1. Hormones and Stress Response

2. The brain controls hormone release

4. Hypothalamic releasing factors

5. Oxytocin and Vasopressin (ADH) are released by the posterior pituitary, others from the anterior pituitary.

6. Environmental factors influence hormone secretion
Social
Mating and breastfeeding both stimulate oxytocin release in females, allowing for formation of pair bonds with partners and offspring
Defeat leads to a reduction in testosterone levels in male rhesus monkeys, can be reversed by exposure to a female companion
Stressful
Physical and psychic stresses (trauma, fear) lead to ACTH release and subsequent glucocorticoid release: these pathways can be strengthened by learning

7. Social anxiety, as determined in a questionnaire, profoundly affects the level of testosterone in males randomly selected to lose a face to face game with a predetermined outcome.

8. Biological rhythms influence hormone secretion
Adrenal steroid hormones are released prior to periods of wakefulness and activity
Waking
Synaptic efficacy for “easy” learning
LTP and memory retention
Hunger (carbs especially) and food seeking
Seasonal and circannual rhythms
Menstrual and estrous cycles
Breeding “season” testes growth

9. LEFT: circadian control of hormone secretion
RIGHT: circadian control of learning and memory, short term recall, in phase with body temp and alertness.

10. Hormones act via receptors
Peptide hormones (grehlin, oxytocin, VP) and amino acid derivatives that act as neuromodulators (norepinephrine)
Bind cell surface receptors—2nd messenger cascades
Steroid hormones (estrogen, progesterone), thyroid hormone, and glucocorticoids
Bind cytoplasmic receptors which become activated and translocate to the nucleus where they act as transcription factors

13. Adrenal Steroids
Left normal, right neonatal neglect.

14. Developmental Experiences Influence Later Responses to Anxiogenic Stimuli High Maternal Care in Rats Alters Adult Offspring
Increased Glucocorticoid Receptor Expression in Hippocampus
Enhanced Glucocorticoid Feedback Sensitivity
Decreased Hypothalamic CRF expression
Reduced HPA axis activity in response to Stressors

15. Impact of Maternal Care :
Increases activation of 5-HT7 Receptors in Offspring: Linked to Gs proteins
Increases expression of a transcription factor, NGFI-A, which binds to a site on a non-coding region of the Glucocorticoid Receptor gene.
Changes methylation state of specific sites of promotor sequence of Glucocorticoid Receptor gene. NGFI-A binding induces DNA demethylation, which will lead to increased transcription.

16. Methylation of GR exon 1
Methylation of GR exon 1. NGFI binding site is circled. NGFI binding reduces methylation, leading to increased transcription

17. Experiment
Hypothesis: Maternal care affects serotonin signaling, leading to increased NGIF transcription, decreased methylation of the GR, and more GR production in the HPC.
Method: Grow two populations of mice, one high maternal care, one low maternal care, then cross foster the pups with the opposite care mother
Monitor adult GR methylation

18. offspring show methylation pattern consistent with rearing mother rather than birth mother (low 5’ methylation for L-H). No effect at 3’ site.
2C. Increased association of aceytlated histone and NGFI-A binding with GR exon 1 in high-LG/ABN reared adult offspring.

20. Societal factors in humans
Childhood abuse or neglect
Trauma
Urban upbringing
Stress
Interpersonal relationships
Environmental factors, particularly during development, can alter susceptibility to mental disorders

21. Social Anatomy
Figure 1 A simplified taxonomy of neural areas supporting human social functions, shown on lateral and medial surfaces (top and bottom, respectively). Yellow, social perceptual processes; red, emotional and motivational appraisal of social stimuli; green, social attribution processes; blue, social categorization processes.
fMRI, lesion studies

22. Interactions that affect mental disorder phenotypes
Genes—environment
Genes—hormones
Hormones—environment
Social hormones
Mediate pair bonding
Gender specific responsiveness

23. Genetic variants of social hormones
AVPR1a (vasopressin receptor)
High levels in ventral pallidum of prairie voles mediates their monogamous behavior
A genetic variant precludes expression in VP in meadow voles and they are promiscuous
Replacing the variant with the prairie vole avpr1a gene induces pair bonding in meadow voles
Human variants in avpr1a also exist and correlate with relationship success in men
Environmental factors don’t act alone to modulate susceptibility to disease. There is genetic variability in the population that interacts with social and stressful cues to determine ones risk for any given disease/disorder.

24. Genetic variants of social hormones
OXTR (oxytocin receptor)
Single nucleotide polymorphisms (SNPs) in intron 3 are associated with decreased maternal sensitivity and empathy
May be over-represented in autism
Another variant is associated with increased depression and social anxiety
A third, protective, variant is associated with decreased stress response, particularly in men

25. Role of Development
Many mental illnesses are only observed at or after adolescence
Extensive plasticity in the brain, pruning of connections, establishment of new connections
Shift from parental support to peer support
Initiation of romantic relationships
:: prime time for interactions between genes and environment to occur
-response to stress, develop and rely on supportive networks, coping mechanisms