotic experiences, we found partial mediating effects of proposed psychological and cognitive mediators in constructed multiple mediation models utilizing bootstrapping approach. Specifically, bullying quantity reflecting the number of victimizations, had its association with psychotic experiences partially mediated by the personality trait of neuroticism. In contrast, bullying duration reflecting the lasting of victimization was associated with psychotic experiences partially mediated by the personality trait of neuroticism and interpretation bias. Our findings enhance our knowledge of mechanisms underpinning the psychosis spectrum development and have implications for school-based intervention programs targeting bullying victims.

Effects of psychosis-associated genetic markers on brain volumetry: a systematic review of replicated findings and an independent validation.

BACKGROUND: Given psychotic illnesses' high heritability and associations with brain structure, numerous neuroimaging-genetics findings have been reported in the last two decades. However, few findings have been replicated. In the present independent sample we aimed to replicate any psychosis-implicated SNPs (single nucleotide polymorphisms), which had previously shown at least two main effects on brain volume. METHODS: A systematic review for SNPs showing a replicated effect on brain volume yielded 25 studies implicating seven SNPs in five genes. Their effect was then tested in 113 subjects with either schizophrenia, bipolar disorder, 'at risk mental state' or healthy state, for whole-brain and region-of-interest (ROI) associations with grey and white matter volume changes, using voxel-based morphometry. RESULTS: We found FWER-corrected (Family-wise error rate) (i.e. statistically significant) associations of: (1) CACNA1C-rs769087-A with larger bilateral hippocampus and thalamus white matter, across the whole brain; and (2) CACNA1C-rs769087-A with larger superior frontal gyrus, as ROI. Higher replication concordance with existing literature was found, in decreasing order, for: (1) CACNA1C-rs769087-A, with larger dorsolateral-prefrontal/superior frontal gyrus and hippocampi (both with anatomical and directional concordance); (2) ZNF804A-rs11681373-A, with smaller angular gyrus grey matter and rectus gyri white matter (both with anatomical and directional concordance); and (3) BDNF-rs6265-T with superior frontal and middle cingulate gyri volume change (with anatomical and allelic concordance). CONCLUSIONS: Most literature findings were not herein replicated. Nevertheless, high degree/likelihood of replication was found for two genome-wide association studies- and one candidate-implicated SNPs, supporting their involvement in psychosis and brain structure.

Correlates of psychotic like experiences (PLEs) during Pandemic: An online study investigating a possible link between the SARS-CoV-2 infection and PLEs among adolescents.

BACKGROUND: This study investigated whether SARS-CoV-2 infection, depression, anxiety, sleep problems, cigarette, alcohol, drug usage contribute to psychotic-like experiences (PLEs) among adolescents during the pandemic. We also aimed to explore whether baseline inflammatory markers or the number of SARS-CoV-2-related symptoms are associated with PLEs, and the latter is mediated by internalizing symptoms. METHODS: Altogether, 684 adolescents aged 12-18 (SARS-CoV-2 group n = 361, control group (CG) n = 323) were recruited. The Community Assessment of Psychic Experiences-42-Positive Dimension (CAPE-Pos), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Pittsburg Sleep Quality Index (PSQI) questionnaires were completed by all volunteers using an online survey. C-reactive Protein and hemogram values, and SARS-CoV-2-related symptoms during the acute infection period were recorded in the SARS-CoV-2 group. Group comparisons, correlations, logistic regression, and bootstrapped mediation analyses were performed. RESULTS: CAPE-Pos-Frequency/Stress scores were significantly higher, whereas GAD-7-Total and PSQI-Total scores were significantly lower in SARS-CoV-2 than CG. Among the SARS-CoV-2 group, monocyte count and the number of SARS-CoV-2-symptoms were positively correlated with CAPE-Pos-Frequency/Stress scores. Besides SARS-CoV-2, cigarette use, GAD-7, and PHQ-9 scores significantly contributed to the presence of at least one CAPE-Pos "often" or "almost always". PHQ-9 and GAD-7 fully mediated the relationship between the number of SARS-CoV-2 symptoms and CAPE-Pos-Frequency. CONCLUSIONS: This study is the first to show a possible relationship between SARS-CoV-2 infection and PLEs among adolescents. Depression, anxiety, and cigarette use also contributed to PLEs. The number of SARS-Cov-2-symptoms and PLEs association was fully mediated by internalizing symptoms, but prospective studies will need to confirm this result.

