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Finding robust brain substrates of mood disorders is an important target for research. The degree to which major depression (MDD) and bipolar disorder (BD) are associated with common and/or distinct patterns of volumetric changes is nevertheless unclear. Furthermore, the extant literature is heterogeneous with respect to the nature of these changes. We report a meta-analysis of voxel-based morphometry (VBM) studies in MDD and BD. We identified studies published up to January 2015 that compared grey matter in MDD (50 data sets including 4101 individuals) and BD (36 data sets including 2407 individuals) using whole-brain VBM. We used statistical maps from the studies included where available and reported peak coordinates otherwise. Group comparisons and conjunction analyses identified regions in which the disorders showed common and distinct patterns of volumetric alteration. Both disorders were associated with lower grey-matter volume relative to healthy individuals in a number of areas. Conjunction analysis showed smaller volumes in both disorders in clusters in the dorsomedial and ventromedial prefrontal cortex, including the anterior cingulate cortex and bilateral insula. Group comparisons indicated that findings of smaller grey-matter volumes relative to controls in the right dorsolateral prefrontal cortex and left hippocampus, along with cerebellar, temporal and parietal regions were more substantial in major depression. These results suggest that MDD and BD are characterised by both common and distinct patterns of grey-matter volume changes. This combination of differences and similarities has the potential to inform the development of diagnostic biomarkers for these conditions.

The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen's d=-0.14, % difference=-1.24). This effect was driven by patients with recurrent MDD (Cohen's d=-0.17, % difference=-1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen's d=-0.20, % difference=-1.85) and a trend toward smaller amygdala (Cohen's d=-0.11, % difference=-1.23) and larger lateral ventricles (Cohen's d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status.

