Changes to Grey Matter Volume Depends on Symptoms, Age in Bipolar Disorder

Brain-related changes in bipolar disorder were found to be related to symptoms and progression.

A systematic review published in Bipolar Disorder found that symptoms and progression were significant contributors to brain-related changes in bipolar disorder (BD).

Investigators from Technische Universität Dresden in Germany searched publication databases for longitudinal imaging studies aimed at quantifying age-related brain changes in BD. A total of 11 studies that included 329 patients with BD and 277 control patients were included in this review.

The most prominent result reported across studies was the decrease over time in frontal brain area grey matter volumes (GMV) and cortical thicknesses (CT). The effects to progressive volume and thickness losses were related with mood episodes.

One study reported that young adults who experienced recurrence after their first manic episode had greater prefrontal regional loss compared with individuals who did not have recurrence. Similarly, another study found that adults with 1 or more manic episode had more cortical thinning of the left inferior frontal cortex compared with patients without recurrence or control patients.

[G]rey matter reductions have been observed after single episodes, indicating that minimizing pathological mood swings in BD-patients may prevent further grey matter decline.

Episodes of depression were similarly related with thinning in the prefrontal cortices, in which patients who had 2 or more depressive episodes had greater thinning in the ventromedial prefrontal cortices over time. The latter relationship, however, did not survive correction for multiple comparisons.

Three studies related mood episodes with structural changes in the temporal lobe. Loss of grey matter in the temporal lobe was related with the number of (hypo-)manic episodes and correlated with the number of depressive episodes. Patients who experienced 2 or more depressive episodes were found to have thinning of the left posterior and inferior temporal cortices.

There was evidence that medications affected brain structures, in which atypical antipsychotics and antiepileptics impacted GMV in the left medial frontal gyrus and in the right cerebellum. One study reported that lithium contributed to changes to the visual-somatosensory network in the medial occipital cortex and central gyrus.

Compared with control patients, adults with BD were found to have reduced GMV in the right superior frontal gyrus but this pattern was not observed among adolescents, indicating decline over time. Conversely, a linear relationship of increased volumes of the limbic subcortical and medial temporal structures were observed.

In studies that included samples from adolescents or young adults, greater volume decreases in the central and rostral prefrontal cortex were observed among patients with BD compared with control patients. One study reported an increase in the right ventrolateral prefrontal cortex among healthy control patients but not among patients with BD and another reported a persistent GMV reduction in the amygdala among patients with BD but not among control patients.

“In the entire sample, grey matter reductions have been observed after single episodes, indicating that minimizing pathological mood swings in BD-patients may prevent further grey matter decline. Appropriate treatment potentially may reduce adverse effects of mood episodes or even revert structural brain alterations, specifically after disease onset in adolescent BD. The current clinical practice should take the high rates of mood episodes in BD-patients into account and provide accurate survey tools to detect and prevent affective episodes appropriate to the age group at hand,” the review authors concluded.

This article originally appeared on Psychiatry Advisor


Förster K, Horstmann RH, Dannlowski U, Houenou J, Kanske P. Progressive grey matter alterations in bipolar disorder across the life span–a systematic review. Bipolar Disord. Published online March 5, 2023. doi:10.1111/bdi.13318