Title |
Sex-specific impact of prenatal androgens on social brain default mode subsystems
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Published in |
Molecular Psychiatry, August 2018
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DOI | 10.1038/s41380-018-0198-y |
Pubmed ID | |
Authors |
Michael V. Lombardo, Bonnie Auyeung, Tiziano Pramparo, Angélique Quartier, Jérémie Courraud, Rosemary J. Holt, Jack Waldman, Amber N. V. Ruigrok, Natasha Mooney, Richard A. I. Bethlehem, Meng-Chuan Lai, Prantik Kundu, Edward T. Bullmore, Jean-Louis Mandel, Amélie Piton, Simon Baron-Cohen |
Abstract |
Early-onset neurodevelopmental conditions (e.g., autism) affect males more frequently than females. Androgens may play a role in this male-bias by sex-differentially impacting early prenatal brain development, particularly neural circuits that later develop specialized roles in social cognition. Here, we find that increasing prenatal testosterone in humans is associated with later reduction of functional connectivity between social brain default mode (DMN) subsystems in adolescent males, but has no effect in females. Since testosterone can work directly via the androgen receptor (AR) or indirectly via the estrogen receptor through aromatase conversion to estradiol, we further examined how a potent non-aromatizable androgen, dihydrotestosterone (DHT), acts via the AR to influence gene expression in human neural stem cells (hNSC)-particularly for genes of high-relevance for DMN circuitry. DHT dysregulates a number of genes enriched for syndromic causes of autism and intellectual disability and for genes that in later development are expressed in anatomical patterns that highly correspond to the cortical midline DMN subsystem. DMN-related and DHT-affected genes (e.g., MEF2C) are involved in a number of synaptic processes, many of which impact excitation-inhibition balance. Androgens have male-specific prenatal influence over social brain circuitry in humans and may be relevant towards explaining some component of male-bias in early-onset neurodevelopmental conditions. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 2 | 11% |
Finland | 1 | 5% |
Japan | 1 | 5% |
Brazil | 1 | 5% |
Italy | 1 | 5% |
Netherlands | 1 | 5% |
United Kingdom | 1 | 5% |
Norway | 1 | 5% |
Canada | 1 | 5% |
Other | 0 | 0% |
Unknown | 9 | 47% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 9 | 47% |
Scientists | 7 | 37% |
Practitioners (doctors, other healthcare professionals) | 3 | 16% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 119 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Bachelor | 18 | 15% |
Researcher | 17 | 14% |
Student > Ph. D. Student | 16 | 13% |
Student > Master | 11 | 9% |
Student > Doctoral Student | 6 | 5% |
Other | 17 | 14% |
Unknown | 34 | 29% |
Readers by discipline | Count | As % |
---|---|---|
Psychology | 27 | 23% |
Neuroscience | 21 | 18% |
Biochemistry, Genetics and Molecular Biology | 7 | 6% |
Medicine and Dentistry | 6 | 5% |
Agricultural and Biological Sciences | 4 | 3% |
Other | 11 | 9% |
Unknown | 43 | 36% |