Psychiatry SC069: Does Alcohol Drive People Nuts? Alcohol And The Brain

Question 1

List of Alcohol-related Psychiatric conditions

Answer 1

1. Alcohol Use Disorder
2. Alcohol intoxication
3. Alcoholic blackout (斷片)
4. Alcohol withdrawal syndrome, **Delirium tremens (DT) (*Emergency)
5. Hepatic encephalopathy
6. Fetal alcohol syndrome
7. Cerebellar degeneration
8. Alcohol-Tobacco Amblyopia
9. Marchiafava-Bignami disease
10. Central pontine myelinolysis (Osmotic demyelination syndrome)
11. Substance/Medication-Induced Major or Mild ***Neurocognitive Disorder
12. Alcohol-induced Neurological deficit
13. Alcohol-related Dementia
14. Alcoholic dementia related to Pellagra
15. Vit B12 and Dementia
16. Wernicke’s encephalopathy (WE), **Korsakoff’s syndrome (*Emergency)
17. Alcohol Dependent Sleep Disorder
18. Alcohol and Suicide
19. ***Alcoholic Hallucinosis
20. Alcohol-induced Schizophrenia-like psychosis
21. Alcohol-induced Delusional Disorder
22. Alcohol-induced Mood Disorder
23. Alcohol-induced Anxiety Disorder
24. Alcohol Comorbid Psychiatric Disorders

Question 2

1. Alcohol Use Disorder

Answer 2

DSM-5 criteria:

(記:
1. **Craving / Urge
2. **Withdrawal
3. **Tolerance
4. **Inability to control
5. ***Impairment on life)

A. A problematic pattern of alcohol use leading to clinically significant impairment / distress, as manifested by **>=2 of the following occurring within a **12-month period:

1. Alcohol is often taken in ***larger amounts or over a longer period than was intended
2. There is a persistent ***desire or unsuccessful efforts to cut down or control alcohol use
3. A ***great deal of time is spent in activities necessary to obtain alcohol, use alcohol or recover from its effects
4. ***Craving, or a strong desire or urge to use alcohol
5. Recurrent alcohol use resulting in a ***failure to fulfill major role obligations at work, school, or home
6. Continued alcohol use despite having persistent or recurrent ***social or interpersonal problems caused or exacerbated by the effects of alcohol
7. Important social, occupational, or recreational activities are ***given up or reduced because of alcohol use
8. Recurrent alcohol use in situation in which it is physically ***hazardous
9. Alcohol use is continued ***despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by alcohol
10. ***Tolerance, as defined by either of the following:
    - A need for markedly increased amounts of alcohol to achieve intoxication or desired effect
    - A markedly diminished effect with continued use of the same amount of alcohol
11. ***Withdrawal, as manifested by either of the following:
    - The characteristic withdrawal syndrome for alcohol (refer to Criteria A and B of the criteria set for alcohol withdrawal)
    - Alcohol (or a closely related substance, such as benzodiazepine) is taken to relieve or avoid withdrawal symptoms

Question 3

Mechanism of action of Alcohol

Answer 3

1. Increase sensitivity of ***GABA receptors
   —> Enhance inhibitory action of GABAergic neurotransmission (Down-regulate in chronic state)
2. Inhibition of ***NMDA receptors
   —> Reduce excitatory action of glutamatergic neurotransmission (Up-regulate in chronic state)
3. Indirectly alter release of other neurotransmitters (e.g. serotonin, dopamine, norepinephrine, aspartate)

Question 4

2. Alcohol intoxication

Answer 4

DSM-5 criteria:

**Behavioural + **Psychological + ***Physical changes

A. Recent ingestion of alcohol

B. Clinically significant problematic behavioural / psychological changes (e.g. inappropriate sexual or aggressive behavior, mood lability, impaired judgment) that developed during, or shortly after, alcohol ingestion

