B&B 9 Psychosis, Addiction, Movement Disorder Flashcards Preview

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Flashcards in B&B 9 Psychosis, Addiction, Movement Disorder Deck (185):
1

Hallucination
...vs...
Delusion
...vs...
Illusion

►Hallucination
• may occur in any sensory modality (e.g., auditory, visual, olfactory, gustatory, and tactile), but auditory hallucinations are by far the most common
• hearing voices

►Delusion
• false unshakable belief that is out of keeping with someone's educational & social background
• "I'm under surveillance"

►Illusion
• distortion of the senses, revealing how the brain normally organizes and interprets sensory stimulation
• fanciful vision or a false impression or idea, a mental state in which one attributes reality to something unreal

►Allusion
• figure of speech
• nothing to do with this term!

2

Akathisia

(patient who told her story had this as a S/E of Risperidone

• movement disorder characterized by a feeling of inner restlessness and a compelling need to be in constant motion
• (eg) rocking while standing or sitting, lifting the feet as if marching on the spot, and crossing and uncrossing the legs while sitting

• People with akathisia are unable to sit or keep still, complain of restlessness, fidget, rock from foot to foot, and pace

3

Schizo-affective Disorder

has features of two different conditions:
►Schizophrenia
... AND ...
►Mood Disorder
(MDD or Bipolar)

Schizophrenia
• distorts the way a person thinks, acts, expresses emotions, perceives reality, and relates to others.

MDD: Major Depressive Disorder
• feelings of sadness, worthlessness, or hopelessness, as well as problems concentrating and remembering details

Bipolar
• cycling mood changes, including severe highs (mania) and lows (depression).

4

We had a patient share her experiences of having hallucinations and later being diagnosed with schizophrenia.

She initially presented to the ER when hearing voices and was seen by a psychiatrist who explained brain chemistry. and sent her off with her meds.

However, the pt doesn't think she is ill. She hears voices and this is her reality.

What would have helped the patient?

Take an interest in how the patient sees the problem.

The voices that they patient hears are REAL to the patient.

We can't simply talking about brain chemistry to patients who are having hallucinations.

5

Patient has delusions.

We don't want to agree with their delusions, but neither do we just want to shut them down. This is their reality.

How do we respond to them?

Help them live with their version of reality.

"If YOU think there are cameras in the bathroom, perhaps you could consider wearing a bathing suit in the shower."

6

DEFINE:

►Dyskinesia

►Bradykinesia

►Choreoathetosis

►Myoclonus

►Ataxia

►Dyskinesia
– abnormal movement of voluntary muscles

►Bradykinesia
– slowness of movement

►Choreoathetosis
– dance-like movement

►Myoclonus
– not a disease of the Basal Ganglia
– shock like movements

►Ataxia
– cerebellar

7

Tremor

regular
repetitive
sinusoidal cycles
alternating contractions of antagonistic pairs of muscles

8

Patient presents with Tremor

What are the questions to ask myself?

Where is the tremor?

What brings out the tremor?

What is the Frequency of the tremor?

9

We all have a minor tremor

What makes it worse?

►Enhanced Physiological tremor
– (anxiety worsens all types of tremor)
– Drugs (caffeine, valproate, theophylline)
– Hyperthyroidism
►Essential tremor
►Parkinson’s disease
►Cerebellar disease

10

What is the oversimplified interpretation of tremors?

►Intention
(Cerebellar disease)

►Postural
(Essential Tremor)

►Rest
(Parkinson’s Disease)

11

Essential Tremor is the common movement disorder

What is the core criteria?

►Bilateral action tremor the hands and forearms (but not rest tremor)

12

If we see a patient who think might have an Essential Tremor.

However, what are some of the red flags that would makes us think that is NOT an essential tremor?

►Unilateral tremor, focal tremor, leg tremor,
gait disturbance, rigidity, bradykinesia, rest tremor

►Sudden or rapid onset

►Current drug treatment that might cause or worsen
tremor

►Isolated head tremor with abnormal posture (head
title or turning)

13

Essential Tremor

Tx?

►1st Choice
– Propanolol (crosses BBB)
– Primidone

►2nd Choice
– Gabapentin
– Clonazepam

►3rd Line
– Topirimate
– Surgery

14

Essential Tremors are often confused with Parkinson's

►Parkinson's
• have rest tremor
• BUT, when asked to do something do it well
• Head tremor uncommon
(but can see lip, chin tremor)
• Asymmetric
• Rigidity
• Writing small, tremor not prominent
• Typically worse while walking
• Alcohol has no effect
• can draw an Archimedes circle

►Essential Tremor
• Head/voice may be affected
• Relatively symmetric
• Cogwheeling may be present
• Writing large, tremulous
• Typically better while walking
• Often improves with alcohol

15

►Parkinson's

►Parkinson's
• have rest tremor
• BUT, tremor disappears when asked to do action
• Head tremor uncommon
(but can see lip, chin tremor)
• Asymmetric
• Rigidity
• Writing small, tremor not prominent
• Typically worse while walking
• Alcohol has no effect
• can draw an Archimedes circle

16

►Essential Tremor

►Essential Tremor
• Head/voice may be affected
• Relatively symmetric
• Cogwheeling may be present
• Writing large, tremulous
• Typically better while walking
• Often improves with alcohol

17

►Parkinson's

Mnemonic

TRAP
• Tremor
• Rigidity
• Akinesia/Bradykinesia
• Postural Instability

Masked Face
Micrographia

18

Parkinsonian Gait

Slow small steps
shuffling gait
one of the arms does not swing

19

Parkinson's

Pathophysiology?

Loss of dopamine secreting cells from Substantia Nigra

Lewi Bodies will be present

20

Parkinson's

Why do these cells die early?

►Genetics
may be a genetic predisposition

►Toxins in the Environment
• Lacquer thinner, cyanide ...
• some yahoos in California tried to make synthetic opioids in their bathtub. Accidentally, they made MPTP → they all developed Parkinons

21

Parkinson's

Crazy, but true, these actually have been shown to be protective against developing Parkinson's!

• Caffeine
• Smoking!

