Understanding mechanisms of depression prevention: study protocol of a randomized cross-over trial to investigate mechanisms of mindfulness and positive fantasizing as intervention techniques for reducing perseverative cognition in remitted depressed individuals.

BACKGROUND: Major Depressive Disorder (MDD) is one of the most prevalent psychiatric disorders, and involves high relapse rates in which persistent negative thinking and rumination (i.e., perseverative cognition [PC]) play an important role. Positive fantasizing and mindfulness are common evidence-based psychological interventions that have been shown to effectively reduce PC and subsequent depressive relapse. How the interventions cause changes in PC over time, is unknown, but likely differ between the two. Whereas fantasizing may change the valence of thought content, mindfulness may operate through disengaging from automatic thought patterns. Comparing mechanisms of both interventions in a clinical sample and a non-clinical sample can give insight into the effectivity of interventions for different individuals. The current study aims to 1) test whether momentary psychological and psychophysiological indices of PC are differentially affected by positive fantasizing versus mindfulness-based interventions, 2) test whether the mechanisms of change by which fantasizing and mindfulness affect PC differ between remitted MDD versus never-depressed (ND) individuals, and 3) explore potential moderators of the main effects of the two interventions (i.e., what works for whom). METHODS: In this cross-over trial of fantasizing versus mindfulness interventions, we will include 50 remitted MDD and 50 ND individuals. Before the start of the measurements, participants complete several individual characteristics. Daily-life diary measures of thoughts and feelings (using an experience sampling method), behavioural measures of spontaneous thoughts (using the Sustained Attention to Response Task), actigraphy, physiological measures (impedance cardiography, electrocardiography, and electroencephalogram), and measures of depressive mood (self-report questionnaires) are performed during the week before (pre-) the interventions and the week during (peri-) the interventions. After a wash-out of at least one month, pre- and peri-intervention measures for the second intervention are repeated. DISCUSSION: This is the first study integrating self-reports, behavioural-, and physiological measures capturing dynamics at multiple time scales to examine the differential mechanisms of change in PC by psychological interventions in individuals remitted from multiple MDD episodes and ND individuals. Unravelling how therapeutic techniques affect PC in remitted individuals might generate insights that allows development of personalised targeted relapse prevention interventions. TRIAL REGISTRATION: ClinicalTrials.gov: NCT06145984, November 16, 2023.

Effects of right prefrontal theta-burst transcranial magnetic stimulation or transcranial direct current stimulation on apathy in patients with schizophrenia: A multicenter RCT.

Apathy is a core negative symptom associated with an unfavorable functional outcome. Noninvasive brain stimulation has shown promise in the treatment of schizophrenia but has not been tested specifically for apathy. We conducted a randomized controlled trial of intermittent theta-burst (iTBS) transcranial magnetic stimulation and transcranial direct current stimulation (tDCS) targeted at the right dorsolateral prefrontal cortex (DLPFC) in patients diagnosed with a psychotic disorder suffering from apathy. The study was a multicenter, randomized, placebo-controlled, and rater-blinded trial. Patients (N = 88) were randomized into active iTBS, active tDCS, sham iTBS or sham tDCS treatment, daily for two weeks (excluding weekends). Effects were measured post-treatment and at four week and ten week follow-up. Primary outcome was apathy severity (Apathy Evaluation Scale, clinician-rated). Additional measures included assessment of negative symptoms, depression, anhedonia and quality of life. No significant difference in improvement of apathy or negative symptoms was observed for real versus sham treatment with either iTBS or tDCS, though all groups improved to a small extent. We conclude that two weeks of brain stimulation over the right DLPFC with either iTBS or tDCS is not effective for improving apathy or negative symptoms. Longer and more intensive protocols may yield different results.

Abnormal functional neurocircuitry underpinning emotional processing in fibromyalgia.

