Prevalence of post-traumatic stress disorder and depressive symptoms among civilians residing in armed conflict-affected regions: a systematic review and meta-analysis.

Background: Globally, populations afflicted by armed conflict are known to have high rates of mental health disorders. Aims: This meta-analysis aims to estimate the prevalence of post-traumatic stress disorder (PTSD) and depressive symptoms among civilians residing in armed conflict-affected regions. Methods: This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. A literature search employing MEDLINE(R), Embase Classic+Embase, APA PsycINFO, Ovid Healthstar, Journal@Ovid Full Text, Cochrane, PTSDpubs and CINAHL was conducted from inception until 19 March 2024 to identify relevant studies. Quality assessment was performed using the Joanna Briggs Institute Critical Appraisal Checklist for Prevalence Studies, and a Comprehensive Meta-Analysis was used to conduct the statistical analysis. Results: The search yielded 38 595 articles, of which 57 were considered eligible for inclusion. The included studies comprised data from 64 596 participants. We estimated a prevalence of 23.70% (95% CI 19.50% to 28.40%) for PTSD symptoms and 25.60% (95% CI 20.70% to 31.10%) for depressive features among war-afflicted civilians. The subgroup analysis based on time since the war and the country's economic status revealed the highest prevalence for both PTSD and depressive symptoms was present during the years of war and in low/middle-income countries. Conclusions: The results of this study provide conclusive evidence of the detrimental impacts of armed conflict on mental health outcomes. Hence, it is crucial to emphasise the significance of both physical and mental health in the aftermath of war and take appropriate humanistic measures to overcome challenges in the management of psychiatric illnesses. PROSPERO registration number: CRD42023416096.

Efficacy, safety, and tolerability of xanomeline for schizophrenia spectrum disorders: a systematic review.

INTRODUCTION: We systematically reviewed extant studies evaluating the efficacy and tolerability of xanomeline and xanomeline-trospium (KarXT) for treatment of adults with schizophrenia. METHODS: In accordance with PRISMA guidelines, articles were systematically searched for in databases and clinical trial registries. RESULTS: A total of 4 preclinical trials and 3 randomized controlled trials (RCTs) were included in this review. A 4-week RCT observed a difference of 24.0 points (SD 21.0) in the Positive and Negative Syndrome Scale (PANSS) total score between xanomeline and placebo groups (p = 0.039). A 5-week RCT observed PANSS total score changes from baseline to week 5, including -17.4 and -5.9 points in KarXT and placebo groups, respectively (LSMD -11.6 points; 95% CI -16.1 to -7.1; p < 0.001; d = 0.75). Another 5-week RCT observed PANSS total score changes from baseline to week 5, including -21.2 (SE 1.7) and -11.6 (SE 1.6) points in KarXT and placebo groups, respectively (LSMD -9.6; 95% CI -13.9 to -5.2; p < 0.0001; d = 0.61). Side effects include constipation, nausea, vomiting, dyspepsia, and dry mouth. CONCLUSION: KarXT offers an innovative non-D2 blocking approach, representing a promising treatment avenue for schizophrenia.

Psychological impact of the COVID-19 pandemic in children with autism spectrum disorder - a literature review.

