The document discusses psychoneuroendocrinology, highlighting the interaction between the nervous and endocrine systems and their impact on cognitive, emotional, and behavioral functions. It explains the role of the hypothalamus and pituitary gland in hormone regulation, the classification of hormones, and their effects on various psychiatric disorders such as depression, PTSD, and schizophrenia. The document also covers the implications of chronic stress, hormone action mechanisms, and therapeutic approaches in managing endocrine-related psychiatric conditions.

1. Psychoneuroendocrinology
Dr. Ruchi Mittal
Resident
Department of psychiatry
NMC-TH, Birgunj
10/01/2024

2. Contents

3. Introduction
Study of the interaction between the nervous and endocrine system and the effect
of various hormones on COGNITIVE, EMOTIONAL AND BEHAVIOURAL
FUNCTIONING.
Endocrine disorders are frequently associated with secondary psychiatric
symptoms, such as depressed mood and disturbances in thought also certain
psychiatric syndromes are associated with distinct patterns of endocrine
dysfunction.

4. The term psychoneuroendocrinology encompasses the inextricable structural and
functional relationships between hormonal systems and the CNS and behaviors that
modulate and are derived from both.
Classically, hormones have been defined as the products of endocrine glands
transported by the blood to exert their action at sites distant from their release.
The neuroendocrine system is the mechanism by which the hypothalamus
maintains homeostasis, regulating reproduction, metabolism, eating and drinking
behaviour, energy utilization, osmolarity and blood pressure.

5. Hypothalamus
• The hypothalamus is commonly known as the relay center of the brain because of
its role in integrating inputs from all areas of the brain and producing a
specific response.
• In the neuroendocrine system, the hypothalamus receives electrical signals from
different parts of the brain and translates those electrical signals into chemical
signals in the form of hormones or releasing factors.
• These chemicals are then transported to the pituitary gland and from there to the
systemic circulation.

6.  The hypothalamus controls the
anterior pituitary's hormone
secretion by sending releasing
factors, called tropic hormones,
down the hypothalamo-
hypophysial portal system.
 For example,
thyrotropin-releasing hormone
released by the hypothalamus in to
the portal system stimulates the
secretion of
thyroid-stimulating hormone by the
anterior pituitary.

7. • The posterior pituitary is directly
innervated by the hypothalamus;
the hormones oxytocin and
vasopressin are synthesized by
neuroendocrine cells in the
hypothalamus and stored at the
nerve endings in the posterior
pituitary.
• They are secreted directly into
systemic circulation by the
hypothalamic neurons

8. The pituitary endocrine gland
- is located in bony sella turcica
- attached to the base of the brain and
- has a unique connection with the
hypothalamus.
This gland consists of two anatomically
and functionally distinct regions,
 the anterior lobe (adenohypophysis) and
 the posterior lobe (neurohypophysis).

9. The Anterior Pituitary (Adenohypophysis)
• Derived from embryonic ectoderm.
• Secretes 5 endocrine hormones from 5 different types of epithelial endocrine cells.
• Release is regulated by hypothalamic hormones (releasing or inhibitory), synthesized in the
cell bodies of neurons located in several nuclei that surround the third ventricle.
• These include the arcuate, the paraventricular and ventromedial nuclei and the medial
preoptic and paraventricular regions.
• In response to neural activity, the hypothalamic hormones are released from the nerve
endings into the hypophyseal portal blood and are then carried down to the anterior pituitary

10. The Posterior Pituitary
(Neurohypophysis)
• Neural in origin.
• Unlike the anterior pituitary, the posterior pituitary is connected directly to the
hypothalamus via a nerve tract (hypothalamohypophyseal nerve tract).
• It secretes two hormones: oxytocin and antidiuretic hormone (ADH) or vasopressin.
• The hormones are synthesized by the magnocellular neurons located in the supraoptic
and paraventricular nuclei of the hypothalamus.
• The hormones are transported in association with neurophysins proteins along the
axons of these neurons to end in nerve terminals within the posterior pituitary.

