کاهش هایپو سوخت و ساز بدن مغزی منطقه ای در زنان مبتلا به بی اشتهایی عصبی با تجویز تستوسترون
|کد مقاله||سال انتشار||مقاله انگلیسی||ترجمه فارسی||تعداد کلمات|
|33730||2004||11 صفحه PDF||سفارش دهید||محاسبه نشده|
Publisher : Elsevier - Science Direct (الزویر - ساینس دایرکت)
Journal : Psychiatry Research: Neuroimaging, Volume 132, Issue 3, 30 December 2004, Pages 197–207
Abnormalities in brain metabolism have not been consistently well localized in anorexia nervosa (AN), and effects of specific therapies on these functional abnormalities have not been studied. Androgen replacement therapy improves mood, well-being and cognitive function in men with androgen deficiency. We therefore hypothesized that women with AN and relative androgen deficiency would exhibit regional brain hypometabolism compared with healthy controls, and that low-dose physiologic androgen replacement would attenuate the hypometabolism in some of these brain loci. We used FDG PET and statistical parametric mapping methods to investigate regional brain glucose metabolism in (1) 14 women with AN and 20 healthy control subjects of similar mean age and (2) women with AN after randomization to low-dose replacement testosterone therapy or placebo. Cerebral metabolism was decreased in the posterior cingulate, pregenual anterior cingulate, left middle temporal, right superior temporal, and left dorsolateral prefrontal cortex in the AN group compared with controls. In AN patients receiving testosterone, cerebral metabolism increased in the posterior cingulate, subgenual anterior cingulate, premotor cortex, right caudate and right parietal lobes. In conclusion, our data demonstrate distinct loci of regional brain hypometabolism in women with AN compared with controls. Moreover, abnormalities in one of these regions—the posterior cingulate cortex—were attenuated towards normal with low-dose testosterone replacement therapy. Further study is warranted to replicate these findings, as well as to determine their physiological and clinical significance.
Anorexia nervosa (AN), with a prevalence of 0.5–1% of college-age women (Jones et al., 1980, Lucas et al., 1991, Pope et al., 1984 and Wakeling, 1996), is a psychiatric disorder characterized by self-starvation, impaired body image and amenorrhea (DSM-IV). Neuroimaging studies have demonstrated structural and functional brain abnormalities in women with AN. Structural findings include a generalized decrease in brain volume (Husain et al., 1992 and Katzman et al., 1996), which has been shown to normalize with weight gain (Golden et al., 1996, Katzman et al., 1997 and Swayze et al., 2003). Functional abnormalities have been identified using positron emission tomography (PET), single photon emission computed tomography (SPECT) and functional magnetic resonance imaging (fMRI) in small numbers of patients. PET studies have demonstrated decreased cerebral glucose metabolism in the parietal (Delvenne et al., 1995, Delvenne et al., 1996 and Delvenne et al., 1997) and superior frontal cortices (Delvenne et al., 1995 and Delvenne et al., 1996) and increased metabolism in the caudate nuclei (Delvenne et al., 1996, Delvenne et al., 1999, Herholz et al., 1987 and Krieg et al., 1991) and inferior frontal cortex (Delvenne et al., 1996 and Delvenne et al., 1999). In addition, cerebral activity has been shown to normalize with weight gain in these patients (Delvenne et al., 1996 and Herholz et al., 1987). One small study has suggested a possible role for the anterior cingulate gyrus (Naruo et al., 2001). Exposure to high caloric food stimuli has been shown to cause greater activation within the anterior cingulate gyrus in two studies (Ellison et al., 1998 and Uher et al., 2003) and left occipital cortex and right temporo-occipital cortex in another study of young women with AN compared with control subjects (Gordon et al., 2001). However, to our knowledge, the effects of specific therapies on functional abnormalities in AN have not been studied. Women with AN are at risk for androgen deficiency (Monteleone et al., 2001 and Soyka et al., 1999). Although testosterone levels in women are only one-tenth those of men, testosterone deficiency in women may be associated with similar effects. Hypogonadism in men is characterized by depression (Burris et al., 1992, Seidman and Rabkin, 1998 and Shores et al., 2004), diminished libido (Bagatell et al., 1994) and poor quality of life (Howell et al., 2000). Moreover, testosterone administration reverses many of these abnormalities (Janowsky et al., 1994 and Wang et al., 1996). For example, Grinspoon et al. (2000) reported that testosterone administration in hypogonadal men with HIV-associated weight loss improved indices of depression. In addition, testosterone administration may result in improvement of psychiatric symptoms in men with refractory depression (Perry et al., 2002, Pope Jr. et al., 2003 and Seidman and Rabkin, 1998). Although few studies have examined the effects of low-dose androgen therapy in women, the available data suggest that administration of testosterone or testosterone precursors, including DHEA, may result in improvements in libido, mood and well-being in women with androgen deficiency (Arlt et al., 2000 and Shifren et al., 2000). Androgen administration may affect brain function directly through androgen receptors and indirectly through conversion to estrogen and dihydrotestosterone, both of which are important neuromodulators capable of stimulating 5-hydroxytryptamine receptors and serotonin transporter protein metabolism (Simerly, 1993 and Celotti et al., 1997). We hypothesized that (1) women with AN would exhibit regional brain hypometabolism compared with control subjects and (2) low-dose testosterone replacement therapy would normalize regional brain hypometabolism in women with relative testosterone deficiency associated with AN. We therefore studied 14 women with AN, using FDG PET, and compared them with 20 healthy control subjects to identify specific regions of cerebral hypometabolism. Twelve of the women with AN were randomized to receive low-dose testosterone by transdermal patch (Intrinsa™, Procter and Gamble Pharmaceuticals, Cincinnati, OH) or placebo to determine whether testosterone therapy attenuated any of the abnormalities observed in the women with AN at baseline.