Lithium has been a cornerstone treatment for bipolar disorder (BD). Despite descriptions in the literature regarding associations between long-term lithium therapy (LTLT) and development of a thyroid disorder (overt/subclinical hypo/hyperthyroidism, thyroid nodule, and goiter) in BD, factors such as time to onset of thyroid abnormalities and impact on clinical outcomes in the course of illness have not been fully characterized. In this study we aimed to compare clinical characteristics of adult BD patients with and without thyroid disorders who were on LTLT. We aimed to identify the incidence of thyroid disorders in patients with BD on LTLT and response to lithium between patients with and without thyroid disorders in BD. The Cox proportional model was used to find the median time to the development of a thyroid disorder. Our results showed that up to 32% of patients with BD on LTLT developed a thyroid disorder, of which 79% developed hypothyroidism, which was corrected with thyroid hormone replacement. We did not find significant differences in lithium response between patients with or without thyroid disorders in BD. Findings from this study suggest that patients with BD and comorbid thyroid disorders when adequately treated have a response to lithium similar to patients with BD and no thyroid disorders.

The increasing prevalence and magnitude of harmful effects of substance use disorders (SUDs) in low- and middle-income countries (LMICs) make it imperative to embrace interventions which are acceptable, feasible, and effective in reducing this burden. Globally, the use of telehealth interventions is increasingly being explored as possible effective approaches in the management of SUDs. Using a scoping review of literature, this article summarizes and evaluates evidence for the acceptability, feasibility, and effectiveness of telehealth interventions for SUDs in LMICs. Searches were conducted in five bibliographic databases: PubMed, Psych INFO, Web of Science, Cumulative Index of Nursing and Allied Professionals and the Cochrane database of systematic review. Studies from LMICs which described a telehealth modality, identified at least one psychoactive substance use among participants, and methods that either compared outcomes using pre- and post-intervention data, treatment versus comparison groups, post-intervention data, behavioral or health outcome, and outcome of either acceptability, feasibility, and/or effectiveness were included. Data is presented in a narrative summary using charts, graphs, and tables. The search produced 39 articles across 14 countries which fulfilled our eligibility criteria over a period of 10 years (2010 to 2020). Research on this topic increased remarkably in the latter five years with the highest number of studies in 2019. The identified studies were heterogeneous in their methods and various telecommunication modalities were used to evaluate substance use disorder, with cigarette smoking as the most assessed. Most studies used quantitative methods. The highest number of included studies were from China and Brazil, and only two studies from Africa assessed telehealth interventions for SUDs. There has been an increasingly significant body of literature which evaluates telehealth interventions for SUDs in LMICs. Overall, telehealth interventions showed promising acceptability, feasibility, and effectiveness for SUDs. This article identifies gaps and strengths and suggests directions for future research.

Ketamine has shown rapid antidepressant and anti-suicidal effects in treatment-resistant depression (TRD) with single and serial intravenous (IV) infusions, but the effectiveness for depressive episodes of bipolar disorder is less clear. We conducted an updated systematic review and meta-analysis to appraise the current evidence on the efficacy and tolerability of ketamine/esketamine in bipolar depression. A search was conducted to identify randomized controlled trials (RCTs) and non-randomized studies examining single or multiple infusions of ketamine or esketamine treatments. A total of 2657 articles were screened; 11 studies were included in the systematic review of which 7 studies were included in the meta-analysis (five non-randomized, N = 159; two RCTs, N = 33) with a mean age of 42.58 ± 13.1 years and 54.5% females. Pooled analysis from two RCTs showed a significant improvement in depression symptoms measured with MADRS after receiving a single infusion of ketamine (1-day WMD = −11.07; and 2 days WMD = −12.03). Non-randomized studies showed significant response (53%, p < 0.001) and remission rates (38%, p < 0.001) at the study endpoint. The response (54% vs. 55%) and remission (30% vs. 40%) rates for single versus serial ketamine infusion studies were similar. The affective switch rate in the included studies approximated 2.4%. Esketamine data for bipolar depression are limited, based on non-randomized, small sample-sized studies. Further studies with larger sample sizes are required to strengthen the evidence.

Age at depressive onset (AAO) corresponds to unique symptomatology and clinical outcomes. Integration of genome-wide association study (GWAS) results with additional “omic” measures to evaluate AAO has not been reported and may reveal novel markers of susceptibility and/or resistance to major depressive disorder (MDD). To address this gap, we integrated genomics with metabolomics using data-driven network analysis to characterize and differentiate MDD based on AAO. This study first performed two GWAS for AAO as a continuous trait in (a) 486 adults from the Pharmacogenomic Research Network-Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS), and (b) 295 adults from the Combining Medications to Enhance Depression Outcomes (CO-MED) study. Variants from top signals were integrated with 153 p180-assayed metabolites to establish multi-omics network characterizations of early (<age 18) and adult-onset depression. The most significant variant (p = 8.77 × 10⁻⁸) localized to an intron of SAMD3. In silico functional annotation of top signals (p < 1 × 10⁻⁵) demonstrated gene expression enrichment in the brain and during embryonic development. Network analysis identified differential associations between four variants (in/near INTU, FAT1, CNTN6, and TM9SF2) and plasma metabolites (phosphatidylcholines, carnitines, biogenic amines, and amino acids) in early- compared with adult-onset MDD. Multi-omics integration identified differential biosignatures of early- and adult-onset MDD. These biosignatures call for future studies to follow participants from childhood through adulthood and collect repeated -omics and neuroimaging measures to validate and deeply characterize the biomarkers of susceptibility and/or resistance to MDD development.