Reward-Related Processes and Brain Function

Impaired motivated behaviors, including aspects of decision-making and reward-related processes, lie at the root of maladaptive behavior in many psychiatric disorders, including major depression (MD). Little is known of the cognitive and neural mechanisms that underlie MD in adolescents. Adolescence is a key period during which many psychiatric disorders first emerge, and studies during this developmental stage may provide a unique window to address primary deficits associated with the disorders. In particular, major depression shows a marked increase in prevalence at adolescence. Data from family-based and longitudinal studies suggest that anxiety disorders (AD), often preceding MD, may index childhood vulnerabilities for the development of MD. The concomitant examination of MD and AD can help interpret these findings. We propose to examine, in adolescents, the manner in which the various elemental emotional-cognitive processes are differentially affected in MD and AD compared to healthy controls. This investigation will be done in two phases. In Phase I, using fMRI, we will test two tasks in the decision-making model of gambling that have similarly been tested in adults in a group of healthy adolescents and healthy adults. This phase will serve as a test of the feasibility and validity of using these tasks in adolescents, and will provide normative developmental data by comparing healthy adults with healthy adolescents. In addition to showing the feasibility of using these tasks in normal adolescents, we will also test task performance behaviorally in healthy, anxious and depressed adolescents. Measures will include psychophysiological and eye tracking measures, and behavioral variables. Once task performance is well characterized behaviorally, we will conduct in Phase II an fMRI study in independent groups of depressed and anxious adolescents and compare the findings with those obtained in healthy adolescents.

• INCLUSION CRITERIA:

• Age: Subjects will be males and females, 9-17 and 20-40 years of age.
• Psychiatric history: Subjects in Group 3, and 4 will be diagnosed with current MD, and current AD (generalized anxiety disorder, social phobia, or/and separation anxiety disorder) respectively, based on k-SADS interviews of parents and adolescents for minors (<18 years old), and SCID for adults. History of anxiety disorders in individuals with MD is acceptable, if current symptoms are mild or absent (see exclusion criteria). Similarly, history of depression in individuals with AD is acceptable, if current symptoms are mild or absent (see exclusion criteria). AD and MD patients should have a CGAS< 70.
• Medication status: No history of medication treatment or use of an SSRI > one month prior to entering the study and fluoxetine > six months prior to entering the study.

Exclusion criteria

Because factors such as psychiatric disease, or CNS disease, can influence functional brain activity, and pregnancy precludes participation in fMRI studies, these factors are exclusionary.

• Psychiatric disease: Any current history of an axis I diagnosis other than adjustment disorder, simple phobia, Social Phobia, Separation Anxiety, dysthymia, GAD and MD is exclusionary. Subjects will be assessed using DSM-IV criteria via standardized psychiatric interviews conducted by trained examiners (K-SADS in minors and SCID in adults). Any current suicidal ideation, and severe ADHD requiring pharmacotherapy will be exclusionary.
• History of Drug Abuse: Axis I diagnoses of substance use disorders will be exclusionary.
• Severe acute and chronic medical illnesses
• CNS disease: History of brain abnormalities (e.g., neoplasms, subarachnoid cysts), cerebrovascular disease, infectious disease (e.g., abscess), or other neurological disease, or history of head trauma (defined as loss of consciousness > 3 min).
• IQ lower than 70.
• Metal or electronic objects: Metal plates, certain types of dental braces, cardiac pacemakers, etc., that are sensitive to electromagnetic fields contraindicate MRI scans.
• Claustrophobia: Subjects will be questioned about potential discomfort in being in an enclosed space, such as an MRI scanner.
• Pregnancy status: Because of the potential effects of hormonal changes on brain function as well as the unknown effects of electromagnetic field on the fetus, pregnancy is an exclusion criterion. Sexually mature female participants must have a negative urine pregnancy test performed within 24 hours of the fMRI scan.