Psycho neuro endocrine

1. PsychoNeuroEndocrinology
Dr. Rency Raj Rajan

2. • Defn:
– Structural and functional relationship
– between hormonal system and CNS &
– Behaviours that modulate and are derived from both.
• Hormones: Products of endocrine glands- transported by blood-
exert action at a distant site.
• Pleiotropy: Single hormone may
– Act at multiple sites
• Bind to receptor on memb., cytoplasm, nucleus
• Each with different effects
– & Subtle differences in
• molecular structure
• Metabolic processing
– Have profound physiological consequences

3. • Brain: Regulatory control of hormonal release
– But also has
• Secretory Function
• End organ of some hormonal actions
• Hypothalamus > Transducer cells > hormone regulator > secretion
of hormone.
• Chemical Signals > cause release of neurohormones from median
eminence of Hypothalamus > to portal hypophyseal blood stream >
transported to pituitary > release of hormones

4. • Actions:
– Act directly on target cells
– Stimulate relese of other hormones from peripheral endocrine
organs
– Feedback action
• Eg:
– CRH -----------------> ACTH
– TRH -----------------> TSH
– GnRH ---------------> LH & FSH
– Somatostatin(Somatotropin release inhibiting factor) -----> - GH
– Growth hormone releasing hormone(GHRH) ----------------> + GH
– Progesterone, oxytocin----------------> Prolactin

5. Structure Eg: Storage
Proteins, Polypeptides, Glycoproteins ACTH, TRH, LH, FSH Vesicles
Steroid, Steroid like compounds Estrogen, Cortisol,
Thyroxine
Diffusion after synthesis
Site of action Function
Autocrine Self regulatory effects
Paracrine Local / Adjacent cellular action
Endocrine Distant Target site

6. Neuro development
• Hormones have both Organisational and Activational effects
• Eg:
– During neurodevelopment > exposure to gonadal
hormones > changes in brain Morphology & Function
– Post natal thyroid deficiency > impaired growth and
development of brain > behavioural disturbances
(reversible if treated and vice versa)
– Maternal depriviation----->anxiety, addiction, spatial
learning difficulty

7. Endocrine assessment
1. Assess baseline values
– Measure at a single time point
– Cons: hormones released in pulsatile nature – error
– Measure 24 hr urine sample / blood drawn xle times
2. Neuroendocrine challenge tests:
– Drug/hormone/substance administered- follow up
– No disease = Less marked variability

8. 1. Hypothalamic- Pituitary- Adrenal axis(HPA)
2. Endogenous Opioids
3. Hypothalamic- Pituitary- Gonadal axis
a. Testosterone
b. Dihydroepiandrosterone
c. Estrogen and progesterone
4. Hypothalamic- Pituitary- Thyroid axis
5. Growth Hormone
6. Prolactin
7. Melatonin
8. Oxytocin
9. Insulin

9. HPA axis
• Stress > Rise in CRH, ACTH, cortisol levels
• Why?
– To maintain homeostasis
– Develop adaptive responses
• Hormonal response depends upon:
– Characteristics of stressor
– How individual assess it & able to cope up with it
• What happens:
– Generalised effects on arousal,
– distinct effects in sensory processing, stimulus habituation & sensitisation,
– pain, sleep,
– memory storage and retrieval.

10. • Alterations in HPA > mood disorders, PTSD, Dementia in AD,
Substance use disorders.
• ↑cortisol(cushings)> mood disorders(50%){10%psychosis/suicidal
ideations}
• Addisons disease(adrenal insufficiency) fatigue, apathy, social
withdrawal, impaired sleep, decreased conc.
• HPA abnormalities reversed in person treated with anti-depressants
• Failure to normalise HPA abnormalitypoor prognosis

11. • MDD> cognitive impairment(visual memory, higher cortical
functions)severity of hypercortisolemia & reduction in
hippocampal size
• Depression:
• Elev cortisol
• Fail to suppress cortisol in response to dexamethasone
• Increased adrenal size
• Elev CRH levels in brain

