Search

The burden of large and rare copy number genetic variants (CNVs) as well as certain specific CNVs increase the risk of developing schizophrenia. Several cognitive measures are purported schizophrenia endophenotypes and may represent an intermediate point between genetics and the illness. This paper investigates the influence of CNVs on cognition. We conducted a systematic review and meta-analysis of the literature exploring the effect of CNV burden on general intelligence. We included ten primary studies with a total of 18,847 participants and found no evidence of association. In a new psychosis family study, we investigated the effects of CNVs on specific cognitive abilities. We examined the burden of large and rare CNVs (>200 kb, This work was supported by the Medical Research Council (G0901310) and the Wellcome Trust (grants 085475/B/08/Z, 085475/Z/08/Z). This study was supported by the NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust and University College London and by the NIHR Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust at King’s College London. Further support to EB: Mental Health Research UK’s John Grace QC award, BMA Margaret Temple grants 2016 and 2006, MRC—Korean Health Industry Development Institute Partnering Award (MC_PC_16014), MRC New Investigator Award and a MRC Centenary Award (G0901310), National Institute of Health Research UK post-doctoral fellowship, the Psychiatry Research Trust, the Schizophrenia Research Fund, the Brain and Behaviour Research foundation’s NARSAD Young Investigator Awards 2005, 2008, Wellcome Trust Research Training Fellowship, the NIHR Biomedical Research Centre at UCLH, and the NIHR Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust and Institute of Psychiatry King’s College London. Further support to co-authors: The Brain and Behaviour Research foundation’s (NARSAD’s) Young Investigator Award (Grant 22604, awarded to CI). The BMA Margaret Temple grant 2016 to JT. A 2014 European Research Council Marie Curie award to A Díez-Revuelta. HI has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 747429. A Medical Research Council doctoral studentship to JH-S, IA-Z and AB. A Mental Health Research UK studentship to RM. VB is supported by a Wellcome Trust Seed Award in Science (200589/Z/16/Z). FWO Senior Clinical Fellowship to RvW. The infrastructure for the GROUP consortium is funded through the Geestkracht programme of the Dutch Health Research Council (ZON-MW, grant number 10-000-1001), and matching funds from participating pharmaceutical companies (Lundbeck, AstraZeneca, Eli Lilly, Janssen Cilag) and universities and mental health care organisations (Amsterdam: Academic Psychiatric Centre of the Academic Medical Centre and the mental health institutions: GGZ Ingeest, Arkin, Dijk en Duin, GGZ Rivierduinen, Erasmus Medical Centre, GGZ Noord Holland Noord. Groningen: University Medical Centre Groningen and the mental health institutions: Lentis, GGZ Friesland, GGZ Drenthe, Dimence, Mediant, GGNet Warnsveld, Yulius Dordrecht and Parnassia psycho-medical centre The Hague. Maastricht: Maastricht University Medical Centre and the mental health institutions: GGZ Eindhoven en De Kempen, GGZ Breburg, GGZ Oost-Brabant, Vincent van Gogh voor Geestelijke Gezondheid, Mondriaan, Virenze riagg, Zuyderland GGZ, MET ggz, Universitair Centrum Sint-Jozef Kortenberg, CAPRI University of Antwerp, PC Ziekeren Sint-Truiden, PZ Sancta Maria Sint-Truiden, GGZ Overpelt, OPZ Rekem. Utrecht: University Medical Centre Utrecht and the mental health institutions Altrecht, GGZ Centraal and Delta). The Santander cohort was supported by Instituto de Salud Carlos III (PI020499, PI050427, PI060507), SENY Fundació (CI 2005-0308007), Fundacion Ramón Areces and Fundacion Marqués de Valdecilla (API07/011, API10/13). We thank Valdecilla Biobank for providing the biological PAFIP samples and associated data included in this study and for its help in the technical execution of this work; we also thank IDIVAL Neuroimaging Unit for its help in the acquisition and processing of imaging PAFIP data.

Prospective momentary psychological and biological measures of real-time daily life stress experiences have been examined in several psychiatric disorders, but not in adults with an autism spectrum disorder (ASD). The current electronic self-monitoring study examined associations between momentary daily life stressors and (i) negative affect (NA; emotional stress reactivity) and (ii) cortisol levels (biological stress reactivity) in males and females with ASD (N = 50) and without ASD (N = 51). The Experience Sampling Method, including saliva sampling, was used to measure three types of daily life stress (activity-related, event-related, and social stress), NA, and cortisol. Multilevel regression analyses demonstrated significant interactions between group and stress (i.e., activity-related and event-related stress) in the model of NA, indicating stronger emotional stress reactivity in the ASD than in the control group. In the model of cortisol, none of the group × stress interactions were significant. Male/female sex had no moderating effect on either emotional or biological stress reactivity. In conclusion, adults with ASD showed a stronger emotional stress (but not cortisol) reactivity in response to unpleasant daily life events and activities. The findings highlight the feasibility of electronic self-monitoring in individuals with ASD, which may contribute to the development of more personalized stress-management approaches. ispartof: SCIENTIFIC REPORTS vol:11 issue:1 ispartof: location:England status: published