Objective: This review summarizes evidence pertaining to the impact of the COVID-19 pandemic on the psychological health of children and adolescents with autism spectrum disorder (ASD). Materials and Methods: An electronic search was conducted using four major databases: PubMed, ScienceDirect, Web of Science, and Google Scholar. Using an umbrella methodology, the reference lists of relevant papers were reviewed, and citation searches were conducted. The study included articles written in English between January 2020 and March 2021 that focused on the psychological health of autistic children and adolescents. Results: All eight studies included in the final review were cross-sectional. Three of the eight studies were conducted in Italy, two in Turkey, and one study each in Portugal, Spain, and the United Kingdom, with a total of 1,407 participants. All studies used a mixture of standardized and non-standardized questionnaires to collect data. The total number of patients were 1407 at a mean age of 9.53 (SD = 2.96) years. Seven studies report gender; male 74.7% (657/880) and female 25.3% (223/880). The finding showed that behavioral issues in children and adolescents with ASD have significantly increased; 521 (51.9 percent) of the 1004 individuals with ASD presented with behavioral changes, including conduct problems, emotional problems, aggression, and hyperactivity. Some studies also found increased anxiety and difficulties managing emotions. Only one study reported clinical stabilization in children with ASD during COVID-19. Finally, 82.7% of families and caregivers of children with ASD (544 out of 658) faced challenges during COVID-19. Conclusion: Although the studies in this review suggest a general worsening of ASD children's clinical status, it remains difficult to draw definitive conclusions at this moment, with newer COVID-19 variants on the rise worldwide. During this difficult pandemic period, caregivers, families, and healthcare professionals are recommended to pay more attention to the ASD patients' health and care needs.

Association of SARS-CoV-2 infection with neurological impairments in pediatric population: A systematic review.

Neurological manifestations have been widely reported in adults with COVID-19, yet the extent of involvement among the pediatric population is currently poorly characterized. The objective of our systematic review is to evaluate the association of SARS-CoV-2 infection with neurological symptoms and neuroimaging manifestations in the pediatric population. A literature search of Cochrane Library; EBSCO CINAHL; Global Index Medicus; OVID AMED, Embase, Medline, PsychINFO; and Scopus was conducted in accordance with the Peer Review of Electronic Search Strategies form (October 1, 2019 to March 15, 2022). Studies were included if they reported (1) COVID-19-associated neurological symptoms and neuroimaging manifestations in individuals aged <18 years with a confirmed, first SARS-CoV-2 infection and were (2) peer-reviewed. Full-text reviews of 222 retrieved articles were performed, along with subsequent reference searches. A total of 843 no-duplicate records were retrieved. Of the 19 identified studies, there were ten retrospective observational studies, seven case series, one case report, and one prospective cohort study. A total of 6985 individuals were included, where 12.8% (n = 892) of hospitalized patients experienced neurocognitive impairments which includes: 1) neurological symptoms (n = 294 of 892, 33.0%), 2) neurological syndromes and neuroimaging abnormalities (n = 223 of 892, 25.0%), and 3) other phenomena (n = 233 of 892, 26.1%). Based on pediatric-specific cohorts, children experienced more drowsiness (7.3% vs. 1.3%) and muscle weakness (7.3% vs. 6.3%) as opposed to adolescents. Agitation or irritability was observed more in children (7.3%) than infants (1.3%). Our findings revealed a high prevalence of immune-mediated patterns of disease among COVID-19 positive pediatric patients with neurocognitive abnormalities.

The Effect of Internet-Based Cognitive Behavioral Therapy on Major Depressive Disorder: Randomized Controlled Trial.

BACKGROUND: Many people living with major depressive disorder (MDD) in China do not receive treatment owing to a lack of mental health services, along with significant stigma toward mental illness. Internet-based cognitive behavioral therapy (ICBT) has been proposed to increase access to mental health care for people with MDD. OBJECTIVE: The aims of this study were to (1) evaluate the efficacy of ICBT for depressive symptoms in patients with MDD; (2) evaluate the effect of ICBT on anxiety symptoms, nonspecific psychological distress, general self-efficacy, depression stigma, social function, and health-related quality of life (HRQoL); and (3) explore the acceptability of and satisfaction with the ICBT program among participants. METHODS: Patients with MDD were enrolled and randomized to the ICBT group or the waiting-list control (WLC) group. The ICBT group received ICBT delivered through a WeChat mini-program with general support by nonspecialists. Participants in the 2 groups were self-evaluated online at baseline and posttreatment for changes in the primary outcome (ie, depressive symptoms) and secondary outcomes (ie, anxiety symptoms, nonspecific psychological distress, general self-efficacy, depression stigma, social functional impairment, and HRQoL). Changes in outcomes were measured by changes in overall scores on respective scales, and response and remission rates were calculated based on depressive symptoms. The acceptability of and satisfaction with the ICBT program were measured by treatment adherence and participants' feelings (ie, modules seriously completed, perceived benefit, and satisfaction). RESULTS: We included 40 patients who were randomly assigned to the ICBT group and 44 who were assigned to the WLC group. Compared with the WLC group, the ICBT group had fewer depressive symptoms, fewer anxiety symptoms, less nonspecific psychological distress, and greater general self-efficacy. Moreover, the ICBT group had higher response (18/31, 58%) and remission rates (17/31, 55%). The adherence rate in the ICBT group was 78% (31/40), and the majority of participants who completed all ICBT modules were satisfied with the ICBT program. CONCLUSIONS: ICBT demonstrated greater improvements in depressive symptoms, anxiety symptoms, nonspecific psychological distress, and general self-efficacy among selected patients with MDD in comparison with the findings in waiting-list controls. The ICBT program in this study had good acceptability and satisfaction among participants. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2100046425); https://tinyurl.com/bdcrj4zv.