12. Endogenous Opioids
• Opioid receptors(μ, δ, κ) activated by endogenous ligands(β-endorphin,
enkephalin, dynorphin) respectively.
• Effects :
– Analgesia, altered pain perception,
– Stress, appetite regulation, learning & memory, motor activity
• PTSD > ↑opioid secretion(adaptive to trauma)
– CSF β-endorphin levels inversely related to intrusive & avoidant symptoms
• Naltrexone:
– ↓ symptoms in autistic children, improve functioning
– Alcohol dependence adjunct > reduce drinking, craving, high (kick)
• Exercise ↑release of endogenous opioids > euphoria

13. Hypothalamo pituitary Gonadal axis
• Gonadal hormone > steroids
– Progesterone
– Androstenedione
– Testosterone
– Estradiol
• Secreted by
– Ovary , Testes, Adrenal Cortex
• Dihydrotestosterone
– Synthesis and storage - Prostate gland and Adipose tissue
• Timing and presence – sexual dimorphism in brain
– Hypothalamus nuclei & corpus callosum size
– Language ability and response  Broca’s motor speech area
– Neuronal density in Temporal cortex
– Women with CAH > high exposure to Adrenal androgens in pre and post
natal> more aggressive, less traditional female roles.

14. Testosterone
• Androgenic steroid androgenic & anabolic effects.
• Sexual desire  men & women
• Muscle mass, strength
• Sexual activity, desire,
• Testosterone improve mood and decrease irritability in
– Hypogonadal men
– Postmenopausal women – small amt test in hormone
replacement therapy
• Anabolic-androgenic steroid administration > increased
– Positive symptoms: euphoria, incr. energy, sexual arousal
– Neg sympt: irritability, anger, hostility, mood swings

15. Dihydroepiandrosterone
• DHEA & DHEA-S( DHEA- sulfate)
– Adrenal androgens
– Secreted in response to ACTH
– Most abundant circulating steroids
• DHEA – also a neurosteroid – synthesised in brain

16. EFFECTS:
• Reduce neuronal damage in response to oxidative stress & gluco
corticoid excess
• Adrenarche – prepubertal onset of adrenal prodn of DHEA
– Play role in maturation
• ↑ activity of Amygdala & Hippocampus
• synaptogenesis
• DHEA administration in depressed, Addisons’s disease(women)
– Improve mood, well-being, energy, libido, functioning
• ↑DHEA-S=↓ADHD
• DHEA improves antipsychotic induced EPS in SCZ

17. Estrogen & Progesterone
• Estradiol(E2)*, Estrone(E1), Estriol(E3)
• Estrogen influence neural activity
– in Hypothalamus & Limbic system
• How?
– Modulation of neuronal excitability
– Have complex multiphasic effects on Nigrostriatal dopamine
receptor sensitivity.
• Antipsychotic’s effect change over menustral cycle
• Tardive Dyskinesia – estrogen conc.

18. • Gonadal steroids
– modulate
• Spatial cognition
• Verbal memory
– Impede age related neuronal degeneration
• Postmenopausal > estogen suppliment
– ↓risk and severity of Alzhimers Dementia
• Estrogen (mood enhancer)
– Increase sensitivity to Serotonin
• How? Oophorectomy pts. – significant ↓ in Tritiated
Imipramine binding sites(indirect measure of presynaptic
serotonin uptake) – restored with estrogen treatment
– Hence hypothesised with Mood changes in Pre-menustral &
post partum

19. Hypothalamic Pituitary Thyroid Axis
• Thyroid Hormones
– Metabolism of food
– Temp regulation
– Optimal development and function of ALL body tissues
• TRH
– Neuronal excitability
– Behaviour
– Neurotransmitter regulation

20. • Hyperthyroidism
– Fatigue, irritability, insomnia, anxiety,restlessness, weightloss,
– emotional lability, impaired conc. , memory,
– (some cases)↓PMA, apathy.
• Hypothyroidism
– Fatigue,
– Decreased Libido, memory impairement,
– Secondary psychotic disorder
– Dementia
– suicidal ideations & ATTEMPTS

21. Growth Hormone
• GH is released as pulses throughout the day
• Pulses are close together during intial hours of sleep
• Deficiency > delay growth, delay onset of puberty
• Stress > Low GH levels
• GH deficiency seen in MDD and Dysthymic pts.
• MDD (pre pubertal & adult pts.) > Hyposecretion of GHRH in Insulin
tolerance test
• Anorexia Nervosa:
– Administer GHRH > increase food consumption
• GH admini. to elderly men  increase lean body mass & vigour