22

What is an early sign that someone might go on to develop Parkinson's

►Anosmia (loss of smell)

►Sleep Disturbances
• people with REM Sleep Disorder have a 50% chance of going to develop Parkinson's

►Stiffneck → frozen shoulder

►Depression & Anxiety

►Masked Face

►Small Hand writing (micrographia)

►Constipation

23

What is Parkinsonism?

Have Sx that look like Parkinsons', however, they actually do not have Parkinson's!

The main difference is that these pts do NOT respond to medications

24

What is the basis of Parkinson's Tx?

If we can’t prevent the cell loss, can we replace the missing dopamine? YES!

L-Dopa!
• crosses the BBB

25

►D-Dopa
– A/E?

►Dopamine Agonists
– A/E?

Dyskinesia
– abnormal movement of voluntary muscles
– goes away if the pt was to stop the medication

Dopamine Agonists
– compulsive bahviours (gambling, shopping, sex, eating)

26

What is critical to know about medication treatment for Parkinsons'?

As patients are treated over time for the Parkinson's, the therapeutic window becomes more and more narrow!

27

Chorea

What is it?

• irregular
• involuntary
• non-repetitive
• non-purposeful
• random
• unpredictable
• smooth, flowing, fast/slow
• not suppressible
• can stop it when pays attention
• seems to flow randomly from one part of the body to another

28

HUNTINGTON’S DISEASE

• Chorea
• Dementia (“subcortical dementia”)
• Autosomal dominant
• CAG triplet repeats >38 times

29

HUNTINGTON’S DISEASE

Tx?

►Chorea
anti-dopaminergic drugs. Dopamine depleting agents (e.g. tetrabenazine) preferred to dopamine receptor blockers (e.g. haloperidol)

►Dementia: unfortunately no treatment

►Counseling

30

Tic

• Irregular, Non purposeful movements
• Perdictable in pattern, but NOT in time
• Stereotypic
• Suppressible

31

Tourette's Syndrome

►Multiple Tics

►Childhood Onset

►Persistant for >1 year

►Coprolalia
– involuntary swearing or the involuntary utterance of obscene words or socially inappropriate and derogatory remarks

32

Tourette's Syndrome

Tx?

Treat with anti-dopaminergic drugs

Dopamine depleting agents (tetrabenazine) preferred rather than receptor blockers (haloperidol)

33

BALLISM

• irregular
• non-repetitive
• non-purposeful
• unpredictable
• violent, proximal
• not suppressible
• Normally associated with damage to the subthalamic nucleus

34

BALLISM

Tx

Dopamine depleting agents preferred (tetrabenazine)

35

Dystonia

• involuntary muscle contractions
• co-contraction of antagonists
• abnormal postures
• may be worse with specific actions
• disappears during sleep

36

Suspecting Dystonia

What is important to rule out?

• drug induced
• DOPA-responsive dystonia
• Wilson’s disease
• Huntington’s disease (Westphal variant)

37

FOCAL DYSTONIA

Eyelids (blepharospasm)
Face (facial dystonia)
Jaws (oromandibular dystonia)
Neck (cervical dystonia, or spasmodic torticollis))
Voice (laryngeal dystonia, or spasmodic dysphonia)

38

Dystonia

Tx?

Treat primary cause, if any

Discontinue drugs if possible

39

Myoclonus

• Shock-like movements caused by sudden muscle contraction (positive myoclonus), or by muscle relaxation (negative myoclonus)

• Asterixis (seen in liver disease) is a type of negative myoclonus

40

Drug-Induced Akathisia

• “inability to remain seated”
• Often seen with neuroleptic use
• sensation of inner restlessness, dysphoria, and anxiety
• compulsion to move legs - walking on the spot
• may be associated with Parkinson’s disease
• usually 1 hour after administration, but may be several weeks later

41

Neuroleptic malignant syndrome

• uncommon (0.01-2%) but can be fatal
• agitation, lethargy, confusion, delirium, stupor,
coma
• hyperthermia, tachypnea, BP changes
• rigidity, akinesia, tremor, dystonia, chorea
• seizures
• elevated creatinine kinase (CK)
• myoglobinuria

42

Neuroleptic malignant syndrome

• May occur with first exposure to neuroleptics, or when re-instituting therapy after a long period of time

• Acute withdrawal of dopaminergic drugs (e.g. suddenly stopping treatment in PD)

• General supportive measures, management of hyperthermia, adequate hydration, dopamine agonists

43

Tardive Dyskinesia

Tardive = slow or belated onset

Difficult-to-treat and often incurable form of dyskinesia, a disorder resulting in involuntary, repetitive body movements

Can get almost any movement disorder as a tardive phenomemon:
• Dyskinesia (chorea + dystonia)

44

Psychosis

Def

loss of contact with reality

45

DSM-5 has moved towards Dimensional Classification

• Based upon quantification and for attributes.
• Works best for phenomenon distributed continuously.
• Numerical dimensional descriptors are less vivid.
• Sometimes there is no agreement on optimal dimensions.
• Uses Neurosis (OCD) Psychosis
• DSM V plans to use various dimensional scales to measure severity

46

What was the criticism of DSM-4?

Narrow diagnostic criteria

"Psychosis not otherwise specified" was used when criteria was not fully made

Did not capture clinical reality, symptom heterogenicity within disorders, sharing of symptoms across disorders

47

What did the DSM-5 change to from DSM-4?

► Non-axial documentation of diagnosis
(formerly Axis I, II, III)

►Separate notation for psychosocial and contextual factors (formerly Axis IV)

►Disability (formerly Axis V)

48

Psychotic Disorders

Overview

• Schizophrenia.
• Schizophrenieform psychosis.
• Schizoaffective psychosis.
• Delusionald isorder.
• Brief psychotic disorder.
• Shared psychotic disorder.
• Psychotic disorder due to general medical condition.
• Substance induced psychotic disorders.

49

Schizophrenia.

►Characteristic symptoms (two for at least one month)
• Delusions
• hallucinations
• disorganized speech
• disorganized or catatonic behaviour
• "negative" symptoms.

