Chapter 15 – Mood Disorders And Schizophrenia

Question 1

A condition in which people feel sad and helpless every day for weeks at a time

Answer 1

Major depression

Question 2

Describe the symptoms of major depression

Answer 2

Feeling sad and helpless every day for weeks at a time

Have a little energy, feel worthless, contemplate suicide, have trouble sleeping, cannot concentrate, find little pleasure, and can hardly even imagine being happy again

Absence of happiness is a more reliable symptom than increased sadness

Although some people suffer from long-term depression, it is more common to have episodes of depression separated by periods of normal mood. For later episodes, people are less likely to identify a triggering event, as if the brain learns how to be depressed and gets better at it

Question 3

Describe the evidence for a genetic contribution to depression

Answer 3

Twin and adoption studies indicate a moderate degree of heritability for depression.

Although researchers have identified several genes linked to depression, none of the genes by itself has a large effect.
Reason why no gene shows a strong linked to Depression – when we talk about depression, we are probably lumping together at least to distinguishable syndromes, early onset and late onset.
Early onset depression before age 30 – have a high probability of other relatives with depression, as well as relatives with anxiety disorders, attention deficit disorder, alcohol and marijuana abuse, obsessive-compulsive disorder, bulimia, migraine headaches, and irritable bowel syndrome.
Late onset depression, especially after 45 to 50 – have a high probability of relatives with circulatory problems.

Another hypothesis: the effect of a gene may vary with the environment. An investigation of the serotonin transporter genes identified the “short” type and the “long” type. For people with too short forms of the gene, increasing numbers of stressful experiences lead to a big increase in the probability of depression. For those with two long forms, stressful events only slightly increased the risk of depression. Those with one short and one long gene were intermediate. The short form of a gene by itself did not lead to depression, but it might magnify the reaction to stressful events. Further studies have failed to replicate the result.

Question 4

What evidence suggests two types of depression influenced by different genes?

Answer 4

Relatives of people with early-onset depression have a high risk of depression and many other psychological disorders. Relatives of people with late-onset depression have a high probability of circulatory problems.

Question 5

What did Caspi and colleagues report to be the relationship between depression and the gene controlling the serotonin transporter protein?

Answer 5

People with the short form of a gene are more likely than other people to react to stressful experiences by becoming depressed. However, in the absence of stressful experiences, their probability is not increased.

Question 6

What should we conclude from the fact that most researchers have not been able to replicate Caspi et al.’s finding?

Answer 6

Either variation in this gene is not really related to depression, or the studies so far have been hampered by inaccurate measurement.

For example, the measurements of stress, in which different stressful events have different levels of stress.

Question 7

Describe the possible role of viruses in the onset or worsening of depression

Answer 7

A few cases of depression or link to viral infections. Borna disease, a viral infection of farm animals, produces periods of frantic activity alternating with periods of inactivity.

Study: 370 people were tested for possible exposure to this virus. Only 12 people tested positive for Borna disease virus, but all 12 or suffering from major depression or bipolar disorder. None of the 105 nondepressed people had the virus.
Since then, the virus is found in about 5% of normal people and about 1/3 of people with severe depression or schizophrenia.

Question 8

Depression after giving birth

Answer 8

Postpartum depression

Question 9

Describe the possible role of hormones in the onset or worsening of depression

Answer 9

About 20% of women report some degree of postpartum depression and many researchers suspect that hormonal fluctuations are a contributing factor. Stress hormones reach a peak in late pregnancy, and ovarian hormones go through major changes around the time of delivery. After a drug-induced drop in estradiol and progesterone levels, women with history of postpartum depression suddenly show new symptoms of depression, whereas other women do not.

A declining level of the hormone testosterone is associated with increased probability of depression in older men

Question 10

Describe the possible role of abnormalities of hemispheric dominance in depression

Answer 10

Studies of normal people have found a fairly strong relationship between happy mood and increased activity in the left prefrontal cortex. Most people with depression have decreased activity in the left and increased activity in the right prefrontal cortex, and this imbalance is stable over years despite changes in symptoms of depression.

