This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. OBJECTIVE: Neuroimaging studies conducted over the past few years suggested that mood disorders involve anatomical and functional brain abnormalities in brain regions involved in mood regulation. Such abnormalities may underlie the causation of this illness. However, very little is known about brain mechanisms involved in early onset cases of depression that present in children and adolescents. Those early onset cases are often more severe on their clinical presentation and more difficult to treat, which may indicate a larger biological vulnerability among these patients. To this date, very few studies attempted to investigate brain mechanisms in children and adolescents suffering from these disorders. Having available substantially improved tools from neuroimaging, it is now imperative that new studies will take advantage of such approaches to begin to investigate brain mechanisms possibly involved in depression in children and adolescents. Such studies will be of utmost importance, as they will allow investigation of the clinical relevance of specific brain abnormalities in the course of the illness, and to determine whether such abnormalities have a neurodevelopmental origin or are neurodegenerative. METHODS: We will utilize magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) to examine the existence of brain abnormalities in children and adolescents with unipolar depression, through morphometric measurements of specific brain regions involved in mood regulation, as well as neurochemical measures of the levels of a brain chemical called N-Acetyl Aspartate (NAA), a non-specific marker of neuronal viability/function. We will recruit 15 untreated depressed DSM-IV unipolar disorder patients and 15 matched healthy controls. RESEARCH PLAN: The proposed protocol will investigate the following hypotheses: (1) Anatomical abnormalities are present in specific brain regions in children and adolescents with unipolar depression. We predict that such abnormalities will be found in specific sub-regions of the prefrontal cortex and medial temporal lobe regions. (2) NAA levels will be reduced in pre-frontal cortex in adolescent unipolar patients, suggesting compromised neuronal integrity in this brain region. CLINICAL
The proposed project will tackle this very important mental health problem among children and adolescents, and will allow completion of a pilot study that will provide needed preliminary data to apply for support form NIMH to develop a full study. Considering the dimensions of this important health problem, we believe it could be extremely relevant to contribute to address this important mental health problem.
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