Psychological Disorders Chapter 14

1
Psychological DisordersChapter 14

• Schizophrenia
• Affective disorders
• Anxiety disorders

2
Schizophrenia

• Mental disorders are common and disabling,
  affecting 1 in 3 people over their lifetime.
• Schizophrenia is a psychosis that is
  characterized by perceptual, emotional, and
  intellectual deficits loss of contact with
  reality and inability to function in life.
• The term means split-mind, a distortion of
  thought and emotion it is not the same as
  multiple personality.
• Schizophrenia is currently divided into
  diagnostic subtypes, such as paranoid
  schizophrenia, but these are now more often
  considered symptoms rather than separate disease
  processes.

3
Schizophrenia

• Schizophrenia afflicts men and women about
  equally often.
• Men usually show the first symptoms during the
  teens or twenties, while the onset for women
  ordinarily comes about a decade later.
• Acute symptoms develop suddenly and are typically
  more responsive to treatment.
• The prognosis is reasonably good in spite of
  brief relapses.
• Symptoms that develop gradually and persist for a
  long time with poor prognosis are called chronic.

4
Schizophrenia

• Schizophrenia is a familial disorderincidence is
  higher among the relatives of schizophrenics.
• Heritability for schizophrenia has been estimated
  at between .60 and .90.
• Identical twins of schizophrenics are three times
  as likely to be schizophrenic as the fraternal
  twins of schizophrenics.

5
Concordance for Schizophrenia Among
RelativesFigure 14.5
6
Schizophrenia

• Adopting a child out of a schizophrenic home
  provides no protection from developing the
  disorder.
• Discordance in identical twins means that some
  other factor must play a role.
• However, risk is the same in the offspring of the
  affected and unaffected members of a discordant
  pair.
• This suggests that the genes are not expressed in
  the unaffected twins.
• ?

7
Risk in Offspring of Normal Schizophrenic
TwinsFigure 14.6
8
Schizophrenia

• Various problems make the identification of
  candidate genes difficult.
• Not all studies include the spectrum diagnosis.
• The effects of multiple genes are small and
  cumulative.
• A significant cause is rare copy number
  variations.
• The genes that have been identified play a role
  in
• Neurotransmission and transmitter deactivation
• Neural development, such as axon guidance
• Neurodegeneration
• Immune factors and the inflammatory response
• ?

9
Schizophrenia

• The Vulnerability Model
• Some threshold of causal forces must be exceeded
  in order for the illness to occur.
• Environmental challenges combine with a persons
  genetic vulnerability to exceed that threshold.
• Environmental influences work in part by
  epigenetic means, by upregulating and
  downregulating gene functioning.
• ?

10
Schizophrenia

• Positive symptoms involve the presence or
  exaggeration of behaviors, such as
• delusions,
• hallucinations,
• thought disorder,
• and bizarre behavior.
• Positive symptoms
• are more often acute and
• are more likely to respond to antipsychotic
  medications.
• ?

11
Schizophrenia

• Negative symptoms are characterized by the
  absence or insufficiency of normal behaviors, and
  include
• lack of affect (emotion)
• inability to experience pleasure
• lack of motivation, poverty of speech, and
  impaired attention.
• Negative symptoms tend to be chronic.
• Patients typically have
• poorer adjustment prior to onset
• poorer prognosis after diagnosis
• tissue deficits and intellectual and cognitive
  deficits.

12
Schizophrenia

• The dopamine hypothesis states that schizophrenia
  is caused by excess dopamine activity in the
  brain.
• Amphetamine, a dopamine agonist, can cause
  hallucinations and delusions that look very much
  like those in schizophrenia.
• Drugs that block dopamine receptors are useful in
  treating schizophrenia, particularly the positive
  symptoms.
• Schizophrenics typically have higher dopamine
  activity in the striatum.
• However, some schizophrenics are deficient in
  dopamine, and 30 to 40 are not helped by
  anti-dopamine drugs.

