Cognitive subgroups in first episode bipolar I disorder: Relation to clinical and brain volumetric variables

Abstract

Objective Distinct cognitive subgroups are seen in patients with long duration bipolar I disorder (BDI), possibly reflective of underlying pathophysiological differences. It is unknown whether such cognitive heterogeneity is present at illness onset. We applied latent class analysis (LCA) to cognitive test scores in first episode BDI patients. Exploratory analysis elucidated whether impaired subgroups were characterized by ‘early neurodevelopmental’ (low premorbid IQ and intracranial volume) versus ‘later neurodevelopmental’ (decline from premorbid to current IQ, changes in relative grey (GM)/white (WM) matter volumes) pathology. Methods Recently recovered first manic episode BDI patients (n = 91) and healthy controls (HC, n = 63) comprised the study sample. LCA identified subgroups based on processing speed, verbal memory, non‐verbal memory, executive functioning, attention and working memory scores. Subgroups were compared amongst each other and HC on premorbid/current IQ, intracranial (ICV), total brain and regional volumes. Results Three cognitive subgroups emerged: (i) globally impaired (GI, n = 31), scoring 0.5‐1 SD below demographically corrected norms across domains, (ii) selectively impaired (SI, n = 47), with predominant processing speed deficits and (iii) high performing (HP, n = 13), with above‐average cognitive performance. GI patients showed a ‘later neurodevelopmental’ pattern, with normal ICV, significant decline from premorbid to current IQ, higher total GM and lower total WM (with respect to total brain volume) versus SI and HC (p = 0.003). GI patients had higher left frontal pole GM versus HC (p < 0.05, FWE corrected). Conclusions A globally impaired patient subgroup is identifiable in first episode BDI, possibly characterized by unique neurodevelopmental pathologic processes proximal to illness onset.

Structural brain abnormalities associated with cognitive impairments in bipolar disorder

“…Our main findings in CI patients extend recent evidence of greater prefrontal grey matter volume (in the left frontal pole) and corroborated the lower cerebral white matter volume found in globally impaired BD compared to selectively impaired and HC 49 . Interestingly, these findings are comparable despite differences between the studied cohorts.…”

“…Global or regional white matter disruptions have consistently been reported in BD patients, both recently diagnosed, 49 patients with longer duration of illness 80 and young first‐degree relatives of patients with BD 81,82 . Our demonstration of lower cerebral white matter volume in CI patients extends previous findings by suggesting these deficits may be specific to cognitively impaired patients.…”

“…In order to confirm previous findings in cognitively impaired BD patients, 49 we tested whether there were any differences in total cerebral white matter volume and cortical grey matter volume or average thickness between the patient subgroups and the HC. These global measurements were automatically estimated by the FreeSurfer pipeline, and we assessed group differences in SPSSv25 following outlier removal as above using GLMs with group as fixed factor and age, sex and TIV as covariates.…”

“…Interestingly, these findings are comparable despite differences between the studied cohorts. The previous study 49 investigated first episode BD Type I patients who had only recently recovered from their first manic episode and were not all remitted at the time of investigation. In contrast, we included both BD Type I and Type II patients who were in remission or partial remission and had a longer illness duration (mean ± SD: 12.7 ± 10.0 years).…”

“…Potential differences between cognitively normal (CN) and cognitively impaired (CI) patient subgroups risk thus to be masked. To date only one study investigated the structural brain correlates of cognitive impairments by comparing CI and CN patients 49 . This study revealed that newly diagnosed BD patients with globally impaired cognition showed lower white matter volume but greater grey matter volume in the prefrontal pole compared to selectively impaired and CN patients and HC.…”