Evaluating the neural substrates of effort-expenditure for reward in adults with major depressive disorder and obesity.

Converging evidence has suggested that disturbances in monetary reward processing may subserve the shared biosignature between major depressive disorder (MDD) and obesity. However, there remains a paucity of studies that have evaluated the deficits in specific subcomponents of reward functioning in populations with MDD and obesity comorbidity. We evaluated the association between effort-expenditure for monetary reward and neural activation in regions associated with reward-based decision making (i.e., the caudate nucleus, anterior cingulate cortex (ACC) and hippocampus) in people with MDD and obesity comorbidity. We acquired structural and functional magnetic resonance imaging (fMRI) in 12 participants and performed a spherical region-of-interest analysis (ROI) using previously defined peak MNI coordinates. A one-sample t-test was employed to compare ROI-specific blood-oxygen-level-dependent (BOLD) signal change during the task choice selection window (i.e., high-effort vs. low-effort task) of the effort-expenditure for reward task (EEfRT). We observed no change in activation of the caudate nucleus, ACC or hippocampus in participants with increased BMI when contrasting the high effort > low effort reward magnitude condition for the EEfRT. The findings from our exploratory study evaluated the disturbances in fundamental reward processes, including cost-benefit decision making, in people MDD and obesity. Future studies should further investigate this relationship with a larger sample size.

The Effects of Psilocybin in Adults with Major Depressive Disorder and the General Population: Findings from Neuroimaging Studies.

The use of psilocybin as treatment for major depressive disorder (MDD) has been examined as a promising alternative to traditional first-line options. We reviewed existing literature to provide a synthesis of the extant neuroimaging observations with psilocybin, and to identify putative therapeutic targets for target engagement studies with psilocybin, and potentially other psychedelics. We assessed neuroimaging observations with psilocybin among participants with MDD and healthy populations. A systematic search was conducted on PubMed, Google Scholar and PsycINFO from database inception to November 17th, 2021. The study quality (i.e., risk of bias) was assessed using the revised Cochrane risk-of-bias tool for randomized trials. A total of ten studies evaluated psilocybin in healthy populations and three studies assessed psilocybin in MDD participants using neuroimaging techniques. Following psilocybin administration, a decrease in amygdala activity and a reduction in depressive symptoms was observed in two studies. Changes in functional connectivity and activation of prefrontal limbic structures, specifically the ventral medial prefrontal cortex and amygdala, was seen in healthy populations. There was high heterogeneity in methodology (e.g., dosing schedule and imaging methods) amongst included studies. Longitudinal studies are needed to further elucidate psilocybin treatment for MDD, its long-term effects and the possibility of sustained therapeutic effects.

The effects of antidepressant medications on antiretroviral treatment adherence in HIV-positive individuals with depression.

Background Extant literature has identified Major Depressive Disorder (MDD) as a comorbid disorder in individuals with seropositive human immunodeficiency disorder (HIV), and this may affect HIV-treatment efficacy. However, there is a paucity of literature evaluating the effects of antidepressant use on antiretroviral therapies (ART) in HIV-positive individuals. Herein, the following review assesses the effects of antidepressant medications on ART adherence in HIV-positive individuals with diagnosed MDD. Methods A systematic search on PubMed, Scopus, Web of Science, and Google Scholar search engines were conducted between database inception to June 12th, 2020 using the search and MeSH terms: (HIV) AND (antiretroviral or treatment) AND (depress*) AND (antidepressants) AND (adherence). Results We identified nine articles that evaluated ART adherence in HIV-positive individuals using antidepressants. Of the nine included articles, eight articles evaluated participants undergoing ART, and one article evaluated participants undergoing highly active antiretroviral therapy (HAART). Our primary findings suggest that patients who took antidepressant treatment for depression demonstrated greater adherence to HIV treatments and a reduction in missed HIV medication dosage. Limitations The heterogeneity of study design between the included studies was high. Conclusion The current review suggests that response to antidepressant medication may improve adherence to HIV treatments in HIV-positive individuals with comorbid depression. Further studies should expand the findings to explore the effects of disparate psychotropic agents on adherence behaviors among patients with HIV to identify the benefits of these agents on long-term health outcomes in this vulnerable clinical population.

Social Isolation, Loneliness and Generalized Anxiety: Implications and Associations during the COVID-19 Quarantine.