►Social/occupational dysfunction.

►Duration six months
(one month of characteristic symptoms).

50

Hx of Schizophrenia

Originally called "dementia praecox" because it produces severe incapacity: "dementia"

Typically begins in adolescence

51

Schizophrenia.

Suicide Risk

persists chronically

10% suicide risk

very common 0.5 to 1% of population

52

Schizophrenia.

• No single defining feature
• Sx from multiple domains (emotion, personality, cognition, motor activity)
• Probably a multisystem disorder (like SLE!)

53

What are "Positive" vs "Negative" features of Schizophrenia?

►POSITIVE:
something ADDED to personality
• hallucinations
• delusions
• disorganized speech
• bizarre behavior

►NEGATIVE
Something lost from personolity
• Alogia - impaired speech
• Affective blunting - flat affect
• Avolition Loss of volition & drive
• Anhedonia - loss of pleasure (like depression)

54

Types of Hallucinations

Can affect any sense (gustatory difficult to assess)

• Auditory (Most common!)
• Visual (usually drug induced)
• Tactile (cocaine use)
• Olfactory (temporal lobe epilepsy)

55

Delusions

►Persecutory

►Grandiose
able to achieve something or something that

►Religious

►Jealous
• common in alcohol abuse

►Somatic
• pts who keep coming back with Sx that cannot be put into any category; believe they have a disease

56

Catatonia

What is it?

extreme pyscho-motor retardation

Has been removed in DSM-5 as its own subtype of schizophrenia

Rather, it is now considered a specifier within other conditions

57

Key Features of Schizophrenia

• Delusions
• Hallucinations
• Disorganized Thinking (speech)
• Grossly Disorganized or Abnormal Motor Behaviour (including Catatonia)
• Negative Symptoms – prominently diminished
emotional expression and avolition (‘decreased purposeful behavior’)

58

What is a bizarre delusion?

Delusion that does not follow the laws of physics

If present, these are considered to be more severe illness

59

What are the things that we need to measure on a 4-point scale?

We assess this to determine how MUCH each of the following have affected the individual

►Hallucinations
►Delusions
►Disorganized Speech
►Abnormal Psychomotor Behvr
►Negative Symptoms (Restricted Emotional Expression or Avolition)
►Impaired Cognition
►Depression
►Mania

60

Schizoaffective Disorder

Now based on the lifetime (rather than episodic) duration of illness in which the mood and psychotic symptoms described in Criterion A occur

Episodes of Mood Disorder & Psychotic Sx

61

Attenuated Psychosis Syndrome
(APS)

A. At least 1/3 core psychosis symptoms with relatively intact reality testing, and warrants clinical attention
B. Symptoms ≥ 1x/week in past month
C. Symptoms began or worsened in past year
D. Not better explained by other mental disorder
E. Criteria for another psychotic disorder never met

62

DSM-5

Advantages
... vs ...
Disadvantages

Advantages:
– Emphasis on domains of symptoms
– Moves us toward dimensional ratings
– Criteria somewhat simplified and possibly more clinically meaningful
– Maintains clear boundary with Bipolar

Disadvantages:
– Limited advance in clarifying the heterogeneity of these disorders
– APS proposal controversial as example of DSM’s ‘mission creep’ and potential increase of stigma and false positive

63

Schizophreniform Disorder

<6 months
Good prognosis
Maintains function

64

Schizoaffective Disorder

• Characteristic symptoms of schizophrenia plus depressed, manic or mixed episode of mood.

• Presence of delusions or hallucinations for at least two weeks in the absence of mood symptoms.

• Specifiers (bipolar type, depressive type)

• Combination of Schizophrenia and Mood Disorder

• Better prognosis than Schizophrenia but not as good as Mood Disorder

• Tx: Antipsychotics.

65

Delusional Disorder

Non-bizarre delusions (paranoia, infection, deception or having a disease) at least one month.
• Characteristic Sx of schizophrenia not present (tactile and olfactory hallucinations may be present if related to delusion).
• Functioning not impaired.
• Subtypes (erotomanic, grandiose, jealous, persecutory, somatic, mixed).
• Lack of functional impairment
• Poor response to treatment.
• Bizzare delusions added.

66

Brief Psychotic Disorder

• Presence of one or more of: delusions, hallucinations, disorganized speech, disorganized behaviour

• Duration, at least one day but less than one month - eventual return to premorbid functioning

• Specifiers with marked stressors, without marked stressors, or post-partum onset (within four weeks).

• Good prognosis.

67

Psychotic Disorder Due to General Medical Condition

• Subtypes with delusions or with hallucinations

• Prominent hallucinations or delusions

• Evidence of dire physiological consequence of general medical condition.

• Not accounted for by another mental disorder

• Disturbance not exclusively during course of delirium

68

What are medical conditions that may present with Psychosis?

• Temporal lobe epilepsy
• Tumor
• Stroke
• Trauma
• Endocrine / Metabolic Abnormalities
• Infections
• MS
• Autoimmune

69

Substance Induced Psychotic Disorder

Specifiers onset during intoxication, onset during withdrawal.
• Prominent hallucinations or delusions (without insight)
• Evidence Sx develop during or within a month of substance intoxication or withdrawal.
• Substance use etiology clearly related to the disturbance.

70

Which drugs induce Psychosis?

Amphetamines
Marijuana
Hallucinagns
Cocaine

71

Can Marijuana cause Schizophrenia?

Cannabis consumption, particularly at younger ages (teenagers) has been shown to induce schizophrenia

Cannabis use before age 16 increased risk of schizophreniform disorders by age 26

72

What does Dopamine say?