11. Classification of hormone
• Classified in two classes:
- Structure
- Location of function

12. Structural classification
Structure Examples Storage Lipid Soluble
Proteins,
polypeptides,
and glycoproteins
Adrenocorticotropic
hormone, β-
endorphin,
thyrotropin releasing
hormone, luteinizing
hormone, follicle
stimulating hormone
Vesicles No
Steroids and
steroid-like
compounds
Cortisol, estrogens,
testosterone,
progesterone,
dehydroepiandrostero
ne
Diffusion after
synthesis
Yes

13. Functional classification
Hormone classification Function
Autocrine Self-regulatory effects
Paracrine Local or adjacent cellular
action
Endocrine Local or adjacent cellular
action

14. Hormone secretion
• Hormone secretion is stimulated by the action of a neuronal
secretory product of neuroendocrine tranducer cells of
hypothalamus.(CRH stimulating ACTH release)

15. Examples of Regulating Hormones
Regulating Hormone Hormone Stimulated (or
Inhibited)
Corticotropin-Releasing Hormone Adrenocorticotropic Hormone
Thyrotropin-Releasing Hormone Thyroid Stimulated Hormone
Luteinizing Hormone Releasing Hormone Luteinizing Hormone
Gonadotropin Releasing Hormone Follicle Stimulating Hormone
Somatostatin Growth Hormone (inhibited)
Growth Hormone Releasing Hormone Growth Hormone
Progesterone, Oxytocin Prolactin
Arginine Vasopressin Adrenocorticotropic Hormone

16. CELLULAR MODE OF ACTION
Genomic:
• 1st
known mode of action of steroid hormones (glucocorticoids, estrogen, and testosterone)
and thyroid hormones (T3, T4 ) is by binding to intracellular receptors in the cytoplasm.
• Hormone–receptor complex binds with DNA and alters transcription.
• Can also interact with transcription factors (as those produced by c-fos, c-jun) or activator
protein-1 (AP-1) to modify gene expression.

17. Nongenomic:
• Has faster effect (seconds-minutes).
• Binds with membrane hormone receptors.
• Hormones may act through ion-gated NT receptors as coagonist or antagonists
other ions (as in modulation of GABA-A receptors by neurosteroids) by
altering of membrane fluidity through the intercalation of steroid in
phospholipid bilayer.

18. Combined action:
• An example of hormone-induced behavioral response with both genomic and
nongenomic mechanisms is corticosteroid stimulation of aggressive behaviour in rats.
• A rapid surge of glucocorticoids precedes the aggressive behaviour,but early and later
stimulation of aggressive behaviour is medited differently.
• Initial phase is promoted by Nongenomic ( fight or flight, Immediate aggression).
• Later phases by Genomic ( Delayed, metabolic changes needed to maintain the stress
response).

19. Tissue specificity:
• Hormones are tissue specific eg: Selective Estrogen Receptor Modulator.
SERM are synthetic hormones developed to target certain actions while
avoiding other unwanted actions through coactivators or repressors that donot
recognize the SERM in certain tissues.
• Certain tissues can convert a prohormone into other hormones eg: DHEA.

20. • For example,tibolone is a aynthetic hormone structurally related to 19-
nortestosterone derivatives that has weak estrogen, progestogen, and
androgen effects in specific tissues, in part because it is differentially
metabolized.
• Accordingly, it has been used to reduce hot flashes and sweating, improve
mood and libido and sexual functioning, decrease bone loss, stimulate
semantic memory, and lessen vaginal atrophy without stimulating the
growth of endometrium or breast tissue as do estrogens.

21. Developmental psychoneuroendocrinology:
• Hormones can have organizational as well as activational effects.
• Exposure to gonadal hormones during critical stages of neural development directs
changes in brain morphology and function, and differentiation of dopaminergic neurons.
• Thyroid hormones are essential for the normal development of the CNS.
• Prenatal exposure to glucocorticoids or stress can have lasting effects on immunity, CVS
etc.