Study: most people gaze to the right during verbal tasks, but most individuals with depression gaze to the left, suggesting right-hemisphere dominance

Question 11

Some people offer to train you to use the right hemisphere of your brain more strongly, allegedly to increase creativity. If they were successful, can you see any disadvantage?

Answer 11

People with predominant right-hemisphere activity and decreased left-hemisphere activity show an increased tendency toward depression

Question 12

Antidepressant drug that blocks the uptake of catecholamines and serotonin by presynaptic terminals

Answer 12

Tricyclic

Imipramine (Tofranil)

Operate by blocking the transporter proteins that reabsorb serotonin, dopamine, and norepinephrine into the presynaptic neuron after their release. The result is to prolong the presence of the neurotransmitters in the synaptic cleft, where they continue stimulating the postsynaptic cell.
Also block histamine receptors, acetylcholine receptors, and certain sodium channels. Blocking histamine produces drowsiness, blocking acetylcholine leads to dry mouth and difficulty urinating, blocking sodium channels causes heart irregularities

Question 13

Drug that blocks the reuptake of serotonin in the presynaptic terminal

Answer 13

Selective serotonin reuptake inhibitor or SSRI

Fluoxetine (prozac), sertraline (Zoloft), fluvoxamine (Luvox), Citalopram (Celexa), paroxetine (Paxil).

Similar to tricyclics but specific to the neurotransmitter serotonin.

Produce milder side effects than the tricyclics, but their effectiveness is about the same

Question 14

Drugs that block the uptake of serotonin and norepinephrine

Answer 14

Serotonin norepinephrine reuptake inhibitors or SNRIs

Example: duloxetine (Cymbalta) and venlafaxine (Effexor)

Question 15

Drugs that block the enzyme monoamine oxidase MAO, a presynaptic terminal enzyme that metabolizes catecholamines and serotonin into inactive forms

Answer 15

Monoamine oxidase inhibitors MAOIs

Example: phenelzine (Nardil)

When MAOIs block this enzyme, the presynaptic terminal has more of its transmitter available for release. Generally physicians prescribe tricyclics or SSRIs first and then try MAOIs with people who did not respond to the other drugs.

Must avoid foods containing tyramine, including cheese, raisins, and many others because the combination increases blood pressure

Question 16

Miscellaneous group of drugs with antidepressant effects but only mild side effects

Answer 16

Atypical antidepressants

Example: bupropion (Wellbutrin)

Saint Johns wort, a Herb marketed as a nutritional supplement instead of a drug. Has a potential he dangerous side effect – increases the effectiveness of the enzyme that breaks down plants toxins, which breaks down most medicines and decreases the effectiveness of other drugs you might be taking

Question 17

What are the effects of tricyclic drugs?

Answer 17

Tricyclic drugs block reuptake of serotonin and catecholamines. They also block histamine receptors, acetylcholine receptors, and certain sodium channels, thereby producing unpleasant side effects

Question 18

What are the effects of SSRIs?

Answer 18

SSRIs selectively inhibit the reuptake of serotonin.

Question 19

What are the effects of MAOIs?

Answer 19

MAOIs block the enzyme MAO, which breaks down catecholamines and serotonin. The result is increased availability of these transmitters

Question 20

Describe how antidepressants work

Answer 20

The commonly used antidepressants increase the presence of serotonin or other neurotransmitters at the synapse. However, people with depression have approximately normal levels of release of neurotransmitters, and sometimes increased serotonin release. Also, it is possible to decrease serotonin levels by suddenly consuming all the amino acids except tryptophan, and this decrease does not provoke any feelings of depression.

As far as we can tell, all of the antidepressants are about equal in effectiveness.