C. One (or more) of the following signs or symptoms developing during, or shortly after, alcohol use:
1. Slurred speech
2. Incoordination
3. Unsteady gait
4. Nystagmus
5. Impairment in attention or memory
6. Stupor or coma

D. The signs or symptoms are not attributable to another medical condition and are not better explained by another mental disorder, including intoxication with another substance

If only 1 sip of alcohol —> Intoxication symptoms —> called Pathological intoxication (Mania a potu)

Question 5

Impairment at different Blood alcohol concentration (BAC)

Answer 5

20-30 mg/dL: Slowed motor performance and decreased thinking ability
30-80 mg/dL: Increases in motor and cognitive problems
80-200 mg/dL: Increases in incoordination and judgment errors / Mood lability / Deterioration in cognition
200-300 mg/dL: Nystagmus, marked slurring or speech, and alcoholic blackouts
>300 mg/dL: Impaired vital signs and possible death

Breathalyser 0.1 mg/L = Blood level 21 mg/dL (x2100 times)

Question 6

3. Alcoholic blackout (斷片)

Answer 6

• ***Transient amnesia
• ***Last hours
• Memory impairment
• ***No impairment of conscious level
• Inhibition of NMDA receptors in hippocampus
• Failure of ***long-term potentiation (LTP) (process involving persistent strengthening of synapses that leads to a long-lasting increase in signal transmission between neurons: major cellular mechanisms that underlies learning and memory)

Question 7

***4. Alcohol withdrawal syndrome, Delirium tremens (DT)

Answer 7

1. **Alcohol withdrawal syndrome:
   - Occur **6-24 hours after last drink
   - Autonomic **hyperactivity:
   —> Tremulousness
   —> Sweating
   —> N+V
   —> **Anxiety (vs Alcohol-induced Anxiety Disorder)
   —> Agitation
   —> Tachycardia
   - Hypertension, Hyperreflexia, Insomnia, Nightmares, Sweating, Hyperthermia
   - **Down-regulation of GABA receptor in chronic alcoholics
   - **Reversal of inhibition (i.e. Up-regulation) of NMDA receptor —> ***glutamate overactivity
   - Disappears in 2-7 days
2. Delirium tremens (Delirium + Tremor):
   - Severe form of alcohol withdrawal
   - Occur in about **24-96 hours (1-4 days) of abstention, a course of 3-7 days (SpC Psychi PP)
   - **Confusion
   - **Hallucination (Visual hallucination: Lilliputian hallucination (M18 pp), Tactile hallucinations (SpC Psychi PP))
   - **Severe agitation
   - ***Seizure
   - Mortality 5%
   - Medical emergency requiring hospitalisation

Treatment of Delirium tremens:
1. **BDZ in decreasing dosage (~giving alcohol to patient)
- Lorazepam (Ativan, short acting, given for patient with liver impairment)
- Diazepam (Valium, long acting)
- Others
2. **Anticonvulsants (Carbamazepine)
3. ***Thiamine (B1) (Proactive use of Parenteral vitamins) (only CI is allergy)
4. Neuroleptics for control of agitation
5. Fluid + Electrolyte balance

Other use of Thiamine (important in glucose metabolism):
- ***Wernicke-Korsakoff syndrome
- Alcoholism-related nutritional problem

Question 8

5. Hepatic encephalopathy

Answer 8

***West Haven criteria:
Stage 1:
- Trivial lack of awareness
- Shortened attention span
- Impaired addition / subtraction
- Hypersomnia, Insomnia / Inversion of sleep pattern
- Euphoria / Depression
- Asterixis can be detected

Stage 2:
- Lethargy / Apathy
- Mild disorientation
- Inappropriate behaviour
- Slurred speech
- Obvious asterixis

Stage 3:
- Gross disorientation
- Bizarre behavior
- Semi-stupor to stupor
- Asterixis generally absent

