Claudia J. P. Simons

Are Psychotic Psychopathology and Neurocognition Orthogonal? A Systematic Review of their Associations.

A systematic review (58 studies, 5,009 individuals) is presented of associations between psychopathological dimensions of psychosis and measures of neurocognitive impairment in subjects with a lifetime history of nonaffective psychosis. Results showed that negative and disorganized dimensions were significantly but modestly associated with cognitive deficits (correlations from -.29 to -.12). In contrast, positive and depressive dimensions of psychopathology were not associated with neurocognitive measures. The patterns of association for the 4 psychosis dimensions were stable across neurocognitive domains and were independent of age, gender, and chronicity of illness. In addition, significantly higher correlations were found for the negative dimension in relation to verbal fluency (p = .005) and for the disorganized dimension in relation to reasoning and problem solving (p = .004) and to attention/vigilance (p = .03). Psychotic psychopathology and neurocognition are not entirely orthogonal, as heterogeneity in nonaffective psychosis is weakly but meaningfully associated with measures of neurocognition. This association suggests that differential latent cerebral mechanisms underlie the cluster of disorganized and negative symptoms versus that of positive and affective symptoms.

Genetic Risk and Outcome of Psychosis (GROUP), a multi site longitudinal cohort study focused on gene-environment interaction : objectives, sample characteristics, recruitment and assessment methods

A longitudinal focus on gene–environment vulnerability and resilience in both patients, their unaffected family members and non‐related controls offers the opportunity to elucidate etiological and pathogenetic factors influencing the onset and course of psychotic disorders. The current paper delineates the objectives, sample characteristics, recruitment and assessment procedures of the Genetic Risk and Outcome of Psychoses (GROUP) study.

Unveiling patterns of affective responses in daily life may improve outcome prediction in depression: A momentary assessment study

OBJECTIVE Daily life affective responses are closely linked to vulnerability and resilience in depression. Prediction of future clinical course may be improved if information on daily life emotional response patterns is taken into account. METHOD Female subjects with a history of major depression (n=83), recruited from a population twin register, participated in a longitudinal study using momentary assessment technology with 4 follow-up measurements. The effect of baseline daily life emotional response patterns (affect variability, stress-sensitivity and reward experience) on follow-up depressive symptomatology was examined. RESULTS Both reward experience (B=-0.30, p=0.001) and negative affect variability (B=0.46, p=0.001) predicted future negative affective symptoms independent of all other dynamic emotional patterns and conventional predictors. CONCLUSION Daily life information on dynamic emotional patterns adds to the prediction of future clinical course, independent of severity of symptoms and neuroticism score. Better prediction of course may improve decision-making regarding quantitative and qualitative aspects of treatment.

A therapeutic application of the experience sampling method in the treatment of depression: a randomized controlled trial

In depression, the ability to experience daily life positive affect predicts recovery and reduces relapse rates. Interventions based on the experience sampling method (ESM‐I) are ideally suited to provide insight in personal, contextualized patterns of positive affect. The aim of this study was to examine whether add‐on ESM‐derived feedback on personalized patterns of positive affect is feasible and useful to patients, and results in a reduction of depressive symptomatology. Depressed outpatients (n=102) receiving pharmacological treatment participated in a randomized controlled trial with three arms: an experimental group receiving add‐on ESM‐derived feedback, a pseudo‐experimental group participating in ESM but receiving no feedback, and a control group. The experimental group participated in an ESM procedure (three days per week over a 6‐week period) using a palmtop. This group received weekly standardized feedback on personalized patterns of positive affect. Hamilton Depression Rating Scale – 17 (HDRS) and Inventory of Depressive Symptoms (IDS) scores were obtained before and after the intervention. During a 6‐month follow‐up period, five HDRS and IDS assessments were completed. Add‐on ESM‐derived feedback resulted in a significant and clinically relevant stronger decrease in HDRS score relative to the control group (p<0.01; −5.5 point reduction in HDRS at 6 months). Compared to the pseudo‐experimental group, a clinically relevant decrease in HDRS score was apparent at 6 months (B=−3.6, p=0.053). Self‐reported depressive complaints (IDS) yielded the same pattern over time. The use of ESM‐I was deemed acceptable and the provided feedback easy to understand. Patients attempted to apply suggestions from ESM‐derived feedback to daily life. These data suggest that the efficacy of traditional passive pharmacological approach to treatment of major depression can be enhanced by using person‐tailored daily life information regarding positive affect.

FKBP5 as a possible moderator of the psychosis-inducing effects of childhood trauma

BACKGROUND FK506 binding protein 5 (FKBP5) has repeatedly been shown to be a critical determinant of post-traumatic stress disorder (PTSD) and depression following childhood trauma. AIMS To examine the role of FKBP5-trauma interactions in the partly stress-related psychosis phenotype. METHOD In 401 general population twins, four functional polymorphisms were examined in models of psychosis and cortisol, and followed up in models of psychosis in three samples at different familial liability (175 controls, 200 unaffected siblings and 195 patients with a psychotic disorder). RESULTS The most consistent finding was an interaction between childhood trauma and rs9296158/rs4713916 on psychotic symptoms and cortisol in the twin sample, combined with a directionally similar interaction in siblings (rs4713916) and patients (rs9296158), A-allele carriers at both polymorphisms being most vulnerable to trauma. CONCLUSIONS Trauma may increase the risk of psychosis through enduring changes in the cortisol feedback loop, similar to that for PTSD, suggesting comparable biological mechanisms for psychosis across diagnostic boundaries.