Antidepressant drugs produce their effects on neurotransmitters in the synapses within minutes to hours, depending on the drug, but people need to take the drugs for two or more weeks before they experience any mood elevation, which suggests that increasing levels of neurotransmitters at synapses does not explain the benefits of the drop

The action of antidepressants may be due to neurotrophins, which aid in the survival, growth, and connections of neurons. Most people with depression have lower than average levels of a neurotrophin called brain-derived neurotrophic factor BDNF that is important for synaptic plasticity, learning, and proliferation of new neurons in the hippocampus. As a result of low BDNF, most people with depression have a smaller than average hippocampus, impaired learning, and reduced production of new hippocampal neurons. Prolonged use of antidepressant drugs generally increases BDNF production and improves learning and formation of new neurons, which takes weeks.
- The time course for BDNF and changes in the hippocampus matches the time course for behavioural recovery when taking antidepressants

BDNF by itself does not automatically elevate mood, but it helps by facilitating new learning that builds new synapses and removes many old ones

Question 21

In what way does the time course of antidepressants conflict with the idea that they improve mood by increasing neurotransmitter levels?

Answer 21

Antidepressants produce their effects on serotonin and other neurotransmitters quickly, but their behavioural benefits develop gradually over 2 to 3 weeks

Question 22

As opposed to an interpretation in terms of neurotransmitter levels, what is an alternative explanation for the benefits of antidepressant drugs?

Answer 22

Antidepressant drugs increase production of BDNF, which gradually promotes growth of new neurons, new synapses, and new learning in the hippocampus

Question 23

As depression becomes more severe, what happens to the percentage of patients showing improvement while taking antidepressant drugs or placebos?

Answer 23

For more severe cases, the percentage of patients who improve remains about the same for patients taking antidepressant drugs, but fewer patients taking placebos show improvement

For patients with mild to moderate depression, the results for placebo groups overlap those for drug groups, and the differences between the groups are, on average, too small to be of much clinical significance. Only for people with severe depression do the drugs show a meaningful advantage

Question 24

What is an advantage of psychotherapy over antidepressant drugs?

Answer 24

People who respond well to psychotherapy have a lower risk of later relapse than people who respond to antidepressant drugs. Also, antidepressant drugs produce unpleasant side effects and appear to be less effective for people with multiple disorders or people who suffered abuse or neglect in childhood

Question 25

Compare the effectiveness of antidepressants and psychotherapy

Answer 25

Research finds that antidepressant drugs and psychotherapy are about equally effective for treating all levels of depression, from mild to severe, with three exceptions: first, the drugs work better for dysthymia, a long term, almost lifelong condition of unhappy mood. Second, antidepressants are generally ineffective for patients who had suffered abuse or neglect during early childhood or patients with multiple psychological disorders, who usually respond better to psychotherapy. Third, psychotherapy is more likely to have long-term benefits, reducing the likelihood of a relapse months or years after the end of treatment.

A combination of antidepressant drugs and psychotherapy: on average, people who improve while receiving both treatments improve more than people receiving either one alone. However, the percentage of people showing improvement increases only slightly with combined treatment

Question 26

A treatment for depression by electrically inducing a seizure

Answer 26

Electroconvulsive therapy ECT

Originally used to treat people with epilepsy and schizophrenia

Patients are given muscle relaxants or anaesthetics to minimize discomfort and the possibility of injury. Usually applied every other day for about two weeks.

Most common side effect: memory loss, but limiting the shock to the right hemisphere reduces the memory loss, and the memory impairment last no more than a few months, not forever. Another serious drawback is the high risk of relapsing into another episode of depression within a few months.

No one is yet sure how it relieves depression, but it increases the proliferation of new neurons in the hippocampus just like antidepressants

Question 27

Describe sleep patterns in people with depression

Answer 27

Almost everyone with depression has sleep problems, and the sleep problems generally precede the mood changes.

Usual pattern: resembles the sleep of healthy people who travel a couple times zones west and have to go to bed later than usual – they fall asleep but awaken early, unable to get back to sleep, and they enter REM sleep within 45 minutes after going to sleep. In addition, they have more than the average number of eye movements per minute during REM sleep.

Although most people feel worse after a sleepless night, a night of total sleep deprivation is the quickest know when method of relieving depression, but the benefit is brief. More practical solution is to alter the sleep schedule, going to bed earlier than usual

Question 28

How can one decrease the memory loss associated with ECT?

