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PSY4080 6.0DPSY4080 6.0D Stress Disorders, Sleep DisordersStress Disorders, Sleep Disorders 11

Stress Disorders,Stress Disorders,Sleep DisordersSleep Disorders


Stress DisordersStress Disorders

Stress (response)Stress (response): physiological and : physiological and behavioural reaction caused by the behavioural reaction caused by the perceptionperception of of aversive or threatening stimuli (Cannon, 1921).aversive or threatening stimuli (Cannon, 1921).

StressorsStressors: Environmental triggers of stress: Environmental triggers of stress PTSD requires an identifiable stressor for PTSD requires an identifiable stressor for

diagnosisdiagnosis Often the association between the stressor and Often the association between the stressor and

the stress response is not clearthe stress response is not clear


Stress ResponseStress Response

Fight or flight response:Fight or flight response: mobilization of resources to mobilization of resources to prepare us to face stressorsprepare us to face stressors• Effects of the Hypothalamic-Pituitary-Adrenal axisEffects of the Hypothalamic-Pituitary-Adrenal axis

Mobilization of energy in face of the stressors includes:Mobilization of energy in face of the stressors includes:1.1. Activation of sympathetic nervous system Activation of sympathetic nervous system

• increased heart rate, increased muscular contractions, increased heart rate, increased muscular contractions, increased blood pressure, decreased digestion/metabolismincreased blood pressure, decreased digestion/metabolism

2.2. Adrenal hormones are releasedAdrenal hormones are released• EpinephrineEpinephrine• Norepinephrine (activation of NE receptors in brain)Norepinephrine (activation of NE receptors in brain)• Steroid stress hormones (cortisol)Steroid stress hormones (cortisol)



1. Norepinephrine 1. Norepinephrine • Stressful situations (e.g. social isolation in rats) will Stressful situations (e.g. social isolation in rats) will

increase release of NE increase release of NE • hypothalamus, frontal cortex, and lateral basal forebrain hypothalamus, frontal cortex, and lateral basal forebrain

including portions of amygdala including portions of amygdala (Yokoo et al., 1990, Cenci et al., (Yokoo et al., 1990, Cenci et al., 1992; van Bockstaele et al., 2001)1992; van Bockstaele et al., 2001)

• Downregulation of the alpha-2 receptor in response to Downregulation of the alpha-2 receptor in response to hight NE levelshight NE levels

2. Serotonin2. Serotonin• 5HT is 5HT is decreaseddecreased• Raphe nucleus, frontal areas involved in extinctionRaphe nucleus, frontal areas involved in extinction



3. Glucocorticoids and corticotropin releasing hormone (CRH)3. Glucocorticoids and corticotropin releasing hormone (CRH) Receptors throughout the brain (and rest of body)Receptors throughout the brain (and rest of body) Controlled by the hypothalamus, CRH serves as a Controlled by the hypothalamus, CRH serves as a

neuromodulator in the limbic system, periaqueductal gray neuromodulator in the limbic system, periaqueductal gray matter, locus coeruleus, and amygdalamatter, locus coeruleus, and amygdala

Injection of CRH into rats’ brains induces fear reactions Injection of CRH into rats’ brains induces fear reactions (Britton et al., 1982)(Britton et al., 1982)

Antagonists of CRH reduce anxiety caused by stressors Antagonists of CRH reduce anxiety caused by stressors (Heinrichs et al., 1994)(Heinrichs et al., 1994)Heightened activation of sympathetic nervous Heightened activation of sympathetic nervous systemsystem


1. Sufficient sensory information is present for assessment.

Vermetten & Bremmer, 2002


2. Assessment based on access to prior experience.



3. Encode memory of (potential) threat.



4. Access to neuroendocrine, autonomic, motor responses.



PTSD: Prevalence, InfoPTSD: Prevalence, Info

Prevalence: 5-10% (U.S), higher in war-torn Prevalence: 5-10% (U.S), higher in war-torn areasareas

Three themes of PTSD:Three themes of PTSD:

