Familial Schizophrenia Research Articles

Genome-wide association study of multiplex schizophrenia pedigrees.

The authors used a genome-wide association study (GWAS) of multiply affected families to investigate the association of schizophrenia to common single-nucleotide polymorphisms (SNPs) and rare copy number variants (CNVs). The family sample included 2,461 individuals from 631 pedigrees (581 in the primary European-ancestry analyses). Association was tested for single SNPs and genetic pathways. Polygenic scores based on family study results were used to predict case-control status in the Schizophrenia Psychiatric GWAS Consortium (PGC) data set, and consistency of direction of effect with the family study was determined for top SNPs in the PGC GWAS analysis. Within-family segregation was examined for schizophrenia-associated rare CNVs. No genome-wide significant associations were observed for single SNPs or for pathways. PGC case and control subjects had significantly different genome-wide polygenic scores (computed by weighting their genotypes by log-odds ratios from the family study) (best p=10(-17), explaining 0.4% of the variance). Family study and PGC analyses had consistent directions for 37 of the 58 independent best PGC SNPs (p=0.024). The overall frequency of CNVs in regions with reported associations with schizophrenia (chromosomes 1q21.1, 15q13.3, 16p11.2, and 22q11.2 and the neurexin-1 gene [NRXN1]) was similar to previous case-control studies. NRXN1 deletions and 16p11.2 duplications (both of which were transmitted from parents) and 22q11.2 deletions (de novo in four cases) did not segregate with schizophrenia in families. Many common SNPs are likely to contribute to schizophrenia risk, with substantial overlap in genetic risk factors between multiply affected families and cases in large case-control studies. Our findings are consistent with a role for specific CNVs in disease pathogenesis, but the partial segregation of some CNVs with schizophrenia suggests that researchers should exercise caution in using them for predictive genetic testing until their effects in diverse populations have been fully studied.

Executive Functions in Patients with Familial versus Sporadic Schizophrenia and Their Parents

Background: The aim of this study was to investigate the executive functions in patients with sporadic schizophrenia (SS) and familial schizophrenia (FS), and the executive functions in their parents. Methods: The study included 30 patients with FS and their 37 parents with a positive family history of schizophrenia; 30 patients with SS and their 44 parents; 30 controls matched with the patients for gender, age and education, and 40 controls matched with the parents for gender, age and education (211 subjects in total). All the subjects were interviewed with the Structured Clinical Interview for DSM-IV-Axis I (SCID-I). The executive functions were assessed using the Verbal Fluency Test (VFT), the Trail Making Test (TMT), the Wisconsin Card Sorting Test (WCST) and the Stroop Test. Results: Patients with FS and their parents, and patients with SS performed significantly worse than their controls on the VFT, TMT, WCST and the Stroop test. There were no statistically significant differences between parents of patients with SS and their controls on any of the tests except for the Stroop color score. FS parents performed significantly worse than SS parents on all tests. FS patients performed significantly worse than SS patients on the VFT, TMT, Stroop test. Conclusion: Previous studies that investigated the cognitive functions of relatives of patients with schizophrenia brought out inconsistent results. The present study investigated relatives with and without a family history of schizophrenia separately and found that executive functions were impaired only in parents with a positive family history of schizophrenia. These findings suggest that impairment in executive functions may represent a genetic endophenotype for schizophrenia.

Variation in the major histocompatibility complex [MHC] gene family in schizophrenia: Associations and functional implications

Schizophrenia is a chronic debilitating neuropsychiatric disorder with a complex genetic contribution. Although multiple genetic, immunological and environmental factors are known to contribute to schizophrenia susceptibility, the underlying neurobiological mechanism(s) is yet to be established. The immune system dysfunction theory of schizophrenia is experiencing a period of renewal due to a growth in evidence implicating components of the immune system in brain function and human behavior. Current evidence indicates that certain immune molecules such as Major Histocompatibility Complex (MHC) and cytokines, the key regulators of immunity and inflammation are directly involved in the neurobiological processes related to neurodevelopment, neuronal plasticity, learning, memory and behavior. However, the strongest support in favor of the immune hypothesis has recently emerged from on-going genome wide association studies advocating MHC region variants as major determinants of one's risk for developing schizophrenia. Further identification of the interacting partners and receptors of MHC molecules in the brain and their role in down-stream signaling pathways of neurotransmission have implicated these molecules as potential schizophrenia risk factors. More recently, combined brain imaging and genetic studies have revealed a relationship between genetic variations within the MHC region and neuromorphometric changes during schizophrenia. Furthermore, MHC molecules play a significant role in the immune-infective and neurodevelopmental pathogenetic pathways, currently hypothesized to contribute to the pathophysiology of schizophrenia. Herein, we review the immunological, genetic and expression studies assessing the role of the MHC in conferring risk for developing schizophrenia, we summarize and discuss the possible mechanisms involved, making note of the challenges to, and future directions of, immunogenetic research in schizophrenia.

