Background/Objectives: Bipolar disorder is characterized by psychosocial dysfunction, cognitive impairment, and incomplete recovery. Although inflammatory and neurotrophic mechanisms have been implicated, their relationships with multidimensional recovery outcomes remain unclear. We examined the relationships of inflammatory cytokines, brain-derived neurotrophic factor (BDNF), and vascular endothelial growth factor (VEGF) with depressive symptoms, psychosocial functioning, cognitive performance, personal recovery, and quality of life (QOL) in patients with bipolar disorder. Methods: This cross-sectional study of 24 patients with bipolar disorder assessed depressive symptoms, psychosocial functioning, cognitive functions, personal recovery, and QOL. Plasma tumor necrosis factor alpha, interleukin (IL)-6, IL-1β, IL-2, BDNF, and VEGF-A were measured by assay. Results: Subjective cognitive dysfunction was significantly associated with depressive symptom severity (rho = 0.53, p = 0.0083) and reduced QOL (rho = −0.56, p = 0.0042). Depressive symptoms were also associated with lower WHO-QOL-26 scores (rho = −0.43, p = 0.038). Significant interrelationships were observed among objective cognitive measures, and after false discovery rate (FDR) correction, the associations between FAST and PDQ-5-D, Symbol Check and Codebreaker, and Codebreaker and Trail remained statistically significant. High plasma IL-6 levels were associated with worse executive function (rho = 0.43, p = 0.0068). Higher VEGF levels were associated with better attentional performance (rho = −0.42, p = 0.042). Plasma IL-1β levels were positively associated with QOL (rho = 0.54, p = 0.02). After FDR correction, only the association between IL-1β and QOL remained statistically significant. Conclusions: This pilot study suggests that there may be associations between cognitive impairment and cytokines, as well as between quality of life and VEGF, in bipolar disorder. Further studies with larger sample sizes are needed.

Background: Several schizophrenia guidelines have been published, showing treatment efficacy. However, no studies have examined recovery and pharmacological therapy or guideline adherence's impact on various schizophrenia states. This study aimed to investigate adherence to pharmacological guidelines across recovery, remission, and non‐remission states in patients with schizophrenia. Methods: This cross‐sectional study included 72 patients with schizophrenia who met the criteria for recovery, remission, or non‐remission. Adherence to pharmacological guidelines was measured using the Individual Fitness Score (IFS). Results: IFS was significantly higher in the recovery (88.1 ± 18.9) and remission (89.0 ± 16.7) groups than in the non‐remission group (65.59 ± 21.8) ( p < 0.01). However, no significant differences were observed between the recovery and remission groups. Receiver operating characteristic analysis identified 72 points on the IFS as a potential cutoff point between remission and non‐remission. Conclusion: These results show that higher adherence to pharmacological guidelines may be associated with recovery and remission state, compared with non‐remission state. The cutoff point between remission and non‐remission should be considered preliminary and exploratory because of a small sample. Clinical practice guidelines have been developed to standardize and improve the quality of medical care. Treatments following these guidelines have been reported to be effective.

Background/Objectives: Bipolar depression impairs psychosocial functioning, cognition, and quality of life. Evidence regarding adjunctive exercise remains limited. This pilot study evaluated the clinical and biological effects of adjunctive exercise in patients with bipolar depression. Methods: In this multicenter cluster-randomized controlled trial, 26 hospitalized patients were assigned by facility to treatment as usual plus supervised exercise (TAU + Ex) or supervised stretching (TAU + SC) for 6 weeks. Twenty-four completed the study (TAU + Ex, n = 14; TAU + SC, n = 10). Clinical outcomes and plasma tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-1β, IL-2, brain-derived neurotrophic factor (BDNF), and vascular endothelial growth factor-A (VEGF-A) were assessed at baseline and week 6. The trial was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR; UMIN000045877; registered on 1 December 2021). Results: FAST and QIDS-SR scores improved significantly in both the exercise and stretching groups after the 6-week intervention, but no significant group × time interactions were observed. No significant group, time, or group × time effects were observed for any plasma biomarker. Before correction for multiple comparisons, nominal correlations were observed between changes in IL-1β and FAST, BDNF and FAST, and VEGF-A and Spotter performance. None remained statistically significant after Benjamini–Hochberg FDR correction. Conclusions: Adjunctive exercise therapy was not superior to active stretching. The exploratory biomarker–outcome correlations did not remain significant after correction for multiple comparisons and should be considered hypothesis-generating. Larger, adequately powered randomized controlled trials are warranted.