International Society for Bipolar Disorders (ISBD) 2025: an update

For those of you who are or were unable to attend the 2025 ISBD Annual Conference held in Chiba, Japan (just outside of Tokyo), September 17-19, 2025. Venue Makuhari Messe; we present a few selected highlights.

Recommendations for a Safe and Effective Therapeutic Range for Lithium Levels in Older Adults with Bipolar Disorder (OABD)
Kenneth Shulman of Sunnybrook Health Science Centre reported “Stable serum levels of lithium over many years may rapidly switch to much higher and even toxic levels in OABD. Moreover, the clinical symptoms of lithium toxicity are easily mistaken for other common conditions in old age. Cognitive change may be mistaken for onset of dementia. Falls and balance difficulties are often attributed to frailty in old age. Diarrhea may be attributed to gastrointestinal disease. These mistaken diagnoses can lead to a pharmacological cascade of increasing drugs rather than decreasing the maintenance dose of lithium. … The survey also recommended lower reference intervals including serum levels of 0.4 to 0.8 mmol/L for 60 to 79-year age group and levels of lithium of 0.4 to 0.7 mmol/L in those 80 and over.”

Elevated C-Reactive Protein is Associated with Suicide Attempts in Youth With Bipolar Disorder
Mikaela Dimick of the Centre for Addiction and Mental Health concluded that in 211 youth “Suicide attempts among youth with BD are associated with elevated CRP. Given the wide availability and low cost of CRP testing, findings from this study have potential clinical implications,” that should be pursued.

Inflammation-ImpulsivityDual Pathways in Non-Suicidal Self-Injury (NSSI) Among Bipolar Disorder: A24-Week Longitudinal Cohort Study
yinglin han of the Affiliated Brain Hospital of Nanjing Medical University reported that “Over the 24-week follow-up, IL-6 levels in the BD+NSSI group showed a sustained increase (p<0.001) and significantly influenced NSSI severity,” another immunological to NSSI.

Higher Blood Pressure is Associated With Greater Mood Symptom Severity in Youth with Mood Disorders

Kody G. Kennedy of the Center for Youth Bipolar Disorder reported that “BP was elevated during mixed/hypomanic states and was associated with greater mania and depression symptom severity in youth with mood disorders.”

Aberrant Cav1.2-BK Channel Interaction as a Key Pathophysiological Mechanism for Mood Switch in Bipolar Disorder

Rupali Srivastava ofJohns Hopkins University School of Medicine used “patient-derived neuronal cells (induced neuronal cells and induced pluripotent stem cells-derived neurons) in comparison with clinical phenotypes of each individual… utilizing calcium imaging, electrophysiology, and proximity ligation assay for protein interactions….We discovered attenuated interaction between the L-type CaV1.2channel and the calcium-voltage activated big potassium channel, manifested as downstream calcium kinetics deficits, which are specifically and tightly associated with a clinical phenotype underlying mood switch…. Importantly, the pharmacological impacts are seen in cells from both patients who clinically responded to and those who don’t well responded to lithium.”

Neural and Inflammatory Signatures of Obesity in Bipolar Disorder
Manli Huang of The First Affiliated Hospital, Zhejiang University School of Medicine reported that “Obese bipolar disorder patients exhibited significant gray matter volume reduction in the right supplementary motor area and right superior medial frontal gyrus compared to normal-weight patients…. These neural changes were more pronounced in patients with weight gain after medication use. Elevated inflammatory cytokines, particularly high-sensitivity C-reactive protein, correlated with reduced gray matter volume and increased functional connectivity.”

Lithium in old age bipolar disorders – safety, neuroprotection and molecular mechanisms of treatment response
Orestes Forlenza of the University of Sao Paulo found that  “patients treated with lithium had lower scores on depression rating scales (HAMD, MADRS, CES-D) and were more often ranked as having ‘no depression’. Lithium users were prescribed antipsychotics less often than non-users, and had less cardiovascular comorbidities. Patients in the lithium group had slightly better global cognitive (MMSE) and functional status (GAF).”

