DE LA SALLE – HEALTH SCIENCES INSTITUTE
COLLEGE OF MEDICINE – Batch 2016
PSYCHONEURO-ENDOCRINOLOGY, PSYCHONEURO-
IMMUNOLOGY AND CHRONOBIOLOGY
Michelle Marie M. Marinas, M.D.
Introduction
 Medicine is integrated and dynamic
 First year as NORMALITY
Objectives
 To understand how the nervous, endocrine and
immune systems interact with one another
 To integrate these interactions
 To identify psychiatric disorders that have
endocrinologic and immunologic manifestations and
symptoms
 To identify endocrine and immune disorders that
have psychiatric and neurological symptoms
PSYCHONEUROENDOCRINOLOGY
 Structural and functional relations between the
hormonal system and the CNS and the
 Behaviors that modulate and arise from both
 Endocrine roles of neurotransmitters
Hormone Secretion
Chemical signals cause release of neurohormones
Hypothalamus
↓ o Hyperthyroidism – fatigue, irritability, insomnia,
Portal hypophyseal bloodstream
↓ o Hypothyroidism – fatigue, decreased libido,
Anterior pituitary
↓
Release of target hormones
 Pituitary hormones act directly on target cells (ACTH
on adrenal glands)
 Or stimulate release of other hormones from
peripheral endocrine organs (thyroid, adrenals)
 Feedback actions that regulate neurohormone
secretion and effects in the brain itself (directly or
neuromodulation)
 Neurohormones:
o CRH (Corticotrophin-releasing hormone)
o TRH (Thyrotrophin-releasing hormone)
o GnRH (Gonadotrophin-releasing hormone)
o Somatostatin
 What are the hormones stimulated by these
neurohormones?
o HPAdrenal Axis
o HPGonadal Axis
o HPThyroid Axis
o Growth Hormone
o Prolactin
o Melatonin
o Oxytocin
o Insulin
HPA Axis
 CRH, ACTH and Cortisol levels all rise in response to a
variety of physical and psychic stresses
 Serve as prime factors in maintaining homeostasis
and developing adaptive responses to new or
challenging stimuli
 General effects on arousal
 Distinct effects on sensory processing, habituation
and sensitization, pain, sleep and memory
 Pathological alterations:
o Mood disorders
o Post-traumatic Stress Disorder
o Dementia of the Alzheimer’s type
 Disturbances of mood:
o Cushing’s syndrome – elevated cortisol levels
(psychosis and suicidal thoughts)
o Addison’s disease – adrenal insufficiency
(apathy, social withdrawal, impaired sleep,
decreased concentration)
To God be the Glory!
HPG Axis
 Gonadal hormones are steroids that are secreted
principally by the ovaries and the testes
 Timing and presence of gonadal hormones play a
critical role in the development of sexual dimorphisms
in the brain
 Congenital adrenal hyperplasia (women)
o Deficiency of enzyme 21-hydroxylase
o More aggressive and assertive
o Less interested in traditional female roles
 Testosterone
o Primary androgenic steroid
o Increased violence and aggression
o Important for sexual desire
 Estrogen and Progesterone
o Has mood-enhancing properties
o Can increase sensitivity to serotonin (possibly by
inhibiting monoamine oxidase)
HPT Axis
 Thyroid hormones are involved in the regulation of
nearly every organ system:
o Metabolism of food
o Regulation of temperature
o Optimal development of body tissues
 Thyroid disorders can induce virtually any psychiatric
symptom
anxiety
depression
Growth Hormone
 Deficiencies interfere with growth and delay onset of
puberty
 Low GH levels can result from a stressful experience
 Some patients with depression – hyposecretion of
GHRH
 GH abnormalities in anorexia nervosa
 Released in pulses throughout the day, closer
together during the first hours of sleep
Prolactin
 Primarily involved in reproductive functions
 Regulation of behavioral aspects of reproduction
and infant care, breastfeeding
 Normally inhibited by dopamine in the brain – side
effect of antipsychotics is prolactinemia
 Hyperprolactinemia – depression, irritability,
decreased libido
Melatonin
 Pineal hormone
 Derived from serotonin molecule
 Also modulates immune function, mood,
reproductive performance
 Tx of circadian phase disorders
Oxytocin
 Posterior pituitary hormone
 Milk ejection reflex, female maternal and sexual
behaviors
Insulin
 May be integrally involved in learning and memory
 Thought to help neurons metabolize glucose
PSYCHONEUROIMMUNOLOGY
 Direct interactions between the nervous system and
the immune system
 Until the 1980’s, considered as parallel but
independent entities
 Behavioral conditioning
o Learning processes can influence immune
response
 Stress and the immune response
o Stressful life events can increase susceptibility to
infectious diseases
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 DE LA SALLE – HEALTH SCIENCES INSTITUTE
COLLEGE OF MEDICINE – Batch 2016
o Med students – exam period – decreased T cell
activity
 Psychiatric Disorders and Manifestations
o Infectious agents can lead to psychiatric
disorders
o MR – after congenital infection with Rubella
o Schizophrenia – hypothesized to have a viral
etiology
o Major Depressive Disorder – elevated serum
concentrations of proinflammatory cytokines IL-1
and IL-6
o HIV – immunological disease with neurological
manifestations
CHRONOBIOLOGY AND BIOLOGICAL RHYTHMS
 Physical cycles to which a person’s biological rhythms
conform:
o Day-night cycle
o Lunar month
o Solar year
o Patterned mealtimes and 9-to-5 workdays are
exogenous influences
 Sleep
o One of several biological rhythms in the body
o Circadian biological rhythms are set by both
internal and external forces, called zeitgebers
(time givers)
o Principal circadian influences are from:
 Pontine reticular formation
 Suprachiasmic nuclei of the hypothalamus
 Question:
o In the absence of exogenous clues, the period of
human circadian rhythm is ???