13
Schizophrenia

• The effectiveness of new drugs has supported
  alternative explanations for schizophrenia.
• Atypical or second generation antipsychotics
• are as effective as older drugs
• are more effective in 15-25 of cases
• help treatment-resistant schizophrenics.
• Atypical antipsychotics increase glutamate
  levels.
• They affect serotonin levels, and several block
  5-HT2 serotonin receptors.
• They also target D2 receptors less and produce
  less tardive dyskinesia.

14
Schizophrenia

• The glutamate theory states that schizophrenia is
  due to reduced glutamate activity.
• PCP blocks NMDA glutamate receptors and can cause
  a type of psychosis that resembles schizophrenia.
• Glycine activates the NMDA receptor, and improves
  negative and cognitive symptoms.
• Atypical antipsychotics downregulate the
  transporter gene, hence decreasing reuptake.
• There is evidence that the dopamine imbalance may
  be a result of reduced glutamate activity in the
  prefrontal cortex.

15
Schizophrenia

• Some schizophrenics have enlarged ventricles,
  indicating brain tissue deficits.
• Most schizophrenics have normal-sized ventricles.
• The changes in ventricle size are small.

Figure 14.8 The brain on the left is from a
schizophrenic patient.
16
Schizophrenia

• Hypofrontality, a decline in frontal lobe
  function, is characteristic of schizophrenia.
• The Wisconsin Card Sorting Test, which requires
  reversing strategies, is used to assess
  hypofrontality.
• Schizophrenics perform poorly on the task.
• Their hypofrontality involves a dopamine
  deficiency in the dorsolateral prefrontal cortex.
• Amphetamine, which increases dopamine, improves
  prefrontal blood flow and performance.
• Dorsolateral prefrontal damage causes symptoms
  seen in schizophrenia, including flat affect,
  social withdrawal, and cognitive impairments.

17
Blood Flow During Card Sorting TaskFigure 14.9
(a) During the task, blood flow is greater in the
control brain (above) than in the brain of a
schizophrenic (below).
18
Schizophrenia

• Recent attention is shifting from localized
  deficits to disrupted coordination of neural
  activity.
• In schizophrenics, the normal coordination of
  activity between the hippocampus and prefrontal
  cortex during a working memory task is absent.
• This is at least partly due to decreased white
  matter in the frontal and temporal areas.
• Lack of coordination probably explains
  hypofrontality.
• Abnormal synchronization in sensory areas may
  explain visual and auditory hallucinations.
• Impaired auditory gating, the inability to
  suppress environmental sounds, is associated with
  synchrony deficits across wide areas.

19
Schizophrenia

• Some of the brain defects in schizophrenia
  apparently stem from problems during pregnancy or
  at the time of birth.
• Winter Birth Effect More schizophrenics are born
  during the winter and spring.
• Infants born during this time would have been in
  the second trimester in the fall or early winter,
  when there is a high incidence of infectious
  diseases.
• Incidence of schizophrenia is higher in
  individuals born following influenza epidemics.
• The effect is likely caused by the immune
  reaction to the virus rather than by the virus
  itself.

20
Schizophrenic Births, Season, InfluenzaFigure
14.12
21
Schizophrenia

• At least some of the prenatal effects are likely
  epigenetic.
• Schizophrenic births doubled following the
  1944-1945 food blockade of the Netherlands.
• This effect was confirmed in a larger study of
  famine in China. (See Chapter 6 for epigenetic
  effects of starvation.)
• Risk for schizophrenia increases if the father is
  older than 25 at the time of conception beyond
  age 50 the risk increases by two-thirds.
• ?

22
Schizophrenia

• Most researchers agree that schizophrenia is a
  disorder of early development. Brains show
• problems in migration of cells in the temporal
  and frontal lobes
• a deficiency of Reelin, a protein that functions
  as a stop signal for migrating cells,
  particularly in the hippocampus and prefrontal
  areas
• gray matter deficits and ventricular enlargement
  at the time of diagnosis.
• Behavioral evidence from home movies suggest that
  symptoms are present long before diagnosis is
  made.
• There is also evidence for severe pruning of
  synapses during adolescence involving both
  dopamine and glutamate pathways.

