Axo-axonic cells in neuropsychiatric disorders: a systematic review

Imbalance between excitation and inhibition in the cerebral cortex is one of the main theories in neuropsychiatric disorder pathophysiology. Cortical inhibition is finely regulated by a variety of highly specialized GABAergic interneuron types, which are thought to organize neural network activities. Among interneurons, axo-axonic cells are unique in making synapses with the axon initial segment of pyramidal neurons. Alterations of axo-axonic cells have been proposed to be implicated in disorders including epilepsy, schizophrenia and autism spectrum disorder. However, evidence for the alteration of axo-axonic cells in disease has only been examined in narrative reviews. By performing a systematic review of studies investigating axo-axonic cells and axo-axonic communication in epilepsy, schizophrenia and autism spectrum disorder, we outline convergent findings and discrepancies in the literature. Overall, the implication of axo-axonic cells in neuropsychiatric disorders might have been overstated. Additional work is needed to assess initial, mostly indirect findings, and to unravel how defects in axo-axonic cells translates to cortical dysregulation and, in turn, to pathological states

Neuromodulation Treatments of Pathological Anxiety in Anxiety Disorders, Stressor-Related Disorders, and Major Depressive Disorder: A Dimensional Systematic Review and Meta-Analysis

BackgroundPathological anxiety is responsible for major functional impairments and resistance to conventional treatments in anxiety disorders (ADs), posttraumatic stress disorder (PTSD) and major depressive disorder (MDD). Focal neuromodulation therapies such as transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS) and deep brain stimulation (DBS) are being developed to treat those disorders.MethodsWe performed a dimensional systematic review and meta-analysis to assess the evidence of the efficacy of TMS, tDCS and DBS in reducing anxiety symptoms across ADs, PTSD and MDD. Reports were identified through systematic searches in PubMed/Medline, Scopus and Cochrane library (inception to November 2020), followed by review according to the PRISMA guidelines. Controlled clinical trials examining the effectiveness of brain stimulation techniques on generic anxiety symptoms in patients with ADs, PTSD or MDD were selected.ResultsNineteen studies (RCTs) met inclusion criteria, which included 589 participants. Overall, focal brain activity modulation interventions were associated with greater reduction of anxiety levels than controls [SMD: −0.56 (95% CI, −0.93 to−0.20, I2 = 77%]. Subgroup analyses revealed positive effects for TMS across disorders, and of focal neuromodulation in generalized anxiety disorder and PTSD. Rates of clinical responses and remission were higher in the active conditions. However, the risk of bias was high in most studies.ConclusionsThere is moderate quality evidence for the efficacy of neuromodulation in treating pathological anxiety.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=233084, identifier: PROSPERO CRD42021233084. It was submitted on January 29th, 2021, and registered on March 1st, 2021. No amendment was made to the recorded protocol. A change was applied for the subgroup analyses based on target brain regions, we added the putative nature (excitatory/inhibitory) of brain activity modulation

Relationship between body mass index and neuropsychiatric symptoms: Evidence and inflammatory correlates

Objective : Neuropsychiatric symptoms are frequent in obese individuals. Mounting evidence suggests that adiposity-related inflammation contributes to this effect. This study assessed the relationship between adiposity, neuropsychiatric symptom dimensions and systemic inflammation in subjects stratified by body-mass-index (BMI). Methods : The study included 165 subjects, of whom 70 were very severely obese (BMI ≥ 40 kg/m2), 50 severely obese (BMI: 35–39.99 kg/m2), 21 overweight or moderately obese (BMI: 25–34.9 kg/m2), and 24 lean (BMI < 25 kg/m2). Depressive symptoms were assessed using the Montgomery-Asberg Depression Rating Scale (MADRS) and the Mini-International Neuropsychiatric Interview (MINI). Fatigue and general neurobehavioral symptoms were assessed using the Multidimensional Fatigue Inventory (MFI) and Neurotoxicity Rating Scale (NRS) respectively. Serum levels of the inflammatory markers, high-sensitive (hs) CRP and hsIL-6, were determined by ELISA. Results : Severely obese subjects exhibited higher MADRS, MFI and NRS scores and were more frequently afflicted with current diagnosis of major depression than lean participants. Scores on psychometric scales were also increased in very severely obese subjects, although to a lesser extent. Alterations in neuropsychiatric dimensions were highly inter-related. HsCRP was significantly increased in subjects with severe or very severe obesity, while hsIL-6 was augmented in all obese groups. Overall, increased neuropsychiatric comorbidity was associated with greater systemic inflammation, notably hsCRP. Conclusion : Obesity is characterized by an increased prevalence of inter-related neuropsychiatric symptoms together with low-grade systemic inflammation augmenting with adiposity. The association between adiposity, systemic inflammation and neuropsychiatric alterations supports the contribution of adiposity-related inflammatory processes to neuropsychiatric comorbidities in obesity. These data suggest that consideration of adiposity characteristics may help identifying subjects at increased risk for neuropsychiatric comorbidity.Rôle de l'Inflammation dans la Symptomatologie Neuropsychiatrique chez le Sujet Obès

