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It remains unexplored in the field of fear memory whether functional neuronal connectivity between two brain areas is necessary for one sex but not the other. Here, we show that chemogenetic silencing of centromedial (CeM)-Tac2 fibers in the lateral posterior BNST (BNSTpl) decreased fear memory consolidation in male mice but not females. Optogenetic excitation of CeM-Tac2 fibers in the BNSTpl exhibited enhanced inhibitory postsynaptic currents in males compared to females. In vivo calcium imaging analysis revealed a sex-dimorphic fear memory engram in the BNSTpl. Furthermore, in humans, the single-nucleotide polymorphism (SNP) in the Tac2 receptor (rs2765) (TAC3R) decreased CeM-BNST connectivity in a fear task, impaired fear memory consolidation, and increased the expression of the TAC3R mRNA in AA-carrier men but not in women. These sex differences in critical neuronal circuits underlying fear memory formation may be relevant to human neuropsychiatric disorders with fear memory alterations such as posttraumatic stress disorder.

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, pFWE = 0.037; right: d = -0.104, pFWE = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = -0.034, pFWE = 0.045). Smaller bilateral putamen volumes (left: d = -0.141, pFWE < 0.001; right: d = -0.158, pFWE < 0.001) and larger bilateral pallidum volumes (left: d = 0.129, pFWE = 0.006; right: d = 0.099, pFWE = 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.

The substantial individual heterogeneity that characterizes people with mental illness is often ignored by classical case-control research, which relies on group mean comparisons. Here we present a comprehensive, multiscale characterization of the heterogeneity of gray matter volume (GMV) differences in 1,294 cases diagnosed with one of six conditions (attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, depression, obsessive-compulsive disorder and schizophrenia) and 1,465 matched controls. Normative models indicated that person-specific deviations from population expectations for regional GMV were highly heterogeneous, affecting the same area in <7% of people with the same diagnosis. However, these deviations were embedded within common functional circuits and networks in up to 56% of cases. The salience-ventral attention system was implicated transdiagnostically, with other systems selectively involved in depression, bipolar disorder, schizophrenia and attention-deficit/hyperactivity disorder. Phenotypic differences between cases assigned the same diagnosis may thus arise from the heterogeneous localization of specific regional deviations, whereas phenotypic similarities may be attributable to the dysfunction of common functional circuits and networks.

Objective: Electroconvulsive therapy (ECT) is the most effective treatment for patients with severe major depressive disorder (MDD). Given the known sex differences in MDD, improved knowledge may provide more sex-specific recommendations in clinical guidelines and improve outcome. In the present study we examine sex differences in ECT outcome and its predictors. Methods: Clinical data from 20 independent sites participating in the Global ECT-MRI Research Collaboration (GEMRIC) were obtained for analysis, totaling 500 patients with MDD (58.6 % women) with a mean age of 54.8 years. Severity of depression before and after ECT was assessed with validated depression scales. Remission was defined as a HAM-D score of 7 points or below after ECT. Variables associated with remission were selected based on literature (i.e. depression severity at baseline, age, duration of index episode, and presence of psychotic symptoms). Results: Remission rates of ECT were independent of sex, 48.0 % in women and 45.7 % in men (X2(1) = 0.2, p = 0.70). In the logistic regression analyses, a shorter index duration was identified as a sex-specific predictor for ECT outcome in women (X2(1) = 7.05, p = 0.01). The corresponding predictive margins did show overlapping confidence intervals for men and women. Conclusion: The evidence provided by our study suggests that ECT as a biological treatment for MDD is equally effective in women and men. A shorter duration of index episode was an additional sex- specific predictor for remission in women. Future research should establish whether the confidence intervals for the corresponding predictive margins are overlapping, as we find, or not.

