About health grants awarded by National Institute of Mental Health (NIMH)

The epidemiology and disability burden of mental disorders provide clear evidence of the value of a focus on sex and gender differences research. There are differences in both the prevalence and clinical course of mental disorders between men and women. Starting in childhood, girls have higher rates of anxiety disorders than boys. Boys have higher rates of autism and attention deficit disorder. After puberty, women have higher rates than men of depression, eating disorders, and anxiety disorders, including post-traumatic stress disorder. Men are more likely to suffer from substance abuse disorders. For other serious mental disorders, such as schizophrenia and bipolar disorder, gender disparities in incidence are not found. However, significant differences in clinical course have been demonstrated. This pattern of disparities in the epidemiology of mental disorders in males and females provides indirect evidence of genetic, hormonal, biological, social, cultural and developmental factors in etiology and course. An increasing body of basic and clinical research also provides evidence of neurobiological sex differences that may predispose to clinical differences in mental disorders. The finding of sex/gender differences in epidemiological, basic, and clinical studies has also increased interest in the application of that knowledge to improving interventions and services for males and females. In recognition of the importance of studying sex/gender differences in health outcomes, the National Institutes of Health (NIH) has provided guidelines to researchers for inclusion of women and men in clinical research and for gender analysis of clinical trials outcomes. Through research such as that called for in this Funding Opportunity Announcement (FOA), the National Institute of Mental Health (NIMH) seeks to increase the understanding of the significance of sex/gender differences in mental health outcomes and to assess their significance for basic neuroscience, mental health prevention, treatment, and services.

1) Basic and Clinical Neuroscience - There is increasing evidence that neurobiological sex differences influence a wide array of behaviors and may alter vulnerability to: different mental illnesses, severity of course, and/or treatment response. Basic studies in animals and humans as well as human clinical studies in subjects with mental illnesses are appropriate for developing knowledge of the processes underlying sex differences.

Examples of research areas include, but are not limited to, studies of:

• Sex differences in brain processes contributing to cognitive, affective and social behaviors as determined by structural and functional brain imaging of normative and clinical populations or by a systems level of analysis in appropriate animal models.
• Sex differences in the molecular and cellular bases of behavior, including neurotransmitter and peptide signaling, trophic factor response, neurogenesis and glial biology, synaptic plasticity and neural circuitry mediating cognition and mood.
• Sex differences in genetic and/or epigenetic factors and/or gene-environment interactions contributing to mental disorders.
• Sex differences in the developmental-organizing and activating influences of sex steroids on brain and behavior, as well as interactions with thyroid- and hypothalamic-pituitary adrenal axes, the neuroimmune system, and neurotransmitters and peptides in brain.
• Sex differences in, and sex hormone influences on, the pharmacokinetics, pharmacodynamics and pharmacogenetics of psychotropic medications across the lifespan.
• The influence of hormonal transitions across the lifespan on brain physiology and function, including, for example, neural plasticity, cognition, social behavior and affective behavior.
• Determination of the functional significance of molecular and cellular effects of estrogen, progesterone, and related molecules within circuits mediating cognition, social behavior, and affect.
• Development of selective ligands to explore the role of brain hormones and hormone receptors in behavioral regulation and for in vivo imaging of receptor dynamics across the female lifespan.
Evidence suggests that sex differences in hormone actions contribute to differences in physiological and behavioral responses to stress relevant to cognitive and emotional regulation and mental disorders. There are also sex/gender differences in the types of stressors to which an individual is likely to be exposed. For example, epidemiological studies show that females are more likely to have experienced early childhood sexual abuse, a severe stress with potential long-term impact on stress responsiveness. To understand this complex area, multidisciplinary approaches are required, ranging from basic research in animals and humans to clinical research in children, adults, and the elderly.

Examples of relevant research areas include, but are not limited to:

• Examination of genetic, molecular, and cellular brain mechanisms mediating sex differences in the stress effects on mood, arousal, sleep, cognition, affiliative behavior, and susceptibility to mental disorders
• Elucidation of how biological sex influences developmental mechanisms that underlie susceptibility to adverse consequences of stress and risk for mental disorders throughout life.
2) Epidemiology and Risk Factors - During the past two decades, advances in diagnosis and in survey methodologies have enabled researchers to establish general estimates of the impact of mental disorders in women and men and their intervention and service needs. Such research remains to be done for children and adolescents and is particularly pressing, because in many disorders, gender differences first emerge in adolescence when early intervention strategies may be most effective in preventing full-blown mental disorders. There is also relatively little information about the influence of gender-related or gender-specific factors on such important clinical aspects of mental disorders as risk for recurrence, chronicity, comorbidity and disability in later life. Studies to further elucidate the role of sex/gender-related or sex/gender-specific factors in diagnosis, epidemiology, risk for onset or recurrence, and in the course of mental disorders across the lifespan and across ethnic and cultural groups are needed.

Examples of relevant research areas include, but are not limited to:

• Elucidation of disparities in prevalence of mental illness and related disability, and in access to care among women and girls of different ethnic and socioeconomic backgrounds.
• Assessment of the reliability, validity and predictive value of approaches to conceptualizing and measuring psychopathology in female populations.
• Identification of demographic variables and social, cultural, behavioral and environmental factors related to gender differences in mental disorders (e.g., work and family roles, marriage, gender discrimination, response to psychosocial stressors, propensity to use substances).
• Elucidation of childhood risk and protective factors related to the emergence of gender disparities in incidence and course of mental disorders (particularly mood, anxiety, and eating disorders).
• The roles of hormonal, genetic, and social factors in the emergence of sex/gender differences in susceptibility to mental disorders, mood, and cognitive disruption during defined transitional periods including puberty, pregnancy, the postpartum period, and perimenopause.
3) Intervention and Services Research - There are an increasing number of findings indicating sex/gender differences in response to interventions as well as in preferences for different kinds of services and interventions. Additionally, women's social roles and reproductive status raise special issues related to choices of treatments and services. Interventions are defined here to include preventive, treatment, services-system and rehabilitative strategies at the individual, provider, organizational and systems levels. There is a need to incorporate consideration of such issues in the design and analysis of outcomes in mental health research.
Examples of relevant research areas include, but are not limited to, studies of:
• Sex/gender differences in acute and maintenance treatment outcomes for mental disorders and suicidal behaviors.
• Sex/gender differences in treatment adherence and side effects of treatments and in treatment preferences, expectancies, provider behaviors, and services use.
• Drug-drug interactions (e.g., supplements, replacement hormones, and psychotropic and other medications) in females across the life span.
• Strategies for early detection of precursors to depression, anxiety, eating disorders, suicidality, and other behavioral disorders in female children and adolescents; the development of interventions targeting these manifestations; and the development of effective mechanisms for successful referral and adherence to treatment.
• Interventions aimed at improving outcomes in women and girls at risk for mental disorders or diagnosed with mental disorders co-morbid with other disorders (e.g., anxiety disorders in depression; substance abuse in women with bipolar disorder or schizophrenia, depression, and medical illness).
• Preventive interventions for mental disorders with female-specific risk factors (e.g., stressors in caregiver roles, etc.).
• Taxonomies of functional outcomes and disabilities in women and girls with mental disorders and instruments to measure functional changes following interventions.
• Screening and identification of women with mental disorders and of women who are at high risk for the development of such disorders in general medical settings and in non-traditional settings, with the development of effective strategies for referral and treatment.

Source: http://grants.nih.gov/grants/guide/pa-files/PA-09-109.html