Severe allergic asthma: Does alexithymia interfere with omalizumab treatment outcome?

BACKGROUND: Alexithymia is among psychological factors reported to interfere with asthma management. Severe allergic asthma (SAA) is characterized by uncontrolled asthma despite maximal standard pharmacological treatment which can benefit from an add-on treatment with Omalizumab, an anti-IgE monoclonal antibody. OBJECTIVE: To evaluate if alexithymia influences the efficacy of omalizumab in SAA. METHODS: The total alexithymia score 20 (TAS 20) questionnaire allowed to detect alexithymia. SAA was monitored recording number of exacerbations, asthma control test (ACT) and asthma quality of life questionnaire (AQLQ) scores, as well as forced expiratory volumes in 1 second % (FEV1%) levels before starting omalizumab, 1 and 2 years after. RESULTS: The study was conducted on 18 patients; Group 1, TAS 20 ≥ 61, was of 2 males and 4 females with SAA and alexithymia, while Group 2 , TAS 20 ≤ 51, was of 8 males and 4 females, without alexithymia. Group 1 had a statistically significant decrease in asthma exacerbations "p = 0.004", while ACT "p = 0.008" and AQLQ scores statistically increased. FEV1 values increased but not statistically significantly. Group 2 had a highly statistically significant decrease in the number of exacerbations and a highly statistically significant increase of ACT "p < 0.0001", FEV1 "p = 0.008" and AQLQ scores. CONCLUSIONS: Regardless the presence or not of alexithymia, all patients with SAA obtained a marked improvement after starting treatment with omalizumab. Therefore alexithymia does not seem to influence the treatment outcome of omalizumab.

Study on the use, acceptability and implementation of the Unified Protocolin general health psychologists in Spain / Estudio sobre el uso, aceptabilidad e implementación del Protocolo Unificado en psicólogos generales sanitarios en España

The dissemination of evidence-based psychological treatments (EBPT) is a pending task for Clinical Psychology. Through an online sur-vey and following the Theoretical Framework of Acceptability, we ana-lyzed the opinions about use, acceptability and intention to use in the fu-ture of the Unified Protocol for the transdiagnostic treatment of emotional disorders (UP) in a sample of 153 professionals of General Health Psy-chology (GHPs). All participants took a training course in the UP and were grouped depending on their previous experience in the UP application. The results showed high scores in acceptability and intention to use in the future in GHPs regardless of the group. Finally, statistically significant cor-relations were found between intention to use in the future and affective attitude, consistency of the intervention and perceived efficacy (in both groups) and self-efficacy (in the group of GHPs without experience in the use of UP). The UP is an EBPT that presents high levels of acceptance and intention to use by the GHPs who received training in this interven-tion, this will facilitate its dissemination and implementation and will allow a greater number of people to benefit from this treatme.(AU)

La diseminación de tratamientos psicológicos basados en la evidencia (TPBE) es una tarea pendiente para la Psicología Clínica. A través de una encuesta online y siguiendo el Modelo Teórico sobre Aceptabilidad, analizamos las opiniones sobre el uso, aceptabilidad e intención de uso en el futuro del Protocolo Unificado para el tratamiento transdiagnóstico de los trastornos emocionales (PU) en una muestra de 153 profesionales de la Psicología General Sanitaria (PGS). Todos los participantes habían realizado un curso de formación sobre el PU y se agruparon según su experiencia previa con la aplicación del PU. Los resultados mostraron altas puntuaciones en aceptabilidad e intención de uso en los PGS con independencia del grupo. Se encontraron correlaciones estadísticamente significativas entre la intención de uso en el futuro y la actitud afectiva, coherencia de la intervención y eficacia percibida (en ambos grupos) y autoeficacia (en el grupo de PGS sin experiencia en el uso del PU). El PU es un TPBE que presenta altos niveles de aceptación e intención de uso por parte de los PGS que recibieron formación en esta intervención, esto facilitará su diseminación e implementación y permitirá que un mayor número de personas puedan beneficiarse de este tratamiento.(AU)

Craving Moderates the Effects of Intranasal Oxytocin on Anger in Response to Social Stress Among Veterans With Co-Occurring Posttraumatic Stress Disorder and Alcohol Use Disorder.

