Schizophrenia and the Affective Disorders
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Transcript Schizophrenia and the Affective Disorders
Carlson (7e)
Chapter 17: Schizophrenia and
the Affective Disorders
Schizophrenia
Schizophrenia represents a disorder of thought
and emotion but not a “split-personality”
Thought disorder (e.g., loose associations)
Hallucinations (e.g., auditory)
Delusions (e.g., paranoia)
Bizarre behaviors
The incidence of schizophrenia is about 1-2%
No clear gender differences in incidence
17.2
Symptoms of Schizophrenia
Positive symptoms include delusions, hallucinations
and thought disorder
Delusions are beliefs that are contrary to reality
Delusions
can involve control, grandeur, or persecution
Hallucinations are perceptions that occur in the absence of
stimuli (often auditory and/or olfactory)
Thought disorder: disorganized and irrational
Negative symptoms involve a loss of normal behaviors,
such as
Poverty of speech and low initiative
Social withdrawal and diminished affect
Anhedonia
17.3
Heritability of Schizophrenia
The heritability of schizophrenia is a strong
indicator of a biological basis for schizophrenia
Adoption studies
Adult
schizophrenics that were adopted as children are
likely to have schizophrenic biological relatives.
Twin studies
Concordance
rates for schizophrenia are higher for
identical than for fraternal twins:
No single gene has been identified for schizophrenia
Genes
may pass on a susceptibility to develop
schizophrenia
17.4
The Dopamine Hypothesis of
Schizophrenia
The “dopamine hypothesis” is that the positive
symptoms of schizophrenia involve over activity of
brain dopaminergic synapses
Chlorpromazine (CPZ) was identified as an effective
antipsychotic (AP) agent
CPZ
was later found to block DA receptors (D2 receptors)
D2 receptor blockade correlates with clinically effective dose
of typical antipsychotic medications
Stimulants such as amphetamine that release DA can
produce the positive symptoms of schizophrenia in
“normals” and relapse in schizophrenics
17.5
Pharmacological Revolution in Treating
Severe Mental Disorders
DA Activity in Schizophrenia
PET studies indicate greater activity of dopamine in the
striatum of schizophrenics to a test dose of amphetamine
Amount of dopamine activity was related to the increase in
positive schizophrenia symptoms
Studies of dopamine receptors in schizophrenic brain have
provided mixed results (but generally supportive)
Postmortem studies suggest increased numbers of D2 receptors
in striatum (but may be due to exposure to antipsychotic drugs)
The striatum is a motor control region: may be the wrong site
Schizophrenia may be related to D4 or D3 receptors
Clozapine is an effective (atypical) antipsychotic drug that
interacts with D4 and not D2 receptors
strong effect on mesolimbic/mesocortical dopamine system (A10)
17.7
little effect on nigrostriatal dopamine system (A9)
Dopamine Augmentation & Schizophrenia
Psychomotor stimulants (e.g., amphetamine)
‘normals’ develop paranoid psychosis
schizophrenics release -- subjectively indistinguishable
for worsening of endogenous illness (cf. LSD)
L-DOPA (precursor loading)
little or no effect in ‘normals’
worsening of psychotic symptoms in schizophrenics
schizophrenic symptoms in some Parkinson’s patients
Stress (increased dopaminergic activity)
precipitate relapse & perhaps even initiate disorder
Dopamine Attenuation & Schizophrenia
DA synthesis inhibitors (e.g., AMPT) abate
schizophrenia
DA storage depleters (e.g., reserpine) abate
schizophrenia
D2 receptor blockers (e.g., typical
antipsychotics) abate schizophrenia
Even atypical antipsychotics (which do not
effectively block D2 receptors) influence
mesolimbic DA activity
Antipsychotic Medications
Antipsychotic medications diminish the thought
disorder & disruptive behavior evident in schizophrenia
Side effects of antipsychotic medications include
Major
Extrapyramidal
(Parkinsonism-like) side effects due to blockade of
DA receptors
Tardive dyskinesia: facial tics and gestures due to an over stimulation
of DA receptors (may be related to CNS sensitization and relapse)
Minor
Autonomic
problems (dry mouth)