22. • Maternal deprivation in strains of rats with increased
glucocorticoid response to stress
increased startle responses,
anxiety-like behavior,
 increased alcohol preference, and
difficulties with spatial learning in adulthood

23. Epigenetic Transmission:
• Epigenetic transmission occurs through changes in chromatin and DNA
structure.
• Maternal behavior can cause epigenetic alterations to steroid receptor genes and
produce long-term changes influencing postpartum behavior.

24. Hypothalamic-Pituitary-Adrenal Axis:
• CRH, ACTH, and cortisol
are elevated in physical and
psychological stresses.
• Glucocorticoids regulates many functions.
• CRH, ACTH and Cortisol has
effects on:
- Sensory processing
- Stimulus habituation and sensitization
- Pain, sleep
- Memory storage and retrieval.

25. Chronic stress:
• Increased concentrations of CRH and AVP leading to reduction in CRH receptors in
anterior pituitary.
• Release of CRH results in a simultaneous activation of the locus ceruleus which
functionally increases arousal and selective attention and decreases vegetative
functions like appetite and sex drive.
• ACTH concentrations increase in acute stress but gradually reduces over the time in
chronic stress.

26. Types of glucocortocoid receptor:
Mineralocorticoid
• Type 1 (MR)
• High Affinity, Low
capacity
Glucocorticoid
• Type 2 (GR)
• Low affinity, High
capacity

27. • At low steroid level during initial stress MR is stimulated.
• At high steroid level during later response, habituation/sensitization GRs are
involved.
• In continuous stress there is sustained hypercortisolemia and metabolic changes.

28. Feedback systems:
• Fast, rate-sensitive feedback occurs when plasma
concentrations of the glucocorticoid are rising and regulate release rather than synthesis of CRH and ACTH.
• Intermediate, delayed feedback occurs from 1 to 2 hours after steroid administration, is dose-sensitive and duration-
sensitive rather than rate-sensitive, and inhibits the release of CRH and ACTH as well as the synthesis of CRH.
• Slow, delayed feedback is similar to intermediate feedback but occurs over a longer period of time and is
distinguished by decreased synthesis of CRH and ACTH

29. Other factors:
• Glucocorticoid release is amplified, by serotonergic and cholinergic input and is inhibited by GABA and opioids.
• Catecholamines play a role in response to stress and interact with the limbic– hypothalamic–pituitary–adrenal axis.
• Acute addition of glucocorticoids can increase dopaminergic activity in but chronic hypercortisolemia may decrease
dopamine activity.

30. Clinical implications
• Involved in number of psychiatric disorders, including mood disorders, PTSD,
dementias, and substance use disorders.
• Cushing’s Disorder: Mood disturbance(50%), Psychosis & suicide(10%), Cognitive
impairment.
• Mifepristone (RU486) has been reported to ameliorate psychosis and depression in
Cushing’s patients, and several studies have reported that it also alleviated
psychosis or depression in psychotic depression not associated with Cushing
syndrome
• Addison’s disease: Apathy, Social withdrawal, Poor sleep, Fatigue (Role of
Glucocoticoid replacement improves).

31. Dexamethasone Suppression Test(DST)
• 1 mg of Dexamethasone in the evening (11pm)
• Plasma cortisol level ( 8 AM, 4PM,11PM next day).
• Plasma cortisol concentrations above 5mg/dl ( known as non suppression) and are
considered abnormal

32. • Low-dose dexamethasone suppression tests(1mg)
• In a subject with a normal hypothalamic–pituitary–adrenal (HPA) axis, a
supraphysiological dose of dexamethasone can inhibit ACTH secretion by the
pituitary leading to drop in cortisol level in serum, urine and saliva; such inhibition
does not occur in patients with Cushing syndrome.
• High-dose dexamethasone suppression test(8mg)
• In subjects with Cushing disease, a higher dose of dexamethasone (usually 8 mg)
is required to suppress ACTH secretion and drop cortisol level in serum, urine, and
saliva.

