Philippe Delespaul

A systematic review and meta-analysis of the psychosis continuum: evidence for a psychosis proneness–persistence–impairment model of psychotic disorder

A systematic review of all reported incidence and prevalence studies of population rates of subclinical psychotic experiences reveals a median prevalence rate of around 5% and a median incidence rate of around 3%. A meta-analysis of risk factors reveals associations with developmental stage, child and adult social adversity, psychoactive drug use, and also male sex and migrant status. The small difference between prevalence and incidence rates, together with data from follow-up studies, indicates that approximately 75-90% of developmental psychotic experiences are transitory and disappear over time. There is evidence, however, that transitory developmental expression of psychosis (psychosis proneness) may become abnormally persistent (persistence) and subsequently clinically relevant (impairment), depending on the degree of environmental risk the person is additionally exposed to. The psychosis proneness-persistence-impairment model considers genetic background factors impacting on a broadly distributed and transitory population expression of psychosis during development, poor prognosis of which, in terms of persistence and clinical need, is predicted by environmental exposure interacting with genetic risk.

Emotional reactivity to daily life stress in psychosis and affective disorder: an experience sampling study.

Objective:  To investigate the emotional reactivity to small disturbances in daily life in patients with non‐affective psychosis (NAP), bipolar disorder (BD) and major depression [major depressive disorder (MDD)].

Determinants of occurrence and recovery from hallucinations in daily life

Background Data related to the dynamics of hallucinatory experiences of patients suffering from schizophrenia are scarce. Detecting antecedent conditions and coping strategies may aid development of targeted psychological interventions. Method We studied hallucinating and non-hallucinating patients suffering from schizophrenia spectrum disorder (n = 57), and non-schizophrenic severe mentally ill patients with depression (n = 37). Data were collected using the Experience Sampling Method (ESM) over a period of 1 week. Contingent on a randomly signalling beep, subjects filled in reports of ongoing hallucinations as well as thought, mood, current activity, social circumstances and places frequented. Results More subjects suffering from schizophrenia reported hallucinations, but for all hallucinating subjects the qualities of hallucination episodes were quite similar. More subjects reported visual hallucinations at least once. In contrast, the intensity of auditory hallucinations was higher. Anxiety was the most prominent emotion during hallucinations and reports of anxiety intensity exceeded baseline levels before the first report of auditory hallucinations. Context modified hallucination intensity over the course of an episode. Social withdrawal resulted in a decrease of hallucinatory intensity (AH > VH), while social engagement slightly raised intensity levels (VH > AH). Doing nothing (VH > AH) and work activities (AH > VH) led to decreases in intensity levels over time, while passive leisure activities (watching TV) resulted in increases in intensity levels of hallucinations (AH > VH). Conclusion The results suggest that hallucinating experiences are subject to a host of contextual influences. Understanding variation offers useful insights for therapy.

The schizophrenia envirome

Purpose of review To show which aspects of the environment increase the risk for schizophrenia and how they interact with pre-existing liability for psychosis. Recent findings Not only does cannabis survive as a risk factor for psychosis, but the evidence is showing concrete synergistic effects between cannabis and pre-existing liability to psychosis. The urban environment is, in terms of attributable risk, the most important proxy environmental risk factor. There is evidence that it interacts with genetic risk and it has been hypothesized that the mechanism involves the cumulative effects of altered social interactions at the individual level and possibly also at the level of the wider social environment, such as the neighbourhood. Early trauma is another aspect of the environment that has recently been linked prospectively to psychosis, and meta-analytic work demonstrates conclusively that minority status is a risk factor, part of which may be mediated by chronic exposure to discrimination. Prenatal environmental effects may involve folate or vitamin D deficiency, viral infections or adverse effects associated with low or high birth weight. The mechanism by which the environment is likely to impact on risk is through cognitive and emotional pathways on the one hand, and biological pathways, possibly involving dopamine sensitization, on the other. Summary Several synergistic mechanisms involving proxy measures of genes and proxy measures of the environment, such as gene–cannabis, gene–urbanicity and gene–stress interactions, offer concrete avenues to pursue research that stands a good chance of elucidating at least some of the causes of schizophrenia.

A momentary assessment study of the relationship between affective and adrenocortical stress responses in daily life

The tendency to experience negative emotions in the face of stress may lead to repeated overactivation of the hypothalamic-pituitary-adrenal axis. In a sample of 556 women, this study used the Experience Sampling Method to assess different daily stressors, current mood, and salivary cortisol, 10 times daily for 5 days. Multilevel analyses estimated the contributions of stressors and mood states as predictors of salivary cortisol secretion. Results showed that minor stressors were associated with decreased positive affect and increased negative affect, agitation, and cortisol. Of the mood states, only negative affect was independently associated with cortisol. Negative affect also mediated effects of daily stressors on cortisol. Although further research is needed to clarify: (i) the causal pathways between daily stress, mood, and cortisol and (ii) the importance of daily stress reactivity as a prospective risk factor, these findings confirm that minor daily stressors can influence emotional and biological processes involved in subjective well-being.

