•Short-term efficacy of IV and IN ketamine/esketamine is established for TRD.•Interpretation the efficacy of oral ketamine in TRD is limited.•Insufficient data on disparate formulations and routes of ...delivery of ketamine.
Ketamine is established as a rapid and effective treatment in adults with treatment-resistant depression (TRD). The availability of different formulations and routes of delivery invites the need for evaluating relative effect sizes.
Effect size with respect to depression symptom reduction for each formulation and route of delivery was compared at discrete time-points (i.e., 24 h, 2–6 days, 7–20 days, 21–28 days) in adults with TRD. A random-effects meta-analysis was conducted to evaluate the effect size across intravenous, intranasal and oral routes of administration. Analysis was also conducted evaluating the effect size of racemic ketamine to esketamine.
The pooled effect size for intranasal ketamine/esketamine at 24 h was g = 1.247 (n = 5, 95% CI: 0.591–1.903, p < 0.01). At 2–6 days, the pooled effect size for intravenous ketamine/esketamine was g = 0.949 (n = 14, 95% CI: −0.308–2.206, p = 0.139). At 7–20 days, intranasal ketamine had a pooled effect size of g = 1.018 (n = 4, 95% CI: 0.499–1.538, p < 0.01). At 21–28 days, oral ketamine had a pooled effect size of g = 0.633 (n = 2, 95% CI: 0.368–0.898, p < 0.01).
Additional comparative studies are needed with regards to the efficacy of different formulations and routes of delivery.
The short-term efficacy of intravenous and intranasal ketamine/esketamine for adults with TRD was established. Interpreting the efficacy of oral ketamine was limited by the need for studies with larger samples across independent sites. No conclusions regarding comparative efficacy of the disparate formulations and routes of delivery can be derived from this analysis. Direct comparative studies are needed to further inform treatment options for TRD.
•Loneliness has been associated with adverse health outcomes, but few studies have evaluated its comparative effects on distinct health outcomes.•A scoping review reveals medium to large effects of ...loneliness on all health outcomes, with the largest effects on mental health outcomes and overall well-being.•Healthcare providers should be adequately trained to perceive and respond to loneliness due to its strong associations with adverse health outcomes.
The primary objective was to evaluate the comparative effects of loneliness on multiple distinct health outcomes. The literature was qualitatively reviewed to identify loneliness risk factors, explore mechanisms, and discuss potential evidence-based interventions for targeting loneliness. 114 identified studies were systematically reviewed and analyzed to examine for associations between loneliness (as measured by the UCLA Loneliness or de Jong Gierveld Loneliness Scales) and one or more health outcome(s). Health outcomes were broadly defined to include measures of mental health (i.e., depression, anxiety, suicidality, general mental health), general health (i.e., overall self-rated health), well-being (i.e., quality of life, life satisfaction), physical health (i.e., functional disability), sleep, and cognition. Loneliness had medium to large effects on all health outcomes, with the largest effects on mental health and overall well-being; however, this result may have been confounded by the breadth of studies exploring the association between loneliness and mental health, as opposed to other health outcomes. A significant effect of gender on the association between loneliness and cognition (i.e., more pronounced in studies with a greater proportion of males) was also observed. The adequate training of health care providers to perceive and respond to loneliness among patients should be prioritized.
•Longer screen time aggravated adolescents’ depressive symptoms•More time spent with screen-device was associated with shorter sleep duration•Screen time aggravated depressive symptoms partially by ...shortening sleep duration
Relatively few studies have explored the inter-relationship between screen time (ST), sleep duration and depressive symptoms. The study herein sought to determine (1) the relationships between ST, sleep duration and depressive symptoms among Chinese adolescents; (2) whether sleep duration mediates the relationships between ST and depressive symptoms.
1st grade students (n=1,976) from ten high schools in Guangzhou, China were invited through cluster sampling between January and April 2019. Self-reported ST with electronic devices and Internet, sleep duration, and The Center for Epidemiology Scale for Depression (CES-D) score were collected. Generalized mixed linear models and mediation analyses were conducted.
