Associations of TNF-α, MIF, and cortisol with cognitive function in patients with bipolar disorder during acute manic episodes: a short-term follow-up study

BackgroundBipolar disorder (BD) is frequently accompanied by cognitive impairment, and growing evidence suggests that immune-inflammatory activation and hypothalamic-pituitary-adrenal axis dysregulation may contribute to its pathophysiology. This study aimed to examine the associations of tumor necrosis factor-α (TNF-α), macrophage migration inhibitory factor (MIF), and cortisol (COR) with cognitive function in patients with BD during manic episodes and to characterize their short-term changes.MethodsIn this short-term follow-up study, 53 patients with BD during manic episodes and 53 healthy controls (HCs) were enrolled. Plasma TNF-α, MIF, and COR levels were measured using enzyme-linked immunosorbent assay. Cognitive function was assessed using the Chinese Brief Cognitive Test, including information processing speed (IPS), executive function (EF), sustained attention (SAT), and working memory (WM). Patients were evaluated at baseline and after 8 weeks of treatment, whereas HCs were assessed once at baseline. Group comparisons and biomarker–cognition correlation analyses were performed. Multiple testing in the correlation analyses was controlled using the Benjamini–Hochberg false discovery rate (FDR) procedure.ResultsAt both baseline and follow-up, patients with BD had significantly lower IPS, EF, SAT, and WM scores, but significantly higher plasma TNF-α, MIF, and COR levels, than HCs. After 8 weeks of treatment, cognitive scores in the BD group improved significantly, whereas reductions in TNF-α, MIF, and COR did not reach statistical significance. In exploratory unadjusted Pearson analyses, several biomarker–cognition associations survived FDR correction. However, in the primary adjusted partial correlation analyses, only the negative association between TNF-α and WM remained significant after adjustment for covariates and FDR correction at both baseline and follow-up.ConclusionPatients with BD during manic episodes exhibited widespread cognitive impairment accompanied by elevated inflammatory and neuroendocrine markers. TNF-α showed the most robust association with working memory after adjustment for covariates and correction for multiple comparisons. Associations involving MIF or cortisol and executive function should be interpreted as exploratory and require validation in larger longitudinal studies.
<![CDATA[David Dunner, MD, FACPsych, reveals insights into rapid cycling roots, bipolar II, and weighing lithium as an often overlooked treatment option.]]>
<![CDATA[Explore how circadian gene rhythms differ in schizophrenia, depression, and bipolar disorder—and why stable sleep timing may curb addiction risk.]]>
<![CDATA[Sleep and circadian rhythm disruption shape psychiatric symptoms and bipolar mood shifts.]]>

A high-dimensional atlas of parvalbumin interneuron soma morphology in mouse visual and somatosensory cortex

Parvalbumin-positive (PV+) inhibitory interneurons are central components of experience-dependent plasticity in the visual cortex (V1). Anatomically, they are distributed across cortical layers and are traditionally classified as basket, chandelier, or bipolar cells based on dendritic and axonal arborization patterns. In parallel, physiological, transcriptomic, connectomic, and multimodal studies have revealed substantial diversity within PV+ populations, raising the question of how this diversity is organized within cortical circuits. In contrast, light microscopy studies based on soma labeling have primarily quantified PV+ cells using size and density, and the potential of soma morphology to capture this diverse organization remains unclear. To address this, we developed a high-throughput, data-driven approach to quantify PV+ soma morphology in > 14,000 cells from mouse V1 and somatosensory cortex (S1). Using 97 morphological features combined with clustering, phenotyping, and laminar mapping, we identified structured diversity in PV+ somas. PV+ cells were organized into 13 morphological clusters along partially independent gradients of size and shape. Phenotyping identified four size and five shape categories that describe PV+ cell diversity across cortical areas. Mapping these categories onto cortical layers revealed a structured organization in which specific morphologies are enriched within distinct laminar compartments. This organization aligns with cortical architecture and suggests that PV+ interneuron morphology is systematically related to circuit structure. These findings demonstrate that substantial morphological information can be extracted from standard PV+ labeling approaches using quantitative analysis. Together, this work provides a high-dimensional atlas of PV+ interneuron soma morphology in mouse V1 and S1 and establishes a framework for linking cellular anatomy to circuit organization and experience-dependent plasticity.

Recommendations for Research and Clinical Implementation of Ambulatory Assessment, Mood Monitoring, Digital Phenotyping, and Remote Measurement Technology in Mood Disorders: Synthesis of Systematic Review Findings

Background: Ambulatory assessment and active and passive monitoring all offer a real-time, flexible approach to assessing mood and behavior in mood disorders. Despite their potential, concerns remain regarding the performance, usability, adherence, and potential safety of these tools. Objective: This study synthesizes the findings from 7 systematic reviews, integrating quantitative and qualitative data from randomized trials, observational studies, and user experience research to evaluate the performance, feasibility, acceptability, and clinical impact of ambulatory assessment and mood monitoring in people with depression and bipolar disorder. We assessed studies over the medium or long term (3 months or more). Methods: A summary of a series of systematic reviews was carried out by the authors—including meta-analyses (for quantitative data) and meta-syntheses (for qualitative data). Eight electronic databases were searched, and mixed methods studies were included. Studies were assessed for risk of bias. The results were checked for coherence, and recommendations were made by individuals with lived experience, methodologists, and psychiatrists. GRADE (Grading of Recommendations Assessment, Development, and Evaluation) was used to assess the quality and strength of the evidence. Results: The 111 included studies included 19,945 participants and used 69 different ambulatory assessment protocols or mood-monitoring interventions. Key barriers to implementation were identified, including performance inconsistency, adverse effects, and user disengagement. Evidence-based recommendations are provided to guide future clinical and research applications. Conclusions: Ambulatory assessment and mood monitoring hold promise in research and clinical practice, yet their implementation requires more rigorous evaluation, greater personalization, and responsible, user-centered design. Crucially, these measures can add granularity and confirmation, but additional context is often required, and none of these measures are robust enough yet to replace current outcomes.
<img src="https://jmir-production.s3.us-east-2.amazonaws.com/thumbs/a83582c454b5b6028210d2cb063318df" />

Personalized Pharmaco-Lifestyle Interventions for Severe Mental Illnesses (LIFETRAIN)

Conditions: Severe Mental Illness; Depression / Major Depressive Disorder; Bipolar Disorder (BD); Schizophrenia

Interventions: Drug: Semaglutide (SEMA); Behavioral: Exercise module; Behavioral: Anti-inflammatory diet module; Behavioral: Sleep intervention module; Behavioral: Social prescribing module; Device: Closed-loop transcranial alternating current stimulation (CL-tACS); Behavioral: Structured lifestyle psychoeducation; Device: Sham CL-tACS

Sponsors: Ludwig-Maximilians – University of Munich

Not yet recruiting
<![CDATA[Experts discuss rapid cycling and bipolar II, and weigh lithium as an often overlooked treatment option. ]]>

Erratum

Erratum to: “The Link Between Weight Gain and Hippocampal Atrophy in Bipolar Disorder: A Longitudinal Investigation in 934 Participants,” by Fraiha-Pegado et al. (Biol Psychiatry 2026); https://doi.org/10.1016/j.biopsych.2026.01.020.