Transcript Psychopathology

Psychopathology
Rains Chapter 13
What is Psychopathology
• Major psychiatric disorders can severely
disrupt behavior and cause enormous
suffering.
• Biological factors
– medical model
– illness
– lesion responsible for disorder
• psychosocial factors
– Problems in living
What is Psychopathology
• Gleitman (1995) example
• individual with no cognitive disability but has
simply not been taught to read.
• Someday may identify brain circuits for reading
and be able reprogram them through microsurgery
or gene therapy
• Probably better to understand inability to read in
terms of lack of training
What is Psychopathology
• General paresis as an example
• syphilis caused by bacterial infection
• in a few cases, symptoms seem to clear up then later
general paresis appears
• at first, thought general paresis was psychological disorder
• progressive general decline of physical and psychological
functioning culminating in personality changes, disturbed
gait, delusions, dementia, and death
The Schizophrenic Disorders
•
•
•
•
1-1.5% of population
400,000 persons hospitalized in US
about 30% of all hospital beds
Typically chronic
– symptoms may be more or less intense but
seldom recover completely
• Onset in early 20’s
Positive Symptoms
•
•
•
•
Delusions
Hallucinations
Bizarre behavior
Formal thought disorder
– loose associations
– word salad
Negative Symptoms
•
•
•
•
•
•
•
•
•
Apparent absence of motivation (avolition)
social withdrawal
diminished emotional expression (blunted affect)
diminished verbal expression (alogia)
poor judgment
poor personal hygiene
decrease in level of attention
decrease in activity level
decrease in self direction
The hypothesis of multiple
etiologies of schizophrenia
• May be a group of disorders
• Perhaps with different underlying
neurobiological abnormalities
Genetic Factors
• Twin studies
• Concordance rate
– 55% for monozygotic twins
– 10% for dizygotic twins
• Adoption studies
– 15% of children of schizophrenic mothers
become schizophrenic whether adopted by non
schizophrenic mother or not
Dopamine Hypothesis of
Schizophrenia
• Schizophrenia due to abnormally increased
dopamine activity in the brain
Evidence for Dopamine
Hypothesis
• Antipsychotic (neuroleptic) drugs such as
chlorpromazine (Thorazine) or haloperidol
(Haldol) control symptoms in many patients
• neuroleptics block dopamine receptors
• magnitude of therapeutic effect of different
neuroleptics is proportional to the
magnitude of dopamine blocking effect
Neuroleptics as Antischizophrenic
• not just anti-anxiety or sedative
• If sedatives then barbiturates should work but they
don’t
• If anti-anxiety then neuroleptics should work with
anxiety disorders but virtually ineffective
• Neuroleptics calm hyperactive patients and make
withdrawn patients more active
• Anti-anxiety drugs are not effective with
schizophrenia
Amphetamine Psychosis
• The only drug effect that is clinically
indistinguishable from schizophrenia
• True drug effect not a result of sleep loss or
activation of latent schizophrenia
• Phenothiazines are effective in treating
amphetamine psychosis
• Amphetamines in small doses activate
schizophrenic symptoms
Schizophrenia and Parkinson’s
Disease
• Parkinson’s disease is a degenerative
(progressive and incurable) disease which
results from a deficiency of dopamine or at
least an insensitivity to dopamine. It is
treated with L-dopa a precursor of
dopamine which in some patients results in
relief of the symptoms during the early
stages.
Schizophrenia and Parkinson’s
Disease
• In many ways schizophrenia is the opposite
of Parkinson’s disease. Schizophrenics act
as if they have too much dopamine.