Fibromyalgia, a condition characterized by chronic pain, is frequently accompanied by emotional disturbances. Here we aimed to study brain activation and functional connectivity (FC) during processing of emotional stimuli in fibromyalgia. Thirty female patients with fibromyalgia and 31 female healthy controls (HC) were included. Psychometric tests were administered to measure alexithymia, affective state, and severity of depressive and anxiety symptoms. Next, participants performed an emotion processing and regulation task during functional magnetic resonance imaging (fMRI). We performed a 2 × 2 ANCOVA to analyze main effects and interactions of the stimuli valence (positive or negative) and group (fibromyalgia or HC) on brain activation. Generalized psychophysiological interaction analysis was used to assess task-dependent FC of brain regions previously associated with emotion processing and fibromyalgia (i.e., hippocampus, amygdala, anterior insula, and pregenual anterior cingulate cortex [pACC]). The left superior lateral occipital cortex showed more activation in fibromyalgia during emotion processing than in HC, irrespective of valence. Moreover, we found an interaction effect (valence x group) in the FC between the left pACC and the precentral and postcentral cortex, and central operculum, and premotor cortex. These results suggest abnormal brain activation and connectivity underlying emotion processing in fibromyalgia, which could help explain the high prevalence of psychopathological symptoms in this condition.

The efficacy of combining cognitive training and noninvasive brain stimulation: A transdiagnostic systematic review and meta-analysis.

Over the past decade, an increasing number of studies investigated the innovative approach of supplementing cognitive training (CT) with noninvasive brain stimulation (NIBS) to increase the effects on outcomes. In this review, we aim to summarize the evidence for this treatment combination. We identified 72 published and unpublished studies (reporting 773 effect sizes), including 2,518 participants from healthy and clinical populations indexed in PubMed, MEDLINE, APA PsycInfo, ProQuest, Web of Science, and https://ClinicalTrials.gov (last search: August 9, 2022) that compared the effects of NIBS combined with CT on cognitive, symptoms, and everyday functioning to CT alone at postintervention and/or follow-up. We performed random-effects meta-analyses with robust variance estimation and assessed risk of bias with the Cochrane ROB tool. Only four studies had low risk of bias in all domains, and many studies lacked standard controls such as keeping the outcome assessor and trainer unaware of the treatment condition. Following sensitivity analyses, only learning/memory robustly improved significantly more when CT was combined with NIBS compared to CT only (g = 0.18, 95% CI [0.07, 0.29]) at postintervention, but not in the long term. The effect was small and limited by substantial heterogeneity. The other seven cognitive outcome domains, symptoms, and everyday functioning did not benefit from adding NIBS to CT. Given the methodological limitation of prior studies, more high-quality trials that focus on the potential of combining NIBS and CT to enhance benefits in everyday functioning in the short and long term are needed to evaluate whether combining NIBS and CT is relevant for clinical practice. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Functional MRI correlates of emotion regulation in major depressive disorder related to depressive disease load measured over nine years.

Major Depressive Disorder (MDD) often is a recurrent and chronic disorder. We investigated the neurocognitive underpinnings of the incremental risk for poor disease course by exploring relations between enduring depression and brain functioning during regulation of negative and positive emotions using cognitive reappraisal. We used fMRI-data from the longitudinal Netherlands Study of Depression and Anxiety acquired during an emotion regulation task in 77 individuals with MDD. Task-related brain activity was related to disease load, calculated from presence and severity of depression in the preceding nine years. Additionally, we explored task related brain-connectivity. Brain functioning in individuals with MDD was further compared to 35 controls to explore overlap between load-effects and general effects related to MDD history/presence. Disease load was not associated with changes in affect or with brain activity, but with connectivity between areas essential for processing, integrating and regulating emotional information during downregulation of negative emotions. Results did not overlap with general MDD-effects. Instead, MDD was generally associated with lower parietal activity during downregulation of negative emotions. During upregulation of positive emotions, disease load was related to connectivity between limbic regions (although driven by symptomatic state), and connectivity between frontal, insular and thalamic regions was lower in MDD (vs controls). Results suggest that previous depressive load relates to brain connectivity in relevant networks during downregulation of negative emotions. These abnormalities do not overlap with disease-general abnormalities and could foster an incremental vulnerability to recurrence or chronicity of MDD. Therefore, optimizing emotion regulation is a promising therapeutic target for improving long-term MDD course.

Understanding and predicting future relapse in depression from resting state functional connectivity and self-referential processing.

