The funding agency, the NICHD, did not make a non-competing continuation award for the fifth and final year of the project and moved the grant into closeout.

This study will provide valuable information on the neurobiological underpinning of gender dysphoria (GD) and the effects of sex hormones, and promises to uncover functional or structural neural patterns that could predict outcome in terms of body image and quality of life after cross-sex hormone treatment.

The purpose of this study is to understand the neurobiology of gender dysphoria (GD) and the interactions between cross hormone treatment, the brain, and the body phenotype. The investigators also aim to identify pre-treatment neurobiological and other factors to help predict body congruence and quality of life outcomes from hormone treatment. There is mounting interest in gender identity issues worldwide, as requests for gender-confirming treatments have increased in the past 3 decades, and alarmingly high suicide rates have recently been reported in those with GD. Despite this, little is known about neurobiological or other etiological factors contributing to GD or gender incongruence. This study will address a core feature of GD that has been little studied in terms of the neurobiology: the incongruence between perception of self and one's own body.

Participants with gender dysphoria (GD)

Inclusion Criteria:

• Females and males from any racial or ethnic background, between the ages of 18 years and 40 years.
• Participants must meet Diagnostic and Statistical Manual-5 criteria for GD (302.85)
• Intelligence quotient (IQ) > 80

Participants with GD

Exclusion Criteria:

• Previous or on-going sex hormone medication
• Previous sex reassignment surgery
• Oral contraceptives
• Participants with GD are not be taking any other psychotropic medication. (No participant will be recommended to discontinue or taper medications for the purpose of participating in the study.)
• Irregular menstrual cycles

Control participants

Inclusion Criteria:

• Females and males from any racial or ethnic background, between the ages of 18 and 40.
• IQ > 80

Control participants

Exclusion Criteria:

• Psychiatric medications
• A score of ≥ 1 standard deviation higher than population norms on the MADRS depression or the Hamilton anxiety scale (HAMA)
• Sex hormone treatment
• Irregular menstrual cycles

Exclusion criteria for all participants:

• Any known chromosomal or hormonal disorder
• Current substance abuse or dependence
• Current neurological disorder or psychiatric disorder
• Pregnancy
• Current major medical disorders that may affect cerebral metabolism such as diabetes or thyroid disorders
• Head trauma associated with loss of consciousness
• HIV positive individuals
• Individuals with ferromagnetic metal implantations or devices. This includes any electronic implants or devices, braces, infusion pumps, aneurysm clips, metal fragments or foreign bodies, metal prostheses, joints, rods or plates
• Visual acuity worse than 20/35 for each eye as determined by Snellen close vision acuity chart. Acuity may be met with corrective lenses

Investigators will enroll 150 participants between the ages of 18 and 40 (25 trans males; 25 trans females; 25 cis gender females; 25 cis gender males; 25 homosexual males; 25 homosexual females)