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Yuru He,1,2 Xing Wang,1,2 Zuowei Wang,3,4 Ping Zhang,5 Xiaojia Huang,3,4 Meihong Yu,5 Jill K Murphy,6 Erin E Michalak,6 Jing Liu,6 Tao Yang,1,2 Xiaorui Yang,7 Yiru Fang,1,8,9 Raymond W Lam,6 Jun Chen1,2 1Clinical Research Center, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Psychotic Disorders, Shanghai, People’s Republic of China; 3Division of Mood Disorders, Shanghai Hongkou Mental Health Center, Shanghai, People’s Republic of China; 4Clinical Research Center for Mental Health, School of Medicine, Shanghai University, Shanghai, People’s Republic of China; 5Fengxian District Mental Health Center, Shanghai, People’s Republic of China; 6Department of Psychiatry, University of British Columbia, Vancouver, Canada; 7Department of Psychology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 8Department of Psychiatry & Affective Disorders Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 9CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai, People’s Republic of ChinaCorrespondence: Jun Chen, Clinical Research Center, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, People’s Republic of China, Tel +86 21-34773367, Email doctorcj2010@gmail.com Raymond W Lam, Department of Psychiatry, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, V6T 2A1, Canada, Tel +1 604-822-7325, Email r.lam@ubc.caPurpose: To validate the efficacy of enhanced measurement-based care against standard measurement-based care in patients with major depressive disorder.Patients and Methods: In this pilot study of an ongoing multicenter cluster randomized controlled trails, 160 patients diagnosed with major depressive disorder were enrolled from 2 mental health centers, with a plan to include 12 centers in total. One hundred patients engaged in a six-month evaluation using a technology-enhanced measurement-based care tool, including assessments of clinical symptoms, side effects, and functionality at baseline, two months, four months and six months. Simultaneously, the remaining 60 patients underwent standard paper-based measurement-based care, utilizing the same set of scales over the same six-month period, with assessments at the same time points.Results: Patients utilizing the enhanced measurement-based care tool demonstrated a significantly higher reduction rate in PHQ-9 scores compared to those using standard paper-based measurement-based care during the two-month follow-up. Additionally, a notable positive correlation was observed between the frequency of enhanced measurement-based care tool usage and the quality of life during the two-month follow-up.Conclusion: Enhanced measurement-based care has the effect of reducing depressive symptoms. Our study emphasized that using enhanced measurement-based care via smartphones is a feasible tool for patients with major depressive disorder. Our future study, including results from additional research centers, may further validate the effectiveness of enhanced measurement-based care.Keywords: major depressive disorder, measurement-based care, enhanced measurement-based care, smartphone-based intervention

Tao Yang,1,2 Raymond W Lam,2 Jia Huang,1 Yousong Su,1 Jing Liu,2 Xiaorui Yang,1 Lu Yang,1 Na Zhu,3 Guoqing Zhao,4 Ruizhi Mao,1 Rubai Zhou,1 Weiping Xia,5 Hongmei Liu,1 Zuowei Wang,6 Jun Chen,1 Yiru Fang1,7,8 1Clinical Research Center & Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada; 3Shanghai Pudong New Area Mental Health Center, Tongji University School of Medicine, Shanghai, People’s Republic of China; 4Department of Psychology, Provincial Hospital Affiliated to Shandong University, Jinan, People’s Republic of China; 5Department of Medical Psychology, Xinhua Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, People’s Republic of China; 6Division of Mood Disorders, Shanghai Hongkou District Mental Health Center, Shanghai, People’s Republic of China; 7CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai, People’s Republic of China; 8Shanghai Key Laboratory of Psychotic Disorders, Shanghai, People’s Republic of ChinaCorrespondence: Yiru FangClinical Research Center & Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Room B2409, Building 2, 600 South Wan Ping Road, Shanghai 200030, People’s Republic of ChinaTel +86 139 0199 7089Email yirufang@aliyun.comJun ChenClinical Research Center & Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Room B2411, Building 2, 600 South Wan Ping Road, Shanghai 200030, People’s Republic of ChinaTel +86 180 1731 1373Email doctorcj2010@gmail.comBackground: Patients with bipolar disorder (BD) and patients with major depressive disorder (MDD) have relatively specific temperament and structural abnormalities of brain regions related to emotion and cognition. However, the effects of temperament factors on the structure of frontal and temporal cortex is still unclear. The aims of this study were to explore the differences and relationships between temperament characteristics and the gray matter volume of frontal and temporal cortex in patients with BD or MDD.Methods: T1-weighted magnetic resonance imaging (MRI) data, demographic and clinical information were obtained from 279 depressed patients (90 patients with BD, 189 patients with MDD) and 162 healthy controls (HC). Temperament was assessed with the Chinese short version of Temperament Evaluation of Memphis, Pisa and San Diego – Auto questionnaire (TEMPS-A). The Desikan-Killiany atlas was used for yielding gray matter volume by FreeSurfer 6.0 software suite. A total of 22 frontal and temporal regions were chosen as regions of interest (ROIs).Results: Compared with patients with MDD, patients with BD had higher TEMPS-A total scores and scores on cyclothymic, irritable and hyperthymic subscales. The gray matter volume in bilateral rostral middle frontal gyrus (RMFG), left temporal pole and right superior frontal gyrus were reduced in patients with BD. Patients with MDD only had lower gray matter volume in bilateral temporal pole. In the pooled patients, there were negative associations between hyperthymia and gray matter volume in right RMFG.Conclusion: Patients with BD and MDD had different temperament characteristics. The prominent temperament subscales in patients with BD were cyclothymia, irritable and hyperthymia. Patients with greater hyperthymia had lower gray matter volume in right frontal gyrus. Temperament may reflect an endophenotype in patients with mood disorders, especially in BD.Keywords: bipolar disorder, major depressive disorder, temperament, gray matter volume

Ran Ha Hong,1 Jill K Murphy,1 Erin E Michalak,1 Trisha Chakrabarty,1 Zuowei Wang,2 Sagar V Parikh,3 Larry Culpepper,4 Lakshmi N Yatham,1 Raymond W Lam,1,* Jun Chen5,* 1Department of Psychiatry, University of British Columbia, Vancouver, Canada; 2Hongkou Mental Health Center, Shanghai, People’s Republic of China; 3Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA; 4Department of Family Medicine, Boston University, Boston, MA, USA; 5Shanghai Mental Health Center, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Raymond W LamDepartment of Psychiatry, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC V6T 2A1, CanadaTel +1 604-822-7325Email r.lam@ubc.caAbstract: Measurement-based care (MBC) can be defined as the clinical practice in which care providers collect patient data through validated outcome scales and use the results to guide their decision-making processes. Despite growing evidence supporting the effectiveness of MBC for depression and other mental health conditions, many physicians and mental health clinicians have yet to adopt MBC practice. In part, this is due to individual and organizational barriers to implementing MBC in busy clinical settings. In this paper, we briefly review the evidence for the efficacy of MBC focusing on pharmacological management of depression and provide example clinical scenarios to illustrate its potential clinical utility in psychiatric settings. We discuss the barriers and challenges for MBC adoption and then address these by suggesting simple solutions to implement MBC for depression care, including recommended outcome scales, monitoring tools, and technology solutions such as cloud-based MBC services and mobile health apps for mood tracking. The availability of MBC tools, ranging from paper-pencil questionnaires to mobile health technology, can allow psychiatrists and clinicians in all types of practice settings to easily incorporate MBC into their practices and improve outcomes for their patients with depression.Keywords: measurement-based care, major depressive disorder, depression, scales, outcomes, patient-reported outcome measures, implementation, measurement

Chris Dowrick,1,2 Ryuki Kassai,2,3 Cindy LK Lam,2,4 Raymond W Lam,5,6 Garth Manning,2 Jill Murphy,5,6 Chee H Ng,7,8 Chandramani Thuraisingham2,9 1Department of Primary Care and Public Health, University of Liverpool, Liverpool, UK; 2World Organization of Family Doctors (WONCA), Bangkok, Thailand; 3Department of Community and Family Medicine, Fukushima Medical University, Fukushima, Japan; 4Department of Family Medicine & Primary Care, The University of Hong Kong, Hong Kong; 5Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada; 6Asia-Pacific Economic Cooperation (APEC) Digital Hub for Mental Health, Vancouver, BC, Canada; 7Department of Psychiatry, University of Melbourne, Melbourne, Australia; 8Asia-Pacific Economic Cooperation(APEC) Digital Hub for Mental Health, Melbourne, Australia; 9Department of Family Medicine, International Medical University, Kuala Lumpur, MalaysiaCorrespondence: Cindy LK Lam; Chee H Ng Email clklam@hku.hk; cng@unimelb.edu.auAbstract: Mental ill health affects individual well-being and national economic prosperity and makes up a substantial portion of the burden of disease globally, especially in the Asia-Pacific region. Integrating mental health into primary care is widely considered a key strategy to improve access to mental health care. Integration, however, is a complex process that needs to be addressed at multiple levels. A collaboration between the Asia-Pacific Economic Cooperation (APEC) Digital Hub for Mental Health and the World Organization of Family Doctors (WONCA) is described in this paper, which outlines a framework and next steps to improve the mental health of communities in APEC economies. This paper notes gaps related to the integration of mental health into primary care across the region and identifies enablers and current best practices from several APEC economies. The potential of digital technology to benefit primary mental health care for populations in the APEC region, including delivery of training programs for healthcare staff and access to resources for patients, is described. Finally, key next steps are proposed to promote enhanced integration into primary care and improve mental health care throughout the APEC region.Keywords: mental health, primary care, Asia Pacific, digital

Raymond W Lam,1 François-Xavier Lamy,2 Natalya Danchenko,2 Aaron Yarlas,3 Michelle K White,3 Benoît Rive,2 Delphine Saragoussi2 1Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada; 2Global Outcomes Research, Lundbeck SAS, Issy-les-Moulineaux, France; 3Optum Patient Insights, Optum, Inc., Lincoln, RI, USA Background: Although depression and cognitive dysfunction are connected, limited tools exist to capture the patient’s perspective on cognitive dysfunction and its impact on major depressive disorder (MDD). We report results of a psychometric validation of the Perceived Deficits Questionnaire-Depression (PDQ-D), a self-report measure of cognitive dysfunction for use in MDD.Methods: A non-interventional, prospective, panel-recruited, online survey was conducted using the PDQ-D in adults with and without MDD in the US and UK. Respondents were assessed at baseline and after 6 weeks (MDD only) (baseline: US n=418, UK n=437, 49% MDD; follow-up: US n=169, UK n=153, all MDD). The criterion measures included: Medical Outcomes Study Cognitive Functioning Scale-Revised-acute form (MOS COG-R), Patient Health Questionnaire-9 (PHQ-9), Patient Global Impression of Severity scale (PGI-Severity), Sheehan Disability Scale (SDS), Work Productivity and Activity Impairment Questionnaire: Specific-Health Problem (WPAI:SHP), and modified Lam Employment Absence and Productivity Scale (LEAPS). US and UK data were analyzed separately.Results: Internal consistency was high for PDQ-D total scale and four subscales (Cronbach’s alpha 0.81–0.96). Convergent validity was good, with strong concordance with MOS COG-R and moderate/small correlations with PHQ-9, SDS, WPAI:SHP, LEAPS, and PGI-Severity. Significant differences (all P

Global inequity in access to and availability of essential mental health services is well recognized. The mental health treatment gap is approximately 50% in all countries, with up to 90% of people in the lowest-income countries lacking access to required mental health services. Increased investment in global mental health (GMH) has increased innovation in mental health service delivery in LMICs. Situational analyses in areas where mental health services and systems are poorly developed and resourced are essential when planning for research and implementation, however, little guidance is available to inform methodological approaches to conducting these types of studies. This scoping review provides an analysis of methodological approaches to situational analysis in GMH, including an assessment of the extent to which situational analyses include equity in study designs. It is intended as a resource that identifies current gaps and areas for future development in GMH. Formative research, including situational analysis, is an essential first step in conducting robust implementation research, an essential area of study in GMH that will help to promote improved availability of, access to and reach of mental health services for people living with mental illness in low- and middle-income countries (LMICs). While strong leadership in this field exists, there remain significant opportunities for enhanced research representing different LMICs and regions.

