Schizophrenia (SZ), bipolar disorder (BD) and depression (D) run in families. This susceptibility is partly due to hundreds or thousands of common genetic variants, each conferring a fractional risk. The cumulative effects of the associated variants can be summarised as a polygenic risk score (PRS). Using data from the EUropean Network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) first episode case–control study, we aimed to test whether PRSs for three major psychiatric disorders (SZ, BD, D) and for intelligent quotient (IQ) as a neurodevelopmental proxy, can discriminate affective psychosis (AP) from schizophrenia-spectrum disorder (SSD).

Participants (842 cases, 1284 controls) from 16 European EU-GEI sites were successfully genotyped following standard quality control procedures. The sample was stratified based on genomic ancestry and analyses were done only on the subsample representing the European population (573 cases, 1005 controls). Using PRS for SZ, BD, D, and IQ built from the latest available summary statistics, we performed simple or multinomial logistic regression models adjusted for 10 principal components for the different clinical comparisons.

In case–control comparisons PRS-SZ, PRS-BD and PRS-D distributed differentially across psychotic subcategories. In case–case comparisons, both PRS-SZ [odds ratio (OR) = 0.7, 95% confidence interval (CI) 0.54–0.92] and PRS-D (OR = 1.31, 95% CI 1.06–1.61) differentiated AP from SSD; and within AP categories, only PRS-SZ differentiated BD from psychotic depression (OR = 2.14, 95% CI 1.23–3.74).

Combining PRS for severe psychiatric disorders in prediction models for psychosis phenotypes can increase discriminative ability and improve our understanding of these phenotypes. Our results point towards the potential usefulness of PRSs in specific populations such as high-risk or early psychosis phases.

Studies that examine course and outcome in psychosis have reported considerable heterogeneity in terms of recovery, remission, employment, symptom presentation, social outcomes, and antipsychotic medication effects. Even with demonstrated heterogeneity in course and outcome, prophylactic antipsychotic maintenance therapy remains the prominent practice, particularly in participants with schizophrenia. Lack of efficacy in maintenance antipsychotic treatment and concerns over health detriments gives cause to re-examine guidelines.

This study was conducted as part of the Chicago follow-up study designed as a naturalistic prospective longitudinal research study to investigate the course, outcome, symptomatology, and effects of antipsychotic medication on recovery and rehospitalization in participants with serious mental illness disorders. A total of 139 participants with 734 observations were included in the analysis. GEE logistic models were applied to adjust for confounding factors measured at index hospitalization and follow-ups.

Our data show that the majority of participants with schizophrenia or affective psychosis experience future episodes of psychosis at some point during the 20-year follow-up. There was a significant diagnostic difference between groups showing an increase in the number of future episodes of psychosis in participants with schizophrenia. Participants with schizophrenia not on antipsychotics after the first 2 years have better outcomes than participants prescribed antipsychotics. The adjusted odds ratio of not on antipsychotic medication was 5.989 (95% CI 3.588–9.993) for recovery and 0.134 (95% CI 0.070–0.259) for rehospitalization. That is, regardless of diagnosis, after the second year, the absence of antipsychotics predicted a higher probability of recovery and lower probability of rehospitalization at subsequent follow-ups after adjusting for confounders.

This study reports multiple findings that bring into question the use of continuous antipsychotic medications, regardless of diagnosis. Even when the confound by indication for prescribing antipsychotic medication is controlled for, participants with schizophrenia and affective psychosis do better than their medicated cohorts, strongly confirming the importance of exposing the role of aiDSP and antipsychotic drug resistance.

Research has consistently shown that language abilities represent a core dimension of psychosis; however, to date, very little is known about syntactic comprehension performance in the early stages of psychosis. This study aims to compare the linguistic abilities involved in syntactic comprehension in a large group of First Episode Psychosis (FEP) patients and healthy controls (HCs).

A multiple choice test of comprehension of syntax was administered to 218 FEP patients (166 non-affective FEP patients [FEP-NA] and 52 affective FEP patients [FEP-A]) and 106 HCs. All participants were asked to match a sentence they listen with one out of four vignettes on a pc screen. Only one vignette represents the stimulus target, while the others are grammatical or non-grammatical (visual) distractors. Both grammatical and non-grammatical errors and performance in different syntactic constructions were considered.

FEP committed greater number of errors in the majority of TCGB language domains compared to HCs. Moreover, FEP-NA patients committed significantly more non-grammatical (z = −3.2, p = 0.007), locative (z = −4.7, p < 0.001), passive-negative (z = −3.2, p = 0.02), and relative (z = −4.6, p < 0.001) errors compared to HCs as well as more passive-affirmative errors compared to both HCs (z = −4.3, p < 0.001) and FEP-A (z = 3.1, p = 0.04). Finally, we also found that both FEP-NA and FEP-A committed more grammatical (FEP-NA: z = −9.2, p < 0.001 and FEP-A: z = −4.4, p < 0.001), total (FEP-NA: z = −8.2, p < 0.001 and FEP-A: z = 3.9, p = 0.002), and active-negative (FEP-NA: z = −5.8, p < 0.001 and FEP-A: z = −3.5, p = 0.01) errors compared to HCs.

