Transcript Chapter 18 Biopsychology of Psychiatric Disorders

Chapter 18
Biopsychology of Psychiatric
Disorders
The Brain Unhinged
Psychiatric Disorders
• AKA psychological disorders
• Disorders of psychological function that require
treatment by a mental health professional
• Neuropsychological disorders - a product of
dysfunctional brains – but so are psychiatric
disorders
• Historically:
– Neuropsychological disorders – brain problem
– Psychiatric – mind problem
Psychiatric Disorders
• More influenced by experiential factors
• Tend to be the product of more subtle
forms of brain pathology
– Underlying dysfunction may yet to be
identified, but are suggested by the
effectiveness of treatments
• Tend to be less well understood
Psychiatric Disorders
• What are the advantages and
disadvantages of societal acceptance of
psychological disorders as diseases with a
biological basis?
• Are there some conditions for which this
acceptance already exists?
Anxiety Disorders
• Anxiety – fear in the absence of threat
• Anxiety disorder – when anxiety interferes
with normal functioning
– Accompanied by physiological symptoms –
tachycardia, hypertension, sleep
disturbances, nausea, etc.
• Most prevalent psychiatric disorders
Anxiety Disorders
• Generalized – stress and anxiety in the absence
of a causal stimulus
• Phobic – similar to generalized, but triggered by
a stimulus
• Panic disorders – may occur with other
disorders, but also alone
• Obsessive-compulsive disorders (OCDs) –
obsessive thoughts alleviated by compulsive
actions
• Posttraumatic stress disorder
Treatment of Anxiety Disorders
• Benzodiazepines (Librium, Valium)
– Also used as hypnotics, anticonvulsants, muscle
relaxants
– GABAA agonists – bind to receptor and facilitate
effects of GABA
– Highly addictive
• Serotonin agonists (Buspirone, SSRIs)
– Reduce anxiety without sedation and other side
effects
The GABA Receptor
Animal Models of Anxiety
• Assess anxiolytic potential of drugs - assume
that defensive behaviors are motivated by fear,
and that fear and anxiety are comparable
– Elevated-plus-maze: time in open arms indicates less
anxiety
– Defensive-burying: More time burying, more anxiety
– Risk-assessment test: Time freezing and assessing
risk indicate anxiety level
• Validated by effectiveness of benzodiazepines –
but not all anxiety treated with such drugs
Neural Bases of Anxiety Disorders
• Drugs suggest a role for serotonin and
GABA
• Amygdala, due to its role in fear and
defensive behavior, thought to be involved
– No pathology yet identified
Affective Disorders
• Depression – normal reaction to loss,
abnormal when it persists or has no cause
• Mania – opposite of depression
• Bipolar affective disorder
– Depression with periods of mania
• Unipolar – depression only
– Reactive – triggered by negative event
– Endogenous – no apparent cause
Causal Factors in Affective
Disorders
• Affective disorders are very common
– ~6% suffer from unipolar affective disorder at some
point, ~1% from bipolar
• Genetics
– Concordance rate higher for bipolar than unipolar
• Stressful experiences
– More stress reported by those seeking treatment for
depression than controls
Antidepressant Drugs
• Monoamine oxidase inhibitors (MAOIs)
– Prevent breakdown of monoamines
– Must avoid foods high in tyramine – ‘cheese effect’
• Tricyclic antidepressants
– Block reuptake of serotonin and norepinephrine
– Safer than MAOIs
• Selective monoamine reuptake inhibitors
• Lithium – mood stabilizer
– Not a drug – treats bipolar
Selective monoamine reuptake
inhibitors
• Selective serotonin-reuptake inhibitors (SSRIs)
– Prozac, Paxil, Zoloft
– No more effective than tricyclics, but side effects are
few and they are effective at treating other things
• Selective norepinephrine-reuptake inhibitors
(SNRIs)
– Also effective
Effectiveness of Drug in Treating
Affective Disorders
• Results are comparable with MAOIs,
tricyclics, and SSRIs
– About 50% improve, compared to 25% of
controls
• Drugs help those experiencing depression,
but do not prevent future episodes
Monoamine Theory of Depression
• Underactivity of serotonin (5HT) and
norepinephrine (NE)
– Consistent with drug effects
– Up-regulation of receptors at autopsy of
depressed individuals consistent with this
• Problem with theory – not all respond to
monoamine agonists
Diathesis-Stress Model
• Inherited genetic susceptibility (diathesis)
+ stress = depression
• Support is indirect
– Depressed people tend to release more
stress hormones
– Fail dexamethasone suppression test –
normal negative feedback on stress
hormones not functioning
Sleep Deprivation
• More than 50% of depressed patients
improve after one night of sleep deprivation.