Beyond physical health: the role of psychosocial challenges and stigma in tackling the COVID-19 pandemic-A scoping review.

Background: The socio-cultural response to the Coronavirus Disease 2019 (COVID-19) and the level of adherence to evidence-based guidelines played a crucial role in determining the morbidity and mortality outcomes during the pandemic. This review aims to evaluate the impact of stigma and psycho-socio-cultural challenges on efforts to control the COVID-19 pandemic and to identify ways to mitigate such challenges in future pandemics. Methods: Using keywords including COVID-19, coronavirus, stigma, psychosocial challenges, and others, the authors searched seven major databases with a time limitation of July 2021, which yielded 2,038 results. Out of these, 15 papers were included in this review. Results: The findings of the review indicated that several psychosocial, socio-economic, and ethno-cultural factors are linked to the transmission and control of COVID-19. The research revealed that stigma and related psychosocial challenges and others, such as anxiety, fear, and stigma-driven social isolation, have resulted in significant mental health problems. Discussion: The review underscores the negative impact of stigma on COVID-19 patients, survivors, and the general population. Addressing stigma and psychosocial challenges is crucial to effectively manage the current pandemic and to prevent similar challenges during future public health crises.

The Role of Ketamine in the Treatment of Bipolar Depression: A Scoping Review.

Bipolar depression remains a clinical challenge with a quarter of patients failing to respond to initial conventional treatments. Although ketamine has been extensively studied in unipolar depression, its role in bipolar disorder remains inconclusive. The aim of our scoping review was to comprehensively synthesize the current clinical literature around ketamine use in bipolar depression. A total of 10 clinical studies (5 randomized controlled trials and 5 open label studies) were selected. The preliminary evidence, albeit weak, suggests that ketamine is a promising treatment and calls for further interest from the research community. Overall, ketamine treatment appeared to be tolerable with minimal risk for manic/hypomanic switching and showed some effectiveness across parameters of depression and suicidality. Moreover, ketamine is a potential treatment agent in patients with treatment-resistant bipolar depression with promising data extracted from extant controlled trials and real-world effectiveness studies. Future studies are needed to identify ketamine's role in acute and maintenance treatment phases of bipolar depression. Moreover, future researchers should study the recurrence prevention and anti-suicidal effects of ketamine in the treatment of bipolar depression.

Glucagon-like peptide 1 (GLP-1) receptor agonists as a protective factor for incident depression in patients with diabetes mellitus: A systematic review.