Stage 4:
- Coma

GCS score may also be used

Question 9

6. Alcohol Induced Neurodevelopmental Disorder: Fetal alcohol syndrome

Answer 9

Fetus of Alcoholic mother
- 1% of all live births (U.S.)
- Impaired fine motor skills (e.g. gait disturbance)
- Sensorineural deafness
- Poor hand eye co-ordination
- Learning difficulties
- Poor impulse control
- Impaired memory, attention, judgment
- Speech difficulty

Fetal alcohol effect:
- 3-5 per thousand live births
- in a child with history of maternal alcohol abuse
(a) Prenatal & postnatal growth retardation
(b) Neurological abnormality, developmental delay / intellectual impairment
(c) Craniofacial abnormalities

Fetal alcohol syndrome:
- Heavy drinking 30%
- 1-4 per 1000 live births (U.S.)
1. Most common cause of preventable mental retardation
2. **Microcephaly
- Agenesis of corpus callosum
- Cerebellar hypoplasia
3. **Low birth weight
4. **Facial dysmorphology
- Small head
- Short eyelid opening
- Epicanthal folds
- Low nasal bridge
- Short nose
- Flat midface
- Smooth philtrum
- Thin upper lip
- Underdeveloped jaw
5. **Growth retardation

Question 10

7. Cerebellar degeneration

Answer 10

• ***Thiamine deficiency
• Atrophy of cerebellum (vermis)

Clinical features:
- Unsteady gait
- Truncal instability
- Lower limb ataxia
- Postural hand tremor
- Dysarthria
- Nystagmus
- Degeneration of Purkinje’s cells

Question 11

8. Alcohol-Tobacco Amblyopia

Answer 11

• Heavy drinker + smoker
• **Thiamine / **B12 deficiency

Clinical features:
- Loss of visual acuity
- Central scotoma
- Loss of colour vision
- Optic atrophy

Question 12

9. Marchiafava-Bignami disease

Answer 12

• Severe chronic drinkers
• **Subacute **demyelination disease
• 40-60 years old

Clinical features
- **Fits, spasticity, rigidity, paralysis
- Coma, death
- Main site: Mid **corpus callosum —> Vacuolation + Degeneration of corpus callosum
- Other site: Frontal lobe syndrome —> Dementia / Personality change

Question 13

10. Central pontine myelinolysis (Osmotic demyelination syndrome)

Answer 13

• ***Demyelination of pons

Clinical features:
- **Dysarthria / Dysphagia
- **Spastic paralysis of 4 limbs
- Caused by infusion of hypertonic saline for treatment of hyponatraemia
- Personality change, inappropriate affect, delusion

Other causes:
- Cirrhosis, Liver transplant, Uraemia, Haemodialysis, Prolonged vomiting, Diuretics

Question 14

Alcohol, Wine and Stroke

Answer 14

Alcohol:
- Light / Moderate drinking: ↓ Risk of Ischaemic stroke
- Heavy drinking: ↑ Risk of Haemorrhagic stroke

Copenhagen City Heart Study:
- Intake of beer, wine, spirits and Risk of stroke
- Adjustment for confounding variables
- Beer / Spirits: No relation
- ***Wine: ↓ Risk

Question 15

Alcohol and Dementia

Answer 15

Alcohol:
Rotterdam Study 2002:
- ***Light-Moderate drinking: ↓ Dementia risk
- 1-3 drinks / day —> Hazard ratio: 0.58

Wine:
- Orgogozo 1997, Rev Neurology
- ***Moderate drinker:
—> Dementia OR: 0.18
—> Alzheimer’s disease OR: 0.25

Question 16

11. Substance/Medication-Induced Major or Mild ***Neurocognitive Disorder

Answer 16

DSM-5:
A. The criteria are met for major or mild neurocognitive disorder
B. The neurocognitive impairments do **not occur exclusively during the course of a delirium and persist **beyond the usual duration of intoxication and acute withdrawal
C. The involved substance or medication and duration and extent of use are **capable of producing the neurocognitive impairment
D. The **temporal course of the neurocognitive deficits is consistent with the timing of substance or medication use and abstinence (e.g. the deficits remain stable or improve after a period of abstinence)
E. The neurocognitive disorder is ***not attributable to another medical condition or is not better explained by another mental disorder