01 september 2023, Contains fulltext : 296133.pdf (Publisher’s version ) (Open Access), The substantial individual heterogeneity that characterizes people with mental illness is often ignored by classical case-control research, which relies on group mean comparisons. Here we present a comprehensive, multiscale characterization of the heterogeneity of gray matter volume (GMV) differences in 1,294 cases diagnosed with one of six conditions (attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, depression, obsessive-compulsive disorder and schizophrenia) and 1,465 matched controls. Normative models indicated that person-specific deviations from population expectations for regional GMV were highly heterogeneous, affecting the same area in <7% of people with the same diagnosis. However, these deviations were embedded within common functional circuits and networks in up to 56% of cases. The salience-ventral attention system was implicated transdiagnostically, with other systems selectively involved in depression, bipolar disorder, schizophrenia and attention-deficit/hyperactivity disorder. Phenotypic differences between cases assigned the same diagnosis may thus arise from the heterogeneous localization of specific regional deviations, whereas phenotypic similarities may be attributable to the dysfunction of common functional circuits and networks.

BACKGROUND: Pituitary adenylate cyclase-activating polypeptide (PACAP) receptor gene polymorphism has been postulated as a potential sex-specific diagnostic biomarker of trauma-related disorders. However, no research to date has evaluated whether the PACAPergic system may act as a vulnerability/resilience neuromechanism to trauma-induced psychopathology in healthy participants without heightened risk to experience traumatic events. METHODS: Here, we compared the amygdala and hippocampus response to fearful faces in participants with at-risk genotype versus non-risk participants from the Human Connectome Project (n = 991; 53.4% female). RESULTS: Increased hippocampal response to fearful faces in the female risk group emerged in sex by genetic risk interaction. CONCLUSIONS: Our findings revealed the first sex-specific neurogenetic vulnerability factor to trauma-related disorders, and emphasize the importance of prevention-based strategies to ameliorate neuropsychiatric pathophysiology.

