Acetylcholine and α₁-Adrenergic Sensitivity in the Separation of Depression and Anxiety

Abstract

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 α-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.

Nonorganic Insomnia in Generalized Anxiety Disorder

“…Akiskal et al [ 17] also described difficulties initiating and maintaining sleep in a mixed sample of anxious patients including some patients with G A D or panic attacks. The latter was also described by Sitaram et al [18].…”

Acetylcholine and the Regulation of REM Sleep: Basic Mechanisms and Clinical Implications for Affective Illness and Narcolepsy

“…Further studies in identical twins suggested that the response on the CRIT might be partially under genetic control (131). Since the original study, Sitaram and his colleagues have confirmed the general cholinergic muscarinic supersensitivity in patients with endogenous depres sion using the CRIT (132)(133)(134). Our own recent preliminary results confirm a faster REM induction in patients with major depressive disorder and bipolar depression with an arecoline dose of 1.0 mg than with a 0.5-mg dose.…”

Insomnia in Generalized Anxiety Disorder: Polysomnographic, Psychometric and Clinical Investigations before, during and after Therapy with a Long- versus a Short-Half-Life Benzodiazepine (Quazepam versus Triazolam)

“…Akiskal et al [16] also described difficulties initiating and maintaining sleep in a mixed sample of anxious patients including some with general ized anxiety or panic attacks. The latter was also de scribed by Sitaram et al [17], As far as sleep architecture is concerned, Papadimi triou et al [18] observed a decreased stage 2 in their hos pitalized GAD patients, as compared with controls, Lauer et al [59] an increased stage 1. These data are in agree ment with our present findings.…”