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BackgroundA transdiagnostic and contextual framework of ‘clinical characterization’, combining clinical, psychopathological, sociodemographic, etiological, and other personal contextual data, may add clinical value over and above categorical algorithm-based diagnosis.MethodsPrediction of need for care and health care outcomes was examined prospectively as a function of the contextual clinical characterization diagnostic framework in a prospective general population cohort (n = 6646 at baseline), interviewed four times between 2007 and 2018 (NEMESIS-2). Measures of need, service use, and use of medication were predicted as a function of any of 13 DSM-IV diagnoses, both separately and in combination with clinical characterization across multiple domains: social circumstances/demographics, symptom dimensions, physical health, clinical/etiological factors, staging, and polygenic risk scores (PRS). Effect sizes were expressed as population attributable fractions.ResultsAny prediction of DSM-diagnosis in relation to need and outcome in separate models was entirely reducible to components of contextual clinical characterization in joint models, particularly the component of transdiagnostic symptom dimensions (a simple score of the number of anxiety, depression, mania, and psychosis symptoms) and staging (subthreshold, incidence, persistence), and to a lesser degree clinical factors (early adversity, family history, suicidality, slowness at interview, neuroticism, and extraversion), and sociodemographic factors. Clinical characterization components in combination predicted more than any component in isolation. PRS did not meaningfully contribute to any clinical characterization model.ConclusionA transdiagnostic framework of contextual clinical characterization is of more value to patients than a categorical system of algorithmic ordering of psychopathology.

Background Empirical evidence suggests that people use cannabis to ameliorate anxiety and depressive symptoms, yet cannabis also acutely worsens psychosis and affective symptoms. However, the temporal relationship between cannabis use, anxiety and depressive symptoms and psychotic experiences (PE) in longitudinal studies is unclear. This may be informed by examination of mutually mediating roles of cannabis, anxiety and depressive symptoms in the emergence of PE. Methods Data were derived from the second longitudinal Netherlands Mental Health Survey and Incidence Study. Mediation analysis was performed to examine the relationship between cannabis use, anxiety/depressive symptoms and PE, using KHB logit in STATA while adjusting for age, sex and education status. Results Cannabis use was found to mediate the relationship between preceding anxiety, depressive symptoms and later PE incidence, but the indirect contribution of cannabis use was small (for anxiety: % of total effect attributable to cannabis use = 1.00%; for depression: % of total effect attributable to cannabis use = 1.4%). Interestingly, anxiety and depressive symptoms were found to mediate the relationship between preceding cannabis use and later PE incidence to a greater degree (% of total effect attributable to anxiety = 17%; % of total effect attributable to depression = 37%). Conclusion This first longitudinal cohort study examining the mediational relationship between cannabis use, anxiety/depressive symptoms and PE, shows that there is a bidirectional relationship between cannabis use, anxiety/depressive symptoms and PE. However, the contribution of anxiety/depressive symptoms as a mediator was greater than that of cannabis.

BackgroundThere is evidence that environmental and genetic risk factors for schizophrenia spectrum disorders are transdiagnostic and mediated in part through a generic pathway of affective dysregulation.MethodsWe analysed to what degree the impact of schizophrenia polygenic risk (PRS-SZ) and childhood adversity (CA) on psychosis outcomes was contingent on co-presence of affective dysregulation, defined as significant depressive symptoms, in (i) NEMESIS-2 (n = 6646), a representative general population sample, interviewed four times over nine years and (ii) EUGEI (n = 4068) a sample of patients with schizophrenia spectrum disorder, the siblings of these patients and controls.ResultsThe impact of PRS-SZ on psychosis showed significant dependence on co-presence of affective dysregulation in NEMESIS-2 [relative excess risk due to interaction (RERI): 1.01, p = 0.037] and in EUGEI (RERI = 3.39, p = 0.048). This was particularly evident for delusional ideation (NEMESIS-2: RERI = 1.74, p = 0.003; EUGEI: RERI = 4.16, p = 0.019) and not for hallucinatory experiences (NEMESIS-2: RERI = 0.65, p = 0.284; EUGEI: −0.37, p = 0.547). A similar and stronger pattern of results was evident for CA (RERI delusions and hallucinations: NEMESIS-2: 3.02, p < 0.001; EUGEI: 6.44, p < 0.001; RERI delusional ideation: NEMESIS-2: 3.79, p < 0.001; EUGEI: 5.43, p = 0.001; RERI hallucinatory experiences: NEMESIS-2: 2.46, p < 0.001; EUGEI: 0.54, p = 0.465).ConclusionsThe results, and internal replication, suggest that the effects of known genetic and non-genetic risk factors for psychosis are mediated in part through an affective pathway, from which early states of delusional meaning may arise.