33. Depression:
• Elevated cortisol concentrations, DST abnormalities increased adrenal size and sensitivity to ACTH, a
blunted ACTH response to CRH and elevated CRH concentrations.
• Decreased sensitivity to glucocorticoid fast feedback as well as slow feed back.
• Increased cortisol near sleep onset and on first awakening.
• Excessive glucocorticoid activity may contribute to the symptoms of psychotic mood disorders.

34. Post traumatic stress disorder
• In one study, patients with PTSD exhibited low cortisol levels despite high CRH
activity, while in another cortisol response to ACTH was increased.
• One imaging study of identical twins discordant for PTSD showed similarly
diminished hippocampal volume, but treatment of the symptoms of PTSD with
SSRIs is followed by increase in hippocampal volume and improvement in memory.
• Hypercotisolemia can lead to hippocampal cell death
& hippocampal damage may impair cortisol negative feedback.

35. Schizophrenia
• Difficulty suppressing cortisol after dexamethasone is associated with negative
symptoms and cognitive impairment.
• Clozapine improves cognitive functioning, possibly in part through preventing or
reversing cortisol-induced hippocampal damage, and reverses stress-induced
impairment of LTP.

36. Substance Use Disorder
• Glucocorticoid acute enhancement of dopamine activity likely contributes to the motivational changes.
• Alcohol usage and withdrawal produce profound changes in HPA regulation, pseudocushingoid state.
• HPA adaptation to alcohol withdrawal varies by family history of alcoholism.
• CRH is involved not only in the HPA axis but also in extrahypothalamic systems that play a role in the relapse to alcohol and other
drug use after stress.

37. Polydipsia
• Polydipsic schizophrenic patients, particularly those with hyponatremia, show
marked impairment in cortisol suppression of ACTH.

38. Metabolic Syndrome
• Metabolic syndrome is a cluster
of multiple metabolic risk factors
including elevated insulin levels
and resistance, hyperglycemia,
visceral obesity, hyperlipidemia,
and hypertension.
• Glucocorticoids interfere with glucose transport and utilization, causing insulin resistant
and increased insulin concentration causing lipid deployment & increase lipid
accumulation.

39. • Elevated intracellular glucocorticoid is thought to be etiology of this sundrome.
• Selective inhibitors of 11β- hydroxysteroid dehydrogenase 1, which decrease cortisol
production, are thus being tested as a therapeutic intervention.
• Many patients with schizophrenia who exhibit increased cortisol and epinephrine have
more central obesity, higher plasma cortisol, and an increased risk of diabetes, even when
medication free.
• Many of the atypical antipsychotics and some of the other psychotropic medications also
can cause hyperglycemia, hyperlipidemia, and visceral obesity, limiting their use

40. Prooipiomelanocortin:
• POMC is a prohormone
ACTH
Melanocortins
Melanocyte stimilating hormone(MSH)
Melanocortin:
• To treat women with hypoactive sexual desire.
• Protective for ischemic neurotoxicity.
• Melanocortin 4 receptor: Decrease effect of cocaine.
• Melanocortin 5 receptor: Reduction in aggression.

41. MSH:
• Anterior pituitary peptide, controls the secretion of melatonin and melanin.
• Melatonin has major role in regulating the circadian rhythm.
• Phenothiazines increase pituitary MSH secretion and
pigmentation.
• MSH interacts with leptin to counteract NPY,decrease food intake, and increase energy
expenditure.
• Antagonize the antidepressant effects and anxiolytic effects of NPY.

