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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., Competing Interests: Declaration of Competing Interest Dr. Roger McIntyre has received research grant support from CIHR/GACD/Chinese National Natural Research Foundation; speaker/consultation fees from Lundbeck, Janssen, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Abbvie. Dr. Roger McIntyre is a CEO of Braxia Scientific Corp. Funding for the study was provided by Bausch Health. Dr. Joshua D Rosenblat has received research grant support from the Canadian Institute of Health Research (CIHR), Labatt Family Innovation Fund, Canadian Cancer Society, Canadian Psychiatric Association, Academic Scholars Award, American Psychiatric Association, American Society of Psychopharmacology, University of Toronto, University Health Network Centre for Mental Health, Joseph M. West Family Memorial Fund and Timeposters Fellowship and industry funding for speaker/consultation/research fees from Janssen, Allergan, Lundbeck, Sunovion and COMPASS. He is the Chief Medical and Scientific Officer of Braxia Scientific and the medical director of Braxia Health (Canadian Rapid Treatment Centre of Excellence). Dr. Rodrigo B. Mansur has received research funding from the Canadian Institutes of Health Research, Physician Services Incorporated foundation, the Baszucki Brain Research Fund, and an Academic Scholar Award from the University of Toronto, Department of Psychiatry. All other authors have no conflicts of interest to disclose., (Copyright © 2023. Published by Elsevier B.V.)

Objective: To evaluate the safety, tolerability, and effectiveness of repeated doses of intravenous (IV) ketamine in older adults (i.e., ≥60 years of age) with treatment-resistant depression., Method: In this case series, fifty-three older adults (M age  = 67, SD = 6; 57% female [n = 30]) received 4 IV ketamine infusions, administered over 1-2 weeks. Effectiveness of IV ketamine was measured using the Quick Inventory for Depressive Symptomatology-Self Report 16 (QIDS-SR16) approximately 2 days after infusions 1-3, and 1-2 weeks after infusion 4. Safety was measured as hemodynamic changes before, during, immediately after, and 20 minutes after each infusion. Tolerability was assessed via systematic reporting of treatment-emergent adverse events during and after each infusion, in addition to symptoms of dissociation measured using the Clinician Administered Dissociative States Scale. Partial response (25%-50% symptomatic improvement from baseline), response (≥50% symptomatic improvement from baseline), clinically significant improvements (≥25% symptomatic improvement from baseline), and remission rates (QIDS-SR16 ≤5) were also calculated., Results: Participants reported significant decreases in depressive symptoms (i.e., as measured by the QIDS-SR16) with repeated ketamine infusions (F(4, 92) = 7.412, p <0.001). The mean QIDS-SR16 score was 17.12 (SD = 5.33) at baseline and decreased to 12.52 (SD = 5.79) following 4 infusions. After 4 infusions, 31% (n = 8) of participants partially responded to IV ketamine, 27% (n = 7) responded, 58% (n = 15) experienced clinically significant improvements, and 10% (n = 3) met remission criteria. Thirty-six participants (69%) experienced treatment-emergent hypertension during at least 1 infusion, and 10 (19%) required intervention with an antihypertensive. Drowsiness was the most commonly reported adverse event (50% of infusions; n = 73)., Conclusion: Ketamine was associated with transient treatment-emergent hypertension. Response and remission rates were comparable to those reported in general adult samples. Findings are limited by the open-label, chart review nature of this study., (Copyright © 2021 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Cognitive deficits are a core feature across psychiatric disorders. Emerging evidence indicates that metabolic pathways are highly relevant for the substrates and phenomenology of the cognitive domain. Herein, we aimed to determine the effects of liraglutide, a GLP-1R agonist, on brain structural/volumetric parameters in adults with a mood disorder. This is the secondary analysis of a 4-week, pilot, proof-of-concept, open-label study. Participants (N=19) exhibiting impairments in executive function with either major depressive disorder (MDD) or bipolar disorder (BD) were recruited. Liraglutide 1.8mg/day was added as an adjunct to existing pharmacotherapy. Structural magnetic resonance imaging (MRI) scanning was obtained at baseline and endpoint. Results showed that at endpoint there was significant weight loss (mean: 3.15%; p<0.001). Changes in frontal and striatal volumes were significantly correlated with changes in body mass index (BMI), indicating the weight loss was associated with volume increase in most regions (e.g. r=-0.561, p=0.042 in the left superior frontal area). After adjusting for intracranial volume, age, gender, and BMI, we observed significant changes from baseline to endpoint in multiple regions (e.g. RR: 1.011, p=0.049 in the left rostral middle frontal area). Changes in regional volumes were associated with improvement in executive function (e.g. r=0.698, p=0.003 for the right superior frontal area). Adjunctive liraglutide results in clinically significant weight loss, with corresponding improvement in cognitive function; changes in cognitive function were partially moderated by changes in brain morphometry, underscoring the interrelationship between weight and brain structure/function., (Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.)

