Effect of Gonadal Hormones on Neurotransmitters Implicated in the Pathophysiology of Obsessive-Compulsive Disorder: A Critical Review

Abstract

Obsessive-compulsive disorder (OCD) is a relatively common neuropsychiatric disorder affecting between 1.6 and 3.2% of the population. A number of studies have previously reported increased incidence of OCD, or exacerbation of preexisting symptoms in females during reproductive events. Since these periods are known to involve fluctuating levels of gonadal hormones, these steroids have been suggested to be involved in modulating the course of the disorder. However, to date, only a few studies have measured hormone levels and obsessive-compulsive (OC) symptoms concurrently; thus, direct evidence for this relationship is limited. In turn, investigations into neurotransmission in OC individuals have been more extensive, and have implicated the serotonergic, dopaminergic, and glutamatergic neurotransmitter systems in OCD pathology. There is evidence suggesting that reproductive hormones estrogens and progesterone can modulate neurotransmission in the aforementioned signaling pathways by regulating the expression of receptors and channels, as well as the synthesis and release of the neurotransmitter itself. Overall, estrogen and progesterone appear to enhance serotonin signaling, which has been associated with improved OC symptoms. The effect of the gonadal hormones in dopaminergic and glutamatergic signaling is much more variable, highlighting the need for further research in this field. The existing evidence shows that gonadal hormones can have profound impacts on neurotransmission in the brain, leading to the conclusion that the hormonal fluctuations during reproductive events are a plausible factor contributing to the change in OCD course during these times.

Sex-Specific Involvement of Estrogen Receptors in Behavioral Responses to Stress and Psychomotor Activation

“…Both male and female Esr1 −/− mice display highly atrophied reproductive organs and are infertile (50–53) and female Esr1 −/− mice are anovulatory and acyclic (54, 55). Considering that gonadal hormones can affect dopamine response [see (56–58)], the difference in the hormonal status of these mice could contribute to the observed differences in amphetamine-induced hyperlocomotion. An enhancement of amphetamine-induced hyperlocomotion was also observed in female Esr2 knockout mice compared with their respective controls, whereas no difference was observed in male Esr2 −/− mice.…”

Potential Role of PlantsHordeum vulgareL. andPanax ginsengL. in Resolving the Fertility Disorders and Stress-Induced Oxidative Stress Arises from Hypothyroidism in Adult Female Rats

“…The binding of serotonin to 5-TH2 receptors stimulates ERK1/2 phosphorylation via the release of epidermal growth factor (EGF) agonist and transactivation of (EFG) receptors [41]. The improvement of serum oestradiol in hypothyroid-barley-treated groups as mentioned before could explain the positive effect of barley on restoring dopamine levels in brain tissues because the reproductive hormones, estrogen and progesterone, modulate the dysregulated serotonergic, dopaminergic, and glutamatergic neurotransmission by regulating the expression of receptors, the synthesis, reuptake, and release of the neurotransmitter serotonin and dopamine, which interact with dopaminergic neurons directly to downregulate D2 autoreceptors and indirectly by inhibiting GABAergic transmission [42].…”

Autoreceptor control of serotonin dynamics

“…All other parameters were as in the standard normal model described in the Methods. It is not surprising that the average response curves are different for males and females and that the best fit parameters are different because estradiol affects both TPH expression and a variety of 5HT receptors [ 84 – 86 ].…”