Glucagon-like peptide 1 (GLP-1) receptor agonists are widely used for glycemic control in patients with diabetes mellitus (DM) and are primarily indicated for type 2 diabetes mellitus (T2DM). GLP-1 receptor agonists have also been shown to have neuroprotective and antidepressant properties. Replicated evidence suggests that individuals with DM are significantly more likely to develop depression. Herein, we aim to investigate whether GLP-1 receptor agonists can be used prophylactically on patients with DM to lower the risk of incident depression. We conducted a systematic search for English-language articles published on the PubMed/MEDLINE, Scopus, Embase, APA, PsycInfo, Ovid and Google Scholar databases from inception to June 6, 2022. Four retrospective observational studies were identified that evaluated the neuroprotective effects of GLP-1 receptor agonists on incident depression in patients with DM. We found mixed results with regards to lowering the risk of incident depression, with two studies demonstrating a significant reduction in risk and two studies showing no such effect. A single study found that dulaglutide may lower susceptibility to depression. Our results were limited by high interstudy heterogeneity, paucity of literature, and lack of controlled trials. While we did not find evidence of GLP-1 receptor agonists significantly lowering risk of incident depression in patients with DM, promising neuroprotective data presented in two of the included papers, specifically on dulaglutide where information is scarce, provide the impetus for further investigation. Future research should focus on better elucidating the neuroprotective potential of different classes and doses of GLP-1 receptor agonists using controlled trials.

Neurobiological Correlates of Psilocybin Response in Depression.

Objective: To synthesize the neurobiological basis of brain-resetting effects of psilocybin and identify neuroimaging correlates of psilocybin response in depressed patients.Data Sources: MEDLINE(R), Embase, APA PsycINFO, Cochrane, and CINAHL were systematically searched on June 3, 2022, with no date restrictions using the following string: (psilocybin) AND (psychedelics) AND (MRI) OR (fMRI)) OR (PET)) OR (SPECT)) OR (imaging)) OR (neuroimaging)).Study Selection: After duplicates were removed from 946 studies, 391 studies remained, of which 8 qualified for full-text analysis, but only 5 fulfilled the eligibility criteria of randomized, double-blind, or open-label neuroimaging study with psilocybin treatment in depressed patients.Data Extraction: The Covidence platform was used for deduplication and bias assessment. The a priori data points included concomitant psychological intervention, modality of neuroimaging technique, changes in depression scores, brain functional changes, and association between functional and psilocybin response. Assessment bias was assessed with the standard risk of bias tool for randomized controlled trials and the tool for risk of bias in nonrandomized studies of interventions.Results: Four studies were open-label, and one was a combined open-label and randomized controlled trial using functional magnetic resonance imaging. Psilocybin-assisted psychotherapy was administered in 3 studies, 1 in refractory and 2 in nonrefractory patients. The remaining 2 studies were in refractory patients. The transient increase in psilocybin-induced global connectivity in major neural tracts and specific areas of brain activation was associated with antidepressant response.Conclusions: Transient functional brain changes with psilocybin therapy resemble the "brain reset" phenomenon and may serve as the putative predictors of psilocybin antidepressant response.

Can antidepressant use be associated with emotional blunting in a subset of patients with depression? A scoping review of available literature.

INTRODUCTION: Despite frequent recognition of emotional blunting in the published literature, either as a primary symptom of depression or as an adverse effect of antidepressants, there is no systematic synthesis on this topic to our knowledge. We undertook this scoping review to assess the prevalence, clinical features, implicated causes and management of emotional blunting, outlining the phenomenological and clinical gaps in research. METHOD: A systematic search was done until March 15, 2022, to include all original studies (i.e., interventional trials, cohort & cross-sectional studies, case reports, and case series). All reviewed data were delineated to answer pertinent clinical, phenomenological, and management questions related to the phenomenon of emotional blunting. RESULTS: A total of 25 original studies were included in our scoping review. Emotional blunting was described as a persistent diminution in both positive and negative feelings in depressed patients, who could subjectively differentiate it from their acute symptoms. However, the literature lacked the distinction between emotional blunting as a primary symptom of depression or an adverse effect of antidepressants. Common clinical strategies to manage antidepressant-induced emotional blunting included dose reduction or switching to a different antidepressant. CONCLUSION: Emotional blunting was a significant patient-reported concern with antidepressants. Future research should clarify phenomenological and neurobiological constructs underlying emotional blunting to improve diagnostic and management skills.