• Short-lasting: depression returns when
normal sleep pattern resumes.
• Not explained by any theory.
• What does this suggest?
Brain Damage and Unipolar
Depression
• Amygdala
• Prefrontal cortex
– Both involved in perception and experience of
emotion
• Terminal structures of the
mesotelencephalic DA system
– Consistent with anhedonia (lack of pleasure)
experienced by the depressed
Tourette’s Syndrome
• A disorder of tics, involuntary movements or
vocalizations
• Begins in childhood
• Major genetic component
• Many also have signs of ADHD and/or OCD
• No animal models, no genes identified, imaging
difficult due to tics
Tourette’s Syndrome
• Usually treated with neuroleptics –
although effectiveness is not wellestablished
• Effectiveness of D2 blockers suggests
abnormality in basal ganglia-thalamuscortex feedback circuit
Schizophrenia
• “splitting of psychic functions”
– Refers to the breakdown of integration of emotion,
thought, and action
• Affects 1% of the population
• A diverse disorder – multiple types exist with
varied profiles
• Some symptoms: delusions, hallucinations, odd
behavior, incoherent thought, inappropriate
affect
– Only 1 needed for 8 months for diagnosis
Causal Factors in Schizophrenia
• Clear genetic basis
– Inherit an increased risk for the disorder
• Multiple causes
– Several different chromosomes implicated
– Associated with various early insults – infections,
autoimmune reactions, toxins, traumatic injury, stress
• Appears that interference with the normal
development of susceptible individuals may lead
to development of the disorder
Antipsychotic Drugs
• Much of our understanding of schizophrenia is a
consequence of the drugs that are able to treat it
• Chlorpromazine – calms many agitated
schizophrenics and activates many emotionally
blunt
• Reserpine – also found to be effective
• Both drugs are not effective for 2-3 weeks and
Parkinson-like motor effects are seen
– Suggesting a role for what neurotransmitter?
Dopamine (DA) Theory of
Schizophrenia
• 1960 – link between DA and Parkinson’s Disease
established
• Side effects of antipsychotic drugs suggests role for
dopamine: Drugs work by decreasing DA levels, disorder
is a consequence of DA overactivity
– Reserpine depletes brain of DA and other monoamines by
making vesicles leaky
– Amphetamine and cocaine are DA agonists and produce
psychosis
– Chlorpromazine antagonizes DA activity by binding and blocking
DA receptors
Dopamine (DA) Theory of
Schizophrenia
• In general, the higher affinity a drug has for DA
receptors, the more effective it is in treating
schizophrenia
• Haloperidol – an exception
– While most antipsychotics bind to D1 and D2
receptors, it and the other butyrophenones bind to D2
• Degree that neuroleptics bind to D2 receptors is
correlated with their effectiveness
Problems with the D2 Theory
• Clozapine, an atypical and effective neuroleptic,
acts at D1, D4, and serotonin receptors. But –
some binding to D2
• Neuroleptics act quickly at the synapse, but
don’t alleviate symptoms for weeks.
– Indicates some slow-acting change must occur.
• Schizophrenia associated with brain damage.
– Little damage to DA circuitry
– Damage not explained by DA theory
• Neuroleptics are only effective for some
Problems with the D2 Theory
• Positive symptoms - presence of abnormal
– incoherence, hallucinations, delusions
• Negative – absence of normal
– flat affect, cognitive deficits, little speech
• Conventional neuroleptics (D2 blockers) mainly
effective at treating positive
• Negative – might be caused by brain damage
• May be best to think of schizophrenia as multiple
disorders with multiple causes