42. Endogenous opioids:
• Effects on stress, appetite regulation, learning and memory, motor activity & immunity.
• Interact to coregulate the locus coeruleus, a role important in early adaptation to stress.
• Hypersecretion of opioids in the patients with PTSD has been developed an adaptive response to traumatic experience .
• Naltrexone an opioid receptor antagonist is used in:
 Autism
Eating disorders
Substance abuse

43. • In addition to the μ agonist methadone, buprenorphine, a partial μ agonist, has
been helpful for opioid dependence probably both because of its alleviation of
withdrawal and because of its blockade of opioid-induced euphoria.
• Exogenous opioids (e.g., heroin and morphine) can induce a euphoric mood state and
that exercise increases the release of endogenous opioids and is associated with
mood enhancement
• These observations, together with findings that exercise-induced mood enhancement
is blocked by naloxone, suggest that endogenous opioids are also involved in the
mediation of mood

44. Hypothalamic-Pituitary-Gonadal Axis

45. Gonadotrophin Releasing Hormone(GnRH)
• Located on arcuate area of Hypothalamus.
• GnRH release is stimulated by norepinephrine and is inhibited through negative feedback of gonadal steroids.
• Administration of GnRH can result in a depressive-like state.
• GnRH analog has been found to have some efficacy in the treatment of paraphilia by decreasing testosterone.

46. Gonadal Hormones
• The gonadal hormones (progesterone, androstenedione, testosterone, E2) are steroids that are secreted principally by the
ovary, testis and adrenal cortex.
• Gonadal hormones play a critical role in the development of sexual dimorphisms in the brain.
• Sexual dimorphisms may also reflect acute and reversible actions of relative steroid concentrations.
• The importance of timing in the exposure to sex steroids is in gender identity disordered adults.

47. Testosterone:
• Testosterone is the primary androgenic steroid, having androgenic and anabolic
functions.
• Important for sexual desire in men and women.
• In males, muscle mass and strength, sexual activity, desire, thoughts and intensity of
sexual feelings are
dependent on normal testosterone levels.

48. • Testosterone administration has been associated with increased violence and
aggression in animals but unclear in humans.
• Improves mood and decreases irritability in hypogonadal males.

49. • Anabolic-androgenic steroid administration in
normal subjects cause euphoria, increased energy, and sexual arousal and in addition to increases
irritability, mood swings, violent feelings, anger and hostility.
• Anabolic steroids can cause a variety of adverse psychiatric effects, including aggressive behavior, mood
and psychotic disturbances, and substance dependence.

50. Dehydroepiandrosterone(DEHA)
• DEHA are the adrenal androgens secreted in response to ACTH and neurosteroid that
is synthesized in brain.
• Increases the activity of the amygdala and hippocampus and promoting cortical
synaptogenesis.

51. • DHEA administration point to an improvement in well-being, mood, energy, libido,
and functional status in depressed individuals, adrenal insufficiency and HIV
positive patient.
• Can reduce antipsychotic induced EPS.
• Anti GC effects( Cortisol:DHEA): This is the ratio determines buffer against
negative effects of stress(PTSD).

52. Estrogen & Progesterone:
Estrogens:
• The primary estrogens:
 Estrone (E1)
 Estradiol (E2)
 Estriol (E3)
• Two different estrogen receptors α and β , each with different anatomical distributions
and physiological effects.
• Estrogens can influence neural activity in the
hypothalamus and limbic system directly through the modulation of neuronal
excitability and have complex multiphasic effects on nigrostriatal dopamine receptor
sensitivity.

53. • The antipsychotic effects of psychiatric drugs may change over the menstrual cycle
and that the risk of tardive dyskinesia is partly dependent on estrogen
concentrations.
• Lower levels of estrogen are associated with episodes of acute psychosis in both
women and men and with more severe negative symptomatology as well as poorer
cognitive function.
• Estrogen administration may decrease the risk and delay the onset of dementia of
the Alzheimer type in postmenopausal women.

54. Progesterone
• Progesterone, the primary progestin, is produced by the corpus luteum of the ovary.
• Has anxiolytic and hypnotic properties via GABA-A agonistic activity.
• Has antiestrogen effects.
• Associated with dysphoric mood.
• Role in PMDD, postpartum disorder, substance use disorder.

55. Pregnenolone & Allopregnanolone
• Modulate activity at GABA-A, NMDA, σ-1, 5-HT3, nicotinic, kainate, oxytocin,
and glycine receptors.
• Pregnenolone is a neurosteroid synthesized from cholesterol in the brain.
• Pregnenolone sulfate is an excitatory neurosteroid
and has GABA inhibitory effects.
• Allo is a GABA-A agonist which causes decrease in CRH and is stimulated by
SSRIs.