Identification and characterization of three inherited genomic copy number variations associated with familial schizophrenia

Schizophrenia is a complex mental disorder with high degree of genetic influence in its etiology. Several recent studies revealed that copy number variations (CNVs) of genomic DNA contributed significantly to the genetic architecture of sporadic schizophrenia. This study aimed to investigate whether CNVs also contribute to the familial forms of schizophrenia. Using array-based comparative genomic hybridization technology, we searched for pathogenic CNV associated with schizophrenia in a sample of 60 index cases from multiplex schizophrenia families. We detected three inherited CNVs that were associated with schizophrenia in three families, including a microdeletion of ~4.4Mb at chromosome 6q12–q13, a microduplication of ~1Mb at chromosome 18q12.3, and an interstitial duplication of ~5Mb at chromosome 15q11.2–q13.1. Our data indicate that CNVs contribute to the genetic underpinnings of the familial forms of schizophrenia as well as of the sporadic form. As 15q11–13 duplication is a well-known recurrent CNV associated with autism in the literature, the detection of the 15q11.2–q13.1 duplication in our schizophrenia patients provides additional support to other studies reporting that schizophrenia is part of the clinical spectrum of 15q11–q13 duplication syndrome.

Heritability of functioning in families with schizophrenia in relation to neurocognition

The role of daily functioning is an integral part of the schizophrenia (SZ) phenotype and deficits in this trait appear to be present in both affected persons and some unaffected relatives; hence we have examined its heritability in our cohort of African American schizophrenia families. There is now ample evidence that deficits in cognitive function can impact family members who are not themselves diagnosed with SZ; there is some, but less evidence that role function behaves likewise. We evaluate whether role function tends to “run in families” who were ascertained because they contain an African American proband diagnosed with SZ. MethodsWe analyzed heritability for selected traits related to daily function, employment, living situation, marital status, and Global Assessment Scale (GAS) score; modeling age, gender, along with neurocognition and diagnosis as covariates in a family based African-American sample (N=2488 individuals including 979 probands). ResultsMeasures of role function were heritable in models including neurocognitive domains and factor analytically derived neurocognitive summary scores and demographics as covariates; the most heritable estimate was obtained from the current GAS scores (h2=0.72). Neurocognition was not a significant contributor to heritability of role function. ConclusionsCommonly assessed demographic and clinical indicators of functioning are heritable with a global rating of functioning being the most heritable. Measures of neurocognition had little impact on heritability of functioning overall. The family covariance for functioning, reflected in its heritability, supports the concept that interventions at the family level, such as evidenced-based family psychoeducation may be beneficial in schizophrenia.

Cancer in parents of persons with schizophrenia: Is there a genetic protection?

A reduced risk for cancer has been noted among persons with schizophrenia as well as their first degree relatives. One explanation for these findings suggests that genes associated with schizophrenia confer reduced cancer susceptibility. Given the well documented genetic factor in schizophrenia it could thus be expected that cancer incidence rates should be lower in persons with schizophrenia with a known family history of schizophrenia compared to persons with sporadic schizophrenia, as well as their first degree relatives. This study investigated the risk for cancer among the biological parents of persons with schizophrenia accounting for the familial aggregation. Linkage was conducted between national population, psychiatric and cancer databases. Standardized incidence rates for all cancer sites were calculated by comparing the parents' rates with those of the general population. In addition, the association between familial aggregation of schizophrenia and risk for cancer was calculated among the parents. A reduced cancer risk was found among the parents compared to the general population (SIR 0.8, 95% CI 0.8–0.9). However, no evidence of decreased risk was associated with familial schizophrenia. Thus, no association between familial aggregation and cancer incidents was found with regard to most cancer sites. Moreover, a small, but not statistically significant increased risk of colon cancer was associated with familial aggregation scores among the parents (OR 1.2, 95% CI 1.0–1.5). These findings undermine the support to the genetic explanation for the reduced risk for cancer in schizophrenia among patients and their biological parents.

