DEPRESSION, VULNERABILITY, AND CATECHOLAMINE DEFICIENCY

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DESCRIPTION (Adapted from applicant's abstract): The search for markers associated with the risk of developing major depression (i.e., associated with a personal history of Major Depressive Disorder (MDD), or a family history of MDD in first-degree relatives) has been relatively unsuccessful to date. Furthermore, there is a lack of reliable trait markers for unipolar major depression. Preliminary data from the investigator's group, presented herein, shows that euthymic, unmedicated subjects with a personal history of major depression commonly experience marked, but transient, depressive reactions induced by catecholamine depletion; whereas, historical controls without a personal or family history do not experience significant mood changes when undergoing catecholamine depletion. Therefore, a depressive reaction induced by catecholamine depletion may represent a reliable marker for a history of prior depression, a vulnerability marker for the development of a consequent depression, and/or a marker of previous treatment. The following aim will begin clarifying the significance of the above findings. Aim: To demonstrate that catecholamine depletion induces a depressive reaction in euthymic, unmedicated subjects with a frequency and intensity that reflects the relative risk of developing a future depressive episode: subjects with a personal history of MDD > subjects without a personal history of MDD but with a positive family history of MDD in first-degree relatives > subjects with neither a personal nor family history of MDD. This aim represents a replication and extension of preliminary findings. Preliminary Data Gathering: Should initial observations be further substantiated, this study will also provide preliminary data for determining the clinical correlates of an induced relapse (e.g., number of previous episodes, age of onset, duration of remission, and, previous use of antidepressant medications or electroconvulsive therapy). Furthermore, preliminary data will be gathered to assess the prognostic utility of this challenge paradigm (i.e., correlation with future clinical relapse). In order to assess feasibility of the latter aim, subjects from each group will be followed prospectively for the duration of the study.