There is significant heterogeneity in cognitive function in patients with bipolar I disorder (BDI); however, there is a dearth of research into biological mechanisms that might underlie cognitive heterogeneity, especially at disease onset. To this end, this study investigated the association between accelerated or delayed age-related brain structural changes and cognition in early-stage BDI.

First episode patients with BDI (n = 80) underwent cognitive assessment to yield demographically normed composite global and domain-specific scores in verbal memory, non-verbal memory, working memory, processing speed, attention, and executive functioning. Structural magnetic resonance imaging data were also collected from all participants and subjected to machine learning to compute the brain-predicted age difference (brainPAD), calculated by subtracting chronological age from age predicted by neuroimaging data (positive brainPAD values indicating age-related acceleration in brain structural changes and negative values indicating delay). Patients were divided into tertiles based on brainPAD values, and cognitive performance compared amongst tertiles with ANCOVA.

Patients in the lowest (delayed) tertile of brainPAD values (brainPAD range −17.9 to −6.5 years) had significantly lower global cognitive scores (p = 0.025) compared to patients in the age-congruent tertile (brainPAD range −5.3 to 2.4 yrs), and significantly lower verbal memory scores (p = 0.001) compared to the age-congruent and accelerated (brainPAD range 2.8 to 16.1 yrs) tertiles.

These results provide evidence linking cognitive dysfunction in the early stage of BDI to apparent delay in typical age-related brain changes. Further studies are required to assess how age-related brain changes and cognitive functioning evolve over time.

Patients with major depressive disorder (MDD) display cognitive deficits in acutely depressed and remitted states. Childhood maltreatment is associated with cognitive dysfunction in adults, but its impact on cognition and treatment related cognitive outcomes in adult MDD has received little consideration. We investigate whether, compared to patients without maltreatment and healthy participants, adult MDD patients with childhood maltreatment display greater cognitive deficits in acute depression, lower treatment-associated cognitive improvements, and lower cognitive performance in remission.

Healthy and acutely depressed MDD participants were enrolled in a multi-center MDD predictive marker discovery trial. MDD participants received 16 weeks of standardized antidepressant treatment. Maltreatment and cognition were assessed with the Childhood Experience of Care and Abuse interview and the CNS Vital Signs battery, respectively. Cognitive scores and change from baseline to week 16 were compared amongst MDD participants with (DM+, n = 93) and without maltreatment (DM−, n = 90), and healthy participants with (HM+, n = 22) and without maltreatment (HM−, n = 80). Separate analyses in MDD participants who remitted were conducted.

DM+ had lower baseline global cognition, processing speed, and memory v. HM−, with no significant baseline differences amongst DM−, HM+, and HM− groups. There were no significant between-group differences in cognitive change over 16 weeks. Post-treatment remitted DM+, but not remitted DM−, scored significantly lower than HM− in working memory and processing speed.

Childhood maltreatment was associated with cognitive deficits in depressed and remitted adults with MDD. Maltreatment may be a risk factor for more severe and persistent cognitive deficits in adult MDD.