The nature of schizotypy among multigenerational multiplex schizophrenia families.

Identification of endophenotypes (Gottesman & Gould, 2003; Gottesman & Shields, 1972) that genetically correlate with schizophrenia and are genetically homogeneous is an important strategy for detecting genes that affect schizophrenia risk. Symptoms of schizotypy may familially correlate with schizophrenia; however, there are critical limitations of the current literature concerning this association. The present study examined the genetic architecture and genetic associations between schizotypy and schizophrenia among multigenerational, multiplex schizophrenia families. Genetic schizotypy factor scales were developed that genetically correlated with schizophrenia, although some relations were unexpected in direction suggesting minimization of "psychotic-like" symptoms. These genetic schizotypy factor scales did not genetically correlate with major depressive disorder or substance dependence indicating specificity to schizophrenia. The results highlight the possibility of significant response bias in schizophrenia families, particularly among close relatives, and suggest an important consideration when acquiring self-report information. This is a topic that deserves future study as the origins of this putative bias in relatives are unclear. In addition, the results support the identification of genetic schizotypy factors as a promising technique for maximizing genetic correlation of endophenotypes with schizophrenia.

Mismatch negativity and low frequency oscillations in schizophrenia families

ObjectiveTheta-alpha range oscillations have been associated with MMN in healthy controls. Our previous studies showed that theta-alpha activities are highly heritable in schizophrenia patients’ families. We aimed to test the hypothesis that theta-alpha activities may contribute to MMN in schizophrenia patients and their family members. MethodsWe compared MMN and single trial oscillations during MMN in 95 patients, 75 first-degree relatives, 87 controls, and 34 community subjects with schizophrenia spectrum personality (SSP) traits. ResultsWe found that (1) MMN was reduced in patients (p<0.001) and SSP subjects (p=0.047) but not in relatives (p=0.42); (2) there were augmented 1–20Hz oscillations in patients (p=0.02 to <0.001) during standard and deviant stimuli; (3) theta-alpha (5–12Hz) oscillations had the strongest correlation to MMN in controls and relatives (ΔR2=21.4–23.9%, all p<0.001), while delta (<5Hz) showed the strongest correlation to MMN in schizophrenia and SSP trait subjects; and, (4) MMN (h2=0.56, p=0.002) and theta-alpha (h2=0.55, p=0.004) were heritable traits. ConclusionsLow frequency oscillations have a robust relationship with MMN and the relationship appears altered by schizophrenia; and schizophrenia patients showed augmented low frequency activities during the MMN paradigm. SignificanceThe results encourage investigation of low frequency oscillations to elucidate the neurophysiological pathology underlying MMN abnormalities in schizophrenia.

Poster #254 CHILDHOOD ADVERSITY AND PREMORBID SCHIZOTYPAL TRAITS: FINDINGS FROM THE AESOP FIRST-EPISODE PSYCHOSIS CASE-CONTROL STUDY

Disrupted in Schizophrenia 1 (DISC1) is currently one of the most interesting candidate genes for major mental illness, having been demonstrated to associate with schizophrenia, bipolar disorder, major depression, autism, and Asperger's syndrome. We have previously reported a DISC1 haplotype, HEP3, and an NDE1 spanning tag haplotype to associate to schizophrenia in Finnish schizophrenia families. Because both DISC1 and NDE1 display association in our study sample, we hypothesized that other genes interacting with DISC1 might also have a role in the etiology of schizophrenia.We selected 11 additional genes encoding components of the “DISC1 pathway” and studied these in our study sample of 476 families including 1857 genotyped individuals. We performed single nucleotide polymorphism (SNP) and haplotype association analyses in two independent sets of families. For markers and haplotypes found to be consistently associated in both sets, the overall significance was tested with the combined set of families.We identified three SNPs to be associated with schizophrenia in PDE4D (rs1120303, p = .021), PDE4B (rs7412571, p = .018), and NDEL1 (rs17806986, p = .0038). Greater significance was observed with allelic haplotypes of PDE4D (p = .00084), PDE4B (p = .0022 and p = .029), and NDEL1 (p = .0027) that increased or decreased schizophrenia susceptibility.Our findings with other converging lines of evidence support the underlying importance of DISC1-related molecular pathways in the etiology of schizophrenia and other major mental illnesses.