DNA methylation meta-analysis reveals cellular alterations in psychosis and markers of treatment-resistant schizophrenia.

We performed a systematic analysis of blood DNA methylation profiles from 4483 participants from seven independent cohorts identifying differentially methylated positions (DMPs) associated with psychosis, schizophrenia, and treatment-resistant schizophrenia. Psychosis cases were characterized by significant differences in measures of blood cell proportions and elevated smoking exposure derived from the DNA methylation data, with the largest differences seen in treatment-resistant schizophrenia patients. We implemented a stringent pipeline to meta-analyze epigenome-wide association study (EWAS) results across datasets, identifying 95 DMPs associated with psychosis and 1048 DMPs associated with schizophrenia, with evidence of colocalization to regions nominated by genetic association studies of disease. Many schizophrenia-associated DNA methylation differences were only present in patients with treatment-resistant schizophrenia, potentially reflecting exposure to the atypical antipsychotic clozapine. Our results highlight how DNA methylation data can be leveraged to identify physiological (e.g., differential cell counts) and environmental (e.g., smoking) factors associated with psychosis and molecular biomarkers of treatment-resistant schizophrenia.

Genetic copy number variants, cognition and psychosis: a meta-analysis and a family study.

The burden of large and rare copy number genetic variants (CNVs) as well as certain specific CNVs increase the risk of developing schizophrenia. Several cognitive measures are purported schizophrenia endophenotypes and may represent an intermediate point between genetics and the illness. This paper investigates the influence of CNVs on cognition. We conducted a systematic review and meta-analysis of the literature exploring the effect of CNV burden on general intelligence. We included ten primary studies with a total of 18,847 participants and found no evidence of association. In a new psychosis family study, we investigated the effects of CNVs on specific cognitive abilities. We examined the burden of large and rare CNVs (>200 kb, <1% MAF) as well as known schizophrenia-associated CNVs in patients with psychotic disorders, their unaffected relatives and controls (N = 3428) from the Psychosis Endophenotypes International Consortium (PEIC). The carriers of specific schizophrenia-associated CNVs showed poorer performance than non-carriers in immediate (P = 0.0036) and delayed (P = 0.0115) verbal recall. We found suggestive evidence that carriers of schizophrenia-associated CNVs had poorer block design performance (P = 0.0307). We do not find any association between CNV burden and cognition. Our findings show that the known high-risk CNVs are not only associated with schizophrenia and other neurodevelopmental disorders, but are also a contributing factor to impairment in cognitive domains such as memory and perceptual reasoning, and act as intermediate biomarkers of disease risk.

Schizophrenia polygenic risk score influence on white matter microstructure.

Schizophrenia (SZ) and bipolar disorder (BD) are highly heritable, share symptomatology, and have a polygenic architecture. The impact of recent polygenic risk scores (PRS) for psychosis, which combine multiple genome-wide associated risk variations, should be assessed on heritable brain phenotypes also previously associated with the illnesses, for a better understanding of the pathways to disease. We have recently reported on the current SZ PRS's ability to predict 1st episode of psychosis case-control status and general cognition. Herein, we test its penetrance on white matter microstructure, which is known to be impaired in SZ, in BD and their relatives, using 141 participants (including SZ, BP, relatives of SZ or BP patients, and healthy volunteers), and two white matter integrity indexes: fractional anisotropy (FA) and mean diffusivity (MD). No significant correlation between the SZ PRS and FA or MD was found, thus it remains unclear whether white matter changes are primarily associated with SZ genetic risk profiles.

Biased cognition in East Asian and Western cultures.

The majority of cognitive bias research has been conducted in Western cultures. We examined cross-cultural differences in cognitive biases, comparing Westerners' and East Asians' performance and acculturation following migration to the opposite culture. Two local (UK, Hong Kong) and four migrant (short-term and long-term migrants to each culture) samples completed culturally validated tasks measuring attentional and interpretation bias. Hong Kong residents were more positively biased than people living in the UK on several measures, consistent with the lower prevalence of psychological disorders in East Asia. Migrants to the UK had reduced positive biases on some tasks, while migrants to Hong Kong were more positive, compared to their respective home counterparts, consistent with acculturation in attention and interpretation biases. These data illustrate the importance of cultural validation of findings and, if replicated, would have implications for the mental health and well-being of migrants.