Antidepressants were traditionally considered to have delayed onset of action, and clinical opinion often stated that patients may not experience noticeable improvement for 4-6 weeks. Recent studies have shown, however, that antidepressants have more rapid onset of effect, within 1-2 weeks, and that this early response may be associated with later sustained response. Moreover, there is emerging evidence that some medications may have faster onset of therapeutic effect than others. The new antidepressant agomelatine, with its novel pharmacological profile as an agonist at melatonergic (MT(1) and MT(2)) receptors and antagonist at 5-HT(2C) receptors, has in several studies produced earlier symptom improvement than comparator selective serotonin reuptake inhibitors and serotonin-noradrenaline reuptake inhibitors. In particular, beneficial effects on sleep and daytime functioning are noticeable as early as the first week of treatment. These therapeutic benefits may, in part, be related to its regulatory effects on circadian and sleep- wake cycles. Agomelatine therefore combines early symptom relief with a favorable side-effect profile and short-term and long-term antidepressant efficacy. These properties suggest that agomelatine can be considered a first-line treatment for patients with major depression. [ABSTRACT FROM AUTHOR]

Bipolar disorder is a complex, chronic psychiatric condition characterized by recurring episodes of depressive illness and mania or hypomania. Although the manic or hypomanic episodes define the disorder, recent research has shown that depressive symptoms predominate over manic symptoms in the majority of patients, and that bipolar depression accounts for much of the significant morbidity and mortality associated with bipolar disorder. Given these findings, there has been a recent upsurge of interest in furthering our understanding of the burden of depression in bipolar disorder. At the same time, increasing scientific attention is now being paid to expanding the measurement of outcome in bipolar disorder to encompass broader indicators of response, one of which is the assessment of quality of life (QOL). In this review, we provide a summary of the current knowledge about QOL in the depressive phase of bipolar disorder, and the effects of pharmacological treatment interventions for bipolar disorder upon QOL. It appears that QOL is poorer in bipolar disorder than in other mood disorders and anxiety disorders, but that schizophrenia might compromise QOL more severely than bipolar disorder. Existing data also suggest that, for patients with bipolar disorder, QOL is negatively associated with depression, both as a cross-sectional mood state and perhaps also as a feature of the patient's course. Despite its clinical and public health importance, bipolar depression has only recently started to receive the attention it warrants in clinical trials, and many important questions about its optimal pharmacological management remain to be answered. There is also a paucity of information about the impact of pharmacological interventions on QOL in bipolar depression. To our knowledge, only two clinical trials to date have specifically examined the impact of medications on QOL in patients with bipolar depression. A small number of other studies have examined the effects of depressive symptoms on QOL in patients who are experiencing manic or mixed episodes. Nonetheless, QOL appears to be a meaningful and important indicator of outcome and recovery in this patient population, and one that warrants further scientific interest and energy. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although a host of studies have now examined the relationship between quality of life (QoL) and non-seasonal depression, few have measured QoL in seasonal affective disorder (SAD). We report here on results from the Can-SAD trial, which assessed the impact of treatment with either antidepressant medication or light therapy upon QoL in patients diagnosed with SAD. METHOD: This Canadian double-blind, multicentre, randomized controlled trial included 96 patients who met strict diagnostic criteria for SAD. Eligible patients were randomized to 8 weeks of treatment with either: (1) 10000 lux light treatment and a placebo capsule or (2) 100 lux light treatment (placebo light) and 20 mg fluoxetine. QoL was measured with the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) and the Medical Outcomes Study (MOS) Short-Form General Health Survey (SF-20) at baseline and 8 weeks. RESULTS: Both intervention groups showed significant improvement in QoL over time with no significant differences being detected by treatment condition. Q-LES-Q scores increased significantly in seven of eight domains, with the average scores rising from 48 x 0 (S.D.=10 x 7) at baseline to 69 x 1 (S.D.=15 x 6) at week 8. Treatment-related improvement in QoL was strongly associated with improvement in depression symptoms. DISCUSSION: Patients with SAD report markedly impaired QoL during the winter months. Treatment with light therapy or antidepressant medication is associated with equivalent marked improvement in perceived QoL. Studies of treatment interventions for SAD should routinely include broader indices of patient outcome, such as the assessment of psychosocial functioning or life quality. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Light therapy and antidepressants have shown comparable efficacy in separate studies of seasonal affective disorder treatment, but few studies have directly compared the two treatments. This study compared the effectiveness of light therapy and an antidepressant within a single trial. METHOD: This double-blind, randomized, controlled trial was conducted in four Canadian centers over three winter seasons. Patients met DSM-IV criteria for major depressive disorder with a seasonal (winter) pattern and had scores >/=23 on the 24-item Hamilton Depression Rating Scale. After a baseline observation week, eligible patients were randomly assigned to 8 weeks of double-blind treatment with either 1) 10,000-lux light treatment and a placebo capsule, or 2) 100-lux light treatment (placebo light) and fluoxetine, 20 mg/day. Light treatment was applied for 30 minutes/day in the morning with a fluorescent white-light box; placebo light boxes used neutral density filters. RESULTS: A total of 96 patients were randomly assigned to a treatment condition. Intent-to-treat analysis showed overall improvement with time, with no differences between treatments. There were also no differences between the light and fluoxetine treatment groups in clinical response rates (67% for each group) or remission rates (50% and 54%, respectively). Post hoc testing found that light-treated patients had greater improvement at 1 week but not at other time points. Fluoxetine was associated with greater treatment-emergent adverse events (agitation, sleep disturbance, palpitations), but both treatments were generally well-tolerated with no differences in overall number of adverse effects. CONCLUSIONS: Light treatment showed earlier response onset and lower rate of some adverse events relative to fluoxetine, but there were no other significant differences in outcome between light therapy and antidepressant medication. Although limited by lack of a double-placebo condition, this study supports the effectiveness and tolerability of both treatments for seasonal affective disorder and suggests that other clinical factors, including patient preference, should guide selection of first-line treatment. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Escitalopram is the most selective of the selective serotonin reuptake inhibitor (SSRI) antidepressants. Previous studies have suggested that escitalopram is superior to citalopram in efficacy. We conducted a meta-analysis of studies in which escitalopram was compared with other antidepressants to assess the relative efficacy of these agents. METHODS: Data from all randomized, double-blind studies in major depression in which escitalopram was compared with active controls (citalopram, fluoxetine, paroxetine, sertraline and venlafaxine XR [extended release]) were pooled. The 10 studies were conducted in both specialist settings and general practice. Patients met the criteria of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), for major depressive disorder and were at least 18 years old. In all but 2 studies, patients were required to have a score of 22 or more on the Montgomery-Asberg Depression Rating Scale (MADRS). The primary outcome measure was the estimated difference in treatment effect in MADRS total score at the end of the study. Secondary outcome measures were the response to treatment (defined as a > or = 50% reduction in baseline MADRS total score) and remission rate (defined as MADRS total score < or = 12 at end of study). RESULTS: A total of 2687 patients were included in the analyses (escitalopram n = 1345, conventional SSRIs n = 1102, venlafaxine XR n = 240). Escitalopram was superior to all comparators in overall treatment effect, with an estimated difference in treatment effect of 1.07 points (95% confidence interval [CI] 0.42-1.73, p < 0.01), and in response (odds ratio [OR] 1.29, 95% CI 1.07-1.56, p < 0.01) and remission (OR 1.21, 95% CI 1.01-1.46, p < 0.05) rates. In analysis by medication class, escitalopram was significantly superior to the SSRIs and comparable to venlafaxine, although the overall results do not necessarily reflect a significant difference between escitalopram and individual SSRIs. These results were similar in the severely depressed population (patients with baseline MADRS > or = 30). The withdrawal rate due to adverse events was 6.7% for escitalopram compared with 9.1% for the comparators (p < 0.05). CONCLUSIONS: In this meta-analysis, escitalopram showed significant superiority in efficacy compared with the active controls. [ABSTRACT FROM AUTHOR]

It has been hypothesized that a decrease in the synthesis of new neurons in the adult hippocampus might be linked to major depressive disorder (MDD). This hypothesis arose after it was discovered that antidepressant medications increased the synthesis of new neurons in the brain, and it was noted that the therapeutic effects of antidepressants occurred over a time span that approximates the time taken for the new neurons to become functional. Like antidepressants, exercise also increases the synthesis of new neurons in the adult brain: a 2-3-fold increase in hippocampal neurogenesis has been observed in rats with regular access to a running wheel when they are compared with control animals. We hypothesized, based on the adult-neurogenesis hypothesis of MDD, that exercise should alleviate the symptoms of MDD and that potential mechanisms should exist to explain this therapeutic effect. Accordingly, we evaluated studies that suggest that exercise is an effective treatment for MDD, and we explored potential mechanisms that could link adult neurogenesis, exercise and MDD. We conclude that there is evidence to support the hypothesis that exercise alleviates MDD and that several mechanisms exist that could mediate this effect through adult neurogenesis. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To describe the effectiveness and tolerability of mirtazapine, a noradrenergic and specific serotonergic antidepressant, in the open-label treatment of patients with depression who were resistant to other antidepressant agents. METHODS: The charts of 24 patients who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (DSM-IV) criteria for major depressive disorder and were treated with mirtazapine after partial or nonresponse to standard antidepressants were reviewed for clinical response. Outcome was determined by using the Clinical Global Impressions of Improvement (CGI-I) Scale. RESULTS: Symptomatic improvement was observed in 9 (38%) of 24 patients during an average of 14.1 months of mirtazapine treatment at a mean dose of 36.7 mg/day. Five (21%) patients discontinued mirtazapine because of side effects such as fatigue, weight gain and nausea. Five (21%) patients were receiving combination therapy with another antidepressant when mirtazapine treatment was initiated. CONCLUSIONS: This open-label study suggests that a subgroup of patients with treatment-resistant depression may benefit from mirtazapine treatment. Further controlled studies are required to demonstrate the efficacy of mirtazapine in treatment-resistant depression. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Recent research has suggested that a large proportion of patients with bulimia nervosa have seasonal (winter) worsening of mood symptoms similar to seasonal affective disorder (SAD). The objectives of this study were to determine the specificity of this finding in anorexia and bulimia nervosa, and to further delineate the seasonal mood and eating patterns in bulimia nervosa. METHOD: A modified Seasonal Pattern Assessment Questionnaire (SPAQ) was administered to consecutive female patients assessed at an Eating Disorders Clinic with DSM-III-R diagnoses of bulimia nervosa (BN, N = 60) and anorexia nervosa (AN, N = 31), and to female nonclinical comparison subjects (NC, N = 50). RESULTS: The BN group had higher global seasonality scores and more presumptive diagnoses of SAD than the other two groups; the AN patients, whether they had the restricting or binge eating/purging subtype, did not differ from the NC subjects. Thirty-two percent of the identified seasonal BN patients did not have parallel worsening of mood and eating symptoms in the same season. DISCUSSION: These results suggest that seasonality of symptoms is specific to BN and that there may be separate mechanisms for the seasonality of mood and eating symptoms in some BN patients. [ABSTRACT FROM AUTHOR]

A study was done on prevalence, use patterns, and behaviors associated with chemical substance use among diagnostic medical sonographers, radiographers, nuclear medicine technologists, and radiation therapists registered in Georgia. In this article, the researchers emphasize the sonography data, and how they compare with the collective nonsonography radiologic science group data and to U.S. southern region and national population data. Results showed that sonographers had the highest past year nonmedical use rates compared with all other groups for alcohol, marijuana, stimulants, and cocaine, although none were statistically significant. Sonographers reported lowest past year use compared with all other groups for smoking tobacco, which was not statistically significant, as well as for smokeless tobacco, which was not statistically significant. Sonographers also indicate no nonmedical use of sedatives, inhalers, hallucinogens, crack, or heroin during the previous 12 months. Recommendations include the need for further study to draw a more accurate picture of sonographers' substance use effects on work performance, the need for increased drug education, and increased attention to customized employee assistance programs. [ABSTRACT FROM AUTHOR]

