Pituitary volume and third ventricle width in euthymic patients with bipolar disorder

Many of the clinical and neuroendocrine features of bipolar disorder involve hypothalamic structures. Although current neuroimaging techniques inadequately resolve the structural components of the hypothalamus, evidence of derangement can be sought by examining the adjacent third ventricle and the functionally related pituitary.

To investigate the structure and function of the hypothalamic-pituitary-adrenal axis in euthymic patients with bipolar disorder.

Euthymic adult patients with bipolar disorder (n=49) were compared with matched normal control subjects (n=47). Pituitary volume and third ventricle width were assessed on MRI scans. Basal salivary cortisol levels were measured.

The width of the third ventricle in patients with bipolar disorder exceeded that of controls (mean +/- SD (in mm): 3.87 +/- 1.96 versus 2.56 +/- 1.34; d=0.76, ANOVA F=12.7, p=0.001), with the greatest differences found in males. Third ventricle width increased with age across the groups (F=16.97, p<0.001). Pituitary volumes did not differ between patients and controls (mean +/- SD (in mm(3)): 632 +/- 176 versus 679 +/- 159). Overall, females had larger pituitaries than males (703 +/- 160 versus 595 +/- 161; d=0.67, F=9.65, p=0.003; all subjects), but female patients had smaller pituitaries compared to female controls (637 +/- 178 versus 756 +/- 126; d=0.65, F=5.04, p=0.03). No difference was found in a comparable analysis of males. Pituitary volume did not differ between patients prescribed and not prescribed antipsychotic drugs. Basal salivary cortisol levels did not differ between patients and controls.

In euthymic patients with normal basal cortisol levels, pituitary volume and third ventricle width were found to differ from normal controls. These differences were related to gender, may be important in the pathogenesis of bipolar disorder and could link the vegetative and endocrine abnormalities seen in this condition. Such findings may reflect a trait abnormality or be a consequence of previous episodes.