23
Gray Matter Loss During AdolescenceFigure 14.14
Schizophrenic adolescents show much more gray
matter loss during circuit pruning.
24
Affective Disorders

• One in five people will experience a mood
  disorder in their lifetime. The financial cost is
  almost 19 billion a year in the U.S.
• In major depression a person often
• feels sad to the point of hopelessness for weeks
  at a time
• loses the ability to enjoy life, relationships,
  and sex
• and experiences loss of energy and appetite,
  slowness of thought, and sleep disturbance.
• Mania involves excess energy and confidence that
  often lead to grandiose schemes.
• Decreased need to sleep, increased sexual drive,
  and abuse of drugs are common.

25
Affective Disorders

• Depression alone is called unipolar depression.
• Females are three times more likely to be
  depressed than males.
• Risk for men increases with age women are most
  vulnerable between the ages of 35 and 45.
• In bipolar disorder, the individual alternates
  between periods of depression and mania.
• Mania can occur alone, but this is rare.
• Bipolar patients often show psychotic symptoms
  such as delusions, hallucinations, paranoia, or
  bizarre behavior.
• Bipolar disorder occurs equally in males and
  females, usually in the early 20s to age 30.

26
Affective Disorders

• Concordance for affective disorders is about 69
  in identical twins, compared to 13 in fraternal
  twins.
• In depression, heritability is somewhere around
  .37, with the number somewhat higher for women
  than for men.
• Different genes may be involved in depression in
  males and females.
• This genetic difference may explain why females
  more often suffer from depression whereas males
  are more likely to commit suicide.
• ?

27
Affective Disorders

• People with the short allele for the 5-HTTLPR
  serotonin transporter gene are more vulnerable to
  depression.
• They show tissue loss in the amygdala and the
  subgenual anterior cingulate cortex.
• Their amygdala is hyperreactive to stress,
  apparently due to lack of damping by the
  subgenual anterior cingulate cortex.
• An allele of the gene for brain-derived
  neurotrophic factor, which encourages neuron
  survival, protects against the effects of the
  short 5-HTTLPR allele.
• ?

28
Depression and the Serotonin Transporter
GeneFigure 14.15
People with the short allele had more depressive
episodes as stress increased.
29
Affective Disorders

• The heritability for bipolar disorder has been
  estimated between 85 and 93.
• In one study that examined large sets of data, 69
  genes for bipolar disorder were identified.
• Many of these genes overlap with those that play
  a role in substance abuse.
• Some mutations found in bipolar disorder are also
  involved in the control of circadian rhythms.
• ?

30
Affective Disorders

• The monoamine hypothesis states that depression
  involves reduced activity at norepinephrine and
  serotonin synapses.
• All the effective antidepressant drugs increase
  the activity of one or both transmitters at the
  synapses.
• Monoamine oxidase inhibitors block the
  destruction of excess monoamines in the
  terminals.
• Tricyclic antidepressants block reuptake at the
  synapse.
• Atypical or second-generation antidepressants
  affect a single transmitter fluoxetine (Prozac)
  is a selective serotonin reuptake inhibitor.
• Synaptic effects take hours improvement takes
  weeks.

31
Affective Disorders

• Electroconvulsive Therapy (ECT)
• A convulsive seizure is produced by applying 70
  to 130 volts of electricity to the head of an
  anesthetized patient.
• Therapeutic effect is rapid, a benefit for
  suicidal patients.
• ECT is usually reserved for patients who do not
  respond to the medications or who cannot take
  them.
• Like the drugs, ECT increases the sensitivity of
  postsynaptic serotonin receptors.
• Sensitivity of presynaptic autoreceptors is
  reduced, increasing norepinephrine and dopamine
  release.
• Brain excitability decreases, probably due to an
  increase in diminished GABA.

32
Affective Disorders

• Other types of electrical stimulation have also
  been used to treat depression.
• Fast TMS (transmagnetic stimulation) produces
  effects similar to traditional ECT.
• Deep brain stimulation of the subgenual anterior
  cingulate gyrus is another approach that can
  produce immediate effects.
• Stimulation of the vagus nerve relieves
  depression, probably because it increases GABA
  levels in the cortex.
• ?