Objective: Cognitive alterations putatively contribute to the risk for suicide in individuals with psychosis. Yet, a comprehensive assessment of social-and general-cognitive abilities in a large sample is lacking. Methods: Seven-hundred -fifteen individuals diagnosed with a psychotic disorder performed tasks of facial emotion recognition, Theory of Mind, and general cognitive functioning (sustained attention, set-shifting, IQ-tests and verbal learning) as part of the Genetic-Risk-and-Outcome-of-Psychosis (GROUP) study. Presence of past suicide attempt/s and/or current suicidal ideation was reported by 261 individuals and 454 individuals reported no suicide attempt or ideation. We used general linear models to investigate group differences in task performance. All analysis were controlled for age, sex, education, and psychotic symptom severity. Results: Individuals with suicide attempt and/or ideation showed better performance on the facial emotion recognition task and lower performance on tasks of sustained attention and verbal learning, compared to individuals without suicide attempt and/or ideation, without a clear effect of attempt or ideation. Theory of Mind performance was also better for individuals with suicide attempt and/or ideation, with largest differences between individuals who reported both attempts and ideation compared to individuals without suicide attempt and/or ideation. No effect of suicide attempt and/or ideation was found on misperception of facial emotions, IQ and set-shifting. Overall, effect sizes were small. Conclusion: Higher sensitivity to social-emotional cues together with weakened attentional control and learning capacity was observed in individuals with psychosis and suicide attempt and/or ideation. This may suggest that insufficient capacity for regulating perceived social stress contributes to suicidal thoughts and behavior. (c) 2021 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).

Introduction: Depressive symptoms are highly prevalent and clinically relevant in schizophrenia spectrum disorder (SSD) patients. So far, little is known about to what extent the depressive symptom profile in SSD is comparable to that seen in major depressive disorder (MDD).Methods: Data were derived from the Genetic Risk and Outcome of Psychosis study (GROUP) and the Netherlands Study of Depression and Anxiety (NESDA). We examined differences in severity of depressive symptom profiles and distribution of mood/cognition and somatic/vegetative depressive symptoms using the Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR) within SSD patients (n = 449), MDD patients (n = 816) and healthy controls (n = 417), aged 18 to 50. Within SSD, associations between depression severity and clinical and demographic data were examined.Results: 60.4% of SSD patients showed substantial depressive symptomatology (QIDS-SR >= 6). The difference in mood/cognition symptoms between SSD and MDD was larger (higher symptoms in MDD, effect size = 1.13), than the differences in somatic/vegetative symptoms (effect size 0.74). In patients with SSD, multivariable regression analyses showed that lower social functioning, male gender, use of benzodiazepine and more severe positive symptoms were associated with higher overall depressive symptomatology. The use of antipsychotics or anti-depressants was associated with more somatic/vegetative symptoms.Conclusion: More than half of SSD patients have considerable depressive symptomatology, with a relative preponderance of somatic/vegetative symptoms compared to the profile seen in MDD. Future research could explore whether depressive symptom profile in SSD may also be associated with biological dysregulations like in MDD.

Introduction: In patients with psychotic disorders, both tobacco smoking and deficits in social cognition and social functioning are highly prevalent. However, little is known about their relationship in psychosis. The authors sought to evaluate the multi-cross-sectional and longitudinal associations between tobacco smoking, social cognition and social functioning in a large prospective study.Methods: This study was performed within the Genetic Risk and Outcome of Psychosis (GROUP) Study, a cohort study conducted in patients with non-affective psychosis (N = 1074), their unaffected siblings (N = 1047) and healthy controls (N = 549). At baseline, three years and six years of follow-up, data on tobacco smoking (using the Composite International Diagnostic Review), social cognition (emotion processing and theory of mind) and social functioning were collected. To assess associations between tobacco smoking and social cognition or social functioning, multivariate linear mixed-effects models and multiple linear regression models were used. Bon-ferroni correction for multiple testing was applied.Results: A significant positive association was found between smoking and emotion processing (as part of social cognition) in the patient group (estimate = 1.96, SE = 0.6, p = 0.003). However, smoking was significantly negatively associated with participating in pro-social activities compared with non-smoking (estimate =-2.55, SE = 0.9, p = 0.004). Change in smoking behaviour was not associated with social cognition or social functioning in the longitudinal analyses.Conclusion: Findings indicate that smoking patients with a non-affective psychotic disorder slightly outperformed their non-smoking peers on a task on social cognition, but participated less in pro-social activities. Commencement or cessation of smoking was not related to social cognition or functioning.

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.

What drives the large differences across patients in terms of treatment efficacy of major depressive disorder (MDD) is unclear. A network approach to psychopathology may help to reveal underlying mechanisms determining patients' capacity for recovery. We used daily diary MDD symptom data and six-month follow-up data on depression to examine how dynamic associations between symptoms relate to the future course of MDD. Daily experiences of depressive symptoms of 69 participants were assessed by means of the SCL-90-R depression subscale, three days a week for a period of six weeks, as part of a larger intervention study. Multilevel vector autoregressive modelling was used to estimate networks of dynamic symptom connections. Long-term outcome was determined by the percentage change in Hamilton Depression Rating Scale (HDRS) score between pre-intervention and six-month follow-up. For patients with more persisting symptoms, the symptom 'feeling everything is an effort' most strongly predicted other symptoms. The networks of the two groups did not significantly differ in overall connectivity. Findings suggest that future research should not solely focus on the presence or intensity of individual symptoms when predicting long-term outcomes, but should also examine the role of a specific symptom in the larger network of dynamic symptom-to-symptom interactions.