BACKGROUND: The recurrent nature of Major Depressive Disorder (MDD) asks for a better understanding of mechanisms underlying relapse. Previously, self-referential processing abnormalities have been linked to vulnerability for relapse. We investigated whether abnormalities in self-referential cognitions and functioning of associated brain-networks persist upon remission and predict relapse. METHODS: Remitted recurrent MDD patients (n = 48) and never-depressed controls (n = 23) underwent resting-state fMRI scanning at baseline and were additionally assessed for their implicit depressed self-associations and ruminative behaviour. A template-based dual regression approach was used to investigate between-group differences in default mode, cingulo-opercular and frontoparietal network resting-state functional connectivity (RSFC). Additional prediction of relapse status at 18-month follow-up was investigated within patients using both regression analyses and machine learning classifiers. RESULTS: Remitted patients showed higher rumination, but no implicit depressed self-associations or RSFC abnormalities were observed between patients and controls. Nevertheless, relapse was related to i) baseline RSFC between the ventral default mode network and the precuneus, dorsomedial frontal gyrus, and inferior occipital lobe, ii) implicit self-associations, and iii) uncontrollability of ruminative thinking, when controlled for depressive symptomatology. Moreover, preliminary machine learning classifiers demonstrated that RSFC within the investigated networks predicted relapse on an individual basis. CONCLUSIONS: Remitted MDD patients seem to be commonly characterized by abnormal rumination, but not by implicit self-associations or abnormalities in relevant brain networks. Nevertheless, relapse was predicted by self-related cognitions and default mode RSFC during remission, suggesting that variations in self-relevant processing play a role in the complex dynamics associated with the vulnerability to developing recurrent depressive episodes. CLINICAL TRIAL REGISTRATION: Netherlands Trial Register, August 18, 2015, trial number NL53205.042.15.

The impact of mood-induction on maladaptive thinking in the vulnerability for depression.

BACKGROUND AND OBJECTIVES: Mind-wandering, and specifically the frequency and content of mind-wandering, plays an important role in the psychological well-being of individuals. Repetitive negative thinking has been associated with a high risk to develop and maintain Major Depressive Disorder. We here combined paradigms and techniques from cognitive sciences and experimental clinical psychology to study the transdiagnostic psychiatric phenomenon of repetitive negative thinking. This allowed us to investigate the adjustability of the content and characteristics of mind-wandering in individuals varying in their susceptibility to negative affect. METHODS: Participants high (n = 42) or low (n = 40) on their vulnerability for negative affect and depression performed a Sustained Attention to Response Task (SART) after a single session of positive fantasizing and a single session of stress induction in a cross-over design. Affective states were measured before and after the interventions. RESULTS: After stress, negative affect increased, while after fantasizing both positive affect increased and negative affect decreased. Thoughts were less off-task, past-related and negative after fantasizing compared to after stress. Individuals more susceptible to negative affect showed more off-task thinking after stress than after fantasizing compared to individuals low on this. LIMITATIONS: In this cross-over design, no baseline measurement was included, limiting comparison to 'uninduced' mind-wandering. Inclusion of self-related concerns in the SART could have led to negative priming. CONCLUSIONS: Stress-induced negative thinking underlying vulnerability for depression could be partially countered by fantasizing in a non-clinical sample, which may inform the development of treatments for depression and other disorders characterized by maladaptive thinking.