Momentary assessment technology as a tool to help patients with depression help themselves

Wichers M, Simons CJP, Kramer IMA, Hartmann JA, Lothmann C, Myin‐Germeys I, van Bemmel AL, Peeters F, Delespaul P, van Os J. Momentary assessment technology as a tool to help patients with depression help themselves.

Subtle gene–environment interactions driving paranoia in daily life

It has been suggested that genes impact on the degree to which minor daily stressors cause variation in the intensity of subtle paranoid experiences. The objective of the present study was to test the hypothesis that catechol‐O‐methyltransferase (COMT) Val158Met and brain‐derived neurotrophic factor (BDNF) Val66Met in part mediate genetic effects on paranoid reactivity to minor stressors. In a general population sample of 579 young adult female twins, on the one hand, appraisals of (1) event‐related stress and (2) social stress and, on the other hand, feelings of paranoia in the flow of daily life were assessed using momentary assessment technology for five consecutive days. Multilevel regression analyses were used to examine moderation of daily life stress‐induced paranoia by COMT Val158Met and BDNF Val66Met genotypes. Catechol‐O‐methyltransferase Val carriers displayed more feelings of paranoia in response to event stress compared with Met carriers. Brain‐derived neurotrophic factor Met carriers showed more social‐stress‐induced paranoia than individuals with the Val/Val genotype. Thus, paranoia in the flow of daily life may be the result of gene–environment interactions that can be traced to different types of stress being moderated by different types of genetic variation.

AKT1 Moderation of Cannabis-Induced Cognitive Alterations in Psychotic Disorder

Genetic variation in AKT1 may be associated with sensitivity to the psychotomimetic effects of cannabis as well as with increased risk for psychotic disorder following cannabis use. Investigation of the effect of this interaction on relevant intermediate phenotypes for psychosis, such as cognition, may help to clarify the underlying mechanism. Thus, verbal memory (visually presented Word Learning Task), sustained attention (Continuous Performance Test, CPT), AKT1 rs2494732 genotype, and cannabis use were examined in a large cohort of patients with psychotic disorder. No evidence was found for AKT1 × cannabis interaction on verbal memory. Cannabis use preceding onset of psychotic disorder did interact significantly with AKT1 rs2494732 genotype to affect CPT reaction time (β=8.0, SE 3.9, p=0.037) and CPT accuracy (β=−1.2, SE 0.4, p=0.003). Cannabis-using patients with the a priori vulnerability C/C genotype were slower and less accurate on the CPT, whereas cannabis-using patients with the T/T genotype had similar or better performance than non-using patients with psychotic disorder. The interaction was also apparent in patients with psychotic disorder who had not used cannabis in the 12 months preceding assessment, but was absent in the unaffected siblings of these patients and in healthy controls. In conclusion, cannabis use before onset of psychosis may have long-lasting effects on measures of sustained attention, even in the absence of current use, contingent on AKT1 rs2494732 genotype. The results suggest that long-term changes in cognition may mediate the risk-increasing effect of the AKT1 × cannabis interaction on psychotic disorder.

Functional magnetic resonance imaging of inner speech in schizophrenia

BACKGROUND Auditory verbal hallucinations in schizophrenia have been linked to defective monitoring of ones own verbal thoughts. Previous studies have shown that patients with auditory verbal hallucinations show attenuated activation of brain regions involved with auditory processing during the monitoring of inner speech. However, there are no functional magnetic resonance imaging studies explicitly comparing the perception of external speech with internal speech in the same patients with schizophrenia. The present study investigated the functional neuroanatomy of inner and external speech in both patients with schizophrenia and healthy control subjects. METHODS Fifteen patients with schizophrenia and 12 healthy control subjects were studied using functional magnetic resonance imaging while listening to sentences or imagining sentences. RESULTS Significant interactions between group (control subjects vs. patients) and task (listening vs. inner speech) were seen for the left superior temporal gyrus, as well as regions within the cingulate gyrus. CONCLUSIONS Attenuated deactivation of the left superior temporal gyrus in schizophrenia patients during the processing of inner speech may reflect deficits in the forward models subserving self-monitoring.

Time-Lagged Moment-to-Moment Interplay Between Negative Affect and Paranoia: New Insights in the Affective Pathway to Psychosis

Evidence suggests that affect plays a role in the development of psychosis but the underlying mechanism requires further investigation. This study examines the moment-to-moment dynamics between negative affect (NA) and paranoia prospectively in daily life. A female general population sample (n = 515) participated in an experience sampling study. Time-lagged analyses between increases in momentary NA and subsequent momentary paranoia were examined. The impact of childhood adversity, stress sensitivity (impact of momentary stress on momentary NA), and depressive symptoms on these time-lagged associations, as well as associations with follow-up self-reported psychotic symptoms (Community Assessment of Psychic Experiences and the Symptom Checklist-90-Revised) were investigated. Moments of NA increase resulted in a significant increase in paranoia over 180 subsequent minutes. Both stress sensitivity and depressive symptoms impacted on the transfer of NA to paranoia. Stress sensitivity moderated the level of increase in paranoia during the initial NA increase, while depressive symptoms increased persistence of paranoid feelings from moment to moment. Momentary paranoia responses to NA increases were associated with follow-up psychotic symptoms. Examination of microlevel momentary experience may thus yield new insights into the mechanism underlying co-occurrence of altered mood states and psychosis. Knowledge of the underlying mechanism is required in order to determine source and place where remediation should occur.