Brain Correlates of Antidepressant Treatment Outcome from Neuroimaging Studies in Depression Darin D. Dougherty, MD a, * , Scott L. Rauch, MD b a Department of Psychiatry, Massachusetts General Hospital, 15 Parkman Street, Boston, MA 02114, USA b Department of Psychiatry, McLean Hospital, 116 Mill Street, Belmont, MA 02478, USA P sychiatric research, including postmortem and neuroimaging studies, has contributed a great deal to the understanding of the pathophysiology of major depressive disorder (MDD). The ultimate goal of this psychiatric research is better diagnosis and treatment of individuals who have MDD. In this context, a growing number of neuroimaging studies have focused on cor- relates of treatment response. This review begins by reviewing findings from psychiatric research involving subjects who have major depression. It then dis- cusses general issues involved in conducting neuroimaging studies that seek to identify correlates of treatment response. It concludes with a review of neuro- imaging studies of treatment response in depression and integrates these find- ings into current models regarding the pathophysiology of major depression. NEUROIMAGING STUDIES OF MAJOR DEPRESSION An integrated cortical-limbic network is implicated in normal affective process- ing and in the pathophysiology of mood disorders [1–6]. Structures in this net- work interact with one another extensively, including contributing to cortico- thalamo-striatal circuits that seem to be related importantly to both affective and cognitive processing. This article reviews neuroimaging studies in mood disorders, focusing on key elements of these circuits. Converging data implicate the previously mentioned network of brain regions in the pathophysiology of major depressive episodes, regardless of whether they occur in the context of unipolar major depression or bipolar disorder. Prefrontal Cortex and Anterior Paralimbic Regions The prefrontal cortex (PFC) is not a monolithic entity; there are multiple subregions associated with discrete functions. In general, however, PFC func- tion can be divided into two broad categories: (1) working memory-executive function-attention, and (2) the coupling of thoughts, memories, and experience *Corresponding author. E-mail address: ddougherty@partners.org (D.D. Dougherty). 0193-953X/07/$ – see front matter ª 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.psc.2006.12.007 psych.theclinics.com Psychiatr Clin N Am 30 (2007) 91–103 PSYCHIATRIC CLINICS OF NORTH AMERICA