Eat food
Have sex
Bond with your clan

73

Risk Factors for Addiction

► Agent
– Availability, cost, rapidity to reach brain,
efficacy as a tranquilizer (to relieve withdrawal)

►Host
– Genetic predisposition, multi-problem family,
co-morbid psych (med) disorders (age, gender)

►Environment
– Occupation, peer group, culture, instability
– Sanctioned use, prohibition, restrictions

74

DSM-V Substance Use Disorders


aka Addiction

• Larger amounts or longer time than intended
• Attempts to cut down or control
• Time is spent obtaining, using, or recovering
• Craving or urge
• Failure to fulfill major role or obligations
• Use despite social or interpersonal problems
• Activities given up due to using or recovering
• Use under hazardous conditions
• Use despite knowledge of med/psych problem
• Gaining Tolerance
• Having withdrawal

75

DSM-V Substance Use Disorders

Qualifiers
(from the previous list)

►Severity
– Mild: 2-3 symptoms
– Moderate: 4-5 symptoms
– Severe: 6 or more symptoms

►Remission
– Early – 3-12 mo. -only criteria left may be craving – Sustained – 12 mo. or longer, craving may remain
– In a controlled environment (access restricted)

►On maintenance therapy
– Agonist, agonist/antagonist, full antagonist

76

Risk Factors for Psychosis

Agent
►Agent
– Amount of dopamine stimulation +/- serotonin stimulation produced, damage to neurons, certain withdrawal states

►Host
– Genetic predispositions to addiction and mood
or psychotic disorders, previous head injury

►Environment
– Social stressors, nutrition, access to treatment

77

Risk Factors for Movement Disorders

►Agent
– Exposure to substances that affect brain dopamine levels and/or damage dopamine neurons in the CNS.

►Host
– Genetic predisposition – family history of
movement disorders, previous head injury

►Environment
– Occupational exposure (eg. solvents, heavy metals), social stressors, access to treatment

78

People who have mental health issues have a higher rate of substance use disorders.

People who have substance use disorders have a higher rate of mental health issues.

Which came first?

If can be really tricky to sort out. Go back in Hx.

►Use a timeline
– Any mental health symptoms prior to substance initiation? During periods of prolonged abstinence? Under acute stress?

►Take a family history
– Any first or second degree relatives with mental health issues?

79

Social risk and protective factors

►Role modeling
– drinking & drugging vs sober

►Family disruption:
– bonding, abuse, neglect vs
stable and supportive

►Coping strategy:
– bury TRAUMA, pain, mental health vs healthy ways to self soothe & cope

►Economic:
– poverty-hopelessness-addiction cycle, alcohol industry pressure vs stable employment with a chance for a future

80

What is the hallmark of addicting substance?

↑dopamine in nucleus accumbans

Dopamine (and serotonin) excess when using stimulants/hallucinogens/alcohol can cause psychosis – too much meaning

Dopamine depletion through lowered set point or damaged neurons can produce movement disorders, and low mood

81

Cocaine
Alcohol
Heroin

What happens to the brain?

When people get addicted there D2 receptors get depleted

People who use these substances get a different brain

82

Alcohol

• Classed as a sedative-hypnotic
• GABAa & glycine agonist, NMDA receptor antagonist

►Use:
↑ opiate, ↑ dopamine (DA), ↑ serotonin, ↑ GABA  Decrease in glutamate (from NMDA blocking)

►Withdrawal:
• Decrease in inhibitory neurotransmitters
• Increase in excitatory neurotransmitters
• Insomnia, irritation, tremor, risk of seizure

83

Genetics of Alcohol

►Twin studies
• Concordance rates for alcoholism in monozygotic
twins higher (60%) than dizygotic twins (39%)

Adoption Studies
• Sons of alcoholics 4x more likely to develop alcohol dependence even if raised by non - drinking surrogate parents. Less clear for women
• Sons without alcoholic parents raised by alcoholics have no increased risk of alcohol dep.

84

Lacking which enzyme is protective against developing alcoholism?

Acetyaldehyde dehydrogenase def is protective. These people (Asians, Jewish etc) have buildup of acetaldehyde feel like crap and so do not drink!

Alcohol
⬇︎ Alcohol dehydrogenase
Acetaldehyde (S/E)
⬇︎ Acetaldehyde dehydrogenase
Acetate

85

What are the greatest genetic risk factors for developing alcoholism?

• Male
• Positive family history of alcohol dependence
• Low response - little intoxication
• Novelty seeking (DRD4 polymorphism)
• Little acetaldehyde build-up

86

Alcohol Induced Psychosis, Tremor

►Alcohol intoxication
– Can get impaired motor control, ataxia  Altered reality and judgement

►In withdrawal
– Hallucinations – visual, tactile and/or auditory
– Due to low GABA, high glutamate, and can get tremor (even a tongue tremor), seizures, and if severe, status epilepticus
– Late withdrawal – Delirium Tremens (DTs)

87

Alcohol & Movement Disorders

►Wernike-Korsicoff’s syndrome:
• ETOH blocks NMDA, in withdrawal glutamate slams away at the NMDA receptor
• Oculogyric crisis, ataxia, tremor

►Long Term:
• Cerebellar cell destruction – ataxia, tremor
• Peripheral neuropathy – stocking-glove anesthesia or burning, can affect gait

88

Cannabis

Endogenous cannabinoid system – infant bonding, regulates dopamine, sleep

THC
• Often desired: ↑ appetite, ↓nausea, ↓pain

89

Cannabis Adverse Reactions

• Dry mouth, conjunctiva injection
• ↓BP, ↑↓HR (arrhythmias), inter-ocular pressure
• Affects memory, motivation, false novelty
• Lowers IQ: If initiation started as a youth prior to age 18 then IQ does not recover when detoxed, if adult onset of initial use then can recover IQ after 1+ mo.
• Anxiety – fear, panic attacks, up phase of bipolar
• De-realization, paranoia, delusions, hallucinations

90

Some people use Marijuana to "treat" their anxiety. What do these folks not realize?

Withdrawal from marijuana is panic, fear. People do not realize this. It gets stored in fat stores throughout the body, and can take weeks to detox.

91

THC
...vs...
CBD

THC - Tetrahydrocannabinol

Cannabidiol (CBD) natural plant product (protective)

As the marijuana THC content goes up, the CBD content goes down

In 1960s marijuana had 3-4% content of each.
Now ... THC content is 18-25% & CBD very low

92

What about marijuana for chronic pain?