eHealth-Based Psychosocial Interventions for Adults With Insomnia: Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Worldwide, insomnia remains a highly prevalent public health problem. eHealth presents a novel opportunity to deliver effective, accessible, and affordable insomnia treatments on a population-wide scale. However, there is no quantitative integration of evidence regarding the effectiveness of eHealth-based psychosocial interventions on insomnia. OBJECTIVE: We aimed to evaluate the effectiveness of eHealth-based psychosocial interventions for insomnia and investigate the influence of specific study characteristics and intervention features on these effects. METHODS: We searched PubMed, Embase, Web of Science, PsycINFO, and the Cochrane Central Register of Controlled Trials from database inception to February 16, 2021, for publications investigating eHealth-based psychosocial interventions targeting insomnia and updated the search of PubMed to December 6, 2021. We also screened gray literature for unpublished data. Eligible studies were randomized controlled trials of eHealth-based psychosocial interventions targeting adults with insomnia. Random-effects meta-analysis models were used to assess primary and secondary outcomes. Primary outcomes were insomnia severity and sleep quality. Meta-analyses were performed by pooling the effects of eHealth-based psychosocial interventions on insomnia compared with inactive and in-person conditions. We performed subgroup analyses and metaregressions to explore specific factors that affected the effectiveness. Secondary outcomes included sleep diary parameters and mental health-related outcomes. RESULTS: Of the 19,980 identified records, 37 randomized controlled trials (13,227 participants) were included. eHealth-based psychosocial interventions significantly reduced insomnia severity (Hedges g=-1.01, 95% CI -1.12 to -0.89; P<.001) and improved sleep quality (Hedges g=-0.58, 95% CI -0.75 to -0.41; P<.001) compared with inactive control conditions, with no evidence of publication bias. We found no significant difference compared with in-person treatment in alleviating insomnia severity (Hedges g=0.41, 95% CI -0.02 to 0.85; P=.06) and a significant advantage for in-person treatment in enhancing sleep quality (Hedges g=0.56, 95% CI 0.24-0.88; P<.001). eHealth-based psychosocial interventions had significantly larger effects (P=.01) on alleviating insomnia severity in clinical samples than in subclinical samples. eHealth-based psychosocial interventions that incorporated guidance from trained therapists had a significantly greater effect on insomnia severity (P=.05) and sleep quality (P=.02) than those with guidance from animated therapists or no guidance. Higher baseline insomnia severity and longer intervention duration were associated with a larger reduction in insomnia severity (P=.004). eHealth-based psychosocial interventions significantly improved each secondary outcome. CONCLUSIONS: eHealth interventions for insomnia are effective in improving sleep and mental health and can be considered a promising treatment for insomnia. Our findings support the wider dissemination of eHealth interventions and their further promotion in a stepped-care model. Offering blended care could improve treatment effectiveness. Future research needs to elucidate which specific intervention components are most important to achieve intervention effectiveness. Blended eHealth interventions may be tailored to benefit people with low socioeconomic status, limited access to health care, or lack of eHealth literacy.

Musical and Multilingual Experience Are Related to Healthy Aging: Better Some Than None But Even Better Together.

OBJECTIVES: Life experiences that are complex, sustained, and intense, such as active participation in music and speaking multiple languages, have been suggested to contribute to maintaining or improving cognitive performance and mental health. The current study focuses on whether lifetime musical and multilingual experiences differentially relate to cognition and well-being in older adults, and tests whether there is a cumulative effect of both experiences. METHODS: A total of 11,335 older adults from the population-based Lifelines Cohort Study completed a musical and multilingual background and experience questionnaire. Latent class analysis was used to categorize individuals into subgroups according to their various musical and multilingual experiences resulting in a (1) nonmusical, low-multilingual group; (2) nonmusical, high-multilingual group; (3) musical, low-multilingual group; and (4) musical high-multilingual group. To determine whether the groups differed in terms of cognition or emotional affect, differences in Ruff Figural Fluency Test (RFFT) and Positive and Negative Affect Schedule scores were investigated by means of multinomial logistic regression analysis. RESULTS: Having high-multilingual, and not musical, experience was related to better RFFT performance compared to no experience, but not to more positive affect. Having both musical and high-multilingual experiences is related to better RFFT performance and more positive affect in advanced age compared to having only one experience or none. Importantly, these results were found independently of age, level of education, and socioeconomic status. DISCUSSION: Musical and multilingual experiences are related to healthy aging, especially when combined, which supports the suggestion that a broader spectrum of lifetime experiences relates to cognitive reserve.

A behavioral and brain imaging dataset with focus on emotion regulation of women with fibromyalgia.

Fibromyalgia is a chronic condition characterized by widespread pain, as well as numerous symptoms related to central sensitization such as: fatigue, cognitive disturbances, constipation/diarrhea and sensory hypersensitivity. Furthermore, depression and anxiety are prevalent comorbidities, accompanied by emotion processing and regulation difficulties. Although fibromyalgia physiopathology is still not fully understood, neuroimaging research methods have shown brain structural and functional alterations as well as neuroinflammation abnormalities. We believe that open access to data may help fibromyalgia research advance more. Here, we present an open dataset of 33 fibromyalgia female patients and 33 paired healthy controls recruited from a Mexican population. Dataset includes demographic, clinical, behavioural and magnetic resonance imaging (MRI) data. The MRI data consists of: structural (T1- and T2- weighted) and functional (task-based and resting state) sequences. The task was an emotion processing and regulation task based on visual stimuli. The MRI data contained in the repository are unprocessed, presented in Brain Imaging Data Structure (BIDS) format and available on the OpenNeuro platform for future analysis.