This study shows that the access to syntactic structures is already impaired in FEP patients, especially in those with FEP-NA, ultimately suggesting that language impairments represent a core and inner feature of psychosis even at early stages.

Schizophrenic patients have fewer offspring than the general population but it is unclear whether (i) this persists for more than one generation, (ii) the reduced fertility is compensated by increased fertility in unaffected relatives, (iii) sociodemographic factors confound or interact with the association, and (iv) patients with affective psychosis have a similar fertility disadvantage. This study measured biological fitness over two generations in patients with schizophrenia or affective psychosis, and their unaffected siblings.

We conducted a historical cohort study using a Swedish birth cohort of 12 168 individuals born 1915–1929 and followed up until 2002. We compared biological fitness over two generations in patients with schizophrenia (n=58) or affective psychosis (n=153), and their unaffected siblings, with the population, adjusting for a range of sociodemographic variables from throughout the lifespan.

Patients with schizophrenia had fewer children [fertility ratio (FR) 0.42, 95% confidence interval (CI) 0.29–0.61] and grandchildren (FR 0.51, 95% CI 0.33–0.80) than the population. Some of this reduction was related to lower marriage rates in schizophrenic patients. The unaffected siblings of schizophrenic patients showed no evidence of any compensatory increase in fitness, but there was a trend towards enhanced fertility among the offspring of schizophrenia patients. Patients with affective psychosis and their relatives did not differ from the general population on any fertility measure.

Schizophrenia, but not affective psychosis, is associated with reduced biological fertility; this disadvantage is partly explained by marital status and persists into the second generation.

Few studies have examined the underlying factor structure of signs and symptoms occurring before the first psychotic episode. Our objective was to determine whether factors derived from early signs and symptoms are differentially associated with non-affective versus affective psychosis.

A principal components factor analysis was performed on early signs and symptoms reported by 128 individuals with first-episode psychosis. Factor scores were examined for their associations with duration of untreated illness, drug abuse prior to onset of psychosis, and diagnosis (schizophrenia versus affective psychosis).

Of the 27 early signs and symptoms reported by patients, depression and anxiety were the most frequent. Five factors were identified based on these early signs and symptoms: depression, disorganization/mania, positive symptoms, negative symptoms and social withdrawal. Longer duration of untreated illness was associated with higher levels of depression and social withdrawal. Individuals with a history of drug abuse prior to the onset of psychosis scored higher on pre-psychotic depression and negative symptoms. The two mood-related factors, depression and disorganization/mania, distinguished the eventual first-episode diagnosis of affective psychosis from schizophrenia. Individuals with affective psychosis were also more likely to have a ‘mood-related’ sign and symptom as their first psychiatric change than individuals later diagnosed with schizophrenia.

Factors derived from early signs and symptoms reported by a full diagnostic spectrum sample of psychosis can have implications for future diagnostic trajectories. The findings are a step forward in the process of understanding and characterizing clinically important phenomena to be observed prior to the onset of psychosis.

Psychotic illness is strongly associated with the maternal uniparental disomy (mUPD) genetic subtype of Prader–Willi syndrome (PWS), but not the deletion subtype (delPWS). This study investigates the clinical features of psychiatric illness associated with PWS. We consider possible genetic and other mechanisms that may be responsible for the development of psychotic illness, predominantly in those with mUPD.

The study sample comprised 119 individuals with genetically confirmed PWS, of whom 46 had a history of psychiatric illness. A detailed clinical and family psychiatric history was obtained from these 46 using the PAS-ADD, OPCRIT, Family History and Life Events Questionnaires.

Individuals with mUPD had a higher rate of psychiatric illness than those with delPWS (22/34 v. 24/85, p<0.001). The profile of psychiatric illness in both genetic subtypes resembled an atypical affective disorder with or without psychotic symptoms. Those with delPWS were more likely to have developed a non-psychotic depressive illness (p=0.005) and those with mUPD a bipolar disorder with psychotic symptoms (p=0.00005). Individuals with delPWS and psychotic illness had an increased family history of affective disorder. This was confined exclusively to their mothers.

Psychiatric illness in PWS is predominately affective with atypical features. The prevalence and possibly the severity of illness are greater in those with mUPD. We present a ‘two-hit’ hypothesis, involving imprinted genes on chromosome 15, for the development of affective psychosis in people with PWS, regardless of genetic subtype.