Research has found that Obsessive Compulsive Symptoms (OCS) in schizophrenia are associated with either more or less negative symptoms and either better or poorer cognitive functioning. In order to explain these contradictory results, (Lysaker et al., 2004), performed a cluster analysis resulting in 2 OCS positive (OCSpos) clusters, one with higher functioning (HF) and one with poorer functioning (PF) compared to 2 OCS negative (OCSneg) clusters. The OCSpos/HF cluster had less negative symptoms compared to all other clusters, while the OCSpos/PF cluster showed poorer executive functioning. We performed a replication study, in an almost 10 times larger, representative sample, using both a longitudinal and cross-sectional design. Similar to Lysaker et al., we found a group with mild OCS and HF (OCSmild/HF) showing less negative symptoms compared to the PF groups. We also found an OCSmild/PF group, which did not significantly differ in executive functioning from the other groups. Moreover, we did not find evidence for a better prognosis in the OCSmild/HF group, and thus found no support for the assumption that for some patients OCS might be an effective coping mechanism. ispartof: PSYCHIATRY RESEARCH vol:271 pages:421-427 ispartof: location:Ireland status: published

Neuroticism is associated with increased stress reactivity. In autism spectrum disorders (ASD), emotional stress reactivity is increased and there is some evidence for an increased negative affect (NA) when with less familiar people. The aim of this study was to compare adults with ASD and controls on levels of neuroticism and on interactions between neuroticism and appraised stress or social context in models of NA. This is a cross-sectional observational study comprising a group of 50 adults with ASD and 51 controls. Experience sampling method (ESM) reports were collected for 10 days to measure daily life stress, mood, and social context. Multilevel regression analyses revealed significantly higher neuroticism levels in ASD than in controls. Adults with ASD who scored high on neuroticism showed a significantly stronger association between activity/social stress and NA (i.e., higher stress reactivity) than those with low scores. Furthermore, the association between neuroticism and NA was stronger when adults with ASD were with less familiar people compared with being alone or with familiar people. No consistent corresponding significant interactions were found in the control group. In conclusion, in ASD, neuroticism moderates the association between appraised stress and NA as well as the association between social context and NA.

Accurate real-life monitoring of motor and non-motor symptoms is a challenge in Parkinson’s disease (PD). The unobtrusive capturing of symptoms and their naturalistic fluctuations within or between days can improve evaluation and titration of therapy. First-generation commercial PD motion sensors are promising to augment clinical decision-making in general neurological consultation, but concerns remain regarding their short-term validity, and long-term real-life usability. In addition, tools monitoring real-life subjective experiences of motor and non-motor symptoms are lacking. The dataset presented in this paper constitutes a combination of objective kinematic data and subjective experiential data, recorded parallel to each other in a naturalistic, long-term real-life setting. The objective data consists of accelerometer and gyroscope data, and the subjective data consists of data from ecological momentary assessments. Twenty PD patients were monitored without daily life restrictions for fourteen consecutive days. The two types of data can be used to address hypotheses on naturalistic motor and/or non-motor symptomatology in PD.

Objectives: A psychosocial intervention for spousal carers of people with dementia promoted emotional well-being through self-monitoring and personalized feedback, as demonstrated in a previous randomized controlled trial. The mechanism behind the intervention effects is thought to lie in increased awareness of, and thus, engagement in behaviours that elicit positive emotions (PA). This secondary analysis tests the assumption by investigating momentary data on activities, affect, and stress and explores the relevance of personalized feedback compared to self-monitoring only.Methods: The intervention was based on the experience sampling method (ESM), meaning that carers self-monitored own affect and behaviours 10 times/day over 6 weeks. The experimental group received personalized feedback on behaviours that elicit PA, while the pseudo-experimental group performed self-monitoring only. A control group was also included. ESM-data of 72 carers was analysed using multilevel mixed-effects models.Results: The experimental group reported significant increases in passive relaxation activities over the 6 weeks (B = 0.28, SE = 0.12, Z = 2.43, p < .05). Passive relaxation in this group was negatively associated with negative affect (r = -0.50, p = .01) and positively associated with activity-related stress (r = 0.52, p = .007) from baseline to post-intervention. Other activities in this or the other groups did not change significantly.Conclusion: Carer's daily behaviours were only affected when self-monitoring was combined with personalized feedback. Changing one's daily behaviour while caring for a person with dementia is challenging and aligned with mixed emotions. Acknowledging simultaneously positive and negative emotions, and feelings of stress is suggested to embrace the complexity of carer's life and provide sustainable support. ispartof: AGING & MENTAL HEALTH vol:26 issue:2 pages:294-304 ispartof: location:England status: published

