[Interplay between genetic background and environmental factors in psychiatry: current situation and future prospects]. / Samenspel tussen genetische achtergrond en omgevingsfactoren in de psychiatrie: stand van zaken en toekomstperspectief.

BACKGROUND: The hypothesis that etiopathogeneses of psychiatric disorders are determined by interplay between genetic background and environmental factors, as well their interactions can increasingly be put to direct scientific test, based on a wave of methodological, technological and knowledge developments.
AIM: To provide insight into and to provide perspective on some important scientific developments and facilitate challenges in this area.
METHOD: Narrative overview of the scientific literature and formulation of a concept and future perspective.
RESULTS: The overview points to concrete progress in the fields of genetic epidemiology, environmental analyses, gene-environment interactions and epigenetics in psychiatry. For example, recent studies have provided evidence for the existence of interactions and correlations between genetic and environmental factors, interdependence of risk-influencing effects of environmental factors, and translational neurobiological studies have identified biological processes that influence the impact of (or the response to) environmental influences on individuals mediate. These important steps to translate epidemiological research into testable biological hypotheses are facilitated by new techniques and the availability of large and relevant clinical and biological datasets.
CONCLUSION: Scientific progress on the interplay between genetic background and environmental factors enriches the conceptual framework of the etiopathogenesis of mental disorders and provides a future perspective in which we are likely to receive answers to a number of clinically relevant questions in the coming decade.
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Polygenic liability for schizophrenia and childhood adversity influences daily-life emotion dysregulation and psychosis proneness.

OBJECTIVE: To test whether polygenic risk score for schizophrenia (PRS-S) interacts with childhood adversity and daily-life stressors to influence momentary mental state domains (negative affect, positive affect, and subtle psychosis expression) and stress-sensitivity measures. METHODS: The data were retrieved from a general population twin cohort including 593 adolescents and young adults. Childhood adversity was assessed using the Childhood Trauma Questionnaire. Daily-life stressors and momentary mental state domains were measured using ecological momentary assessment. PRS-S was trained on the latest Psychiatric Genetics Consortium schizophrenia meta-analysis. The analyses were conducted using multilevel mixed-effects tobit regression models. RESULTS: Both childhood adversity and daily-life stressors were associated with increased negative affect, decreased positive affect, and increased subtle psychosis expression, while PRS-S was only associated with increased positive affect. No gene-environment correlation was detected. There is novel evidence for interaction effects between PRS-S and childhood adversity to influence momentary mental states [negative affect (b = 0.07, P = 0.013), positive affect (b = -0.05, P = 0.043), and subtle psychosis expression (b = 0.11, P = 0.007)] and stress-sensitivity measures. CONCLUSION: Exposure to childhood adversities, particularly in individuals with high PRS-S, is pleiotropically associated with emotion dysregulation and psychosis proneness.

The role of stress-regulation genes in moderating the association of stress and daily-life psychotic experiences.

OBJECTIVE: The interaction of single nucleotide polymorphisms with both distal and proximal environmental factors across the extended psychosis phenotype is understudied. This study examined (i) the interaction of relevant SNPs with both early-life adversity and proximal (momentary) stress on psychotic experiences (PEs) in an extended psychosis sample; and (ii) differences between early-psychosis and non-clinical groups for these interactions. METHODS: Two hundred and forty-two non-clinical and 96 early-psychosis participants were prompted randomly eight times daily for 1 week to complete assessments of current experiences, including PEs and stress. Participants also reported on childhood trauma and were genotyped for 10 SNPs on COMT, RGS4, BDNF, FKBP5, and OXTR genes. RESULTS: Unlike genetic variants, distal and proximal stressors were associated with PEs in both samples and were more strongly associated with PEs in the early-psychosis than in the non-clinical group. The RGS4 TA and FKBP5 CATT haplotypes interacted with distal stress, whereas the A allele of OXTR (rs2254298) interacted with proximal stress, increasing momentary levels of PEs in the early-psychosis group. No interactions emerged with COMT or BDNF variants. CONCLUSION: Individual differences in relevant stress-regulation systems interact with both distal and proximal psychosocial stressors in shaping the daily-life manifestation of PEs across the psychosis continuum.

The functional and clinical relevance of childhood trauma-related admixture of affective, anxious and psychosis symptoms.

