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

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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

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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) little effect on nigrostriatal dopamine system (A9)

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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 dopamine

neurons)

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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

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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

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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?)

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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 Data are less compelling that dopamine-agonist effect

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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

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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

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Antidepressant Medication and 5-HT

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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)

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Sleep Patterns in Depression

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Mood and Sleep Deprivation

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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)

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