2002 International International Biennial Scientific Meeting

CORTICAL GABA LEVELS IN HEALTHY AND DEPRESSED PUERPERAL AND NON-PUERPERAL WOMEN: A 1H-MRS STUDY

Neill Epperson*, Graeme Mason, Gerard Sanacora, Kristen Haga, Michael Appel, Kathryn Czarkowski, Douglas L Rothman, and John H Krystal

* Psychiatry and Obstetrics/Gynecology, Yale University School of Medicine, New Haven, CT

neill.epperson@yale.edu

Whether postpartum affective disorders have a distinct pathophysiology has been a subject of intense debate. Given the temporal relationship between symptom onset and the hormonal changes associated with parturition, investigators have long assumed that neuroactive steroids play a distinct role in the pathophysiology of puerperal affective disorders. However, peripheral measures of sex hormones have failed to consistently distinguish women with postpartum major depression (PPD) from their healthy postpartum counterparts. The prevailing theory that there is a subpopulation of postpartum women who are "vulnerable" to sex steroid fluctuations and onset of mood disorders in the puerperium is supported by findings from Bloch et al., (2000) that women with a history of puerperal depression were more likely to experience a return of depressive symptoms during a pseudopregnancy and parturition, than parturient women with no such history.

Although there are a plethora of neuroimaging studies focusing brain neurochemistry and activation patterns in subjects with major depression, there are no such studies examining these aspects of brain function in women with onset of depression in the context of dramatic hormonal fluctuations such as those occurring with parturition. Both animal and human studies suggest that modulation of gamma-aminobutyric acid function by sex steroids and inspecific the progesterone derivative and neurosteroid, allopregnanolone play a major role in pathophysiology of reproductive endocrine-related mood disorders. To follow-up the findings of our colleagues Sanacora et al, (1999) that subjects with major depression compared to controls have reduced occipital cortex GABA levels, we have measured cortical GABA levels using proton magnetic resonance spectroscopy (1H-MRS) in depressed and non-depressed puerperal women.

Eleven women with PPD and 6 postpartum healthy controls (HCs) who were within 3 months of delivery and were still hypogonadal underwent occipital cortex GABA measurements using 1H-MRS. There was a trend (p=.10) for reduced cortical GABA levels (mean ± SD GABA in mmoles/kg brain) in the PPD group (1.40 ± .28) compared to the postpartum HCs (1.13 ± .34). Cortical GABA levels in both puerperal groups (PPD, p=.02; postpartum HC, p<.001) were significantly lower than those (1.67 ± .25) found in healthy menstruating women (n=12) during the follicular phase. Cortical GABA levels in women (n=4) with non-puerperal depression were lower (1.10 ± .66) than those found in the PPD group and similar to those found in the postpartum HCs.

These data suggest that with respect to cortical GABA levels postpartum women who are hypogonadal are not similar to those women who are in the "hypogonadal' phase of the menstrual cycle. In addition, the relationship between depressed and healthy subjects in the puerperium is opposite to that found between depressed and healthy subjects outside the pueperium. The implications of these findings will be further discussed. In addition, preliminary data demonstrating the impact of treatment with the selective serotonin reuptake inhibitor sertraline on cortical GABA levels in women with PPD will be presented.

References:

Bloch M, Schmidt PJ, Danaceau M, Murphy J, Nieman L, Rubinow DR. Effects of gonadal steroids in women with a history of postpartum depression. American Journal of Psychiatry (2000) 157:924-930.

Sanacora G, Mason GF, Rothman DL, Behar KL, Hyder F, Petroff OA, Berman RM, Charney DS, Krystal JH. Reduced cortical g-aminobutryric acid levels in depressed patients determined by 1H-magnetic resonance spectroscopy. Archives General Psychiatry (1999) 56:1043-1047.