PURPOSE/BACKGROUND: Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) commonly co-occur among US military veterans. Oxytocin may have therapeutic value in treating both conditions. The potential for oxytocin to augment affective features common to PTSD and AUD, such as anger, is relevant to inform emerging treatments. METHODS/PROCEDURES: We examined the influence of intranasally administered oxytocin on connections between alcohol craving and stress-induced anger in a sample of 73 veterans (91.3% men) with co-occurring PTSD and AUD. Participants self-administered oxytocin (40 IU) or placebo (saline) 45 minutes before completing the Trier Social Stress Task (TSST). Self-reports of alcohol craving and anger were assessed pre- and post-TSST using a modified visual analog scale. Multiple regression analysis, including main effects for group, baseline craving, and their interaction, was used to predict post-TSST anger. FINDINGS/RESULTS: A marginally significant interaction was observed, suggesting a positive association between baseline craving and anger for those in the oxytocin group (B = 0.65, P = 0.01). Among those reporting low craving, participants in the oxytocin group reported significantly lower post-TSST anger than those in the placebo group. IMPLICATIONS/CONCLUSIONS: The current study is among the first to examine relevant psychosocial moderators that may influence the effects of oxytocin among veterans with comorbid PTSD and AUD. Although oxytocin attenuated ratings of anger after a stress task among those with low baseline craving, findings suggest that oxytocin may not be as effective at reducing anger, a highly salient factor in PTSD, for individuals experiencing high levels of craving. Findings are consistent with the social salience hypothesis and suggest that individual differences in alcohol craving should be considered when evaluating oxytocin as a potential treatment for individuals with comorbid PTSD and AUD.

Effect of Exenatide Use on Cognitive and Affective Functioning in Obese Patients With Type 2 Diabetes Mellitus: Exenatide Use Mediates Depressive Scores Through Increased Perceived Stress Levels.

PURPOSE/BACKGROUND: Glucagon-like peptide-1 (GLP-1) is a molecule used to treat type 2 diabetes mellitus (T2DM). Given their widespread expression in the nervous system, GLP-1 receptors also play a role in regulating mood and cognitive function. Here, we aimed to compare obese patients with T2DM, with or without exenatide (a GLP-1R agonist) use on cognitive and affective functioning. METHODS/PROCEDURES: A total of 43 patients with T2DM (23 on exenatide and 20 without exenatide) were evaluated with the Snaith-Hamilton Pleasure Scale, Cognitive Failures Questionnaire, Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7, Childhood Trauma Questionnaire, Perceived Stress Scale (PSS), and Chronic Stress Scale, in addition to laboratory-based measures of reward learning (the probabilistic reward task) and working memory (Letter-N-Back task). FINDINGS/RESULTS: Patients on exenatide had higher body mass index (BMI) (37.88 ± 5.44 vs 35.29 ± 6.30; P = 0.015), PHQ-9 (9.70 ± 4.92 vs 6.70 ± 4.66; P = 0.026), and PSS (29.39 ± 6.70 vs 23.35 ± 7.69; P = 0.015) scores. Other stress scales (Childhood Trauma Questionnaire and Chronic Stress Scale), Generalized Anxiety Disorder-7 scores, response bias, or discriminability as assessed by probabilistic reward task and self-report (Cognitive Failures Questionnaire) and laboratory-based (Letter-N-Back) cognitive measures were not significantly different between groups (both Ps > 0.05). Multivariate linear regression analyses adding BMI and PSS as covariates revealed that although BMI had no effect (P = 0.5), PSS significantly predicted PHQ-9 scores (P = 0.004). Mediation analysis showed that exenatide users reported higher PSS, with greater PSS associated with higher PHQ-9 levels (b = 0.236). There was no evidence on exenatide directly influencing PHQ-9 independent of PSS (c' = 1.573; P = 0.305; 95% bootstrap confidence interval, -1.487 to 4.634). IMPLICATIONS/CONCLUSIONS: Based on previous research and our findings, exenatide use might be mediating depression scores through disrupting stress responses.

Effects of celecoxib augmentation of antidepressant or anxiolytic treatment on affective symptoms and inflammatory markers in patients with anxiety disorders: exploratory study.

