ALCOHOL AND THE BRAIN
ALCOHOL AND THE BRAIN
GENERAL OVERVIEW
Presentation by: Dr. Heid Lo, Clinical Assistant Professor, Department of Psychiatry, HKU
Artwork Reference: Vincent van Gogh's "Agostina Segatori Sitting in the Café du Tambourin" (1887)
AREAS TO BE COVERED
Alcohol-related addictive problems
Alcohol-related medical conditions and brain changes
Alcohol-related psychiatric disorders (alcohol-induced psychiatric disorders and comorbid conditions)
Relationship between alcohol and psychiatric disorders
Six causes of confusion in alcoholism
ALCOHOL-RELATED ADDICTIVE PROBLEMS
Alcohol Use Disorder (DSM-5)
Definition: A problematic pattern of alcohol use leading to clinically significant impairment or distress, as manifested by at least two of the following criteria occurring within a 12-month period:
Alcohol is often taken in larger amounts or over a longer period than was intended.
There is a persistent desire or unsuccessful efforts to cut down or control alcohol use.
A great deal of time is spent in activities necessary to obtain alcohol, use alcohol or recover from its effects.
Craving, or a strong desire or urge to use alcohol.
Recurrent alcohol use resulting in a failure to fulfill major role obligations at work, school, or home.
Continued alcohol use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of alcohol.
Important social, occupational, or recreational activities are given up or reduced because of alcohol use.
Recurrent alcohol use in situations in which it is physically hazardous.
Alcohol use is continued despite knowledge of having a persistent or recurrent physical or psychological problem likely caused or exacerbated by alcohol.
Tolerance, defined as:
a. A need for markedly increased amounts of alcohol to achieve intoxication or the desired effect.
b. A markedly diminished effect with continued use of the same amount of alcohol.Withdrawal, as manifested by:
a. Characteristic withdrawal syndrome for alcohol.
b. Alcohol (or closely related substance, such as benzodiazepine) taken to relieve or avoid withdrawal symptoms.
MECHANISM OF ACTION
GABA Receptors
Alcohol increases the sensitivity of GABA receptors, enhancing the inhibitory action of GABAergic neurotransmission; there is downregulation in the chronic state.
NMDA Receptors
Alcohol inhibits NMDA receptors, reducing the excitatory action of glutamatergic neurotransmission; there is upregulation in the chronic state.
Neurotransmitter Release
Alcohol indirectly alters the release of other neurotransmitters such as serotonin, dopamine, norepinephrine, and aspartate.
ALCOHOL INTOXICATION (DSM-5)
Criteria for Diagnosis
A. Recent ingestion of alcohol.
B. Clinically significant behavior or 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, which are not attributable to another medical condition or another mental disorder, including intoxication with another substance:
Slurred speech
Incoordination
Unsteady gait
Nystagmus
Impairment in attention or memory
Stupor or coma
IMPAIRMENT AT DIFFERENT ALCOHOL CONCENTRATIONS
Concentration Levels and Effects:
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 of speech, and alcoholic blackouts.
>300 mg/dL: Impaired vital signs and possible death.
Blood Alcohol Content Measurement:
Breathalyzer reading of 0.1 mg/L correlates to blood level of 21 mg/dL (x2100).
ALCOHOLIC BLACKOUT
Description:
Transient amnesia lasting hours, with memory impairment but no impairment of conscious level.
Neurological Mechanism:
Inhibition of NMDA receptors in the hippocampus leading to a failure of long-term potentiation (LTP).
ALCOHOL WITHDRAWAL SYNDROME
Timeline: Occurs 6-24 hours after last drink.
Symptoms:
Autonomic hyperactivity: tremulousness, sweating, nausea, vomiting, anxiety, agitation, and tachycardia.
Other features: Hypertension, hyperreflexia, insomnia, nightmares, sweating, hyperthermia.
Chronic alcoholics show downregulation of GABA receptors.
Symptoms disappear in 2-7 days.
DELIRIUM TREMENS
Severe Form of Alcohol Withdrawal:
Occurs within 24-96 hours of abstention.
Symptoms include confusion, hallucination, severe agitation, and seizure.
Mortality rate: 5%.
Treatment:
Benzodiazepines in decreasing dosage (e.g., lorazepam, diazepam).
Anticonvulsants (e.g., carbamazepine).
Proactive use of parenteral vitamins (thiamine).
Neuroleptics for controlling agitation.
Management of fluid and electrolyte balance.
