¹The National Cheng Kung University, Institute of Behavioral Medicine, Tainan, Taiwan, ²National Hospital of Sri Lanka, Operation Theater Department, Colombo, Sri Lanka, ³The National Cheng Kung University, School of Pharmacy, Tainan, Taiwan, ⁴The National Cheng Kung University Hospital, Department of Psychiatry, Tainan, Taiwan

Background: Bipolar disorder (BD) is a severe mental health condition characterized by episodic mania, and depression, with some individuals also experiencing psychosis. A history of psychotic features is associated with poor prognosis, significant treatment challenges, and substantial functional impairments. While brain structural and neurochemical alterations, chronic inflammation and cognitive deficits are recognized as prognostic factors of BD, adverse childhood experiences (ACEs) and social support are crucial environmental factors that modulate the course. The interplay of these variables, particularly in cases with a history of psychotic features, remains poorly understood.

Aims & Objectives: This study aims to explore the role of adverse experiences, social support, neurochemical (midline structure Glutamate and GABA levels), peripheral inflammatory markers (hs-CRP, TNF-α) and neuropsychological variables in patients with BD (with a history of psychotic features: BDP+; and without: BDP-) compared to healthy controls (HC).

Method: This cross-sectional study employed purposive sampling to recruit 57 BD patients (18 BDP+, 39 BDP-) and 41 HCs. Key clinical characteristics were evaluated, including ACEs (Childhood Trauma Questionnaire, CTQ), social support (Measurement of Support Function questionnaire, MSF), brain neurochemical (Glutamate levels Glu and Glx in the medial prefrontal cortex, measured with proton Magnetic Resonance Spectroscopy), and peripheral inflammatory markers (hs-CRP, TNF-α). Independent t-tests were used to assess differences between groups.

Results: Regarding ACEs, CTQ scores were notably higher in BDP-, but not in BDP+, compared to HC (t = 3.56, p = 0.01; t=1.62, p = 0.11, respectively). Social support was significantly lower in BDP- than in HC, particularly in perceived social support (t = -3.64, p = 0.01). Regarding inflammatory markers, hs-CRP levels were significantly elevated in BDP+ compared to BDP- (t = -2.90, p = 0.01). Regarding brain neurochemical measures, Both Glx and Glu levels in the mPFC were markedly higher in BDP+ than in both BDP- (t =-2.00, p = 0.05; t = -3.05, p = 0.01, respectively) and HC (t = 2.70, p = 0.01; t = 3.24, p = 0.01, respectively).

Discussion & Conclusions: This study highlights an increased systemic inflammation, and elevated medial prefrontal glutamatergic activity in BDP+ compared to BDP-, but environmental factors including increased childhood trauma and reduced social support, are more prominent in BDP-. Addressing psychosocial and biological factors differently in those with and without a history of psychosis through early trauma mitigation, enhanced support, and targeted therapies could improve outcomes and quality of life for BD patients, emphasizing a biopsychosocial care framework.