Exploring the Role of Antidepressants on Mitochondrial Energetics and Risk of Antidepressant Induced Mania (AIM)

Manuel Gardea Resendez of the Universidad Autonoma de Nuevo Leon reported on “692 participants with BD from a biobank were classified as AIM+ or AIM- based on clinical phenotyping; ADs were categorized as Mito+ (↑activity) or Mito− (↓activity) based on their impact on the electron transport chain (ETC) activity…. Individuals treatedwith Mito+ ADs had a significantly higher risk of AIM+ compared to those onMito- ADs(OR= 2.21; p= 0.000009)…. This study highlights the potential for a novel approach to AD classification and treatment in BD, focusing on mitochondrial function rather than solely on the traditional monoaminergic drug mechanism of action.”

Sodium-glucose Cotransporter 2inhibitors (SAGLT2i) for Lithium-Associated Kidney Dysfunction in Mood Disorders
Balwinder Singh. of the Mayo Clinic stated that “Sodium-glucosecotransporter-2 inhibitors (SGLT2i), initially developed for type 2 diabetes, have shown promise in slowing chronic kidney disease (CKD) progression…. Initiating SGLT2i therapy was associated with a significant improvement in eGFR trajectory in patients with mood disorders who had been on long-term lithium therapy.”

Lumateperone for Major Depressive Episodes with Mixed Features in Major Depressive Disorder and Bipolar I or Bipolar II Disorder

Suresh Durgam of Intra-CellularTherapies, Inc. reported that “Lumateperone 42mg demonstrated efficacy in improving both depressive and manic symptoms, measured by composite response and remission, in patients with depressive episodes with mixed features associated with MDD or bipolar disorder. “

Role of the Paraventricular Thalamic Nucleus in Bipolar Disorder: Insights from the Mitochondrial Dysfunction Hypothesis

In a Keynote Presentation, Tadafumi Kato of Juntendo University Graduate School of Medicine stated that “In 2000, we proposed the mitochondrial dysfunction hypothesis of bipolar disorder based on imaging, genetic, and pharmacological findings. Supporting evidence has since accumulated. To further explore this, we developed neuron-specific Polg mutant mice (seen in mitrochondrial disorders), which exhibited spontaneous, recurrent depression-like episodes, lithium responsiveness, and antidepressant-induced mania-like behavior—meeting key criteria for a valid animal model.

We identified the paraventricular thalamic nucleus (PVT) as the site accumulating mitochondrial DNA mutations in these mice. Manipulating PVT activity induced depression-like behavior, implicating it in mood regulation. To translate this to humans, we performed single-nucleus RNA sequencing and spatial transcriptomics on postmortem thalamus from bipolar patients, confirming PVT-specific cellular and molecular alterations.  These findings support a new hypothesis: hyperactivity in PVT-centered neural circuits underlies bipolar disorder, offering insights into its pathophysiology and treatment mechanisms.”

Mood and Resilience in Offspring; the Impact of Type, Severity and Timing of Exposure to Parental Psychopathology.

Manon Hillegers of ErasmusMC-Sophia Childern's Hospital presented data that “Offspring of parents with a mood disorder more often have mood disorders (χ2=14.91, p<0.001) and higher levels of comorbidity compared to control offspring. Offspring of parents with BD and MDD show similar levels of mood disorders. Mental health status of the co-parent and family factors are important resilience factors. Our 22 year follow-up… study findings illustrate the impact of exposure to multiple episodes of parental psychopathology on problem behavior in offspring.”

Impact of Solar Insolation in Bipolar disorder: The Global Sunlight Project
Michael Bauer of Technische Universität Dresden reported on “a multinational study involving more than 7000 participants with bipolar I disorder from 75data collection sites located in 41 countries in both hemispheres to investigate the influence of solar insolation (sunlight) on various illness variables. Global sunlight data are provided by the NASA POWER database. The main findings were that a large change in solar insolation was associated with an increased risk of suicide attempts, and a large increase in springtime solar insolation may impact the onset of bipolar disorder, especially in people with a family history of mood disorders. Physicians should be aware of these associations, especially those who practice in locations with a large change in solar insolation across the year.”  The magnitude of these changes in solar insolation in the US are illustrated below.

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