WERNICKE’S ENCEPHALOPATHY
Symptoms:
Confusion, memory impairment, attention problems, hallucinations, ophthalmoplegia, nystagmus, ataxia (truncal), and peripheral neuropathy (50%).
Rarely, hypothermia, apathy, and coma.
Cause:
Primarily thiamine deficiency, common in alcoholics.
Detection:
20% detected in life (Harper 1983).
Medical emergency with a mortality rate of 20%.
Treatment:
Intramuscular (IM) or intravenous (IV) thiamine.
High risk of progression to Korsakoff’s Psychosis (84%).
KORSAKOFF’S SYNDROME
Symptoms:
Severe irreversible loss of short-term memory, inability to learn and recall new information, and possible confabulation (±).
No clouding of consciousness or general impairment of other cognitive functions.
WERNICKE-KORSAKOFF’S SYNDROME
Non-Alcoholic Causes
Conditions leading to thiamine deficiency:
Hyperemesis of pregnancy
Systemic malignancy
Gastrointestinal surgery
Hemodialysis or peritoneal dialysis
Prolonged intravenous feeding
Refeeding after prolonged fasting or starvation
Anorexia nervosa
Dieting/starvation
Gastric plication
AIDS
Common Defect: Primarily thiamine deficiency.
WERNICKE-KORSAKOFF’S SYNDROME PATHOLOGY
Pathological Features:
Petechial hemorrhages
Neuronal loss
Gliosis
Brown discoloration
Regions Affected:
Periventricular grey matter
Third ventricle
Sylvian aqueduct
Fourth ventricle
Diencephalon, midbrain, pons, medulla
ALCOHOL-RELATED PSYCHIATRIC DISORDERS
AMNESIC SYNDROME (KORSAKOFF’S PSYCHOSIS)
Other Causes of Medial Temporal Lobe Lesion
Causes include:
Closed head trauma
Penetrating wounds
Focal tumor
Encephalitis
Hypoxia (carbon monoxide)
Infarction (posterior cerebral artery)
Surgery
BRAIN CIRCUIT IN WERNICKE-KORSAKOFF’S SYNDROME
Key Areas:
Medial diencephalon: midline thalamic nuclei, dorsomedial thalamus, anterior thalamus.
Medial temporal lobe: hippocampal region, entorhinal cortex, mammillary nuclei, perirhinal cortex, parahippocampal cortex.
Cerebral cortex: frontal and sensory association areas.
HEPATIC ENCEPHALOPATHY
West Haven Criteria for Severity
Stage 1:
Trivial lack of awareness, shortened attention span, impaired simple math, hypersomnia or insomnia, euphoria, or depression present. Asterixis can be detected.
Stage 2:
Lethargy or apathy, mild disorientation, inappropriate behavior, slurred speech, and obvious asterixis.
Stage 3:
Gross disorientation, bizarre behavior, semi-stupor to stupor; asterixis generally absent.
Stage 4:
Coma; the Glasgow Coma Scale may also be used to assess.
FOETAL ALCOHOL SYNDROME
Incidence: Heavy drinking affects 30% of pregnancies, with 1-4 per 1000 live births in the U.S.
Effects:
Microcephaly, agenesis of corpus callosum, and cerebellar hypoplasia.
Most common cause of preventable mental retardation.
Includes low birth weight, facial dysmorphology, and growth retardation.
FAS Facial Characteristics
Characteristics include:
Small head
Short eyelid opening
Low nasal bridge
Epicanthal folds
Flat midface
Short nose
Smooth philtrum
Underdeveloped jaw and thin upper lip
CEREBELLAR DEGENERATION
Cause: Thiamine deficiency leading to atrophy of the cerebellum (vermis).
Symptoms:
Unsteady gait, truncal instability, lower limb ataxia, postural hand tremor, dysarthria, nystagmus.
Degeneration of Purkinje's cells.
Imaging
MRI Findings:
Sagittal T1 weighted MRI showing atrophy of cerebellar vermis.
Mid-line section comparisons of alcoholic and non-alcoholic patients showing abnormalities in the cerebellum.
MARCHIAFAVA-BIGNAMI DISEASE
Affected Population: Severe chronic drinkers, particularly Italian drinkers of crude red wine.
Symptoms:
Subacute demyelination disease resulting in fits, spasticity, rigidity, paralysis, coma, and death.
Affects the mid corpus callosum, primarily found in individuals aged 40-60.
May lead to frontal lobe syndrome, dementia, and personality changes.
MARCHIAFAVA-BIGNAMI DISEASE PATHOLOGY
Histological Findings: Vacuolation and degeneration of the corpus callosum.