Genetic associations between neuregulin-1 SNPs and neurocognitive function in multigenerational, multiplex schizophrenia families

Recent work shows promising associations between schizophrenia and polymorphisms in neuregulin-1 (NRG1) and a large literature also finds strong familial relationships between schizophrenia and cognitive deficits. Given the role of NRG1 in glutamate regulation and glutamate's effect on cognition, we hypothesized that cognitive deficits may be related to variation within NRG1, providing a possible mechanism to increase risk for schizophrenia. This study examined the associations between NRG1, cognition, and schizophrenia using a multigenerational multiplex family sample (total N=419, 40 families), including 58 affected participants (schizophrenia or schizoaffective disorder-depressed type) and their 361 unaffected relatives. Participants were genotyped for 40 NRG1 single nucleotide polymorphisms (SNPs), chosen largely based on previous associations with schizophrenia. All participants completed structured diagnostic interviews and a computerized neurocognitive battery assessing eight cognitive domains. Variance component quantitative trait analyses tested for associations between individual NRG1 SNPs and cognitive performance in the total sample, a subsample of healthy participants with no Diagnostic and Statistical Manual of Mental Disorders diagnosis, and using general intelligence as a covariate. Effect sizes (within-family β coefficients) ranged from 0.08 to 0.73, and 61 of these associations were nominally significant (P≤0.05), with 12 associations at P≤0.01, although none achieved the modified Bonferroni significance threshold of P<0.0003. Attention was the most frequently nominally associated domain and rs10503929, a nonsynonymous SNP, was the most frequently nominally associated SNP. Although not significant experiment-wise, these findings suggest that further study of the associations between variation in NRG1 and cognition may be productive.

Investigating association of four gene regions (GABRB3, MAOB, PAH, and SLC6A4) with five symptoms in schizophrenia

Recently, microsatellite polymorphisms have been reported to be associated with four genes, GABRB3, MAOB, PAH, and SLC6A4, and their relationships have been tested to five symptom factors: hallucinations, delusions, negative symptoms, mania, and depression. These factors were frequently present in schizophrenia spectrum disorders in the Irish Study of High Density Schizophrenia Families (ISHDSF) with a proband with the diagnosis of schizophrenia (Bergen et al., 2009). Of these, GABRB3 and PAH were reported to be significantly associated with hallucinations and delusions in a 90-family subset of the ISHDSF, respectively. In this study, we tested the association of genetic markers from these four gene regions with the approximate five clinical symptoms, based upon 256 schizophrenia patients, with genotypic data obtained by higher resolution single nucleotide polymorphism (SNP) genotyping. We found one GABRB3 SNP (rs1426891, 70.8kb downstream of this gene) and haplotype constructed by three SNPs (rs1426891, rs2912602, and rs2912600) were significantly associated with hallucinations in Caucasians after Bonferroni correction for multiple testing (Bonferroni corrected P: 0.032 and 0.016, respectively). Additionally, we found one haplotype constructed by two SNPs, rs5905587–rs37615860, in MAOB/NDP gene region was significantly associated with delusions in all samples tested (Bonferroni corrected P: 0.048). These results provide additional evidence that GABRB3 and MAOB/NDP gene regions might constitute risk factors for hallucinations and delusions in schizophrenia.

Journal Digest

Journal Digest

Principal Components of Heritability From Neurocognitive Domains Differ Between Families With Schizophrenia and Control Subjects

Objective: Various measures of neurocognitive function show mean differences among individuals with schizophrenia (SZ), their relatives, and population controls. We use eigenvector transformations that maximize heritability of multiple neurocognitive measures, namely principal components of heritability (PCH), and evaluate how they distribute in SZ families and controls. Methods: African-Americans with SZ or schizoaffective disorder (SZA) (n = 514), their relatives (n = 1092), and adult controls (n = 300) completed diagnostic interviews and computerized neurocognitive tests. PCH were estimated from 9 neurocognitive domains. Three PCH, PCH1–PCH3, were modeled to determine if status (SZ, relative, and control), other psychiatric covariates, and education were significant predictors of mean values. A small-scale linkage analysis was also conducted in a subset of the sample. Results: PCH1, PCH2, and PCH3 account for 72% of the genetic variance. PCH1 represents 8 of 9 neurocognitive domains, is most highly correlated with spatial processing and emotion recognition, and has unadjusted heritability of 68%. The means for PCH1 differ significantly among SZ, their relatives, and controls. PCH2, orthogonal to PCH1, is most closely correlated with working memory and has an unadjusted heritability of 45%. Mean PCH2 is different only between SZ families and controls. PCH3 apparently represents a heritable component of neurocognition similar across the 3 diagnostic groups. No significant linkage evidence to PCH1–PCH3 or individual neurocognitive measures was discovered. Conclusions: PCH1 is highly heritable and genetically correlated with SZ. It should prove useful in future genetic analyses. Mean PCH2 differentiates SZ families and controls but not SZ and unaffected family members.