Answer 28

ECT over just the right hemisphere produces less memory loss

Question 29

What change in sleep habits sometimes relieves depression?

Answer 29

Getting people with depression to go to bed earlier sometimes relieves depression

Question 30

Mood disorder with only one extreme or pole, generally depression

Answer 30

Unipolar disorder

Question 31

A condition including full-blown episodes of mania

Answer 31

Bipolar I disorder

In addition to the mood swings, most people with bipolar disorder have attention deficit’s, poor impulse control, and impairments a verbal memory

Question 32

A condition with milder manic phases, characterized mostly by agitation or anxiety

Answer 32

Bipolar II disorder

Question 33

A condition characterized by restless activity, excitement, laughter, self-confidence, rambling speech, and loss of inhibitions

Answer 33

Mania

Question 34

Describe the possible contributions of genetics to bipolar disorder

Answer 34

A genetic predisposition for bipolar disorder is supported by twin studies and adoption studies. Researchers have also located two genes that appear to increase the probability of bipolar II disorder. Have also demonstrated that some of the same genes that predispose to major depression also predispose to bipolar disorder, however the genes merely increase the risk and none show a strong relationship to the disorder

Question 35

Element whose salts are often used as a therapy for bipolar disorder

Answer 35

Lithium

Stabilizes mood, preventing a relapse into either mania or depression.

Dose must be regulated carefully as a low-dose is ineffective and a high dose is toxic.

If these drugs are not fully effective, physician sometime supplement them with anti-depressant drugs or antipsychotic drugs

Discovered by accident by an investigator who believed Uric acid might relieve mania and depression, and mixed uric acid with a lithium salt to help it dissolve

Question 36

Describe possible treatments for bipolar disorder

Answer 36

Lithium, and if that doesn’t work, antidepressants or anti-psychotic drugs.

Eating foods high in omega-3 fatty acids

Sleep: getting people to maintain a consistent sleeping schedule in a dark, quiet room reduces the intensity of mood swing

Question 37

Describe the action of the drugs that help to treat bipolar disorder, such as lithium, valproate, and carbamazepine

Answer 37

One effect these drugs share is that they decrease the number of AMPA type glutamate receptors in the hippocampus. Excessive glutamate activity is responsible for some aspects of media.

Also, the drugs that are effective against bipolar disorder block the synthesis of a brain chemical called arachidonic acid, which is produced during brain inflammation. Bipolar patients show an increased expression of genes associated with inflammation

Question 38

What are two common treatments for bipolar disorder?

Answer 38

The common treatments for bipolar disorder are lithium salts and certain anticonvulsant drugs – Valproate and carbamazepine

Question 39

Depression that recurs during a particular season, such as winter

Answer 39

Seasonal affective disorder SAD

Most prevalent near the poles, where the winter nights are long

Differs from other types of depression, for example, patients have phase delayed sleep and temperature rhythms, becoming sleepy and wakeful later than normal – unlike most other patients with depression, whose rhythms are phase-advanced.
Seldom as severe as major depression

Many people with SAD have a mutation in one of the genes responsible for regulating the circadian rhythm

It is possible to treat it with very bright lights for an hour or more each day

Question 40

What are the advantages of bright light treatment compared to antidepressant drugs?

Answer 40

It is cheaper, has no side effects, and produces its benefits more quickly

Question 41

A psychotic disorder characterized by a deteriorating ability to function in every day life and by some combination of hallucinations, delusions, thought disorder, movement disorder, and inappropriate emotional expressions

Answer 41

Schizophrenia

Question 42

Unjustifiable beliefs

Answer 42

Delusions

A characteristic of people with schizophrenia

Question 43

False sensory experiences

Answer 43

Hallucinations

A characteristic of people with schizophrenia

Question 44

According to the DSM-IV, to be diagnosed with schizophrenia, someone must have deteriorated in every day functioning– such as work, interpersonal relations, self-care, etc.– for at least six months, and must show at least two of the following that are not attributable to other disorders:

Answer 44

Delusions – unjustifiable beliefs

Hallucinations – false sensory experiences

Disorganized speech – rambling or incoherent

Grossly disorganized behaviour

Weak or absent signs of emotion, speech, and socialization

Question 45

Presence of behaviours not seen in normal people.