OBJECTIVE: Previous work has shown that across different patient samples, patients with childhood trauma are more likely to have co-occurrence of affective, anxious and psychosis symptoms than non-traumatized patients. However, the clinical relevance of trauma-related admixture remains to be established. METHOD: We examined patients with mood disorder (NEMESIS-2; n = 1260), anxiety disorder (NEMESIS-2; n = 896) or psychotic disorder (GROUP; n = 532) in terms of symptom profiles, quality of life (QOL) and social functioning. RESULTS: Results showed that mood disorder patients with both trauma and co-occurrence of affective, anxious and psychosis symptoms had a lower QOL (B-12.6, 95% CI -17.7 to -7.5, P < 0.001), more help-seeking behaviour [odds ratio (OR) 2.5, 95% CI 1.1-5.7, P = 0.031] and higher prevalence of substance use disorders (OR 7.8, 95% CI 1.1-58.0, P = 0.044), compared with patients without trauma history and symptom admixture (Trauma-/CL-). Similar results were found in patients with an anxiety disorder. Traumatized patients with a psychotic disorder and admixture showed lower QOL (B-0.6, 95% CI -0.9 to -0.4, P < 0.001), higher prevalence of drug disorders (OR 2.2, 95% CI 1.2-3.9, P = 0.008) and lower global assessment of functioning (B-12.8, 95% CI -17.1 to -8.5, P < 0.001) than Trauma-/CL- patients. CONCLUSION: Stratification according to childhood trauma exposure thus identifies a phenotype characterized by admixture of affective, anxiety and psychotic symptoms that, when combined, has clinical relevance. Identification of functionally meaningful aetiological subgroups may aid clinical practice.

Evidence that the presence of psychosis in non-psychotic disorder is environment-dependent and mediated by severity of non-psychotic psychopathology.

BACKGROUND: Evidence suggests that in affective, non-psychotic disorders: (i) environmental exposures increase risk of subthreshold psychotic experiences (PEs) and strengthen connectivity between domains of affective and subthreshold psychotic psychopathology; and (ii) PEs are a marker of illness severity. METHOD: In 3021 adolescents from the Early Developmental Stages of Psychopathology cohort, we tested whether the association between PEs and presence of DSM-IV mood disorder (MD)/obsessive-compulsive disorder (OCD) would be moderated by risk factors for psychosis (cannabis use, childhood trauma and urbanicity), using the interaction contrast ratio (ICR) method. Furthermore, we analysed whether the interaction between environment and PEs was mediated by non-psychotic psychopathology. RESULTS: The association between PEs and MD/OCD was moderated by urbanicity (ICR = 2.46, p = 0.005), cannabis use (ICR = 3.76, p = 0.010) and, suggestively, trauma (ICR = 1.91, p = 0.063). Exposure to more than one environmental risk factor increased the likelihood of co-expression of PEs in a dose-response fashion. Moderating effects of environmental exposures were largely mediated by the severity of general non-psychotic psychopathology (percentage explained 56-68%, all p < 0.001). Within individuals with MD/OCD, the association between PEs and help-seeking behaviour, as an index of severity, was moderated by trauma (ICR = 1.87, p = 0.009) and urbanicity (ICR = 1.48, p = 0.005), but not by cannabis use. CONCLUSIONS: In non-psychotic disorder, environmental factors increase the likelihood of psychosis admixture and help-seeking behaviour through an increase in general psychopathology. The findings are compatible with a relational model of psychopathology in which more severe clinical states are the result of environment-induced disturbances spreading through a psychopathology network.

Childhood trauma is associated with a specific admixture of affective, anxiety, and psychosis symptoms cutting across traditional diagnostic boundaries.

