Allopregnanolone impairs episodic memory in healthy women

Kask, Kristiina; Bäckström, Torbjörn; Nilsson, Lars‐Göran; Sundström‐Poromaa, Inger

doi:10.1007/s00213-008-1150-7

Cited by 58 publications

(40 citation statements)

References 36 publications

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“…Neurosteroids potentiate the GABA A receptor, where they increase hyperpolarization and act in a similar manner to barbiturates and benzodiazepines (Melcangi et al, 2011). As GABA is the major inhibitory transmitter in the central nervous system, acute administration of allopregnanolone has sedative, anxiolytic, anti-convulsant properties but may also negatively influence cognitive function (Johansson et al, 2002; Kask et al, 2008a; Melcangi et al, 2011). A functionally relevant amount of allopregnanolone is synthesized in the brain, but the main source of brain and serum allopregnanolone in non-pregnant women is progesterone synthesized by the corpus luteum (Ottander et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Menstrual cycle influence on cognitive function and emotion processingâ€”from a reproductive perspective

2014

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The menstrual cycle has attracted research interest ever since the 1930s. For many researchers the menstrual cycle is an excellent model of ovarian steroid influence on emotion, behavior, and cognition. Over the past years methodological improvements in menstrual cycle studies have been noted, and this review summarizes the findings of methodologically sound menstrual cycle studies in healthy women. Whereas the predominant hypotheses of the cognitive field state that sexually dimorphic cognitive skills that favor men are improved during menstrual cycle phases with low estrogen and that cognitive skills that favor women are improved during cycle phases with increased estrogen and/or progesterone, this review has not found sufficient evidence to support any of these hypotheses. Mental rotation has gained specific interest in this aspect, but a meta-analysis yielded a standardized mean difference in error rate of 1.61 (95% CI −0.35 to 3.57), suggesting, at present, no favor of an early follicular phase improvement in mental rotation performance. Besides the sexually dimorphic cognitive skills, studies exploring menstrual cycle effects on tasks that probe prefrontal cortex function, for instance verbal or spatial working memory, have also been reviewed. While studies thus far are few, results at hand suggest improved performance at times of high estradiol levels. Menstrual cycle studies on emotional processing, on the other hand, tap into the emotional disorders of the luteal phase, and may be of relevance for women with premenstrual disorders. Although evidence at present is limited, it is suggested that emotion recognition, consolidation of emotional memories, and fear extinction is modulated by the menstrual cycle in women. With the use of functional magnetic resonance imaging, several studies report changes in brain reactivity across the menstrual cycle, most notably increased amygdala reactivity in the luteal phase. Thus, to the extent that behavioral changes have been demonstrated over the course of the menstrual cycle, the best evidence suggests that differences in sexually dimorphic tasks are small and difficult to replicate. However, emotion-related changes are more consistently found, and are better associated with progesterone than with estradiol such that high progesterone levels are associated with increased amygdala reactivity and increased emotional memory.

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Section: Introductionmentioning

confidence: 99%

Menstrual cycle influence on cognitive function and emotion processingâ€”from a reproductive perspective

2014

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“…In an investigation of verbal memory, high doses of exogenously administered progesterone impaired immediate verbal recall (Freeman et al 1992) and facial recognition (van Wingen et al 2008a). Similarly, the progesterone metabolite allopregnanolone has been shown to impair episodic memory (Kask et al 2008). Importantly, however, these findings are based on progesterone levels 10-fold higher than those observed in the luteal phase, suggesting that progesterone's cognitive effects may be dose dependent.…”

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confidence: 99%

Progesterone at encoding predicts subsequent emotional memory

Ertman¹,

Andreano²,

Cahill³

2011

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Significant sex differences in the well-documented relationship between stress hormones and memory have emerged in recent studies. The potentiating effects of glucocorticoids on memory vary across the menstrual cycle, suggesting a potential interaction between these stress hormones and endogenously cycling sex hormones. Here, we show that memory for emotional materials changes significantly in accordance with hormonal changes across the menstrual cycle, suggesting that ovarian sex hormones influence the modulation of emotional memories. Sixty healthy, naturally cycling women rated 120 images on arousal and valence. One week later they completed free recall and recognition memory tests. Their menstrual cycle phases were estimated by self-report and confirmed by salivary assay of 17b-estradiol and progesterone. Memory for emotional items only was significantly better in the high hormone (luteal) phase compared with the low hormone (follicular) phase on the free recall test; on both tests memory correlated positively with progesterone collected at the time of encoding. These findings suggest that emotional memory performance changes across the menstrual cycle, and that this change is in part mediated by endogenous progesterone cycling.

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“…After delivery, the allopregnanolone level rapidly drops to 2 nmol/l within a few days, but slightly elevated levels (approximately 1 nmol/l) are seen several weeks following parturition [7,8]. When intravenously administered to nonpregnant women, pregnancy-like allopregnanolone serum concentrations are sedative [9], and impair immediate recall [10], symptoms which do not affect late pregnant women in general [11]. These observations suggest that a tolerance to allopregnanolone develops during pregnancy.…”

Section: Introductionmentioning

confidence: 99%

Low Serum Allopregnanolone Is Associated with Symptoms of Depression in Late Pregnancy

et al. 2014

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Background: Allopregnanolone (3α-hydroxy-5α-pregnan-20-one) is a neurosteroid which has an inhibitory function through interaction with the GABA_A receptor. This progesterone metabolite has strong sedative and anxiolytic properties, and low endogenous levels have been associated with depressed mood. This study aimed to investigate whether the very high serum allopregnanolone levels in late pregnancy covary with concurrent self-rated symptoms of depression and anxiety. Methods: Ninety-six women in pregnancy weeks 37-40 rated symptoms of depression and anxiety with the Montgomery-Åsberg Depression Rating Scale (MADRS-S) and Spielberger State-Trait Anxiety Inventory. Their serum allopregnanolone was analyzed by Celite chromatography and radioimmunoassay. Results: Ten women had elevated depression scores (MADRS-S ≥13), and this group had significantly lower allopregnanolone levels compared to women with MADRS-S scores in the normal range (39.0 ± 17.9 vs. 54.6 ± 18.7 nmol/l, p = 0.014). A significant negative correlation was found between self-rated depression scores and allopregnanolone concentrations (Pearson's correlation coefficient = -0.220, p = 0.031). The linear association between self-rated depression scores and allopregnanolone serum concentrations remained significant when adjusted for gestational length, progesterone levels, and parity. Self-rated anxiety, however, was not associated with allopregnanolone serum concentrations during pregnancy. Conclusion: High allopregnanolone serum concentrations may protect against depressed mood during pregnancy.

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Allopregnanolone impairs episodic memory in healthy women

Abstract: Intravenous allopregnanolone impairs episodic memory in healthy women, but there is a high degree of individual variability.

Cited by 58 publications

References 36 publications

Menstrual cycle influence on cognitive function and emotion processingâ€”from a reproductive perspective

Menstrual cycle influence on cognitive function and emotion processingâ€”from a reproductive perspective

Progesterone at encoding predicts subsequent emotional memory

Low Serum Allopregnanolone Is Associated with Symptoms of Depression in Late Pregnancy

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