Prolonged stress has been associated with elevated levels of circulating proinflammatory cytokines. Cyclo-oxygenase-2 inhibitors such as celecoxib exert anti-inflammatory effects and may enhance the response to antidepressant drug treatment in patients with depressive disorders, but their effect on anxiety symptoms in patients with anxiety disorders is uncertain. Patients with a primary diagnosis of an anxiety disorder, with stabilised symptoms, underwent either 6 weeks of celecoxib augmentation of continued treatment (n = 18) or continued 'treatment as usual' (n = 9). Assessments included the Warwick-Edinburgh mental well-being Scale (WEMWEBS), Hospital Anxiety and Depression Scale (HADS), Oxford questionnaire of emotional side effects of antidepressants (OQUESA) and Clinical Global Impression of Illness Severity (CGI-S). Venous blood samples were collected for assays of inflammatory cytokines. Patients who underwent celecoxib augmentation showed significant reductions in anxiety (HADS-A -3.17) and depressive (HADS-D -2.11) symptoms and in overall illness severity (CGI-S -1.11), and improvements in mental well-being (WEMWBS 7.5) and positive changes in emotional responsiveness (OQUESA-RP -3.56; OQUESA-AC -4.22): these were not seen with 'treatment as usual'. There were no significant changes in blood levels of inflammatory cytokines in either group. Celecoxib augmentation appeared associated with beneficial effects on anxiety and depressive symptoms and mental well-being. The findings from this pilot study merit further exploration within a double-blind, randomised placebo-controlled study.

Brief psychological treatments for emotional disorders in Primary and Specialized Care: A randomized controlled trial / Tratamientos psicológicos breves para trastornos emocionales en Atención Primaria y Especializada: un ensayo clínico aleatorizado

Background/Objective Brief transdiagnostic psychotherapies are a possible treatment for emotional disorders. We aimed to determine their efficacy on mild/moderate emotional disorders compared with treatment as usual (TAU) based on pharmacological interventions. Method: This study was a single-blinded randomized controlled trial with parallel design of three groups. Patients (N = 102) were assigned to brief individual psychotherapy (n = 34), brief group psychotherapy (n = 34) or TAU (n = 34). Participants were assessed before and after the interventions with the following measures: PHQ-15, PHQ-9, PHQ-PD, GAD-7, STAI, BDI-II, BSI-18, and SCID. We conducted per protocol and intention-to-treat analyses. Results: Brief psychotherapies were more effective than TAU for the reduction of emotional disorders symptoms and diagnoses with moderate/high effect sizes. TAU was only effective in reducing depressive symptoms. Conclusions: Brief transdiagnostic psychotherapies might be the treatment of choice for mild/moderate emotional disorders and they seem suitable to be implemented within health care systems. (AU)

Antecedentes/Objetivo: Las psicoterapias breves son un posible tratamiento para los trastornos emocionales. Nuestro propósito fue determinar su eficacia en los trastornos emocionales leves/moderados en comparación con el tratamiento habitual basado en intervenciones farmacológicas. Método: Este estudio fue un ensayo clínico aleatorizado simple ciego con diseño paralelo de tres grupos. Los pacientes (N = 102) fueron asignados a psicoterapia breve individual (n = 34), psicoterapia breve grupal (n = 34) o tratamiento habitual (n = 34). Los participantes fueron evaluados antes y después del tratamiento con los siguientes instrumentos: PHQ-15, PHQ-9, PHQ-PD, GAD-7, STAI, BDI-II, BSI-18 y SCID. Se realizaron análisis por protocolo y por intención de tratar. Resultados: Las psicoterapias breves fueron más efectivas que el tratamiento habitual para la reducción de síntomas y diagnósticos de los trastornos emocionales. El tratamiento habitual solo fue efectivo en reducir los síntomas depresivos. Conclusiones: Las psicoterapias breves pueden ser el tratamiento de elección para los trastornos emocionales leves/moderados y podrían implementarse en los sistemas de salud. (AU)

Xiangshao granules can relieve emotional symptoms in menopausal women: a randomized controlled trial.