1.1. Re-experiencing of stressful eventRe-experiencing of stressful event

2.2. Avoidance of stimuliAvoidance of stimuli

3.3. Persistent, increased arousal Persistent, increased arousal


PTSD: Prevalence, InfoPTSD: Prevalence, Info In adults, traumatic events occur more often to In adults, traumatic events occur more often to

men, but PTSD is 4 times more common in women men, but PTSD is 4 times more common in women (Fullerton et al., 2001)(Fullerton et al., 2001)

In children:In children:

1.1. Loss of acquired language skillsLoss of acquired language skills

2.2. Regression of toilet trainingRegression of toilet training

3.3. Somatic complaints (stomachaches or headaches)Somatic complaints (stomachaches or headaches)

Delayed onset of PTSD often occurs for chronic Delayed onset of PTSD often occurs for chronic abuseabuse


PTSD: DSM-IV CriteriaPTSD: DSM-IV Criteria

A. The person has been exposed to a traumatic event in which both of the following have been present:

(1) the person experienced, witnessed, or was confronted with an event or events that involved actual or threatened death or serious injury, or a threat to the physical integrity of self or others

(2) the person's response involved intense fear, helplessness, or horror. Note: In children, this may be expressed instead by disorganized or agitated behavior.



B. The traumatic event is persistently re-experienced in one (or more) of the following ways:

(1) recurrent and intrusive distressing recollections of the event, including images, thoughts, or perceptions. Note: In young children, repetitive play may occur in which themes or aspects of the trauma are expressed.

(2) recurrent distressing dreams of the event. Note: In children, there may be frightening dreams without recognizable content.



(3) acting or feeling as if the traumatic event were recurring sense of reliving the experience illusions, hallucinations, and dissociative flashback

episodes young children: trauma-specific reenactment may occur.

(4) intense psychological distress at exposure to internal or external cues that symbolize or resemble an aspect of the traumatic event.

(5) physiological reactivity on exposure to internal or external cues that symbolize or resemble an aspect of the traumatic event.



C. Persistent avoidance of stimuli associated with the trauma and numbing of general responsiveness (three or more of the following):

(1) efforts to avoid thoughts, feelings, or conversations associated with the trauma

(2) efforts to avoid activities, places, or people that arouse recollections of the trauma

(3) inability to recall an important aspect of the trauma

(4) markedly diminished interest or participation in significant activities



(5) feeling of detachment or estrangement from others

(6) restricted range of affect unable to have loving feelings

(7) sense of a foreshortened future does not expect to have a career, marriage,

children, or a normal life span



D. Persistent symptoms of increased arousal (not present before the trauma), as indicated by two (or more) of the following:

(1) difficulty falling or staying asleep (2) irritability or outbursts of anger (3) difficulty concentrating (4) hypervigilance (5) exaggerated startle response



E. Duration of the disturbance is more than one month.

F. The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.

Specify if: Acute: if duration of symptoms is less than 3 months Chronic: if duration of symptoms is 3 months or more

Specify if: With Delayed Onset: if onset of symptoms is at least 6 month


Health effects of long term stressHealth effects of long term stress

Chronic stressChronic stress is thought to be most is thought to be most problematic for long-term healthproblematic for long-term health

Acute traumatic stressAcute traumatic stress, in a few cases, may be , in a few cases, may be equally as devastating equally as devastating

(e.g. war, natural disasters, rape, witnessing (e.g. war, natural disasters, rape, witnessing murder)murder)• Exacerbation of initial traumatic eventExacerbation of initial traumatic event


Health effects of long term stressHealth effects of long term stress

Selye (1976) – long-term effects of stress are Selye (1976) – long-term effects of stress are caused by chronic release of glucocorticoidscaused by chronic release of glucocorticoids• Increased blood pressureIncreased blood pressure• Damage to muscle tissueDamage to muscle tissue• Steroid diabetesSteroid diabetes• InfertilityInfertility• Inhibition of growthInhibition of growth• Inhibition of inflammatory responsesInhibition of inflammatory responses• Suppression of immune system Suppression of immune system

Loss of brain tissueLoss of brain tissue• Elevated levels of CRH in women and men with PTSD Elevated levels of CRH in women and men with PTSD

