Spectroscopic & Functional Magnetic Resonance Imaging of First and Multiple Episode Depressed Patients

Abstract

<p> Major Depressive Disorder (MDD) is a common affective disorder associated with persistent states of negative mood and selective cognitive impairments. Fronto-temporal dysregulation in MDD patients is thought to contribute to the symptoms seen in these patients.</p> <p> Based on prior evidence of structural and functional alterations in the hippocampus (Hc) and prefrontal cortex (PFC) in MDD patients, we were interested in examining the changes in cerebral function that underlie the cognitive dysfunction seen in two different MDD populations. We studied psychotropically naïve depressed patients experiencing their first treated episode (FTE) of depression, MDD patients who had experienced multiple past treated episodes (MTE) of MDD and healthy controls.</p> <p> Two functional magnetic resonance imaging studies (fMRI) were conducted. The first study used an Hc dependent process dissociation task to examine Hc activation during recollection memory. The second fMRI study examined the activation in the PFC during reward and punishment conditions of a reversal-learning paradigm. Finally, we conducted magnetic resonance spectroscopy scans to measure levels of metabolites indicative of neuronal and glial cell integrity in the Hc of depressed patients and controls. </p> <p> We observed differing results across all three studies in our FTE and MTE depression groups. Our studies examining the Hc suggest that MTE patients have decreased activation in this region as well as corresponding memory errors during recollection memory. Additionally, these patients have smaller Hc volume and signs of increased neuronal membrane turnover. Conversely, our FTE patients displayed heightened Hc activation without memory deficits. Moreover, FTE patients had signs of increased glial cell density in the Hc without volumetric differences in this region. Our examination of reward processing revealed several health-to-illness gradients of activation in areas as the nucleus accumbens, anterior cingulate and ventral prefrontal cortices during the processing of rewards and punishers. </p> <p> These findings suggest that several regions in the brain may be sensitive to the impact of disease burden and repeated episodes of MDD. In the Hc, first treatment patients may engage in compensatory processes during the early stages of illness that are attenuated with repeated episodes of illness. Moreover, reward processing may be affected in the early course of the disorder, however with a protracted course of illness these regional alterations in activation become more pronounced.</p>