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Sex Differences in Affective Disorders: A Developmental Neuroscience Framework on the Role of Puberty
1Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA;
Annual Review of Clinical Psychology
|May 7, 2026
Summary
Adolescent girls face higher risks for affective disorders due to sex-specific hormonal influences on brain development. This impacts neural sensitivity and reward processing, increasing vulnerability to anxiety and depression.
Area of Science:
- Neuroscience
- Developmental Psychology
- Endocrinology
Background:
- Affective disorders significantly increase during adolescence.
- Girls exhibit approximately double the risk of affective disorders compared to boys.
- The neurodevelopmental mechanisms driving this sex difference are not fully understood.
Purpose of the Study:
- To propose a heuristic model explaining sex-specific neurodevelopmental mechanisms underlying adolescent affective disorders.
- To elucidate the role of pubertal hormones in modulating mesocorticolimbic circuitry maturation.
- To identify potential sex-specific risk markers for early intervention.
Main Methods:
- Review of existing human neuroimaging and animal studies.
- Integration of evidence on hormonal pathways and neuroplasticity.
- Development of a heuristic model of sex-specific vulnerability.
Main Results:
- Pubertal hormones modulate mesocorticolimbic circuitry (amygdala, nucleus accumbens, ventral tegmental area, ventromedial prefrontal cortex) in sex-specific ways.
- In girls, gonadal hormones may increase threat sensitivity and dampen reward responsiveness.
- This can bias socio-affective learning towards avoidance during adolescence.
Conclusions:
- Convergent hormonal pathways shape adolescent brain circuitry, conferring risk for affective disorders.
- Developmental neuroscience frameworks are crucial for identifying sex-specific risk markers.
- Understanding these mechanisms can inform mechanism-based early interventions for affective disorders.
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