Early Adversity and Emotion Processing From Faces: A Meta-analysis on Behavioral and Neurophysiological Responses.

BACKGROUND: Although the link between early adversity (EA) and later-life psychiatric disorders is well established, it has yet to be elucidated whether EA is related to distortions in the processing of different facial expressions. We conducted a meta-analysis to investigate whether exposure to EA relates to distortions in responses to different facial emotions at three levels: 1) event-related potentials of the P100 and N170, 2) amygdala functional magnetic resonance imaging responses, and 3) accuracy rate or reaction time in behavioral data. METHODS: The systematic literature search (PubMed and Web of Science) up to April 2020 resulted in 29 behavioral studies (n = 8555), 32 functional magnetic resonance imaging studies (n = 2771), and 3 electroencephalography studies (n = 197) for random-effect meta-analyses. RESULTS: EA was related to heightened bilateral amygdala reactivity to sad faces (but not other facial emotions). Exposure to EA was related to faster reaction time but a normal accuracy rate in response to angry and sad faces. In response to fearful and happy faces, EA was related to a lower accuracy rate only in individuals with recent EA exposure. This effect was more pronounced in individuals with exposure to EA before (vs. after) the age of 3 years. These findings were independent of psychiatric diagnoses. Because of the low number of eligible electroencephalography studies, no conclusions could be reached regarding the effect of EA on the event-related potentials. CONCLUSIONS: EA relates to alterations in behavioral and neurophysiological processing of facial emotions. Our study stresses the importance of assessing age at exposure and time since EA because these factors mediate some EA-related perturbations.

High frequency repetitive transcranial magnetic stimulation treatment for major depression: Dissociated effects on psychopathology and neurocognition.

OBJECTIVES: This open-label pilot study explored the effects of a course of accelerated high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) on two neurocognitive domains (decision-making and impulse control) in patients with major depressive disorder (MDD). METHODS: Participants with MDD and a treatment resistant major depressive episode (n=24) underwent twice-daily HF-rTMS targeted at the left dorsolateral prefrontal cortex (lDLPFC) over two weeks. Psychopathology was assessed by clinician-administered and self-reported measures of depression and anxiety; decision-making was assessed by the Iowa Gambling Task, the Balloon Analog Risk Task and the Game of Dice Task; impulse control was assessed by the Stroop Color-Word Task, the Continuous Performance Task and the Stop-Signal Task. RESULTS: Depression and anxiety scores significantly improved from pre-post HF-rTMS treatment. However, none of the decision-making or impulse control variables of interest changed significantly from pre-post HF-rTMS. Moreover, there was no correlation between changes in psychopathological symptoms and in neurocognition. LIMITATIONS: This is a moderately sized open label trial, and the confounds of ongoing psychotropics and illness chronicity can not be excluded in this treatment resistant sample. CONCLUSIONS: There is dissociation between acute symptomatic benefit after a course of accelerated HF-rTMS applied to the lDLPFC in treatment resistant MDD and performance on tests of decision making and impulse control. Though rTMS appears cognitively safe, additional research is warranted to understand this potential dissociation and its putative clinical implications.

Effectiveness and acceptability of accelerated repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant major depressive disorder: an open label trial.

BACKGROUND: Major depressive disorder (MDD) is a significant cause of worldwide disability and treatment resistance is common. High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has emerged as a treatment for MDD, and while efficacious, the daily commitment for typical 4-6 weeks of treatment poses a significant challenge. We aimed to determine the effectiveness and acceptability of an accelerated rTMS protocol for MDD. METHODS: In this naturalistic trial, 27 patients with moderate to severe chronic and treatment-resistant MDD were treated with twice-daily HF-rTMS (10 Hz) applied over the left dorsolateral prefrontal cortex for 2 consecutive weeks (60,000 pulses). The primary outcomes were rates of clinical remission and response (16-item Quick Inventory of Depressive Symptomatology post-treatment score ≤ 6, and ≥ 50% reduction, respectively). Secondary outcomes were self-reported anxious symptoms, depressive symptoms and quality of life, and dropout rates as a proxy for acceptability. RESULTS: Ten (37.0%) patients met criteria for clinical remission and 15 (55.6%) were classified as responders, with comparable outcomes for both moderate and severe MDD. Clinician-rated improvements in depressive symptoms were paralleled in self-reported depressive and anxious symptoms, as well as quality of life. No patient discontinued treatment. LIMITATIONS: This study is limited by short treatment duration that might be lengthened with corresponding improvements in effectiveness, limited duration of follow-up, small sample size, and an open-label design requiring randomized controlled replication. CONCLUSION: An accelerated protocol involving twice-daily sessions of HF-rTMS over the left DLPFC for 2 weeks was effective in treatment-resistant MDD, and had excellent acceptability. Additional research is required to optimize accelerated rTMS treatment protocols and determine efficacy using sham-controlled trials.

Augmenting antidepressants with deep transcranial magnetic stimulation (DTMS) in treatment-resistant major depression.