QUESTION: How do anti-depressants and psychotherapy compare in generating full remission in major depressive disorder?Design:Systematic review with meta-analysis.Data sources:Studies were identified using Medline and PsychInfo (to November 2000).Study selection:Eligible studies were randomised controlled trials with blinded participants and assessors that (1) directly compared medications, psychotherapy and controls for well defined major depressive disorder; (2) included remission data. 6 studies were included with 883 outpatients with mild to moderate non-psychotic major depressive disorder. Mean age ranged from 32-40 years; 77% women (range 68-85%). Median treatment duration was 16 weeks (range 10-34).Data extraction:Data were extracted on baseline measurements, sample size, duration of treatment, remission, follow up and dropout rates. The main outcome was full remission.Main results:Tricyclic antidepressants, phenelzine and psychotherapy (primarily cognitive behaviour and interpersonal therapies) were more effective at promoting remission than control conditions. There was no difference in remission between antidepressants and psychotherapy regimens (table).Conclusions:Antidepressants and psychotherapy may both be effective first-line treatments for outpatients with mild to moderate depression. [ABSTRACT FROM AUTHOR]

Background: A critical challenge in the study and management of major depressive disorder (MDD) is predicting relapse. We examined the temporal correlation/coupling between depression and anxiety (called Depression-Anxiety Coupling Strength, DACS) as a predictor of relapse in patients with MDD., Methods: We followed 97 patients with remitted MDD for an average of 394 days. Patients completed weekly self-ratings of depression and anxiety symptoms using the Quick Inventory of Depressive Symptoms (QIDS-SR) and the Generalized Anxiety Disorder 7-item scale (GAD-7). Using these longitudinal ratings we computed DACS as random slopes in a linear mixed effects model reflecting individual-specific degree of correlation between depression and anxiety across time points. We then tested DACS as an independent variable in a Cox proportional hazards model to predict relapse., Results: A total of 28 patients (29 %) relapsed during the follow-up period. DACS significantly predicted confirmed relapse (hazard ratio [HR] 1.5, 95 % CI [1.01, 2.22], p = 0.043; Concordance 0.79 [SE 0.04]). This effect was independent of baseline depressive or anxiety symptoms or their average levels over the follow-up period, and was identifiable more than one month before relapse onset., Limitations: Small sample size, in a single study. Narrow phenotype and comorbidity profiles., Conclusions: DACS may offer opportunities for developing novel strategies for personalized monitoring, early detection, and intervention. Future studies should replicate our findings in larger, diverse patient populations, develop individual patient prediction models, and explore the underlying mechanisms that govern the relationship of DACS and relapse., Competing Interests: Declaration of competing interest RM has received consulting and speaking honoraria from AbbVie, Eisai, Janssen, Lallemand, Lundbeck, Neonmind, and Otsuka, and research grants from CAN-BIND, CIHR, Janssen, Nubiyota, OBI and OMHF. RWL has received honoraria for ad hoc speaking or advising/consulting, or received research funds, from: Abbvie, Asia-Pacific Economic Cooperation, Bausch, BC Leading Edge Foundation, Brain Canada, Canadian Institutes of Health Research, Canadian Network for Mood and Anxiety Treatments, CAN-BIND Solutions, Carnot, Grand Challenges Canada, Healthy Minds Canada, Janssen, Lundbeck, Lundbeck Institute, Medscape, Michael Smith Foundation for Health Research, MITACS, Neurotorium, Ontario Brain Institute, Otsuka, Pfizer/Viatris, Shanghai Mental Health Center, Sunnybrook Health Sciences Center, Unity Health, Vancouver Coastal Health Research Institute, and VGH-UBCH Foundation. JAF has served on the Scientific Advisory Board for MRM Health NL and has received consulting/speaker fees from Klaire Labs, WebMD, Takeda Canada and Rothman, Benson, Hedges Inc. QSL is an employee of Janssen Research & Development, LLC and is a shareholder in Johnson & Johnson, which is the parent company of the Janssen companies. QSL declares that, except for income received from her primary employer, no financial support or compensation has been received from any individual or corporate entity over the past 3 years for research or professional service, and there are no personal financial holdings that could be perceived as constituting a potential conflict of interest. JJN is partially supported by a Marshall Fellowship Award from the UBC Institute of Mental Health. RU is supported by the Canada Research Chairs program. CS has received research funds from Clairvoyant Therapeutics, Otsuka, Eisai Inc. and served as an Advisory Board Member for Bayer, Pfizer, Eisai, Boheringer-Ingelheim. SHK has received engagements from Boehringer-Ingelheim, Janssen, Lundbeck, Merck, Neurotorium, Otsuka. CAN-BIND is an Integrated Discovery Program carried out in partnership with, and financial support from, the Ontario Brain Institute, an independent non-profit corporation, funded partially by the Ontario government. The opinions, results and conclusions are those of the authors and no endorsement by the Ontario Brain Institute is intended or should be inferred. Additional funding is provided by the Canadian Institutes of Health Research (CIHR), Lundbeck, Servier. Funding and/or in kind support is also provided by the investigators' universities and academic institutions. All study medications for the CAN-BIND-1 Trial were independently purchased at wholesale market values. The Wellness Monitoring Study was partially funded by Janssen Research & Development, LLC with research funding from Janssen to University Health Network., (Copyright © 2024. Published by Elsevier B.V.)

Background: The Canadian Network for Mood and Anxiety Treatments (CANMAT) last published clinical guidelines for the management of major depressive disorder (MDD) in 2016. Owing to advances in the field, an update was needed to incorporate new evidence and provide new and revised recommendations for the assessment and management of MDD in adults., Methods: CANMAT convened a guidelines editorial group comprised of academic clinicians and patient partners. A systematic literature review was conducted, focusing on systematic reviews and meta-analyses published since the 2016 guidelines. Recommendations were organized by lines of treatment, which were informed by CANMAT-defined levels of evidence and supplemented by clinical support (consisting of expert consensus on safety, tolerability, and feasibility). Drafts were revised based on review by patient partners, expert peer review, and a defined expert consensus process., Results: The updated guidelines comprise eight primary topics, in a question-and-answer format, that map a patient care journey from assessment to selection of evidence-based treatments, prevention of recurrence, and strategies for inadequate response. The guidelines adopt a personalized care approach that emphasizes shared decision-making that reflects the values, preferences, and treatment history of the patient with MDD. Tables provide new and updated recommendations for psychological, pharmacological, lifestyle, complementary and alternative medicine, digital health, and neuromodulation treatments. Caveats and limitations of the evidence are highlighted., Conclusions: The CANMAT 2023 updated guidelines provide evidence-informed recommendations for the management of MDD, in a clinician-friendly format. These updated guidelines emphasize a collaborative, personalized, and systematic management approach that will help optimize outcomes for adults with MDD., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Camelia Adams has nothing to disclose. Anees Bahji has nothing to disclose. Serge Beaulieu reports research grants, personal fees, and/or nonfinancial support from Abbvie, Boehringer-Ingelheim, Canadian Institutes for Health Research (CIHR), DiaMentis, Idorsia, Eisai, Janssen, and Otsuka-Lundbeck. Venkat Bhat reports research grants from the American Foundation for Suicide Prevention, AMS, Brain and Behaviour Research Foundation, CIHR, Department of Defense, Eisai, New Frontiers in Research Fund, Novartis, Ontario Ministry of Health, Roche, Royal College of Physicians and Surgeons of Canada, and the University of Toronto. Pierre Blier received research grants and/or personal fees from Abbvie, Allergan, CIHR, Janssen, Lundbeck, Merck, Ontario Brain Institute (OBI), Otsuka, Pfizer, University of Ottawa Medical Research Fund, and VilaNova. Daniel M. Blumberger reports research grants, nonfinancial support, and/or other support from Brain Canada, CIHR, Magventure, National Institutes of Health (NIH), and Welcony Inc. Elisa Brietzke reports research grants from Queen’s University Centre for Neuroscience and the PSI Foundation. Trisha Chakrabarty has nothing to disclose. Dr. André Do reports research grants and/or personal fees from AbbVie, CIHR, Janssen, and Otsuka. Benicio N. Frey has nothing to disclose. Dr. Peter Giacobbe reports research grants from CIHR and salary support from the Academic Scholars Fund, Department of Psychiatry, University of Toronto. David David Gratzer has nothing to disclose. Dr. Sophie Grigoriadis reports personal fees from the Canadian Pharmacists Association, Norton, and UptoDate. Jeffrey Habert reports research grants, personal fees and/or other support from Abbvie, Amgen, Astra-Zeneca, Bausch, Bayer, BMS, Boehringer-Ingelheim, Eisai, Eli-Lilly, Elvium, GSK, HLS, Idorsia, Janssen, Lundbeck, Novartis, Novo-Nordisk, Otsuka, Pfizer, and Valeo. M. Ishrat Husain reports research grants and/or other support from the Centre for Addiction and Mental Health (CAMH) Foundation, CIHR, COMPASS Pathfinder, MindSet Pharma, Psyched Therapeutics, University of Toronto, and Wake Network. Zahinoor Ismail reports personal fees from Lundbeck and Otsuka. Sidney H. Kennedy reports research grants, personal fees and/or other support from Abbott, Abbvie, Boehringer-Ingelheim, Brain Canada, Canada’s Strategy for Patient-Oriented Research (SPOR), CIHR, -, Janssen, Lundbeck, Merck, -, OBI, Otsuka, - Servier, and Sunovion. Raymond W. Lam reports research grants, personal fees and/or other support from AbbVie, Asia-Pacific Economic Cooperation (APEC), Bausch, BC Leading Edge Endowment Fund, Brain Canada, CANMAT, Carnot, CIHR, Grand Challenges Canada, Healthy Minds Canada, Janssen, Lundbeck, Michael Smith Health Research BC, MITACS, Neurotorium, OBI, Otsuka, Pfizer/Viatris, Unity Health, and VGH-UBCH Foundation. Alexander McGirr reports other support from Allergan Canada; he holds a patent 63/193,643 pending. Roger S. McIntyre reports research grants and/or personal fees from Abbvie, Alkermes, Atai Life Sciences, Axsome, Bausch, Biogen, Boehringer Ingelheim, Braxia Scientific Corp., CIHR, Eisai, Global Alliance for Chronic Diseases, Intra-Cellular, Janssen, Kris, Lundbeck, Milken Institute, Mitsubishi Tanabe, National Natural Science Foundation of China, Neumora Therapeutics, Neurocrine, NewBridge Pharmaceuticals, Novo Nordisk, Otsuka, Pfizer, Purdue, Sage, Sanofi, Sunovion, Takeda, and Viatris. Erin E. Michalak reports research grants from the Otsuka-Lundbeck Alliance. Roumen V. Milev reports research grants and/or personal fees from AbbVie, Allergan, Canadian Biomarker Integration Network in Depression (CAN-BIND), CIHR, Eisai, Janssen, KYE, Lallemand, Lundbeck, Neonmind, Nubiyota, OBI, Ontario Mental Health Foundation, Otsuka, and Sunovion. Daniel J. Müller reports research grants or personal fees from CAMH AFP Innovation Fund, CAMH Foundation, CIHR, Novagenic, Nubiyota, and OBI. Sagar V. Parikh is the Medical Director for the National Network of Depression Centers and reports research grants, honoraria and/or personal fees from Aifred, Boehringer Ingelheim, Janssen, Medscape, Mensante, Merck, Myriad/Assurex, Otsuka, and Sage; and private shares in Mensante. Lena S. Quilty has nothing to disclose. Arun V. Ravindran has nothing to disclose. Nisha Ravindran has nothing to disclose. Johanne Renaud has nothing to disclose. Joshua D. Rosenblat reports research grants and/or personal fees from Academic Scholars Award, Allergan, American Psychiatric Association, American Society of Psychopharmacology, Boehringer Ingelheim, Braxia Health (Chief Medical and Scientific Officer of Braxia Scientific; Medical Director of the Canadian Rapid Treatment Centre of Excellence [Braxia Health]), Brain and Cognition Discovery Foundation, Canadian Cancer Society, Canadian Psychiatric Association, CIHR, COMPASS, iGan, Janssen, Joseph M. West Family Memorial Fund, Labatt Brain Health Network, Lundbeck, Physician Services Inc. (PSI) Foundation, Sunovion, Timeposters Fellowship, University Health Network Centre for Mental Health, and University of Toronto. Zainab Samaan has nothing to disclose. Gayatri Saraf has nothing to disclose. Kathryn Schade has nothing to disclose. Ayal Schaffer reports personal fees from AbbVie, Lundbeck, and Otsuka. Mark Sinyor has nothing to disclose. Claudio N. Soares reports research grants and/or personal fees from Bayer, Boehinger-Ingelheim, Clairvoyant Therapeutics, Diamond Therapeutics, Eisai, OBI, and Otsuka, Jennifer Swainson reports personal fees, nonfinancial support, and/or other support from AbbVie, Bausch, Eisai, Idorsia, Janssen, Lundbeck, Newly Institute, and Otsuka. Valerie H. Taylor has nothing to disclose. Smadar V. Tourjman reports personal fees from AbbVie, Elvium, Esai, Idorsia, Janssen, Lundbeck, Otsuka, Pfizer, Sunovion, and Takeda. Rudolf Uher has nothing to disclose. Michael van Ameringen reports research grants, personal fees, and/or other support from Abbvie, Bausch Health, Biohaven, Boehringer Ingelheim, CIHR, Elvium (Purdue), Jazz, Lundbeck, Michael G. DeGroote Centre for Medicinal Cannabis Research, Otsuka, Sunovion, Takeda, UptoDate, and Vistagen. Gustavo Vazquez reports personal fees for Abbvie, Allergan, Asofarma, Elea/Phoenix, Eurofarma, Gador, Janssen, Lundbeck/Otsuka, NeonMind Biosciences, Psicofarma, Raffo, Sunovion, and Tecnofarma. Simone Vigod reports royalties from UpToDate. Daphne Voineskos holds the Labatt Family Professorship in Depression Biology, a University Named Professorship at the University of Toronto; she reports research grants from CIHR, CAMH, Centre for Mental Health at University Health Network, Department of Psychiatry at the University of Toronto, and the National Institute of Mental Health. Lakshmi N. Yatham reports research grants and/or personal fees from Abbvie, Alkermes, Allergan, Dainippon Sumitomo, Gedeon Richter, GSK, Intracellular Therapies, Merck, Sanofi, and Sunovion.