BACKGROUND: Meta-analyses link childhood trauma to depression, mania, anxiety disorders, and psychosis. It is unclear, however, whether these outcomes truly represent distinct disorders following childhood trauma, or that childhood trauma is associated with admixtures of affective, psychotic, anxiety and manic psychopathology throughout life. METHOD: We used data from a representative general population sample (NEMESIS-2, n = 6646), of whom respectively 1577 and 1120 had a lifetime diagnosis of mood or anxiety disorder, as well as from a sample of patients with a diagnosis of schizophrenia (GROUP, n = 825). Multinomial logistic regression was used to assess whether childhood trauma was more strongly associated with isolated affective/psychotic/anxiety/manic symptoms than with their admixture. RESULTS: In NEMESIS-2, largely comparable associations were found between childhood trauma and depression, mania, anxiety and psychosis. However, childhood trauma was considerably more strongly associated with their lifetime admixture. These results were confirmed in the patient samples, in which it was consistently found that patients with a history of childhood trauma were more likely to have a combination of multiple symptom domains compared to their non-traumatized counterparts. This pattern was also found in exposed individuals who did not meet criteria for a psychotic, affective or anxiety disorder and who did not seek help for subclinical psychopathology. CONCLUSIONS: Childhood trauma increases the likelihood of a specific admixture of affective, anxiety and psychotic symptoms cutting across traditional diagnostic boundaries, and this admixture may already be present in the earliest stages of psychopathology. These findings may have significant aetiological, pathophysiological, diagnostic and clinical repercussions.

Childhood abuse and neglect in relation to the presence and persistence of psychotic and depressive symptomatology.

BACKGROUND: The association between childhood trauma and psychotic and depressive symptomatology is well established. However, less is known about the specificity and course of these symptoms in relation to childhood trauma. METHOD: In a large sample (n = 2765) of patients with psychosis (n = 1119), their siblings (n = 1057) and controls (n = 589), multivariate (mixed-effects) regression analyses with multiple outcomes were performed to examine the association between childhood trauma and psychotic and depressive symptomatology over a 3-year period. RESULTS: A dose-response relationship was found between childhood trauma and psychosis. Abuse was more strongly associated with positive symptoms than with negative symptoms whereas the strength of the associations between neglect and positive and negative symptoms was comparable. In patients, similar associations between childhood trauma and psychotic or depressive symptoms were found, and in siblings and controls, stronger associations were found between trauma and depressive symptomatology. Childhood trauma was not related to a differential course of symptoms over a 3-year time period. CONCLUSIONS: In congruence with earlier work, our findings suggest that childhood trauma, and abuse in particular, is associated with (subthreshold) psychosis. However, childhood trauma does not seem to be associated with a differential course of symptoms, nor does it uniquely heighten the chance of developing (subthreshold) psychotic symptomatology. Our results indicate that trauma may instead contribute to a shared vulnerability for psychotic and depressive symptoms.

Systematic review and collaborative recalculation of 133,693 incident cases of schizophrenia.

BACKGROUND: This systematic review and collaborative recalculation was set up to recalculate schizophrenia incidence rates from previously published studies by age and sex. METHOD: PubMed, EMBASE and PsycINFO databases were searched (January 1950 to December 2009) for schizophrenia incidence studies. Numerator and population data were extracted by age, sex and, if possible, study period. Original data were requested from the authors to calculate age- and sex-specific incidence rates. Incidence rate ratios (IRRs) with their 95% confidence intervals (CIs) were computed by age and sex from negative binomial regression models. RESULTS: Forty-three independent samples met inclusion criteria, yielding 133 693 incident cases of schizophrenia for analysis. Men had a 1.15-fold (95% CI 1.00-1.31) greater risk of schizophrenia than women. In men, incidence peaked at age 20-29 years (median rate 4.15/10,000 person-years, IRR 2.61, 95% CI 1.74-3.92). In women, incidence peaked at age 20-29 (median rate 1.71/10,000 person-years, IRR 2.34, 95% CI 1.66-3.28) and 30-39 years (median rate 1.24/10,000 person-years, IRR 2.25, 95% CI 1.55-3.28). This peak was followed by an age-incidence decline up to age 60 years that was stronger in men than in women (χ² = 57.90, p < 0.001). The relative risk of schizophrenia was greater in men up to age 39 years and this reversed to a greater relative risk in women over the age groups 50-70 years. No evidence for a second incidence peak in middle-aged women was found. CONCLUSIONS: Robust sex differences exist in the distribution of schizophrenia risk across the age span, suggesting differential susceptibility to schizophrenia for men and women at different stages of life.

Does social defeat mediate the association between childhood trauma and psychosis? Evidence from the NEMESIS-2 Study.

