Schizophrenia is a disorder of thought and emotion characterized by thought disorders like loose associations, hallucinations such as auditory ones, and delusions like paranoia. The incidence is about 1-2% with no clear gender differences. The dopamine hypothesis posits that positive symptoms involve overactivity of dopaminergic synapses in the brain. Antipsychotic medications help diminish thought disorder and disruptive behaviors by blocking dopamine receptors. Brain damage, particularly in regions like the prefrontal cortex, may underlie negative symptoms.

1. Carlson (7e)
Chapter 17: Schizophrenia and
the Affective Disorders

2. 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

3. 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

4. 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

5. 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

6. 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
 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)
17.6
 little effect on nigrostriatal dopamine system (A9)


7. 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

8. 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


9. 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
17.9
dopamine neurons)

10. 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

17.10

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
17.11

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?)
17.12

13. Hypofrontality and Schizophrenia

Hypofrontality refers to the decreased activity of the
frontal lobe (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
17.13
Data are less compelling that dopamine-agonist effect

16. 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
17.16

17. 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

17.17

18. 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 (metabolite of serotonin)
 Antidepressant medications increase either NE or
5-HT (serotonin)

 Usually

via blockade of monoamine reuptake
Tryptophan (precursor to 5-HT) deletion procedure:
 Reduces
brain 5-HT levels
 Reinstates depression in former depressed patients
17.18

19. REM Sleep and Depression

Sleep pattern is disrupted in depressed persons
Reduced REM latency (duration of sleep, from sleep onset to
the onset of the first REM sleep period)
 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
17.19
sleep deprivation (effects last longer)


20. 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)
17.20

22. Anxiety Disorders, Autistic
Disorder, AttentionDeficit/Hyperactivity Disorder, and
Stress Disorders
Chapter 17

23. Lecture Preview




Anxiety Disorders
Autistic Disorder
Attention-Deficit/Hyperactivity Disorder
Stress Disorders

24. Anxiety Disorders

Panic Disorder, Generalized Anxiety
Disorder, and Social Anxiety Disorder

Description
Disorder – a disorder characterized by episodic
periods of symptoms such as shortness of breath,
irregularities in heartbeat, and other autonomic
symptoms, accompanied by intense fear.
Anticipatory Anxiety – a fear of having a panic attack;
may lead to the development of agoraphobia.
Panic

25. Anxiety Disorders (Continued)
Anxiety Disorder – characterized by
excessive anxiety and worry serous enough to cause
disruption to one’s life.
Social Anxiety Disorder – characterized by excessive
fear of being exposed to the scrutiny of other people
that leads to avoidance of social situations in which
the person is called on to perform.
Generalized

Possible Causes
May
involved alleles of the 5-HTT.

26. Anxiety Disorders (Continued)

Obsessive-Compulsive Disorder

Description
A
mental disorder characterized by obsessions and
compulsions.
Obsessions – unwanted thought or idea with which a
person is preoccupied.
Compulsion – feel that one is obliged to perform a
behavior, even if one prefers not to do so.

Possible Causes
Tourette’s
Syndrome
Streptococcal Hemolytic Infection

27. Autism

Autism: impairments of
Social relations with others
 Ability to communicate
 Imaginative ability


Incidence of autism is 4/10,000

Males are 3 times more likely to develop autism

28. Autistic Disorder

Description


A chronic disorder whose symptoms include
failure to develop normal social relations with
other people, impaired development of
communicative ability, lack of imaginative ability,
and repetitive, stereotyped movements.
Possible Causes
Heritability
 Brain Pathology


29. Biological Bases of Autism


Heritability: MZ twins exhibit a 96% concordance rate for
autism
Autism is associated with neurological disorders:
 Phenylketonuria (PKU)
 Tourette‟s syndrome
 Fragile

X syndrome (mental retardation)
Factors that impair development lead to autism:
 Rubella,
hydroencephalus
 Drugs such as Thalidomide

30. Attention-Deficit/Hyperactivity
Disorder

Description


A disorder characterized by uninhibited
responses, lack of sustained attention, and
hyperactivity.
Possible Causes

Delays in reinforcement render reinforcement
relatively ineffective, but immediate
reinforcement is highly effective.

31. Figure 17.9 Delay of Reinforcement Gradients in
ADHD

32. Stress

Stress – a general, imprecise term that can
refer either to a stress response or to a situation
that elicits a stress response.

33. Stress

Aversive stimuli can elicit emotional responses:
Behavioral
component: Fight or Flight response
Autonomic component: Sympathetic activation
Endocrine: secretion of epinephrine, NE

Physiological reactions to chronic aversive
stimuli/situations can be damaging
Stressors: the aversive stimuli
 Stress Response: our reaction to stressors


34. Hormone Secretion during Stress


Stressors evoke activity in sympathetic N.S.
Adrenal glands release
 Epinephrine:
biases energy flow to muscles, increases blood pressure
and blood flow to heart
 Norepinephrine: increases blood flow and pressure
 Glucocorticoids: break down protein and fats to glucose

35. Physiology of the Stress Response

Glucocorticoid – one of a group of hormones of
the adrenal cortex that are important in protein
and carbohydrate metabolism, secreted
especially in times of stress.