OBJECTIVE: This study aimed to investigate the safety and efficacy of Xiangshao granules for treating emotional disorders in perimenopausal and postmenopausal women. METHODS: The current investigation was a double-blind, randomized, placebo-controlled, multicenter trial that included 300 perimenopausal and postmenopausal Chinese women aged 40-60 years. Participants received either a placebo (n = 150) or Xiangshao granules (n = 150) for 8 weeks. Outcome measures included Hamilton Depression Rating Scale (HAMD) and Hamilton Anxiety Rating Scale (HAMA) scores, which were assessed at baseline, 4 weeks, and 8 weeks. The primary efficacy variables were changes in HAMD and HAMA scores after 8 weeks. RESULTS: After 8 weeks, the mean HAMD scores decreased from 15.0 to 7.9 in the Xiangshao group and from 16.3 to 10.0 in the placebo group, and the respective mean reductions in HAMA scores were from 16.0 to 8.5 and from 17.1 to 10.9. Clinical improvements in symptoms of both depression and anxiety after 8 weeks differed significantly in the two groups (p < 0.05). The cure rate was significantly higher in the Xiangshao group. There were no significant differences in the rates of adverse events in the two groups. CONCLUSIONS: Xiangshao granules can relieve symptoms of depression and anxiety significantly and safely.

Hop Bitter Acids Increase Hippocampal Dopaminergic Activity in a Mouse Model of Social Defeat Stress.

As daily lifestyle is closely associated with mental illnesses, diet-based preventive approaches are receiving attention. Supplementation with hop bitter acids such as iso-α-acids (IAA) and mature hop bitter acids (MHBA) improves mood states in healthy older adults. However, the underlying mechanism remains unknown. Since acute oral consumption with IAA increases dopamine levels in hippocampus and improves memory impairment via vagal nerve activation, here we investigated the effects of chronic administration of hop bitter acids on the dopaminergic activity associated with emotional disturbance in a mouse model of repeated social defeat stress (R-SDS). Chronic administration of IAA and MHBA significantly increased dopaminergic activity based on the dopamine metabolite to dopamine ratio in the hippocampus and medial prefrontal cortex following R-SDS. Hippocampal dopaminergic activity was inversely correlated with the level of R-SDS-induced social avoidance with or without IAA administration. Therefore, chronic treatment with hop bitter acids enhances stress resilience-related hippocampal dopaminergic activity.

The endocannabinoid system in modulating fear, anxiety, and stress
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The endocannabinoid system is widely expressed in the limbic system, prefrontal cortical areas, and brain structures regulating neuroendocrine stress responses, which explains the key role of this system in the control of emotions. In this review, we update recent advances on the function of the endocannabinoid system in determining the value of fear-evoking stimuli and promoting appropriate behavioral responses for stress resilience. We also review the alterations in the activity of the endocannabinoid system during fear, stress, and anxiety, and the pathophysiological role of each component of this system in the control of these protective emotional responses that also trigger pathological emotional disorders. In spite of all the evidence, we have not yet taken advantage of the therapeutic implications of this important role of the endocannabinoid system, and possible future strategies to improve the treatment of these emotional disorders are discussed.
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El sistema endocannabinoide tiene una amplia expresión en el sistema límbico, las áreas corticales prefrontales y las estructuras cerebrales que regulan las respuestas al estrés neuroendocrino, lo que explica el papel clave de este sistema en el control de las emociones. En esta revisión, se actualizan los avances recientes sobre la función del sistema endocannabinoide para determinar el valor de los estímulos que provocan miedo y promueven respuestas conductuales apropiadas para la resiliencia frente al estrés. También se revisan las alteraciones en la actividad del sistema endocannabinoide durante el miedo, el estrés y la ansiedad, y el papel fisiopatológico de cada componente de este sistema en el control de estas respuestas emocionales protectoras que también desencadenan trastornos emocionales patológicos. A pesar de todas las evidencias, todavía no se han aprovechado las traducciones terapéuticas de este importante papel del sistema endocannabinoide. También se discuten las posibles estrategias futuras para mejorar el tratamiento de estos trastornos emocionales.

Abondamment retrouvé dans le système limbique, le cortex préfrontal et les structures cérébrales régulant les réponses neuroendocriniennes au stress, le système endocannabinoïde joue un rôle clé dans le contrôle des émotions. Sa fonction dans la détermination de l'intensité des stimuli déclenchant la peur et dans l'amélioration des réponses comportementales adaptées à la résistance au stress est étudiée ici à l'aune des données récentes actualisées. Nous reconsidérons également les modifications de l'activité du système endocannabinoïde face à la peur, au stress et à l'anxiété, ainsi que le rôle physiopathologique de chaque composante de ce système dans le contrôle de ces réponses émotionnelles protectrices, elles-mêmes génératrices de troubles émotionnels pathologiques. Malgré toutes les données disponibles, le rôle crucial du système endocannabinoïde sur le plan thérapeutique n'a pas encore été exploité. Nous analysons les futures stratégies possibles pour améliorer le traitement de ces troubles émotionnels.