There were 1,956 self-reported questionnaires received (response rate: 98.99%). Approximately 25% (471/1,929 for Internet use, 399/1,928 for electronic device) of the total sample reported ST >2 hours/day. Approximately 8.9% (169/1,894) reported a CES-D score >28. Longer ST with electronic devices (estimate=0.52, 95%CI: 0.24~0.80), Internet usage (estimate=0.82, 95%CI: 0.53~1.11) were positively associated with depressive symptoms, while less sleep (estimate=-1.85, 95%CI: -2.27~-1.43) was negatively associated with depressive symptoms. There is significant indirect effect of electronic device usage on depressive symptoms through sleep duration (indirect effect=0.08, 95%CI: 0.01~0.15).
This study only included school students from Guangzhou. Causal relationship cannot be inferred by this cross-sectional design.
ST and sleep duration were significantly associated with depressive symptoms severity. The indirect effect of sleep duration suggests a possible mechanism of the association between ST and depressive symptoms. Future interventions to manage depressive symptoms should target sleep time and decrease ST among adolescents.
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•Mood disorders involve disturbances in reward and cognitive functions.•TAAR1 mutations correlate with such disturbances in humans and rodents.•TAAR1 agonists alleviate reward and ...cognitive symptoms in animals and schizophrenics.•TAAR1 agonists seem to enhance limbic ion-homeostasis, neuroplasticity, and metabolism.•TAAR1 agonists may be therapeutic in mood disorders by improving cognitive control.
There is a need for innovation with respect to therapeutics in psychiatry. Available evidence indicates that the trace amine-associated receptor 1 (TAAR1) agonist SEP-363856 is promising, as it improves measures of cognitive and reward function in schizophrenia. Hedonic and cognitive impairments are transdiagnostic and constitute major burdens in mood disorders. Herein, we systematically review the behavioural and genetic literature documenting the role of TAAR1 in reward and cognitive function, and propose a mechanistic model of TAAR1’s functions in the brain. Notably, TAAR1 activity confers antidepressant-like effects, enhances attention and response inhibition, and reduces compulsive reward seeking without impairing normal function. Further characterization of the responsible mechanisms suggests ion-homeostatic, metabolic, neurotrophic, and anti-inflammatory enhancements in the limbic system. Multiple lines of evidence establish the viability of TAAR1 as a biological target for the treatment of mood disorders. Furthermore, the evidence suggests a role for TAAR1 in reward and cognitive function, which is attributed to a cascade of events that are relevant to the cellular integrity and function of the central nervous system.
The COVID-19 pandemic has resulted in a predominantly global quarantine response that has been associated with social isolation, loneliness, and anxiety. The foregoing experiences have been amply ...documented to have profound impacts on health, morbidity, and mortality. This narrative review uses the extant neurobiological and theoretical literature to explore the association between social isolation, loneliness, and anxiety in the context of quarantine during the COVID-19 pandemic. Emerging evidence suggests that distinct health issues (e.g., a sedentary lifestyle, a diminished overall sense of well-being) are associated with social isolation and loneliness. The health implications of social isolation and loneliness during quarantine have a heterogenous and comorbid nature and, as a result, form a link to anxiety. The limbic system plays a role in fear and anxiety response; the bed nucleus of the stria terminalis, amygdala, HPA axis, hippocampus, prefrontal cortex, insula, and locus coeruleus have an impact in a prolonged anxious state. In the conclusion, possible solutions are considered and remarks are made on future areas of exploration.
•Mood disorders are associated with an increased prevalence of irritable bowel syndrome (IBS) and history of adverse childhood experiences (ACEs)•In total, 69 of the 498 mood disorder participants ...reported a diagnosis of IBS (13.8%)•BD was associated with elevated rates of IBS compared to MDD•History of childhood sexual abuse was associated with increased rates of IBS in mood disorder participants•In the subgroups, history of sexual abuse was associated with an increased prevalence of IBS in BD, but not in MDD.