Background Parkinson disease monitoring is currently transitioning from periodic clinical assessments to continuous daily life monitoring in free-living conditions. Traditional Parkinson disease monitoring methods lack intraday fluctuation detection. Electronic diaries (eDiaries) hold the potential to collect subjective experiences on the severity and burden of motor and nonmotor symptoms in free-living conditions. Objective This study aimed to develop a Parkinson disease–specific eDiary based on ecological momentary assessments (EMAs) and to explore its validation. Methods An observational cohort of 20 patients with Parkinson disease used the smartphone-based EMA eDiary for 14 consecutive days without adjusting free-living routines. The eDiary app presented an identical questionnaire consisting of questions regarding affect, context, motor and nonmotor symptoms, and motor performance 7 times daily at semirandomized moments. In addition, patients were asked to complete a morning and an evening questionnaire. Results Mean affect correlated moderate-to-strong and moderate with motor performance (R=0.38 to 0.75; P Conclusions We presented a Parkinson disease–specific EMA eDiary. Correlations between given answers support the internal validity of the eDiary and underline EMA’s potential in free-living Parkinson disease monitoring. Careful patient selection and EMA design adjustment to this targeted population and their fluctuations are necessary to generate robust proof of EMA validation in future work. Combining clinical Parkinson disease knowledge with practical EMA experience is inevitable to design and perform studies, which will lead to the successful integration of eDiaries in free-living Parkinson disease monitoring.

Many individuals with severe mental disorders have difficulties in vocational and social functioning, which are regarded the most important outcomes, together with clinical symptoms. To understand the underlying mechanisms, research is increasingly focused on factors influencing functional outcomes. One established association has been shown between cognition and community functioning with negative symptoms as a possible mediator. Although it has been shown that negative symptoms consist of two subdomains, thus far negative symptoms have been assessed as one unitary construct. This study considers for the first time subdomains of negative symptoms as putative mediators (expressive deficits, amotivation) of the association between cognition (neuro- and social cognition) and functional outcome (living situation, occupation, social functioning). We expected that specific subdomains of negative symptoms (e.g. amotivation) would mediate the effect of cognition on specific functional outcomes (e.g. social functioning) independently from illness duration. To assess this, we included two independent cohorts, consisting of participants with different illness duration. These two independent cohorts consisted of patients with a recent-onset psychotic disorder: PROGR-S (first time treated; N = 1129) and GROUP (illness duration preferably

As executive functioning (EF) is especially sensitive to age-related cognitive decline, EF was evaluated by using a multi-method assessment. Fifty males (60–85 years) with a late adulthood autism spectrum condition (ASC) diagnosis and 51 non-ASC males (60–83 years) were compared on cognitive tests across EF domains (cognitive flexibility, planning, processing speed, and working memory) and a self- and proxy report of the Behavior Rating Inventory of Executive Function-Adult Version. While no objective performance differences emerged, autistic males and their proxies did report more EF challenges than non-ASC males on the subjective measure. In order to know how to support the older autistic men who received their ASC diagnosis in late adulthood with their daily life EF challenges, it is important to understand what underlies these subjective EF problems.

BackgroundThe prevalence of psychotic experiences (PEs) is higher in low-and-middle-income-countries (LAMIC) than in high-income countries (HIC). Here, we examine whether this effect is explicable by measurement bias.MethodsA community sample from 13 countries (N = 7141) was used to examine the measurement invariance (MI) of a frequently used self-report measure of PEs, the Community Assessment of Psychic Experiences (CAPE), in LAMIC (n = 2472) and HIC (n = 4669). The CAPE measures positive (e.g. hallucinations), negative (e.g. avolition) and depressive symptoms. MI analyses were conducted with multiple-group confirmatory factor analyses.ResultsMI analyses showed similarities in the structure and understanding of the CAPE factors between LAMIC and HIC. Partial scalar invariance was found, allowing for latent score comparisons. Residual invariance was not found, indicating that sum score comparisons are biased. A comparison of latent scores before and after MI adjustment showed both overestimation (e.g. avolition, d = 0.03 into d = −0.42) and underestimation (e.g. magical thinking, d = −0.03 into d = 0.33) of PE in LAMIC relative to HIC. After adjusting the CAPE for MI, participants from LAMIC reported significantly higher levels on most CAPE factors but a significantly lower level of avolition.ConclusionPrevious studies using sum scores to compare differences across countries are likely to be biased. The direction of the bias involves both over- and underestimation of PEs in LAMIC compared to HIC. Nevertheless, the study confirms the basic finding that PEs are more frequent in LAMIC than in HIC.

