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Background: Obesity is a frequent somatic comorbidity of major depression, and it has been associated with worse clinical outcomes and brain structural abnormalities. Converging evidence suggests that electroconvulsive therapy (ECT) induces both clinical improvements and increased subcortical grey matter volume in patients with depression. However, it remains unknown whether increased body weight modulates the clinical response and structural neuroplasticity that occur with ECT., Methods: To address this question, we conducted a longitudinal investigation of structural MRI data from the Global ECT-MRI Research Collaboration (GEMRIC) in 223 patients who were experiencing a major depressive episode (10 scanning sites). Structural MRI data were acquired before and after ECT, and we assessed change in subcortical grey matter volume using FreeSurfer and Quarc., Results: Higher body mass index (BMI) was associated with a significantly lower increase in subcortical grey matter volume following ECT. We observed significant negative associations between BMI and change in subcortical grey matter volume, with pronounced effects in the thalamus and putamen, where obese participants showed increases in grey matter volume that were 43.3% and 49.6%, respectively, of the increases found in participants with normal weight. As well, BMI significantly moderated the association between subcortical grey matter volume change and clinical response to ECT. We observed no significant association between BMI and clinical response to ECT., Limitations: Because only baseline BMI values were available, we were unable to study BMI changes during ECT and their potential association with clinical and grey matter volume change., Conclusion: Future studies should take into account the relevance of body weight as a modulator of structural neuroplasticity during ECT treatment and aim to further explore the functional relevance of this novel finding., Competing Interests: A. Dale reports that he was a founder of and holds equity in CorTechs Labs, Inc., and serves on its scientific advisory board; he is a member of the scientific advisory boards of Human Longevity, Inc., the Mohn Medical Imaging and Visualization Centre; he receives funding through research grants from GE Healthcare to UCSD. The terms of these arrangements have been reviewed by and approved by the University of California, San Diego in accordance with its conflict of interest policies. No other competing interests declared., (© 2021 CMA Joule Inc. or its licensors.)

Background: Childhood maltreatment has been associated with reduced hippocampal volume in healthy individuals, whereas social support, a protective factor, has been positively associated with hippocampal volumes. In this study, we investigated how social support is associated with hippocampal volume in healthy people with previous experience of childhood maltreatment., Methods: We separated a sample of 446 healthy participants into 2 groups using the Childhood Trauma Questionnaire: 265 people without maltreatment and 181 people with maltreatment. We measured perceived social support using a short version of the Social Support Questionnaire. We examined hippocampal volume using automated segmentation (Freesurfer). We conducted a social support × group analysis of covariance on hippocampal volumes controlling for age, sex, total intracranial volume, site and verbal intelligence., Results: Our analysis revealed significantly lower left hippocampal volume in people with maltreatment (left F1,432 = 5.686, p = 0.018; right F1,433 = 3.371, p = 0.07), but no main effect of social support emerged. However, we did find a significant social support × group interaction for left hippocampal volume (left F1,432 = 5.712, p = 0.017; right F1,433 = 3.480, p = 0.06). In people without maltreatment, we observed a trend toward a positive association between social support and hippocampal volume. In contrast, social support was negatively associated with hippocampal volume in people with maltreatment., Limitations: Because of the correlative nature of our study, we could not infer causal relationships between social support, maltreatment and hippocampal volume., Conclusion: Our results point to a complex dynamic between environmental risk, protective factors and brain structure - in line with previous evidence - suggesting a detrimental effect of maltreatment on hippocampal development., Competing Interests: None declared., (© 2021 CMA Joule Inc. or its licensors.)

Background: Alexithymia is a risk factor for major depressive disorder (MDD) and has been associated with diminished treatment response. Neuroimaging studies have revealed structural aberrations of the anterior cingulate cortex and the fusiform gyrus in healthy controls with high levels of alexithymia. The present study tried to corroborate and extend these results to patients with MDD compared with healthy controls., Methods: We investigated the relationship between alexithymia, depression and grey matter volume in 63 patients with MDD (mean age ± standard deviation = 42.43 yr ± 11.91; 33 female) and 46 healthy controls (45.35 yr ± 8.37; 22 female). We assessed alexithymia using the Toronto Alexithymia Scale. We conducted an alexithymia × group analysis of covariance; we used a region-of-interest approach, including the fusiform gyrus and anterior cingulate cortex, and conducted whole brain analysis using voxelbased morphometry., Results: Our analysis revealed a significant alexithymia × group interaction in the fusiform gyrus (left, pFWE = 0.031; right, pFWE = 0.010). Higher alexithymia scores were associated with decreased grey matter volume in patients with MDD (pFWE = 0.009), but with increased grey matter volume of the fusiform gyrus in healthy controls (pFWE = 0.044). We found no significant main effects in the region-of-interest analysis., Limitations: Owing to the naturalistic nature of our study, patients with MDD and healthy controls differed significantly in their alexithymia scores., Conclusion: Our results showed the fusiform gyrus as a correlate of alexithymia. We also found differences related to alexithymia between patients with MDD and healthy controls in the fusiform gyrus. Our study encourages research related to the transition from risk to MDD in people with alexithymia., Competing Interests: H. Kugel received consultation fees from MR:comp GmbH, Testing Services for MR Safety, unrelated to the present work. V. Arolt is a member of the advisory board of, or has given presentations on behalf of, the following companies: Astra-Zeneca, Janssen-Organon, Lilly, Lundbeck, Servier, Pfizer, Otsuka,and Trommsdorff. K. Förster, V. Enneking, K. Dohm, R. Redlich, S. Meinert, A. Geisler, E. Leehr, B. Baune, P. Zwitserlood, D. Grotegerd and U. Dannlowski declare no competing interests., (© 2020 Joule Inc. or its licensors)