The objective of the current study was to assess the association between adverse childhood experiences (ACEs) and irritable bowel syndrome (IBS) in mood disorder patients. Self-report data from the International Mood Disorders Collaborative Project were cross-sectionally analyzed to compare rates of IBS in participants with confirmed diagnoses of major depressive disorder (MDD; n = 279) or bipolar disorder (BD; n = 219). Data was sub-grouped and compared based on history of ACEs. In total, 69 of the 498 participants reported a diagnosis of IBS (13.8%). BD was associated with significantly elevated rates of IBS compared to MDD (18.5% versus 10.1% respectively). After adjusting for age and sex, history of childhood sexual abuse was associated with increased rates of IBS in mood disorder participants adjusted odds ratio (aOR) = 1.95. In the MDD subgroup, ACEs (all categories and individual categories) were not associated with increased rates of IBS. In the BD subgroup, history of childhood sexual abuse was associated with significantly increased rates of IBS (38% versus 14%; aOR = 3.7). In summary, BD was associated with a higher prevalence of IBS compared to MDD. Additionally, history of sexual abuse was associated with an increased prevalence of IBS in BD, but not in MDD.
Purpose of Review
This paper aims to provide a succinct and narrative review of key developments in the diagnostic criteria, neurobiology, and treatment of bipolar disorder (BD).
Recent Findings
...Depressive symptoms/episodes and cognitive dysfunction are critical mediators of human capital, quality of life, and wellness in persons with BD. Significant advances in tolerability and incremental advances in efficacy exist with antimanic agents. Bipolar depression treatment options remain suboptimal with relatively few being metabolically neutral. In silico modeling and advanced computational methods provide promise to further illuminate the neurobiology of BD and identify novel disease modifying therapies.
Summary
Optimal outcomes in BD depend on careful comprehensive assessment, timely accurate diagnosis, with attention to treating and preventing depressive symptoms, cognitive deficits, psychosocial impairment, comorbidity, and suicidality. Attention to wellness is underemphasized in BD and should be contemporaneous with symptom mitigation strategies.
•The reward system is an influencing factor in the loneliness-depression pathway•Brain inflammation leads to insulin resistance, which impairs the reward system•‘Reward’ depression presents comorbid ...symptoms (with other mental disorders)•Early childhood factors play a role in the formulation of an impaired reward system•Consecutive losses will trigger similar defensive response from earlier childhood
Loneliness is a key determinant in the etiology of mental health disorders such as depression and has profound impacts on health, quality of life, and economic productivity. This narrative review uses extant neurobiology and evolutionary literature to propose a construct through which loneliness may induce depression in adulthood via the reward system (including symptom and treatment aspects). Early childhood (distal) factors were found to be important in influencing adult (proximal) factors, which lead to the formulation of the construct. Due to the heterogenous and comorbid nature of depression, a new subtype known as 'reward depression' was distinguished along with distinct symptoms to aid practitioners when assessing patient treatment options. Furthermore, an evolutionary perspective was applied to the current impaired reward construct to discuss how the ancestral purpose and environment (in terms of reward) clashes with the modern one. Finally, theoretical treatment and prevention ideas were examined and discussed, leading into future work that needs to build upon and confirm the outlined construct.
To evaluate the development and implementation of clinical practice guidelines for the management of depression globally.
We conducted a systematic review of existing guidelines for the management of ...depression in adults with major depressive or bipolar disorder. For each identified guideline, we assessed compliance with measures of guideline development quality (such as transparency in guideline development processes and funding, multidisciplinary author group composition, systematic review of comparative efficacy research) and implementation (such as quality indicators). We compared guidelines from low- and middle-income countries with those from high-income countries.
We identified 82 national and 13 international clinical practice guidelines from 83 countries in 27 languages. Guideline development processes and funding sources were explicitly specified in a smaller proportion of guidelines from low- and middle-income countries (8/29; 28%) relative to high-income countries (35/58; 60%). Fewer guidelines (2/29; 7%) from low- and middle-income countries, relative to high-income countries (22/58; 38%), were authored by a multidisciplinary development group. A systematic review of comparative effectiveness was conducted in 31% (9/29) of low- and middle-income country guidelines versus 71% (41/58) of high-income country guidelines. Only 10% (3/29) of low- and middle-income country and 19% (11/58) of high-income country guidelines described plans to assess quality indicators or recommendation adherence.
Globally, guideline implementation is inadequately planned, reported and measured. Narrowing disparities in the development and implementation of guidelines in low- and middle-income countries is a priority. Future guidelines should present strategies to implement recommendations and measure feasibility, cost-effectiveness and impact on health outcomes.
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