Example: delusions, hallucinations, disorganized speech, and disorganized behaviour in people with schizophrenia

Answer 45

Positive symptoms

Question 46

Absence of behaviours ordinarily seen in normal people, such as a lack of emotional expression

Example: weak or absent emotion, speech, and socialization in people with schizophrenia

Answer 46

Negative symptoms

Usually stable over time and difficult to treat

Question 47

Distinguish some of the cognitive symptoms (limitations of thought and reasoning) in people with schizophrenia

Answer 47

On average, IQ scores are a few points below those of the rest of the population

Most typical type of thought disorder – a difficulty understanding and using abstract concepts, as well as deficits in attention and working memory

Main problem – disordered thoughts that result from abnormal interactions between the cortex and the thalamus and cerebellum. The disordered thinking may lead to the hallucinations, delusions, and other symptoms

Question 48

Why are hallucinations considered a positive symptom?

Answer 48

Hallucinations are considered a positive symptom because they are present when they should be absent. A “positive” symptom is not a “good” symptom

Question 49

A diagnosis that rules out other conditions with similar symptoms

Answer 49

Differential diagnosis

Question 50

Describe six conditions resembling schizophrenia, with which it may be confused

Answer 50

1. Mood disorder with psychotic features: people with depression frequently have delusions, especially delusions of guilt or failure and some report hallucinations as well
2. Substance abuse: many of the positive symptoms of schizophrenia can develop from prolonged use of amphetamine, methamphetamine, cocaine, LSD, or phencyclidine (“Angel dust”). Substance abuse is more likely than schizophrenia to produce visual hallucinations.
3. Brain damage: damage or tumours in the temporal or prefrontal cortex often produce some of the symptoms of schizophrenia
4. Undetected hearing deficits: sometimes, someone who is starting to have trouble hearing thinks that everyone else is whispering and starts to worry and delusions of persecution can develop
5. Huntington’s disease: symptoms include hallucinations, delusions, and disordered thinking, as well as motor symptoms. An uncommon type of schizophrenia, catatonic schizophrenia, includes motor abnormalities, so a mixture of psychological and motor symptoms could represent either schizophrenia or Huntington’s disease
6. Nutritional abnormalities: niacin deficiency can produce hallucinations and delusions, and so can a deficiency of vitamin C or an allergy to milk proteins. Can also occur in people who cannot tolerate wheat gluten or other proteins.

Question 51

Describe the demographic factors related to schizophrenia

Answer 51

About 1% of people worldwide suffer from schizophrenia at some point in life, and the reported prevalence of schizophrenia has been declining in many countries since the mid-1900s.
Occurs in all ethnic groups in all parts of the world, but is significantly more common in cities than in rural areas, and is 10 to 100 times more common in the United States and Europe than in most Third World countries, which could be due to differences in record keeping, but could also be due to social support and diet (eg. A diet high in sugar and saturated fat, which aggravates schizophrenia or a diet high in omega-3 fatty acids such as those found in seafood, which can alleviate it)
- more common for men than women by a ratio of about 7:5, and is also more severe in man and has an earlier onset

Other interesting factors:

• significantly less common than average among people with type 1 or juvenile-onset diabetes, and more common than average in people with type 2 or adult-onset diabetes
• have an increased risk of colon cancer but below average probability of respiratory cancer or brain cancer
• seldom develop rheumatoid arthritis or allergies
• Women who have a schizophrenic breakdown during pregnancy usually give birth to daughters, and those who have a break down shortly after giving birth usually give birth to sons
• have a characteristic body voter, attributed to the chemical trans-3-methyl-2-hexanoic acid, and decreased ability to smell that chemical themselves
• many and their unaffected relatives have deficits in pursuit eye movements – the ability to keep their eyes on a moving target

Question 52

Has the reported prevalence of schizophrenia been increasing, decreasing, or staying the same?