La teràpia electroconvulsiva (TEC) és una tècnica útil, a la fase aguda i de manteniment, en el tractament dels trastorns mentals greus. Malgrat això, la TEC s'utilitza de forma heterogènia a nivell mundial. Existeixen estudis que conclouen que presentar una millora precoç o early improvement (EI) amb el tractament, en el Trastorn Depressiu Major (TDM), prediu el resultat final del tractament, però existeixen poques dades respecte a la TEC. En aquests estudis, per a la definició d'EI, s'han utilitzat diverses reduccions de la Hamilton Depression Rating Scale (HDRS), en diversos punts temporals, però no existeix un consens respecte la definició d'EI en la TEC. L'eficàcia de la TEC com a tractament a llarg termini (TEC de continuació i/o manteniment; TEC-c/m) ha estat contrastada, a través d'estudis de diversa metodologia i revisions, però existeixen pocs estudis aleatoritzats. Així mateix, existeixen escasses dades sobre l'evolució dels pacients al retirar la TEC-c/m i quins son els possibles factors de risc per presentar recidives. Finalment, el darrer any 2020, amb la pandèmia COVID-19, els sistemes sanitaris han estat duts al límit i molts aspectes de la pràctica clínica habitual s'han hagut de replantejar. En aquest context, l'aplicació de la TEC a tot al mon s'ha vist fortament afectada. El treball de tesi posa el focus en aprofundir en el coneixement de la TEC, per tal de garantir el bon ús, permetent, si és possible, uns millors resultats. Els objectius son: 1) Conèixer el patró d'ús i les condicions d'aplicació de la TEC a Catalunya, així com la opinió dels professionals; 2) Estudiar aspectes clínics rellevants de: a) la TEC aguda, quant a la identifació d'una possible definició d'EI a la TEC en el TDM i el possible valor predictiu d'aquesta en el resultat final o remissió, i b) la TEC-c/m, respecte el seu paper en la prevenció de recaigudes i recurrències en el TDM, així com conèixer l'evolució dels pacients al discontinuar la TEC-c/m; 3) Avaluar l'impacte d, La terapia electroconvulsiva (TEC) es una técnica útil, en la fase aguda y de mantenimiento, en el tratamiento de los trastornos mentales graves. Aun así, la TEC se utiliza de forma heterogénea a nivel mundial. Existen estudios que concluyen que presentar una mejoría precoz o early improvement (EI), en el Trastorno Depresivo Mayor (TDM), predice el resultado final del tratamiento, pero existen pocos datos respecto a la TEC. Para la definición de EI, se han utilizado varias reducciones de la Hamilton Depression Rating Scale (HDRS), en varios puntos temporales, pero no existe un consenso respecto a la definición de EI en la TEC. La eficacia de la TEC como tratamiento a largo plazo (TEC de continuación y/o mantenimiento; TEC-c/m) ha sido contrastada, a través de estudios de diversa metodología y revisiones, pero existen pocos estudios aleatorizados. Además, existen escasos datos sobre la evolución de los pacientes al retirar la TEC-c/m y cuáles son los posibles factores de riesgo para recidivas. Finalmente, en 2020, con la pandemia COVID-19, los sistemas sanitarios han sido llevados al límite y muchos aspectos de la práctica clínica habitual se han tenido que replantear. En esto contexto, la aplicación de la TEC en todo el mundo se ha visto fuertemente afectada. El trabajo de tesis pone el foco en profundizar en el conocimiento de la TEC, para garantizar el buen uso, permitiendo unos mejores resultados. Los objetivos fueron: 1) Conocer el patrón de uso y las condiciones de aplicación de la TEC en Cataluña, así como la opinión de los profesionales; 2) Estudiar aspectos clínicos relevantes de: a) la TEC aguda, respecto a la identifación de una posible definición de EI con la TEC en el TDM y el posible valor predictivo de ésta en el resultado final o remisión, i b) la TEC-c/m, respecto a su papel en la prevención de recaídas y recurrencias en el TDM, así como conocer la evolución de los pacientes al retirar la TEC-c/m; 3) Evaluar el impacto de la COVID-19 en la TEC-c/m. L, Electroconvulsive therapy (ECT) is a useful technique in the acute and maintenance treatment of severe mental disorders. Even so, ECT is used heterogeneously worldwide. There are studies that conclude that early improvement (EI) in Major Depressive Disorder (MDD) predicts the final outcome of treatment, but there are few data regarding ECT. For the definition of EI, several reductions of the Hamilton Depression Rating Scale (HDRS) have been used at various time points, but there is no consensus regarding the definition of EI in ECT. The efficacy of ECT as a long-term treatment (continuation and/or maintenance ECT; c/m-ECT) has been contrasted, through studies of diverse methodology and reviews, but there are few randomized studies. In addition, there is little data on the evolution of patients after discontinuation of c/m-ECT and what are the possible risk factors for relapse. Finally, in 2020, with the COVID-19 pandemic, healthcare systems have been pushed to the limit and many aspects of routine clinical practice have had to be rethought. In this context, the application of ECT worldwide has been strongly affected. The thesis work focuses on deepening the knowledge of ECT, to ensure its proper use, allowing better results. The objectives were: 1) To know the pattern of use and the conditions of application of ECT in Catalonia, as well as the opinion of professionals; 2) To study relevant clinical aspects of: (a) acute ECT, regarding the identification of a possible definition of IE with ECT in MDD and the possible predictive value of this in the final outcome or remission, i (b) c/m-ECT, regarding its role in the prevention of relapses and recurrences in MDD, as well as to know the evolution of patients upon discontinuation of c/m ECT; 3) To evaluate the impact of COVID-19 on c/m ECT. The results suggest that the practice of ECT in Catalonia has changed since the 1990s, being administered more frequently, in a more standardized manner and in a greater number of un, Universitat Autònoma de Barcelona. Programa de Doctorat en Psiquiatria

The high comorbidity of Major Depressive Disorder (MDD), Anxiety Disorders (ANX), and Posttraumatic Stress Disorder (PTSD) has hindered the study of their structural neural correlates. The authors analyzed specific and common grey matter volume (GMV) characteristics by comparing them with healthy controls (HC). The meta-analysis of voxel-based morphometry (VBM) studies showed unique GMV diminutions for each disorder (p < 0.05, corrected) and less robust smaller GMV across diagnostics (p < 0.01, uncorrected). Pairwise comparison between the disorders showed GMV differences in MDD versus ANX and in ANX versus PTSD. These results endorse the hypothesis that unique clinical features characterizing MDD, ANX, and PTSD are also reflected by disorder specific GMV correlates.

