Acetylcholine and alpha 1-adrenergic sensitivity in the separation of depression and anxiety

Three relatively clear-cut diagnostic groups, namely primary major depressive disorder-endogenous subtype (PRI MDD-E), primary anxiety disorder with no depression (PRI ANX), and normal controls as well as two additional patient groups with mixed or coexisting anxious/depressive diagnoses were studied. Clinical assessment was made by routine psychiatric interview, Schedule of Affective Disorder and Schizophrenia (SADS) research interview, and obtaining family history of MDD. Subjects underwent both routine 'baseline' sleep EEG polygraphic arecoline, a muscarinic, cholinergic agonist infused during sleep. Cholinergic sensitivity was assessed by measuring the time to induction of REM sleep after arecoline infusion. In addition, a subgroup of MDD patients underwent pupillographic testing. Peripheral alpha-adrenergic responsivity was measured by the magnitude of pupillary mydriatic response after local ocular instillation of phenylephrine. Successful separation (83% correct classification) of the 'pure' groups (PRI MDD-E, PRI ANX, and normal) was achieved by discriminant function analysis of sleep EEG variables. Compared to PRI ANX and normal groups, patients with PRI MDD-E had supersensitive cholinergic REM-induction response, shorter REM latency, increased first REM density and REM percent. Separation of the PRI ANX and normal groups was by intermittent awake time, delta sleep percent, and total REM density. Classification of the mixed anxious/depressive groups was next attempted using the discriminant coefficients derived from the above analysis of 'pure' groups. We found that the presence of absence of family history of MDD in patients with mixed diagnosis offered the best prediction of classification into PRI MDD-E and PRI ANX groups, respectively. MDD patients with coexisting panic disorder were significantly subsensitive to phenylephrine-induced mydriasis compared to MDD patients without anxiety.