THE IOWA GAMBLING TASK NET SCORES IS ASSOCIATED WITH SOCIAL FUNCTION IN BIPOLAR DISORDER

Abstract Background Bipolar Disorder (BD) is closely associated with dysfunctional reward systems1, a condition measurable through the Iowa Gambling Task (IGT). The complex interplay between reward sensitivity, neurobiological systems, and social functions in BD patients constitutes the core of our upcoming study. While oxytocin has been identified as a significant modulator of reward systems, a disruption in this mechanism is evident in those with BD2. The integration of oxytocin and dopamine is crucial for enhancing striatal reactivity, a cornerstone for effective social behaviors3. Here we are set to investigate the correlation between elevated reward sensitivity in BD patients and its subsequent impacts on social functions and experiences, underlined by weakened corticostriatal connectivity. Aims & Objectives We aimed to draw a comprehensive comparison between BD patients with contrasting levels of reward sensitivity. Additionally, we will explore the genetic framework, with an emphasis on unearthing the variations in the oxytocin receptor (OXTR) single-nucleotide polymorphisms (SNP) and their alignment with distinct reward sensitivities in BD patients. Method Seventy-two euthymic BD patients completed the IGT. Social function was measured with the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT), and social experience was measured with the UCLA loneliness scale and social relationship subscale of World Health Organization Quality-of-Life Scale (WHOQOL). Striatum-seeded resting-state functional connectivity (FC) was examined using functional magnetic resonance imaging; in parallel, blood samples were taken for genotyping of OXTR SNP rs53576 and rs2228485. Results The BD patients with positive IGT net scores (n=35) exhibited lower emotional intelligence, higher loneliness scores, worse social relationships, and less rs2228485 AA homozygotes compared with the BD patients with negative IGT net scores (n=37). In addition, there were hypo-FC between dorsal caudal putamen and dorsal anterior cingulate cortex, while hyper-FC between dorsal caudate and ventrolateral prefrontal cortex. Discussion &Conclusion This study is the first to investigate IGT net scores as a biomarker and its relationship with social function and experience. The rs2228485 AA homozygotes in healthy subjects is associated with a lower score for loneliness4 and a better ability to read emotional responses in male faces5, which could provide a genetic predisposition for the social behaviors in BD patients. The poor automatic emotional regulation and compensatory increase in voluntary emotion regulation6 may provide the underlying neural mechanism in the BD patients with positive IGT net scores. References 1.Trost S, Diekhof EK, Zvonik K, et al. Disturbed anterior prefrontal control of the mesolimbic reward system and increased impulsivity in bipolar disorder. Neuropsychopharmacology 2014;39:1914-23. 2. Wei SY, Tseng HH, Chang HH, et al. Dysregulation of oxytocin and dopamine in the corticostriatal circuitry in bipolar II disorder. Transl Psychiatry 2020;10:281. 3.Charlet A, Grinevich V. Oxytocin Mobilizes Midbrain Dopamine toward Sociality. Neuron 2017;95:235- 7. 4.Lucht MJ, Barnow S, Sonnenfeld C, et al. Associations between the oxytocin receptor gene (OXTR) and affect, loneliness and intelligence in normal subjects. Progress in neuro-psychopharmacology & biological psychiatry 2009;33:860-6. 5.Lucht MJ, Barnow S, Sonnenfeld C, et al. Associations between the oxytocin receptor gene (OXTR) and "mind-reading" in humans--an exploratory study. Nordic journal of psychiatry 2013;67:15-21.6. 6.Phillips ML, Ladouceur CD, Drevets WC. A neural model of voluntary and automatic emotion regulation: implications for understanding the pathophysiology and neurodevelopment of bipolar disorder. Mol Psychiatry 2008;13:829, 33-57.