OBJECTIVES: Deep transcranial magnetic stimulation (DTMS) has been shown to be efficacious and relatively safe for major depressive disorder (MDD). However, its clinical utility as an augmenting strategy for treatment-resistant depression (TRD) remains unexplored. METHODS: In an open label trial, 17 outpatients with severe TRD received 4 weeks of daily high frequency DTMS over the left dorsolateral prefrontal cortex. Depressive and anxious symptoms, suicidality and quality of life (QOL) were measured at baseline (i.e., in the week prior to the start of the DTMS treatment) and at week 5 (i.e., in the week following the end of the DTMS treatment). Primary outcome measures were rates of response and remission at week 5 using an intention-to-treat approach. RESULTS: Response and remission rates at week 5 were 70.6 and 41.2%, respectively. Also, depression, anxiety, and suicidality ratings were significantly improved by week 5 (with Hedges' g estimates ranging from 0.6 to 1.72), as well as four of the five QOL domain scores (i.e., global, psychological, environmental and social). Finally, two patients dropped out of the study at week 1 because of significant scalp discomfort during stimulation. CONCLUSIONS: Our study suggests that DTMS, when used as an augmenting strategy for antidepressants in severe TRD, is efficacious, safe and relatively well tolerated. However, controlled studies with larger samples are needed to confirm and expand our preliminary findings.

Obsessive-Compulsive Disorder Symptoms in Huntington’s Disease: A Case Report / Síntomas del trastorno obsesivocompulsivo en la enfermedad de Huntington: reporte de caso

Introduction: Few cases of obsessive-compulsive disorder (OCD) symptoms preceding the clinical onset of Huntington Disease (HD) or during later stages of the disease have been reported in the literature, but the nature of this association and its neurobiological mechanisms have not been well-investigated. Objectives: To review the scientific literature regarding OCD symptoms in patients with HD and describe a case study from our clinic. Methods: Extensive literature searches were performed to identify reports of patients with concurrent HD and OCD symptoms. Results: Recent studies and the current case report suggest that OCD symptoms may predate or coincide with motor, affective or behavioral symptoms in patients with HD. The development of OCD and HD symptoms may involve structural and functional changes affecting the orbital and medial prefrontal cortex, ventromedial caudate nucleus, and pallidal sites. Conclusions: Some patients with HD develop symptoms associated with OCD. Progressive and differential neuropathological changes in the ventromedial caudate nucleus and related neural circuits may underlie this association. No specific treatment strategy has been developed to treat these patients; however some medications attenuate associated symptoms. Further testing is needed to determine the neurobiological mechanisms of these disorders.

Introducción: Algunos reportes de caso indican que pacientes con enfermedad de Huntington (EH) pueden presentar síntomas obsesivo-compulsivos (TOC) antes del desarrollo de la enfermedad y durante ésta, pero no se ha estudiado la naturaleza de esta asociación y sus mecanismos neurobiológicos. Objetivos: Revisar la literatura científica acerca de la asociación entre EH y síntomas TOC y reportar el caso de un paciente con estas condiciones. Método: Búsqueda selectiva de literatura relevante. Resultados: Estudios recientes y el caso aquí reportado sugieren que los síntomas TOC pueden presentarse antes de la EH y durante ésta. El desarrollo concurrente de estas patologías puede estar mediado por cambios estructurales y funcionales de la corteza prefrontal orbital y medial, región ventromedial del núcleo caudado y regiones palidales. Conclusiones: Algunos pacientes con EH desarrollan síntomas de TOC. Cambios neuropatológicos progresivos y diferenciales en el caudado ventromedial y circuitos dependientes pueden mediar esta asociación. No se ha desarrollado una estrategia terapéutica para el tratamiento de estos pacientes; sin embargo, algunos medicamentos parecen ofrecer mejoría sintomática parcial a los sujetos afectados. Se requieren mayores estudios acerca de los mecanismos neuropatológicos involucrados en esta asociación.

Obsessive-Compulsive Disorder Symptoms in Huntington's Disease: A Case Report.

INTRODUCTION: Few cases of obsessive-compulsive disorder (OCD) symptoms preceding the clinical onset of Huntington Disease (HD) or during later stages of the disease have been reported in the literature, but the nature of this association and its neurobiological mechanisms have not been well-investigated. OBJECTIVES: To review the scientific literature regarding OCD symptoms in patients with HD and describe a case study from our clinic. METHODS: Extensive literature searches were performed to identify reports of patients with concurrent HD and OCD symptoms. RESULTS: Recent studies and the current case report suggest that OCD symptoms may predate or coincide with motor, affective or behavioral symptoms in patients with HD. The development of OCD and HD symptoms may involve structural and functional changes affecting the orbital and medial prefrontal cortex, ventromedial caudate nucleus, and pallidal sites. CONCLUSIONS: Some patients with HD develop symptoms associated with OCD. Progressive and differential neuropathological changes in the ventromedial caudate nucleus and related neural circuits may underlie this association. No specific treatment strategy has been developed to treat these patients; however some medications attenuate associated symptoms. Further testing is needed to determine the neurobiological mechanisms of these disorders.