CENTRAL PONTINE MYELINOLYSIS (OSMOTIC DEMYELINATION SYNDROME)
Pathophysiology: Demyelination of the pons caused by rapid correction of hyponatremia with hypertonic saline.
Symptoms:
Dysarthria, dysphagia, spastic paralysis of all four limbs.
Personality change, inappropriate affect, delusions.
Associated Conditions: Cirrhosis, liver transplant, uremia, hemodialysis, prolonged vomiting, diuretics.
Imaging
MRI Findings:
Axial T2 weighted MRI showing a region of demyelination in the central pons.
Histology showing absence of myelin in the affected regions.
ALCOHOL AND STROKE
Stroke Analysis by Drinking Type
Type and Risk Relationship:
Hemorrhagic Stroke: 15% risk with light/moderate drinking.
Ischaemic Stroke: 85% risk decreased with heavy drinking.
References: Studies by Van Gign (1993), Camargo (1996), Sacco (1999), Klatsky (2001) indicate this to be a controversial subject.
WINE & STROKE RISK
Study Reference: Copenhagen City Heart Study indicating the intake of beer, wine, and spirits and risk of stroke with adjustments for confounding variables.
Beer/spirit consumption showed no relation, while wine consumption was associated with a decreased risk (Truelsen et al, 1998).
ALCOHOL-INDUCED NEUROLOGICAL DEFICIT
Symptoms include impairment in visuospatial processing, memory impairment, EEG abnormalities, and reduction in cerebral blood flow and cerebral glucose metabolism.
ALCOHOL AND SUICIDE
Statistics:
7% of alcohol abusers die by suicide.
Alcoholism is a factor in 30% of all completed suicides.
50% of suicide attempts involve alcohol consumption at the time.
96% of alcoholics who die by suicide continue alcohol use until the end of life (American Foundation of Suicide Prevention).
ALCOHOLIC HALLUCINOSIS
Occurrence: Found in chronic heavy drinkers; characterized by auditory hallucinations, clear consciousness, and distressing content.
Some may develop schizophrenia, while others remit after abstaining from alcohol.
Treatment:
Antipsychotics and advice for abstaining from alcohol are recommended.
Must differentiate from delirium tremens.
ALCOHOL-INDUCED SCHIZOPHRENIA-LIKE PSYCHOSIS
Description:
Occurs in the context of chronic heavy drinking.
Characterized by a clear sensorium and a schizophrenia-like syndrome.
Symptoms may remit upon stopping alcohol and recur with relapse of alcoholism.
ALCOHOL-INDUCED MOOD DISORDER
Characteristics: Associated with moderate or heavy alcohol use leading to major depression or mania, which may persist for up to 4 weeks after abstinence but typically resolves after stopping alcohol consumption.
ALCOHOL-INDUCED ANXIETY DISORDER
Symptoms: Occur during heavy alcohol consumption, subsiding gradually on abstinence but may persist for up to 6 months.
Included are generalized anxiety disorders, panic disorder, phobic anxiety disorders, social phobia, obsessive-compulsive disorder, and post-traumatic stress disorder (PTSD).
Must be distinguished from alcohol withdrawal syndrome.
ALCOHOL COMORBID PSYCHIATRIC DISORDERS
Indicators: Evidence of psychiatric disorders before onset of alcohol abuse or dependence; persistent psychiatric symptoms during extended alcohol-free periods (over 4 weeks); documented psychiatric disorders in first-degree biological relatives.
Prevalence of Specific Disorders
Antisocial personality disorders: 80% co-morbidity with alcoholism.
Bipolar I disorder: 60% co-morbidity.
Schizophrenia: 30% co-morbidity.
Drug addiction: 20% co-morbidity.
Anxiety disorders include social phobia and panic disorder.
ALCOHOL COMORBID PSYCHIATRIC DISORDERS: IMPACT ON ALCOHOLISM
Schizophrenia is present in 30% of alcohol-related cases.
Alcohol may temporarily decrease feelings of isolation and reduce anxiety/depression/insomnia symptoms but can increase psychotic symptoms and mood swings.
Associated with disruptive behavior, suicide, treatment non-compliance, drug abuse, and poor clinical outcomes.
Drug accumulation due to hepatic damage complicates treatment.
CAUSES OF CONFUSION IN ALCOHOLISM
Six key causes:
Intoxication
Delirium Tremens (DT)
Head injury
Metabolic disturbances (e.g., hypoglycaemia)
Hepatic encephalopathy
Wernicke encephalopathy
ACKNOWLEDGEMENT
Special thanks to Dr. Lam Tat Chung, Paul
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