OBJECTIVE: Research suggests abnormalities in reward-based processes in anorexia nervosa (AN). However, few studies have explored if such alterations might be associated with different temporal activation patterns. This study aims to characterize alterations in time-dependent processes in the ventral striatum (VS) during social feedback in AN using functional magnetic resonance imaging (fMRI). METHOD: Twenty women with restrictive-subtype AN and 20 age-matched healthy controls (HC) underwent a social judgment experimental fMRI task. Temporal VS hemodynamic responses were extracted in SPM for each participant and each social condition (acceptance/rejection). RESULTS: Compared with age-matched HC, patients with AN showed a significant time by group interaction of peak VS response throughout the task, with a progressive blunting of peak activation responses, accompanied by a progressive increase in baseline activity levels over time. DISCUSSION: The results suggest an attenuated response pattern to repetitive social rejection in the VS in patients with AN, together with a difficulty in returning to baseline. The information obtained from this study will guide future, design-specific studies to further explore alterations temporal dynamics.

BACKGROUND: One common denominator to the clinical phenotypes of borderline personality disorder (BPD) and major depressive disorder (MDD) is emotion regulation impairment. Although these two conditions have been extensively studied separately, it remains unclear whether their emotion regulation impairments are underpinned by shared or distinct neurobiological alterations. METHODS: We contrasted the neural correlates of negative emotion regulation across an adult sample of BPD patients (n = 19), MDD patients (n = 20), and healthy controls (HCs; n = 19). Emotion regulation was assessed using an established functional magnetic resonance imaging cognitive reappraisal paradigm. We assessed both task-related activations and modulations of interregional connectivity. RESULTS: When compared to HCs, patients with BPD and MDD displayed homologous decreased activation in the right ventrolateral prefrontal cortex (vlPFC) during cognitive reappraisal. In addition, the MDD group presented decreased activations in other prefrontal areas (i.e., left dorsolateral and bilateral orbitofrontal cortices), while the BPD group was characterized by a more extended pattern of alteration in the connectivity between the vlPFC and cortices of the visual ventral stream during reappraisal. CONCLUSIONS: This study identified, for the first time, a shared neurobiological contributor to emotion regulation deficits in MDD and BPD characterized by decreased vlPFC activity, although we also observed disorder-specific alterations. In MDD, results suggest a primary deficit in the strength of prefrontal activations, while BPD is better defined by connectivity disruptions between the vlPFC and temporal emotion processing regions. These findings substantiate, in neurobiological terms, the different profiles of emotion regulation alterations observed in these disorders.

Recent genome-wide association studies have demonstrated that the genetic burden associated with depression correlates with depression severity. Therefore, conducting genetic studies of patients at the most severe end of the depressive disorder spectrum, those with treatment-resistant depression and who are prescribed electroconvulsive therapy (ECT), could lead to a better understanding of the genetic underpinnings of depression. Despite ECT being one of the most effective forms of treatment for severe depressive disorders, it is usually placed at the end of treatment algorithms of current guidelines. This is perhaps because ECT has controlled risk and logistical demands including use of general anaesthesia and muscle relaxants and side-effects such as short-term memory impairment. Better understanding of the genetics and biology of ECT response and of cognitive side-effects could lead to more personalized treatment decisions. To enhance the understanding of the genomics of severe depression and ECT response, researchers and ECT providers from around the world and from various depression or ECT networks, but not limited to, such as the Psychiatric Genomics Consortium, the Clinical Alliance and Research in ECT, and the National Network of Depression Centers have formed the Genetics of ECT International Consortium (Gen-ECT-ic). Gen-ECT-ic will organize the largest clinical and genetic collection to date to study the genomics of severe depressive disorders and response to ECT, aiming for 30,000 patients worldwide using a GWAS approach. At this stage it will be the largest genomic study on treatment response in depression. Retrospective data abstraction and prospective data collection will be facilitated by a uniform data collection approach that is flexible and will incorporate data from many clinical practices. Gen-ECT-ic invites all ECT providers and researchers to join its efforts.