36. Physiology of the Stress Response
(Continued)
The process involved in the production of
glucocorticoids:

Corticotropin-Releasing Hormone (CRH) –
hypothalamic hormone that stimulates the
anterior pituitary gland to secrete ACTH.

Adrenocorticotropic Hormone (ACTH) –
hormone released by the anterior pituitary gland
in response to CRH; stimulates the adrenal
cortex to produce glucocorticoids.

37. Figure 17.12 Control of Secretion of Stress
Hormones

38. Stress Disorders (Continued)

Effects of Stress on the Brain
Elevates glucocorticoid levels.
 Impairs development of primed-burst
potentiation.
 Disrupts learning.
 Prenatal Stress:

Increases
size of the lateral nucleus of the amygdala.
Elevates glucocorticoid response to stress.

Hippocampal Damage

39. Chronic Exposure to Stressors

Chronic stress is damaging to health

Air traffic controllers: more likely to develop



High blood pressure
Ulcers and diabetes
Chronic secretion of glucocorticoids leads to:
Increased
blood pressure (--> stroke, heart attacks)
Loss of neurons in brain (e.g. hippocampal field CA1)
Suppression of the immune system (--> illness)
Suppression of the inflammatory system (delays healing)

40. Stress Disorders (Continued)

Health Effects of Long-Term Stress
Hypertension – stress causes an increase in
hypertension.
 Wound Healing – stress causes an increase in
the time to heal wounds.


42. Posttraumatic Stress Disorder

Posttraumatic Stress Disorder (PTSD):

Acute exposure to intense stressors can have delayed
effects (Air disasters, war, assault)
Dreams,
recall of trauma event
Flashback episodes of event
Intense distress

43. Stress Disorders (Continued)

Posttraumatic Stress Disorder
A psychological disorder caused by exposure to
a situation of extreme danger and stress;
symptoms include recurrent dreams or
recollections; can interfere with social activities
and cause a feeling of hopelessness.
 Involves many brain regions, including the
amygdala and prefrontal cortex.


44. Predisposing Factors for PTSD

Personality variables that predispose to PTSD:


Tendency to brood about feelings
Vietnam Veterans study:





Family financial difficulty
History of drug abuse/dependence
History of affective disorders
History of childhood behavior problems
Genetic factors for PTSD:
 Vietnam
PTSD soldiers were more likely to possess an allele of the
dopamine D2 receptor

45. Coping Responses and Stress


Stress reflects our reaction to stressors
Coping implies modifying our responses:

Exerting control over aversive stimuli can reduce stress
responses
 Weiss
study: rats that avoid shock show fewer ulcers
 Coping may involve an increase in the level of benzodiazepines in
brain (would act via GABA sites to reduce anxiety)

46. Psychoneuroimmunology

Psychoneuroimmunology: Study of the
interactions between the immune system and
behavior.
The
branch of neuroscience involved with
interactions between environmental stimuli, the
nervous system, and the immune system.

Stress responses can impair the immune system

Leading to illness and potential death

47. Psychoneuroimmunology

Antigen – protein present on a microorganism
that permits the immune system to recognize the
microorganism as an invader.

Antibody – protein produced by a cell of the
immune system that recognizes antigens present
on invading microorganisms

48. Stress Disorders (Continued)
B-Lymphocyte – a white blood cell that
originates in the bone marrow.
 Immunoglobulin – an antibody released by Blymphocytes that bind with antigens and help
destroy invading microorganisms.
 T-Lymphocyte – a white blood cell that
originates in the thymus gland.


49. Overview of the Immune System

Immune system destroys foreign organisms (viruses,
bacteria, fungi)

Nonspecific reaction: act to destroy organisms or infected
cells
 Inflammatory
reaction: damaged cells leak substances that increase
blood flow
 Phagocytotic white blood cells: destroy damaged cells
 Cell infection --> interferon secretion (reduces viral replication
 Natural killer cells: detect and destroy infected cells

50. Immune System Overview,
continued

Specific Immune reactions:

Chemically-mediated: immune system produces antibodies
that recognize the antigens present on surface of a foreign cell
 B-lymphocytes:
produce immunoglobulin antibodies that destroy
foreign cells

Cell-mediated: antibodies on exterior of T-lymphocytes detect
foreign antigens (viruses)

52. Stress and the Immune Response

Stress increases likelihood of infectious disease


Students are more likely to be ill during exam times
Death of a spouse leads to illness of survivor
 Explanation:
stress releases glucocorticoids that in turn impair the
immune system
 Supporting Evidence:



Bereavement leads to reduced immune response
Alzheimer‟s caregivers have impaired immune response
Inescapable shock in rats reduces T-cells, B-cells and natural killer cells

53. Stress Disorders (Continued)

Stress, Health, and Disease
Stress decreases immune function.
 Stress increases the susceptibility to infection.
