Revisiting Cognitive Deficits in Outpatients with Psychotic Disorders: A Transdiagnostic Comparison of Cognitive Performance While Accounting for Putative Confounding Factors.

Recent research suggests that cognitive deficits in individuals with psychotic disorders could be overestimated because poor cognitive test performance is partly attributable to non-cognitive factors. To further test this, we included non-hospitalized individuals with psychotic disorders (PSY, n = 38), individuals with attenuated psychotic symptoms (n = 40), individuals with obsessive-compulsive disorders (n = 39), and healthy controls (n = 38). Relevant cognitive domains were assessed using the MATRICS Consensus Cognitive Battery. Putative confounding non-cognitive factors-heart rate, self-reported stress, negative affect, performance-related beliefs, and actigraphy-derived sleep-were assessed before cognitive testing. A multivariate analysis of covariance was calculated to examine group differences in cognitive performance while controlling for non-cognitive factors. PSY showed decreased test performance in graphomotor speed, attention, and verbal tasks compared to the other groups, whereas non-verbal/visual-spatial tasks were unimpaired. After accounting for non-cognitive factors, group differences diminished in verbal learning, whereas differences in the other domains remained significant. Against our hypotheses, the present findings indicate that some cognitive deficits in PSY cannot be attributed to momentary confounding factors.

An experience-sampling study on the relevance of affect dynamics to paranoid ideation.

Affective functioning is compromised in people who develop persecutory delusions, but the specifics of these affective disturbances remain unclear. To better understand the precise nature of affective disturbances in this group, it could prove helpful to focus not only on average or momentary affect intensities but also on the dynamic properties of affect, that is, the patterns and regularities with which affect fluctuates over time. This study used experience-sampling in a community sample with varying levels of paranoid ideation (n = 144) to capture different aspects of temporal affect dynamics in the two affective dimensions of valence and arousal. Specifically, we aimed to elucidate whether paranoid ideation is associated with high affective instability (i.e., both high affective variability and low inertia) or only with high affective variability or low affective inertia and whether these effects would be maintained when mean affect levels are controlled for. Results showed that the intensity and frequency of paranoid ideation were significantly associated with high variability of affective arousal, but for paranoia frequency, the effect was not robust against controlling for average arousal levels. Paranoia frequency was also associated with low inertia in affective valence, and paranoia intensity was associated with high valence variability. We discuss the implications of these findings for future research and clinical practice. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Aberrant adapting of beliefs under stress: a mechanism relevant to the formation of paranoia?

BACKGROUND: Difficulties in the ability to adapt beliefs in the face of new information are associated with psychosis and its central symptom - paranoia. As cognitive processes and psychotic symptoms are both known to be sensitive to stress, the present study investigated the exact associations between stress, adapting of beliefs [reversal learning (RL), bias against disconfirmatory evidence (BADE), and jumping to conclusions (JTC)] and paranoia. We hypothesized that paranoia would increase under stress and that difficulties in adapting of beliefs would mediate or moderate the link between stress and paranoia. Furthermore, we hypothesized that the investigated effects would be strongest in the group of individuals diagnosed with a psychotic disorder. METHODS: We exposed 155 participants (38 diagnosed with a psychotic disorder, 40 individuals with attenuated psychotic symptoms, 39 clinical controls diagnosed with an obsessive-compulsive disorder, and 38 healthy controls) to a control condition and a stress condition, in which we assessed their levels of paranoia and their ability to adapt beliefs. We applied multilevel models to analyze the data. RESULTS: Paranoia was higher in the stress condition than in the control condition, b = 1.142, s.e. = 0.338, t(150) = 3.381, p < 0.001. RL, BADE, and JTC did not differ between conditions and did not mediate or moderate the association between stress and paranoia (all ps > 0.05). CONCLUSIONS: The results support the assumption that stress triggers paranoia. However, the link between stress and paranoia does not seem to be affected by the ability to adapt beliefs.

Are paranoid ideation and hallucination spectrum experiences differently associated with affect dynamics? A continuous-time modeling approach.

Psychotic experiences have been associated with distortions in affective functioning, including aberrancies in affect dynamics. However, it remains unclear whether the two principal symptom dimensions of psychosis, namely paranoid ideation and hallucination spectrum experiences, are differently associated with affect dynamics, and whether associations hold after statistically controlling for depressive symptoms. We investigate this by using a novel statistical approach, the hierarchical Ornstein-Uhlenbeck (OU) process model. This is a continuous-time stochastic differential equations model in a Bayesian framework that describes dynamics in affective valence and arousal via three core parameters: attractor point, variability, and attractor strength. In a community sample with varying levels of psychotic experiences (n = 116), we measured affective valence and arousal 10 times per day for 7 days, using the experience-sampling method. We found-while statistically controlling for depressive symptoms-credible between-subjects associations between paranoid ideation and attractor points of negative valence and high arousal. We also found a credible positive association between hallucination spectrum experiences and arousal variability. Limited evidence emerged for small associations between paranoid ideation and high valence variability as well as between paranoid ideation and high attractor strengths of valence and arousal. Hallucination spectrum experiences showed some evidence for a small association with high arousal attractor points. The detailed picture of affect dynamics provided by the OU model reveals different cross-sectional affective profiles associated with paranoid ideation versus hallucination spectrum experiences that suggest different affective mechanisms of their formation and maintenance. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Pinpointing affective disturbances in psychosis: A comparison of temporal affect dynamics in individuals with psychotic disorders, individuals with attenuated psychotic symptoms, and clinical and healthy controls.

