Previous work suggests that reaction time variability (RTV) in attentional tasks, as a measure of cognitive stability, is associated with degree of Val loading in COMT Val158Met genotype, and that this association may be relevant for the aetiology of schizophrenia. This study examined (i) to what degree RTV pertaining to tasks of varying cognitive complexity would be associated with increased risk for schizophrenia and (ii) to what degree this would be mediated by Val loading.

COMT genotyping was investigated in a sample of 23 patients with schizophrenia, 33 first-degree relatives, and 21 controls. All participants performed the Flanker continuous performance test.

Schizophrenia liability was associated with number of correct trials of the Flanker test, but not with RTV, and this association was not mediated by COMT Val158Met genotype. Similarly, Met loading was associated with number of correct trials and with RTV, but this was not mediated by schizophrenia liability.

Associations between COMT Val158Met genotype and RTV do not appear to reflect transmission of schizophrenia liability in families. Differential associations with Val and Met alleles across studies suggest indirect effects through gene–gene interactions or the influence of a functional polymorphism near COMT Val158Met.

Psychosis is characterized by problems in social functioning that exist well before illness onset, and in individuals at clinical high risk (CHR) for psychosis. Trust is an essential element for social interactions that is impaired in psychosis. In the trust game, chronic patients showed reduced baseline trust, impaired response to positive social feedback, and attenuated brain activation in reward and mentalizing areas. We investigated whether first-episode psychosis patients (FEP) and CHR show similar abnormalities in the neural and behavioral mechanisms underlying trust.

Twenty-two FEP, 17 CHR, and 43 healthy controls performed two trust games, with a cooperative and an unfair partner in the fMRI scanner. Region of interest analyses were performed on mentalizing and reward processing areas, during the investment and outcome phases of the games.

Compared with healthy controls, FEP and CHR showed reduced baseline trust, but like controls, learned to trust in response to cooperative and unfair feedback. Symptom severity was not associated with baseline trust, however in FEP associated with reduced response to feedback. The only group differences in brain activation were that CHR recruited the temporo-parietal junction (TPJ) more than FEP and controls during investment in the unfair condition. This hyper-activation in CHR was associated with greater symptom severity.

Reduced baseline trust may be associated with risk for psychotic illness, or generally with poor mental health. Feedback learning is still intact in CHR and FEP, as opposed to chronic patients. CHR however show distinct neural activation patterns of hyper-activation of the TPJ.

Psychotic patients with COMTVal158Met Met alleles were recently found to display more intense psychotic and affective responses to daily life stressors. We aimed to test the hypothesis that the Met allele is implicated in the development of affective and psychotic symptomatology in subjects genetically at risk for schizophrenia, by testing if unaffected first-degree relatives of patients with schizophrenia who share a Met allele have greater concordance of symptomatology than relatives not sharing a Met allele.

Unaffected relatives (n = 38) were arranged in as many genetically related pairs as possible (n = 26), and Met-sharing between Index Unaffected Subject (IUS) and Related Unaffected Subject (RUS) was assessed. Symptomatology was assessed with the Brief Psychiatric Rating Scale (BPRS) total score.

Multilevel regression revealed an interaction between RUS BPRS score and Met-sharing in the model of IUS BPRS score (interaction χ2 = 3.78, p = 0.05). Stratified analyses revealed that IUS–RUS total BPRS scores were significantly associated in the case of Met-sharing (B = 0.57, 95% CI: 0.22–0.93, p = 0.002), but were not when there was no Met-sharing.

These findings support the hypothesis that the Met allele may be involved in the causation of psychopathology, at least in populations with a genetic predisposition to psychosis.

A disorder of self-monitoring may underlie the positive symptoms of psychosis. The cognitive mechanisms associated with these symptoms may also be detectable in individuals at risk of psychosis

To investigate (a) whether patients with psychosis show impaired self-monitoring, (b) to what degree this is associated with positive symptoms, and (c) whether this is associated with liability to psychotic symptoms

The sample included: individuals with a lifetime history of non-affective psychosis (n=37), a genetically defined risk group (n=41), a psychometrically defined risk group (n=40), and control group (n=49). All participants carried out an action-recognition task

Number of action – recognition errors was associated with psychosis risk (OR linear trend over 3 levels: 1.12, 95% CI 1.04–1.20) and differential error rate was associated with the degree of delusional ideation in a dose–response fashion (OR linear trend over 3 levels: 1.13, 95% CI 1.00–1.26)

Alterations in self-monitoring are associated with psychosis with evidence of specificity for delusional ideation. In the risk state, this is expressed more as failure to recognise self-generated actions, whereas in illness failure to recognise alien sources come to the fore

The reported link between psychological trauma and onset of psychosis remains controversial.

To examine associations between self-reported psychological trauma and psychotic symptoms as a function of prior evidence of vulnerability to psychosis (psychosis proneness).

At baseline, 2524 adolescents aged 14–24 years provided self-reports on psychological trauma and psychosis proneness, and at follow-up (on average 42 months later) participants were interviewed for presence of psychotic symptoms.

Self-reported trauma was associated with psychotic symptoms, in particular at more severe levels (adjusted OR 1.89, 95% CI 1.16–3.08) and following trauma associated with intense fear, helplessness or horror. The risk difference between those with and without self-reported trauma at baseline was 7% in the group with baseline psychosis proneness, but only 1.8% in those without (adjusted test for difference between these two effect sizes: χ2=4.6, P=0.032).

Exposure to psychological trauma may increase the risk of psychotic symptoms in people vulnerable to psychosis.

Contemporary cognitive psychological theories suggest that distress plays a mediating role in delusion formation.

To study the amplifying role of distress from early perceptual intrusions to delusion formation.

A general population sample of 7076 individuals was interviewed with the Composite International Diagnostic Interview (CIDI) in 1996 (baseline), 1997 (T1) and 1999 (T2). At T2, clinicians also scored the Brief Psychiatric Rating Scale (BPRS) item ‘unusual thought content’. Analyses compared hallucinatory experiences with and without subjective distress at baseline for risk of delusion formation at follow-up.

Individuals experiencing hallucinations with distress, compared with those without distress had a fourfold increased risk of subsequent delusion formation.

This finding corroborates the hypothesis that distress associated with early perceptual intrusions serves as a catalyst in the development of delusions.