Biopsies of skeletal muscle, which include subterminal motor nerves, will be obtained from 250 psychiatric patients (mostly acutely or chronically psychotic, some neurotic), 50 first degree relatives of these patients and 50 normal controls. We will continue to study the type and incidence of anatomic pathology in skeletal muscle fibers and subterminal nerves to confirm or refute a theory of neurogenic muscle disease in psychotic patients. Multiple muscle specimens from deseased psychotic patients under age 40 will be sought. The effect of MAO inhibitors on muscle of depressed patients will be studied. The relationship of the nerve and muscle pathology in patients to clinical features will be studied by careful examination and follow up of the outcome of all subjects. The relationship of the nerve and muscle pathology to concomitant neuropsychologic (Halstead-Retain) tests and neurophysiological studies of muscle and the alpha-motor neuron will be studied. The neurophysiological studies include quantification of nerve conduction, velocity, distal latency, H-reflex studies, motor unit counts, proprioception function and pendulum tracking. Studies in animals will focus on the relationship between muscle pathology and efflux of CPK (which occurs in psychotic patients) produced by the psychotomimetic drug phencyclidine and restraint stress. The mechanism of the muscle pathology produced by the indole hallucinogen harmaline, in rabbits, will be explored, focusing on the monoamine oxidase-inhibiting properties of harmaline. The effect of monoamine oxidase inhibitors such as pargyline and iproniazid and will also be studied. The effect of altering brain amines with pharmacologic doses of precursors, inhibitors of synthesis or blocking agents on rator rabbit muscle will be studied. Study of the effect of brain lesions in rats and possibly other species on muscle and motor nerve morphology will be continued with particular focus on lesions of the substantia nigra and lateral hypothalamus which we have demonstrated can produce muscle pathology in the rat. We will also study the effect of chronic severe stress with and whithout neuroleptics on neuromuscular pathology.