Polygenic risk score increases schizophrenia liability through cognition-relevant pathways.

Cognitive deficit is thought to represent, at least in part, genetic mechanisms of risk for schizophrenia, with recent evidence from statistical modelling of twin data suggesting direct causality from the former to the latter. However, earlier evidence was based on inferences from twin not molecular genetic data and it is unclear how much genetic influence 'passes through' cognition on the way to diagnosis. Thus, we included direct measurements of genetic risk (e.g. schizophrenia polygenic risk scores) in causation models to assess the extent to which cognitive deficit mediates some of the effect of polygenic risk scores on the disorder. Causal models of family data tested relationships among key variables and allowed parsing of genetic variance components. Polygenic risk scores were calculated from summary statistics from the current largest genome-wide association study of schizophrenia and were represented as a latent trait. Cognition was also modelled as a latent trait. Participants were 1313 members of 1078 families: 416 patients with schizophrenia, 290 unaffected siblings, and 607 controls. Modelling supported earlier findings that cognitive deficit has a putatively causal role in schizophrenia. In total, polygenic risk score explained 8.07% [confidence interval (CI) 5.45-10.74%] of schizophrenia risk in our sample. Of this, more than a third (2.71%, CI 2.41-3.85%) of the polygenic risk score influence was mediated through cognition paths, exceeding the direct influence of polygenic risk score on schizophrenia risk (1.43%, CI 0.46-3.08%). The remainder of the polygenic risk score influence (3.93%, CI 2.37-4.48%) reflected reciprocal causation between schizophrenia liability and cognition (e.g. mutual influences in a cyclical manner). Analysis of genetic variance components of schizophrenia liability indicated that 26.87% (CI 21.45-32.57%) was associated with cognition-related pathways not captured by polygenic risk score. The remaining variance in schizophrenia was through pathways other than cognition-related and polygenic risk score. Although our results are based on inference through statistical modelling and do not provide an absolute proof of causality, we find that cognition pathways mediate a significant part of the influence of cumulative genetic risk on schizophrenia. We estimate from our model that 33.51% (CI 27.34-43.82%) of overall genetic risk is mediated through influences on cognition, but this requires further studies and analyses as the genetics of schizophrenia becomes better characterized.

Use of schizophrenia and bipolar disorder polygenic risk scores to identify psychotic disorders.

BACKGROUND: There is increasing evidence for shared genetic susceptibility between schizophrenia and bipolar disorder. Although genetic variants only convey subtle increases in risk individually, their combination into a polygenic risk score constitutes a strong disease predictor.AimsTo investigate whether schizophrenia and bipolar disorder polygenic risk scores can distinguish people with broadly defined psychosis and their unaffected relatives from controls. METHOD: Using the latest Psychiatric Genomics Consortium data, we calculated schizophrenia and bipolar disorder polygenic risk scores for 1168 people with psychosis, 552 unaffected relatives and 1472 controls. RESULTS: Patients with broadly defined psychosis had dramatic increases in schizophrenia and bipolar polygenic risk scores, as did their relatives, albeit to a lesser degree. However, the accuracy of predictive models was modest. CONCLUSIONS: Although polygenic risk scores are not ready for clinical use, it is hoped that as they are refined they could help towards risk reduction advice and early interventions for psychosis.Declaration of interestR.M.M. has received honoraria for lectures from Janssen, Lundbeck, Lilly, Otsuka and Sunovian.

A polygenic risk score analysis of psychosis endophenotypes across brain functional, structural, and cognitive domains.

This large multi-center study investigates the relationships between genetic risk for schizophrenia and bipolar disorder, and multi-modal endophenotypes for psychosis. The sample included 4,242 individuals; 1,087 patients with psychosis, 822 unaffected first-degree relatives of patients, and 2,333 controls. Endophenotypes included the P300 event-related potential (N = 515), lateral ventricular volume (N = 798), and the cognitive measures block design (N = 3,089), digit span (N = 1,437), and the Ray Auditory Verbal Learning Task (N = 2,406). Data were collected across 11 sites in Europe and Australia; all genotyping and genetic analyses were done at the same laboratory in the United Kingdom. We calculated polygenic risk scores for schizophrenia and bipolar disorder separately, and used linear regression to test whether polygenic scores influenced the endophenotypes. Results showed that higher polygenic scores for schizophrenia were associated with poorer performance on the block design task and explained 0.2% (p = 0.009) of the variance. Associations in the same direction were found for bipolar disorder scores, but this was not statistically significant at the 1% level (p = 0.02). The schizophrenia score explained 0.4% of variance in lateral ventricular volumes, the largest across all phenotypes examined, although this was not significant (p = 0.063). None of the remaining associations reached significance after correction for multiple testing (with alpha at 1%). These results indicate that common genetic variants associated with schizophrenia predict performance in spatial visualization, providing additional evidence that this measure is an endophenotype for the disorder with shared genetic risk variants. The use of endophenotypes such as this will help to characterize the effects of common genetic variation in psychosis.

