'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.

Is sensitivity to daily stress predictive of onset or persistence of psychopathology?

PURPOSE: The aim of the current study was to replicate findings in adults indicating that higher sensitivity to stressful events is predictive of both onset and persistence of psychopathological symptoms in a sample of adolescents and young adults. In addition, we tested the hypothesis that sensitivity to mild stressors in particular is predictive of the developmental course of psychopathology. METHODS: We analyzed experience sampling and questionnaire data collected at baseline and one-year follow-up of 445 adolescent and young adult twins and non-twin siblings (age range: 15-34). Linear multilevel regression was used for the replication analyses. To test if affective sensitivity to mild stressors in particular was associated with follow-up symptoms, we used a categorical approach adding variables on affective sensitivity to mild, moderate and severe daily stressors to the model. RESULTS: Linear analyses showed that emotional stress reactivity was not associated with onset (ß=.02; P=.56) or persistence (ß=-.01; P=.78) of symptoms. There was a significant effect of baseline symptom score (ß=.53; P<.001) and average negative affect (NA: ß=.19; P<.001) on follow-up symptoms. Using the categorical approach, we found that affective sensitivity to mild (ß=.25; P<.001), but not moderate (ß=-.03; P=.65) or severe (ß=-.06; P=.42), stressors was associated with symptom persistence one year later. DISCUSSION: We were unable to replicate previous findings relating stress sensitivity linearly to symptom onset or persistence in a younger sample. Whereas sensitivity to more severe stressors may reflect adaptive coping, high sensitivity to the mildest of daily stressors may indicate an increased risk for psychopathology.

Does the Social Functioning Scale reflect real-life social functioning? An experience sampling study in patients with a non-affective psychotic disorder and healthy control individuals.

BACKGROUND: The ecological validity of retrospective measures of social functioning is currently unknown in patients with schizophrenia. In the present study, patients with a diagnosis of non-affective psychosis were compared with controls on two measures of social functioning: the Social Functioning Scale (SFS) and daily-life measures collected with the Experience Sampling Methodology (ESM). The associations between both measures were examined in each group of participants to test for the ecological validity of the SFS. METHODS: A total of 126 participants with a non-affective psychotic disorder and 109 controls completed the SFS and a 6-day momentary ESM protocol assessing various aspects of social functioning. Multiple linear and multilevel regression analyses were performed to test for group differences in social functioning level and examine associations between the two assessment techniques. RESULTS: Lower social functioning was observed in patients compared with controls on retrospective and momentary measures. The SFS interpersonal domain (social engagement/withdrawal and interpersonal behaviour dimensions) was associated with the percentage of time spent alone and negative appraisal of social interactions. The SFS activity domain (pro-social and recreational activities dimensions) was negatively associated with time spent in leisure activities. CONCLUSIONS: The SFS showed some degree of ecological validity at assessing broad aspects of social functioning. Low scores on the SFS social engagement/withdrawal and interpersonal behaviour dimensions captured social isolation and social avoidance in daily life, but not lack of interest in socializing. Ecological validity of the SFS activity domain was low. ESM offers a rich alternative to classical assessment techniques of social functioning.

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 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.

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.

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.

A computer program using BALF-analysis results as a diagnostic tool in interstitial lung diseases.

Recently, we showed that it is possible to distinguish between three common interstitial lung diseases (ILD) with similarities in clinical presentation by using a number of selected variables derived from bronchoalveolar lavage fluid (BALF) analysis. The aim of this study was to develop a more general discriminant model, based on polychotomous logistic regression analysis. The 277 patients involved in the study belonged to diagnostic groups with sarcoidosis (n = 193), extrinsic allergic alveolitis (EAA; n = 39), and idiopathic pulmonary fibrosis (IPF; n = 45). The diagnosis had been established independently of the BALF-analysis results. The variables used to discriminate among these patient groups were the yield of recovered BALF, total cell count, and percentages of alveolar macrophages, lymphocytes, neutrophils, and eosinophils. In order to test the predictive power of the logistic model, we used 128 patients having sarcoidosis (n = 91), EAA (n = 5), or IPF (n = 32) from another hospital. In this test set the agreement of predicted with actual diagnostic-group membership was the same as in the learning set in which the logistic model was fitted: 94.5% of the cases were correctly classified. A validated computer program based on the polychotomous logistic regression model can be used to predict the diagnosis for an arbitrary patient with information provided by BALF analysis, and is thought to be of diagnostic value in patients suspected of having ILD.

Tracheobronchopathia osteochondroplastica. Report of four cases.

Tracheobronchopathia osteochondroplastica is a rare abnormality, characterised by the presence of polyps in the trachea and main bronchi; these polyps consist of cartilaginous and/or osseous metaplastic tissue. The clinical findings in four patients are described. The pathogenesis is unknown. Treatment is usually not indicated and the prognosis is good. Where there is significant obstruction of the airways, endoscopic removal seems to be the treatment of choice.