**10.4 Postpartum depression (PPD)**

*Vitamin D Deficiency*

**10.2 Major depressive disorders**

independent correlative associated with depression [16].

decisive role in mood disorder case studies [4, 22, 24].

**10.3 Premenstrual syndrome**

For example, initiation of the behavioral changes such as migration patterns and breeding behavior is conserved in many species, primates, and humans which are evident with changes in season and intensity of sunrays. Further, the scientists pointed out that the regulation of circadian phase shift is located in the suprachiasmatic nucleus (SCN) of the hypothalamus. The SCN has been shown to be involved in seasonal affective mood disorders. Further it was also presented that the SCN has an inhibitory action to the hypothalamic–pituitary–adrenal (HPA) axis and that this action can be altered by vitamin D dietary and supplementation restrictions [23].

Major depressive disorder is a type of depressive disorder that is most likely to observe an association between vitamin D deficiency and anxio-depressive disorders. This association can be demonstrated with a parallel comparison between the motor and behavioral disorders observed in animal models of depression and VDR-KO mice [13]. Several theories are suggesting seasonal mood swings in humans. The binding of vitamin D on the ligand binding site of VDR present on the hypothalamic core (which plays a crucial role in mood regulation) can be witnessed to have a link between several seasonal changes in photoperiod and seasonal mood swings. Epidemiological data are coherent with such a cross-linking hypothesis. As an instance, the evidence is suggestive that the established low serum 25(OH) vitamin D2 concentrations are closely related to the active experience of mood disorders in 80 subjects aging 65 years and older. Many studies have demonstrated that significant lower serum 25(OH) vitamin D2 and 1,25(OH)2 vitamin D3 concentrations are observed in depressive sample subjects than healthy controlled subjects. Indirect confirmation was made by studying the association between depression and osteoporosis in around 4000 women aged 67 years [15]. Nevertheless, these results can also be mitigated and potentially related to functional impairment and physical inactivity, both of which reasons to increase with osteoporosis and have an

Various clinical trials support the theory of the efficacy of vitamin D supplementation on mood disorders by varied sources like vitamin D-fortified diet, sunsoaking, etc. [17]. Improvement in depression scale experiments was noted, and the improvements were associated with vitamin D supplementation technique, while not much improvement was observed with the phototherapy technique. It is specifically prescribed to have at least 800 IU daily dose of vitamin D which plays a major

Premenopausal women face one of the most common disorders known as premenstrual syndrome. Up to 20% of reproductive-aged women are affected in the range of moderate-to-severe premenstrual syndrome and is associated with significant levels of mood impairment. Irritability, mood swings, anxiety, depression, breast tenderness, bloating, and headaches are some of the most common symptoms included in PMS. Women are reported to have a depressed mood during the last week of the luteal phase which resides within for few days from the onset of menses [9]. Many studies have postulated that blood serum calcium levels and vitamin D levels are lower in women with PMS and that vitamin D supplementation

and calcium supplementation may reduce the severity of the symptoms [25].

It is hypothesized that the dysregulation of calciotropic hormone is seen to be a major provocative factor in premenstrual syndrome. The severity of the symptoms of PMS is directly linked to calcium homeostasis, regulated directly by vitamin D

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Vitamin D insufficiency is common in its most vulnerable pregnant population, and several studies have demonstrated the association of diminished levels of 25(OH) vitamin D with depressive symptoms [4]. Further, the diagnosis of low levels of 25(OH) vitamin D in maternal serum during pregnancy is associated with a higher incidental risk of postpartum depressive symptoms [26, 27]. Serum 25(OH) vitamin D levels for pregnant and postpartum women with major depressive episode, beginning within the first 4 weeks after childbirth, can be influenced by a multitude of factors like age, race/ethnicity, marital status, type of insurance, educational level, feeding type, and others. In addition, the season that accounts for the amount and strength of UVB exposure, i.e., photoperiod and vitamin D supplementation, also are found to be responsible for the episodes of major depression [28]. Vitamin D supplementation during pregnancy increases maternal serum 25(OH) vitamin D levels and thereby ensures higher availability for the offspring neuronal development. Vitamin D levels can also be inversely associated with infertility parameters, preeclampsia, blood glucose, bacterial vaginosis, primary caesarean section, and postpartum depression, but direct correlation is seen in pregnancy associated with breast cancer [28, 29].

The core symptoms of PPD are similar to that of any major depressive disorder like depressed mood or loss of interest in normal activities, sleep and appetite disturbances, loss of energy, feelings of guilt, and suicidal thoughts. Hence, the diagnosis of PPD becomes challenging as the sleep pattern changes and weight changes are also often observed in the normal postpartum period. It is further also exhibited that the lower maternal 1,25(OH)2 vitamin D levels have been found to be associated with higher levels of postpartum depressive symptoms as per the Edinburgh Postpartum Depression Scale scores. The promising results were observed by only one randomized clinical trial wherein the assessment was done by administration of high-dose vitamin D therapy in depressed subjects [6, 7].

Following birth in the first few days, the lower levels of 25(OH) vitamin D are reported for a greater risk of postnatal depressive symptoms and are also linked to serum vitamin D level in the second trimester of pregnancy. Further, the association of low 25(OH) vitamin D level was established with a continuous enhancing risk of reported level of symptoms that may indicate any one type of mood disturbance. Thus, it is confirmed that adequate intake of vitamin D is essential during pregnancy not only for the positive impact on the health and development of the offspring but also is a way to protect against postpartum mood disturbance in mothers [26]. Also, estrogen supplementation and vitamin D therapies have beneficiary effects on inflammatory response and related factors in women suffering from PPD [6, 29, 30].

When accounting the cortisol levels and hypothalamic–pituitary–adrenal axis reactivity in postpartum women, during the third trimester, maternal cortisol levels reach approximately three times that of nonpregnant levels. While the basal levels of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone, and cortisol are high, the HPA axis reactivity to stressful stimuli is dampened in late pregnancy. Furthermore, while the baseline cortisol levels return to normal within a couple of days after parturition, the hyporesponsiveness of HPA axis is found to be persistent in breastfeeding women [6].

The HPA axis hyperactivation or hypoactivation has always been associated with depressive states. It has also been hypothesized that depression during pregnancy

and postpartum depression may have different pathogenesis; the first is found to be dejected with hyperactivity in the HPA axis and the second being atypical. The activity of the HPA axis is usually reduced in seasonal affective disorder, atypical depression, and PPD, which could point to a similar pathologic mechanism in all the three conditions mentioned. Furthermore, the physiological excess production of CRH at the end of pregnancy leads to a transient downregulation of hypothalamic CRH postpartum, which could possibly lead to an elevated risk for depression. Indeed, the hypothesis of PPD being related to hypoactivation of the HPA axis has been substantiated by a number of studies where women with PPD display lower baseline or reduced HPA responsiveness than controls, although conflicting data are available. In addition, women with a history of PPD appear to have increased levels of corticotropin-releasing hormone which further stimulates the dependent cortisol response in the experimental conditions of pregnancy. PPD can also be predicted by increased stress-induced cortisol levels or CRH levels [6, 20].

Together with SAD, PPD has also been classified, under the depressive states characterized by hypoactivation of the HPA axis. Increased serum concentrations of biomarkers detecting the inflammatory response, for example, IL-6, a proinflammatory cytokine with a variety of endocrine and metabolic actions, have been observed in major depressive conditions. In this, IL-6 interacts with the HPA axis, and the interacted complex has significant higher serum levels in women with postpartum depressive symptomatology. Conclusively, vitamin D affects monoamine functional groups, the HPA axis, and immune responses to stress and symptom production [20, 38].
