Cyclic nucleotides in mental disorder.
Human CSF cyclic nucleotides do not distinguish manic-depresive patients or schizophrenic patients from controls, although a "high CSF cyclic AMP" subgroup of poor-prognosis schizophrenics is still under investigation. Neuroleptic therapy raises CSF cyclic GMP and lowers CSF cyclic AMP, at least in the responder subgroup of a clinically heterogeneous patient population when neuroleptics that are good adenylate cyclase inhibitors in vitro are used in the treatment. This is consistent with the concept that neuroleptic treatment in humans involves blockade of dopamine neurotransmission. Attempts to correlate the decline in CSF cyclic AMP concentration with clinical improvement may be important. Lithium treatment does not alter the level of CSF cyclic AMP, which probably derives largely from dopamine-related neurotransmission that lithium does not affect. However, the plasma cyclic AMP response to epinephrine is inhibited by lithium at therapeutic doses in vivo after chronic treatment. The lithium effect is somewhat specific in that the glucagon-stimulated rise in plasma cyclic AMP is not affected. The results in clinical experiments support the theory that norepinephrine-sensitive adenylate cyclase inhibition in brain is involved in lithium action. Research to attempt to distinguish lithium-responsive from lithium nonresponsive patients on the basis of sensitivity to lithium inhibition of the epinephrine-induced rise in plasma cyclic AMP is of considerable potential practical importance.
D000293:Adolescent; D000328:Adult; D001714:Bipolar Disorder / Q000134:cerebrospinal fluid* / Q000188:drug therapy; D000242:Cyclic AMP / Q000097:blood / Q000134:cerebrospinal fluid*; D006152:Cyclic GMP / Q000134:cerebrospinal fluid*; D005260:Female; D005934:Glucagon; D006801:Humans; D008094:Lithium / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011433:Propranolol / Q000627:therapeutic use; D012044:Regression Analysis; D012075:Remission, Spontaneous; D012559:Schizophrenia / Q000134:cerebrospinal fluid* / Q000188:drug therapy
D005934:Glucagon; D008094:Lithium; D011433:Propranolol; D000242:Cyclic AMP; D006152:Cyclic GMP