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Estrogen could control photoperiodic adjustment in seasonal affective disorder
Medical Hypotheses Medical Hypotheses(1995) 45, 35-36 © PearsonProfessionalLtd 1995
Estrogen Could Control Photoperiodic Adjustment in Seasonal Affective Disorder T. PARTONEN Department of Psychiatry, University of Helsinki, Tukholmankatu 8 C, FIN-O0290 Helsinki, Finland (Tel: +358-04713505; Fax: +358-0-4715478)
Abstract - - Women are affected by winter seasonal affective disorder (SAD) more often than men. The female/male ratio is reported to range from 2:1 to 40:1 in samples of patients with winter SAD. It is suggested that this preponderance of women is based on the action of the ovarian steroid hormones estrogen and progesterone. However, the detailed mechanisms of action are not well understood to date. A new hypothesis claims that, in women with winter SAD, decreased levels of estradiol in the ventromedial hypothalamus are associated with the occurrence of atypical symptoms of depression, including increased daytime sleepiness and hypersomnia during the winter. Introduction
suprachiasmatic nucleus (SCN) of the hypothalamus mediate different biological functions that depend on circadian information (1). The dorsal projections from the SCN to the paraventricular nucleus within the hypothalamus mediate photoperiodic information, such as gonadal responses to short photoperiods. However, the photoperiod-induced changes in behavioural sensitivity to gonadal steroids is suggested to be mediated by neural pathways distinct from those that mediate the gonadal responses. In fact, estradiol seems to be vital for high activity levels in long photoperiods (2). On the other hand, in short photoperiods, estradiol advances the peak of locomotor activity rhythm towards the period of darkness and stabilizes the onset of activity, having influence on the circadian time-keeping system. In female rats, the estrogen-receptive neurons are distributed in the periventricular preoptic nucleus and medial preoptic area of the hypothalamus (3). Estradiol decreases tyrosine hydroxylase activity in the former region but increases it in the latter.
The molecular basis for the increased vulnerability of women compared with men to the effects of the decreasing photoperiod is not understood, but it has been hypothesized to be based on the cellular actions of the ovarian steroid hormones estrogen and progesterone. Patients with winter seasonal affective disorder (SAD) may, in this respect, serve as good biological models for studies of this vulnerability. The female/male ratio ranges from 2:1 to 40:1 in various clinical samples, consisting of over 900 patients with winter SAD. This preponderance of women among the patients seems to become even more evident at high latitudes. The more northern the location, the greater the sex ratio will be in favour of women.
Discussion In female hamsters, efferent projections from the Date received 7 O c t o b e r 1994 Date accepted 28 D e c e m b e r 1994
35
36 Therefore, the dopaminergic as well as the noradrenergic neurons are, in all probability, influenced by estradiol. Estradiol decreases dopamine content via receptor down-regulation mechanisms in the medial basal hypothalamus but, conversely, enhances noradrenaline release by attenuating alpha2-adrenergic autoreceptor-mediated inhibition independent of variation in receptor density in the ventromedial hypothalamus (4). The steroid hormone receptors, including the human estrogen receptor, have been hypothesized to function as nuclear transcription factors that alter the expression of specific genes in the hypothalamus. In addition, the neurotransmitter dopamine has been shown to be capable of activating certain steroid hormone receptors, among them the chicken progesterone receptor (5). I hypothesize that, in women with winter SAD, decreased levels of estradiol in the ventromedial hypothalamus are likely to be associated with depressive symptoms including decreased physical activity, fatigue, increased sleepiness, and hypersomnia during the winter. The decrease in estradiol activity is hypothesized to be induced by the decreasing photoperiod. Forming an analogy with
MEDICALHYPOTHESES animal models, hypothalamic estradiol content might be vital for normal activity in humans as well, especially in those individuals with the genetic hypersensitivity to the effects of the decreasing photoperiod.
References 1. Badura L L, Sisk C L, Nunez A A. Neural pathways involved in the photoperiodic control of reproductive physiology and behavior in female hamsters (Mesocricetus auratus). Neuroendocrinology 1987; 46: 339-344. 2. Widmaier E P, Campbell C S. Interaction of estradiol and photopefiod on activity patterns in the female hamster. Physiol Behav 1980; 24: 923-930. 3. Yuri K, Kawata M. Region-specific changes of tyrosine hydroxylase-immunoreactivity by estrogen treatment in female rat hypothalamus. Brain Res 1994; 645: 278-284. 4. Etgen A M, Karkanias G B. Estrogen regulation of noradrenergic signaling in the hypothalamus. Psychoneuroendocrinology 1994; 19: 603--610. 5. Mani S K, Allen J M C, Clark J H, Blaustein J D, O'Malley B W. Convergent pathways for steroid hormone- and neurotransmitter-induced rat sexual behavior. Science 1994; 265: 1246-1249.