The association between clinical and biological characteristics of depression and structural brain alterations.

BACKGROUND: Structural brain alterations are observed in major depressive disorder (MDD). However, MDD is a highly heterogeneous disorder and specific clinical or biological characteristics of depression might relate to specific structural brain alterations. Clinical symptom subtypes of depression, as well as immuno-metabolic dysregulation associated with subtypes of depression, have been associated with brain alterations. Therefore, we examined if specific clinical and biological characteristics of depression show different brain alterations compared to overall depression. METHOD: Individuals with and without depressive and/or anxiety disorders from the Netherlands Study of Depression and Anxiety (NESDA) (328 participants from three timepoints leading to 541 observations) and the Mood Treatment with Antidepressants or Running (MOTAR) study (123 baseline participants) were included. Symptom profiles (atypical energy-related profile, melancholic profile and depression severity) and biological indices (inflammatory, metabolic syndrome, and immuno-metabolic indices) were created. The associations of the clinical and biological profiles with depression-related structural brain measures (anterior cingulate cortex [ACC], orbitofrontal cortex, insula, and nucleus accumbens) were examined dimensionally in both studies and meta-analysed. RESULTS: Depression severity was negatively associated with rostral ACC thickness (B = -0.55, pFDR = 0.03), and melancholic symptoms were negatively associated with caudal ACC thickness (B = -0.42, pFDR = 0.03). The atypical energy-related symptom profile and immuno-metabolic indices did not show a consistent association with structural brain measures across studies. CONCLUSION: Overall depression- and melancholic symptom severity showed a dose-response relationship with reduced ACC thickness. No associations between immuno-metabolic dysregulation and structural brain alterations were found, suggesting that although both are associated with depression, distinct mechanisms may be involved.

Neural correlates of anxious distress in depression: A neuroimaging study of reactivity to emotional faces and resting-state functional connectivity.

BACKGROUND: Comorbid anxiety disorders and anxious distress are highly prevalent in major depressive disorder (MDD). The presence of the DSM-5 anxious distress specifier (ADS) has been associated with worse treatment outcomes and chronic disease course. However, little is known about the neurobiological correlates of anxious distress in MDD. METHODS: We probed the relation between the DSM-5 ADS and task-related reactivity to emotional faces, as well as resting-state functional connectivity patterns of intrinsic salience and basal ganglia networks in unmedicated MDD patients with (MDD/ADS+, N = 24) and without ADS (MDD/ADS-, N = 48) and healthy controls (HC, N = 59). Both categorical and dimensional measures of ADS were investigated. RESULTS: MDD/ADS+ patients had higher left amygdala responses to emotional faces compared to MDD/ADS- patients (p = .015)-part of a larger striato-limbic cluster. MDD/ADS+ did not differ from MDD/ADS- or controls in resting-state functional connectivity of the salience or basal ganglia networks. CONCLUSIONS: Current findings suggest that amygdala and striato-limbic hyperactivity to emotional faces may be a neurobiological hallmark specific to MDD with anxious distress, relative to MDD without anxious distress. This may provide preliminary indications of the underlying mechanisms of anxious distress in depression, and underline the importance to account for heterogeneity in depression research.

Neural basis of positive and negative emotion regulation in remitted depression.

The recurrent nature of Major Depressive Disorder (MDD) necessitates a better understanding of mechanisms facilitating relapse. MDD has often been associated with abnormal emotion regulation, underpinned by aberrant interactions between the prefrontal cortex and subcortical areas. We assessed whether neural regulation abnormalities remain after remission and relate to emotion regulation problems in daily life. At the baseline measurement of a randomized controlled trial, an emotion regulation task was performed during fMRI scanning by 46 remitted recurrent (rrMDD) patients and 24 healthy controls. We assessed both fMRI peak activity and the temporal dynamics of the neural response during passive attendance and explicit regulation of positive and negative emotions. Furthermore, we assessed regulation strategy use in daily life using questionnaires, and attentional biases using a modified attentional dot-probe task. RrMDD patients showed lower activation and different temporal dynamics in occipital, parietal, and prefrontal brain regions during passive attendance of emotional material compared to healthy controls. During explicit downregulation of negative emotions, no group differences were found. However, during explicit upregulation of positive emotions, rrMDD patients showed a different neural response over time in the insula. Behaviourally, rrMDD patients were characterized by dysfunctional regulation strategies in daily life. Within rrMDD patients, rumination was associated with activation within a limbic- prefrontal network. After remission, immediate emotional processing seems unaffected, but regulatory abnormalities remain, especially uninstructed and in daily life. Abnormal insula activation during positive upregulation suggests decreased monitoring of positive emotions. The relation between inadequate rumination and brain activity during emotion regulation suggests that regulation of both positive and negative affect is important in understanding neurocognitive underpinnings of resilience.