The impact of psychosis genome-wide associated ZNF804A variation on verbal fluency connectivity.

Schizophrenia (SCZ) and bipolar disorder (BD) have high heritability. Genome-wide association studies (GWAS) have identified ZNF804A as a significant risk gene for both illnesses. A validation of this finding at the brain systems-level is imperative as there is still little understanding of how it heightens risk. Based in part on our recent findings of an effect on widespread decreased white matter microstructural fractional anisotropy (putatively a proxy of its integrity), particularly strong in SCZ, we asked whether the risk allele has a detrimental effect on regional brain activation and functional connectivity during a type of cognitive processing which is, together with its neural correlates, impaired in BD and SCZ: verbal fluency. Functional MRI and genotype data was collected from 80 healthy volunteers, and 54 SCZ and 40 BD patients. A standard multifactorial analysis of variance using statistical parametric mapping and significance correction of FWE p < 0.05 was used. We found the GWAS risk allele A was associated with decreased positive functional coupling between the left precentral gyrus/inferior frontal gyrus (i.e. the most highly recruited area for the task) and: 1) the left inferior frontal gyrus, and 2) the left posterior cingulate gyrus, encompassing the precuneus; both as a main effect across controls and psychosis patients. Such association of the risk allele with reduced functional connectivity (with no area where the opposite main effect was detected), converges with findings in other tasks, our previous finding of its widespread impact on brain white matter microstructure, and with the dysconnectivity hypothesis of SCZ.

Bilingual comparison of Mandarin and English cognitive bias tasks.

Most research into cognitive biases has used Western samples, despite potential East-West socio-cultural differences. One reason is the lack of appropriate measures for non-Westerners. This study is about cross-linguistic equivalence which needs to be established before assessing cross-cultural differences in future research. We developed parallel Mandarin and English measures of interpretation bias and attention bias using back-translation and decentering procedures. We assessed task equivalence by administering both sets of measures to 47 bilingual Mandarin-English speakers. Interpretation bias measurement was similar and reliable across language versions, confirming suitability of the Mandarin versions for future cross-cultural research. By contrast, scores on attention bias tasks did not intercorrelate reliably, suggesting that nonverbal stimuli such as pictures or facial expressions of emotion might present better prospects for cross-cultural comparison. The development of the first set of equivalent measures of interpretation bias in an Eastern language paves the way for future research investigating East-West differences in biased cognition.

Validation of the Chinese version of Community Assessment of Psychic Experiences (CAPE) in an adolescent general population.

The Community Assessment of Psychic Experiences (CAPE) is a popular 42-item self-report assessment of psychosis proneness (PP) that has been widely-translated. However, there is as yet no validation of CAPE in non-Western languages. Here, we validated a Chinese translation of CAPE ("CAPE-C") in a young Chinese community sample. Factor analyses were employed in a sample of 660 individuals (mean age=18.63) to identify a culturally-sensitive factor structure for CAPE-C (Study 1). Since confirmatory factor analysis (CFA) suggested that CAPE-C did not follow the original factor structure, exploratory factor analysis and follow-up CFA were employed to establish an alternative structure, resulting in a 15-item "CAPE-C15" which retained a three-factor structure tapping positive, negative and depressive symptoms. To demonstrate the specificity of CAPE-C15 as a measure of PP, we conducted regression analyses to examine associations between CAPE-C15 dimensions and other measures of psychotic and depressive symptoms (Study 2). Results confirmed that CAPE-C15 dimensions showed specific associations with relevant symptom dimensions of other measures, but not with irrelevant ones. Finally, to aid interpretation of CAPE-C15 scores, Receiver Operating Characteristic analysis was conducted to establish a cut-off score that could indicate test-takers' need for clinical attention (Study 3). We found that a cut-off score of 8.18 on CAPE-C15 positive and negative symptom frequency and distress scores distinguished individuals whose PP was within normal ranges from those at psychometric high-risk (sensitivity: 78.6%; specificity: 77.7%). CAPE-C15 will likely prove relevant to researchers and healthcare providers who serve Chinese-speaking adolescents and young adults.