Cognitive impairments in patients with psychotic disorder have been associated with poor functioning and increased symptom severity. Furthermore, childhood trauma (CT) exposure has been associated with worse cognitive functioning as well as co-occurrence of affective-anxious-psychosis symptoms or a 'mixed phenotype of psychopathology' (MP), which in turn is associated with greater symptom severity, and poor functioning. This study aims to evaluate if cognition could be associated with CT/MP.& para;& para;532 patients with non-affective psychotic patients were assessed on Cl', symptom profile, cognition, functioning, and symptom severity at baseline and 3 and 6-year follow-up. Four subgroups were made according to trauma exposure (CT- or CT+) and presence of a mixed phenotype (MP- or MP +-): CT-/MP (n = 272), CT-I MP+ (n = 157), CT-IMP- (n = 49), and CT+/MP + (n = 54). Mixed-effects multilevel regression, linear regression, and Tobit analyses were performed.& para;& para;Patients with both CT and MP showed lower verbal learning and memory than CT-/MP+ individuals (p

Background:Multimorbidity may impose an overwhelming burden on patients with psychosis and is affected by gender and age. Our aim is to study the independent role of familial liability to psychosis as a risk factor for multimorbidity.Methods:We performed the study within the framework of the Genetic Risk and Outcome of Psychosis (GROUP) project. Overall, we compared 1024 psychotic patients, 994 unaffected siblings and 566 controls on the prevalence of 125 lifetime diseases, and 19 self-reported somatic complaints. Multimorbidity was defined as the presence of two or more complaints/diseases in the same individual. Generalized linear mixed model (GLMM) were used to investigate the effects of gender, age (adolescent, young, older) and familial liability (patients, siblings, controls) and their interactions on multimorbidity.Results:Familial liability had a significant effect on multimorbidity of either complaints or diseases. Patients had a higher prevalence of multimorbidity of complaints compared to siblings (OR 2.20, 95% CI 1.79–2.69, P < 0.001) and to controls (3.05, 2.35–3.96, P < 0.001). In physical health multimorbidity, patients (OR 1.36, 95% CI 1.05–1.75, P = 0.018), but not siblings, had significantly higher prevalence than controls. Similar finding were observed for multimorbidity of lifetime diseases, including psychiatric diseases. Significant results were observed for complaints and disease multimorbidity across gender and age groups.Conclusion:Multimorbidity is a common burden, significantly more prevalent in patients and their unaffected siblings. Familial liability to psychosis showed an independent effect on multimorbidity; gender and age are also important factors determining multimorbidity.

Research suggests that childhood trauma is associated with cognitive alterations, but it is not known whether the cognitive alterations observed in patients with psychotic disorder, and their relatives, is trauma-related. Patients with a schizophrenia-spectrum diagnosis (n = 1119), siblings of patients (n = 1059) and healthy comparison subjects (HCS; n = 586) were interviewed 3 times over a period of 6 years. Repeated measures of IQ were analyzed as a function of childhood trauma and group, controlling for confounders. There were significant differences in the impact of childhood trauma on IQ across the 3 groups. Exposure in HCS was associated with a nearly 5-point reduction in IQ (-4.85; 95% confidence interval [CI]: -7.98 to -1.73, P = .002), a lesser reduction in siblings (-2.58; 95% CI: -4.69 to -0.46, P = .017) and no significant reduction in patients (-0.84; 95% CI: -2.78 to 1.10, P = .398). One-fourth of the sibling-control difference in IQ was reducible to childhood trauma, whereas for patients this was only 5%. Over the 6-year follow-up, those with trauma exposure showed significantly less learning effects with repeated cognitive assessments (b = 1.36, 95% CI: 0.80‒1.92, P < .001) than the nonexposed (b = 2.31, 95% CI: 1.92‒2.71, P < .001; P interaction = .001). Although childhood trauma impacts cognitive ability and learning in non-ill people at low and high genetic risk, its effect on the observed cognitive alterations in psychotic disorder may be minor. Twin and family studies on cognitive alterations in psychotic disorder need to take into account the differential impact of trauma on cognition across ill and non-ill, at risk groups. ispartof: Schizophrenia Bulletin vol:43 issue:2 pages:316-324 ispartof: location:United States status: published

Patients diagnosed with schizophrenia often report a low quality of life (QoL). The purpose of this study was to investigate whether we could replicate a cross-sectional model by Alessandrini et al. (2016, n = 271) and whether this model predicts QoL later in life. This model showed strong associations between schizophrenia spectrum symptoms and depressive symptoms on QoL, but lacked follow-up assessment. This model was adapted in the current study and the robustness was investigated by using a longitudinal design in which the association between baseline variables (including IQ, depression, schizophrenia spectrum symptoms as well as social functioning) and QoL during 3-years of follow-up was investigated. We included patients with a non-affective psychotic disorder (n = 744) from a prospective naturalistic cohort-study. In the cross-sectional model, with good measure of fit, both depression as well as social functioning was associated with QoL (direct path coefficient -0.28 and 0.41, respectively). Additionally, the severity of schizophrenia spectrum symptoms was highly associated with social functioning (direct path coefficient -0.70). Importantly, the longitudinal model showed good measures of fit, which strengthens the validity of the initial model and highlights that depression prospectively affect QoL while schizophrenia spectrum symptoms prospectively influence QoL via social functioning. The negative, longitudinal impact of a depression on QoL highlights the need to focus on treatment of this co-morbidity. ispartof: SCHIZOPHRENIA RESEARCH vol:208 pages:82-89 ispartof: location:Netherlands status: published

