Thus far, a handful of highly penetrant mutations conferring risk of psychosis have been discovered. Here we used whole-genome sequencing and long-range phasing to investigate an Icelandic kindred containing ten individuals with psychosis (schizophrenia, schizoaffective disorder or psychotic bipolar disorder). We found that all affected individuals carry RBM12 (RNA-binding-motif protein 12) c.2377G>T (P = 2.2 × 10), a nonsense mutation that results in the production of a truncated protein lacking a predicted RNA-recognition motif. We replicated the association in a Finnish family in which a second RBM12 truncating mutation (c.2532delT) segregates with psychosis (P = 0.020). c.2377G>T is not fully penetrant for psychosis; however, we found that carriers unaffected by psychosis resemble patients with schizophrenia in their non-psychotic psychiatric disorder and neuropsychological test profile (P = 0.0043) as well as in their life outcomes (including an increased chance of receiving disability benefits, P = 0.011). As RBM12 has not previously been linked to psychosis, this work provides new insight into psychiatric disease.

The contribution of de novo variants in severe intellectual disability (ID) has been extensively studied whereas the genetics of mild ID has been less characterized. To elucidate the genetics of milder ID we studied 442 ID patients enriched for mild ID (>50%) from a population isolate of Finland. Using exome sequencing, we show that rare damaging variants in known ID genes are observed significantly more often in severe (27%) than in mild ID (13%) patients. We further observe a significant enrichment of functional variants in genes not yet associated with ID (OR: 2.1). We show that a common variant polygenic risk significantly contributes to ID. The heritability explained by polygenic risk score is the highest for educational attainment (EDU) in mild ID (2.2%) but lower for more severe ID (0.6%). Finally, we identify a Finland enriched homozygote variant in the CRADD ID associated gene.

Objective We investigated whether T. gondii seropositivity is associated with 12-month depressive, anxiety and alcohol use disorders and current depressive symptoms and whether inflammation, measured by C-reactive protein (CRP) level, explains these associations. Method Health 2000 study (BRIF8901), conducted in years 2000–2001, is based on a nationally representative sample of Finns aged 30 and above, with 7112 participants and 88.6% response rate. DSM-IV depressive, anxiety and alcohol use disorders were assessed with the Composite International Diagnostic Interview and depressive symptoms with the Beck Depressive Inventory (BDI-21). We used logistic regression to investigate the association of T. gondii seropositivity with mental disorders and linear regression with BDI-21 scores. Results T. gondii seroprevalence was significantly associated with 12-month generalized anxiety disorder but not with other anxiety, depressive or alcohol use disorders. T. gondii seropositivity was associated with higher BDI-21 scores (beta 0.56, 95% CI 0.12–1.00, P=0.013) and with having a comorbid depressive and anxiety disorder (OR 1.86, 95% CI 1.16–2.97, P=0.010). Higher CRP levels were associated with these outcomes and with T. gondii seropositivity, but adjusting for CRP did not change the effect of T. gondii seropositivity. Limitations cross-sectional study design with no information on the timing of T. gondii infection. Conclusion T. gondii seropositivity is associated with generalized anxiety disorder, depressive symptoms and comorbid depressive and anxiety disorders, which is not mediated by inflammation.

Objective To assess the employment rate and the related background factors among people with schizophrenia or bipolar disorder. Methods We identified all people in Sweden aged 18–64 years diagnosed with schizophrenia or bipolar disorder in nationwide registers in the years 2006–2013. The identified individuals were grouped by main activity or source of income. The association between background factors and employment was analyzed with generalized estimating equations (GEE). Results Three years before the first psychosis or bipolar disorder diagnosis, 24% of the individuals with schizophrenia and 45% of the individuals with bipolar disorder were employed. However, the employment rate dropped around the time of the first diagnosis. Five years later, 10% of the individuals with schizophrenia and 34% of the individuals with bipolar disorder were employed. The most important factors associated with employment after diagnosis were a high level of education, older age at the first registered diagnosis, no substance use disorder, and a low number of previous hospitalizations. Marriage or cohabiting, higher level of education, and higher age at the first diagnosis were associated with an increased employment rate especially among people with schizophrenia, and substance use was associated with a lower employment rate, especially among people with bipolar disorder. Men with bipolar disorder had a higher employment rate than women. Conclusion The employment rate is low among people with schizophrenia and higher among people with bipolar disorder. The association of background characteristics with employment was mostly in the same direction both in schizophrenia and in bipolar disorder.

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Toxoplasma gondii infection is associated with increased risk for psychosis. However, the possible association between T. gondii and psychotic-like symptoms in the general adult population is unknown. We investigated whether T. gondii is associated with psychotic-like symptoms and psychosis diagnoses using data from Health 2000, a large cross-sectional health survey of the Finnish general population aged 30 and above. Seropositivity to toxoplasma was defined as a cutoff of 50IU/ml of IgG antibodies. Lifetime psychotic-like symptoms were identified with section G of the Composite International Diagnostic Interview, Munich version (M-CIDI). Symptoms were considered clinically relevant if they caused distress or help-seeking or there were at least three of them. Lifetime psychotic disorders were screened from the sample and were diagnosed with DSM-IV using SCID-I interview and information from medical records. All data were available for 5906 participants. We adjusted for variables related to T. gondii seropositivity (age, gender, education, region of residence, cat ownership, and C-reactive protein measuring inflammation) in regression models. We found that T. gondii seropositivity was significantly associated with clinically relevant psychotic-like symptoms (OR 1.77, p=0.001) and with the number of psychotic-like symptoms (IRR=1.55, p=0.001). The association between toxoplasma and diagnosed psychotic disorders did not reach statistical significance (OR 1.45 for schizophrenia). In a large sample representing the whole Finnish adult population, we found that serological evidence of toxoplasma infection predicted psychotic-like symptoms, independent of demographic factors and levels of C-reactive protein. Toxoplasma infection may be a risk factor for manifestation of psychotic-like symptoms.

In addition to severe traumatic experiences, milder, more common childhood adversities reflecting psychosocial burden may also be common in people with psychotic disorders and have an effect on symptomatology and functioning. We explored eleven negative childhood experiences and their influence on clinical symptoms among young adults with first-episode psychosis (FEP, n = 75) and matched population controls (n = 51). Individuals with FEP reported more adversities than controls. Specifically serious conflicts within the family, bullying at school, maternal mental health problems, and one's own and parents' serious illness during childhood were experienced by the patients more often than by controls. In the FEP group, the severity of adversity was associated with increased anxiety, manic, and obsessive-compulsive symptoms, but not with the severity of positive psychotic symptoms. Adversity produced a more pronounced effect on symptoms in male patients than in female patients. To conclude, in line with earlier studies of more chronic psychosis, a majority of the participants with FEP reported exposure to childhood adversities, with the FEP group reporting more adversities than controls. High levels of mood and anxiety symptoms in patients with FEP may be related to cumulative exposure to childhood adversities. This should be taken into account in the treatment for FEP.

The results suggest that adult levels of antibodies to cytomegalovirus and Epstein-Barr virus may not be associated with a significant decline in cognitive function or with dementia at population level.