Project 2: Functional and neurochemical brain changes following successful trea..

University Of Cincinnati, Cincinnati OH

Investigators

Linked publications & trials

Abstract

Depressive states are the predominant feature of bipolar disorder and a major source of morbidity and[unreadable] mortality in bipolar patients. Symptoms include affective changes, neurovegetative signs, and significant[unreadable] cognitive deficits. Several lines of evidence suggest that these symptoms are linked to neuropathological[unreadable] abnormalities in structures making up the anterior limbic network (ALN), a brain network hypothesized to[unreadable] modulate emotional homeostasis. These abnormalities are manifest by functional neuroimaging changes in[unreadable] regions involved in emotional control including the ventrolateral prefrontal cortex (VLPFC), anterior cingulate[unreadable] (ACC) and amygdala, as well as by neurochemical changes consistent with elevated neuronal metabolism.[unreadable] Magnetic resonance spectroscopy (MRS) studies of depressed bipolar patients suggest that abnormalities in[unreadable] energy metabolism may underlie increased prefrontal and medial temporal activity observed with functional[unreadable] magnetic resonance imaging (fMRI) and positron emission tomography (PET). Patients with bipolar disorder[unreadable] demonstrate significant changes in prefrontal concentrations of N-acetyl aspartate (NAA), as well as[unreadable] changes in phosphomonoesters (PME) and the presence of lactate, that suggest altered energy metabolism.[unreadable] Evidence of increased glutamate in the prefrontal cortex suggests that this increased neuronal activity is[unreadable] related to increased intraneuronal excitatory signaling within the prefrontal cortex. Together, these data[unreadable] support a model in which bipolar depression is marked by a loss of emotional modulation linked with[unreadable] increased ACC and VLPFC activation, and inhibition of, or interference with other brain regions, including the[unreadable] dorsolateral prefrontal cortex, which mediates cognitive domains impacted by bipolar disorder. These[unreadable] prefrontal changes in neuronal activity appear to be responsive to pharmacologic intervention.[unreadable] With these consideration in mind, the goals of this study are: 1) To use 1H-MRS to identify neurometabolic[unreadable] abnormalities in early-episode depressed bipolar patients, and to determine how abnormalities change in[unreadable] response to specific treatments; and 2) To identify corresponding changes in fMRI brain activation, in order[unreadable] to provide neurofunctional correlates to neurochemical markers of treatment response. To accomplish these[unreadable] aims, we will acquire integrated neurometabolic (MRS) and neurofunctional (fMRI) measurements in earlyepisode[unreadable] depressed bipolar patients and a matched cohort of healthy subjects in order to refine[unreadable] neurophysiological models of bipolar disorder (Center goal 1); to identify MRS and fMRI markers of[unreadable] treatment response in bipolar depression to two mechanistically different medications (Center goal 2); and to[unreadable] identify potential predictors of treatment response for future studies (Center goal 3).