If schizotypy is a taxonic liability for schizophrenia with a general population prevalence of ~10%, it should also be taxonic among biological siblings of probands with schizophrenia. Moreover, assuming this is so, siblings' schizotypy class membership should be predicted by probands' familial load for psychotic disorder and clinical severity, consistent with a multifactorial polygenic threshold model of schizophrenia. We tested these hypotheses in the Genetic Risk and Outcome of Psychosis (GROUP) Study where siblings of probands (n = 792) and unaffected controls (n = 559) provided self-report ratings on the Community Assessment of Psychic Experiences (CAPE). Maximum covariance analyses of control group ratings led to the identification of CAPE items sensitive to nonredundant positive and negative schizotypy classes in the control group (prevalence = 7.9% and 11.1%, respectively). When the same taxonic solution was applied to siblings' CAPE rating, taxometric analyses yielded evidence for larger positive and negative schizotypy classes among siblings (prevalence = 14.1% and 21.8%, respectively). Whereas probands' familial loads for bipolar disorder or drug use disorders did not predict siblings' membership in the schizotypy classes, probands' familial load for psychotic disorder did. Siblings were more likely to be members of the positive schizotypy class where their probands were more severely affected. The pattern of findings is consistent with Meehl's argument that schizotypy reflects liability for schizophrenia. ispartof: Schizophrenia Bulletin vol:44 issue:4 pages:922-932 ispartof: location:United States status: accepted

BACKGROUND: Major depressive disorder has been linked to an inability to differentiate between negative emotions. The current study investigates whether emotion differentiation improves when individuals with major depressive disorder are required to report on specific emotions multiple times a day through the experience sampling method (ESM) - a structured self-report diary technique. METHODS: Seventy-nine patients diagnosed with major depressive disorder participated in this study, of whom 55 used ESM for 6 weeks (3 days a week, 10 times a day). Changes from baseline to post assessment in positive and negative emotion differentiation were compared between the participants who did and those who did not use ESM. RESULTS: Engaging in ESM related to an improvement in both positive and negative emotion differentiation, but only the latter reached statistical significance. The relationship between the number of ESM measurements (dose) and emotion differentiation change (response) was not significant. LIMITATIONS: The sample size for the dose-response analysis was relatively small (N = 55). It is unknown whether emotion differentiation improvements generalize beyond the emotions (N = 12) we probed in this study. Other factors could also have contributed to the change (e.g., meetings with the researchers). CONCLUSIONS: The present study suggests that patients with depression using ESM for 3 days a week for 6 weeks can improve their negative emotion differentiation. Future studies should assess after what period of ESM changes in emotion differentiation become apparent, and whether these changes are persistent and relate to actual improvement in depressive symptoms. ispartof: Journal of Affective Disorders vol:244 pages:71-77 ispartof: location:Netherlands status: published

Background One of the oldest and most influential theories of psychosis formation states that delusions arise in an attempt to explain unusual experiences, including perceptual aberrations. The White Noise Task by Galdos et al (2011) was developed as an experimental task to assess the tendency to attribute meaning to random perceptual stimuli: speech illusions in white noise. Studies to date have demonstrated that speech illusions as assessed with the White Noise Task are associated with a composite measure of positive symptoms in patients with psychotic disorders (Galdos et al, 2011; Catalan et al, 2014). However, findings in non-clinical samples have been inconsistent: one study found an association with a composite measure of subclinical positive symptoms, including support for a relation with familial psychosis liability (Galdos et al, 2011), whereas other studies did not find any association in non-clinical samples or only partly (Catalan et al, 2014; Rimvall et al, 2016; Pries et al, 2017). The current study aims to further examine whether speech illusions as assessed with the White Noise Task are indicative of psychosis liability and to explore specific symptomatic pathways. Methods We conducted symptom-based network analyses in Ultra-High Risk (UHR) subjects participating in the European network of national networks studying gene-environment interactions in schizophrenia project (EU-GEI, 2014; www.eu-gei.eu). Psychotic symptoms were assessed with the Brief Psychiatric Rating Scale (BPRS). Transition to clinical psychosis was assessed with the Comprehensive Assessment of At Risk Mental State (CAARMS). We used a conservative measure of speech illusions, as described in Catalan et al (2014). Results The current sample consisted of 339 UHR subjects, of which 9.1% (N=31) experienced speech illusions. Preliminary network analyses in cross-sectional baseline data showed potential pathways from speech illusions to delusional ideation, through hallucinatory experiences. We also found evidence of prospective relations between speech illusions at baseline and transition to clinical psychosis. Pathways ran via baseline psychotic symptoms and affective symptoms, as well as a ‘direct’ pathway. Discussion As far as we are aware, this is the first study combining an experimental measure of aberrant experiences with symptom-based network analysis. Although the current reported findings are preliminary and exploratory, they tentatively support a relation between speech illusions as assessed with the White Noise Task and psychosis liability. This relation may be dependent on sample composition, and not generalizable to the general population as a whole. Future studies may benefit from focusing on more detailed trajectories of both susceptibility to speech illusions and course of (sub)clinical psychotic symptom severity in subjects with increased risk for psychosis, with use of more frequent, short assessment periods and inclusion of environmental risk factors for transition to clinical disorder.