(Yehuda, 2001)(Yehuda, 2001)


NeuropathologyNeuropathology

volume loss of hippocampus in veterans with volume loss of hippocampus in veterans with combat-induced PTSD (Bremner et al., 1995)combat-induced PTSD (Bremner et al., 1995)

• brain degeneration occurred in people who had brain degeneration occurred in people who had been subjected to torture been subjected to torture (Jensen et al., 1982)(Jensen et al., 1982) – – note: not by experimentersnote: not by experimenters

• Loss is proportional to amount of combat Loss is proportional to amount of combat exposure (Gurvits et al. 1996)exposure (Gurvits et al. 1996)

• Similar effects in those exposed to severe Similar effects in those exposed to severe childhood abuse (Bremner et al, 1999)childhood abuse (Bremner et al, 1999)


Sleep DisordersSleep Disorders


Sleep DisordersSleep Disorders

1 in 8 Canadians suffer from a Sleep Disorder1 in 8 Canadians suffer from a Sleep Disorder May or may not be related to stressMay or may not be related to stress May be related to undersleeping or oversleepingMay be related to undersleeping or oversleeping Often comorbid with anxiety or depressionOften comorbid with anxiety or depression No age limits for definitionNo age limits for definition Often undiagnosed or untreated for yearsOften undiagnosed or untreated for years Can have profound impact on physical and Can have profound impact on physical and

mental healthmental health


What is normal sleep?What is normal sleep?

1.1. WakingWaking Beta waves: 13-40 Hz, low amplitude, asynchronousBeta waves: 13-40 Hz, low amplitude, asynchronous Alpha waves: 8-13 Hz, higher amplitude (when meditative Alpha waves: 8-13 Hz, higher amplitude (when meditative

or relaxed).or relaxed).

2. Stages 1 and 2 (Light sleep)2. Stages 1 and 2 (Light sleep) Theta waves: 4-7 HzTheta waves: 4-7 Hz May not be aware that you fell asleepMay not be aware that you fell asleep

3. Stages 3 and 4 (Heavy sleep)3. Stages 3 and 4 (Heavy sleep) Delta waves: < 4HzDelta waves: < 4Hz Sleep walking and talkingSleep walking and talking



4. Rapid eye movement (REM) sleep4. Rapid eye movement (REM) sleep Return of alpha and beta activity, like waking statesReturn of alpha and beta activity, like waking states Darting eye movementsDarting eye movements Dramatic loss of muscle tone--effectively paralyzedDramatic loss of muscle tone--effectively paralyzed DreamingDreaming

Stage 1 to REM = 90 minutesStage 1 to REM = 90 minutes As night progresses, amount of REM sleep increases and As night progresses, amount of REM sleep increases and

stage 3-4 sleep decreasesstage 3-4 sleep decreases


Disorders of sleepDisorders of sleep

1.1. InsomniaInsomnia2.2. NarcolepsyNarcolepsy3.3. REM Sleep Behaviour DisorderREM Sleep Behaviour Disorder4.4. Problems associated with slow wave sleepProblems associated with slow wave sleep

• Inability to sleep at night produces many of the same Inability to sleep at night produces many of the same symptoms as the stress response--sleep is critical for symptoms as the stress response--sleep is critical for neural “recovery”neural “recovery”

• Hallmark of all sleep disorders is an inability to maintain Hallmark of all sleep disorders is an inability to maintain normal wakefulness during the day: normal wakefulness during the day: Excessive daytime Excessive daytime sleepiness (EDS)sleepiness (EDS)


InsomniaInsomnia

Feeling that you are not getting enough sleep, Feeling that you are not getting enough sleep, often associated with anxietyoften associated with anxiety

May be difficulty falling asleep or early waking, May be difficulty falling asleep or early waking, often associated with depressionoften associated with depression

Hard to define as people differ in sleep needsHard to define as people differ in sleep needs Often treated with drugs although majority of Often treated with drugs although majority of

patients do not undergo a sleep studypatients do not undergo a sleep study Most drugs are barbiturates which affect GABA Most drugs are barbiturates which affect GABA

receptors (perhaps in reticular activating receptors (perhaps in reticular activating formation)formation)