Introduction: Little is known about the interplay between genetics and epigenetics on antidepressant treatment (1) response and remission, (2) side effects, and (3) serum levels. This study explored the relationship among single nucleotide polymorphisms (SNPs), DNA methylation (DNAm), and mRNA levels of four pharmacokinetic genes, CYP2C19 , CYP2D6 , CYP3A4 , and ABCB1 , and its effect on these outcomes., Methods: The Canadian Biomarker Integration Network for Depression-1 dataset consisted of 177 individuals with major depressive disorder treated for 8 weeks with escitalopram (ESC) followed by 8 weeks with ESC monotherapy or augmentation with aripiprazole. DNAm quantitative trait loci (mQTL), identified by SNP-CpG associations between 20 SNPs and 60 CpG sites in whole blood, were tested for associations with our outcomes, followed by causal inference tests (CITs) to identify methylation-mediated genetic effects., Results: Eleven cis- SNP-CpG pairs (q<0.05) constituting four unique SNPs were identified. Although no significant associations were observed between mQTLs and response/remission, CYP2C19 rs4244285 was associated with treatment-related weight gain ( q =0.027) and serum concentrations of ESC adj ( q <0.001). Between weeks 2-4, 6.7% and 14.9% of those with *1/*1 (normal metabolizers) and *1/*2 (intermediate metabolizers) genotypes, respectively, reported ≥2 lbs of weight gain. In contrast, the *2/*2 genotype (poor metabolizers) did not report weight gain during this period and demonstrated the highest ESC adj concentrations. CITs did not indicate that these effects were epigenetically mediated., Discussion: These results elucidate functional mechanisms underlying the established associations between CYP2C19 rs4244285 and ESC pharmacokinetics. This mQTL SNP as a marker for antidepressant-related weight gain needs to be further explored., Competing Interests: Dr. Benicio N. Frey has no conflicts to disclose. Dr. Roumen V. Milev has received consulting and speaking honoraria from AbbVie, Allergan, Eisai, Janssen, KYE Pharmaceuticals, Lallemand, Lundbeck, Otsuka, and Sunovion, and research grants from CAN-BIND, Canadian Institutes of Health Research (CIHR), Janssen, Lallemand, Lundbeck, Nubiyota, Ontario Brain Institute (OBI), and Ontario Mental Health Foundation (OMHF). Dr. Sagar V. Parikh has received research support or consulting income from Aifred, Assurex (Myriad), Janssen, Mensante, Otsuka, Sage, and Takeda. Dr. Stefanie Hassel has no conflicts of interest to disclose. Dr. Pierre Blier received honoraria for participation in advisory boards, giving lectures, and/or expert consultation from Allergan, Bristol Myers Squibb, Janssen, Lundbeck, Otsuka, Pierre Fabre Medicaments, Pfizer and Sunovion; he received grants from Allergan, Janssen, and Lundbeck/Otsuka. Dr. Faranak Farzan received funding from Michael Smith Foundation for Health Research, Natural Sciences and Engineering Research Council of Canada Discovery, and Canadian Institutes of Health Research. Dr. Raymond W. Lam has received honoraria for ad hoc speaking or advising/consulting, or received research funds, from Abbvie, Asia-Pacific Economic Cooperation, BC Leading Edge Foundation, Boehringer-Ingelheim, Canadian Institutes of Health Research (CIHR), Canadian Network for Mood and Anxiety Treatments, Carnot, Healthy Minds Canada, Janssen, Lundbeck, Michael Smith Foundation for Health Research, MITACS, Neurotorium, Ontario Brain Institute (OBI), Otsuka, Pfizer, Unity Health, and VGH-UBCH Foundation. Dr. Gustavo Turecki has received an Investigator-initiated grant from Pfizer Canada, and honoraria from Bristol-Meyers Squibb Canada and Janssen Canada. Dr. Susan Rotzinger has received grant funding from the Ontario Brain Institute (OBI), and Canadian Institutes of Health Research (CIHR), and holds a patent Teneurin C-Terminal Associated Peptides (TCAP) and methods and uses thereof. Dr. Stefan Kloiber has received honorarium for past consultation from EmpowerPharm. Dr. Sidney H. Kennedy has received research funding or honoraria from the following sources: Abbott, Alkermes, Allergan, Bristol-Myers Squibb (BMS), Brain Canada, Canadian Institutes for Health Research (CIHR), Janssen, Lundbeck, Lundbeck Institute, Ontario Brain Institute (OBI), Ontario Research Fund (ORF), Otsuka, Pfizer, Servier, Sunovion and holds stock in Field Trip Health. Dr. Daniel J. Müller reports to be a co-investigator on two pharmacogenetic studies where genetic test kits were provided as in-kind contributions by Myriad Neuroscience. All other authors report no conflicts of interest related to this work., (Thieme. All rights reserved.)

Background: Patients with major depressive disorder (MDD) can present with altered brain structure and deficits in cognitive function similar to those seen in aging. However, the interaction between age-related brain changes and brain development in MDD remains understudied. In a cohort of adolescents and adults with and without MDD, we assessed brain aging differences and associations through a newly developed tool that quantifies normative neurodevelopmental trajectories., Methods: A total of 304 participants with MDD and 236 control participants without depression were recruited and scanned from 3 studies under the Canadian Biomarker Integration Network for Depression. Volumetric data were used to generate brain centile scores, which were examined for 1) differences between participants with MDD and control participants; 2) differences between individuals with versus without severe childhood maltreatment; and 3) correlations with depressive symptom severity, neurocognitive assessment domains, and escitalopram treatment response., Results: Brain centiles were significantly lower in the MDD group than in the control group. Brain centile was also significantly correlated with working memory in the control group but not the MDD group. No significant associations were observed between depression severity or antidepressant treatment response and brain centiles. Likewise, childhood maltreatment history did not significantly affect brain centiles., Conclusions: Consistent with previous work on machine learning models that predict brain age, brain centile scores differed in people diagnosed with MDD, and MDD was associated with differential relationships between centile scores and working memory. The results support the notion of atypical development and aging in MDD, with implications for neurocognitive deficits associated with aging-related cognitive function., (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: e-Health tools using validated questionnaires to assess outcomes may facilitate measurement-based care for psychiatric disorders. MoodFX was created as a free online symptom tracker to support patients for outcome measurement in their depression treatment. We conducted a pilot randomized evaluation to examine its usability, and clinical utility., Methods: Patients presenting with a major depressive episode (within a major depressive or bipolar disorder) were randomly assigned to receive either MoodFX or a health information website as the intervention and control condition, respectively, with follow-up assessment surveys conducted online at baseline, 8 weeks and 6 months. The primary usability outcomes included the percentage of patients with self-reported use of MoodFX 3 or more times during follow up (indicating minimally adequate usage) and usability measures based on the System Usability Scale (SUS). Secondary clinical outcomes included the Quick Inventory of Depressive Symptomatology, Self-Rated (QIDS-SR) and Patient Health Questionnaire (PHQ-9)., Results: Forty-nine participants were randomized (24 to MoodFX and 25 to the control condition). Of the 23 participants randomized to MoodFX who completed the user survey, 18 (78%) used MoodFX 3 or more times over the 6 months of the study. The mean SUS score of 72.7 (65th-69th percentile) represents good usability. Compared to the control group, the MoodFX group had significantly better improvement on QIDS-SR and PHQ-9 scores, with large effect sizes and higher response rates at 6 months. There were no differences between conditions on other secondary outcomes such as functioning and quality of life., Conclusion: MoodFX demonstrated good usability and was associated with reduction in depressive symptoms. This pilot study supports the use of digital tools in depression treatment., Competing Interests: Declaration of Conflicting InterestsRWL has received honoraria for ad hoc speaking or advising/consulting, or received research funds, from: Abbvie, Asia-Pacific Economic Cooperation, Bausch, BC Leading Edge Foundation, Brain Canada, Canadian Institutes of Health Research, Canadian Network for Mood and Anxiety Treatments, CB Solutions, Carnot, Genome BC, Grand Challenges Canada, Healthy Minds Canada, Janssen, Lundbeck, Michael Smith Foundation for Health Research, MITACS, Neurotorium, Ontario Brain Institute, Otsuka, Pfizer/Viatris, Shanghai Mental Health Center, Unity Health, Vancouver Coastal Health Research Institute, and VGH-UBCH Foundation. AD was partly supported by an unrestricted fellowship grant from Janssen Canada and has received honoraria for ad hoc speaking or advising/consulting, or received research funds, from: AbbVie, Canadian Institutes of Health Research and Otsuka. JJN was partially supported by a Marshall/Institute of Mental Health Fellowship Award and received unrestricted research funding from the BC Cancer Foundation, with funds originating from Pfizer. KK is supported as a health professional investigator by Michael Smith Health Research Foundation of BC, Vancouver Coastal Health Research Institute and VGH & UBC Hospital Foundation and has previously served on the scientific advisory board of AbbVie. EEM has received support for patient education activities from Otsuka-Lundbeck. LNY has received honoraria for ad hoc speaking or advising/consulting, or received research funds, from: AbbVie, Alkermes, Allergan, Canadian Institutes of Health Research, Canadian Network for Mood and Anxiety Treatments, Dainippon Sumitomo Pharma, GlaxoSmithKline, Intracellular Therapies, Lundbeck, Merck, Otsuka, Sanofi, and Sunovion. VWL, VCE, JS, DKD, DDG, AA, EMT and JKM have no disclosures.

