Biochemical abnormalities in basal ganglia and cognitive dysfunction in bipolar disorder comorbid with attention-deficit/hyperactivity disorder patients: A proton magnetic resonance spectroscopy study.

BACKGROUND

Bipolar Disorder (BD) comorbid with Attention-Deficit/Hyperactivity Disorder (ADHD) presents substantial diagnostic and therapeutic challenges, with notable cognitive dysfunction as a core characteristic. The neurobiological mechanisms underlying these cognitive impairments remain inadequately understood.

METHODS

Cognitive performance was comprehensively assessed using the MATRICS Consensus Cognitive Battery (MCCB) among 90 adult participants categorized into three groups: pure BD (n = 26), BD comorbid with ADHD (n = 29), and healthy controls (n = 35). Proton magnetic resonance spectroscopy (1H-MRS) was used to assess neurometabolite ratios including N-acetylaspartate (NAA), choline compounds (Cho), and creatine (Cr) in the basal ganglia region among three groups.

RESULTS

Patients with BD + ADHD demonstrated significant impairments across multiple cognitive domains compared to healthy controls. Regression analyses revealed ADHD severity significantly moderated the relationship between depressive symptoms, and both visual learning performance and overall composite performance. Metabolically, a significant reduction in choline/creatine (Cho/Cr) ratio was observed specifically in the right lentiform nucleus in the BD + ADHD group, correlating positively with visual learning ability.

CONCLUSIONS

The findings suggest that BD comorbid with ADHD is characterized by widespread cognitive dysfunction and exhibits a distinct lateralized metabolic abnormality in the basal ganglia, particularly involving the cholinergic system in the right hemisphere, which may constitute the neural substrate underlying cognitive impairments in these patients. Recognizing these comorbidity-specific neurobiological alterations is crucial for refining diagnostic approaches and improving therapeutic outcomes.