NarcolepsyNarcolepsy

Neurological disorder characterized by sleep at Neurological disorder characterized by sleep at inappropriate times (sleep attack)inappropriate times (sleep attack)• Overwhelming urge to sleep particularly in monotonous Overwhelming urge to sleep particularly in monotonous

conditionsconditions• Sleep appears normal and lasts 2-5 minutesSleep appears normal and lasts 2-5 minutes• Person (temporarily) feels refreshedPerson (temporarily) feels refreshed

CataplexyCataplexy: muscular paralysis while fully awake (similar to : muscular paralysis while fully awake (similar to paralysis during REM)paralysis during REM)• Usually triggered by strong emotion or sudden physical effortUsually triggered by strong emotion or sudden physical effort

Hypnagogic hallucinations:Hypnagogic hallucinations: seeing and hearing things as seeing and hearing things as one is falling asleep. one is falling asleep.

Often skip slow wave sleep at night and move directly to Often skip slow wave sleep at night and move directly to REM from wakingREM from waking

Caused by low levels or absence of a peptide hypocretin in Caused by low levels or absence of a peptide hypocretin in lateral hypothalamus (Saper et al., 2001)lateral hypothalamus (Saper et al., 2001)


REM Sleep Behaviour DisorderREM Sleep Behaviour Disorder

Typically we are paralyzed during REM sleepTypically we are paralyzed during REM sleep In some people, this paralysis does not occur, and In some people, this paralysis does not occur, and

they act out their dreams without awarenessthey act out their dreams without awareness Not necessarily the same as sleepwalking, Not necessarily the same as sleepwalking,

although this may be a componentalthough this may be a component Associated with neurodegenerative disorders Associated with neurodegenerative disorders

(such as Parkinson’s)(such as Parkinson’s) Can be associated with brain damage to pons, Can be associated with brain damage to pons,

reticular activating formation (Culebras and reticular activating formation (Culebras and Moore, 1989)Moore, 1989)

Symptoms are opposite to those of cataplexySymptoms are opposite to those of cataplexy


Slow-wave sleepSlow-wave sleep

Usually occur during stage 4, when a person is difficult to Usually occur during stage 4, when a person is difficult to rouse but not dreamingrouse but not dreaming

Include:Include:• Bedwetting (nocturnal enuresis)Bedwetting (nocturnal enuresis)• Sleepwalking (somnambulism)Sleepwalking (somnambulism)• Night terrors (pavor nocturnis)Night terrors (pavor nocturnis)

All of these tend to occur more frequently in children – they All of these tend to occur more frequently in children – they usually grow out of theseusually grow out of these

No association with other mental health disordersNo association with other mental health disorders Not sure of neurobiology as it is difficult to do sleep studies Not sure of neurobiology as it is difficult to do sleep studies

with childrenwith children



Wake-sleep cycles are regulated by brainstem Wake-sleep cycles are regulated by brainstem structuresstructures

1.1. Thalamic nuclei (which receive direct visual input Thalamic nuclei (which receive direct visual input from the LGN)from the LGN)

a.a. Suprachiasmatic nucleus: circadian clockSuprachiasmatic nucleus: circadian clock

b.b. Ventrolateral preoptic nucleus: wakefulness and Ventrolateral preoptic nucleus: wakefulness and vigilancevigilance

2. Other areas2. Other areas

a.a. Raphe nucleus (pons): general arousalRaphe nucleus (pons): general arousal

b.b. Locus coeruleus: vigilance, arousalLocus coeruleus: vigilance, arousal



A host of different medications are used to A host of different medications are used to increase vigilance and altertnessincrease vigilance and altertness

a.a. Epinephrine and its agonists Epinephrine and its agonists

b.b. Other monoaminergic agonists: MethylphenidateOther monoaminergic agonists: Methylphenidate

c.c. Acetylcholine antagonists: CaffeineAcetylcholine antagonists: Caffeine

Most medications with sedative effects focus on Most medications with sedative effects focus on increasing GABA concentrations increasing GABA concentrations (benzodiazepines, barbiturates)(benzodiazepines, barbiturates)

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