BackgroundAnxiety disorders frequently recur in clinical populations, but the risk of recurrence of anxiety disorders is largely unknown in the general population. In this study, recurrence of anxiety and its predictors were studied in a large cohort of the adult general population.MethodsBaseline, 3-year and 6-year follow-up data were derived from the Netherlands Mental Health Survey and Incidence Study-2 (NEMESIS-2). Respondents (N = 468) who had been in remission for at least a year prior to baseline were included. Recurrence was assessed at 3 and 6 years after baseline, using the Composite International Diagnostic Interview version 3.0. Cumulative recurrence rates were estimated using the number of years since remission of the last anxiety disorder. Furthermore, Cox regression analyses were conducted to investigate predictors of recurrence, using a broad range of putative predictors.ResultsThe estimated cumulative recurrence rate was 2.1% at 1 year, 6.6% at 5 years, 10.6% at 10 years, and 16.2% at 20 years. Univariate regression analyses predicted a shorter time to recurrence for several variables, of which younger age at interview, parental psychopathology, neuroticism and a current depressive disorder remained significant in the, age and gender-adjusted, multivariable regression analysis.ConclusionsRecurrence of anxiety disorders in the general population is common and the risk of recurrence extends over a lengthy period of time. In clinical practice, alertness to recurrence, monitoring of symptoms, and quick access to health care in case of recurrence are needed.

BackgroundEvidence suggests that cannabis use, childhood adversity, and urbanicity, in interaction with proxy measures of genetic risk, may facilitate onset of psychosis in the sense of early affective dysregulation becoming ‘complicated’ by, first, attenuated psychosis and, eventually, full-blown psychotic symptoms.MethodsData were derived from three waves of the second Netherlands Mental Health Survey and Incidence Study (NEMESIS-2). The impact of environmental risk factors (cannabis use, childhood adversity, and urbanicity) was analyzed across severity levels of psychopathology defined by the degree to which affective dysregulation was ‘complicated’ by low-grade psychotic experiences (‘attenuated psychosis’ – moderately severe) and, overt psychotic symptoms leading to help-seeking (‘clinical psychosis’ – most severe). Familial and non-familial strata were defined based on family history of (mostly) affective disorder and used as a proxy for genetic risk in models of family history × environmental risk interaction.ResultsIn proxy gene–environment interaction analysis, childhood adversity and cannabis use, and to a lesser extent urbanicity, displayed greater-than-additive risk if there was also evidence of familial affective liability. In addition, the interaction contrast ratio grew progressively greater across severity levels of psychosis admixture (none, attenuated psychosis, clinical psychosis) complicating affective dysregulation.ConclusionKnown environmental risks interact with familial evidence of affective liability in driving the level of psychosis admixture in states of early affective dysregulation in the general population, constituting an affective pathway to psychosis. There is interest in decomposing family history of affective liability into the environmental and genetic components that underlie the interactions as shown here.

BackgroundThe jumping to conclusions (JTC) reasoning bias and decreased working memory performance (WMP) are associated with psychosis, but associations with affective disturbances (i.e. depression, anxiety, mania) remain inconclusive. Recent findings also suggest a transdiagnostic phenotype of co-occurring affective disturbances and psychotic experiences (PEs). This study investigated whether JTC bias and decreased WMP are associated with co-occurring affective disturbances and PEs.MethodsData were derived from the second Netherlands Mental Health Survey and Incidence Study (NEMESIS-2). Trained interviewers administered the Composite International Diagnostic Interview (CIDI) at three time points in a general population sample (N = 4618). The beads and digit-span task were completed to assess JTC bias and WMP, respectively. CIDI was used to measure affective disturbances and an add-on instrument to measure PEs.ResultsCompared to individuals with neither affective disturbances nor PEs, the JTC bias was more likely to occur in individuals with co-occurring affective disturbances and PEs [moderate psychosis (1–2 PEs): adjusted relative risk ratio (RRR) 1.17, 95% CI 0.98–1.41; and high psychosis (3 or more PEs or psychosis-related help-seeking behaviour): adjusted RRR 1.57, 95% CI 1.19–2.08], but not with affective disturbances and PEs alone, whereas decreased WMP was more likely in all groups. There was some evidence of a dose–response relationship, as JTC bias and decreased WMP were more likely in individuals with affective disturbances as the level of PEs increased or help-seeking behaviour was reported.ConclusionThe findings suggest that JTC bias and decreased WMP may contribute to a transdiagnostic phenotype of co-occurring affective disturbances and PEs.

