Hippocampal and Cognitive Impacts of Depression in Multiple Sclerosis (P4.178)

OBJECTIVE: To determine the imaging and cognitive consequences of comorbid depression in multiple sclerosis BACKGROUND: Depression is a common comorbidity in multiple sclerosis (MS) impacting quality of life, employment status and cognitive performance. Selective subregional hippocampal atrophy, alterations in diurnal cortisol secretion patterns and cognitive impairment have been reported in MS patients with depressive symptoms, similar to idiopathic major depressive disorder (MDD). However, the relationship of comorbid major depressive disorder in MS (MSD) to MDD has not been established. We performed structured interviews, detailed cognitive testing and high resolution structural MR imaging in 4 subject cohorts (MSD, MS without depression (MSN), MDD and healthy controls (HCC)) to contrast comorbid MDD in MS with idiopathic MDD. METHODS: A total of 105 subjects were enrolled at a single center. They underwent a full neuropsychological assessment including a structured interview for psychiatric disorders and detailed cognitive testing. High-resolution structural brain MR imaging was collected on a 3T scanner. Corrected brain volumes were obtained using an automated algorithm (FIRST). Analysis of cognitive testing results were performed with adjustment for age and sex (ANCOVA) using percentile test scores. Subregional hippocampal differences will be explored using surface based mapping validated with manually segmented subregional volumes. RESULTS: All patient groups (MSD, MSN, MDD) demonstrated impaired verbal learning as compared to the healthy controls (ANCOVA p=0.014) with idiopathic MDD the most impaired. Delayed verbal recall (p=0.05) and processing speed (p=0.005) were impaired in MSD versus HCC. Total hippocampal volumes were significantly reduced in the MS patient groups (p < 0.01) compared to healthy controls. CONCLUSIONS: MS related MDD is associated with significant cognitive impairment and hippocampal volume loss. These effects share features with, but are distinct from, idiopathic MDD suggesting that different pathophysiological underpinnings may exist between these forms of major depressive disorder. Study Supported by: NMSS Disclosure: Dr. Sicotte has nothing to disclose. Dr. Gold has received personal compensation for activities with Novartis for consulting. Dr. O9Connor has nothing to disclose. Dr. Lopez has nothing to disclose. Dr. Smith has nothing to disclose. Dr. Yamakawa has nothing to disclose. Dr. Renner has nothing to disclose. Dr. Gahm has nothing to disclose. Dr. Shi has nothing to disclose.