33
Affective Disorders

• Antidepressants, ECT, and Neural Plasticity
• Treatment increases neurogenesis in the
  hippocampus. New cells are thought to be more
  plastic.
• The time required for the new neurons to form
  connections matches the delay in symptom
  improvement.
• There is evidence that treatment increases
  plasticity and synaptic enhancement even when
  neurogenesis is blocked.
• Antidepressants and ECT modify genes that
  contribute to neurogenesis, neuron survival, and
  plasticity.
• ?

34
Neurogenesis During Antidepressant
TreatmentFigure 14.18
(a) Fluoxetine (Prozac) increased neurogenesis.
(b) Brown dots are new cells.
35
Affective Disorders

• The circadian rhythm the one that is a day in
  length tends to be phase advanced in affective
  disorder patients.
• Patients also enter rapid eye movement sleep
  (REM) earlier in the night and spend more time in
  REM than normal.
• Some patients who are unresponsive to medication
  can get relief from their depression by
  readjusting their circadian rhythm.
• Some depressed patients also benefit from a
  reduction in REM sleep.

36
Affective Disorders

• Some peoples depression rises and falls with the
  seasons and is known as seasonal affective
  disorder (SAD).
• Most SAD patients are more depressed during the
  fall and winter, then improve in the spring and
  summer.
• A smaller number experience depression in the
  summer and improve during the cooler winter
  months.
• A treatment for winter depression is
  phototherapyhaving the patient sit in front of
  high-intensity lights for a couple of hours or
  more a day.
• Winter depression involves low serotonin, which
  explains why carbohydrate craving is typical.

37
Affective Disorders

• In bipolar disorder, periods of depression
  typically last longer than mania.
• Cycling is regular in some and unpredictable in
  others cycle length varies from 48 hours to
  months.
• Lithium is the drug of choice for bipolar
  disorder, and usually works best in the manic
  phase.
• The belief has been that lithium works by
  stabilizing many transmitters.
• Recent evidence is that lithium and valproate
  inhibit protein kinase C, an enzyme that
  regulates neuron excitability.
• ?

38
Metabolism in a Rapid-Cycling Bipolar
PatientFigure 14.22
Top The patient during depression. Middle A day
later, during mania.
39
Affective Disorders

• Structural and Functional Alterations
• There are volume deficits in the hippocampus,
  dorsolateral cortex, and subgenual prefrontal
  cortex.
• The amygdala is increased in volume.
• Activity is reduced during depression, though
  unipolars have increases in the amygdala and
  ventral prefrontal cortex.
• The ventral prefrontal cortex may be a
  depression switch its activity varies with the
  mood state.
• Activity increases in the subgenual prefrontal
  cortex at the start of a period of mania, so it
  may be a bipolar switch.

40
Affective Disorders

• Suicide is very common among people with
  psychiatric illnesses.
• Mood disorders account for 60 of all completed
  suicides.
• About 20 of people hospitalized for bipolar
  disorder commit suicide.
• Six chromosome sites have been associated with
  suicide risk.
• Psychiatric patients who attempt suicide are more
  likely to have a low level of the serotonin
  metabolite 5-HIAA.
• Selective serotonin reuptake inhibitors can
  increase risk, possibly because they increase
  agitation.

41
Serotonin Levels and SuicideFigure 14.25
42
Anxiety Disorders

• Generalized Anxiety, Panic Disorder, and Phobia
• People with generalized anxiety disorder
  experience chronic unease and worry, overreacting
  to stressful conditions.
• In panic disorder, the person has a sudden and
  intense attack of anxiety with rapid breathing, a
  high heart rate, and feelings of impending
  disaster.
• Phobias refer to intense fear and avoidance of
  particular objects (for example, dogs) and
  situations (such as heights, crowds, or enclosed
  spaces).
• ?