Effects of Omega 3 Fatty Acids on Main Dimensions of Psychopathology.

The usefulness of polyunsaturated fatty acids on inflammatory, cardiovascular, and the nervous system was studied in the last decades, but the mechanisms underlying their benefic properties are still partially unknown. These agents seem to express their action on the membrane phospholipid composition and permeability and modulation of second messenger cascades. In psychiatry, the efficacy and tolerability of omega-3 fatty acids were investigated in several psychiatric disorders, including major depression, bipolar disorder, personality disorders, high-risk conditions to develop psychosis, attention-deficit hyperactivity disorder, and autism spectrum disorders. Initial findings in this field are promising, and some relevant questions need to be addressed. In particular, the effects of these agents on the main symptom dimensions have to be investigated in a trans-diagnostic perspective. The present systematic review is aimed to examine the available data on the efficacy of omega-3 fatty acids on domains of psychotic symptoms, affective symptoms, impulsivity, and aggressiveness, and harmful behaviors, and suicide risk.

CORM-3 improves emotional changes induced by hemorrhagic shock via the inhibition of pyroptosis in the amygdala.

Hemorrhagic shock and resuscitation (HSR) may lead to long-term neurological dysfunction, such as depression and anxiety. Carbon monoxide (CO) has emerged as an excellent neuroprotective agent against caspase-1-associated pyroptosis, following HSR. We evaluated the effects and determined the mechanism through which CO protects against emotional changes in a model of HSR, in rats. We subjected rats to treatments with an exogenous, CO-releasing compound (CORM-3, 4 mg/kg), in vivo, after HSR. We measured sucrose preference and performed tail suspension and open field tests 7 days after HSR, assessed brain magnetic resonance imaging 12 h after HSR and evaluated pyroptosis, and neuronal and astrocyte death in the amygdala 12 h post-HSR. We also measured changes in behavior and pathology, following an injection of recombinant murine interleukin (IL)-18 into the amygdala. HSR-treated rats displayed increased depression-like and anxiety-like behaviors, increased amygdalar injury, as indicated by T2-weighted magnetic resonance imaging (MRI) and cerebral blood flow with arterial spin labeling (CBFASL), associated with both neuronal and astrocytic death and pyroptosis, and upregulated IL-18 expression was observed in astrocytes. CORM-3 administration after resuscitation, via a femoral vein injection, provided neuroprotection against HSR, and this neuroprotective effect could be partially reversed by the injection of recombinant murine IL-18 into the amygdala. Therefore, CORM-3 alleviated HSR-induced neuronal pyroptosis and emotional changes, through the downregulation of IL-18 in astrocytes.

Neurotropism of SARS-CoV-2: COVID-19 presenting with an acute manic episode.

A 41-year-old man with no significant medical history presented with acute behavioural disruption on the background of a 1-day history of severe headache and a 10-day history of dry cough and fever. He was sexually disinhibited with pressured speech and grandiose ideas. His behaviour worsened, necessitating heavy sedation and transfer to intensive care for mechanical ventilation despite no respiratory indication. Investigations confirmed that he was positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Neuroimaging and a lumbar puncture were normal. Initial screening for SARS-CoV-2 in the cerebrospinal fluid was negative although no validated assay was available. The patient's mental state remained abnormal following stepdown from intensive care. Psychiatric assessment found features consistent with acute mania, and he was detained under the Mental Health Act. This case indicates the need to consider COVID-19 in a wider series of clinical presentations and to develop a validated assay for SARS-CoV-2 in the cerebrospinal fluid.

Irritability in Huntington's Disease.

