Beta-adrenergic-mediated cyclic AMP accumulation was reduced in lymphocytes obtained from depressed patients from that observed in an age- and sex-matched group of control subjects. Among the depressed patients, those not responding to treatment showed significantly lower pretreatment responses to isoproterenol compared with patients who exhibited significant clinical improvement during antidepressant treatment. Late-night (terminal) insomnia was significantly associated with the blunted response to beta-adrenergic stimulation. In depressed patients with the lowest isoproterenol response, the effect of forskolin (which acts distal to the receptor and directly stimulates the catalytic subunit) on cyclic AMP accumulation was also significantly decreased. This suggests that post-receptor modulations of signal amplification also play a role in the reduced response to beta-adrenergic stimulation in depression.

Two hundred ninety-five psychiatric and neurologic patients were randomly screened for aryl sulfatase A (ASA) activity in lymphocyte extracts. Two of these patients showed very low ASA activity, in the range of metachromatic leukodystrophy (MLD)-affected patients. The residual activity in these low ASA patients showed normal enzyme behavior with regard to ASA kinetic features and the ability to catabolize 14C labeled sulfatide by intact fibroblasts. Taking into account that approximately 3% of the general population are homozygous for the pseudo-aryl sulfatase A gene and are clinically unaffected, the data obtained here indicate that the patients studied in this work, as well as most psychiatric patients reported in the literature with low ASA activity, represent the normal ASA polymorphism. Thus, the very low ASA activity patients are in fact homozygous for the pseudo-deficient allele, which does not result in clinical abnormalities. The clinical symptoms in these psychiatric patients and probably other "variant" MLD patients are therefore not related to low ASA activity.

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