Efficacy, safety, and tolerability of ulotaront (SEP-363856, a trace amine-associated receptor 1 agonist) for the treatment of schizophrenia and other mental disorders: a systematic review of preclinical and clinical trials.

INTRODUCTION: Schizophrenia is a mental illness that can disrupt emotions, perceptions, and cognition and reduce quality of life. The classical approach to treat schizophrenia is to use typical and atypical antipsychotics; however, limitations include low efficacy in mitigating negative symptoms and cognitive dysfunctions and a range of adverse effects. Evidence has accumulated on trace amine-associated receptor 1 (TAAR1) as a novel therapeutic target for treating schizophrenia. This systematic review investigates the available evidence on a TAAR1 agonist, ulotaront, as a treatment for schizophrenia. METHODS: A systematic search was conducted on PubMed/MEDLINE and Ovid databases for English-published articles from inception to 18 December 2022. The literature focusing on the association between ulotaront and schizophrenia was evaluated based on an inclusion/exclusion criterion. Selected studies were assessed for the risk of bias, using the Cochrane Collaboration tool, and summarized in a table to generate discussion topics. RESULTS: Three clinical, two comparative, and five preclinical studies examining ulotaront's pharmacology, tolerability and safety, and/or efficacy were identified. Results indicate that ulotaront has a differing adverse effect profile from other antipsychotics, may mitigate metabolic-related adverse effects commonly associated with antipsychotics, and may be effective for treating positive and negative symptoms. CONCLUSIONS: Findings from the available literature present ulotaront as a potential and promising alternative treatment method for schizophrenia. Despite this, our results were limited due to the lack of clinical trials on ulotaront's long-term efficacy and mechanisms of action. Future research should focus on these limitations to elucidate ulotaront's efficacy and safety for the treatment of schizophrenia and other mental disorders with similar pathophysiology.

Indirect Calorimetry to Measure Metabolic Rate and Energy Expenditure in Psychiatric Populations: A Systematic Review.

Psychiatric and metabolic disorders are highly comorbid and the relationship between these disorders is bidirectional. The mechanisms underlying the association between psychiatric and metabolic disorders are presently unclear, which warrants investigation into the dynamics of the interplay between metabolism, substrate utilization, and energy expenditure in psychiatric populations, and how these constructs compare to those in healthy controls. Indirect calorimetry (IC) methods are a reliable, minimally invasive means for assessing metabolic rate and substrate utilization in humans. This review synthesizes the extant literature on the use of IC on resting metabolism in psychiatric populations to investigate the interaction between psychiatric and metabolic functioning. Consistently, resting energy expenditures and/or substrate utilization values were significantly different between psychiatric and healthy populations in the studies contained in this review. Furthermore, resting energy expenditure values were systematically overestimated when derived from predictive equations, compared to when measured by IC, in psychiatric populations. High heterogeneity between study populations (e.g., differing diagnoses and drug regimens) and methodologies (e.g., differing posture, time of day, and fasting status at measurement) impeded the synthesis of results. Standardized IC protocols would benefit this line of research by enabling meta-analyses, revealing trends within and between different psychiatric disorders.

Mediating role of personality traits in the association between multi-dimensional adverse childhood experiences and depressive symptoms among older adults: A 9-year prospective cohort study.

