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