Abstract
OBJECTIVE: This study aimed to identify young adults who met the criteria for bipolar disorder (BD) but had not yet been diagnosed or treated. It also aimed to evaluate their neurocognitive and neurobiological changes compared to healthy controls (HC). METHODS: Individuals at high risk for BD were identified by using the Hypomania Checklist 32 items (HCL-32R). Participants were then assessed with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) to identify previously undiagnosed and drug-naive patients (DNP) (n=27). A matched HC group (n=27) was included for comparison. All participants completed a cognitive battery assessing executive function, attention, working memory, and verbal learning. Magnetic resonance imaging (MRI) was used to assess cortical thickness. Oxidative stress markers - including thiobarbituric acid reactive substances (TBARS), nitric oxide (NO), and the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) - were measured. RESULTS: The DNP group underperformed across all the tests administered but group differences were significant in the Wisconsin Card Sorting Test (WCST) and Rey Auditory Verbal Learning Test (RVALT). Among oxidative stress markers, only CAT levels were significantly higher in the DNP group. Additionally, patients exhibited significant cortical thinning in several brain regions. CONCLUSION: Neurobiological alterations and neurocognitive dysfunction are present in the earlystage, unmedicated stages of BD. However, longitudinal studies are needed to better understand the progression of these changes.