BACKGROUND: To explore the mediating role of personality traits in the correlation between multi-dimensional adverse childhood experiences (ACEs) and depressive symptoms in older adults. METHODS: This cohort study used data from the English Longitudinal Study of Ageing, and included 4050 older adults without depressive symptoms in 2010-2011. Multi-dimensional ACEs were evaluated in 2006-2007. Personality traits were assessed using the Midlife Development Inventory in 2010-2011. Depressive symptoms were measured using the 8-item version of the Center for Epidemiologic Studies Depression Scale during 2012-2019. Cox proportional hazard model was used to explore the associations between ACEs and depressive symptoms. The package named "mediation" in R was used to test mediating role of personality traits. RESULTS: ACEs in each dimension significantly increased the risk of depressive symptoms (all P-values < 0.05). The association of maltreatment (18.18 %) and household dysfunction (19.69 %) with depressive symptoms was significantly mediated by neuroticism. The correlation between poor parent-child bonding and depressive symptoms was significantly mediated by neuroticism (19.43 %), conscientiousness (4.84 %), and extroversion (8.02 %). LIMITATIONS: ACEs were retrospectively assessed based on participants' memories, which may induce recall bias. CONCLUSIONS: Maltreatment and household dysfunction may induce depressive symptoms by increasing neuroticism. Poor parent-child bonding may induce depressive symptoms by increasing neuroticism and reducing conscientiousness and extraversion. In addition to reducing the occurrence of ACEs, reducing neuroticism of individuals with maltreatment and household dysfunction in childhood, and reducing neuroticism, and increasing conscientiousness and extraversion of individuals with poor parent-child bonding in childhood might help to decrease their risk of depressive symptoms.

Association of SARS-CoV-2 Infection with Neurological Symptoms and Neuroimaging Manifestations in the Pediatric Population: A Systematic Review.

Background: Neurological manifestations have been widely reported in adults with COVID-19, yet the extent of involvement among the pediatric population is currently poorly characterized. The objective of our systematic review is to evaluate the association of SARS-CoV-2 infection with neurological symptoms and neuroimaging manifestations in the pediatric population. Methods: A literature search of Cochrane Library; EBSCO CINAHL; Global Index Medicus; OVID AMED, Embase, Medline, PsychINFO; and Scopus was conducted in accordance with the Peer Review of Electronic Search Strategies form (October 1, 2019 to March 15, 2022). Studies were included if they reported (1) COVID-19-associated neurological symptoms and neuroimaging manifestations in individuals aged < 18 years with a confirmed, first SARS-CoV-2 infection and were (2) peer-reviewed. Full-text reviews of 222 retrieved articles were performed, along with subsequent reference searches. Results: A total of 843 nonduplicate records were retrieved. Of the 19 identified studies, there were ten retrospective observational studies, seven case series, one case report, and one prospective cohort study. A total of 6,985 individuals were included, where 12.8% of hospitalized patients experienced neurocognitive impairments: MIS-C (24.2%), neuroinflammation (10.1%), and encephalopathy (8.1%) were the most common disorders; headaches (16.8%) and seizures (3.8%) were the most common symptoms. Based on pediatric-specific cohorts, children experienced more drowsiness (7.3% vs. 1.3%) and muscle weakness (7.3% vs. 6.3%) as opposed to adolescents. Agitation or irritability was observed more in children (7.3%) than infants (1.3%). Conclusion: Our findings revealed a high prevalence of immune-mediated patterns of disease among COVID-19 positive pediatric patients with neurocognitive abnormalities.

The bidirectional association of nonalcoholic fatty liver disease with depression, bipolar disorder, and schizophrenia.

Nonalcoholic fatty liver disease (NAFLD) is a complex metabolic-inflammatory disease associated with poor outcomes and decreased quality of life. NAFLD is overrepresented in patients with psychiatric disorders like depression, bipolar disorder, and schizophrenia; however, a comprehensive review on NAFLD and psychiatric disorders remains to be delineated. This review endeavors to investigate the association of NAFLD with psychiatric disorders, including shared pathogenesis and future clinical derivatives. Extant literature suggests that patients with psychiatric disorders (in particular, mood disorders) are more susceptible to the development of NAFLD due to multiple reasons, including but not limited to hypothalamic-pituitary-adrenal axis dysregulation, metabolic syndrome, and chronic perceived stress. Moreover, the clinical manifestations of mood disorders (e.g., anhedonia, psychomotor retardation, lifestyle modification, etc.), and potentially long-term treatment with weight-gaining agents, differentially affect these patients, making them more prone to NAFLD. Considering the increased morbidity associated with both mood disorders and NAFLD, our review recommends regular screenings for NAFLD in select patients with mood disorders exhibiting signs of increased risk (i.e., obesity, metabolic syndrome, diabetes, or family history of NAFLD) for better diagnosis and holistic care of both potentially interrelated conditions.