Answer 52

Schizophrenia has been decreasing in reported prevalence

Question 53

Describe the evidence for a genetic contribution to schizophrenia as it relates to twin studies

Answer 53

The more closely you are biologically related to someone with schizophrenia, the greater your own probability of schizophrenia

Confirmed by twin studies: monozygotic twins have a much higher concordance/agreement for schizophrenia than do dizygotic twins. Also, twin pairs who are really monozygotic, but thought they weren’t, are more concord and then twin pairs who thought that they were, but really aren’t – being monozygotic is more critical than being treated as monozygotic

Two limitations:

1. Monozygotic twins have only about 50% concordance, not 100%. They could differ because a gene is activated in one individual and suppressed in another, or could differ because of environmental influences
2. There is a greater similarity between dizygotic twins than between siblings. Dizygotic twins have the same genetic resemblance as siblings but greater environmental similarity, including prenatal environment

Question 54

Describe the evidence for a genetic contribution to schizophrenia as it relates to adopted children who develop schizophrenia

Answer 54

When an adopted child develop schizophrenia, the disorder is more common in the person’s biological relatives than adopting relatives.

These results suggest a genetic basis, but they are also consistent with a prenatal influence. Example, many women with schizophrenia smoke, drink, use other drugs, and eat less nutritionally during pregnancy

Other studies have found a high probability of schizophrenia or related conditions among children who had a biological mother with schizophrenia and a severely disordered adopting family. The genetic risk itself or the disorder family itself had less effect

Question 55

Describe the evidence for a genetic contribution to schizophrenia as it relates to efforts to locate a gene

Answer 55

Researchers working with various populations have identified more than a dozen genes that appear to be more common in people with schizophrenia.

DISC1 (disrupted in schizophrenia 1)- has attracted much interest regarding schizophrenia. Controls production of dendritic spines and the generation of new neurons in the hippocampus.

Other genes linked to schizophrenia and several studies are important for brain development, control of transmission at glutamate synapses, and connections between hippocampus and the prefrontal cortex. However, there has not been great success at replicating the results from one population to another.

It’s schizophrenia has a genetic basis but we can’t find any gene with a consistent link, and any gene that leads to schizophrenia can’t be passed down through many generations, what is going on? Hypothesis: many cases of schizophrenia arise from new mutations. Proper brain development depends on hundreds of genes. A mutation in one gene is a rare event, but a mutation in any of several hundred is not so rare. An even more likely possibility is the deletion of a gene, a fairly common error in reproduction. The hypothesis is that a new mutation or deletion of any of a large number of genes disrupts brain development and increases the probability of schizophrenia. One observation supporting this idea is that schizophrenia is somewhat more common among children of older fathers who make new sperm throughout life and have more possibility of mutations accumulating over time

Question 56

The fact that adopted children who develop schizophrenia usually have biological relatives with schizophrenia implies a probable genetic basis. What other interpretation is possible?

Answer 56

A biological mother can influence her child’s development through prenatal environment as well as genetics, even if the child is adopted early

Question 57

Does the hypothesis of new mutations conflict with the results showing that and an aberrant form of the gene DISC1 is often linked to schizophrenia?

Answer 57

No. Although mutations in many genes can, according to the hypothesis, lead to schizophrenia, the DISC1 gene could be one where the mutation is more certain to cause schizophrenia

Question 58

Proposal that schizophrenia begins with abnormalities in the prenatal or neonatal development of the nervous system, based on either genetics or other influences

Answer 58

Neurodevelopmental hypothesis

Question 59

What are the three pieces of evidence supporting the neurodevelopmental hypothesis?