Intravenous (IV) ketamine and intranasal (IN) esketamine are novel therapies to manage treatment resistant depression within major depressive disorder (MDD-TRD). This is a multi-site observational study aiming to assess the real-world effectiveness and tolerability of these novel therapies in the management of MDD-TRD. 53 patients were referred to receive IV ketamine (n = 26, 69.23 % female, 52.81 ± 14.33 years old) or IN esketamine (n = 27, 51.85 % female, 43.93 ± 13.57 years old). Treatment effectiveness was assessed using the Montgomery and Åsberg Depression Rating Scale (MADRS) for depression severity and item 10 of the MADRS for suicidal ideation (SI). Tolerability was assessed by systematically tracking side effects and depersonalization using the 6-item Clinician administered dissociative symptom scale (CADSS-6). The data was analyzed using descriptive statistics, risk ratio and effect size. Both IV ketamine and IN esketamine significantly reduced depressive symptoms and suicidal ideation by treatment endpoint. Patients receiving IN esketamine, and patients receiving IV ketamine had a similar risk of developing side effects. All side effects reported were mild and transient. These results suggested that both IV ketamine and IN esketamine are effective in the management of depressive symptoms and were well tolerated. Therefore, the results of this study could serve to inform clinical practice., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jennifer Swainson reports a relationship with AbbVie Inc that includes: consulting or advisory and speaking and lecture fees. Jennifer Swainson reports a relationship with Bausch Health Companies Inc US that includes: consulting or advisory and speaking and lecture fees. Jennifer Swainson reports a relationship with Biron Health Group that includes: consulting or advisory and speaking and lecture fees. Jennifer Swainson reports a relationship with Eisai Inc that includes: consulting or advisory and speaking and lecture fees. Jennifer Swainson reports a relationship with Idorsia Pharmaceuticals Ltd that includes: consulting or advisory and speaking and lecture fees. Jennifer Swainson reports a relationship with Janssen Pharmaceuticals Inc that includes: consulting or advisory and speaking and lecture fees. Jennifer Swainson reports a relationship with Lundbeck LLC that includes: consulting or advisory and speaking and lecture fees. Jennifer Swainson reports a relationship with Otsuka Pharmaceutical Co Ltd that includes: consulting or advisory and speaking and lecture fees. Jennifer Swainson reports a relationship with Canadian Psychiatric Association that includes: consulting or advisory and speaking and lecture fees. Raymond W. Lam reports a relationship with AbbVie Inc that includes: consulting or advisory, funding grants, and speaking and lecture fees. Raymond W. Lam reports a relationship with Asia-Pacific Economic Cooperation that includes: consulting or advisory, funding grants, and speaking and lecture fees. Raymond W. Lam reports a relationship with Bausch Health Companies Inc US that includes: consulting or advisory, funding grants, and speaking and lecture fees. Raymond W. Lam reports a relationship with BC leading edge foundation that includes: consulting or advisory, funding grants, and speaking and lecture fees. Raymond W. Lam reports a relationship with Brain Canada Foundation that includes: consulting or advisory, funding grants, and speaking and lecture fees. Raymond W. Lam reports a relationship with Canadian Institutes of Health Research that includes: consulting or advisory, funding grants, and speaking and lecture fees. Raymond W. Lam reports a relationship with Canadian Network for Mood and Anxiety Treatments that includes: consulting or advisory, funding grants, and speaking and lecture fees. Raymond W. Lam reports a relationship with Carnot Pharma LLC that includes: consulting or advisory, funding grants, and speaking and lecture fees. Raymond W. Lam reports a relationship with CB solutions that includes: consulting or advisory, funding grants, and speaking and lecture fees. Raymond W. Lam reports a relationship with Genome British Columbia that includes: consulting or advisory, paid expert testimony, and speaking and lecture fees. Raymond W. Lam reports a relationship with Grand Challenges Canada that includes: consulting or advisory, funding grants, and speaking and lecture fees. Raymond W. Lam reports a relationship with Healthy Minds Canada that includes: consulting or advisory, funding grants, and speaking and lecture fees. Raymond W. Lam reports a relationship with Janssen Pharmaceuticals Inc that includes: consulting or advisory, funding grants, and speaking and lecture fees. Raymond W. Lam reports a relationship with Lundbeck LLC that includes: consulting or advisory, funding grants, and speaking and lecture fees. Raymond W. Lam reports a relationship with Michael Smith Foundation for Health Research that includes: consulting or advisory, funding grants, and speaking and lecture fees. Raymond W. Lam reports a relationship with Mitacs that includes: consulting or advisory, funding grants, and travel reimbursement. Raymond W. Lam reports a relationship with Neurotorium that includes: consulting or advisory, funding grants, and speaking and lecture fees. Raymond W. Lam reports a relationship with Ontario Brain Institute that includes: consulting or advisory, funding grants, and speaking and lecture fees. Raymond W. Lam reports a relationship with Otsuka Pharmaceutical Co Ltd that includes: consulting or advisory, funding grants, and speaking and lecture fees. Raymond W. Lam reports a relationship with Shanghai Mental Health Center that includes: consulting or advisory, funding grants, and speaking and lecture fees. Raymond W. Lam reports a relationship with Unity Health that includes: consulting or advisory, funding grants, and speaking and lecture fees. Raymond W. Lam reports a relationship with Vancouver Coastal Health Research Institute that includes: consulting or advisory, funding grants, and speaking and lecture fees. Raymond W. Lam reports a relationship with VGH and UBC Hospital Foundation that includes: consulting or advisory, funding grants, and speaking and lecture fees. Andre Do reports a relationship with Janssen Pharmaceuticals Inc that includes:. Andre Do reports a relationship with AbbVie Inc that includes: consulting or advisory and funding grants. Andre Do reports a relationship with Canadian Institutes of Health Research that includes: consulting or advisory and funding grants. Andre Do reports a relationship with Otsuka Pharmaceutical Co Ltd that includes: consulting or advisory and funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The COVID-19 pandemic had an unprecedented impact on global mental health and well-being, including across the Asia-Pacific. Efforts to mitigate virus spread led to far-reaching disruption in the delivery of health and social services. In response, there was a rapid shift to the use of digital mental health (DMH) approaches. Though these technologies helped to improve access to care for many, there was also substantial risk of access barriers leading to increased inequities in access to mental health care, particularly among at-risk and equity-deserving populations. The objective of this study was to conduct a needs assessment and identify priorities related to equitable DMH access among at-risk and equity-deserving populations in the Asia Pacific region during the first year of the COVID-19 pandemic. The study consisted of a modified Delphi consensus methodology including two rounds of online surveys and online consultations with stakeholders from across the region. Study participants included policy makers, clinicians and service providers, and people with lived experience of mental health conditions. Results demonstrate that vulnerabilities to negative mental health impacts and access barriers were compounded during the pandemic. Access barriers included a lack of linguistically and culturally appropriate DMH options, low mental health literacy and poor access to technological infrastructure and devices, low levels of awareness and trust of DMH options, and lack of policies and guidelines to support effective and equitable delivery of DMH. Recommendations to improve equitable access include ensuring that diverse people with lived experience are engaged in research, co-design and policy development, the development and implementation of evidence-based and equity-informed guidelines and frameworks, clear communication about DMH evidence and availability, and the integration of DMH into broader health systems. Study results can inform the development and implementation of equitable DMH as its use becomes more widespread across health systems., Competing Interests: "I have read the journal’s policy and the authors of this manuscript have the following competing interests: EEM has received funding from Otsuka-Lundbeck for patient educational activities. CHN had served as a consultant for Janssen-Cilag, Lundbeck, Grunbiotics, Servier and Eli Lilly, received research grants from National Health and Medical Research Council and Medical Research Future Funds, and speaker honoraria from Servier, Lundbeck, Eli Lilly, Janssen-Cilag, Astra-Zeneca, and Pfizer – all unrelated to this study. RWL has received honoraria for ad hoc speaking or advising/consulting, or received research funds, from: Abbvie, Asia-Pacific Economic Cooperation, Bausch, BC Leading Edge Foundation, Brain Canada, Canadian Institutes of Health Research, Canadian Network for Mood and Anxiety Treatments, CAN-BIND Solutions, Carnot, Grand Challenges Canada, Healthy Minds Canada, Janssen, Lundbeck, Medscape, Michael Smith Foundation for Health Research, MITACS, Neurotorium, Ontario Brain Institute, Otsuka, Pfizer/Viatris, Shanghai Mental Health Center, Sunnybrook Health Sciences Centre, Unity Health, Vancouver Coastal Health Research Institute, and VGH-UBCH Foundation. This does not alter our adherence to PLOS Global Public Health policies on sharing data and materials JKM, SS, YMC, PAC, MI, MW, AK, AG, JON, VCN, HM, AR, AP, JC, XW, TYH, NI, SH, and VE have declared that no competing interests exist., (Copyright: © 2024 Murphy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Clinical studies of major depression (MD) generally focus on group effects, yet interindividual differences in brain function are increasingly recognized as important and may even impact effect sizes related to group effects. Here, we examine the magnitude of individual differences in relation to group differences that are commonly investigated (e.g., related to MD diagnosis and treatment response). Functional MRI data from 107 participants (63 female, 44 male) were collected at baseline, 2, and 8 weeks during which patients received pharmacotherapy (escitalopram, N  = 68) and controls ( N  = 39) received no intervention. The unique contributions of different sources of variation were examined by calculating how much variance in functional connectivity was shared across all participants and sessions, within/across groups (patients vs controls, responders vs nonresponders, female vs male participants), recording sessions, and individuals. Individual differences and common connectivity across groups, sessions, and participants contributed most to the explained variance (>95% across analyses). Group differences related to MD diagnosis, treatment response, and biological sex made significant but small contributions (0.3-1.2%). High individual variation was present in cognitive control and attention areas, while low individual variation characterized primary sensorimotor regions. Group differences were much smaller than individual differences in the context of MD and its treatment. These results could be linked to the variable findings and difficulty translating research on MD to clinical practice. Future research should examine brain features with low and high individual variation in relation to psychiatric symptoms and treatment trajectories to explore the clinical relevance of the individual differences identified here., Competing Interests: B.N.F. has received grant/research support from Alternative Funding Plan Innovations Award, Brain and Behavior Research Foundation, Canadian Institutes of Health Research, Hamilton Health Sciences Foundation, J. P. Bickell Foundation, Ontario Brain Institute, Ontario Mental Health Foundation, Society for Women's Health Research, Teresa Cascioli Charitable Foundation, Eli Lilly, and Pfizer and has received consultant and/or speaker fees from AstraZeneca, Bristol-Myers Squibb, Canadian Psychiatric Association, CANMAT, Daiichi Sankyo, Lundbeck, Pfizer, Servier, and Sunovion. R.M. has received consulting and speaking honoraria from AbbVie, Allergan, Janssen, KYE, Lundbeck, Otsuka, and Sunovion and research grants from CAN-BIND, CIHR, Janssen, Lallemand, Lundbeck, Nubiyota, OBI, and OMHF. S.P. has been a consultant to Takeda, Bristol Myers Squibb, Lundbeck; has had a research contract with Assurex; and has equity in Mensante. R.W.L. has received speaker and consultant honoraria or research funds from AstraZeneca, Brain Canada, Bristol-Myers Squibb, the Canadian Institutes of Health Research (CIHR), the Canadian Network for Mood and Anxiety Treatments, the Canadian Psychiatric Association, Eli Lilly, Janssen, Lundbeck, Lundbeck Institute, Medscape, Otsuka, Pfizer, Servier, St. Jude Medical, Takeda, the University Health Network Foundation, Vancouver Coastal Health Research Institute, Allergan, Asia-Pacific Economic Cooperation, BC Leading Edge Foundation, Healthy Minds Canada, Michael Smith Foundation for Health Research, MITACS, Myriad Neuroscience, Ontario Brain Institute, Otsuka, Unity Health, Viatris, and VGH-UBCH Foundation. S.H.K. has received honoraria or research funds from Abbott, Alkermes, Allergan, Boehringer Ingelheim, Brain Canada, CIHR, Janssen, Lundbeck, Lundbeck Institute, Ontario Brain Institute, Ontario Research Fund, Otsuka, Pfizer, Servier, Sunovion, and Sun Pharmaceutical and holds stock in Field Trip Health. D.J.M. has received consulting and speaking honoraria from Lundbeck and Genomind. C.S. has received consulting and speaking honoraria from Pfizer, Otsuka, Bayer, Eisai, and research grants from CAN-BIND, CIHR, OBI, and SEAMO. S.C.S. is a senior Scientific Advisor and shareholder in ADMdx, which receives NIH funding, and during the period of this research, he had research grants from Brain Canada, Canada Foundation for Innovation (CFI), Canadian Institutes of Health Research (CIHR), and the Ontario Brain Institute in Canada. Other authors declare no competing financial interests., (Copyright © 2024 van der Wijk et al.)

