Objective: To narratively review currently available antidepressants and future potential antidepressants as monotherapy for the treatment of depressive disorders. Methods: Selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), dopamine reuptake inhibitor (bupropion), tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs) were reviewed according to the results from Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study and systematic reviews. For the rest of the antidepressants, a PubMed/Medline search was conducted with priority for systematic reviews. For drugs in development for depressive disorders, PubMed, Google, and Clinicaltrials.gov databases were used. Results: The STAR*D Study demonstrated that sertraline, venlafaxine, and bupropion monotherapy had similar efficacy in patients with major depressive disorder (MDD) who failed citalopram. A network meta-analyses of randomized, placebo-controlled trials found that SSRIs, SNRIs, bupropion, TCAs, mirtazapine, and agomelatine had similar relative efficacy compared to placebo, but had different acceptability. Gepirone had more failed/negative studies and smaller effect size relative to placebo compared to other antidepressants. The combination of dextromethorphan and bupropion, ketamine infusion, and intranasal esketamine had faster onset of action but similar effect size compared to monoamine-based antidepressants as monotherapy. Brexanolone and zuranolone are effective in postpartum depression (PPD), but the effect size of zuranolone in MDD as monotherapy or adjunctive therapy was very small. Psychedelics, glutamate receptor-related agents, kappa opioid receptor antagonists, orexin receptor antagonists, new anti-inflammatory agents, and biomarker-based antidepressant therapy have been under investigation for depressive disorders. Psychedelics showed faster onset of action, large effect size, and long durability. Conclusions: Monoamine-based antidepressants likely continue to be the mainstream antidepressants for depressive disorder. NMDA receptor antagonists and neurosteroid antidepressants will play a bigger role with the improvement of accessibility. Psychedelics may become a game changer if phase III studies validate their efficacy and safety in depressive disorders.

Previous research has indicated the brain-derived neurotrophic factor (BDNF) level is lower in schizophrenia and associated with cognitive impairment. Irisin-BDNF axis may strengthen learning and memory functions. This study examined associations between BDNF, peroxisome proliferator-activated receptor-gamma (PPAR gamma) and irisin with cognitive deficits in schizophrenia. We enrolled 80 patients with schizophrenia and 80 healthy controls (HCs). The enzyme-linked immunosorbent assay (ELISA) method was used for biochemical analysis. The Stroop Test, Trail Making Test (TMT), and Verbal Fluency Test (VFT) were used for cognitive assessment. Statistical analyses included t-tests, correlations, and analysis of covariance (ANCOVA) controlling key confounders. In unadjusted analyses, patients had significantly lower BDNF and PPARγ levels than HCs (ps < 0.001). After controlling for covariates, the difference in BDNF was still significant (F = 11804.71, p < 0.001, partial η² = 0.989), but not for PPARγ (F = 1.32, p = 0.252, partial η² = 0.010). Irisin levels did not differ between groups. Patients performed worse on all cognitive tests. After adjustments, deficits in processing speed (TMT-A, F = 4.30, p = 0.040) and executive function (Stroop-3, F = 5.89, p = 0.016; Stroop-4, F = 6.54, p = 0.012) remained significant. Longer illness duration correlated with lower BDNF (r=-0.318, p < 0.01), while more severe negative symptoms correlated with lower irisin (r=-0.244, p < 0.05). No biomarkers-cognition correlations were found groups separately. Exploratory analyses in the combined sample suggested nominal associations, but these did not survive correction for multiple comparisons and controlling for diagnostic group status. BDNF demonstrates the most robust association with schizophrenia and cognitive function. The association of PPARγ with schizophrenia is confounded by demographic and metabolic factors, and irisin showed a limited link only to negative symptoms. Not applicable.

Background and Objectives: This methodology-focused narrative review synthesizes the eye-tracking literature in bipolar disorder (BD) to evaluate the utility of such technology in identifying potential state or trait biomarkers for BD. Methods: A PubMed and Scopus search was performed from database inception to August 2026. Eligible studies included adults with BD or individuals at high-risk for BD compared with healthy controls (HCs) that used at least one quantitative eye-tracking paradigm and reported extractable quantitative outcomes. Studies were grouped into eight paradigms: free-viewing task (FVT), antisaccade (AS), prosaccade (PS), memory-guided saccade (MGS), smooth pursuit eye movements (SPEM), vergence, binocular rivalry (BR), and eye-blink rate (EBR). Findings were synthesized narratively based on study designs and outcome measures. Results: 24 studies met inclusion criteria. FVT and PS were the most frequently represented paradigms (n = 8 each), followed by AS (n = 7), BR (n = 4), and SPEM (n = 3); MGS, vergence, and EBR were each represented by one report. Findings from FVT, AS, and PS were inconsistent; the study designs, stimulus types, mood states during the study, and outcome measures of studies with these paradigms were diverse. BR alternation rate was consistently slower in BD across three studies. SPEM deficits were more closely associated with psychotic features. Evidence from single studies of MGS, vergence, and EBR limits their interpretations. Conclusions: Eye-tracking paradigms are promising tools for studying cognitive, affective, perceptual, sensorimotor, and reward-related presentations of BD. However, the field needs standardized protocols that include eye-tracking paradigms, mood states, symptom severity, outcome measures, study samples, and comparison groups to examine the utility of eye-tracking technology in BD.