Nasobuccal Inhaled cannabis not recommended for medicinal purposes, bucal spray (THC+CBD) might be a 3rd or 4th line tx for neuropathic pain

But, for chronic pain, out other agents are much better!

93

Genetics and Psychosis in Marijuana Use

No genoytpe is completely protective from the potential for developing psychosis

Cannabis use may not cause schizophrenia, but can bring out expression of a latent psychotic disorder

94

At what age do brains become mature?

Women: age 23

Men: age 27

95

The young brain is developing and very vulnerable to the effects of substance use.

Our prof made a deal with her daughter that if she got to age 19 without drinking alcohol or doing drugs, she could have $1000. She'll keep doing this every 2 years.

96

Cocaine (crack)

↑DA
↑serotonin (5HT)
↑ noradrenalin (NOR)

This class includes methylphenidate (Ritalin), and
many other medications used to treat ADHD

97

Cocaine & Other Stimulates

Potential A/E

• Alert, powerful, insomnia, anorexia
• ↑HR, ↑BP, ↑arrhythmias, ↑MI, enlarged pupils
• Nasal defects, iv sequelae, stroke, fetal loss
• Anxiety, paranoia, delusions, psychosis, violence
• Tremor, hyper-reflexia, seizure, akathisia, choreiform movements

98

What is the relationship between Cocaine & Anorexia?

Cocaine suppresses appetite.

99

How to distinguish Cocaine from Heroin use by visualization of needle tracks?

►Cocaine:
15x / day
Needle tracks right up the arm

►Heroin:
4 x / day
Needle tracks just at cubital fossa

100

Genetics of Cocaine Dependence

Genetics and exposure to the drug are the primary risk factors to develop cocaine dependence

Making more endogenous opioids may protect you from cocaine dependence

If slow to break down dopamine after cocaine use you can get paranoid

101

Stimulant Induced MVT disorders

►Acute use
– abnormal picking (formication)
– Tremor
– myoclonic jerking
– akathisia (restlessness)
– choreiform (writhing, jerking)
– seizures

►If choreiform movements persist then dopaminergic pathways may be damaged

102

Dopamine overstimulation

Dopamine hypofunction

►Dopamine overstimulation
(like with stimulant use)
can give excessive movements like chorieform gait (writhing movements)

►Dopamine hypofunction
(like after burning out the dopamine system with severe stimulant use)
can cause decreased movements like a Parkinsons gait

103

What can acutely dropping dopamine levels cause?

Akathisia
– Restless Leg

"My legs have a mind of their own!"

104

Stimulant Induced Movement Disorder

Full blown serotonin syndrome:
– Rigidity
– Myoclonic jerking
– Hyper-reflexia
– Vasomotor instability
– Confusion
– Disorientation

105

MSE

Components

ASEPTIC

Appearance & Behavior
Speech
Emotion (mood & affect)
Perception
Thought Content & Process
Insight & Judgement
Cognition

106

Affect

What is the spectrum?

Full
Restricted
Blunted
Flat

107

What are the most common pyschiatric disorders associated with completed suicide?

Mood Disorders

Alcohol Abuse

108

What are Anticholinergics?

Substance that blocks the neurotransmitter Ach in CNS & PNS

Inhibit Parasympathetic nerve impulses

RESULT: stimulate sympathetic response

(eg) Atropine, Diphenhydramine (Benadryl)

109

Anticholinergics

Blind as a bat
Mad as a hatter
Red as a beet
Hot as Heat
Dry as a bone

The bowel and bladder lose their tone

The heart runs alone

blurred vision, mydriasis

hallucinations, psychosis, delirium, memory loss, coma

Flushing

Fever, hyperthermia

Dry mouth, dry eyes

Constipation, urinary retention, ileus

And the heart runs alone (tachycardia, HTN)

110

Anticholinergics

Explain side effects in English!

Dry Mouth
Blurred Vision
Urinary Retention
Constipation
Toxic-confusional state

111

Neuroleptic Malignant Syndrome

Sx?

Psychiatric Emergency
Due to massive dopamine blockade

FARM Sx
►Fever
►Autonomic changes (↑HR, ↑BP, sweating)
►Rigidity of muscles
►Mental Status Changes (confusion)

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Neuro-developmental Hypothesis

Updated version suggest that one (or more) ‘insults’ may occur in utero, perinatal, childhood, or adolescence!

Developmental changes lead to altered brain structure/ function !

113

Neuro-developmental Hypothesis

(A) Child Development

(B) Birth Complications

(C) Prenatal Infection, Famine or Nutrient Def

(D) Increased Rate of Minor Physical Anomalies

(E) Gross pathology

(F) Microscopic Pathology

114

(A) Child Development

• Impairments of motor, cognitive and social function in childhood, years before the onset of psychosis.

• Might include delayed walking, speech problems and lower scores on school tests

115

(B) Birth Complications

• Greater number of birth complications than controls

e.g. Rh incompatibility, preeclampsia, low birth weight, hypoxia, gestational diabetes

116

(C) Prenatal Infection, Famine or Nutrient Def

• Maternal famine
• micronutrient deficiency
• infection

117

(D) Increased Rate of Minor Physical Anomalies

• Anomalies in the face and head region

(e.g. furrowed tongue, shorter and wider palates, protruding ears) more common than in the general population

118

(E) Gross pathology

• Enlargement of lateral (and 3rd) ventricles
• However, ventricular size
i) varies widely between individuals,
ii) is only larger in some patients and
iii) is increased in other situations (e.g. degenerative disorders, alcoholism, perinatal hypoxia)

• Small reduction in total brain weight (more pronounced in
temporal lobe (hippocampus) and frontal lobe); correlates
with poorer function during life

• This pathology is present at the onset of the illness

119

(F) Microscopic Pathology

• Postmortem studies reveal alterations in the position of
neurons in schizophrenia

• Likely due to abnormal cell migration during a critical period of prenatal brain development – evidence for early developmental lesion

• If cell migration is altered then the cerebral cortex forms improperly, leading to aberrant connections and abnormal neurotransmission

120

Pathophysiology of Antipsychotics

What is the main Hypothesis?

