Premenstrual syndrome (PMS) involves an aberrant behavioral response to normal hormone secretion. Pathogenetic theories posit abnormal modulation of γ-aminobutyric acid (GABA) transmission in the brain by neuroactive metabolites of progesterone (neurosteroids). In earlier transcranial magnetic stimulation (TMS) studies of the motor cortex, we showed that inhibition increases in the luteal phase, consistent with neurosteroid action at the GABAA receptor. Here, we studied women with PMS to see if their response to endogenous progesterone differed from that of control subjects.
We studied nine women with PMS and 14 control subjects during the midfollicular and luteal phases with paired TMS. Subthreshold conditioning TMS was followed by test stimulation that produced a motor evoked potential (MEP) in a hand muscle. We gave pairs at each of seven intervals (2–10 msec) and unconditioned stimuli, measuring the amplitude ratio of the average MEP from the pairs at each interval to that from the unconditioned stimuli (ratio < 1 = inhibition).
Both groups showed the same follicular phase response to paired TMS. Control subjects showed more inhibition in the luteal phase. Women with PMS showed relative facilitation.
This is the first physiological evidence for an abnormal brain response to progesterone in PMS.
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- An inventory for measuring depression.Arch Gen Psychiatry. 1961; 4: 561-571
- Allopregnanolone in women with premenstrual syndrome.Horm Metab Res. 1998; 30: 227-230
- Mechanisms influencing stimulus-response properties of the human corticospinal system.Clin Neurophysiol. 2001; 112: 931-937
- The anxiolytic-like effects of the neurosteroid allopregnanolone.Eur J Pharmacol. 1997; 325: 1-7
- Insensitivity to anaesthetic agents conferred by a class of GABA(A) receptor subunit.Nature. 1997; 385: 820-823
- A diagnostic interview.Arch Gen Psychiatry. 1978; 35: 837-844
Epperson CN, Haga K, Mason GF, Sellers E, Gueorguieva R, Zhang W, et al (2002): Cortical γ-aminobutyric acid levels across the menstrual cycle in healthy women and those with premenstrual dysphoric disorder: A 1H-MRS study. Arch Gen Psychiatry59:851–858
- A placebo-controlled study of effects of oral progesterone on performance and mood.Br J Clin Pharmacol. 1992; 33: 293-298
- Altered cortical excitability in obsessive-compulsive disorder.Neurology. 2000; 54: 142-147
- Short-term exposure to a neuroactive steroid increases alpha4 GABA(A) receptor subunit levels in association with increased anxiety in the female rat.Brain Res. 2001; 910: 55-66
- Low plasma gamma-aminobutyric acid levels during the late luteal phase of women with premenstrual dysphoric disorder.Am J Psychiatry. 1996; 153: 718-720
- Premenstrual syndrome. Advances in diagnosis and treatment.Obstet Gynecol Clin North Am. 2000; 27: 625-639
- Glutamate and GABA systems as targets for novel antidepressant and mood-stabilizing treatments.Mol Psychiatry. 2002; 7: S71-S80
- Corticocortical inhibition in human motor cortex.J Physiol (Lond). 1993; 471: 501-519
- Response to flumazenil in women with premenstrual dysphoric disorder.Am J Psychiatry. 2000; 157: 821-823
- GABA as an inhibitory neurotransmitter in human cerebral cortex.J Neurophysiol. 1989; 62: 1018-1027
- Allopregnanolone concentrations and premenstrual syndrome.Eur J Endocrinol. 2000; 142: 269-273
- Epilepsy in women.Neurology. 1999; 53: S42-S48
- Neuroactive steroids.Faseb J. 1992; 6: 2311-2322
- Progesterone metabolite allopregnanolone in women with premenstrual syndrome.Obstet Gynecol. 1997; 90: 709-714
- The neuroendocrinology of menstrual cycle mood disorders.Ann N Y Acad Sci. 1995; 771: 648-659
- Differential behavioral effects of gonadal steroids in women with and in those without premenstrual syndrome.N Engl J Med. 1998; 338: 209-216
- Circulating levels of anxiolytic steroids in the luteal phase in women with premenstrual syndrome and in control subjects.J Clin Endocrinol Metab. 1994; 79: 1256-1260
- Effects of ovarian hormone on human cortical excitability.Ann Neurol. 2002; 51: 599-603
- Menstrual-related changes in cortical excitability in women with PMS and controls.Biol Psychiatry. 2000; 47: 69S
- Menstrual cycle effects on cortical excitability.Neurology. 1999; 53 (abstract): 2069-2072
- GABA(A) receptor alpha4 subunit suppression prevents withdrawal properties of an endogenous steroid.Nature. 1998; 392: 926-930
- Manual for the State-Trait Anxiety Inventory (Form Y). Consulting Psychologists Press, Palo Alto, CA1983
- Structured Clinical Interview for DSM-III-R, Patient Edition. American Psychiatric Press, Washington, DC1990
- Premenstrual tension syndrome.Acta Psychiatr Scand. 1980; 62: 177-190
- Patients with premenstrual syndrome have a different sensitivity to a neuroactive steroid during the menstrual cycle compared to control subjects.Neuroendocrinology. 1998; 67: 126-138
- Patients with premenstrual syndrome have reduced sensitivity to midazolam compared to control subjects.Neuropsychopharmacology. 1997; 17: 370-381
- Motor cortex excitability correlates with an anxiety-related personality trait.Biol Psychiatry. 2001; 50: 377-382
- Nongenomic actions of estrogen in the brain.Crit Rev Neurobiol. 1996; 10: 189-203
- Electrophysiological and cellular effects of estrogen on neuronal function.Crit Rev Neurobiol. 1999; 13: 1-20
- Interaction between intracortical inhibition and facilitation in human motor cortex.J Physiol (Lond). 1996; 496: 873-881
- Transcranial magnetic stimulation.Epilepsy Res. 1998; 30: 11-30
Accepted: November 15, 2002
Received in revised form: November 11, 2002
Received: August 27, 2002
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