Neurocardiac Control in Major Depression

INCLUSION CRITERIA: Two groups of right-handed subjects, male or premenopausal female, who are drug-naive or who have not received psychotropic drugs for at least 3 weeks (8 weeks for fluoxetine), will be recruited for studies under this protocol: unipolar depressives and healthy controls individually matched to depressives by age, gender and smoking status. Because effective treatment will not be discontinued for the purposes of this protocol, subjects in the patient groups will be identified who have never been treated for or who have discontinued medication due to lack of efficacy, noncompliance, physician order or other reason prior to study entry. The presence of inclusion and exclusion criteria will be established using both an unstructured clinical interview with a psychiatrist and the Structure Clinical Interview for DSM-IV (SCID). Family history of mental illness will be obtained using the Family Interview of Genetic Studies. EXCLUSION CRITERIA: Subjects will be excluded if they have: serious suicidal ideation or behavior; inability to provide informed consent; medical or neurological illnesses likely to affect physiology or anatomy; a history of drug or alcohol abuse within 1 year or a lifetime history of alcohol or drug dependence (DSM-IV criteria); current or past history of other axis I disorders that preceded the onset of MDD; current pregnancy (documented by pregnancy testing prior to scanning); current breast feeding; general MRI exclusion criteria; vision and/or hearing problems severe enough to interfere with testing. Exposure within two weeks to medications likely to affect cerebral blood glow or heart rate. Any condition that may prevent the subject from performing the run/walk test, or Irregular menstrual cycles so that menstrual phase cannot be reliably determined, or Any ECG finding that would contraindicate PET scanning or run/walk testing (e.g. non-sinus rhythm, significant tachycardia, ST segment elevation or depression, Q waves) or arrhythmia that would obviate accurate calculation of HRV indices. Cardiology consultation will be obtained for abnormal ECG findings unless it is unequivocally clear in the judgment of the study physician that such consultation is medically unnecessary. Subjects who are beyond age 50 who are either postmenopausal or perimenopausal are excluded to reduce the biological heterogeneity in autonomic function which may be associated with difference in menstrual status.