Biomarkers of ketamine's antidepressant effect: An umbrella review.

Ketamine is a NMDA receptor antagonist that has a rapid acting antidepressant effect with high efficacy in treatment-resistant patients. Ketamine is a beneficial antidepressant for many individuals with depression, but not all of the patients respond, and some even exhibit symptom deterioration. The discovery of repeatable and mechanistically relevant biomarkers would address a major gap in treatment response prediction. Numerous potential peripheral biomarkers have been reported, but their current utility is unclear. We conducted an umbrella review to evaluate the biomarkers of ketamine's antidepressant effect in individuals with depression. PubMed and copus were searched using terms appropriate to each area of research, from their inception until July 2022. Five systematic reviews and meta analyses including 108 studies with 4912 participants were included. Blood-based and neuroimaging biomarkers were investigated. The results of this review indicate that ketamine can produce an anti-inflammatory effect and decrease at least one inflammatory marker following administration. Data from neuroimaging studies demonstrated that the cingulate cortex is the key locus of ketamine's action. The majority of the blood-based, neuroimaging, and neurophysiological investigations reviewed herein indicate ketamine induced normalization of major depressive disorder pathogenesis via synaptic plasticity and functional connectivity. Currently, no biomarker/biosignature is sufficiently validated for clinical utility, but several are promising. Now that ketamine is more widely available, biomarker discovery and replication should be attempted in larger, real-world populations.

The therapeutic role of ketamine and esketamine in treating psychopathological domains of depression.

Over the past two decades, ketamine has emerged as a novel effective and rapid-acting antidepressant. While the vast majority of studies on ketamine have focused on its ability to reduce the severity of depression broadly, its effectiveness in specific domains such as cognition, anhedonia, suicidality, and workplace/social/scholastic functionality has been neglected. Similarly, current treatments (e.g., SSRIs and SNRIs) aim to improve overall depression severity, which often results in the persistence of one or more residual symptom domains and prevents full recovery to premorbid functionality. In this review, we narratively synthesize the literature pertaining to the effectiveness of ketamine in treating key domains of depressive symptomatology (i.e., cognition, anhedonia, suicidality, and psychosocial functionality). Our findings suggest that ketamine is effective across domains varyingly, with the strongest evidence being for its ability to reduce suicidality. The rapid acting nature of ketamine further supports its use in treating suicidality and potentially preventing the completion of suicide. Evidence for the effectiveness of ketamine in other domains is weak, primarily due to a lack of robust studies specifically designed to assess these domains as primary outcomes. Future studies should scrutinize the effects of ketamine on specific domains of depression to optimize its implementation.

Brain-Derived Neurotrophic Factor (BDNF) as a biomarker of treatment response in patients with Treatment Resistant Depression (TRD): A systematic review & meta-analysis.

Multiple lines of evidence have implicated brain-derived neurotrophic factor (BDNF) in treatment-resistant depression (TRD). The aim of this synthesis was to determine the impact of TRD treatments on peripheral BDNF levels, and ascertain whether these changes are associated with antidepressant effects. Thirty-six articles involving 1198 patients with TRD were included herein. Electroconvulsive therapy (ECT), ketamine, and repetitive transcranial magnetic stimulation (rTMS) were the most common TRD treatments investigated. Serum BDNF levels significantly increased in six, two, four and one studies following ECT, ketamine, rTMS and atypical antipsychotics, respectively. The estimated mean baseline serum BDNF concentration in TRD patients ± 95% CI was 15.5 ± 4.34 ng/mL. Peripheral BDNF levels significantly increased overall (Hedges' g ± 95% CI = 0.336 ± 0.302; p < 0.05), but no association with depressive symptoms was found (p ≥ 0.05). These results demonstrate that peripheral measurements of total BDNF (i.e., mature and percursor forms of BDNF) are inadequate predictors of treatment response in TRD patients, and other considerations suggest that this would still apply to separable measurements of mature BDNF and its precursor.