22. Prolactin
• Identified in 1970
• Potential index of
– Dopamine activity
– Dopamine receptor sensitivity
– Antipsychotic drug concentration
• Correlate of Stress responsivity
• Secretion of Prolactin under Direct Inhibitory regulation by
Dopamine neuron in Tuberoinfundibular section of Hypothalamus –
hence increased by classical antipsychotics
• Prolactin negative feed back also inhibits its secretion

23. • Other Prolactin Releasing/ Prolactin-Modifying factors
– Estrogen (promote serotonin-stimulated release of prolactin)
– Serotonin(5-HT2 & 5-HT3 receptors)
– Nor-epinephrine
– Opiods
– TRH
– T4
– Histamine
– Glutamate
– Cortisol
– CRH
– Oxytocin

24. • Functions:
• Primarily involved in reproductive fnx.
– Gondal development(during maturation)
– Adults
• Regulate behavioural aspects of reproduction(estrogen
dependent sexual receptivity)
• Breast feeding
– Postpartum – basasl prolactin levels rise
– Suckling stimulate release
• Hyperprolactinemia
– ↓ testosterone(men), ↓Libido(both sexes)
– ↑sed along with corticosterone in response to stress
– Depression, Stress intolerance, Irritability
• Correlations:
• ↑Prolactin levels = ↑ severity of Tardive dyskinesia
• ↑Prolactin levels = ↑negative symptoms in SCZ.

25. POMC
• Proopiomelanocortin(POMC)melanocortins are derived(ACTH, MSH,
Melanocortins)
• Activate melanocortin receptorsincrease sexual activity
• Block melanocortin-4 receptorsdecrease reinforcing effects of cocaine
• Inactivate melanocortin-5decrease aggression
• Melanocortinsneuroprotective in ischemia, less hippocampal cell
death helps learning
• MSH control secretion of Melatonin & Melanin
• Phenothiazineincrease MSH secretion & pigmentation

26. Melatonin
• Pineal hormone
• Derived from Serotonin molecule
• Controls Photo-periodically mediated endocrine events
• Modulates:
– Immune function
– Mood
– Reproductive perfomance
– Potent anti-oxidant & free radical scavenger

27. • Effects:
• Depressive
• Analgesic – act via opioid receptors
• Seizure inhibitor – neuroprotective
• Regulatory effect on serotonin metabolism
• Useful in treating circadian phase disorders
– ↑speed of falling asleep
– ↑duration
– ↑quality

28. Oxytocin
• Posterior Pituitary hormone
Involved in:
• Osmoregulation
• Milk ejection
• Female maternal & sexual behaviours
• Promotes bonding between sexes (released during orgasm)
– Used in Autistic children experimentally in an attempt to
↑socialisation

29. Insulin
• May be involved in Learning and Memory
• Insulin receptors > high density in Hippocampus > Helps neuronal
glucose metabolism
• Pts with Alzheimer’s disease > have low insulin in CSF
• Depression frequent in Diabetics

30. • Endocrine regulation > in pathophysiology , treatment of Psy disorders
• Base line alteration in Glucocorticoid regulation and Thyroid status
– Useful in subtyping psychiatric disorders &
– In predicting outcome
• But, incorporating these findings into clinical diagnostic assessment and
decision making remain problematic, why?
– Large scale longitudinal / cost-effectiveness studies rare
To conclude…

31. Future:
• Study Genetic polymorphisms in factors regulating hormonal
response help in
– Better understand influence of hormonal variability
– Differences in nature of illness

32. Reference:
• D. S. Harris, O. W. Wolkowitz, V. I. Reus, Chap: 1.12,
Psychoneuroendocrinology, Comprehensive Textbook of Psychiatry,
edited by B. J. Sadock, V. A. Sadock, P. Ruiz, 10th edition, South Asian
Edition, Volume 1, 2017, Pages: 164-178
• B. J. Sadock, V. A. Sadock, P. Ruiz, Chap: 1.5:
Psychoneuroendocrinology, Synopsis of Psychiatry, Eleventh edition,
2015, Pages: 63-67.