OBJECTIVE: Based on theoretical considerations and animal studies, mediation of 'social defeat' (SD) in the association between childhood trauma (CT) and psychosis was investigated. METHOD: Trained interviewers administered a structured interview assessing CT, psychotic experiences and other psychopathology in 6646 participants in the second Netherlands Mental Health Survey and Incidence Study (NEMESIS-2). RESULTS: Childhood trauma was associated with psychotic experiences making up the extended psychosis phenotype (EPP), as well as with a diagnosis of psychotic disorder (PD). Similarly, CT was associated with a priori selected items indexing SD (discouraged, hopeless, worthless, loss of self-confidence, low self-esteem, better off dead, suicidal thoughts) and with a measure of affective dysregulation (AD), which in turn were also associated with psychosis. While SD and AD individually acted as mediators in the association between CT and EPP, only SD acted as a mediator in the association between CT and PD. Cannabis use did not mediate the association between CT and EPP or PD. CONCLUSION: The present results suggest a developmental model implicating SD as an important mediator in the link between childhood adverse experiences and later development of psychotic experiences. The combined mediation by SD and AD is compatible with an 'affective pathway' to early psychosis.

Testing the hypothesis that psychotic illness begins when subthreshold hallucinations combine with delusional ideation.

OBJECTIVE: While hallucinations and delusions are often considered as a single class of 'positive symptoms', little is known about their dynamic cooccurrence in relation to clinical outcome in non-help-seeking people. METHOD: The Netherlands Mental Health and Incidence Study (NEMESIS-1) is a longitudinal study of mental disorders (n = 7075) with three measurements over a 3-year period. Risk factors, persistence of psychotic experiences, and clinical outcome were analyzed for groups with: i) no psychotic experiences, ii) only delusions, iii) only hallucinations, and iv) both delusions and hallucinations. RESULTS: Hallucinations and delusions occurred together more often (T0, 3.5%; T1, 1.0%; T2, 0.9%) than that predicted by chance (T0, 1.0%; T1, 0.1%; T2, 0.04%). The group with both symptoms showed more 'first-rank'-like delusions compared with the group with only delusions. Having both hallucinations and delusions, compared to isolated symptoms, was associated more strongly with risk factors, comorbid affective symptoms, negative symptoms, and persistence of psychotic experiences. This was not an artifact of having more symptoms in general. CONCLUSION: Experiencing both delusions and hallucinations is an indicator of greater etiological load resulting in more clinical outcome. A specific 'hallucinatory-delusional state' may represent an early phase of exacerbation of aberrant attribution of salience, increasing risk for clinical outcome.

[Cannabis use and the risk of psychotic disorders. An update]. / Cannabis als risicofactor voor psychose: een update.

BACKGROUND: The use of cannabis has been linked to an increased risk for psychosis, irrespective of confounding factors such as age, gender, use of other drugs and reverse causality. Over the last few years a great deal of research has been done to broaden our understanding of the underlying mechanisms of this link. AIM: To update studies that have examined the link between cannabis use and psychosis and that have investigated the possible mechanisms underlying this link. METHOD: This article discusses recent epidemiological and experimental research that sheds light on the nature of the link and the influence of interactions between genes and environment. RESULTS: The long-term effects of cannabis on the risk factors for psychosis and psychotic disorders are influenced to a large extent by genetic and environmental factors. Furthermore, patients with a psychotic disorder seem to be extremely vulnerable to the acute effects of cannabis. CONCLUSION: Studies show that cannabis use is an important risk factor for psychosis and psychotic disorders. So far, however, less research has been done into the effects of cannabis use on patients already suffering from a psychotic disorder.

Self-monitoring as a familial vulnerability marker for psychosis: an analysis of patients, unaffected siblings and healthy controls.

