The influence of risk factors on the onset and outcome of psychosis: What we learned from the GAP study.

The GAP multidisciplinary study carried out in South London, recruited 410 first episode of psychosis patients and 370 controls; the aim was to elucidate the multiple genetic and environmental factors influencing the onset and outcome of psychosis. The study demonstrated the risk increasing effect of adversity in childhood (especially parental loss, abuse, and bullying) on onset of psychosis especially positive symptoms. Adverse life events more proximal to onset, being from an ethnic minority, and cannabis use also played important roles; indeed, one quarter of new cases of psychosis could be attributed to use of high potency cannabis. The "jumping to conclusions" bias appeared to mediate the effect of lower IQ on vulnerability to psychosis. We confirmed that environmental factors operate on the background of polygenic risk, and that genetic and environment act together to push individuals over the threshold for manifesting the clinical disorder. The study demonstrated how biological pathways involved in the stress response (HPA axis and immune system) provide important mechanisms linking social risk factors to the development of psychotic symptoms. Further evidence implicating an immune/inflammatory component to psychosis came from our finding of complement dysregulation in FEP. Patients also showed an upregulation of the antimicrobial alpha-defensins, as well as differences in expression patterns of genes involved in NF-κB signaling and Cytokine Production. Being of African origin not only increased risk of onset but also of a more difficult course of illness. The malign effect of childhood adversity predicted a poorer outcome as did continued use of high potency cannabis.

Further evidence of a cumulative effect of social disadvantage on risk of psychosis.

BACKGROUND: A growing body of evidence suggests that indicators of social disadvantage are associated with an increased risk of psychosis. However, only a few studies have specifically looked at cumulative effects and long-term associations. The aims of this study are: To compare the prevalence of specific indicators of social disadvantage at, and prior to, first contact with psychiatric services in patients suffering their first episode of psychosis and in a control sample. To explore long-term associations, cumulative effects, and direction of effects. METHOD: We collected information on social disadvantage from 332 patients and from 301 controls recruited from the local population in South London. Three indicators of social disadvantage in childhood and six indicators of social disadvantage in adulthood were analysed. RESULTS: Across all the domains considered, cases were more likely to report social disadvantage than were controls. Compared with controls, cases were approximately two times more likely to have had a parent die and approximately three times more likely to have experienced a long-term separation from one parent before the age of 17 years. Cases were also more likely than controls to report two or more indicators of adult social disadvantage, not only at first contact with psychiatric services [odds ratio (OR) 9.5], but also at onset of psychosis (OR 8.5), 1 year pre-onset (OR 4.5), and 5 years pre-onset (OR 2.9). CONCLUSIONS: Greater numbers of indicators of current and long-term exposure are associated with progressively greater odds of psychosis. There is some evidence that social disadvantage tends to cluster and accumulate.

Impact of childhood adversities on specific symptom dimensions in first-episode psychosis.

BACKGROUND: The relationship between childhood adversity (CA) and psychotic disorder is well documented. As the adequacy of the current categorical diagnosis of psychosis is being increasingly questioned, we explored independent associations between different types of CA and specific psychotic symptom dimensions in a well-characterized sample of first-episode psychosis (FEP) patients. METHOD: This study involved 236 FEP cases aged 18-65 years who presented for the first time to psychiatric services in South London, UK. Psychopathology was assessed with the Positive and Negative Syndrome Scale and confirmatory factor analysis was used to evaluate the statistical fit of the Wallwork/Fortgang five-factor model of psychosis. CA prior to 17 years of age (physical abuse, sexual abuse, parental separation, parental death, and being taken into care) was retrospectively assessed using the Childhood Experience of Care and Abuse Questionnaire. RESULTS: Childhood sexual abuse [ß = 0.96, 95% confidence interval (CI) 0.40-1.52], childhood physical abuse (ß = 0.48, 95% CI 0.03-0.93) and parental separation (ß = 0.60, 95% CI 0.10-1.11) showed significant associations with the positive dimension; while being taken into care was associated with the excited dimension (ß = 0.36, 95% CI 0.08-0.65), independent of the other types of CA. No significant associations were found between parental death and any of the symptom dimensions. CONCLUSIONS: A degree of specificity was found in the relationships between different types of CA and psychosis symptom dimensions in adulthood, suggesting that distinct pathways may be involved in the CA-psychosis association. These potentially different routes to developing psychosis merit further empirical and theoretical exploration.

Differences in cannabis-related experiences between patients with a first episode of psychosis and controls.

BACKGROUND: Many studies have reported that cannabis use increases the risk of a first episode of psychosis (FEP). However, only a few studies have investigated the nature of cannabis-related experiences in FEP patients, and none has examined whether these experiences are similar in FEP and general populations. The aim of this study was to explore differences in self-reported cannabis experiences between FEP and non-psychotic populations. METHOD: A total of 252 subjects, who met International Classification of Diseases (ICD)-10 criteria for FEP, and 217 controls who reported cannabis use were selected from the Genetics and Psychosis (GAP) study. The Medical Research Council Social Schedule and the Cannabis Experience Questionnaire were used to collect sociodemographic data and cannabis use information, respectively. RESULTS: Both 'bad' and 'enjoyable' experiences were more commonly reported by FEP subjects than controls. Principal components factor analysis identified four components which explained 62.3% of the variance. Linear regression analysis on the whole sample showed that the type of cannabis used and beliefs about the effect of cannabis on health all contributed to determining the intensity and frequency of experiences. Linear regression analysis on FEP subjects showed that the duration of cannabis use and amount of money spent on cannabis were strongly related to the intensity and frequency of enjoyable experiences in this population. CONCLUSIONS: These results suggest a higher sensitivity to cannabis effects among people who have suffered their first psychotic episode; this hypersensitivity results in them reporting both more 'bad' and 'enjoyable' experiences. The greater enjoyment experienced may provide an explanation of why FEP patients are more likely to use cannabis and to continue to use it despite experiencing an exacerbation of their psychotic symptoms.

Failure to find association between childhood abuse and cognition in first-episode psychosis patients.

This study investigated the relationship between severe childhood abuse and cognitive functions in first-episode psychosis patients and geographically-matched controls. Reports of any abuse were associated with lower scores in the executive function domain in the control group. However, in contrast with our hypothesis, no relationships were found amongst cases.