Effects of risk for bipolar disorder on brain function: A twin and family study.

Bipolar disorder (BPD) is associated with altered regional brain function during the performance of cognitive tasks. The relative contribution of genetic and environmental risk factors for BPD to these changes has not yet been quantified. We sought to address this issue in a functional neuroimaging study of people who varied in their risk for BPD. Functional magnetic resonance imaging was used to study 124 subjects (29 twin and 9 sibling pairs with at least one member with BPD, and 24 healthy twin pairs) performing a working memory task. We assessed the influence of risk for BPD on regional brain function during the task in a two stage process. Firstly, we identified areas where there were group differences in activation. Secondly, we estimated the heritability and phenotypic correlation of activation and BPD using genetic modeling. BPD was associated with increased activation in the anterior cingulate, orbitofrontal, medial prefrontal, and left precentral cortices, and in the precuneus. Within these regions, activation in the orbitofrontal cortex rendered the most significant heritability estimate (h2=0.40), and was significantly correlated with BPD phenotype (rph=0.29). A moderate proportion of the genetic influences (rg=0.69) acting on both BPD and on the degree of orbitofrontal activation were shared. These findings suggest that genetic factors that confer vulnerability to BPD alter brain function in BPD.

Familial and environmental influences on brain volumes in twins with schizophrenia.

BACKGROUND: Reductions in whole brain and grey matter volumes are robust features of schizophrenia, yet their etiological influences are unclear. METHODS: We investigated the association between the genetic and environmental risk for schizophrenia and brain volumes. Whole brain, grey matter and white matter volumes were established from structural MRIs from twins varying in their zygosity and concordance for schizophrenia. Hippocampal volumes were measured manually. We conducted between-group testing and full genetic modelling. RESULTS: We included 168 twins in our study. Whole brain, grey matter, white matter and right hippocampal volumes were smaller in twins with schizophrenia. Twin correlations were larger for whole brain, grey matter and white matter volumes in monozygotic than dizygotic twins and were significantly heritable, whereas hippocampal volume was the most environmentally sensitive. There was a significant phenotypic correlation between schizophrenia and reductions in all the brain volumes except for that of the left hippocampus. For whole brain, grey matter and the right hippocampus the etiological links with schizophrenia were principally associated with the shared familial environment. Lower birth weight and perinatal hypoxia were both associated with lower whole brain volume and with lower white matter and grey matter volumes, respectively. LIMITATIONS: Scan data were collected across 2 sites, and some groups were modest in size. CONCLUSION: Whole brain, grey matter and right hippocampal volume reductions are linked to schizophrenia through correlated familial risk (i.e., the shared familial environment). The degree of influence of etiological factors varies between brain structures, leading to the possibility of a neuroanatomically specific etiological imprint.

IQ, the Urban Environment, and Their Impact on Future Schizophrenia Risk in Men.

Exposure to an urban environment during early life and low IQ are 2 well-established risk factors for schizophrenia. It is not known, however, how these factors might relate to one another. Data were pooled from the North Jutland regional draft board IQ assessments and the Danish Conscription Registry for men born between 1955 and 1993. Excluding those who were followed up for less than 1 year after the assessment yielded a final cohort of 153170 men of whom 578 later developed a schizophrenia spectrum disorder. We found significant effects of having an urban birth, and also experiencing an increase in urbanicity before the age of 10 years, on adult schizophrenia risk. The effect of urban birth was independent of IQ. However, there was a significant interaction between childhood changes in urbanization in the first 10 years and IQ level on the future adult schizophrenia risk. In short, those subjects who moved to more or less urban areas before their 10th birthday lost the protective effect of IQ. When thinking about adult schizophrenia risk, the critical time window of childhood sensitivity to changes in urbanization seems to be linked to IQ. Given the prediction that by 2050, over 80% of the developed world's population will live in an urban environment, this represents a major future public health issue.