Question 17

12. Alcohol-induced Neurological deficit

Answer 17

• Impairment in visuospatial processing
• Memory impairment
• EEG abnormalities
• Reduction in cerebral blood flow
• Reduction in cerebral glucose metabolism

Question 18

13. Alcohol-related Dementia

Answer 18

• Cerebral atrophy
• Diagnosed 8 weeks after abstinence
• Cognitive impairment
• Simulate frontal lobe dementia
• ***Partly reversible with sobriety
• ***Direct neuronal toxicity of alcohol
• ***NOT due to thiamine deficiency

Diagnostic criteria (Oslin 1998):
A.
1. A clinical diagnosis of dementia **>=60 days after the last exposure to alcohol
2. Significant alcohol use as defined by a minimum average of **35 standard drinks per week for men (28 for women) for greater than a period of **5 years. The period of significant alcohol use must occur within **3 years of the initial onset of dementia.

B. The diagnosis of alcohol related dementia is ***supported by the presence of any of the following:
1. Alcohol related hepatic, pancreatic or other end organ damage.
2. Ataxia or peripheral sensory polyneuropathy
3. Beyond 60 days of abstinence, the cognitive impairment stabilizes or improves.
4. After 60 days of abstinence, any neuroimaging evidence of ventricular of sulcal dilatation improves.
5. Neuroimaging evidence of cerebellar atrophy, especially the vermis (central part of cerebellum)

C. The following clinical features cast **doubt on the diagnosis of Alcohol Related Dementia. (∵ Impairment is more **specific rather than global)
1. The presence of language impairment, especially dysnomia or anomia.
2. The presence of focal neurologic signs or symptoms (except ataxia or peripheral sensory polyneuropathy).
3. Neuroimaging evidence for cortical or subcortical infarction, subdural hematoma, or other focal brain pathology.
4. Elevated Hachinski Ischemia Scale score.

D. Clinical features that are ***neither supportive nor cast doubt on the diagnosis of Alcohol Related Dementia included:
1. Neuroimaging evidence of cortical atrophy.
2. The presence of periventricular or deep white matter lesions on neuroimaging in the absence of focal infarct(s).
3. The presence of the Apolipoprotein e4 allele.

Question 19

14. Alcoholic dementia related to Pellagra

Answer 19

• Uncommon
• ***Niacin (B3) deficiency
• 3”D”s: **Dementia, **Dermatitis, ***Diarrhoea
• Irritability, Apathy, Depression, Inattention, Memory loss, Stupor, Coma
• Peripheral neuropathy

Question 20

15. Vit B12 and Dementia

Answer 20

Level required for maintaining ***haematological function: 148 pmol/L (200 pg/ml)

Level required for maintaining ***neurological function: ~250 pmol/L (~350 pg/ml)

Neurological impairment:
1. **Combined degeneration of spinal cord
2. **Peripheral neuropathy
3. **Ataxia
4. Optic atrophy
5. **Dementia
6. Depression
7. Psychosis
8. Delirium

Question 21

***16. Wernicke’s encephalopathy (WE), Korsakoff’s syndrome (aka Korsakoff’s psychosis / Amnesic syndrome)

Answer 21

Wernicke’s encephalopathy:
- Mostly alcoholic / some non-alcoholic
- Cause: **Thiamine deficiency
- 20% detected in life
- **Medical emergency
- **20% mortality
- **Progression to Korsakoff’s Psychosis (84%)

Clinical features:
**Triad:
1. **Confusion
2. **Ataxia (truncal) / Tremor
3. **Ophthalmoplegia / Nystagmus

Others:
- Memory Impairment / Attention problems / Hallucination
- Peripheral neuropathy (50%)
- Hypothermia
- Apathy
- Coma (rare)