Increased Risk for Nonfamilial Schizophrenia from De Novo Mutations

Single nucleotide polymorphisms (SNPs) in sporadic (nonfamilial) schizophrenia have been less studied than genetic copy number variants (CNVs) in familial schizophrenia. To identify de novo mutations, these investigators sequenced 795 exomes (i.e., coding regions) from 231 schizophrenia trios (probands and their parents; 146 Afrikaner and 85 U.S. trios) and 34 healthy Afrikaner control trios. By …

The relationship of clinical, cognitive and social measures in schizophrenia: a preliminary finding combining measures in probands and relatives.

This study examines performance of schizophrenia patients, unaffected relatives and controls in social cognition, cognitive and psychiatric scales looking for possible markers of vulnerability in schizophrenia. Performance of schizophrenia patients from multiplex families, first-degree relatives, and matched controls was compared and, subsequently, discriminant analysis method was used for identifying the best predictors for group membership. By using Multigroup Discriminant Analyses on the three groups, the best predictors were PANSS, Premorbid Adjustment Scale, Faux Pas test, and a face/emotion categorizing task. This model obtained 82% correct global classification, suggesting that the combination of psychiatric scales and neuropsychological/social cognition tesks are the best approach for characterizing this disease. Although preliminary, our results suggest that social cognition tasks are robust markers of schizophrenia family impairments, and that combining clinical, social and neuropsychological measures is the best approach to asses patients and relatives vulnerability.

The Relationship of Clinical, Cognitive and Social Measures in Schizophrenia: A Preliminary Finding Combining Measures in Probands and Relatives

This study examines performance of schizophrenia patients, unaffected relatives and controls in social cognition, cognitive and psychiatric scales looking for possible markers of vulnerability in schizophrenia. Performance of schizophrenia patients from multiplex families, first-degree relatives, and matched controls was compared and, subsequently, discriminant analysis method was used for identifying the best predictors for group membership. By using Multigroup Discriminant Analyses on the three groups, the best predictors were PANSS, Premorbid Adjustment Scale, Faux Pas test, and a face/emotion categorizing task. This model obtained 82% correct global classification, suggesting that the combination of psychiatric scales and neuropsychological/social cognition tesks are the best approach for characterizing this disease. Although preliminary, our results suggest that social cognition tasks are robust markers of schizophrenia family impairments, and that combining clinical, social and neuropsychological measures is the best approach to asses patients and relatives vulnerability.

Proton magnetic resonance spectroscopy study on prefrontal lobe and thalamus in schizophrenia with or without mental disorder family history

Objective To compare the metabolic measures on prefrontal lobe and thalamus among schizophrenics with or without mental disorder family history by proton magnetic resonance spectroscopy (1 H-MRS),and to explore the relationship among metabolic measures,clinical symptom,and executive functioning.Methods Thirty-one schizophrenics with schizophrenia family history,21 schizophrenics with the other mental disorder family history,and 78 schizophrenics without mental disorder family history were examined at prefrontal lobe and thalamus by multi-voxel 1H-MRS.The N-acetylaspartate (NAA),Choline-congtaining compounds (Cho),and Creatine compounds (Cr) were measured and the ratios of NAA/Cr and Cho/Cr were determined.Meanwhile,Positive and Negative Syndrome Scale (PANSS) and Wisconsin Card Sorting Test (WCST) were also assessed in all schizophrenics.Results Both in schizophrenics with schizophrenia family history and with the other mental disorder family history,the NAA/Cr ratios showed lower than those in schizophrenics without mental disorder family history both on left prefrontal lobe and on fight thalamus ( P ＜ 0.05 ).Compared with schizophrenics without mental disorder family history,the score of negative symptoms and the perseverative errors demonstrated higher ( P＜ 0.05 or 0.01 ),the categories completed showed lower both in schizophrenics with schizophrenia family history and with the other mental disorder family history ( P＜0.05 ).The NAA/Cr ratios on left prefrontal lobe in all schizophrenics were significantly negatively related with the total score of PANSS and the responses errors (P ＜ 0.05 or P＜ 0.01 ),and positively related with the categories completed and the conceptual level responses ( P＜ 0.05 or P＜ 0.01 ).On left prefrontal lobe both in schizophrenics with schizophrenia family history and with the other mental disorder family history,the ratios of NAA/Cr were negatively related with the score of negative symptoms and the perseverative errors ( P ＜ 0.05 or 0.01 ).Conclusion The damages of neurons on prefrontal lobe and thalamus in schizophrenics with mental disorder family history may be more severe than those in schizophrenics without family history,and the damages on prefrontal lobe are related with negative symptoms and executive functioning. Key words: Schizophrenia; Magnetic resonance spectroscopy; Family history; N-acetylaspartate

