Positron emission tomographic study of affective disorders: problems and strategies

Because anatomical studies of psychiatric disorders in humans have been largely unsuccessful, and because pharmacological interventions in patients with mental illness can be analyzed by means of biochemical assay techniques, positron emission tomography (PET) provides an exciting new means to study mental illness. Using fluorine-18-labeled fluorodeoxyglucose and PET to measure local cerebral glucose utilization, the investigators examined patients with affective disorders and normal age-matched controls. Patients with unipolar depression were studied in a drug-free baseline state following short-term administration of methylphenidate and in a euthymic state in long-term follow-up. Patients with bipolar disorders were studied in either the manic or depressed phases of illness and again in a euthymic state in long-term follow-up. Age-matched controls were studied both with and without methylphenidate administration. The results demonstrate that metabolic subgrouping of patients may be possible. Mood changes produced by pharmacological agents resulted in changes in the patterns of metabolism when compared with the baseline state. Problems associated with the use of PET to study mental illness fall into the categories of patient classification (diagnosis, state, trait, ambient conditions, and mental processes) and data analysis (anatomical and statistical). These problems, the limitations of the present techniques, and strategies for their improvement are discussed. Despite these difficulties, PET should prove to be a fruitful means of exploring the human biochemical abnormalities associated with mental illness.