Huntington's disease (HD) is a heritable and fatal neurodegenerative disease characterized by a triad of motor, cognitive and neuropsychiatric symptoms. A common and particularly detrimental neuropsychiatric alteration in HD gene carriers is irritability, which frequently manifests as abrupt and unpredictable outbursts of anger. This symptom increases the burden of HD in multiple ways, such as jeopardizing employment and straining familial or caregiver support. Although irritability in HD is diagnosed by the administration of standardized rating scales and clinical expertise, measurement of severity and progression is complicated by several factors. Currently, individuals with HD who present with irritability may be managed with a variety of psychotropic medications, primarily antidepressants and antipsychotics. While these therapies offer relief to individuals suffering from irritability in HD, they are often not sufficient. Here, we review irritability in the context of HD and emphasize the need for treatments that are better tailored to mitigate this troublesome symptom. An expeditious strategy in pursuit of this goal involves evaluating the efficacy of approved medications that are used to treat similar neuropsychiatric symptoms.

Paroxetine ameliorates prodromal emotional dysfunction and late-onset memory deficit in Alzheimer's disease mice.

BACKGROUND: Neuropsychiatric symptoms (NPS) such as depression, anxiety, apathy, and irritability occur in prodromal phases of clinical Alzheimer's disease (AD), which might be an increased risk for later developing AD. Here we treated young APP/PS1 AD model mice prophylactically with serotonin-selective re-uptake inhibitor (SSRI) paroxetine and investigated the protective role of anti-depressant agent in emotional abnormalities and cognitive defects during disease progress. METHODS: To investigate the protective role of paroxetine in emotional abnormalities and cognitive defects during disease progress, we performed emotional behaviors of 3 months old APP/PS1 mouse following oral administration of paroxetine prophylactically starting at 1 month of age. Next, we tested the cognitive, biochemical and pathological, effects of long term administration of paroxetine at 6 months old. RESULTS: Our results showed that AD mice displayed emotional dysfunction in the early stage. Prophylactic administration of paroxetine ameliorated the initial emotional abnormalities and preserved the eventual memory function in AD mice. CONCLUSION: Our data indicate that prophylactic administration of paroxetine ameliorates the emotional dysfunction and memory deficit in AD mice. These neuroprotective effects are attributable to functional restoration of glutamate receptor (GluN2A) in AD mice.

Are pharmacological interventions clinically useful to treat emotionalism after stroke? A Cochrane Review update summary with commentary.

BACKGROUND: Emotionalism, i.e. uncontrolled episodes of crying (or less commonly laughing) post stroke that are not triggered by situations that would have previously provoked such behavior occur in stroke survivors, may persist in some, and can be socially embarrassing. OBJECTIVE: To evaluate whether pharmacological interventions are beneficial, acceptable, and safe in the treatment of emotionalism post stroke. METHODS: A Cochrane review by Allida et al. was summarized with comments. RESULTS: From a total of 7 eligible trials with a total of 239 participants included in the review, five with 213 participants could be used for data extraction. Very low to moderate quality evidence pointed to some beneficial effects of antidepressants in the treatment of emotionalism after stroke. CONCLUSIONS: The available data suggest that antidepressants may reduce the frequency and severity of crying or laughing episodes in stroke survivors with emotionalism.

Opioid system modulation of cognitive affective bias: implications for the treatment of mood disorders.

A significant number of patients (30%) do not adequately respond to commonly prescribed antidepressants (e.g. SSRIs, SNRIs, and TCAs). Opioid receptors and their endogenous peptides have demonstrated a clear role in the regulation of mood in animal models and may offer an alternative approach to augment existing therapies. Nevertheless, there is an urgent need to find better ways to predict a patient's response to drug treatment, to improve overall drug responding, and to reduce the time to symptom remission using novel diagnostic and efficacy biomarkers. Cognitive processes, such as perception, attention, memory, and learning, are impaired in patients with mood disorders. These processes can be altered by emotions, a phenomenon called cognitive affective bias. Negative affective biases are a key feature of major depressive disorder (MDD) and may present concurrently with other cognitive deficits. Importantly, a significant percentage of patients report residual cognitive impairments even after effective drug treatment. This approach offers a new opportunity to predict patient treatment responses, potentially improving residual cognitive symptoms and patient outcomes. This review will (1) describe the underlying neurocircuitry of affective cognition and propose how negative biases may occur, (2) outline the role of opioid receptors in affective cognition, executive function, and MDD, and (3) present evidence from the published literature supporting a modulatory role for opioid drugs on negative affective bias, with a focus on kappa-opioid receptor antagonists, currently in development for clinical use for treatment-resistant MDD.