Promoter polymorphisms in two overlapping 6p25 genes implicate mitochondrial proteins in cognitive deficit in schizophrenia

In a previous study, we detected a 6p25-p24 region linked to schizophrenia in families with high composite cognitive deficit (CD) scores, a quantitative trait integrating multiple cognitive measures. Association mapping of a 10 Mb interval identified a 260 kb region with a cluster of single-nucleotide polymorphisms (SNPs) significantly associated with CD scores and memory performance. The region contains two colocalising genes, LYRM4 and FARS2, both encoding mitochondrial proteins. The two tagging SNPs with strongest evidence of association were located around the overlapping putative promoters, with rs2224391 predicted to alter a transcription factor binding site (TFBS). Sequencing the promoter region identified 22 SNPs, many predicted to affect TFBSs, in a tight linkage disequilibrium block. Luciferase reporter assays confirmed promoter activity in the predicted promoter region, and demonstrated marked downregulation of expression in the LYRM4 direction under the haplotype comprising the minor alleles of promoter SNPs, which however is not driven by rs2224391. Experimental evidence from LYRM4 expression in lymphoblasts, gel-shift assays and modelling of DNA breathing dynamics pointed to two adjacent promoter SNPs, rs7752203-rs4141761, as the functional variants affecting expression. Their C-G alleles were associated with higher transcriptional activity and preferential binding of nuclear proteins, whereas the G-A combination had opposite effects and was associated with poor memory and high CD scores. LYRM4 is a eukaryote-specific component of the mitochondrial biogenesis of Fe-S clusters, essential cofactors in multiple processes, including oxidative phosphorylation. LYRM4 downregulation may be one of the mechanisms involved in inefficient oxidative phosphorylation and oxidative stress, increasingly recognised as contributors to schizophrenia pathogenesis.

Health-Related Quality of Life Profiles Among Family Caregivers of Patients With Schizophrenia

This cross-sectional study aims to determine and compare health-related quality of life profiles of schizophrenia family caregivers on the basis of their sociodemographic characteristics. Thirty outpatient family caregivers completed the generic 36-Item Short Form Health Survey instrument (male = 53.5%; mean age = 51 years; married = 76.7%). The highest mean score was reported for social functioning while role limitation-emotional was rated the worst. Significantly better health-related quality of life profiles were demonstrated by caregivers who were male, younger than 50 years, adequately educated, employed, and without health problems and were receiving monthly income. Understanding of on health-related quality of life matters for family caregivers is crucial to improve the quality of care for schizophrenia patients.

Environmental risk factors and their impact on the age of onset of schizophrenia: Comparing familial to non-familial schizophrenia

Background and aims: Several risk factors for schizophrenia have yet been identified. The aim of our study was to investigate how certain childhood and adolescent risk factors predict the age of onset of psychosis in patients with and without a familial component (i.e. a relative with schizophrenia or schizoaffective disorder). Methods: Aside from the age of onset of psychosis, we examined the risk factors for schizophrenia including obstetric complications, birth during winter or spring, behavioral deviances or delayed motor and speech development, exposure to adverse life events and exposure to substance use within a group of 100 patients (45 female, 55 male) with a mean age (± standard deviation) of 35.15 ± 13.21. Results: Birth complications and cannabis abuse are predictors for an earlier onset of schizophrenia in patients with non-familial schizophrenia. No environmental risk factors for an earlier age of onset in familial schizophrenia have been identified. Conclusions: Certain environmental risk factors for schizophrenia seem to have an impact on the age of onset of psychosis in non-familial schizophrenia, they do not seem to have an impact on familial schizophrenia.