BACKGROUND: Alterations in self-monitoring have been reported in patients with psychotic disorders, but it remains unclear to what degree they represent true indicators of familial vulnerability for psychosis. METHOD: An error-correction action-monitoring task was used to examine self-monitoring in 42 patients with schizophrenia, 32 of their unaffected siblings and 41 healthy controls. RESULTS: Significant between-group differences in self-monitoring accuracy were found (χ2=29.3, p<0.0001), patients performing worst and unaffected siblings performing at an intermediate level compared to controls (all between-group differences p<0.05). In the combined group of healthy controls and unaffected siblings, detection accuracy was associated with positive schizotypy as measured by the Structured Interview for Schizotypy - Revised (SIS-R) (ß=-0.16, s.e.=0.07, p=0.026), but not with negative schizotypy (ß=-0.05, s.e.=0.12, p=0.694). In patients, psychotic symptoms were not robustly associated with detection accuracy (ß=-0.01, s.e.=0.01, p=0.094), although stratified analysis revealed suggestive evidence for association in patients not currently using antipsychotic medication (ß=-0.03, s.e.=0.01, p=0.052), whereas no association was found in patients on antipsychotic medication (ß=-0.01, s.e.=0.01, p=0.426). A similar pattern of associations was found for negative symptoms. CONCLUSIONS: Alterations in self-monitoring may be associated with familial risk and expression of psychosis. The association between psychotic symptoms and self-monitoring in patients may be affected by antipsychotic medication, which may explain previous inconsistencies in the literature.

Early trauma and familial risk in the development of the extended psychosis phenotype in adolescence.

OBJECTIVE: Both genetic and environmental factors are thought to play a role in the development of psychotic outcomes; however, their respective contributions over time, including possible developmental interactions, remain largely unknown. METHOD: The contribution of parental general and psychotic psychopathology as proxies of genetic risk to the development of subthreshold psychosis and its hypothesized interaction with childhood trauma were studied in a general population sample of 2230 adolescents, followed from age 10-16 years. Outcome measures were: i) level of psychotic experiences at age 16 years and ii) persistence of such experiences over the total follow-up period. RESULTS: General parental psychopathology was associated with CAPE score (OR = 1.08; P < 0.043 for highest quintile) and suggestively predicted psychosis persistence (OR, 1.16; P < 0.072). Psychotic parental psychopathology was suggestively associated with CAPE score (OR, 2.25; P < 0.063 for highest quintile), predicted membership of the Persistent group (OR, 3.72; P < 0.039) and suggestively predicted membership of the Decreasing group (OR 2.04; P < 0.051). Childhood trauma was associated with CAPE score and with all developmental trajectories of subclinical psychosis. No evidence was found for an interaction between trauma and parental psychopathology. CONCLUSION: The development and persistence of subthreshold psychotic symptoms may be conditional on non-interacting proxy genetic and environmental influences.

Evidence that interactive effects of COMT and MTHFR moderate psychotic response to environmental stress.

OBJECTIVE: A functional interaction between Catechol-O-Methyltransferase (COMT) Val158Met and methylenetetrahydrofolate reductase (MTHFR) C677T has been shown to differentially affect cognition in patients with schizophrenia and healthy controls; the effect of COMT Val158Met × MTHFR interaction on resilience to stress in patients and controls remains to be examined. METHOD: A total of 98 patients with non-affective psychotic disorder and 118 controls were genotyped for MTHFR C677T, MTHFR A1298C, and COMTVal158Met. Daily life reactivity to stress, modelled as the effect of daily life stress on psychotic experiences, was measured using the experience sampling method (ESM). RESULTS: The MTHFR C677T genotype moderated the interaction between COMT Val158Met genotype and stress in patients (P < 0.0001), but not in controls (P = 0.68). Further examination of this interaction revealed that in patients with the MTHFR 677 T-allele, COMT Met/Met individuals displayed the largest increases in psychotic symptoms in reaction to ESM stress [χ(2)(2) = 29.51; P < 0.0001], whereas in patients with the MTHFR 677 C/C genotype no significant COMT Val158Met × ESM stress interaction was apparent [χ(2)(2) = 3.65; P = 0.16]. No moderating effect of MTHFR A1298C was found. CONCLUSION: Stress reactivity associated with COMT Val158Met in patients with psychosis may crucially depend on MTHFR C677T genotype.

Guidelines for screening and monitoring of cardiometabolic risk in schizophrenia: systematic evaluation.