The COVID-19 pandemic has resulted in a predominantly global quarantine response that has been associated with social isolation, loneliness, and anxiety. The foregoing experiences have been amply documented to have profound impacts on health, morbidity, and mortality. This narrative review uses the extant neurobiological and theoretical literature to explore the association between social isolation, loneliness, and anxiety in the context of quarantine during the COVID-19 pandemic. Emerging evidence suggests that distinct health issues (e.g., a sedentary lifestyle, a diminished overall sense of well-being) are associated with social isolation and loneliness. The health implications of social isolation and loneliness during quarantine have a heterogenous and comorbid nature and, as a result, form a link to anxiety. The limbic system plays a role in fear and anxiety response; the bed nucleus of the stria terminalis, amygdala, HPA axis, hippocampus, prefrontal cortex, insula, and locus coeruleus have an impact in a prolonged anxious state. In the conclusion, possible solutions are considered and remarks are made on future areas of exploration.

The impact of overweight/obesity on monetary reward processing: A systematic review.

OBJECTIVE: Converging evidence suggests abnormalities in monetary reward processing may underlie the shared pathophysiology between major depressive disorder and obesity. As such, there is a need to parse deficits in specific subcomponents of monetary reward functioning (i.e., valuation, learning and anticipation). METHODS: PsycINFO, Google Scholar and PubMed databases were searched for English-language articles published between database inception to June 6th, 2020. Studies were identified using the following medical search heading (MeSH) terms and search strings: (reward (valuation OR motivation OR anticipation OR learning OR functioning OR decision-making OR reinforcement)) AND ((obesity OR overweight OR obese). RESULTS: Findings were reviewed from 11 studies evaluating the association between obesity and monetary reward processing. Four studies found significant differences in reward learning in individuals with obesity compared to normal-weight participants. Five studies found body mass index (BMI) to be predictive of willingness to expend effort (i.e., valuation) for a monetary reward. Three studies found changes in neural activations in the ventral striatum during anticipatory phases preceding receipt of a monetary reward in participants with obesity. CONCLUSIONS: Participants with obesity demonstrated significantly poorer performance in task-based measures of reward learning, valuation, and anticipation, resulting in lower monetary reward outcomes across all studies compared to healthy controls. Notably, participants with obesity and comorbid depression performed worse than participants with no comorbid depression. LIMITATIONS: There persists heterogeneity between studies with regards to inclusion of mood disorder populations and exclusion of psychiatric comorbidities in groups with obesity.

The Prevalence of Suicidal Behaviour in Fibromyalgia Patients.

OBJECTIVE: Fibromyalgia (FM) is a condition associated with chronic pain in muscles and soft tissues. Extant literature has demonstrated an association between FM, mood symptoms and suicidal behaviour. This systematic review aims to synthesize available literature assessing the prevalence of suicidality in FM populations and qualitatively review the included articles. METHODS: PsycINFO, Google Scholar and PubMed databases were systematically searched for studies published from database inception to 15 February 2020. Studies were included that assessed FM as a primary or co-primary disease condition, as well as an assessment of suicidal behaviour (suicidal ideations (SI), suicide attempts (SA) and death by suicide (SC)). The quality of the studies was assessed using the Newcastle-Ottawa Scale. RESULTS: 699 unique articles were reviewed for eligibility. Data were derived from nine studies (cross-sectional: k = 5; retrospective cohort: k = 4) that assessed suicidal behaviour in FM participants (SI: k = 5, SC: k = 3, SA: k = 3). Four studies assessing SI found elevated rates of SI among FM participants. Three studies found elevated risk for SC and three studies found increased SA in FM participants relative to the general population. In two studies, this association was no longer significant after adjusting for depression and other psychiatric comorbidities. CONCLUSION: Preliminary findings suggest that FM is associated with significantly higher risks for SI, SA and SC compared to the general population. There may be unique risk factors underlying suicidal behaviour in FM patients and the interaction between FM and other known risk factors (i.e., mental illness) require further investigation.

The Effects of Ketamine on Cognition in Treatment-Resistant Depression: A Systematic Review and Priority Avenues for Future Research.