Aim: In contrast with findings in amyotrophic lateral sclerosis (ALS), cognitive impairments have as yet not been shown in the lower motor neuron variant of motor neuron disease, progressive spinal muscular atrophy (PMA). The objective of this study was to investigate cognitive function in PMA and to compare the cognitive profile with that of ALS. In addition, visuospatial functions were assessed comprehensively; these tests are underrepresented in earlier neuropsychological investigations in ALS.Methods: 23 PMA and 30 ALS patients (vital capacity >70% of predicted value) underwent a neuropsychological assessment adapted to motor impairments: global cognitive and executive functioning, psychomotor speed, memory, language, attention and visuospatial skills. The results were compared with age, education and sex matched controls and with normative data.Results: Compared with controls, PMA patients performed worse on attention/working memory (digit span backward), category fluency and the Mini-Mental State Examination. Compared with normative data, PMA patients most frequently showed impairment on three measures: letter-number sequencing, and immediate and delayed story recall. 17% of PMA patients showed cognitive impairment, defined as performance below 2 SDs from the mean of normative data on at least three neuropsychological tests. In ALS, similar but more extensive cognitive deficits were found. Visuospatial dysfunction was not found in PMA and ALS.Conclusions: 17% of PMA patients have executive and memory impairments. PMA with cognitive impairment adds a formerly unknown phenotype to the existing classification of motor neuron diseases. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To assess the safety and efficacy of intensive immunosuppression followed by T cell-depleted autologous hematopoietic stem cell transplantation (ASCT) for induction of disease remission in children with refractory progressive juvenile idiopathic arthritis (JIA). METHODS: Twenty-two patients with progressive refractory JIA were followed up over a median period of 80 months after pretreatment with intensive immunosuppression followed by ASCT in a multicenter, prospective, phase II clinical trial. Hematopoietic stem cells were harvested from the patients' bone marrow, depleted of T cells, and kept frozen until used for ASCT. Pretreatment of patients consisted of a combination of antithymocyte globulin, cyclophosphamide, and low-dose total body irradiation. Patients were followed up for ASCT-related complications, recovery of hematologic and immune system parameters, and disease outcomes. RESULTS: Reconstitution of hematologic values to normal range was rapid. Recovery of immune system parameters, especially normalization of CD4+, CD45RA+ naive T cells, was delayed, occurring at >/=6 months after ASCT. The prolonged period of immune deficiency resulted in a large number of viral infections and may have contributed to the development of macrophage activation syndrome (MAS), leading to death, in 2 patients. After ASCT, 8 of the 20 evaluable patients reached complete clinical remission of their JIA, 7 were partial responders, and 5 experienced a relapse of their disease (occurring 7 years after ASCT in 1 patient). Later during followup, 2 of the patients whose disease relapsed died from infections that developed after restarting immunosuppressive medication. CONCLUSION: Intensive immunosuppression followed by ASCT resulted in sustained complete remission or marked improvement in 15 of 22 patients with progressive refractory JIA. The procedure, however, is associated with significant morbidity and risk of mortality due to prolonged and severe depression of T cell immunity. After fatal complications due to MAS were observed in some patients, the protocol was amended in 1999, to ensure less profound depletion of T cells, better control of systemic disease before transplantation, antiviral prophylaxis after transplantation, and slow tapering of corticosteroids. Following these protocol modifications, no additional ASCT-related deaths were observed among the 11 patients who received the modified treatment. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine whether vaccinations aggravate the course of autoimmune diseases such as juvenile idiopathic arthritis (JIA) and whether the immune response to vaccinations may be hampered by immunosuppressive therapy for the underlying disease. METHODS: In this multicenter cohort study, 234 patients with JIA (ages 1-19 years) were vaccinated with meningococcal serogroup C (MenC) conjugate to protect against serogroup C disease (caused by Neisseria meningitidis). Patients were followed up for disease activity for 1 year, from 6 months before until 6 months after vaccination. IgG antibody titers against MenC polysaccharide and the tetanus carrier protein were determined by enzyme-linked immunosorbent assay and toxin binding inhibition assay, respectively. A serum bactericidal assay was performed to determine the function of the anti-MenC antibodies. RESULTS: No change in values for any of the 6 components of the core set criteria for juvenile arthritis disease activity was seen after MenC vaccination. Moreover, no increase in the frequency of disease relapse was detected. Mean anti-MenC IgG concentrations in JIA patients rose significantly within 6-12 weeks after vaccination. Of 157 patients tested, 153 were able to mount anti-MenC IgG serum levels >2 micro g/ml, including patients receiving highly immunosuppressive medication. The 4 patients with a lower anti-MenC antibody response displayed sufficient bactericidal activity despite receiving highly immunosuppressive medication. CONCLUSION: The MenC conjugate vaccine does not aggravate JIA disease activity or increase relapse frequency and results in adequate antibody levels, even in patients receiving highly immunosuppressive medication. Therefore, patients with JIA can be vaccinated safely and effectively with the MenC conjugate. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The evolution of the rheumatoid arthritis (RA)-specific anti-cyclic citrullinated peptide (anti-CCP) antibody response, as measured by the isotypes of anti-CCP, has not been described. This study was undertaken to determine anti-CCP isotype usage in patients with undifferentiated arthritis (UA), patients with recent-onset RA, and patients with RA of long duration. METHODS: IgA, IgM, and IgG subclasses of anti-CCP were measured by enzyme-linked immunosorbent assay in serum samples that were obtained from IgG anti-CCP antibody-positive patients with UA (n = 110) and IgG anti-CCP antibody-positive patients with RA (n = 152) early after the onset of arthritis. Patients with UA in whom RA developed within 1 year (UA-->RA) were compared with patients with UA in whom RA did not develop within 1 year (UA-->UA). In addition, baseline serum samples obtained from a subset of patients with RA (n = 64) were compared with sera obtained from the same patients a median of 7 years later. RESULTS: IgM anti-CCP was present in early samples from both patients with UA and patients with RA and in followup samples from patients with RA. Several IgG anti-CCP antibody-positive patients who did not have IgM anti-CCP early after disease onset did display IgM anti-CCP later in the course of the arthritis. A diverse pattern of isotype usage was detected in early samples, with a trend toward lower frequencies of all isotypes of anti-CCP in patients with UA compared with patients with RA and in UA-->UA patients compared with UA-->RA patients. Levels of all isotypes except IgG1 had decreased after 7 years. CONCLUSION: These data indicate development of the anti-CCP isotype repertoire into full usage early in the course of arthritis. The sustained presence of IgM anti-CCP indicates ongoing recruitment of new B cells into the anti-CCP response, reflecting a continuous (re)activation of the RA-specific anti-CCP response during the course of anti-CCP-positive arthritis. [ABSTRACT FROM AUTHOR]