The high and increasing prevalence of medical marijuana consumption in the general population invites the need for quality evidence regarding its safety and efficacy. Herein, we synthesize extant literature pertaining to the phytocannabinoid cannabidiol (CBD) and its brain effects. The principle phytocannabinoid Δ 9 -tetrahydrocannabinol (Δ 9 -THC) and CBD are the major pharmacologically active cannabinoids. The effect of CBD on brain systems as well as on phenomenological measures (e.g. cognitive function) are distinct and in many cases opposite to that of Δ 9 -THC. Cannabidiol is without euphoriant properties, and exerts antipsychotic, anxiolytic, anti-seizure, as well as anti-inflammatory properties. It is essential to parcellate phytocannabinoids into their constituent moieties as the most abundant cannabinoid have differential effects on physiologic systems in psychopathology measures. Disparate findings and reports related to effects of cannabis consumption reflect differential relative concentration of Δ 9 -THC and CBD. Existing literature, notwithstanding its deficiencies, provides empirical support for the hypothesis that CBD may exert beneficial effects on brain effector systems/substrates subserving domain-based phenomenology. Interventional studies with purified CBD are warranted with a call to target-engagement proof-of-principle studies using the research domain criteria (RDoC) framework., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

A post hoc analysis was conducted using data from participants (N=631) with a DSM-IV-TR defined diagnosis of major depressive disorder (MDD) or bipolar disorder (BD) who were enrolled in the International Mood Disorders Collaborative Project (IMDCP) between January 2008 and July 2013. It was determined that 20.6% of adults with mood disorders as part of the IMDCP fulfilled criteria for binge eating behaviour (BE). A higher percentage of individuals with BD met criteria for BE when compared to MDD (25.4% vs. 16%; p=0.004) Univariate analyses indicated that individuals with a mood disorder (i.e., MDD or BD) and BE had greater scores on measures of anxiety severity (p=0.013) and higher rates of lifetime and current substance dependence, lifetime alcohol abuse (p=0.007, p=0.006, and p=0.015, respectively), Attention Deficit Hyperactivity Disorder (ADHD) (p=0.018) and measures of neuroticism (p=0.019). Individuals with a mood disorder and concurrent BE had lower scores on measures of conscientiousness (p=0.019). Individuals meeting criteria for BE were also significantly more likely to be obese (i.e., BMI≥30kg/m 2 ) (50% vs. 25.5%; p<0.001). Binge eating is common amongst adults utilising tertiary care services principally for a mood disorder. The presence of BE identifies a subset of adults with mood disorders who have greater illness complexity as evidenced by course of illness variables and comorbidity. Screening for BE amongst individuals with mood disorders is warranted; parsing neurobiological substrates subserving non-homeostatic eating behaviour amongst individuals with mood disorders is a future research vista., (Copyright © 2015 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Background: While women with breast cancer often face varying levels of psychological distress, there is a subgroup whose symptomatology reaches a threshold for diagnosis of major depressive disorder (MDD). Major depressive disorder is known to influence patient outcomes, such as health-related quality of life and treatment adherence. There are no systematic reviews that evaluate pharmacological and psychotherapeutic treatment trials for MDD among individuals with breast cancer., Methods: Two authors independently searched MEDLINE, EMBASE, Cochrane and Clinical Trials.gov databases through February 20, 2013 without language restrictions. Core journals, reference lists and citation tracking were also searched. Articles on breast cancer patients were included if they (1) included participants with a diagnosis of MDD; (2) investigated pharmacological or psychotherapeutic treatments for MDD compared to placebo or usual care in a randomized controlled trial (RCT)., Results: Two RCTs on antidepressant treatment met inclusion criteria. However, no RCTs investigating the effects of psychological treatments for MDD in breast cancer were identified. Notwithstanding the paucity of data investigating the effects of psychological treatments for MDD in breast cancer, numerous psychotherapeutic strategies targeting depressive symptoms were identified. Mianserin had significant antidepressant effects when compared to placebo in a 6-week, parallel-group, RCT of Stage I-II breast cancer in women with MDD. Desipramine and paroxetine were reported to be no more efficacious than placebo in a 6-week, RCT of Stage I-IV breast cancer in women with MDD., Conclusions: The evidence reviewed herein underscores the paucity of data available to guide clinicians in treatment decisions for MDD in individuals with breast cancer. Therefore, the treatment of MDD in breast cancer is primarily based on clinical experience. Some antidepressants (for example, paroxetine) should be avoided in women concurrently taking tamoxifen due to relevant interactions involving the cytochrome CYP2D6., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

DNA topoisomerase-1 (TOP-1) resolves the topological problems associated with DNA replication, transcription and recombination by introducing temporary single-strand breaks in the DNA. Caenorhabditis elegans TOP-1 has two isoforms, TOP-1α and TOP-1β. TOP-1β is broadly localized to the nuclei of many cells at all developmental stages and concentrated in nucleoli in embryo gut and oogenic cells. However, TOP-1α is specifically localized to centrosomes, neuronal cells, excretory cells and chromosomes of germ cells in embryonic and larval stages. Reporter gene analysis also shows that top-1 transcription is highly activated in several sensory neurons, speculating the possible role of TOP-1α in neuronal development. From RNA interference (RNAi) experiments, we demonstrated that C. elegans TOP-1 is required for chromosomal segregation, germline proliferation and gonadal migration, which are all correlated with the expression and activity of TOP-1. Therefore, our findings may provide an insight into a new role of TOP-1 in development of multicellular organisms., (Published by Elsevier B.V.)