BACKGROUND: Metabolic and cardiovascular health problems have become a major focus for clinical care and research in schizophrenia. AIMS: To evaluate the content and quality of screening guidelines for cardiovascular risk in schizophrenia. METHOD: Systematic review and quality assessment of guidelines/recommendations for cardiovascular risk in people with schizophrenia published between 2000 and 2010, using the Appraisal of Guidelines for Research and Evaluation (AGREE). RESULTS: The AGREE domain scores varied between the 18 identified guidelines. Most guidelines scored best on the domains 'scope and purpose' and 'clarity of presentation'. The domain 'rigour of development' was problematic in most guidelines, and the domains 'stakeholder involvement' and 'editorial independence' scored the lowest. The following measurements were recommended (in order of frequency): fasting glucose, body mass index, fasting triglycerides, fasting cholesterol, waist, high-density lipoprotein/low-density lipoprotein, blood pressure and symptoms of diabetes. In terms of interventions, most guidelines recommended advice on physical activity, diet, psychoeducation of the patient, treatment of lipid abnormalities, treatment of diabetes, referral for advice and treatment, psychoeducation of the family and smoking cessation advice. Compared across all domains and content, four European guidelines could be recommended. CONCLUSIONS: Four of the evaluated guidelines are of good quality and should guide clinicians' screening and monitoring practices. Future guideline development could be improved by increasing its rigour and assuring user and patient involvement.

Evidence for a persistent, environment-dependent and deteriorating subtype of subclinical psychotic experiences: a 6-year longitudinal general population study.

BACKGROUND: Research suggests that subclinical psychotic experiences during adolescence represent the behavioral expression of liability for psychosis. Little is known, however, about the longitudinal trajectory of liability in general population samples. METHOD: Growth mixture modeling was used to examine longitudinal trajectories of self-reported positive psychotic experiences in the Youth Self Report (YSR), completed three times over a period of 6 years by a general population cohort of adolescents aged 10-11 years at baseline (n=2230). RESULTS: Four groups with distinct developmental trajectories of low, decreasing, increasing and persistent levels of mild positive psychotic experiences were revealed. The persistent trajectory was associated strongly with cannabis use, childhood trauma, developmental problems and ethnic minority status, and consistently displayed strong associations with factors known to predict transition from subclinical psychotic experience to clinical psychotic disorder (severity of and secondary distress due to psychotic experiences, social and attentional problems and affective dysregulation) and also with high levels of parental-reported psychotic experiences and use of mental health care at the end of the follow-up period. Progressively weaker associations were found for the increasing, decreasing and low trajectories respectively. CONCLUSIONS: The results suggest that the outcome of early developmental deviation associated with later expression of psychotic experiences is contingent on the degree of later interaction with environmental risks inducing, first, persistence of psychotic experiences and, second, progression to onset of need for care and service use. Insight into the longitudinal dynamics of risk states in representative samples may contribute to the development of targeted early intervention in psychosis.

[Clinical assessment of the ultra high risk of developing a a psychotic disorder; review and critical reflection]. / Klinische beoordeling van sterk verhoogd risico op psychose: overzicht en kritische reflectie.

BACKGROUND: It may be possible to improve the prognosis of psychotic disorders by the timely recognition and treatment of the early stages of these disorders. Since the first psychotic episode is often preceded by a period of non-specific symptoms and functional decline, it could be worthwhile investigating whether this early phase can be detected. AIM: To review existing diagnostic approaches and clinical instruments that are currently used for prospective identification of the prodromal phase. METHOD: We searched the literature between 1995 and 2009 using the search terms 'prodromal' or 'ultra high risk' in combination with 'psychosis' or 'schizophrenia' and 'assessment'. RESULTS: In international literature we found four diagnostic approaches to ultra high risk of psychosis: the attenuated positive symptom approach, the basic symptom approach, the clinical high risk approach and the strictly phenomenological approach. Within each of these approaches specific screening instruments had been developed and tested with regard to their ability to correctly predict a first psychotic episode. CONCLUSION: None of the current diagnostic approaches produces a sufficiently reliable prediction of the risk of a first psychotic episode. Within the group of persons assumed, based on screening, to be at very high risk, only a small percentage will actually develop a psychotic disorder.

[The therapeutic value of physical exercise for people with schizophrenia]. / De therapeutische waarde van bewegen voor mensen met schizofrenie.