Background: Cross-sectional studies have repeatedly shown impaired white matter integrity in patients with major depressive disorder. Longitudinal analyses are missing from the current research and are crucial to elucidating the impact of disease trajectories on white matter impairment in major depressive disorder., Methods: Fifty-nine patients with major depressive disorder receiving inpatient treatment, as well as 49 healthy controls, took part in a prospective study. Participants were scanned twice (baseline and follow-up), approximately 2.25 years apart, using diffusion tensor imaging. We analyzed diffusion metrics using tract-based spatial statistics., Results: At baseline, patients had higher mean diffusivity in a large bilateral frontal cluster comprising the body and genu of the corpus callosum, the anterior and superior corona radiata, and the superior longitudinal fasciculus. A significant group × time interaction revealed a decrease of mean diffusivity in patients with major depressive disorder over time, abolishing group differences at follow-up. This effect was observed irrespective of disease course in the follow-up period., Limitations: Analyzing the course of illness is challenging because of recollection biases in patients with major depressive disorder., Conclusion: This study reports follow-up diffusion tensor imaging data in patients with major depressive disorder after an acute depressive episode. We demonstrated impaired prefrontal white matter microstructure (higher mean diffusivity) at baseline in patients with major depressive disorder, which normalized at follow-up after 2 years, irrespective of disease course. This might have been due to a general treatment effect and might have reflected recovery of white matter integrity., Competing Interests: H. Kugel has received consultation fees from MR:comp GmbH, Testing Services for MR Safety, outside the submitted work. V. Arolt is a member of the advisory boards of Allergan, Janssen-Cilag, Lundbeck, Otsuka, Servier and Trommsdorff and has received speaker fees from Janssen-Cilag, Lundbeck, Otsuka, Servier, outside the submitted work. No other competing interests declared., (© 2019 Joule Inc. or its licensors)

Background: Identifying reliable trait markers of familial risk for major depressive disorder (MDD) is a challenge in translational psychiatric research. In individuals with acute MDD, dysfunctional connectivity patterns of prefrontal areas have been shown repeatedly. However, it has been unclear in which neuronal networks functional alterations in individuals at familial risk for MDD might be present and to what extent they resemble findings previously reported in those with acute MDD., Methods: We investigated differences in blood oxygen level-dependent (BOLD) response of the medial orbitofrontal cortex (OFC) and dorsolateral prefrontal cortex (DLPFC) to aversive stimuli between acute MDD and familial risk for the disorder in healthy first-degree relatives of acutely depressed patients with MDD (HC-FH+), healthy age- and sex-matched controls without any family history of depression (HC-FH-), and acutely depressed patients with MDD with (MDD-FH+) and without a family history of depression (MDD-FH-) during a frequently used emotional face-matching paradigm. Analyses of task-specific network connectivity were conducted in terms of psychophysiological interactions (PPI)., Results: The present analysis included a total of 100 participants: 25 HC-FH+, 25 HC-FH-, 25 MDD-FH+ and 25 MDD-FH-. Patients with MDD exhibited significantly increased activation in the medial OFC to negative stimuli irrespective of familial risk status, whereas healthy participants at familial risk and patients with MDD alike showed significant hypoactivation in the DLPFC compared with healthy participants without familial risk. The PPI analyses revealed significantly enhanced task-specific coupling between the medial OFC and differing cortical areas in individuals with acute MDD and those with familial risk for the disorder., Limitations: The main limitation of our study is its cross-sectional design., Conclusion: Whereas hypoactivation during negative emotion processing in the DLPFC appears as a common feature in both healthy high-risk individuals and acutely depressed patients, activation patterns of the medial OFC and its underlying connectivity seem to distinguish familial risk from acute disorder.

Background: Anhedonia has long been recognized as a key feature of major depressive disorders, but little is known about the association between hedonic symptoms and neurobiological processes in depressed patients. We investigated whether amygdala mood-congruent responses to emotional stimuli in depressed patients are correlated with anhedonic symptoms at automatic levels of processing., Methods: We measured amygdala responsiveness to subliminally presented sad and happy facial expressions in depressed patients and matched healthy controls using functional magnetic resonance imaging. Amygdala responsiveness was compared between patients and healthy controls within a 2 (group) x 2 (emotion) design. In addition, we correlated patients' amygdala responsiveness to sad and happy facial stimuli with self-report questionnaire measures of anhedonia., Results: We included 35 patients and 35 controls in our study. As in previous studies, we observed a strong emotion x group interaction in the bilateral amygdala: depressed patients showed greater amygdala responses to sad than happy faces, whereas healthy controls responded more strongly to happy than sad faces. The lack of automatic right amygdala responsiveness to happy faces in depressed patients was associated with higher physical anhedonia scores., Limitations: Almost all depressed patients were taking antidepressant medications., Conclusion: We replicated our previous finding of depressed patients showing automatic amygdala mood-congruent biases in terms of enhanced reactivity to negative emotional stimuli and reduced activity to positive emotional stimuli. The altered amygdala processing of positive stimuli in patients was associated with anhedonia scores. The results indicate that reduced amygdala responsiveness to positive stimuli may contribute to anhedonic symptoms due to reduced/inappropriate salience attribution to positive information at very early processing levels.