The Problem of Malnutrition Associated with Major Depressive Disorder from a Sex-Gender Perspective

Abstract

Major depressive disorder (MDD) is an incapacitating condition characterized by loss of interest, anhedonia and low mood, which affects almost 4% of people worldwide. With rising prevalence, it is considered a public health issue that affects economic productivity and heavily increases health costs alone or as a comorbidity for other pandemic non-communicable diseases (such as obesity, cardiovascular disease, diabetes, inflammatory bowel diseases, etc.). What is even more noteworthy is the double number of women suffering from MDD compared to men. In fact, this sex-related ratio has been contemplated since men and women have different sexual hormone oscillations, where women meet significant changes depending on the age range and moment of life (menstruation, premenstruation, pregnancy, postpartum, menopause…), which seem to be associated with susceptibility to depressive symptoms. For instance, a decreased estrogen level promotes decreased activation of serotonin transporters. Nevertheless, sexual hormones are not the only triggers that alter neurotransmission of monoamines and other neuropeptides. Actually, different dietary habits and/or nutritional requirements for specific moments of life severely affect MDD pathophysiology in women. In this context, the present review aims to descriptively collect information regarding the role of malnutrition in MDD onset and course, focusing on female patient and especially macro- and micronutrient deficiencies (amino acids, ω3 polyunsaturated fatty acids (ω3 PUFAs), folate, vitamin B12, vitamin D, minerals…), besides providing evidence for future nutritional intervention programs with a sex-gender perspective that hopefully improves mental health and quality of life in women.

Keywords: deficiencies; depression; malnutrition; menopause; menstrual cycle; postpartum; pregnancy; premenstrual dysphoric disorder; premenstrual syndrome; sex differences; stress.

Figure 1

General pathophysiology of MDD. Elevated stress affects the HPA axis involving cellular and molecular changes, resulting in brain structural and functional changes. For instance, abnormal neurotransmission, microglial activation, neuronal damage and dysregulation of neuroplastic and neurotrophic factors can be reported in patients with MDD. These alterations are frequently accompanied by enhanced oxidative stress and circadian rhythms disruption. Exacerbated systemic inflammation and gut dysbiosis and enhanced intestinal barrier permeability are also major characteristics of patients with MDD. It is of note that all these mechanisms boost each other, perpetuating the damage and pathologic environment related to MDD.

Figure 2

Hallmarks in women-specific MDD pathophysiology. Different moments in a woman’s life entail different hormone fluctuations with consequences at the neurotransmitter level. These changes also affect estrobolome functions and positively correlate with MDD severity. Different immune response compared to men is also emphasized. MDD = major depressive disorder; PMS = premenstrual syndrome; PMDD = premenstrual dysphoric disorder; PPD = postpartum depression; E2 = estradiol.

Figure 3

Nutritional deficiencies observed at different moments in a woman’s life that are associated with depressive symptoms. As summarized, there is in general a poor dietary context in women with depression, characterized by low fiber intake, high refined carbohydrates and sugar, unhealthy fats and low-quality protein intake, with detrimental effects on the brain. The improper dietary context is also related to several micronutritional deficiencies in women, with some particularities depending on the moment of their lives. MS: premenstrual syndrome; PMDD: premenstrual dysphoric disorder, PPD: postpartum depression; E2: estradiol.