BACKGROUND: Only about 25% of people with schizophrenia follow the public health recommendations for a minimum of 150 minutes per week of moderate physical exercise. In their leisure time people diagnosed with schizophrenia take considerably less exercise than their healthy counterparts. AIM: To collect scientific evidence of movement-related interventions in patients with schizophrenia. METHOD: PubMed, PEDro, CINAHL, PsychINFO and Sport Discus were searched for the period from 2003 up to April 2009 for reports of randomised controlled trials (RCTs) on the basis of the search terms 'schizophrenia', 'exercise' and 'physical activity'. Relevant literature was also traced by means of the reference lists for selected articles. RESULTS: Eight RCTs were selected. Physical exercise was reported to bring about significant improvements in cardiovascular and metabolic parameters and in psychiatric symptomatology. A physical exercise also has social advantages; it helps patients to cope with stress and improves their quality of life. CONCLUSION: Physical exercise as part of psychomotor therapy should play an important role within the multidisciplinary treatment of schizophrenia. More research is needed into the effect of physical activity on cognitive functioning.

[Stress and psychosis: is sensitisation the underlying mechanism?]. / Stress en psychose: vormt sensitisatie het onderliggend mechanisme?

Epidemiological research has shown that stressful environmental factors can play an aetiological role in the development of psychosis. However, the mechanism underlying the link between stress and psychosis is still not fully understood. In this article it is argued that the interaction between stressful environmental factors and epigenetic factors can bring about psychological and biological changes. Both types of change can be referred to as 'sensitisation'. The underlying mechanism of sensitisation can be interpreted on the one hand as cognitive misinterpretations (psychological sensitisation) and on the other hand as altered dopaminergic neurotransmission (biological sensitisation). Both of these deviations can facilitate the onset and persistence of psychotic symptoms. With the help of epidemiological research at psychometric level sensitisation can be quantified as (i) stress-induced persistence (indicating continuous sensitisation) of the normally transient expression of subclinical psychotic experiences during adolescence and early adulthood and as (ii) the increased risk of transition from gradually more persistent subclinical psychotic experiences to a clinical psychotic disorder.

'False-positive' self-reported psychotic experiences in the general population: an investigation of outcome, predictive factors and clinical relevance.

AIMS.: Self-reported psychotic experiences (SRPE) by individuals from the general population are often unconfirmed by clinical interview and referred to as 'false-positive' (FP) SRPE. FP SRPE have been suggested to represent the mildest form of risk along the extended psychosis continuum. However, little is known about their (clinical) outcome and evolution over time. Aims of this study were to prospectively examine, in individuals with FP SRPE, (1) the prevalence of remission, persistence and transition to validated PE at 3-year follow-up; (2) potential baseline psychopathological and psychosocial predictors of persistence of FP SRPE and transition to validated PE; and (3) whether those with persistent FP SRPE and validated PE already differed on psychopathology and psychosocial factors at baseline. We tested the hypotheses that (i) individuals with FP SRPE would be more likely to have SRPE and validated PE at follow-up; and (ii) that FP SRPE would be predictive of lower functioning and more psychopathology and help-seeking behaviour at follow-up. METHODS.: Baseline (n = 6646) and 3-year follow-up (n = 5303) data of the second the Netherlands Mental Health Survey and Incidence Study (NEMESIS-2), a general population research project on prevalence, incidence, course and consequences of psychiatric disorders was used. Self-report of PE was followed by clinical interview to determine clinical validity. The presence of mood, anxiety and substance use disorders, childhood adversity, help-seeking and functioning as well as PE characteristics (number, frequency, distress and impact) were used in the analyses which included only individuals with complete data for both assessments waves (n = 4683). RESULTS.: At baseline, 454 participants had any FP SRPE; of these 372 participants had complete follow-up data available. Those with baseline FP SRPE were significantly more likely to report SRPE (OR = 3.58; 95% CI 2.38-5.40, p < 0.001) and validated PE (OR = 6.26; 95% CI 3.91-10.02, p < 0.001) at follow-up. Baseline FP SRPE also predicted the presence of mood and anxiety disorders, reduced functioning and help-seeking at follow-up. Several baseline psychopathological, psychosocial and PE characteristics were predictive for the persistence of SRPE. These factors also differentiated groups with FP SRPE or validated PE from those with remitted FP SRPE at follow-up. CONCLUSIONS.: 'FP SRPE' are not truly 'false' as they index risk for the development of clinically relevant psychotic symptoms, development of mood and anxiety disorders and reduced functioning. Self-reported PE, even unconfirmed, warrant 'watchful waiting' and follow-up over time, especially when they are reported by individuals with reduced psychosocial functioning and general psychiatric problems.