Contributing factors to advanced brain aging in depression and anxiety disorders.

Depression and anxiety are common and often comorbid mental health disorders that represent risk factors for aging-related conditions. Brain aging has shown to be more advanced in patients with major depressive disorder (MDD). Here, we extend prior work by investigating multivariate brain aging in patients with MDD, anxiety disorders, or both, and examine which factors contribute to older-appearing brains. Adults aged 18-57 years from the Netherlands Study of Depression and Anxiety underwent structural MRI. A pretrained brain-age prediction model based on >2000 samples from the ENIGMA consortium was applied to obtain brain-predicted age differences (brain PAD, predicted brain age minus chronological age) in 65 controls and 220 patients with current MDD and/or anxiety. Brain-PAD estimates were associated with clinical, somatic, lifestyle, and biological factors. After correcting for antidepressant use, brain PAD was significantly higher in MDD (+2.78 years, Cohen's d = 0.25, 95% CI -0.10-0.60) and anxiety patients (+2.91 years, Cohen's d = 0.27, 95% CI -0.08-0.61), compared with controls. There were no significant associations with lifestyle or biological stress systems. A multivariable model indicated unique contributions of higher severity of somatic depression symptoms (b = 4.21 years per unit increase on average sum score) and antidepressant use (-2.53 years) to brain PAD. Advanced brain aging in patients with MDD and anxiety was most strongly associated with somatic depressive symptomatology. We also present clinically relevant evidence for a potential neuroprotective antidepressant effect on the brain-PAD metric that requires follow-up in future research.

Foreign Language Learning as Cognitive Training to Prevent Old Age Disorders? Protocol of a Randomized Controlled Trial of Language Training vs. Musical Training and Social Interaction in Elderly With Subjective Cognitive Decline.

Introduction: With aging comes a reduction of cognitive flexibility, which has been related to the development of late-life depression and progression of general cognitive decline. Several factors have been linked to attenuating such decline in cognitive flexibility, such as education, physical exercise and stimulating leisure activities. Speaking two or more languages has recently received abundant attention as another factor that may build up cognitive reserve, thereby limiting the functional implications of compromised cognition that accompany old age. With the number of older adults reaching record levels, it is important to attenuate the development of old-age disorders. Learning to speak a foreign language might offer a powerful tool in promoting healthy aging, but up to date effect studies are sparse. Here, the protocol that forms the foundation of the current study is presented. The present study aims to: (1) examine the effects of a foreign language training on cognitive flexibility and its neural underpinnings, and on mental health; and (2) assess the unique role of foreign language training vs. other cognitive or social programs. Method: One-hundred and ninety-eight Dutch elderly participants reporting subjective cognitive decline are included and randomized to either a language intervention, a music intervention, or a social control intervention. During 3 to 6 months, the language group learns English, the music group learns to play the guitar and the social group participates in social meetings where art workshops are offered. At baseline, at a 3-month follow-up, and at 6 months after termination of the training program, clinical, cognitive and brain activity measurements (combined EEG and fNIRS methods) are taken to assess cognitive flexibility and mental health. Discussion: This is the first trial addressing combined effects of language learning in elderly on cognition, language proficiency, socio-affective measures, and brain activity in the context of a randomized controlled trial. If successful, this study can provide insights into how foreign language training can contribute to more cognitively and mentally healthy years in older adulthood. Clinical Trial Registration: The trial is registered at the Netherlands Trial Register, July 2, 2018, trial number NL7137. https://www.trialregister.nl/trial/7137.

Relationship between social cognition, general cognition, and risk for suicide in individuals with a psychotic disorder.