Background: Mental healthcare needs person-tailored interventions. Experience Sampling Method (ESM) can provide daily life monitoring of personal experiences. This study aims to operationalize and test a measure of momentary reward-related Quality of Life (rQoL). Intuitively, quality of life improves by spending more time on rewarding experiences. ESM clinical interventions can use this information to coach patients to find a realistic, optimal balance of positive experiences (maximize reward) in daily life. rQoL combines the frequency of engaging in a relevant context (a ‘behavior setting’) with concurrent (positive) affect. High rQoL occurs when the most frequent behavior settings are combined with positive affect or infrequent behavior settings co-occur with low positive affect.Methods: Resampling procedures (Monte Carlo experiments) were applied to assess the reliability of rQoL using various behavior setting definitions under different sampling circumstances, for real or virtual subjects with low-, average- and high contextual variability. Furthermore, resampling was used to assess whether rQoL is a distinct concept from positive affect. Virtual ESM beep datasets were extracted from 1,058 valid ESM observations for virtual and real subjects.Results: Behavior settings defined by Who-What contextual information were most informative. Simulations of at least 100 ESM observations are needed for reliable assessment. Virtual ESM beep datasets of a real subject can be defined by Who-What-Where behavior setting combinations. Large sample sizes are necessary for reliable rQoL assessments, except for subjects with low contextual variability. rQoL is distinct from positive affect.Conclusion: rQoL is a feasible concept. Monte Carlo experiments should be used to assess the reliable implementation of an ESM statistic. Future research in ESM should asses the behavior of summary statistics under different sampling situations. This exploration is especially relevant in clinical implementation, where often only small datasets are available.

BackgroundAn association between white noise speech illusion and psychotic symptoms has been reported in patients and their relatives. This supports the theory that bottom-up and top-down perceptual processes are involved in the mechanisms underlying perceptual abnormalities. However, findings in nonclinical populations have been conflicting.ObjectivesThe aim of this study was to examine the association between white noise speech illusion and subclinical expression of psychotic symptoms in a nonclinical sample. Findings were compared to previous results to investigate potential methodology dependent differences.MethodsIn a general population adolescent and young adult twin sample (n = 704), the association between white noise speech illusion and subclinical psychotic experiences, using the Structured Interview for Schizotypy-Revised (SIS-R) and the Community Assessment of Psychic Experiences (CAPE), was analyzed using multilevel logistic regression analyses.ResultsPerception of any white noise speech illusion was not associated with either positive or negative schizotypy in the general population twin sample, using the method by Galdos et al. (2011) (positive: ORadjusted: 0.82, 95% CI: 0.6-1.12, p = 0.217; negative: ORadjusted: 0.75, 95% CI: 0.56-1.02, p = 0.065) and the method by Catalan et al. (2014) (positive: ORadjusted: 1.11, 95% CI: 0.79-1.57, p = 0.557). No association was found between CAPE scores and speech illusion (ORadjusted: 1.25, 95% CI: 0.88-1.79, p = 0.220). For the Catalan et al. (2014) but not the Galdos et al. (2011) method, a negative association was apparent between positive schizotypy and speech illusion with positive or negative affective valence (ORadjusted: 0.44, 95% CI: 0.24-0.81, p = 0.008).ConclusionContrary to findings in clinical populations, white noise speech illusion may not be associated with psychosis proneness in nonclinical populations.

OBJECTIVE: The aim of this study was to assess associations between momentary stress and both affective and psychotic symptoms in everyday life of individuals at clinical high risk (CHR), compared to chronic psychotic patients and healthy controls, in search for evidence of early stress sensitization. It also assessed whether psychotic experiences were experienced as stressful.METHOD: The experience sampling method was used to measure affective and psychotic reactivity to everyday stressful activities, events and social situations in 22 CHR patients, 24 patients with a psychotic disorder and 26 healthy controls.RESULTS: Multilevel models showed significantly larger associations between negative affect (NA) and activity-related stress for CHR patients than for psychotic patients (P = 0.008) and for CHR compared to controls (P < 0.001). Similarly, the association between activity-related stress and psychotic symptoms was larger in CHR than in patients (P = 0.02). Finally, the association between NA and symptoms (P < 0.001) was larger in CHR than in patients.CONCLUSION: Stress sensitization seems to play a role particularly in the early phase of psychosis development as results suggest that CHR patients are more sensitive to daily life stressors than psychotic patients. In this early phase, psychotic experiences also contributed to the experience of stress.

BackgroundPoor sleep is a risk factor for depression, but little is known about the underlying mechanisms.AimsDisentangling potential mechanisms by which sleep may be related to depression by zooming downto the ‘micro-level’ of within-person daily life patterns of subjective sleep and affect usingthe experience sampling method (ESM).MethodA population-based twin sample consisting of 553 women underwent a 5-day baseline ESM protocolassessing subjective sleep and affect together with four follow-up assessments of depression.ResultsSleep was associated with affect during the next day, especially positive affect. Daytime negative affect was not associated with subsequent night-time sleep. Baseline sleep predicted depressive symptoms across the follow-up period.ConclusionsThe subtle, repetitive impact of sleep on affect on a daily basis, rather than the subtle repetitive impact of affect on sleep, may be one of the factors on the pathway to depression in women.

BackgroundFK506 binding protein 5 (FKBP5) has repeatedly been shown to be a critical determinant of post-traumatic stress disorder (PTSD) and depression following childhood trauma.AimsTo examine the role of FKBP5-trauma interactions in the partly stress-related psychosis phenotype.MethodIn 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).ResultsThe 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.ConclusionsTrauma 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.

