ultimate question is whether treatments will be optimized by incorporating sex and gender principles into interventions.

Women are 1.5 to 2.5 times more likely to experience major depression than men, from puberty onward. Women have the highest prevalence of depression during the childbearing years and are also at increased risk during the perimenopausal period (the 5-year period before the cessation of menses). According to a World Health Organization study, depression is the leading cause of days lost to disability for women worldwide. Depression is often discussed as if it was a homogeneous illness, but further study is needed into the different subtypes of depression and how they vary by sex and gender.

Wisner cited one recent study that included sex-specific analyses is the STAR*D (Sequenced Treatment Alternatives to Relieve Depression) study, a large-scale clinical trial of multiple depression treatments (Marcus et al., 2005). The investigators found differences in symptoms between the two sexes. Depressed women experienced more anxiety, physical somatoform symptoms, and bulimia. For men, the symptoms concurrent with depression tended to be obsessive-compulsive symptoms and substance use. Depressive episodes were longer in women than men, and suicide attempts occurred more frequently. Interestingly, women were more likely than men to have remission (loss of all symptoms) in response to the drugs under investigation (30 percent of women compared to 24 percent of men), and half of women responded (had symptom reduction) compared to 44 percent of men. The question facing clinicians now is how to apply this information.

Individualized, personalized treatment for depression and other psychiatric illnesses is a primary goal of translational research. In addition to sex and gender, individuals vary with regard to symptoms, comorbidities, clinical factors, personal history, family features, social background, genetic polymorphisms, developmental stage, and characteristics identified from brain imaging or other technologies. Differences in the longitudinal development of males and females also naturally provide a variety of hormonal conditions under which to study sex differences as well as the hormonal changes that are unique to females: in utero differentiation, menarche, the premenstruum, pregnancy, postpartum, and menopause.

When considering a disease state or a process, there is a broad biological-to-societal spectrum of distal health determinants that fluctuate throughout an individual’s lifetime; from basic genetics, to gene–environment interactions, to the physical and social environments (e.g., which pollutants or other stressors an individual is subjected to often vary by gender) (Misra et al., 2003). Proximal determinants, including biomedical responses (e.g., nutritional status, inflammatory response) and behavioral responses (e.g., alcohol use, actively practicing a religion) impact the disease process acutely. Health outcomes are influenced by these distal and proximal determinants, as well as by inputs and processes such as health care.



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