Dopamine Hypothesis
Sx result from increase in Dopamine Transmission

►Drugs that DECREASE DA transmission alleviate psychosis. Antipsychotics are antagonists at DA D2 receptors. Clinical effectiveness of ‘typical’ antipsychotics directly related to D2 receptor affinity

►Drugs that INCREASE DA transmission can cause psychosis
(eg) L-dopa in Parkinson's disease, Cocaine

121

Antipsychotics

MOA?

Block DA Receptors → prevent stimulating postsynaptic neurons

Promote DA Re-uptake → clear DA from cleft

122

Cocaine

MOA?

DA transporters are responsible for removing DA molecules from the synaptic cleft after they they have done their job

Cocaine blocks these transporters, leaving DA trapped in the synaptic cleft. As a result, DA binds again and again to the receptors overstimulating the cell.

123

Amphetamine

MOA?

DA transporters are responsible for removing DA from the synaptic cleft. Because meth mimics DA, it is taken into the cell by the DA transporters

Once inside the cell, meth enters the DA vesicles forcing the DA molecules out.

The excess DA in the cell causes the transporters to start working in reverse, actively pumping DA out of the cell and into the synapse

The excess DA becomes trapped in the cleft. As a result, it binds again and again to the receptors, overstimulating the cell

124

Dopamine Hypothesis


What are the limitations?

• Explains positive Sx but not the negative Sx and cognitive impairment

• Negative and cognitive Sx are not well controlled by (typical) antipsychotics and are not brought on by use of cocaine or amphetamine

125

What do we know now about the Dopamine Hypothesis?

DA is not the only neurotransmitter involved
• Antipsychotics do not only bind at dopamine receptors
• Substances that act on other neurotransmitter systems can also produce psychosis

126

Glutamate Hypothesis of Schizophrenia

• Schizophrenia associated with NMDA R hypofunction

• Phencyclidine (PCP) and ketamine are NMDA antagonists and can mimic positive and negative symptoms and exacerbate symptoms in patients

• Glutamate is ubiquitously distributed in the CNS!

• Glutamate can determine dopamine release, leading to changes in DA transmission similar to those seen in schizophrenia through direct and indirect innervation of dopamine pathways

127

Serotonin Hypothesis of Schizophrenia

• Serotonin hypothesis suggests psychosis could result from INCREASED 5HT transmission

• LSD can produce psychotic symptoms. LSD mimics serotonin and may act through 5HT2A receptors

• Some atypical antipsychotics also act at 5HT2A

• Serotonin system also regulates dopaminergic tone!

128

Other Neurotransmitters?

• GABAergic interneurons have a direct influence on the glutamatergic regulation of dopamine!

• The cholinergic system has also been implicated in disrupting in DA balance

• The rate of smoking in individuals with schizophrenia is 3x that seen in the general population and may represent an attempt to compensate for a deficit in nicotinic acetylcholine transmission ... who knows ...?

129

Pathophysiology of Schizophrenia

SUMMARY
(key points)

• Altered brain development or maturation leads to changes in structural and/or functional connectivity

• Abnormal neurotransmission – involves dopamine system but also others (serotonin, glutamate etc...)

• Early genetic and/or environmental events likely cause! abnormal brain development

• Later factors may worsen brain ‘lesion’, increasing risk, or lessen the expression of previous defects, decreasing risk!

130

Is genetics relevant to mental illness?

• General population have a 3 % chance of developing a serious mental illness (SMI)

• If have a relative with SMI have a higher chance than general population

131

Twin Studies

►Schizophrenia
• Identical: ~50%
• Non-Idenitcal: ~15% (same as child getting it when one parent has it and NO other family Hx

►Bipolar disorder
• Identical: 70%
• Non-Idenitcal:20%

►Depression
• Identical: 35%
• Non-Idenitcal:26%

►Panic
• Identical: 25%
• Non-Idenitcal:10%

132

What is the role of genetic tests in mental illness diagnosis?

There are no genetic tests with which to diagnose psychiatric disorders

Currently, family history evaluation is more useful than most genetic testing for predicting risk estimates for psychiatric illness

In rare cases genetic testing is useful when psychiatric disorder present in an syndromic individual

133

Mental illnesses: caused by genes AND environment

MULTIFACTORIAL
Mental illness is NOT inherited, but one can inherit a vulnerability to it

Run in families, are highly heritable but illness can be etiologically heterogeneous between people

Some genetic variations have been shown to play a role in illness. But, risk is NOT destiny!

A genetic variant does not typically confer vulnerability to a single discrete psychiatric diagnosis

Many environmental factors can contribute to the development of illness

134

Tips for initiating conversation with families about mental illness.

ASK: "What do you think caused the illness?

This can be helpful to find out if the family is coming from a genetics-only or environmental-only standpoint. Or both (multi-factorial)

135

What is the risk of a patient with psychosis having a child with psychosis?

10%

Most patients perceive that there is a much higher risk. Sometimes people even choose to not have children because they perceive there is a high risk. In reality, the risk is much lower!

136

Mesolimbic pathway

For people with Schizophrenia, we want to block about 70% of the D2 receptors in this pathway.

►Associated with memory and emotional behaviors

►High Dopamine

►Positive symptoms
• Delusions
• Hallucinations
• Disorganized speech/thinking
• Disorganized or catatonic behavior

137

Mesocortical pathway

►Associated with cognition and motivation

►Low Dopamine

►Negative symptoms
• Alogia
• Anhedonia
• Affective flattening
• Avolition
• Asociality

138

Nigrostriatal pathway

►Location of Parkinsoins

139

Tubero-infundibular pathway

Controls prolactin secretion

Can cause sexual dysfunction

140

Pharmacodynamics of First Gen Antipsychotics

We are primarily wanting to block D2 in the Mesolimbic Pathway.

The effect on the other 3 pathways is all S/Es.

What are these effects in each?

►Mesolimbic Pathway
– Mediates Antipsychotic Efficacy
– Treats Psychosis
– This is the intended target!