Evaluation of a virtual agent to train medical students conducting psychiatric interviews for diagnosing major depressive disorders

Background: A psychiatric diagnosis involves the physician's ability to create an empathic interaction with the patient in order to accurately extract semiology (i.e., clinical manifestations). Virtual patients (VPs) can be used to train these skills but need to be evaluated in terms of accuracy, and to be perceived positively by users. Methods: We recruited 35 medical students who interacted in a 35-min psychiatric interview with a VP simulating major depressive disorders. Semiology extraction, verbal and non-verbal empathy were measured objectively during the interaction. The students were then debriefed to collect their experience with the VP. Results: The VP was able to simulate the conduction of a psychiatric interview realistically, and was effective to discriminate students depending on their psychiatric knowledge. Results suggest that students managed to keep an emotional distance during the interview and show the added value of emotion recognition software to measure empathy in psychiatry training. Students provided positive feedback regarding pedagogic usefulness, realism and enjoyment in the interaction. Limitations: Our sample was relatively small. As a first prototype, the measures taken by the VP would need improvement (subtler empathic questions, levels of difficulty). The face-tracking technique might induce errors in detecting non-verbal empathy. Conclusion: This study is the first to simulate a realistic psychiatric interview and to measure both skills needed by future psychiatrists: semiology extraction and empathic communication. Results provide evidence that VPs are acceptable by medical students, and highlight their relevance to complement existing training and evaluation tools in the field of affective disorders.Bordeaux Region Aquitaine Initiative for NeurosciencePhénotypage humain et réalité virtuelleInitiative d'excellence de l'Université de Bordeau

Overlap and Mutual Distinctions between Clinical Recovery and Personal Recovery in People with Schizophrenia in a One-Year Study

Recovery is a multidimensional construct that can be defined either from a clinical perspective or from a consumer-focused one, as a self-broadening process aimed at living a meaningful life beyond mental illness. We aimed to longitudinally examine the overlap and mutual distinctions between clinical and personal recovery. Of 1239 people with schizophrenia consecutively recruited from the FondaMental Advanced Centers of Expertise for SZ network, the 507 present at one-year did not differ from those lost to follow-up. Clinical recovery was defined as the combination of clinical remission and functional remission. Personal recovery was defined as being in the rebuilding or in the growth stage of the Stages of Recovery Instrument (STORI). Full recovery was defined as the combination of clinical recovery and personal recovery. First, we examined the factors at baseline associated with each aspect of recovery. Then, we conducted multivariable models on the correlates of stable clinical recovery, stable personal recovery, and stable full recovery after one year. At baseline, clinical recovery and personal recovery were characterized by distinct patterns of outcome (i.e. better objective outcomes but no difference in subjective outcomes for clinical recovery, the opposite pattern for personal recovery, and better overall outcomes for full recovery). We found that clinical recovery and personal recovery predicted each other over time (baseline personal recovery for stable clinical recovery at one year; P =. 026, OR = 4.94 [1.30-23.0]; baseline clinical recovery for stable personal recovery at one year; P =. 016, OR = 3.64 [1.31-11.2]). In short, given the interaction but also the degree of difference between clinical recovery and personal recovery, psychosocial treatment should target, beyond clinical recovery, subjective aspects such as personal recovery and depression to reach full recovery. © 2021 The Author(s). Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved.Sorbonne Universités à Paris pour l'Enseignement et la RechercheFondaMental-Cohorte