56. Prolactin:
• Prolactin has potential effects:
 dopamine activity
 dopamine receptor sensitivity
 antipsychotic drug concentration
 correlation on stress responsivity
• Prolactin is under direct inhibitory
regulation by dopamine neurons
located in the tuberoinfundibular
section of the hypothalamus therefore,
increased by classical antipsychotic medications.

57. • Hyperprolactinemia:
 Depression
 Decreased libido
 Stress intolerance, anxiety
 Increased irritability
• In psychotic patients, prolactin is positively correlated with the severity of tardive
dyskinesia.
• Prolactin levels are also positively correlated with negative symptoms.

58. • Hypothalamo-Pituitary-Thyroid-Axis:

59. • Concerned with food metabolism, body temperature regulation.
• Determines rate of secretion & metabolism of all major hormones.
• The thyroid gland secretes two thyroid hormones; T3 and T4.

60. • Corticotropin releasing hormone is derived from prohormone TRH.
• Has alpha and beta receptors; regulates neuronal differentiation and action of
immediate early genes.
• TSH is stimulated by NE and inhibited by D neurons.

61. • Thyroid disorder induce many psychiatric symptoms or syndrome.
• Hyperthyroidism is associated:
 Fatigue, irritability
 Insomnia, anxiety, restlessness
 Weight loss, and emotional lability
 Marked impairment in concentration &
memory
• Cautious use of MAOIs or TCA medications in hyperthyroid state.
• Enhancement of the neurotoxic effects of antipsychotic medications.

62. • Chronic hypothyroidism is associated:
 Fatigue
 Decreased libido
 Memory impairment
 Irritability
 Secondary psychotic disorder
 Dementia-like state
• Evaluation of the basal TSH concentration or the TSH response to TRH infusion is necessary to arrive
at the proper diagnosis.

63. Major Depression
• Low CSF transthyretin
• Basal T3 is inversely correlated with overall severity.
• Antidepressants, lithium, ECT reduce T3 &T4 which finally increase TSH.
• With lithium, even subclinical changes may be relevant.
• CBZ inhibit T3 and stimulate TSH while Mirtazepine stimulate T3 and inhibit T4.
• T3 increases the antidepressant response and T4 decreases cycling in patient with
rapid cycling bipolar I disorder.

64. Parathyroid Hormone
• Hyperparathyroidism cause:
- Lethargy, stupor, coma,
depression, delirium,
psychosis, primarily
visual hallucinations,
or anxiety.
• Hypoparathyroidism cause:
- cognitive impairment,
psychosis, depression,
or anxiety by alterations
in calcium and magnesium levels.

65. • PTH impair the active uptake and release of norepinephrine and dopamine and result
in adrenergic-like effects, learning and memory problems and a state of hyperalgesia.
• Lithium treatment can raise the concentrations of serum calcium and may increase
PTH over a period of time.

66. Growth Hormone
• Synthesized and released by the anterior pituitary gland.
• Dopamine, serotonin acting at the 5-HT1D receptor, and norepinephrine acting at the α 2-
adrenergic receptor appear to play a role in its release.
• GH stimulates lipolysis and ketogenesis, important in the adaptation to stress, and prevents
hypoglycemia.
• Augmentation of GH secretionin response to GHRH, LH-releasing hormone (LHRH), or TRH in
patients with schizophrenia or dementia of the Alzheimer.

67. • GH is more responsive to exercise and hypoglycemic stress than to psychological stress.
• MDD: Hyposecretion of GHRH
• Panic disorder patients may have a blunted GH response to clonidine.
• GHRH stimulates food consumption in patients with anorexia nervosa and attenuates elevated food
consumption in patients with bulimia.
• GH secretagogue (GHS), ghrelin, may represent an important alternative regulatory influence overfood
intake and sleep pattern.