Affective disturbances in psychosis are well-documented but our understanding of their phenotypic nature in everyday life remains limited. Filling this gap could advance mechanistic models of the affective pathway to psychosis and pave the ground for new research avenues. Therefore, this study focused on temporal affect dynamics in psychosis, i.e., the patterns with which affect fluctuates over time. We applied experience-sampling with nine assessments per day over one week in participants with psychotic disorders (PSY), participants with attenuated psychotic symptoms (AS), clinical controls with obsessive compulsive disorders (OCD) and healthy controls (HC; total N = 139) to assess whether in PSY and AS, dynamics in affective valence and arousal are characterized by higher instability (i.e., extreme and frequent moment-to-moment fluctuations of affect intensities), higher affective variability (i.e., larger range of affect intensities), or lower inertia (i.e., higher frequency of affective changes), compared to the clinical and healthy control samples. Mixed-model ANOVAs revealed higher instability in both PSY and OCD compared to HC, but no significant differences for variability and inertia. AS had an intermediate position and did not differ significantly from any other group. We found evidence for small to medium effect sizes for the influence of mean affect levels on the dynamic indicators. Our findings indicate that individuals with psychotic disorders have increased affective instability and that this could be a transdiagnostic phenomenon. Zooming in on the variability and inertia components did not confer additional benefits. Emotion-focused interventions for psychosis should focus on reducing frequent and extreme affective fluctuations.

How you think about an emotion predicts how you regulate: an experience-sampling study.

Emotion evaluations are assumed to play a crucial role in the emotion regulation process. We tested a postulate from our framework of emotion dysregulation (Nowak, U., Wittkamp, M. F., Clamor, A., & Lincoln, T. M. [2021]. Using the Ball-in-Bowl metaphor to outline an integrative framework for understanding dysregulated emotion. Frontiers in Psychiatry, 12, 118), namely that the extent to which individuals evaluate an emotion as harmful and their personal resources to modify and accept/tolerate the emotion as sufficient predict the subsequent use of regulation strategies. Participants (n = 118) from a community sample took part in an experience-sampling assessment over 7 days including 10 daily paired measurements. The first measured momentary affective valence and arousal along with harmfulness evaluations and evaluations of personal resources to modify and accept/tolerate an emotion. The second followed three minutes later and measured emotion regulation strategies. The more harmful individuals evaluated an emotion, the more likely they were to use an emotion regulation strategy. The more harmful individuals evaluated an emotion, and the less sufficient they evaluated their personal resources to accept/tolerate an emotion, the more likely they were to use a maladaptive emotion regulation strategy. We conclude that emotions that people evaluate as harmful or difficult to accept are most likely to be regulated in a maladaptive manner. This implies that modifying beliefs about emotions could represent a promising treatment approach.

Using the Ball-in-Bowl Metaphor to Outline an Integrative Framework for Understanding Dysregulated Emotion.

Dysregulated emotion plays an important role for mental health problems. To elucidate the underlying mechanisms, researchers have focused on the domains of strategy-based emotion regulation, psychophysiological self-regulation, emotion evaluations, and resulting emotion dynamics. So far, these four domains have been looked at in relative isolation from each other, and their reciprocal influences and interactive effects have seldom been considered. This domain-specific focus constrains the progress the field is able to make. Here, we aim to pave the way towards more cross-domain, integrative research focused on understanding the raised reciprocal influences and interactive effects of strategy-based emotion-regulation, psychophysiological self-regulation, emotion evaluations, and emotion dynamics. To this aim, we first summarize for each of these domains the most influential theoretical models, the research questions they have stimulated, and their strengths and weaknesses for research and clinical practice. We then introduce the metaphor of a ball in a bowl that we use as a basis for outlining an integrative framework of dysregulated emotion. We illustrate how such a framework can inspire new research on the reciprocal influences and interactions between the different domains of dysregulated emotion and how it can help to theoretically explain a broader array of findings, such as the high levels of negative affect in clinical populations that have not been fully accounted for by deficits in strategy-based emotion regulation and the positive long-term consequences of accepting and tolerating emotions. Finally, we show how it can facilitate individualized emotion regulation interventions that are tailored to the specific regulatory impairments of the individual patient.

Emotional sounds guide visual attention to emotional pictures: An eye-tracking study with audio-visual stimuli.