►Mesocortical Pathway
– S/E: Neuroleptic Induced Deficit Syndrome

►Nigrostriatal pathway
– S/E: Extrapyramidal Symptoms (mimic Parkinsons)

►Tubero-infundibular pathway
– S/E: Increase in Prolactin Secretion

141

Pharmacodynamics of First Generation Antipsychotics

►H1
Sedation
Weight Gain

►a1
Decreased Blood Pressure Dizziness Drowsiness

►M1
Dry Mouth
Urinary Retention
Blurred Vision
Constipation

142

Is there any difference between any of the Second Gen Anti-psychotics?

YES
Clozapine

No other Anti-pscyhotic is any different or better than any other Anti-psychotic ... Except Clozapine ... it's special!

143

What do we do about the Extra-pyramdial Extrapyramidal Sx that can occur?

(eg. shaking hands)

We give an Anti-cholinergic agent

But, Anti-cholinergic agents can cause cognitive decline → monitor patient every 3 months

144

SSRI

S/E

Decreased sex drive because of the 2A
Tremors
Panic
Anxiety

145

What's the difference between 1st & 2nd Generation Anti-psychotics

No clear and consistent difference between the 1st and 2nd generation agents with regards to treatment response to positive Sx with the exception of clozapine for treatment-resistant patients.

146

Clozapine

S/E?

►Weight Gain

►Agranulocytosis → can cause death

These patients must be have blood drawn periodically for monitoring

147

Anti-psychotics

S/E
• Acute Dystonia
• Pseudo-parkinsonism
• Akathisia
• Tardive Dyskinesia
• NMS - Neuroleptic Malignant Syndrome

WHEN DO THESE APPEAR?

Min → Hours
►Acute Dystonia
►NMS - Neuroleptic Malignant Syndrome

Days → Weeks
►Pseudo-parkinsonism
►Akathisia

Months → Yrs
►Tardive Dyskinesia

148

Anti-psychotics S/E

►Acute Dystonia




S/E Prevalence ~10%

►Risk Factors:
– Young males
– Neuroleptic naive
– High-potency antipsychotics

►Can occur within hours of starting antipsychotics (minutes if given by IV or IM)

►May involve neck, eyes, jaw, tongue and back. Patient may not be able to swallow.
Can be painful and very frightening

Tx: Anticholinergic drugs
– Benztropine
– Diphenhydramine

149

Anti-psychotics S/E

►Pseudo-parkinsonism




S/E Prevalence ~20%

►Risk Factors:
– Elder females
– pre-existing neurological damage (e.g., head injury, stroke)

►Can occur days to weeks after an antipsychotic is started or after dose has been increased

►Tremor, rigidity, bradykinesia, bradyphrenia, salivation

Tx:
• Reduce dose of antipsychotic
• Change antipsychotic
• Oral anticholinergic
– Benztropine
– Trihexphenidyl

150

Anti-psychotics S/E

►Akathisia



S/E Prevalence ~25%;
(Less with atypicals)

►Occurs within hours to weeks of starting an anti-psychotic
or increasing the dose. May be misinterpreted as psychotic agitation

►Internal dysphoric restlessness. Associated with need to move.

Tx:
Combo: ß-blockers & benzos
– Propranolol
However, may be preferable to try another antipsychotic

151

Anti-psychotics S/E

►Tardive Dyskinesia



S/E Prevalence ~5% per year of antipsychotic exposure.

►Risk Factors:
– elderly women

Occurs in months to years.
Approx. 50% are reversible

►Repetitive purposeless movements may include lip smacking or chewing, tongue protrusion, choreiform hand movements, pelvic thrusting. Movement worse under stress. Stop anticholinergic if prescribed.


Tx:
• Reduce dose of antipsychotic
• Switch to atypical antipsychotic (clozapine or quetiapine)
• Other t/x have included tetrabenazine, benzodiazepines, propranolol, and Vit E

152

Anti-psychotics S/E

►NMS - Neuroleptic Malignant Syndrome

Sympathetic hyperactivity occurring as a result of dopaminergic antagonism
in the context of psychological stressors and genetic predisposition (comparable with Malignant Hyperthermia)

►Risk Factors:
– young male, dehydration, neurologic disabilities, exhaustion, agitation, and rapid or parenteral administration of Anti-psychotic

►Sx: muscle rigidity, confusion, fluctuating consciousness, diaphoresis, fever, hyperthermia, fluctuating BP, tachycardia

MEDICAL EMERGENCY
• has been reported with all antipsychotics

Tx:
• Discontinue antipsychotic
• Bromocriptine + dantrolene
• Amantidine

153

Agitation associated with psychosis

Tx?

►Mild sedation required
– Lorazepam +/- risperidone
– Olanzapine
– Quetiapine

►Mod to significant sedation required
(1) Lorazepam + loxapine
(2) Haloperidol + lorazepam
(3) Haloperidol + antihistamine
(4) Olanzapine IM

►Extended sedation required
– Zuclopenthixol Acetate

154

Insomnia

Drug options?

►Benzos:
– Lorazepam
– Oxazapam
– Temazepam

►Zopilcone

►Trazadone

155

Which Mood Stabilizer Drug is a STRONG Inducer of Cyp450?

Carbamazepine

156

Psychosocial Treatments in Schizophrenia

Take Home Messages

“Psychosis is treatable; recovery is expected”

157

What is the number 1 and number 2 Burden of Diseases?

(1) CV Disease

(2) Mental Illness

158

Genetics has a role in the developing of mental illness, but very low. Acquired biological factors play a role as well.

What are acquired / biological risk factors?

►genetics: hi familiality, not single major locus

►Acquired (biological) risk:
– influenza & starvation in middle trimester
– perinatal and birth complications
– advanced paternal age (increases risk 3x)
– daily dope / marijuana especially < age 15

► brain structure: differences are present at onset

159

Stress-vulnerability models in psychosis

Long history: family hx, stress as risk

Multiple sources of vulnerability, both inherited & acquired

Epidemiology of ‘stress’: early trauma, migration (moving many times in early childhood), urbanicity, cultural density

Progress: stress in etiology, stress in treatment

160

CBT works for many disorders. It is the most common psychotherapy.