Skin-eye pigmentation
Breast development (increased prolactin release after blockade of
17.10
dopamine neurons)
Brain Damage and Schizophrenia
The negative symptoms of schizophrenia may be related
to brain damage
The neurological signs evident in schizophrenia include
Eye tracking problems
Catatonia
Problems with blinking, eye focusing, and visual pursuit
Schizophrenics exhibit enlarged brain ventricles, which
suggests loss of brain cells
Regions of schizophrenic brain that are abnormal include
Prefrontal cortex
Medial temporal lobes
Medial diencephalon
17.11
Causes of Brain Damage in
Schizophrenia
The neurological symptoms of schizophrenia may be
caused by
Birth trauma (obstetrical issues)
Viral infections that impair neural development during the
second trimester
Seasonality
effects (schizophrenia is more likely for winter births)
Nutritional issues (Hunger Winter: female offspring were
more likely to exhibit schizophrenia than male offspring)
Maternal stress may compromise the immune system of the
mother and lead to a greater chance of contracting a viral
infection
17.12
Seasonality and Schizophrenia
Children born during the
late winter and early spring
are more likely to develop
schizophrenia
Seasonality effect occurs in
cities but not the countryside
Seasonality effect may be
related to the mother
contracting a viral infection
during the second trimester
of fetal development (or
astrological sign?)
17.13
Hypofrontality and Schizophrenia
Hypofrontality refers to the decreased activity of the
dorsolateral prefrontal cortex
Damage to the prefrontal cortex
impairs
behavioral flexibility (card sorting task)
may disinhibit mesolimbic dopamine system
Schizophrenics show decreased activity in the prefrontal cortex
Abuse of PCP produces positive and negative symptoms
of schizophrenia
Positive: related to indirect actions of PCP on accumbens DA
Negative: related to decreased DA utilization in prefrontal cortex
following PCP treatment
17.14
Data are less compelling that dopamine-agonist effect
Major Affective Disorders
Affect refers to emotions, moods, and feelings
Our affect is usually a reflection of our experiences
In the major affective disorders, our emotional
reactions are at the extremes and may not be related
to our actual experiences
The major affective disorders include
Bipolar disorder - alternating cycles of
Mania:
euphoria, delusions
Depression: profound sadness, guilt, suicide risk
Unipolar depression: continuous, episodic
17.15
Biological Bases of
Affective Disorder
Heritability of affective disorder (AD) has been
established in twin studies and family studies
Bipolar disorder may be related to a single gene
Depression is amenable to physical treatments
including
Pharmacological treatments
MAO
inhibitors (e.g. iproniazid)
Noradrenergic reuptake inhibitors (desmethylimipramine)
Serotonin reuptake inhibitors (e.g. Prozac)
Electroconvulsive shock therapy (ECS)
Sleep deprivation
17.16
Monoamine Hypothesis of
Depression
Depression results from reduced activity of brain
monoamines
Reserpine depletes monoamines--> depression
Suicidal depression is related to a low level of
5-HIAA
Antidepressant medications increase either NE or
5-HT
Usually
via blockade of monoamine reuptake
Tryptophan deletion procedure:
Reduces
brain 5-HT levels
Reinstates depression in former depressed patients
17.17
Antidepressant Medication and 5-HT
17.18
REM Sleep and Depression
Sleep pattern is disrupted in depressed persons
Reduced REM latency, reduced stages 3 and 4 sleep
REM deprivation improves mood
Antidepressant drugs suppress REM sleep, and
increase slow-wave sleep
Persons who have short REM sleep latency are
more likely to develop depression
REM sleep deprivation is more effective than is
total sleep deprivation (effects last longer)
17.19
Sleep Patterns in Depression
17.20
Mood and Sleep Deprivation
17.21
Seasonal Affective Disorder
SAD is a form of depression evident in winter
months (short days/long nights)
SAD involves
Mood and sleep disturbances
Carbohydrate cravings and weight gain
Phototherapy for SAD: increased exposure to
light improves mood in SAD (and also for
unipolar depression)
17.22