• Parkinson’s patients act as though they have
a deficiency of dopamine
Schizophrenia and Parkinson’s
Disease
• Never been a case on record of a
Parkinson’s patient developing
schizophrenia although if Parkinson’s
patients are overmedicated they show
temporary schizophrenic symptoms
Schizophrenia and Parkinson’s
Disease
• The anti-schizophrenic drugs produce
Parkinson like symptoms as a side effect,
presumably because they block dopamine
and cause the individuals brain to resemble
a Parkinson’s patient
Evidence for Dopamine
Hypothesis
• Dopamine enhancing drugs (eg:
amphetamines and L-dopa) may produce
transient psychotic states indistinguishable
from schizophrenia
• autopsy evidence suggests overabundance
of dopamine receptors rather than too much
dopamine (studies include individuals who
have never been on neuroleptics)
Problems with Dopamine
Hypothesis
• Blockade effect on dopamine occurs in hours, symptoms
don’t start to effect symptoms for weeks
• Some patients respond to dopamine blockers, others don’t
• Positive symptoms seem to be more related to dopamine
abnormality
• Negative symptoms seem more related to structural
abnormalities
Refinement of Dopamine
Hypothesis
• Recent development of atypical antipsychotics
such as clozapine (Clozaril), risperidone
(Risperdal), and olanzapine (Zyprea)
• These block both dopamine and serotonin and are
more effective (particularly with schizophrenics
with mainly negative symptoms)
• led to dopamine-serotonin interaction
hypothesis
Gross Structural Abnormalities
• Enlarged Ventricles
– correlational
– not all schizophrenics show it
• Cortical Atrophy
– generalized atrophy not in particular regions
Two-Syndrome Hypothesis
• Type I
– normal ventricle size and no atrophy
– predominantly positive symptoms
• Type II
– enlarged ventricles and cortical atrophy
– predominantly negative symptoms
Microstructural Abnormalities
• Pyramidal cells show disorganized
orientation
• Disrupted connections in hippocampus
• Also reports of problems in a number of
other areas
Abnormalities from Functional
Imaging
• Hypofrontality
– decreased frontal activity in schizophrenia
– decreased activation of frontal and prefrontal
areas in tasks that normally activate these areas
Neuropsychological Functioning
• Attentional Impairment
– poor performance on Continuous Performance Test (vigilance type
task)
• Temporal Lobe and Prefrontal dysfunction
– tests of verbal and non-verbal memory, working memory,
flexibility, and planning
• Left Hemisphere Hypothesis
– schizophrenia -- abnormality in left hemisphere
• overactivity may produce positive symptoms
– mood disorders -- abnormality in right hemisphere
Prefrontal Dysfunction
Hypothesis
• Positive symptoms result from excessive
dopamine activity in limbic system
• Negative symptoms result in decrease in
dopamine activity in prefrontal cortex
– working memory impaired
Pharmacological Treatment of
Schizophrenia
• Psychotherapy is virtually ineffective with
the schizophrenic symptoms
• Drugs are somewhat effective for about
60%
• Once the drugs have taken effect patient is
in need of therapy, rehabilitation, social
skills training, and help getting re-integrated
into society
Extrapyramidal Side Effects
• Caused by blocking the dopamine in the basal
ganglia and not blocking the cholinergic input
from the cortex
• Produces an inballance
• Can use anticholinergic drugs such as Artane and
Cogentin to bring the Acetylcholine levels in line
with dopamine and stop the Parkinson like or
extrapyramidal side effects
• Anticholinergic psychosis can occur from
overdose (dry mouth, dilated pupils, psychosis)
Side Effects
• Dystonia: tonic movements, twist of body, looks like a
seisure
• Acute dyskinesia: ticks and smacking
• Acathesia: motor restlessness, can’t sit still, pace floor
• Psychic restlessness
• Tardive dyskinesia
–
–
–
–
–
Fly catchers tongue
Smacking
Foot tapping
Irreversible particularly after a long time on high doses
Need to give drug holidays
Side Effects
•
•
•
•
•
Retinal Pigmentation
Jaundice
Leuconemia
Cardiac arythmia
Sexual difficulties
Mood Disorders
• Affective disorders
• Disorders that have a long-term disturbance
of mood as predominant feature.