We examine structural brain characteristics across three diagnostic categories: at risk for serious mental illness; first-presenting episode and recurrent major depressive disorder (MDD). We investigate whether the three diagnostic groups display a stepwise pattern of brain changes in the cortico-limbic regions. Integrated clinical and neuroimaging data from three large Canadian studies were pooled (total n = 622 participants, aged 12-66 years). Four clinical profiles were used in the classification of a clinical staging model: healthy comparison individuals with no history of depression (HC, n = 240), individuals at high risk for serious mental illness due to the presence of subclinical symptoms (SC, n = 80), first-episode depression (FD, n = 82), and participants with recurrent MDD in a current major depressive episode (RD, n = 220). Whole-brain volumetric measurements were extracted with FreeSurfer 7.1 and examined using three different types of analyses. Hippocampal volume decrease and cortico-limbic thinning were the most informative features for the RD vs HC comparisons. FD vs HC revealed that FD participants were characterized by a focal decrease in cortical thickness and global enlargement in amygdala volumes. Greater total amygdala volumes were significantly associated with earlier onset of illness in the FD but not the RD group. We did not confirm the construct validity of a tested clinical staging model, as a differential pattern of brain alterations was identified across the three diagnostic groups that did not parallel a stepwise clinical staging approach. The pathological processes during early stages of the illness may fundamentally differ from those that occur at later stages with clinical progression., Competing Interests: Declaration of competing interest Dr. Sidney Kennedy has received funding for Consulting or Speaking engagements from Abbvie, Boehringer-Ingelheim, Janssen, Lundbeck, Lundbeck Institute, Merck, Otsuka Pfizer, Sunovion and Servier. Dr. Kennedy has received Research Support from Abbott, Brain Canada, CIHR (Canadian Institutes of Health Research), Janssen, Lundbeck, Ontario Brain Institute, Otsuka, Pfizer, SPOR (Canada's Strategy for Patient-Oriented Research); and has stock/stock options in Field Trip Health. No other disclosures or conflict of interests stated by authors of this work. SJR has received consulting or research funding from Allergan, Janssen, Neurocrine, and Pfizer Canada., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: Treatment-emergent sexual dysfunction is frequently reported by individuals with major depressive disorder (MDD) on antidepressants, which negatively impacts treatment adherence and efficacy. We investigated the association of polymorphisms in pharmacokinetic genes encoding cytochrome-P450 drug-metabolizing enzymes, CYP2C19 and CYP2D6 , and the transmembrane efflux pump, P-glycoprotein (i.e., ABCB1 ), on treatment-emergent changes in sexual function (SF) and sexual satisfaction (SS) in the Canadian Biomarker Integration Network in Depression 1 (CAN-BIND-1) sample., Methods: A total of 178 adults with MDD received treatment with escitalopram (ESC) from weeks 0-8 (Phase I). At week 8, nonresponders were augmented with aripiprazole (ARI) (i.e., ESC + ARI, n  = 91), while responders continued ESC (i.e., ESC-Only, n  = 80) from weeks 8-16 (Phase II). SF and SS were evaluated using the sex effects (SexFX) scale at weeks 0, 8, and 16. We assessed the primary outcomes, SF and SS change for weeks 0-8 and 8-16, using repeated measures mixed-effects models., Results: In ESC-Only, CYP2C19 intermediate metabolizer (IM) + poor metabolizers (PMs) showed treatment-related improvements in sexual arousal, a subdomain of SF, from weeks 8-16, relative to CYP2C19 normal metabolizers (NMs) who showed a decline, F (2,54) = 8.00, p  < 0.001, q  = 0.048. Specifically, CYP2C19 IM + PMs reported less difficulty with having and sustaining vaginal lubrication in females and erection in males, compared to NMs. Furthermore, ESC-Only females with higher concentrations of ESC metabolite, S-desmethylcitalopram (S-DCT), and S-DCT/ESC ratio in serum demonstrated more decline in SF ( r  = -0.42, p  = 0.004, q  = 0.034) and SS ( r  = -0.43, p  = 0.003, q  = 0.034), respectively, which was not observed in males. ESC-Only females also demonstrated a trend for a correlation between S-DCT and sexual arousal change in the same direction ( r  = -0.39, p  = 0.009, q  = 0.052)., Conclusions: CYP2C19 metabolizer phenotypes may be influencing changes in sexual arousal related to ESC monotherapy. Thus, preemptive genotyping of CYP2C19 may help to guide selection of treatment that circumvents selective serotonin reuptake inhibitor-related sexual dysfunction thereby improving outcomes for patients. Additionally, further research is warranted to clarify the role of S-DCT in the mechanisms underlying ESC-related changes in SF and SS. This CAN-BIND-1 study was registered on clinicaltrials.gov (Identifier: NCT01655706) on 27 July 2012.

Background: Identifying neuroimaging biomarkers of antidepressant response may help guide treatment decisions and advance precision medicine., Aims: To examine the relationship between anhedonia and functional neurocircuitry in key reward processing brain regions in people with major depressive disorder receiving aripiprazole adjunct therapy with escitalopram., Method: Data were collected as part of the CAN-BIND-1 study. Participants experiencing a current major depressive episode received escitalopram for 8 weeks; escitalopram non-responders received adjunct aripiprazole for an additional 8 weeks. Functional magnetic resonance imaging (on weeks 0 and 8) and clinical assessment of anhedonia (on weeks 0, 8 and 16) were completed. Seed-based correlational analysis was employed to examine the relationship between baseline resting-state functional connectivity (rsFC), using the nucleus accumbens (NAc) and anterior cingulate cortex (ACC) as key regions of interest, and change in anhedonia severity after adjunct aripiprazole., Results: Anhedonia severity significantly improved after treatment with adjunct aripiprazole.There was a positive correlation between anhedonia improvement and rsFC between the ACC and posterior cingulate cortex, ACC and posterior praecuneus, and NAc and posterior praecuneus. There was a negative correlation between anhedonia improvement and rsFC between the ACC and anterior praecuneus and NAc and anterior praecuneus., Conclusions: Eight weeks of aripiprazole, adjunct to escitalopram, was associated with improved anhedonia symptoms. Changes in functional connectivity between key reward regions were associated with anhedonia improvement, suggesting aripiprazole may be an effective treatment for individuals experiencing reward-related deficits. Future studies are required to replicate our findings and explore their generalisability, using other agents with partial dopamine (D2) agonism and/or serotonin (5-HT2A) antagonism.

Neural network-level changes underlying symptom remission in major depressive disorder (MDD) are often studied from a single perspective. Multimodal approaches to assess neuropsychiatric disorders are evolving, as they offer richer information about brain networks. A FATCAT-awFC pipeline was developed to integrate a computationally intense data fusion method with a toolbox, to produce a faster and more intuitive pipeline for combining functional connectivity with structural connectivity (denoted as anatomically weighted functional connectivity ( awFC )). Ninety-three participants from the Canadian Biomarker Integration Network for Depression study (CAN-BIND-1) were included. Patients with MDD were treated with 8 weeks of escitalopram and adjunctive aripiprazole for another 8 weeks. Between-group connectivity (SC, FC, awFC ) comparisons contrasted remitters (REM) with non-remitters (NREM) at baseline and 8 weeks. Additionally, a longitudinal study analysis was performed to compare connectivity changes across time for REM, from baseline to week-8. Association between cognitive variables and connectivity were also assessed. REM were distinguished from NREM by lower awFC within the default mode, frontoparietal, and ventral attention networks. Compared to REM at baseline, REM at week-8 revealed increased awFC within the dorsal attention network and decreased awFC within the frontoparietal network. A medium effect size was observed for most results. AwFC in the frontoparietal network was associated with neurocognitive index and cognitive flexibility for the NREM group at week-8. In conclusion, the FATCAT-awFC pipeline has the benefit of providing insight on the 'full picture' of connectivity changes for REMs and NREMs while making for an easy intuitive approach., (© 2024 The Authors.)

Preclinical research implicates stress-induced upregulation of the enzyme, serum- and glucocorticoid-regulated kinase 1 (SGK1), in reduced hippocampal volume. In the current study, we tested the hypothesis that greater SGK1 mRNA expression in humans would be associated with lower hippocampal volume, but only among those with a history of prolonged stress exposure, operationalized as childhood maltreatment (physical, sexual, and/or emotional abuse). Further, we examined whether baseline levels of SGK1 and hippocampal volume, or changes in these markers over the course of antidepressant treatment, would predict treatment outcomes in adults with major depression [MDD]. We assessed SGK1 mRNA expression from peripheral blood, and left and right hippocampal volume at baseline, as well as change in these markers over the first 8 weeks of a 16-week open-label trial of escitalopram as part of the Canadian Biomarker Integration Network in Depression program (MDD [n = 161] and healthy comparison participants [n = 91]). Childhood maltreatment was assessed via contextual interview with standardized ratings. In the full sample at baseline, greater SGK1 expression was associated with lower hippocampal volume, but only among those with more severe childhood maltreatment. In individuals with MDD, decreases in SGK1 expression predicted lower remission rates at week 16, again only among those with more severe maltreatment. Decreases in hippocampal volume predicted lower week 16 remission for those with low childhood maltreatment. These results suggest that both glucocorticoid-related neurobiological mechanisms of the stress response and history of childhood stress exposure may be critical to understanding differential treatment outcomes in MDD. ClinicalTrials.gov: NCT01655706 Canadian Biomarker Integration Network for Depression Study., Competing Interests: Declaration of Competing Interest RM, SC, SH, LF, NN, BNF, KH reported no relevant conflict of interests. RVM has received consulting and speaking honoraria from AbbVie, Allergan, Eisai, Janssen, KYE, Lallemand, Lundbeck, Otsuka, and Sunovion, and research grants from CAN-BIND, Canadian Institutes for Health Research, Janssen, Lallemand, Lundbeck, Nubiyota, Ontario Brain Institute and Ontario Mental Health Foundation. RWL has received honoraria for ad hoc speaking or advising/consulting, or received research funds, from Asia-Pacific Economic Cooperation, BC Leading Edge Foundation, Canadian Institutes for Health Research, Canadian Network for Mood and Anxiety Treatments, Healthy Minds Canada, Janssen, Lundbeck, Lundbeck Institute, Michael Smith Foundation for Health Research, MITACS, Myriad Neuroscience, Ontario Brain Institute, Otsuka, Pfizer, Sanofi, Unity Health, and VGH-UBCH Foundation. SCS received funding from the Ontario Brain Institute and Canadian Institutes for Health Research (MOP137097) for neuroimaging analysis in CAN-BIND, and SCS is a Senior Scientific Advisor and co-owner of ADMdx, Inc., a neuroimaging consulting company. SRA has carried out consultancy work for Indoc Research. SR holds a patent "Teneurin C-Terminal Associated Peptides (TCAP) and methods and uses thereof. Inventors: David Lovejoy, R.B. Chewpoy, Dalia Barsyte, Susan Rotzinger." SHK has received research funding or honoraria from the following sources: Abbott, Alkermes, Abbvie, Brain Canada, Canadian Institutes for Health Research, Janssen, Lundbeck, Lundbeck Institute, Ontario Brain Institute, Ontario Research Fund, Otsuka, Pfizer, Servier, Sunovion and Xian-Janssen and holds stock in Field Trip Health., (Copyright © 2023 Elsevier B.V. and ECNP. All rights reserved.)

