J. Christian Gillin
By Bruno Nazar
J. Christian Gillin was born, in 1938, in Columbus, Ohio, USA. He received his Medical Degree from Case Western Reserve School of Medicine, in 1966, and completed his psychiatric residency training at Stanford University Medical School, in 1971. In 1982, after 11 years within the Intramural Research Program of the U.S. National Institute of Mental Health, Gillin moved to the Veterans Administration Medical Center in San Diego, California, affiliated with the Department of Psychiatry, University of California San Diego, as professor of psychiatry. He stayed in this position for the rest of his life (Gillin 2011).
In the late 1970s, Gillin became involved in studying the sleep EEG indepressed patients. His early findings, in 1978, provided further substantiation of Kupfer and his associates reports that an early onset of the first period of rapid eye movement (REM) sleep was an indicator of “primary depression”(Kupfer 1976; Kupfer and Foster 1972; Kupfer, Hanin, Spiker, et, al 1978) and that an increase in the latency time of the onset of the first REM period was after the administration of 50 mg of amitriptyline was a predictor for a favorable outcome of treatment with the drug (Gillin, Wyatt, Fram and Snyder 1978). He hypothesized that amitriptyline’s effect on the onset of the first REM period (REM latency) was linked to its anticholinergic properties, and his findings that intravenous administration of the cholinesterase inhibitor, physostigmine (Gillin, Sitaram, Mendelson and Wyatt, 1978),and of the direct muscarinic agonist, arecoline (Sitaram, Nurnberger, Gershon and Gillin, 1980), decreased REM latency, whereas, the infusion of a muscarinic receptor antagonist, scopolamine (Sitaram, Moore, & Gillin, 1978), prolonged it, were supportive of his hypothesis.
Throughout the 1980s and 1990s, Gillin studied the effects of putative antidepressants on the sleep EEG. In one of his first studies, conducted in the early 1980s,he found that both pargyline, a nonselective monoamine oxidase inhibitor (MAOI), and clorgyline, the prototype Type-A MAOI suppressed REM sleep (Cohen, Pickar, Garnett, et al 1982); and in his last study conducted, in the late 1990s, he revealed that fluoxetine, a` selective serotonin re-uptake inhibitor, delayed the onset of the first REM period, whereas nefazodone, a serotonin modulating antidepressant did not (Rush, Armitage, Gillin et al. 1998). To pursue further his research on the biochemical regulation of REM sleep, he developed the “cholinergic rapid eye movement induction test” (CRIT)(Gillin, 1992) and his findings with the employment of this test indicated that patients with primary depression have a supersensitive induction of REM sleep in response to the administration of the muscarinic acetylcholine receptor agonist, arecoline (Gillin et al. 1991). Supplementing the CRIT by using a “tryptophan free drink”, he revealed that while muscarinic acetylcholine receptor stimulation increased, serotonin (5HT) depletion decreased latency of the first REM period (Bhatti, Gillin, Seifritz, et al. 1998). The same study also indicated that 5HT depletion lowered mood and decreased vigor. Finally, in one of their last reports, Gillin and his associates indicated that the decrease of REM latency by 5HTdepletion was mediated by 5HT1A receptors and the increase REM latency by acetylcholine was mediated by M2 muscarinic receptors (Seifritz, Gillin, Rapaport, et al. 1998).
In 1987, Gillin became founding editor of Neuropsychopharmacology, the journal of the American College of Neuropsychopharmacology and served in that position for seven years, until 1994.Christian Gillin died in San Diego, in 2003, at age 65.
Bhatti T, Gillin JC, Seifritz E., et al. Effects of a tryptophan-free amino acid drinkchallange on normal human sleep electroncephalogram and mood.Biological Psychiatry 1998; 43: 52-9.
Cohen RM, Pickar D, Garnett D, Lipper S, Gillin JC, Murphy DL, REM sleep suppression induced by selective monoamine oxidase inhibitors. Psychopharmacology 1982; 78: 137-40.
Gillin JC. Sleep a royal road to pathophysiology. Psychiatric Research 1992; 28: 189-94.
Gillin JC, SitaramN, Mendelson WB, Wyatt RJ. (1978).Physostigmine alters onset but not duration of REM sleep in man. Psychopharmacology 1978; 58: 111–4.
Gillin JC, Sutton L, Ruiz C, et al. The cholinergic rapid eye movement test with arecoline in depression.Archives in General Psychaitry.1991; 48: 264-70.
Kupfer DJ.A psychobiological marker of primary depressive disease. Niol Psyciatry 1976; 11 159-74.,
Kupfer DJ, Foster FG. Interval between onset of sleep and rapid eye movement sleep as an indicator of depression. Lancet 1972; 2: 684-6.
Kupfer DJ, Hanin I, Spiker DG, et al. Amitriptyline pasma levels and clinical responsein primary edepression. II. Communications in Psychopharmacology 1978; 2: 441-50.
Rush AJ, Armitage R, Gillin JC, et al. Comparative effects of nefazodone and fluoxetine on sleep in outopatients with major depressive disorder. Biol Psychiatry 1998; 44: 3-14.
Seifritz E, Gillin J, Rapaport MH, et al. Sleep electroencephalographic response to muscarinic and serotonin 1A recptor probes in patients with major depression and in normal controls. Biological Psychiatry 1998; 44: 21-33.
Sitaram N, Moore AM, GillinJC. Experimental acceleration and slowing REM sleep ulradian rhythm by cholinergic agonist and antagonist.Nature 1978; 274: 490-2.
Sitaram N, NurnbergerJI, Gershon ES, GillinJC.Faster cholinergic M-sleep induction in euthymic patients with primary affective disorder.Science 1980; 208: 200-2.
September 11, 2014