Treatment:
- ***IM/IV Thiamine

Korsakoff’s syndrome:
- **Retrograde amnesia: **Severe + **Irreversible loss of **short term memory
- **Anterograde amnesia: Inability to learn and later recall new information
- +/- **Confabulation (fabricated memories)
- No clouding of consciousness
- No general impairment of other cognitive functions

Other Non-alcoholic causes of Wernicke-Korsakoff’s syndrome:
**Common defect: **Thiamine deficiency
1. Hyperemesis of pregnancy
2. Systemic malignancy
3. GI surgery
4. Haemodialysis / Peritoneal dialysis
5. Prolonged intravenous feeding
6. Refeeding after prolonged fasting / starvation
7. Anorexia nervosa
8. Dieting / Starvation
9. Gastric plication
10. AIDS

Pathology:
- Petechial haemorrhages
- Neuronal loss
- Gliosis
- Brown discolouration

Location of pathology (***Midline structures):
- Periventricular grey matter
- Third ventricle
- Sylvain aqueduct
- Fourth ventricle
- Dienchephalon (Epithalamus, Thalamus, Hypothalamus, Subthalamus)
- Midbrain, pons, medulla

Other causes of Amnesic syndrome (***Medial Temporal Lobe Lesion):
- Closed head trauma
- Penetrating missile wounds
- Focal tumour
- Encephalitis
- Hypoxia (CO poisoning)
- Infarction (posterior cerebral artery)
- Surgery

(簡單而言:
- Thiamine deficiency: affect Midline structures (Diencephalon, Brainstem)
- Non-thiamine deficiency: think about Medial temporal lobe lesion)

Question 22

***Delirium tremens vs Wernicke’s encephalopathy

Answer 22

DT (記: CHS):
- Occur in about 24-96 hours (1-4 days) of abstention, a course of 3-7 days (SpC Psychi PP)
- **Confusion
- **Hallucination (Visual hallucination: Lilliputian hallucination (M18 pp), Tactile hallucinations (SpC Psychi PP))
- **Severe agitation
- **Seizure
- Treatment: BDZ, Anticonvulsants, Thiamine

WE (記: CAO):
**Triad:
1. **Confusion
2. **Ataxia (truncal) / Tremor
3. **Ophthalmoplegia / Nystagmus

Others:
- Memory Impairment / Attention problems / Hallucination
- Peripheral neuropathy (50%)
- Hypothermia
- Apathy
- Coma (rare)

Treatment:
- IM/IV Thiamine

Question 23

Thiamine deficiency in Chronic alcoholism

Answer 23

Causes:
- **Low reserve
- **Impaired storage capacity
- **Decreased intake
- **Impairment of absorption
- **Increased excretion
- **Thiamine dysfunction

Diseases:
1. Alcohol withdrawal syndrome, Delirium tremens (DT)
2. Cerebellar degeneration
3. Alcohol-Tobacco Amblyopia
4. Wernicke’s encephalopathy (WE), Korsakoff’s syndrome

Question 24

17. Alcohol Dependent Sleep Disorder

Answer 24

1. Decrease sleep latency
2. Rebound insomnia
3. Repeated awakening
4. Tolerance

Sleep in abstinent alcoholics:
- Prolonged sleep latency
- Light + fragmented sleep
- Shortened overall sleep time
- Reduced amount of deep sleep
- Persist for 2 years after abstinence

Question 25

18. Alcohol and Suicide

Answer 25

• 7% of alcohol abusers die of suicide
• ***Alcoholism is a factor in 30% of all completed suicides
• 50% of suicide attempts have consumed alcohol at the time of attempt
• 96% of alcoholics who die by suicide continue alcohol use up to the end of their lives

Psychological effects of alcohol that ↑ suicidality:
1. Increased impulsivity
2. Aggressiveness
3. Disinhibition
4. Poor judgement
5. Increase pain threshold
6. Numbing of anxiety response
7. Numbing of thoughts on consequences