Introduction: Repetitive transcranial magnetic stimulation (TMS) is increasingly used to treat neurocognitive symptoms in mood disorders. Intermittent theta burst stimulation (iTBS) is a brief version of TMS that may preferentially target cognitive functions. This study evaluated whether iTBS leads to cognitive improvements and associated increased hippocampal volumes in bipolar depression., Methods: In a two-site double-blind randomised sham controlled trial (NCT02749006), 16 patients received active iTBS to the Left Dorsolateral Prefrontal Cortex (DLPF) and 15 patients received sham stimulation across four weeks. A composite neuropsychological score and declarative memory scores served as the cognitive outcomes. Hippocampal volumes were derived from T1 weighted MRI scans using the longitudinal ComBat method to harmonise data across sites., Results: No significant improvements were observed in any cognitive variables in the active relative to the sham group; however, there was a trend for increased left hippocampal volume in the former. Left hippocampal volume increases were associated with improvements in nonverbal memory in the active group., Conclusions: Although cognitive improvements were not associated with iTBS, the finding that hippocampal volume increases were associated with memory improvement suggests there may be some level of prefrontal-temporal neuroplasticity that could support cognitive change in future studies of iTBS in bipolar disorder.

Identifying clinically relevant predictors of depressive recurrence following treatment for Major Depressive Disorder (MDD) is critical for relapse prevention. Implicit self-depressed associations (SDAs), defined as implicit cognitive associations between elements of depression (e.g., sad, miserable) and oneself, often persist following depressive episodes and may represent a cognitive biomarker for future recurrences. Thus, we examined whether SDAs, and changes in SDAs over time, prospectively predict depressive recurrence among treatment responders in the CAN-BIND Wellness Monitoring for MDD Study, a prospective cohort study conducted across 5 clinical centres. A total of 96 patients with MDD responding to various treatments were followed an average of 1.01 years. Participants completed the Depression Implicit Association Test (DIAT) - a computer-based measure of SDAs - every 8 weeks on a tablet device. Survival analyses indicated that greater SDAs at baseline and increases in SDAs over time predicted shorter time to MDD recurrence, even after accounting for depressive symptom severity. The findings show that SDAs are a robust prognostic indicator of risk for MDD recurrence, and that the DIAT may be a feasible and low-cost clinical screening tool. SDAs also represent a potential mechanism underlying the course of recurrent depression and are a promising target for relapse prevention interventions., Competing Interests: Declaration of Competing Interest KR, JM, IJT, TC, JF, BNF, KLH, KH, LCQ, and RU disclose no relevant conflict of interests. QSL is an employee of Janssen Research and Development, LLC. RM has received consulting and speaking honoraria from AbbVie, Eisai, Janssen, Lallemand, Lundbeck, Neonmind, and Otsuka, and research grants from CAN-BIND, CIHR, Janssen, Nubiyota, OBI and OMHF. SR has grant funding from Ontario Brain Institute and holds a patent “Teneurin C-Terminal Associated Peptides (TCAP) and methods and uses thereof.” CNS has received consulting honoraria from Eisai, Lundbeck, Otsuka, Diamond Therapeutics and Bayer and research grants from Ontario Brain Institute, SEAMO Innovation Funds and Clairvoyant. SHK has received research funding or honoraria from Abbvie, Abbott, Brain Canada, Boehringer-Ingelheim, Canadian Institutes of Health Research, Janssen, Lundbeck, Lundbeck Institute, Merck, Neurocrine, Ontario Brain Institute, Otsuka, Pfizer, SPOR (Canada's Strategy for Patient-Oriented Research), Sunovion and Servier; and holds stock/stock options in Field Trip Health. RWL has received honoraria for ad hoc speaking or advising/consulting, or received research funds, from Abbvie, Asia-Pacific Economic Cooperation, Bausch, BC Leading Edge Foundation, Brain Canada, Canadian Institutes of Health Research, Canadian Network for Mood and Anxiety Treatments, Healthy Minds Canada, CAN-BIND Solutions, Janssen, Lundbeck, Medscape, Michael Smith Foundation for Health Research, MITACS, Neurotorium, Ontario Brain Institute, Otsuka, Pfizer/Viatris, Unity Health, and VGH-UBCH Foundation., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Quality of life (QoL) is an important patient-centric outcome to evaluate in treatment of major depressive disorder (MDD). This work sought to investigate the performance of several machine learning methods to predict a return to normative QoL in patients with MDD after antidepressant treatment., Methods: Several binary classification algorithms were trained on data from the first 2 weeks of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study (n = 651, conducted from 2001 to 2006) to predict week 9 normative QoL (score ≥ 67, based on a community normative sample, on the Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form [Q-LES-Q-SF]) after treatment with citalopram. Internal validation was performed using a STAR*D holdout dataset, and external validation was performed using the Canadian Biomarker Integration Network in Depression-1 (CAN-BIND-1) dataset (n = 175, study conducted from 2012 to 2017) after treatment with escitalopram. Feature importance was calculated using SHapley Additive exPlanations (SHAP)., Results: Random Forest performed most consistently on internal and external validation, with balanced accuracy (area under the receiver operator curve) of 71% (0.81) on the STAR*D dataset and 69% (0.75) on the CAN-BIND-1 dataset. Random Forest Classifiers trained on Q-LES-Q-SF and Quick Inventory of Depressive Symptomatology-Self-Rated variables had similar performance on both internal and external validation. Important predictive variables came from psychological, physical, and socioeconomic domains., Conclusions: Machine learning can predict normative QoL after antidepressant treatment with similar performance to that of prior work predicting depressive symptom response and remission. These results suggest that QoL outcomes in MDD patients can be predicted with simple patient-rated measures and provide a foundation to further improve performance and demonstrate clinical utility., Trial Registration: ClinicalTrials.gov identifiers NCT00021528 and NCT01655706., (© Copyright 2023 Physicians Postgraduate Press, Inc.)

Major depressive disorder (MDD) is a chronic illness wherein relapses contribute to significant patient morbidity and mortality. Near-term prediction of relapses in MDD patients has the potential to improve outcomes by helping implement a 'predict and preempt' paradigm in clinical care. In this study, we developed a novel personalized (N-of-1) encoder-decoder anomaly detection-based framework of combining anomalies in multivariate actigraphy features (passive) as triggers to utilize an active concurrent self-reported symptomatology questionnaire (core symptoms of depression and anxiety) to predict near-term relapse in MDD. The framework was evaluated on two independent longitudinal observational trials, characterized by regular bimonthly (every other month) in-person clinical assessments, weekly self-reported symptom assessments, and continuous activity monitoring data with two different wearable sensors for ≥ 1 year or until the first relapse episode. This combined passive-active relapse prediction framework achieved a balanced accuracy of ≥ 71%, false alarm rate of ≤ 2.3 alarm/patient/year with a median relapse detection time of 2-3 weeks in advance of clinical onset in both studies. The study results suggest that the proposed personalized N-of-1 prediction framework is generalizable and can help predict a majority of MDD relapses in an actionable time frame with relatively low patient and provider burden., (© 2023. The Author(s).)

Introduction: This study explores the perspectives of workers and managers on workplace programs and interventions that seek to promote mental wellbeing, and prevent and treat mental health conditions The results contributed supporting evidence for the development of the WHO's first global guidelines for mental health and work, which provide evidence-based recommendations to support the implementation of workplace mental health programs and supports, to improve their acceptability, appropriateness, and uptake., Methods: An international online survey was used to examine the values and preferences among workers and managers related to workplace mental health prevention, protection, promotion, and support programs and services. The survey was made available in English, French, and Spanish and recruitment consisted of convenience sampling. Descriptive statistics were used to analyse the survey data. Rapid thematic qualitative analysis was used to analyse the results of open-ended questions., Results: N = 451 responses representing all WHO regions were included in the analysis. These results provide a unique international perspective on programs and supports for mental health at work, from the standpoint of workers and managers. Results suggest that workers value interventions developed in consultation with workers (including indicated, selective and universal interventions), increased training and capacity building among managers, and targeted interventions to address the pervasive impact of stigma on perceptions about mental health at work and help-seeking., Conclusion: The findings of this study seek to reflect the perspectives of workers and their managers, and therein to promote improved access, availability and uptake of mental health programs and supports at work and-ultimately- to support the potential of workplaces as environments that promote and support mental health., Competing Interests: JKM, JN, PAC, GM and AG declared that no competing interests exist. EEM has received funding from Otsuka-Lundbeck for patient educational activities. RWL has received honoraria for ad hoc speaking or advising/consulting, or received research funds, from: Abbvie, Asia-Pacific Economic Cooperation, Bausch, BC Leading Edge Foundation, Brain Canada, Canadian Institutes of Health Research, Canadian Network for Mood and Anxiety Treatments, CAN-BIND Solutions, Carnot, Grand Challenges Canada, Healthy Minds Canada, Janssen, Lundbeck, Medscape, Michael Smith Foundation for Health Research, MITACS, Neurotorium, Ontario Brain Institute, Otsuka, Pfizer/Viatris, Shanghai Mental Health Center, Sunnybrook Health Sciences Centre, Unity Health, Vancouver Coastal Health Research Institute, and VGH-UBCH Foundation. This does not alter our adherence to PLOS ONE policies on sharing data and materials, (Copyright: © 2023 Murphy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Monitoring sleep and activity through wearable devices such as wrist-worn actigraphs has the potential for long-term measurement in the individual's own environment. Long periods of data collection require a complex approach, including standardized pre-processing and data trimming, and robust algorithms to address non-wear and missing data. In this study, we used a data-driven approach to quality control, pre-processing and analysis of longitudinal actigraphy data collected over the course of 1 year in a sample of 95 participants. We implemented a data processing pipeline using open-source packages for longitudinal data thereby providing a framework for treating missing data patterns, non-wear scoring, sleep/wake scoring, and conducted a sensitivity analysis to demonstrate the impact of non-wear and missing data on the relationship between sleep variables and depressive symptoms. Compliance with actigraph wear decreased over time, with missing data proportion increasing from a mean of 4.8% in the first week to 23.6% at the end of the 12 months of data collection. Sensitivity analyses demonstrated the importance of defining a pre-processing threshold, as it substantially impacts the predictive value of variables on sleep-related outcomes. We developed a novel non-wear algorithm which outperformed several other algorithms and a capacitive wear sensor in quality control. These findings provide essential insight informing study design in digital health research., (© 2023. Springer Nature Limited.)