Evidence that moment‐to‐moment variation in positive emotions buffer genetic risk for depression: a momentary assessment twin study

Objective:  The negative affective response to daily life stressors, which previous work suggest is a fundamental depression endophenotype, may be moderated by positive emotions. It was investigated whether positive affect (PA) buffers negative affect (NA) reactivity in response to stress and whether PA moderates the genetic predisposition to negative affect reactivity.

Meta-analysis of MTHFR gene variants in schizophrenia, bipolar disorder and unipolar depressive disorder: evidence for a common genetic vulnerability?

Past analyses examining the relationship between genetic variation in the 5, 10-methylenetetrahydrofolate reductase (MTHFR) gene and psychiatric disorders have provided mixed and largely inconclusive findings. MTHFR is involved in the one-carbon metabolic pathway which is essential for DNA biosynthesis and the epigenetic process of DNA methylation. We conducted a meta-analysis of all published case-control studies investigating associations between two common MTHFR single nucleotide polymorphisms (SNPs), MTHFR C677T (sample size 29,502) and A1298C (sample size 7934), and the major psychiatric disorders (i) schizophrenia (SZ), (ii) bipolar disorder (BPD), and (iii) unipolar depressive disorder (UDD). In order to examine possible shared genetic vulnerability, we also tested for associations between MTHFR and all of these major psychiatric disorders (SZ, BPD and UDD) combined. MTHFR C677T was significantly associated with all of the combined psychiatric disorders (SZ, BPD and UDD); random effects odds ratio (OR)=1.26 for TT versus CC genotype carriers; confidence interval (CI) 1.09-1.46); meta-regression did not suggest moderating effects of psychiatric diagnosis, sex, ethnic group or year of publication. Although MTHFR A1298C was not significantly associated with the combination of major psychiatric disorders, nor with SZ, there was evidence for diagnostic moderation indicating a significant association with BPD (random effects OR=2.03 for AA versus CC genotype carriers, CI: 1.07-3.86). Meta-analysis on UDD was not possible due to the small number of studies available. This study provides evidence for shared genetic vulnerability for SZ, BPD and UDD mediated by MTHFR 677TT genotype, which is in line with epigenetic involvement in the pathophysiology of these psychiatric disorders.

The context of delusional experiences in the daily life of patients with schizophrenia

BACKGROUND Global characteristics and psychosocial risk factors related to delusions have been identified. The present study extends these findings to the level of everyday functioning, identifying characteristics of delusional moments (DMs) and contextual risk and protective factors for delusional exacerbations in daily life. METHODS Data were collected using the Experience Sampling Method (ESM), a time-sampling technique. Forty-eight chronic patients diagnosed with schizophrenia rated the intensity of pathological symptoms and mood states and described their thoughts and the environmental context during consecutive moments in daily life. Delusions were defined on the basis of self-rated suspicion, preoccupation, feeling controlled, and coded thought pathology. Daily context included current activity, persons present and location. Characteristics of DMs and non-delusional moments (nDMs) were compared, and a multilevel logistic regression model was used to identify contexts that might trigger or prevent DMs. RESULTS On average, patients experienced delusions less than one-third of the time. DMs were characterized by higher negative affect and lower positive affect. The presence of family or acquaintances decreased the risk of subsequently experiencing a DM, whereas withdrawal from activities increased this risk. CONCLUSIONS Data support the validity of ESM for investigating delusions in schizophrenia. Daily life contexts appear to alter the probability that delusions will occur. Knowledge about such contexts may therefore be useful in helping patients develop better coping strategies and in creating therapeutic interventions that can lessen emotional distress.

Experience sampling research in individuals with mental illness: reflections and guidance

Palmier‐Claus JE, Myin‐Germeys I, Barkus E, Bentley L, Udachina A, Delespaul PAEG, Lewis SW, Dunn G. Experience sampling research in individuals with mental illness: reflections and guidance.

COMT ValMet moderation of cannabis-induced psychosis: a momentary assessment study of 'switching on' hallucinations in the flow of daily life

Objective:  A functional polymorphism in the catechol‐o‐methyltransferase gene (COMT Val158Met) may moderate the psychosis‐inducing effects of cannabis. In order to extend this finding to dynamic effects in the flow of daily life, a momentary assessment study of psychotic symptoms in response to cannabis use was conducted.