• Major depressive disorder
• Seasonal affective disorder
• Bipolar disorder
Major Depressive Disorder
• Also called unipolar depression
• Lifetime risk – 12%
• Prevalence – 5% of population at any given
time
• Suicide risk – 15%
Major Depressive Disorder
• Older classification
– Endogenous depression – biological component
– Reactive depression – external (interpersonal and
social) factors
• Now realize most disorders are result of both
• Vegitative symptoms: loss of appetite, diurnal
mood variation, decreased sex drive, sleep
disturbance
Monoamine Hypothesis of
Depression
• Monoamines
– Catecholamines
• Dopamine
• Norepinephrine
– Indolamine
• Serotonin
Monoamine Hypothesis of
Depression
• Drugs that increase brain monoamine levels
alleviate depression
– Tricyclic antidepressants
– Monoamine oxidase inhibitors
• Drugs that decrease monoamine levels induce
depression
– Reserpine
• Hypothesize that abnormally low levels of
monoamines play role in depression
Major Depressive Disorder
• Dopamine agonists don’t help major depression
• So conclude it is serotonin and norepinephrine
• Many depressives have low levels of serotonin
metabolite
• Selective serotonin reuptake inhibitors (SSRI’s)
work on serotonin alone
– Fluoxetine (Prozac)
– Paroxetine (Paxil)
– Sertaline (Zoloft)
Possible Endocrine Dysfunction
in Depression
• Some depressed patients release too much
cortisol in response to stress
• Don’t know what this means
Abnormalities Revealed by
Functional Imaging
• Hypofrontality similar to that found in
schizophrenia but
• Do not show absence of activation on
specific tasks and
• Do not show cognitive impairments
associated with specific brain areas
• Don’t know what this means
Genetic Factors in Depression
• Concordance rate for major depression for
monozygotic twins is four times higher than
for dizygotic twins
Pharmacological Treatment of
Depression
• Tricyclic Antidepressants
– Tofranil
– Elavil
– Sinequan
• Side Effects
– Dry mouth
– Dizziness
– Cardiovascular
Pharmacological Treatment of
Depression
• MAO Inhibitors
– Phenelzine (Nardil)
– Isocarboxazid (Marplan)
– Tranylcypromine (Parnate)
• Beer-Cheese reaction
– Foods containing tryptamine
– Nose spray
Pharmacological Treatment of
Depression
• SSRI’s
– Prozac
– Paxil
– Zoloft
• Dual Action Antidepressants
– Nefazodone (Serzone)
– Mirtazapine (Remeron)
Seasonal Affective Disorder
• Some people become depressed during the
winter when days are short and nights are
long.
• Treated with exposure to bright lights for
several hours a day
• Don’t know much about biological basis of
this but data doesn’t seem to relate to
cycling of hypothalamus
Bipolar Disorder
• Manic-depressive disorder
• 0.5-1% of population
• Mania
–
–
–
–
Few hours to several months
Elevated, expansive, irritable mood
Inflated self-esteem, decreased need for sleep
Hypersexuality, flight of ideas, high risk taking
Bipolar Disorder
• Neurochemical factors
– Lithium carbonate (Eskalith)
– Anti-convulsant drugs
• Carbamazepine (Tegretol)
• Sodium valproate (Depakote)
• These drugs are highly effective, but
• Don’t know how they work so doesn’t lead
to a theory
Genetic Factors in Bipolar
Disorder
• Specific genetic links have been identified
• No single mechanism accounts for all cases
• We are a long way from understanding
bipolar disorder
Anxiety Disorders
• Phobic disorders
– Specific (snake or spider)
– Social phobia
– Agoraphobia
• Generalized Anxiety Disorder
• Panic Disorder
• Obsessive-Compulsive Disorder
Neurochemical Factors in
Anxiety Disorders
• Anxiolytics bind to benzodiazapine
receptors that are part of the
benxodiazepine-GABA complex
• Serotonin agonists (Proxac) are effective
also
• Don’t know how this fits together
Simple Phobias
• Preparedness theory of phobias
• Phobias develop for snakes, spiders, and heights which
people in modern civilization are rarely threatened by
• Don’t develop to electric sockets and automobiles that are
real threats
• People are genetically programmed to rapidly learn to fear
certain stimuli
• Most people with phobias have never actually been harmed
by the object they fear.
Dementing Diseases
• Alzheimer’s Disease
• Huntington’s Chorea
• Parkinson’s Disease
Alzheimer’s Disease
•
•
•
•
•
•
•
Damage to cholinergic in basal forebrain area
Cortical atrophy
Ventricular enlargement
Thinning of dendritic branches
Neurofibrillary tangles
Granulovacular degeneration
Neuritic plaques – beta amyloid surounded by
deteriorating neurons and glia
Alzheimer’s Disease
• Genetic factors
– Gene may produce defective form of betaamyloid
•
•
•
•
Related to alcohol and drug abuse, toxins
May be slow viruses
Injury to brain (prize-fighters)
Immune system activity