Replicated evidence has documented cognitive deficits in populations with treatment-resistant depression (TRD). Approximately 40 % of patients with MDD present with impairment of one or more cognitive domains. As such, there is an unmet need to discover treatments that have pro-cognitive effects in TRD patients. Ketamine has demonstrated efficacy as a rapid-onset intervention for the treatment of depression. The objective of the current review was to assess the effects of ketamine on cognition in TRD patients. We systematically searched PubMed, Google Scholar and PsycINFO between database inception to March 24th, 2020. We identified five studies that evaluated cognition in TRD populations following ketamine treatment. All studies included a 0.5 mg/kg subanesthetic intravenous (IV) administration of ketamine. One study found significant improvements in complex (p = .008) and simple (p = .027) working memory and one study found improvements in visual learning memory following IV ketamine infusions (p = .014). Improvements in speed of processing and verbal learning memory were observed in anxious TRD participants only. Importantly, a subanesthetic dose of IV ketamine does not worsen cognitive function.

Antidepressant Medications and Weight Change: A Narrative Review.

Antidepressant medications are the first-line treatment option for moderate to severe major depressive disorder. However, most antidepressants have numerous documented adverse events, including cardiometabolic effects and weight gain, which are major public health concerns. Antidepressant agents provide varying risk of associated weight gain, including significant within-class differences. Some agents, such as mirtazapine, show significant levels of weight gain, while others, such as bupropion, demonstrate weight-loss effects. Current findings suggest the role of histamine and serotonin off-target appetite-promoting pathways in adverse weight-gain effects. Therefore, controlling for undesired weight effects is an important consideration for the selection of antidepressants.

The emerging role of psilocybin and MDMA in the treatment of mental illness.

INTRODUCTION: Mental illness has a chronic course of illness with a number of clinical manifestations. Affected individuals experience significant functional, emotional, cognitive, and/or behavioral impairments. The growing prevalence of mental illness has been associated with significant social and economic costs. Indeed, the economic burden of mental illness is estimated to exceed $1.8 trillion USD over the next 30 years. A significant number of individuals affected by mental illness fail to respond to first-line treatment options. Therefore, there remains an unmet need for rapidly attenuating therapeutic options for mental health disorders with minimal social and economic burden. AREAS COVERED: The paucity of novel treatment options warrants a renewed investigation of psychedelic-based psychotherapy. Herein, the authors will evaluate the therapeutic potential of traditional psychedelics, psilocybin, and MDMA, in the treatment of mental illness with a narrative review of available literature. EXPERT OPINION: Psychedelics, such as psilocybin and MDMA, offer an alternative avenue of therapy for many mental health disorders. Available evidence indicates that psychedelics may offer a single-dose, rapid effect model that have robust effects with treatment-resistant mental disorders and a unique advantage as a possible monotherapy for mental illness. Novel clinical trials that evaluate the safety, tolerability, and efficacy in clinically representative populations are warranted.

The Association Between Adverse Childhood Experiences and Inflammation in Patients with Major Depressive Disorder: A Systematic Review.

BACKGROUND: Replicated evidence has documented elevated levels of pro-inflammatory cytokines in populations with major depressive disorder (MDD). However, childhood trauma, a risk factor for MDD, has been separately shown to also impact inflammatory systems; its potential moderating effect on inflammation in MDD has been less frequently investigated. METHODS: We systematically searched the PubMed, Google Scholar, Scopus, Web of Science, and PsycINFO databases between database inception to June 19th, 2019 using the search string: (Childhood trauma or Adverse childhood experiences or childhood abuse or childhood rape or physical abuse or emotional abuse) AND (Inflammation or inflammatory cytokines or interleukin-6 or tumor necrosis factor-alpha or c-reactive protein) AND (Major Depressive Disorder or Depression). RESULTS: We identified nine articles that evaluated inflammatory biomarkers in MDD populations with adverse childhood experiences (ACE). Eight articles evaluated IL-6, three articles evaluated CRP, and five articles evaluated TNF-α. The strongest effects were observed for IL-6; six studies reported significantly elevated levels of IL-6 in MDD and ACE patients compared to healthy controls and/or MDD-only populations. Meanwhile, only three studies found TNF-α to be significantly elevated in the MDD and ACE cohort. In contrast, MDD-ACE populations did not exhibit significantly elevated CRP. LIMITATIONS: The methodological heterogeneity amongst studies was very high. CONCLUSION: The current review suggests that MDD and ACE subpopulations present elevated levels of IL-6 compared to MDD-only and healthy control populations. Therefore, research should consider whether elevated inflammation in MDD is just an epiphenomenon of previous ACE and whether MDD-ACE subgroups are more likely to respond to immune-inflammatory targeted intervention.