Psychosocial effects of alcohol abuse contributing to suicidality:
1. Marital breakdown
2. Domestic violence
3. Job loss
4. Financial difficulty
5. Social isolation
6. Poor physical health
7. Loss of self esteem

Question 26

***19. Alcoholic Hallucinosis

Answer 26

• Chronic heavy drinkers
• ***Auditory hallucination
• ***Clear consciousness (vs Clouded sensorium in DT)
• Distressing in content
• Some develop ***schizophrenia, some remit after stopping alcohol use

(vs Delirium tremens:
- During reduction in alcohol intake
- **Visual hallucination: Lilliputian hallucination (M18 pp)
- **Clouded sensorium)

Treatment:
1. Abstain from alcohol
2. Antipsychotics

Question 27

20. Alcohol-induced Schizophrenia-like psychosis

Answer 27

• Chronic heavy drinking
• ***Clear sensorium
• ***Schizophrenia-like syndrome
• Remission on stopping alcohol
• Recur with relapse of alcoholism

Question 28

21. Alcohol-induced Delusional Disorder

Answer 28

A. Persistent **non-bizarre delusions
B. **No characteristic schizophrenic symptoms
C. Hallucination not prominent + not organised
D. Mood episode **not significant
E. Usually **morbid jealousy

Question 29

22. Alcohol-induced Mood Disorder

Answer 29

• Moderate / Heavy alcohol use
• **Major depression, **Mania
• Persist for up to 4 weeks after abstinence
• Clears up on stopping alcohol

Question 30

23. Alcohol-induced Anxiety Disorder

Answer 30

• Generalised anxiety disorders / Panic disorder / Phobic anxiety disorders / Social phobia / Obsessive compulsive disorder / PTSD
• Symptoms occur while patient on heavy alcohol consumption
• Subside gradually on abstinence, but may persist to up to 6 months
• Must be distinguished from ***Alcohol withdrawal syndrome (severe autonomic NS disturbance, surge of anxiety symptoms)

Question 31

24. Alcohol Comorbid Psychiatric Disorders

Answer 31

• Evidence of psychiatric disorders ***before onset of alcohol abuse or dependence
• Evidence of persistent psychiatric symptoms during extended ***alcohol-free periods (over 4 weeks)
• ***First degree biological relative has documented psychiatric disorder

1. Antisocial personality disorders (80%)
   (i.e. 80% of antisocial personality patients suffer from alcoholism)
   - Begins early in life
   - Severe antisocial behaviour before age 15
   - Impulsive, violent, manipulative
   - Unable to learn from mistakes / benefit from punishment
   - Separate genetic factors
2. Bipolar Ι disorder (60%)
   - Manic episode: hyperexcitable, impulsive
   - Aggravation of Bipolar disorder
   - High suicide rate
3. Schizophrenia (30%)
   - Alcohol decrease feeling of isolation
   - Temporary reduce symptoms of anxiety / depression / insomnia
   - Increase psychotic symptoms + mood swings
   - Disruptive behaviour, suicide, treatment non-compliance, drug abuse, poor clinical outcome
   - Drug accumulation due to hepatic damage
4. Drug addiction (20%)
   - Alcoholics 6x more prone to become drug abusers
5. Anxiety disorders
   - Social phobia
   - Panic disorder

Question 32

Relationship between Alcoholism and Psychiatric symptoms

Answer 32

1. Alcoholism can cause Psychiatric symptoms
2. Psychiatric symptoms can cause Alcoholism
3. Confounding factors can cause both (e.g. Personality, Psychosocial factors, Drugs)

Question 33

***6 Causes of Confusion in Alcoholism

Answer 33

1. Intoxication
2. ***Delirium tremens
3. Head Injury
4. Metabolic disturbances (e.g. hypoglycaemia)
5. Hepatic encephalopathy
6. ***Wernicke encephalopathy