Bipolar Disorder Diagnosis May Affect Total White Matter Volume Over Time

Compared with healthy individuals, patients with a bipolar disorder (BD) diagnosis are found to have reduced total white matter volume and amygdala enlargement, and typically present with cognitive impairment, according to the findings of a small study published in the Journal of Affective Disorders.

Identifying brain aging patterns in patients with BD is important in determining future risk for adverse long-term outcomes, such as illness severity. Therefore, researchers aimed to track the trajectories in brain structure and cognition in patients with newly diagnosed BD.

For the current analysis, the researchers enrolled participants from the Bipolar Illness Onset (BIO) study. Diagnoses of BD were based on the International Classification of Diseases, Tenth Revision (ICD-10) criteria and Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).

Eligible participants were aged between 18 and 60 with disease in full or partial remission, based on total scores of 14 or less on the Hamilton Depression Rating Scale (HDRS) and the Young Mania Rating Scale (YMRS). Age- and sex-matched individuals were included in the control group.

Clinical and cognitive assessments were conducted at baseline and follow-up. Demographic data and verbal intelligence quotient (IQ) were collected from all participants, as well as measurements of cognitive functioning and quality of life. Participants also had available magnetic resonance imaging (MRI) scans.

A total of 163 participants (97 with BD and 66 without BD) were included in the study, of whom 50 and 38, respectively, had follow-up at an average of 16 months after their baseline assessment.

Baseline demographic and clinical characteristics were similar between the groups, except patients with BD had lower educational levels, higher body mass index (BMI), higher HDRS and YMRS scores, more functional impairment, and a lower quality of life (all P <.001).

In the longitudinal analysis, the researchers found no significant differences in trajectories for global cognition or individual cognitive domains (all P ≥.15) between the 2 groups. However, patients with BD had worse performance scores across all cognitive domains at baseline (all P ≤.004).

Of note, there were differences between the groups in longitudinal trajectories for functioning, as measured by Functioning Assessment Short Test (FAST) scores, with the patient vs control group showing lower FAST scores at baseline and follow-up (all P <.001). In addition, patients with BD vs control participants reported a lower quality of life at both timepoints (all P <.001).

The researchers noted significant differences in white matter volume between the patient and control group (P =.006), with BD resulting in a decrease in white matter volume over time. While there were no significant differences between the groups in amygdala volume, patients with BD vs control participants had larger amygdala volume (P =.04).

In the post-hoc analysis, the researchers found significant group differences in white matter trajectories, after adjusting for subsyndromal symptoms (HDRS and YMRS scores, P =.005 and BMI, P =.01). Group differences also persisted for larger amygdala volume, after adjusting for mood symptoms (P =.042). The effect of white matter and amygdala volume was larger in participants with both baseline and follow-up data (P =.003 and P =.017, respectively).

Study limitations included the reduction in the sample size at follow-up from baseline; limited generalizability to patients with more severe and chronic illness; and the variability in the follow-up period (6-27 months).

Overall, the researchers noted, “Cognitive impairment and amygdala enlargement may represent stable markers of BD early in the course of illness, whereas subtle white matter decline may result from illness progression.”

Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of the authors’ disclosures.