For the realm of visual cues, it has been well documented that attention is preferentially oriented toward emotionally relevant cues. Preliminary evidence suggests that emotional cues from other sensory modalities may also steer visual attention toward emotional pictures. However, more research is needed to elucidate the mechanisms that are involved. Therefore, a novel design was used to investigate whether emotional sounds promote attentional orientation toward emotional pictures. To this end, 48 participants viewed pairs of pictures with either neutral or unpleasant content in a free-viewing paradigm. In addition, neutral or unpleasant sounds were presented either on the left-hand or on the right-hand side of the monitor. Eye movements were recorded as an index of visual spatial attention toward the pictures. Most interestingly, position and valence of the sounds independently modulated visual orienting towards unpleasant pictures. For initial capture and sustained attention, orienting towards unpleasant pictures was significantly enhanced when any sound was heard on the same side as the unpleasant picture. In addition, unpleasant sounds (irrespective of the side) boosted leftward bias of initial attention toward emotionally congruent pictures. Taken together, this study clearly shows that emotional auditory cues guide visual spatial allocation of attention specifically to emotionally congruent pictures. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Response to Agomelatine Treatment is Independent of Smoking Status and Dosage: Results From the AGOPSYCH Study.

INTRODUCTION: Cigarette smoking influences response to antidepressant treatment. It accelerates the metabolism of several cytochrome P450 (CYP) subtypes, including CYP1A2, and therefore bears the risk of pharmacokinetic interactions with psychotropic drugs using that pathway. Agomelatine is a substrate of CYP1A2; the association between nicotine use and agomelatine dosage, however, has never been studied before. METHODS: Smoking habits were correlated with agomelatine doses and treatment outcomes in a sample of 27 patients with lifetime diagnoses within the schizophrenia spectrum who received agomelatine treatment in addition to their stable antipsychotic treatment regimen because of depressive symptoms. RESULTS: No interactions were found between smoking status and agomelatine dosage, and treatment outcomes did not differ between smokers and nonsmokers. DISCUSSION: Agomelatine efficacy appears to be independent of dosage and smoking status, pointing toward mechanisms beyond mere dose-response relationships. Further research will be necessary to validate these findings.

Neurocognitive Effects of Agomelatine Treatment in Schizophrenia Patients Suffering From Comorbid Depression: Results From the AGOPSYCH Study.

BACKGROUND: Cognitive impairment in schizophrenia is highly disabling and remains one of the major therapeutic challenges. Agomelatine (AGO), an agonist at melatonergic MT1/MT2 receptors and antagonist at 5-HT2C receptors, increases dopamine and norepinephrine in the prefrontal cortex and may therefore have the potential of improving neurocognition in patients with schizophrenia. METHODS: Twenty-seven patients with schizophrenia and comorbid depression were treated with AGO in addition to stable doses of antipsychotic drugs. Cognitive abilities were assessed with the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB) at study entry and after 12 weeks of AGO treatment after the intention-to-treat principle. RESULTS: We observed statistically significant yet clinically negligible increases of the MCCB composite score and the reasoning/problem solving subscore. Patients with unimpaired sleep at baseline showed greater improvements over time than those with sleep disturbances. Changes on the MCCB were not correlated with other psychometric variables. CONCLUSIONS: Despite statistically significant, cognitive improvements after 12 weeks of AGO treatment were clinically irrelevant. Our findings may be limited by baseline properties of the study sample and the study design. In particular, lacking a control group, it cannot be ruled out that improvements were unrelated to AGO treatment. That is why randomized controlled trials are needed to validate the relevance of AGO as a cognitive enhancer in schizophrenia.

Agomelatine for the Treatment of Major Depressive Episodes in Schizophrenia-Spectrum Disorders: An Open-Prospective Proof-of-Concept Study.

BACKGROUND: Depressive episodes in schizophrenia constitute a major clinical problem, and treatment success is often limited by treatment-emergent side effects. Agomelatine, an agonist at melatonergic MT1/MT2 receptors and 5-HT2C receptor antagonist, is a new antidepressant with a novel mode of action which constitutes a potential therapeutic option for depression in schizophrenia. METHODS: Twenty-seven patients with lifetime diagnoses within the schizophrenia spectrum and comorbid depression were treated with agomelatine in addition to stable doses of antipsychotic agents. Severity of depression and other psychopathological domains (positive/negative symptoms, general psychopathology, psychosocial performance) was assessed regularly by means of standardized rating scales during a 6-week acute treatment phase as well as after a 6-week extension phase. Moreover, safety measures (electrocardiograms, laboratory counts, neurological and non-neurological side effects, sleep quality, sexual functioning) were monitored on a regular basis. RESULTS: Depressive symptoms improved significantly during the 6-week acute treatment phase. In parallel, a significant improvement of negative symptoms, global psychopathology, and psychosocial performance was observed, whereas positive symptoms remained stable. Agomelatine was mostly well tolerated with predominantly mild and self-limiting side effects. However, pharmacokinetic interactions with antipsychotic agents were observed. Interestingly, the quality of sleep did not improve significantly, pointing toward mechanisms that do not depend on resynchronization of circadian rhythms. CONCLUSIONS: Agomelatine appears to be safe and efficacious in treating depressive symptoms in patients with schizophrenia. The risk of pharmacokinetic interactions with antipsychotic agents warrants the need of therapeutic drug monitoring, and regular recording of vital signs seems necessary. Further randomized trials will have to confirm these findings.