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.

Associations between depression, lifestyle and brain structure: A longitudinal MRI study.

BACKGROUND: Depression has been associated with decreased regional grey matter volume, which might partly be explained by an unhealthier lifestyle in depressed individuals which has been ignored by most earlier studies. Also, the longitudinal nature of depression, lifestyle and brain structure associations is largely unknown. This study investigates the relationship of depression and lifestyle with brain structure cross-sectionally and longitudinally over up to 9 years. METHODS: We used longitudinal structural MRI data of persons with depression and/or anxiety disorders and controls (Nunique participants = 347, Nobservations = 609). Cortical thickness of medial orbitofrontal cortex (mOFC), rostral anterior cingulate cortex (rACC) and hippocampal volume were derived using FreeSurfer. Using Generalized Estimating Equations, we investigated associations of depression and lifestyle (Body mass index (BMI), smoking, alcohol consumption, physical activity and sleep duration) with brain structure and change in brain structure over 2 (n = 179) and 9 years (n = 82). RESULTS: Depression status (B = -.053, p = .002) and severity (B = -.002, p = .002) were negatively associated with rACC thickness. mOFC thickness was negatively associated with BMI (B = -.004, p < .001) and positively with moderate alcohol consumption (B = .030, p = .009). All associations were independent of each other. No associations were observed between (change in) depression, disease burden or lifestyle factors with brain change over time. CONCLUSIONS: Depressive symptoms and diagnosis were independently associated with thinner rACC, BMI with thinner mOFC, and moderate alcohol consumption with thicker mOFC. No longitudinal associations were observed, suggesting that regional grey matter alterations are a long-term consequence or vulnerability indicator for depression but not dynamically or progressively related to depression course trajectory.

Insight does not come at random: Individual gray matter networks relate to clinical and cognitive insight in schizophrenia.

BACKGROUND: Impaired clinical and cognitive insight are prevalent in schizophrenia and relate to poorer outcome. Good insight has been suggested to depend on social cognitive and metacognitive abilities requiring global integration of brain signals. Impaired insight has been related to numerous focal gray matter (GM) abnormalities distributed across the brain suggesting dysconnectivity at the global level. In this study, we test whether global integration deficiencies reflected in gray matter network connectivity underlie individual variations in insight. METHODS: We used graph theory to examine whether individual GM-network metrics relate to insight in patients with a psychotic disorder (n = 114). Clinical insight was measured with the Schedule for the Assessment of Insight-Expanded and item G12 of the Positive and Negative Syndrome Scale, and cognitive insight with the Beck Cognitive Insight Scale. Individual GM-similarity networks were created from GM-segmentations of T1-weighted MRI-scans. Graph metrics were calculated using the Brain Connectivity Toolbox. RESULTS: Networks of schizophrenia patients with poorer clinical insight showed less segregation (i.e. clustering coefficient) into specialized subnetworks at the global level. Schizophrenia patients with poorer cognitive insight showed both less segregation and higher connectedness (i.e. lower path length) of their brain networks, making their network topology more "random". CONCLUSIONS: Our findings suggest less segregated processing of information in patients with poorer cognitive and clinical insight, in addition to higher connectedness in patients with poorer cognitive insight. The ability to take a critical perspective on one's symptoms (clinical insight) or views (cognitive insight) might depend especially on segregated specialized processing within distinct subnetworks.

Amygdala-prefrontal connectivity modulates loss aversion bias in anxious individuals.

Anxious individuals tend to make pessimistic judgments in decision making under uncertainty. While this phenomenon is commonly attributed to risk aversion, loss aversion is a critical but often overlooked factor. In this study, we simultaneously examined risk aversion and loss aversion during decision making in high and low trait anxious individuals in a variable gain/loss gambling task during functional magnetic resonance imaging. Although high relative to low anxious individuals showed significant increased risk aversive behavior reflected by decreased overall gamble decisions, there was no group difference in subjective aversion to risk. Instead, loss aversion rather than risk aversion dominantly contributed to predict behavioral decisions, which was associated with attenuated functional connectivity between the amygdala-based emotional system and the prefrontal control regions. Our findings suggest a dominant role of loss aversion in maladaptive risk assessment of anxious individuals, underpinned by disorganization of emotion-related and cognitive-control-related brain networks.