Cholinergic Modulation of Condition and Emotion in Mood Disorders: Functional Neuroimaging Studies

* INCLUSION CRITERIA: Patients with Major Depressive Disorder (MDD): * Age 18-55 * Current diagnosis of MDD, as defined by DSM-IV criteria for recurrent MDD * Current depressive episode * Current IDS score in the moderately-to-severely depressed range * Right handed * Able to provide informed consent Patients with Bipolar Disorder (BD): * Age 18-55 * Current diagnosis of bipolar disorder, as defined by DSM-IV * Current depressive episode * Current IDS score in the moderately-to-severely depressed range * Right handed * Able to provide informed consent Healthy Controls: * Age 18-55 * Able to provide informed consent * Medically healthy EXCLUSION CRITERIA: Patients MDD \& BD: * Serious suicidal ideation or behavior (with a current plan or intent), or current delusions or hallucinations * Medical or neurological illnesses likely to affect physiology or anatomy * 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 or BD * Current pregnancy (documented by pregnancy testing within 24 hours prior to pilot studies and 24 hours prior to scanning) * Current breast feeding * General MRI exclusion criteria (including the presence of pacemakers, cochlear implants, surgical clips or metal fragments in their eyes or body parts) * Vision and/or hearing problems severe enough to interfere with testing * Electrocardiographic evidence of ischemia, arrhythmia, conduction defect, or myocardial infarction * Current blood pressure of \>140 mm Hg or \< 90 mm Hg systolic, or \> 90 mm Hg diastolic (due to the potential cardiovascular effects of scopolamine and physostigmine) * Clinically significant cerebrovascular or cardiovascular disease, hypertension, congestive heart disease, angina pectoris, advanced arteriosclerosis, gross neurological impairment, hyperthyroidism, known hypersensitivity or idiosyncrasy to anticholinergic agents, glaucoma, renal or hepatic impairment * Clinical history of glaucoma or narrow angle glaucoma (due to the possibility of exacerbation of this condition by scopolamine) * Age of onset greater than 45 years (to reduce the biological heterogeneity encompassed by the MDD and BD criteria, since subjects with a late age-at onset for depression have a far greater likelihood of having MRI correlates of cerebrovascular disease than age-matched, healthy controls or age-matched, early-onset depressives) * Exposure within two weeks to medications likely to effect cerebral blood flow and metabolism or likely to interact with anti-cholinergic medications (e.g. narcotics or anti-cholinergic agents)- as verified by history and urine drug screen * HIV positive status * Weight over 275 pounds Healthy Controls: * Medical or neurological illness * Current pregnancy (documented by pregnancy testing within 24 hours prior to pilot studies and 24 hours prior to scanning) * Current breast feeding * General MRI exclusion criteria (including the presence of pacemakers, cochlear implants, surgical clips or metal fragments in their eyes or body parts) * Vision and/or hearing problems severe enough to interfere with testing * Electrocardiographic evidence of ischemia, arrhythmia, conduction defect, or myocardial infarction * Current blood pressure of \>140 mm Hg or \< 90 mm Hg systolic, or \> 90 mm Hg diastolic (due to the potential cardiovascular effects of scopolamine and physostigmine) * Clinically significant cerebrovascular or cardiovascular disease, hypertension, congestive heart disease, angina pectoris, advanced arteriosclerosis, gross neurological impairment, hyperthyroidism, known hypersensitivity or idiosyncrasy to anticholinergic agents, glaucoma, renal or hepatic impairment * Clinical history of glaucoma or narrow angle glaucoma (due to the possibility of exacerbation of this condition by scopolamine) * HIV positive status * Weight over 275 pounds For BD patients being recruited for the scopolamine efficacy trial, they may forgo imaging and thus will not be excluded for imaging related exclusion criteria (including general MRI exclusion criteria and vision and/or hearing problems).