68. Somatostatin
• Inhibits anterior pituitary secretion of ACTH, thyrotropin, GH, and prolactin.
• Alters release of catecholamine neurotransmitters, and stimulates serotonin release.
• Decreased concentrations of Somatostatin are inconsistently found in patients with
depression.
• Sustained elevation due to early stressful experiences.

69. Arginine Vaopressin
• AVP or antidiuretic hormone is a posterior pituitary hormone that maintains plasma osmolarity
stimulates hepatic glycogenolysis.
• AVP release is triggered by pain, emotional stress, dehydration, increased plasma osmolarity, or
decreases in blood volume and acts synergistically with CRH to control ACTH release.
• An AVP receptor antagonist blocks ACTH release, norepinephrine release, and hyperthermic
response to stress.

70. • Hormone may enhance the consolidation and retrieval of memory, particularly that
associated with aversive learning.
• Altered AVP function has been reported in depression and in eating disorders.
• Polydipsia occurs in 10 to 15 percent of hospitalized psychiatric patients and is unrelated to
diagnosis; in many cases, the syndrome is secondary to inappropriate secretion of AVP.
• Fluoxetine treatment of depression decreases the CSF vasopressin levels.

71. Oxytocin
• Oxytocin is a posterior pituitary hormone.
• Involved in
 Osmoregulation,
 Milk ejection reflex,
 Food & sodium intake, and
 Female maternal and sexual behaviors.

72. Neuropeptide Y
• Important role in the regulation of basic physiological function, including learning and memory.
• Marijuana use appears to elevate the expression of NPY.
• Inhibitory relationship with insulin.
• Release is stimulated by stress and corticosteroids and associated with norepinephrine release.

73. Insulin
• Insulin is a protein hormone secreted by the β cells of the pancreas in response to elevations of glucose and amino acids.
• Psychotic stress may impair insulin sensitivity.
• Atypical antipsychotics impair response to insulin and raise blood
glucose, increasing the risk of developing diabetes.
• TCAs, also reduce sensitivity to insulin.
• SSRIs, increase sensitivity to insulin .
• Involved in learning, memory, and mood.

74. Leptin
• Leptin is a protein hormone synthesized and secreted by adipose tissue and involved in the regulation of food intake.
• Leptin stimulates hematopoiesis, T-cell activation,
phagocytosis, and cytokine production and decreases susceptibility to infection.
• Leptin also affects the HPG axis.
• Low leptin: depression

75. CCK
• CCK is a peptide neurotransmitter originally isolated from the gut and is found in high
concentrations in the cerebral cortex, limbic system, and hypothalamus.
• Regulation of such behavioral functions as inhibition of intake of solid and liquid food,
production of satiety, pain relief cardiovascular and respiratory function, neurotoxicity and
seizures, sexual and reproductive behaviors, and memory.

76. • CCK-A antagonist: Treatment of schizophrenia
• CCK-A agonist: Decreasing the severity of parkinsonian symptoms.
• CCK-B antagonist: Treatment of anxiety.
• CCK receptor antagonist : treatment of substance abuse

77. Gastrin
• Gastrin is a peptide hormone closely related to CCK that stimulates the secretion of
gastric acid by the stomach.
• CCK agonist and produces anxiety and panic in patients with anxiety disorders and
to a lesser extent in those without anxiety disorders.
• Increases ACTH and cortisol release.

78. Gastrin-releasing peptide
• Stimulates gastrin release.
• Interacting with GABA, dopamine, and GRs. GRP appears to enhance memory
storage, increased locomotor activity and changes in social behavior.

79. Endocrine variables in psychiatric disorder:
• Endocrine regulation are involved in pathophysiology and treatment
responses of many psychiatric disorder.
• Important in diagnostic assessment and descision making.

80. • Kaplan & Sadock’s Comprehensive Textbook of Psychiatry, 10th
edition.
• Kaplan& Sadock’s Synopsis of Psychiatry, 11th
edition.

81. Thank you

82. References
• Physiology, Pituitary Gland
• Suzan A. El Sayed; Michael W. Fahmy; Janice Schwartz.