Author's reply

We are grateful to Drs Vita, Peri and Sacchetti, who raise the very important point that morphometric abnormalities detectable in first-onset bipolar disorder appear different from those described in chronic patients. An observation which, as Vita et al suggest, may underpin important information about the pathogenesis of the disorder and would benefit from clarification emerging from longitudinal studies. Prompted by their meta-analysis ¹ and our own work, ² we have conducted further analyses by including only patients with first-episode bipolar disorder v. healthy controls. Despite methodological differences and different inclusion and exclusion criteria, we are in agreement with Vita et al. We found no evidence of whole-brain volume reduction in the first-episode patients v. healthy controls (effect size –0.23; 95% CI –0.47 to 0.002; I ² = 0, P = 0.51; Egger's P = 0.31). This finding supports Vita et al's hypothesis that whole-brain volume loss may be occurring with illness progression and/or its epiphenomena (e.g. number of episodes, pharmacological treatment). Similarly we found no evidence of gray matter loss (effect size –0.02; 95% CI –0.40 to 0.37; I ² = 0.02, P = 0.36; Egger's P = 0.16) but significant white matter volumetric reduction in the first-episode patients v. healthy controls (effect size –0.45; 95% CI –0.85 to –0.06; I ² = 0.04, P = 0.35; Egger's P = 0.68). These and other observations ^3,4 support the possibility that white matter deficits have a particular relevance to the aetiology of bipolar disorder. However, the paucity of first-episode studies is reflected in the relatively wide confidence intervals around our estimates. Further studies of patients with first-episode bipolar disorder, as well as cohort and high-risk studies, are necessary if we are to improve our understanding of the role of structural changes in the pathogenesis of this condition.