A bit longer than a day (24.5 hours)
o Name (2) examples of biological rhythms
 In-phase – healthy state
 Out of phase – system is perturbed (sleep deprivation)
 Abnormal phase advance – begins earlier than usual
 Phase delay – begins later than usual
 Sleep-wake cycle is synchronized with cyclical
changes in the levels of several circulating hormones:
o Serum cortisol levels – lowest at the onset of sleep
and highest in the morning
o TSH secretion is suppressed by the onset of sleep
o Melatonin is secreted at night and terminates on
retinal stimulation by sunlight (Ramelteon)
o GH levels surge during deep sleep
 Sleep deprivation causes
o Breakdown in concentration, motor skills, self-
care, attention, judgment and communication
 Depression is the psychiatric symptom most
associated with disruptions in biological rhythms
o Early morning awakening
o Decreased REM latency
NORMAL SLEEP
 Sleep is particularly relevant to psychiatry, because
sleep disturbances occur in virtually all psychiatric
illnesses and are frequently part of the diagnostic
criteria for specific disorders
Electrophysiology of Sleep
 Two physiological states
o NREM – stages 1 to 4
 Peaceful
 Pulse rate slowed 5-10 beats a minute below
the level of restful waking
 Episodic, involuntary body movements
 Blood flow to tissues slightly reduced
o REM – high level of brain activity and
physiological activity similar to wakefulness
 Paradoxical sleep
To God be the Glory!
NREM
 Deepest portion of NREM sleep – stage 3 and 4
 When persons are aroused 30 minutes to 1 hour after
sleep, they are disoriented and thinking is
disorganized
 Enuresis, somnambulism, night terrors
REM
 Pulse, respiration and BP are all high during REM sleep
 Brain oxygen use increases
 Thermoregulation is altered – poikilothermic condition
(state in which animal temperature varies with the
changes in temperature of the surrounding medium)
 Partial or full penile erection
 Near total paralysis of skeletal muscles
Dreams and Sleep
 Dreams during REM – abstract and surreal
 Persons awakened during REM sleep report dreaming
 Dreams during NREM – lucid and purposeful
Cyclical Nature of Sleep
 REM period occurs every 90 to 100 minutes during the
night
 First REM period is the shortest – 10 minutes
 Later REM periods is 15-40 minutes each
 Most REM periods occur in the last third of the night
 Most stage 4 sleep occurs in the first third of the night
 Neonatal – REM is 50% of total sleep time; alert to
REM state
 4 months – REM sleep drops to less than 40%
 Young adult
o NREM – 75%
 Stage 1 – 5%
 Stage 2- 45%
 Stage 3 – 12%
 Stage 4 – 13%
o REM – 25%
Sleep Regulation
 Serotonin
o Prevention of serotonin synthesis/ destruction of
dorsal raphe nucleus of brainstem (contains
nearly all of serotonergic neurons) reduces sleep
 Norepinephrine – drugs that affect these reduce REM
sleep and increase wakefulness
 Acetylcholine – production of REM sleep
 Dopamine – has an alerting effect
Functions of Sleep
 Restorative, homeostatic function
 Crucial for normal thermoregulation and energy
conservation
 Sleep deprivation
o Irritability and lethargy
 Short sleepers
o Fewer than 6 hours of sleep
o Efficient, ambitious, socially adept, content
 Long sleepers
o More than 9 hours
o More REM periods
o More rapid eye movements within each period
(REM density)
o Mildly depressed, anxious, socially withdrawn
Sleep-wake rhythm
 Shift workers
 Jet lag
 Out-of-phase
 Long-term cycle disruption and interference –
disturbances in sleep architecture
itsmebob8
11.09.12
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