43
Anxiety Disorders

• Anxiety disorders
• involve deficits in GABA and serotonin,
• are often treated with antidepressants that
  modulate serotonin.
• Brain areas involved in anxiety include
• amygdala
• locus coeruleus
• parahippocampal gyrus
• ?

44
Anxiety Disorders

• Posttraumatic Stress Disorder (PTSD)
• PTSD is characterized by recurring thoughts and
  images (flashbacks), nightmares, overreactivity
  to environmental stimuli, and lack of
  concentration.
• PTSD can be triggered by combat, sexual assault,
  and other traumatic experiences.
• More men are exposed to traumatic situations than
  females, but females are four times as likely to
  develop PTSD when they are exposed.
• Vulnerability factors include
• a smaller hippocampus, apparently due to
  childhood abuse
• a genetic predisposition heritability is about
  30.

45
Anxiety Disorders

• Treatments for PTSD
• Drugs psychotherapy often do not work with
  PTSD.
• Exposure therapy, an extinction process, is an
  alternative.
• But people with the VAL66MET allele have
  hypoactive connections between the prefrontal
  cortex and the amygdala and are resistant to fear
  extinction.
• Fear erasure during reconsolidation shows some
  promise for relieving PTSD symptoms.
• Virtual reality is another experimental
  treatment.
• The patient uses relaxation techniques while
  controlling progress through a video simulation
  of the traumatic situation.
• Success with this therapy is about 80.
• ?

46
Anxiety Disorders

• Obsessive-compulsive disorder (OCD) consists of
  two behaviors, obsessions and compulsions.
• An obsession is a recurring thought, such as an
  annoying tune or wishing harm to another person.
• The compulsive individual is compelled to engage
  in repetitive behaviors such as hand washing,
  ritualistic touching, or checking appliances to
  make sure they are turned off.
• Serotonin levels are high in OCD antidepressants
  help, by reducing receptor sensitivity.
• Antipsychotics and glutamate blockers help other
  patients.

47
Anxiety Disorders

• OCD patients have increased activity in the
  orbital frontal cortex and in the caudate nuclei
  of the basal ganglia.
• This excess activity decreases following
  successful drug treatment and even after behavior
  therapy.
• Surgery is sometimes used to disconnect the
  orbitofrontal cortex from the anterior cingulate
  cortex or to deliver stimulation.
• OCD occurs with a number of diseases that cause
  basal ganglia damage.
• For example, streptococcus infections in children
  can cause an immune attack on the basal ganglia.

48
Anxiety Disorders

• There are also white matter abnormalities in OCD
• They suggest a defect in connections of the
  cingulate gyrus with a circuit involving the
  basal ganglia, thalamus, and cortex.
• This deficit has two apparent effects
• a loss of impulse control
• inability to activate the orbitofrontal cortex
  when a task requires switching choices.
• ?

49
Anxiety Disorders

• Some researchers cite trichotillomania (hair
  pulling) as evidence OCD is a disorder of
  excessive grooming.
• Both are hereditary and hair pullers have a
  number of relatives with OCD.
• Both respond to serotonin reuptake inhibitors.
• Another condition similar to OCD is hoarding,
  though it may be a separate disorder.
• Tourettes syndrome is also similar to OCD.
• This is a disorder of motor and phonic tics.
• Sufferers often have OCD as well and, like OCD,
  activity is increased in the basal ganglia.
• However, it is usually treated with dopamine
  antagonists.

50
Caudate Nuclei Dopamine Activity in
TourettesFigure 14.30
51
Anxiety Disorders

• Family and twin studies indicate that the anxiety
  disorders are genetically influenced, with
  heritabilities ranging between .20 and .43,
  depending on the disorder.
• Understanding the hereditary underpinnings of
  anxiety is difficult because of significant
  genetic overlap with other disorders.
• Over 90 of individuals with anxiety disorders
  have a history of other psychiatric problems.
• The overlap with affective disorders is
  particularly strong.
• 50-60 of patients with major depression also
  have a history of one or more anxiety disorders
  and panic disorder is found in 16 of bipolar
  patients.