Major Depressive Disorder (MDD) and anxiety disorders are highly comorbid recurrent psychiatric disorders. Reduced dynamic reconfiguration of brain regions across subnetworks may play a critical role underlying these deficits, with indications of normalization after treatment with antidepressants. This study investigated dynamic reconfigurations in controls and individuals with a current MDD and/or anxiety disorder including antidepressant users and non-users in a large sample (N = 207) of adults. We quantified the number of subnetworks a region switched to (promiscuity) as well as the total number of switches (flexibility). Average whole-brain (i.e., global) values and subnetwork-specific values were compared between diagnosis and antidepressant groups. No differences in reconfiguration dynamics were found between individuals with a current MDD (N = 49), anxiety disorder (N = 46), comorbid MDD and anxiety disorder (N = 55), or controls (N = 57). Global and sensorimotor network (SMN) promiscuity and flexibility were higher in antidepressant users (N = 49, regardless of diagnosis) compared to non-users (N = 101) and controls. Dynamic reconfigurations were considerably higher in antidepressant users relative to non-users and controls, but not significantly altered in individuals with a MDD and/or anxiety disorder. The increase in antidepressant users was apparent across the whole brain and in the SMN when investigating subnetworks. These findings help disentangle how antidepressants improve symptoms., Competing Interests: Declaration of competing interest All authors report no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

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., Competing Interests: Declaration of competing interest The authors declare no interests in relationship to the work reported in this manuscript., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

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., (© 2024. The Author(s).)

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).

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., (© 2023. The Author(s).)

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., Competing Interests: Declaration of competing interest The authors have no competing interests to declare that are relevant to the content of this article. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors have no competing interests to disclose., (Copyright © 2023. Published by Elsevier Ltd.)

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Gerontological Society of America.)

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., (©Wenrui Deng, Rianne M J J van der Kleij, Hongxia Shen, Junjie Wei, Evelyn A Brakema, Nick Guldemond, Xiaoyue Song, Xiaoming Li, Marie-José van Tol, André Aleman, Niels H Chavannes. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 14.03.2023.)

There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven subcortical regions in each hemisphere using family-wise error (FWE)-correction. Mixed-effects d effect sizes were calculated. In the full sample, SAD patients showed smaller bilateral putamen volume than controls (left: d = -0.077, p FWE  = 0.037; right: d = -0.104, p FWE  = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = -0.034, p FWE  = 0.045). Smaller bilateral putamen volumes (left: d = -0.141, p FWE  < 0.001; right: d = -0.158, p FWE  < 0.001) and larger bilateral pallidum volumes (left: d = 0.129, p FWE  = 0.006; right: d = 0.099, p FWE  = 0.046) were detected in adult SAD patients relative to controls, but no volumetric differences were apparent in adolescent SAD patients relative to controls. Comorbid anxiety disorders and age of SAD onset were additional determinants of SAD-related volumetric differences in subcortical regions. To conclude, subtle volumetric alterations in subcortical regions in SAD were detected. Heterogeneity in age and clinical characteristics may partly explain inconsistencies in previous findings. The association between alterations in subcortical volumes and SAD illness progression deserves further investigation, especially from adolescence into adulthood., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

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., (© 2022. The Author(s).)

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, p FDR  = 0.03), and melancholic symptoms were negatively associated with caudal ACC thickness (B = -0.42, p FDR  = 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., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

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., (© 2022 The Authors. Depression and Anxiety published by Wiley Periodicals LLC.)

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., (Copyright © 2022. Published by Elsevier Inc.)

Competing Interests: We declare no competing interests. This work was supported by the foundation Researchfonds Stichting Postacademische Psy-opleidingen (awarded to MNS, grant PPO-MS-MH) and the charitable foundation Stichting tot Steun VCVGZ (awarded to HR, grant 239). The authors' funding sources were not involved in writing the manuscript or the decision to submit it for publication.