What is the triangle that CBT addresses?

Thoughts
Behavior
Emotion

161

What is the effect on positive & negative Sx?

►Anti-psychotic medications

►CBT?

►medications
– treats only the positive Sx

►CBT
– treats both post & neg Sx

162

Psychotic Disorders & Employment

85% of people with Schizophrenia do not work

However, work promotes health for most people

The new approach is to place people in work and then train them. Just get them working!

163

More Take Home Points

Schizophrenia is a "Chronic illness," not a "broken brain"

Variable threshold for psychosis: stressors

Risk is not destiny

Medications address the positive Sx only

Meds are not sufficient ... need CBT!
(15-20 sessions of practice, practice practice!)

164

Stress-Vulnerability-Competence Model

The combination of the following determine the "Dimensions of Outcome." That is, do we have relapse? or remission & functional recovery?

►Psychobiological Vulnerability
– genetic diathesis
– neuro-developmental
– anomalies
– neuro-cognitive
– Impairments

►Stressors
– Life Events
– High Expressed Emotion
– Daily Hassles
– Illicit Drug Use

►PROTECTIVE FACTORS
– Social Skills
– Family & Social Support
– Personal Coping Skills & Self Esteem
– Stress Management
– Medication
– Family Counseling

165

What is the advantage of newer medications for Psychotic Disorders?

Not more effective

But less S/E!

166

Movement Disorders

3 categories

►Pyramidal Syndromes
– with spasticity as the major clinical manifestation

►Cerebellar Disorders
– with ataxia as the major clinical manifestation

►Basal Ganglia Disorders
– aka "extraphyramidal disorders"

167

►Chorea

►Dysotonia

►Ataxia

►Myloclonus

►Tremor

►Chorea
– Involuntary
– Irregular
– Random

►Dysotonia
– Involuntary
– Sustained muscle contractions
– Abnormal posture

►Ataxia
– Lack of voluntary coordination
– Unsteady Gait

►Myloclonus
– Involuntary
– Sudden & Brief
– Shock-like Movements

►Tremor
– Oscillatory & Rhythmic
– Involuntary movement disorder

168

Types of Tremor

►Intention
– Cerebellar Disease

►Postural
– Essential Tremor → improves with walking

►Rest
– Parkinson's Disease → worsens with walking
– disappears with voluntary movement

169

● gait apraxia
● urinary incontinence
● cognitive impairment (reversible, unlike dementia)

What is this Triad of Sx?

How to treat?

Normal Pressure Hydrocephalus
(NPH)

due to inability of brain to reabsorb CSF

Tx: lumbar puncture to remove some fluid

170

Parkinson's

Classic Sx

Need 2/4...

– Tremor
– Bradykinesia
– Asymmetric Rigidity
– Postural Instability (mild)

171

Parkinson's Sx
– Tremor
– Bradykinesia
– Asymmetric Rigidity
– Mild Postural Instability

Any Sx beyond these should alert me to the possibility of Atypical Parkinsonim

What is this?

►Progressive Supranuclear Palsy
(PSP)

►Multiple System Atrophy (MSA)

►Cotricobasal Degeneration (CBD)

172

Atypical Parkinsonim

What signs would alert us that we have an Atypical Parkinsonim presentation?

►EM disorder

►Pyramidal signs (pathologically broks or asymmetric reflexes, spastic catch, upgoing plantars

►Severe postural instability (having to catch an early stage patient on the pull test, spontaneous imbalance)

►Symmetry of Parkinsonian findings

►Cerebellar signs such as ataxia, dysmetria (MSA: Multiple System Atrophy)

173

Secondary Parkinsonism
(& other mimics)

►Vascular Parkinsonism

►Normal Pressure Hydrocephalus

►Space Occupying Lesions

►Medication / Intoxication

►Infections

►Repeated Head Trauma

174

How to diagnose Parkinson's Disease?

Initial Sx are termed "Parkinsonian Syndrome"

Must then rule out other causes such as head injury, drug induced, Parkinson mimics, Atypical presentation ...

Finally, the patient must have a demonstrated improvement to L-Dopa.

175

Parkinson's Disease

Tx?

►INITIAL THERAPY
– Dopaminergic therapy
– Levodopa → metabolized to Dopamine

►MORE ADVANCED DISEASE
– Prolong action of dopamine
– MAO B inhibitors (rasagiline, selegiline)
– COMT inhibitors (Entacapone)

176

Both Spasticity and Parkinsonian have rigidity due to increased muscle tone

What's the difference?

►Parkinsons
– increased tone in all muscles
– Reflexes are NOT increased

►Spasticity
– increased tone in flexors of the arm
– no resting tremor

177

Complete anaesthesia on the left side of the body

What is it?

►"Sensory Lemniscus"
– Both PCML & Spinothalamic affected

178

loss of pain and temperature sense on the LEFT side of the face

What could cause it?

Could be either

►Left spinal tract/nucleus of V

... or...

►R trigeminothalamic tract.

179

►Which of the following are associated with the BG?
►Which are associated with Cerebellum?

• abnormal postures
• chorea
• intention tremor
• rigidity
• tremor at rest

►Basal Ganglia
• abnormal postures
• chorea
• intention tremor
• rigidity
• tremor at rest

►Associated with cerebellar hemispheric lesions
• intention tremor

180

A patient has schizophrenia.
No one else in the family has it.

What is the risk of their child having schizophrenia?

9-16%

181

Dopamine Hypothesis

Positive Sx result from ...

Is it HYPER or HYPO-activity of dopamine?

positive symptoms result from dopamine hyperactivity

(pretend its "too much of a good thing")

182

What is the MOST robust imaging-based abnormality observed in schizophrenia?

Ventricular dilation

183

Essential Tremor
...vs...
Parkinson Tremor

►ET
– Alcohol may improve
– improves with walking

►PT
– Alcohol does NOT improve
– Bradykinesia: gets worse with walking

184

Atypical antipsychotics work on ...

BOTH Dopamine & Serotonin receptors

185

Is lower socioeconomic class is a risk factor for developing schizophrenia?

No