BackgroundAlthough hallucinations have been studied in terms of prevalence and its associations with psychopathology and functional impairment, very little is known about sensory modalities other than auditory (i.e. haptic, visual and olfactory), as well the incidence of hallucinations, factors predicting incidence and subsequent course.MethodsWe examined the incidence, course and risk factors of hallucinatory experiences across different modalities in two unique prospective general population cohorts in the same country using similar methodology and with three interview waves, one over the period 1996–1999 (NEMESIS) and one over the period 2007–2015 (NEMESIS-2).ResultsIn NEMESIS-2, the yearly incidence of self-reported visual hallucinations was highest (0.33%), followed by haptic hallucinations (0.31%), auditory hallucinations (0.26%) and olfactory hallucinations (0.23%). Rates in NEMESIS-1 were similar (respectively: 0.35%, 0.26%, 0.23%, 0.22%). The incidence of clinician-confirmed hallucinations was approximately 60% of the self-reported rate. The persistence rate of incident hallucinations was around 20–30%, increasing to 40–50% for prevalent hallucinations. Incident hallucinations in one modality were very strongly associated with occurrence in another modality (median OR = 59) and all modalities were strongly associated with delusional ideation (median OR = 21). Modalities were approximately equally strongly associated with the presence of any mental disorder (median OR = 4), functioning, indicators of help-seeking and established environmental risk factors for psychotic disorder.ConclusionsHallucinations across different modalities are a clinically relevant feature of non-psychotic disorders and need to be studied in relation to each other and in relation to delusional ideation, as all appear to have a common underlying mechanism.

Background. There is increasing evidence that subthreshold forms of psychopathology are both common and clinically relevant. To enable classification of these subthreshold forms of psychopathology, it may be useful to distinguish not only a threshold for illness but also for health. Our aim was to investigate this with regard to panic.Method. Data were derived from the Netherlands Mental Health Survey and Incidence Study (NEMESIS), which is based on a large representative sample of the adult general population (18–65 years) of The Netherlands (n=7076). The Composite International Diagnostic Interview was used as a diagnostic instrument. By defining two thresholds, three groups were formed: panic disorder, subthreshold panic disorder and no-panic. These groups were compared using multinomial regression analysis, χ2 and analysis of variance.Results. The 12-month prevalence of panic disorder was 2·2% while that of subthreshold panic disorder was 1·9%. Symptom profiles and risk indicators associated with panic disorder and subthreshold panic disorder were similar, and half of the risk indicators were more strongly associated with panic disorder than with subthreshold panic disorder. Subthreshold panic disorder occupied an intermediate position between panic disorder and no-panic with regard to the number of symptoms, the percentage of subjects with co-morbidity, and functioning.Conclusions. Subthreshold panic disorder is common, and seems clinically relevant, but is milder than panic disorder. These results thus support the use of a double threshold in panic. Further research should focus on the positioning of the thresholds, the course of subthreshold panic disorder and its treatment options.

Background. Developmental adversities may be risk factors for adult suicidal behavior, but this relationship has rarely been studied prospectively. The present study examined the association between childhood adversities and new onset suicidal ideation and attempts in an adult population-based sample.Method. The study used a large community mental health survey (the Netherlands Mental Health Survey and Incidence Study; n=7076, age range 18–64 years). Logistic regression analyses were used to evaluate the relationship between childhood adversities and new onset of suicidal ideation and attempts over 3 years of longitudinal follow-up.Results. During the study period 85 new cases of suicidal ideation and 39 new onset suicide attempts were observed. The incidence rate for new suicide ideation was 0·67% per year and the incidence rate for new suicide attempts was 0·28% per year. Childhood neglect, psychological abuse and physical abuse were strongly associated with new onset suicidal ideation and suicide attempts. Odds ratios (ORs) ranged from 2·80 to 4·66 for new onset suicidal ideation and from 3·60 to 5·43 for new onset suicide attempts. The total number of adversities reported had a strong graded relationship to new onset suicidal ideation and attempts. These associations remained significant after controlling for the effects of mental disorders.Conclusions. Childhood abuse and multiple adversities are strongly associated with future suicidal behavior and the mental disorders assessed in the present study do not fully account for this effect. A comprehensive understanding of suicidal behavior must take childhood adversities into account.