The COVID-19 pandemic has amplified mental health problems and highlighted inequitable gaps in care worldwide. In response there has been an explosion of digital interventions such as smartphone applications ("apps") to extend care. The objective of this trial is to evaluate the effectiveness and cost-effectiveness of a digital depression intervention (VMood), delivered via a smartphone app. VMood is adapted from an in-person intervention that was delivered by non-specialist providers and shown to be effective in the Vietnamese context in our previous trial (2016-2019). A stepped-wedge, randomized controlled trial will be conducted across eight provinces in Vietnam. Adults aged 18 years and over will be recruited through community-based primary care centres and screened for depression using the embedded Patient Health Questionnaire-9 (primary outcome measure). Participants scoring 10-19, indicating depression caseness, will be randomly allocated to the intervention or control group until the target of 336 is reached. Secondary outcome measures will examine the effect of the intervention on commonly co-occuring anxiety, quality of life and work productivity, along with use of alcohol and tobacco products. Assessments will be administered through an online survey platform (REDCap) at baseline, and at every 3 months until 3 months post-intervention. Intervention-group participants will receive VMood for a 3-month period, with online support provided by social workers. Control-group participants will receive a limited version of the app until they cross into the intervention group. Generalized Linear Mixed-effect Models for clustered measures will be used for all outcomes data. We will conduct a cost-effectiveness analysis alongside the trial to capture VMood's costs and benefits. This trial will provide evidence on the effectiveness and cost-effectiveness of a digital mental health intervention adapted from an in-person intervention. This trial will also contribute important information to the growing and promising field of digital mental health. Trail regulation. Registered at ClinicalTrials.gov, identifier [NCT05783531]., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Chau et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Importance: Untreated depression is a growing public health concern, with patients often facing a prolonged trial-and-error process in search of effective treatment. Developing a predictive model for treatment response in clinical practice remains challenging., Objective: To establish a model based on electroencephalography (EEG) to predict response to 2 distinct selective serotonin reuptake inhibitor (SSRI) medications., Design, Setting, and Participants: This prognostic study developed a predictive model using EEG data collected between 2011 and 2017 from 2 independent cohorts of participants with depression: 1 from the first Canadian Biomarker Integration Network in Depression (CAN-BIND) group and the other from the Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) consortium. Eligible participants included those aged 18 to 65 years who had a diagnosis of major depressive disorder. Data were analyzed from January to December 2022., Exposures: In an open-label trial, CAN-BIND participants received an 8-week treatment regimen of escitalopram treatment (10-20 mg), and EMBARC participants were randomized in a double-blind trial to receive an 8-week sertraline (50-200 mg) treatment or placebo treatment., Main Outcomes and Measures: The model's performance was estimated using balanced accuracy, specificity, and sensitivity metrics. The model used data from the CAN-BIND cohort for internal validation, and data from the treatment group of the EMBARC cohort for external validation. At week 8, response to treatment was defined as a 50% or greater reduction in the primary, clinician-rated scale of depression severity., Results: The CAN-BIND cohort included 125 participants (mean [SD] age, 36.4 [13.0] years; 78 [62.4%] women), and the EMBARC sertraline treatment group included 105 participants (mean [SD] age, 38.4 [13.8] years; 72 [68.6%] women). The model achieved a balanced accuracy of 64.2% (95% CI, 55.8%-72.6%), sensitivity of 66.1% (95% CI, 53.7%-78.5%), and specificity of 62.3% (95% CI, 50.1%-73.8%) during internal validation with CAN-BIND. During external validation with EMBARC, the model achieved a balanced accuracy of 63.7% (95% CI, 54.5%-72.8%), sensitivity of 58.8% (95% CI, 45.3%-72.3%), and specificity of 68.5% (95% CI, 56.1%-80.9%). Additionally, the balanced accuracy for the EMBARC placebo group (118 participants) was 48.7% (95% CI, 39.3%-58.0%), the sensitivity was 50.0% (95% CI, 35.2%-64.8%), and the specificity was 47.3% (95% CI, 35.9%-58.7%), suggesting the model's specificity in predicting SSRIs treatment response., Conclusions and Relevance: In this prognostic study, an EEG-based model was developed and validated in 2 independent cohorts. The model showed promising accuracy in predicting treatment response to 2 distinct SSRIs, suggesting potential applications for personalized depression treatment.

Depression is a leading global cause of disability, yet about half of patients do not respond to initial antidepressant treatment. This treatment difficulty may be in part due to the heterogeneity of depression and corresponding response to treatment. Unsupervised machine learning allows underlying patterns to be uncovered, and can be used to understand this heterogeneity by finding groups of patients with similar response trajectories. Prior studies attempting this have clustered patients using a narrow range of data primarily from depression scales. In this work, we used unsupervised machine learning to cluster patients receiving escitalopram therapy using a wide variety of subjective and objective clinical features from the first eight weeks of the Canadian Biomarker Integration Network in Depression-1 trial. We investigated how these clusters responded to treatment by comparing changes in symptoms and symptom categories, and by using Principal Component Analysis (PCA). Our algorithm found three clusters, which broadly represented non-responders, responders, and remitters. Most categories of features followed this response pattern except for objective cognitive features. Using PCA with our clusters, we found that subjective mood state/anhedonia is the core feature of response with escitalopram, but there exists other distinct patterns of response around neurovegetative symptoms, activation, and cognition., Competing Interests: Declaration of Competing Interest RVM has received consulting and speaking honoraria from AbbVie, Allergan, Eisai, Janssen, KYE, Lallemand, Lundbeck, Otsuka, and Sunovion, and research grants from CAN-BIND, CIHR, Janssen, Lallemand, Lundbeck, Nubiyota, OBI and OMHF. SR holds a patent “Teneurin C-Terminal Associated Peptides (TCAP) and methods and uses thereof. SHK has received research funding or honoraria from the following sources: Abbott, Alkermes, Allergan Abbvie, Brain Canada, Canadian Institutes for Health Research, Janssen, Lundbeck, Lundbeck Institute, Ontario Brain Institute, Ontario Research Fund, Otsuka, Pfizer, Servier, Sunovion and Xian-Janssen and holds stock in Field Trip Health. RWL has received honoraria for ad hoc speaking or advising/consulting, or received research funds, from: Abbvie, Asia-Pacific Economic Cooperation, Bausch, BC Leading Edge Foundation, Brain Canada, Canadian Institutes of Health Research, Canadian Network for Mood and Anxiety Treatments, CAN-BIND Solutions, Carnot, Grand Challenges Canada, Healthy Minds Canada, Janssen, Lundbeck, Medscape, Michael Smith Foundation for Health Research, MITACS, Neurotorium, Ontario Brain Institute, Otsuka, Pfizer/Viatris, Shanghai Mental Health Center, Sunnybrook Health Sciences centre, Unity Health, Vancouver Coastal Health Research Institute, and VGH-UBCH Foundation. JJN received unrestricted research funding from the BC Cancer Foundation, with funds originating from Pfizer. CNS has received consulting honoraria from Eisai, Lundbeck, Otsuka, Diamond Therapeutics and Bayer and research grants from Ontario Brain Institute, SEAMO Innovation Funds and Clairvoyant; VHT has received consulting honoraria from Abbvie and research grants from Ontario Brain Institute, MITACS, Brain Canada, Canadian Institute of Health Research. YSL, BC, BNF, DJM, and RU have no disclosures., (Copyright © 2023. Published by Elsevier B.V.)

Background: Prediction of treatment outcomes is a key step in improving the treatment of major depressive disorder (MDD). The Canadian Biomarker Integration Network in Depression (CAN-BIND) aims to predict antidepressant treatment outcomes through analyses of clinical assessment, neuroimaging, and blood biomarkers., Methods: In the CAN-BIND-1 dataset of 192 adults with MDD and outcomes of treatment with escitalopram, we applied machine learning models in a nested cross-validation framework. Across 210 analyses, we examined combinations of predictive variables from three modalities, measured at baseline and after 2 weeks of treatment, and five machine learning methods with and without feature selection. To optimize the predictors-to-observations ratio, we followed a tiered approach with 134 and 1152 variables in tier 1 and tier 2 respectively., Results: A combination of baseline tier 1 clinical, neuroimaging, and molecular variables predicted response with a mean balanced accuracy of 0.57 (best model mean 0.62) compared to 0.54 (best model mean 0.61) in single modality models. Adding week 2 predictors improved the prediction of response to a mean balanced accuracy of 0.59 (best model mean 0.66). Adding tier 2 features did not improve prediction., Conclusions: A combination of clinical, neuroimaging, and molecular data improves the prediction of treatment outcomes over single modality measurement. The addition of measurements from the early stages of treatment adds precision. Present results are limited by lack of external validation. To achieve clinically meaningful prediction, the multimodal measurement should be scaled up to larger samples and the robustness of prediction tested in an external validation dataset.

Background: Antidepressants are used to treat acute depression in patients with bipolar I disorder, but their effect as maintenance treatment after the remission of depression has not been well studied., Methods: We conducted a multisite, double-blind, randomized, placebo-controlled trial of maintenance of treatment with adjunctive escitalopram or bupropion XL as compared with discontinuation of antidepressant therapy in patients with bipolar I disorder who had recently had remission of a depressive episode. Patients were randomly assigned in a 1:1 ratio to continue treatment with antidepressants for 52 weeks after remission or to switch to placebo at 8 weeks. The primary outcome, assessed in a time-to-event analysis, was any mood episode, as defined by scores on scales measuring symptoms of hypomania or mania, depression, suicidality, and mood-episode severity; additional treatment or hospitalization for mood symptoms; or attempted or completed suicide. Key secondary outcomes included the time to an episode of mania or hypomania or depression., Results: Of 209 patients with bipolar I disorder who participated in an open-label treatment phase, 150 who had remission of depression were enrolled in the double-blind phase in addition to 27 patients who were enrolled directly. A total of 90 patients were assigned to continue treatment with the prescribed antidepressant for 52 weeks (52-week group) and 87 were assigned to switch to placebo at 8 weeks (8-week group). The trial was stopped before full recruitment was reached owing to slow recruitment and funding limitations. At 52 weeks, 28 of the patients in the 52-week group (31%) and 40 in the 8-week group (46%) had a primary-outcome event. The hazard ratio for time to any mood episode in the 52-week group relative to the 8-week group was 0.68 (95% confidence interval [CI], 0.43 to 1.10; P = 0.12 by log-rank test). A total of 11 patients in the 52-week group (12%) as compared with 5 patients in the 8-week group (6%) had mania or hypomania (hazard ratio, 2.28; 95% CI, 0.86 to 6.08), and 15 patients (17%) as compared with 35 patients (40%) had recurrence of depression (hazard ratio, 0.43; 95% CI, 0.25 to 0.75). The incidence of adverse events was similar in the two groups., Conclusions: In a trial involving patients with bipolar I disorder and a recently remitted depressive episode, adjunctive treatment with escitalopram or bupropion XL that continued for 52 weeks did not show a significant benefit as compared with treatment for 8 weeks in preventing relapse of any mood episode. The trial was stopped early owing to slow recruitment and funding limitations. (Funded by the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00958633.)., (Copyright © 2023 Massachusetts Medical Society.)

Objective: Childhood maltreatment is a potent enviromarker of risk for poor response to antidepressant medication (ADM). However, childhood maltreatment is a heterogeneous construct that includes distinct exposures that have distinct neurobiological and psychological correlates. The purpose of the current study is to examine the differential associations of emotional, physical, and sexual maltreatment to ADM outcome and to examine the unique role of anhedonia in driving poor response in patients with specific maltreatment histories., Methods: In a multicentre clinical trial of major depression, 164 individuals were assessed for childhood emotional, physical, and sexual maltreatment with a contextual interview with independent, standardized ratings. All individuals received 8 weeks of escitalopram, with nonresponders subsequently also receiving augmentation with aripiprazole, with outcomes measured with depression rating scales and an anhedonia scale., Results: Greater severity of emotional maltreatment perpetrated by the mother was a significant and direct predictor of lower odds of week 16 remission (odds ratio [OR] = 1.68, P  = 0.02). In contrast, the relations of paternal-perpetrated emotional maltreatment and physical maltreatment to week 16 remission were indirect, mediated through greater severity of anhedonia at week 8., Conclusions: We identify emotional maltreatment as a specific early exposure that places patients at the greatest risk for nonremission following pharmacological treatment. Further, we suggest that anhedonia is a key symptom domain driving nonremission in patients with particular maltreatment histories.