Answer 59

1. Several kinds of prenatal or neonatal difficulties are linked to later schizophrenia
2. People with schizophrenia have minor brain abnormalities that apparently originate early in life
3. It is possible that abnormalities of early development could impair behaviour in adulthood

Question 60

Tendency for people born in winter to have a slightly greater probability of developing schizophrenia than people born at other times of the year

Answer 60

Season-of-birth effect

Question 61

Describe the evidence regarding prenatal a neonatal environment regarding the Neurodevelopmental hypothesis

Answer 61

The risk of schizophrenia is elevated among people who had problems that could have affected their brain development, including poor nutrition of the mother during pregnancy, premature birth, low birth weight, and complications during delivery. Risk is also elevated if the mother was exposed to extreme stress. None of these influences by itself accounts for many cases of schizophrenia, although together their influence is greater.

Also been linked to head injuries in early childhood.

A mother with RH-negative and a baby with RH-positive blood, which may trigger an immunological rejection by the mother. Stronger in later pregnancies, and more intense with a boy than girl babies.

Season-of-birth effect – the tendency for people born in winter to have a slightly, 5% 8%, greater probability of developing schizophrenia than people born at other times of the year. Particular pronounced in latitudes far from the equator. May be due to viral infection which is more common in the fall.

Certain childhood infections, such as the parasite toxoplasma gondii which reproduces in cats

Question 62

What does the season-of-birth effect suggest about a possible cause of schizophrenia?

Answer 62

The season-of-birth effect is the observation that schizophrenia is slightly more common among people who were born in the winter. One interpretation is that influenza or other infections of the mother during the fall impair brain development of a baby born in the winter

Question 63

Describe the evidence regarding mild brain abnormalities as it relates to the Neurodevelopmental hypothesis

Answer 63

Some people with schizophrenia show mild abnormalities of brain anatomy that vary from one individual to another

On average, people with schizophrenia have less than average gray matter and white matter, and larger than average ventricles – the fluid-filled spaces within the brain

Studies have shown the strongest deficits to be in the left temporal and frontal areas of the cortex. Has also shown that the thalamus is also smaller than average.

The areas with consistent signs of abnormality include some that mature slowly, such as the dorsolateral prefrontal cortex. Abnormalities here include weaker than average connections from the dorsolateral prefrontal cortex to other brain areas, and less than normal activity in this area during tasks requiring attention and memory. Most people with schizophrenia perform poorly at task that depend on the prefrontal cortex, and show deficits of memory and attention similar to those of people with damage to the temporal or prefrontal cortex.

At a cell level: cell bodies are smaller than normal, especially in the hippocampus and prefrontal cortex

Lateralization also differs from the normal pattern: in most people, the left hemisphere slightly larger than the right, especially in the planum temporale of the temporal lobe, but in people with schizophrenia, this area is equal or larger. They also have lower than normal overall activity in the left hemisphere and are more likely than other people to be left-handed.

The brains of people with schizophrenia do not show the signs that accompany neuron death – proliferation of glia cells and activation of the genes responsible for repair after injury. Possibly, the neurons are shrinking without dying.

Question 64

Describe the evidence of early development and later psychopathology as it relates to the Neurodevelopmental hypothesis

Answer 64

If schizophrenia may be due to abnormalities in early development, why is the disorder usually diagnosed after age 20?
Most of the people who develop schizophrenia in adulthood had shown other problems since childhood, including deficits in attention, memory, and impulse control. Furthermore, the prefrontal cortex, an area that shows consistent signs of deficit and schizophrenia, is one of the slowest brain areas to mature – later, when these areas begin assuming important functions, the damage begins to make a difference

Question 65

If schizophrenia is due to abnormal brain development, why do behavioural symptoms not become apparent until later in life?

Answer 65

Parts of the pre-frontal cortex are very slow to reach maturity; therefore, early disruption of this area’s development might not produce any symptoms early in life, when the prefrontal cortex is contributing little anyway

Question 66

Antipsychotic drug that relieves the positive symptoms of schizophrenia for most, though not all, patients

Answer 66

Chlorpromazine (thorazine)

Question 67

Drugs that tend to relieve schizophrenia and similar conditions

Answer 67

Antipsychotic or neuroleptic drugs

Question 68

What are the two families of antipsychotic or neuroleptic drugs?