Estrogen Could Control Photoperiodic Adjustment in Seasonal Affective Disorder T. PARTONEN Department of Psychiatry, University of Helsinki, Tukholmankatu 8 C, FIN-O0290 Helsinki, Finland (Tel: +358-04713505; Fax: +358-0-4715478)
Abstract - - Women are affected by winter seasonal affective disorder (SAD) more often than men. The female/male ratio is reported to range from 2:1 to 40:1 in samples of patients with winter SAD. It is suggested that this preponderance of women is based on the action of the ovarian steroid hormones estrogen and progesterone. However, the detailed mechanisms of action are not well understood to date. A new hypothesis claims that, in women with winter SAD, decreased levels of estradiol in the ventromedial hypothalamus are associated with the occurrence of atypical symptoms of depression, including increased daytime sleepiness and hypersomnia during the winter. Introduction
suprachiasmatic nucleus (SCN) of the hypothalamus mediate different biological functions that depend on circadian information (1). The dorsal projections from the SCN to the paraventricular nucleus within the hypothalamus mediate photoperiodic information, such as gonadal responses to short photoperiods. However, the photoperiod-induced changes in behavioural sensitivity to gonadal steroids is suggested to be mediated by neural pathways distinct from those that mediate the gonadal responses. In fact, estradiol seems to be vital for high activity levels in long photoperiods (2). On the other hand, in short photoperiods, estradiol advances the peak of locomotor activity rhythm towards the period of darkness and stabilizes the onset of activity, having influence on the circadian time-keeping system. In female rats, the estrogen-receptive neurons are distributed in the periventricular preoptic nucleus and medial preoptic area of the hypothalamus (3). Estradiol decreases tyrosine hydroxylase activity in the former region but increases it in the latter.
The molecular basis for the increased vulnerability of women compared with men to the effects of the decreasing photoperiod is not understood, but it has been hypothesized to be based on the cellular actions of the ovarian steroid hormones estrogen and progesterone. Patients with winter seasonal affective disorder (SAD) may, in this respect, serve as good biological models for studies of this vulnerability. The female/male ratio ranges from 2:1 to 40:1 in various clinical samples, consisting of over 900 patients with winter SAD. This preponderance of women among the patients seems to become even more evident at high latitudes. The more northern the location, the greater the sex ratio will be in favour of women.
Discussion In female hamsters, efferent projections from the Date received 7 O c t o b e r 1994 Date accepted 28 D e c e m b e r 1994
35
36 Therefore, the dopaminergic as well as the noradrenergic neurons are, in all probability, influenced by estradiol. Estradiol decreases dopamine content via receptor down-regulation mechanisms in the medial basal hypothalamus but, conversely, enhances noradrenaline release by attenuating alpha2-adrenergic autoreceptor-mediated inhibition independent of variation in receptor density in the ventromedial hypothalamus (4). The steroid hormone receptors, including the human estrogen receptor, have been hypothesized to function as nuclear transcription factors that alter the expression of specific genes in the hypothalamus. In addition, the neurotransmitter dopamine has been shown to be capable of activating certain steroid hormone receptors, among them the chicken progesterone receptor (5). I hypothesize that, in women with winter SAD, decreased levels of estradiol in the ventromedial hypothalamus are likely to be associated with depressive symptoms including decreased physical activity, fatigue, increased sleepiness, and hypersomnia during the winter. The decrease in estradiol activity is hypothesized to be induced by the decreasing photoperiod. Forming an analogy with
MEDICALHYPOTHESES animal models, hypothalamic estradiol content might be vital for normal activity in humans as well, especially in those individuals with the genetic hypersensitivity to the effects of the decreasing photoperiod.
References 1. Badura L L, Sisk C L, Nunez A A. Neural pathways involved in the photoperiodic control of reproductive physiology and behavior in female hamsters (Mesocricetus auratus). Neuroendocrinology 1987; 46: 339-344. 2. Widmaier E P, Campbell C S. Interaction of estradiol and photopefiod on activity patterns in the female hamster. Physiol Behav 1980; 24: 923-930. 3. Yuri K, Kawata M. Region-specific changes of tyrosine hydroxylase-immunoreactivity by estrogen treatment in female rat hypothalamus. Brain Res 1994; 645: 278-284. 4. Etgen A M, Karkanias G B. Estrogen regulation of noradrenergic signaling in the hypothalamus. Psychoneuroendocrinology 1994; 19: 603--610. 5. Mani S K, Allen J M C, Clark J H, Blaustein J D, O'Malley B W. Convergent pathways for steroid hormone- and neurotransmitter-induced rat sexual behavior. Science 1994; 265: 1246-1249.