BackgroundAuditory verbal hallucinations (AVH) are common during development and may arise due to dysregulation in top-down processing of sensory input. This study was designed to examine the frequency and correlates of speech illusions measured using the White Noise (WN) task in children from the general population. Associations between speech illusions and putative risk factors for psychotic disorder and negative affect were examined.MethodA total of 1486 children aged 11–12 years of the Copenhagen Child Cohort 2000 were examined with the WN task. Psychotic experiences and negative affect were determined using the Kiddie-SADS-PL. Register data described family history of mental disorders. Exaggerated Theory of Mind functioning (hyper-ToM) was measured by the ToM Storybook Frederik.ResultsA total of 145 (10%) children experienced speech illusions (hearing speech in the absence of speech stimuli), of which 102 (70%) experienced illusions perceived by the child as positive or negative (affectively salient). Experiencing hallucinations during the last month was associated with affectively salient speech illusions in the WN task [general cognitive ability: adjusted odds ratio (aOR) 2.01, 95% confidence interval (CI) 1.03–3.93]. Negative affect, both last month and lifetime, was also associated with affectively salient speech illusions (aOR 2.01, 95% CI 1.05–3.83 and aOR 1.79, 95% CI 1.11–2.89, respectively). Speech illusions were not associated with delusions, hyper-ToM or family history of mental disorders.ConclusionsSpeech illusions were elicited in typically developing children in a WN-test paradigm, and point to an affective pathway to AVH mediated by dysregulation in top-down processing of sensory input.

Background Experience sampling, a method for real-time self-monitoring of affective experiences, holds opportunities for person-tailored treatment. By focussing on dynamic patterns of positive affect, experience sampling method interventions (ESM-I) accommodate strategies to enhance personalized treatment of depression―at potentially low-costs. This study aimed to investigate the cost-effectiveness of an experience sampling method intervention in patients with depression, from a societal perspective. Methods Participants were recruited between January 2010 and February 2012 from out-patient mental health care facilities in or near the Dutch cities of Eindhoven and Maastricht, and through local advertisements. Out-patients diagnosed with major depression (n = 101) receiving pharmacotherapy were randomized into: (i) ESM-I consisting of six weeks of ESM combined with weekly feedback regarding the individual’s positive affective experiences, (ii) six weeks of ESM without feedback, or (iii) treatment as usual only. Alongside this randomised controlled trial, an economic evaluation was conducted consisting of a cost-effectiveness and a cost-utility analysis, using Hamilton Depression Rating Scale (HDRS) and quality adjusted life years (QALYs) as outcome, with willingness-to-pay threshold for a QALY set at €50,000 (based on Dutch guidelines for moderate severe to severe illnesses). Results The economic evaluation showed that ESM-I is an optimal strategy only when willingness to pay is around €3000 per unit HDRS and around €40,500 per QALY. ESM-I was the least favourable treatment when willingness to pay was lower than €30,000 per QALY. However, at the €50,000 willingness-to-pay threshold, ESM-I was, with a 46% probability, the most favourable treatment (base-case analysis). Sensitivity analyses confirmed the robustness of these results. Conclusions We may tentatively conclude that ESM-I is a cost-effective add-on intervention to pharmacotherapy in outpatients with major depression. Trial registration Netherlands Trial register, NTR1974. Electronic supplementary material The online version of this article (10.1186/s12888-017-1577-7) contains supplementary material, which is available to authorized users.

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. ispartof: Neuropsychopharmacology vol:36 issue:12 pages:2529-37 ispartof: location:England status: published

OBJECTIVE: Studies have linked cognitive functioning to everyday social functioning in psychotic disorders, but the nature of the relationships between cognition, social cognition, symptoms, and social functioning remains unestablished. Modelling the contributions of non-social and social cognitive ability in the prediction of social functioning may help in more clearly defining therapeutic targets to improve functioning. METHOD: In a sample of 745 patients with a non-affective psychotic disorder, the associations between cognition and social cognition at baseline on the one hand, and self-reported social functioning three years later on the other, were analysed. First, case-control comparisons were conducted; associations were subsequently further explored in patients, investigating the potential mediating role of symptoms. Analyses were repeated in a subsample of 233 patients with recent-onset psychosis. RESULTS: Information processing speed and immediate verbal memory were stronger associated with social functioning in patients than in healthy controls. Most cognition variables significantly predicted social functioning at follow-up, whereas social cognition was not associated with social functioning. Symptoms were robustly associated with follow-up social functioning, with negative symptoms fully mediating most associations between cognition and follow-up social functioning. Illness duration did not moderate the strength of the association between cognitive functioning and follow-up social functioning. No associations were found between (social) cognition and follow-up social functioning in patients with recent-onset psychosis. CONCLUSIONS: Although cognitive functioning is associated with later social functioning in psychotic disorder, its role in explaining social functioning outcome above negative symptoms appears only modest. In recent-onset psychosis, cognition may have a negligible role in predicting later social functioning. Moreover, social cognition tasks may not predict self-reported social functioning. ispartof: Plos One vol:11 issue:4 ispartof: location:United States status: published