Answer 68

The phenothiazines, which include chlorpromazine

The butyrophenones, which include Haloperidol

Behavioural benefits of any of these drugs develop gradually over a month or more. Symptoms generally return after cessation of treatment

Question 69

A chemical family that includes antipsychotic drugs such as chlorpromazine, that relieve the positive symptoms of schizophrenia

Answer 69

Phenothiazines

Question 70

A chemical family that includes antipsychotic drugs (haloperidol) that relieve the positive symptoms of schizophrenia

Answer 70

Butyrophenones

Question 71

Describe the action of antipsychotic or neuroleptic drugs such as chlorpromazine and butyrophenones

Answer 71

Each of these drugs blocks dopamine synapses. The drugs that are most effective against schizophrenia, and therefore used in the smallest doses, are the most effective at blocking dopamine receptors. This finding inspired the dopamine hypothesis of schizophrenia

Question 72

Idea that schizophrenia results from excess activity at dopamine synapses in certain brain areas

Answer 72

Dopamine hypothesis of schizophrenia

Question 73

Describe the evidence for and against the dopamine hypothesis of schizophrenia

Answer 73

This hypothesis holds that schizophrenia results from excess activity at dopamine synapses in certain brain areas. Although the concentration of dopamine in the brain is no higher than normal, the turnover is elevated, especially in the basal ganglia – that is, neurons release dopamine at a faster than average rate and synthesize more to replace the molecules that they do not reabsorb.

Support: elevated dopamine release occurs in people showing the first symptoms of schizophrenia.
- large, repeated use of amphetamine, methamphetamine, or cocaine induces a substance-induced psychotic disorder, characterized by hallucinations and delusions, the positive symptoms of schizophrenia. Each of these drugs increases or prolong the activity at dopamine synapses.
- researchers used a radioactively labelled drug, IBZM that binds to dopamine type D2 receptors that only binds to receptors that dopamine did not already blind. Measuring the radioactivity counts the number of vacant dopamine receptors. They then used a second drug, AMPT, that blocks all synthesis of dopamine and again used IBZM do you count the number of vacant D2 receptors. Because AMPT had prevented production of dopamine, all D2 receptors should be vacant at this time, so the researchers got a count of the total. Then they subtracted the first count from the second count, yielding the number of D2 receptors occupied by dopamine at the first count:
The researchers found that people with schizophrenia had about twice as many D2 receptors occupied as normal. Another study found that among patients with schizophrenia, the greater amount of D2 receptor activation in the prefrontal cortex, the greater the cognitive impairment.

Against: glutamate may play a role

Question 74

Condition similar to schizophrenia, provoked by large, repeated doses of a drug

Answer 74

Substance-induced psychotic disorder

Question 75

Proposal that schizophrenia relates in part to deficient activity at glutamate synapses, especially in the prefrontal cortex

Answer 75

Glutamate hypothesis of schizophrenia

In many brain areas, dopamine inhibits glutamate release, or glutamate stimulates neurons that inhibit dopamine release. Therefore, increased dopamine would produce the same affects as decreased glutamate. The antipsychotic effects of drugs that block dopamine are compatible with either the excess-dopamine hypothesis or the deficient-glutamine hypothesis

Question 76

Describe the evidence for the glutamate hypothesis of schizophrenia

Answer 76

Schizophrenia is associated with lower than normal release of glutamate and fewer than normal receptors in the prefrontal cortex and hippocampus. Similar abnormalities occur in people known to be at high risk for developing schizophrenia, because of their family background and early behaviors. Mice with a deficiency of glutamate receptors show some abnormal behaviors, including increased anxiety, impaired memory, and impaired social behaviours.

Further support comes from the effects of phencyclidine PCP (“Angel dust”), A drug that inhibits the NMDA glutamate receptors. At low doses, it produces intoxication and slurred speech. At larger doses, it produces both positive and negative symptoms of schizophrenia, including hallucinations, thought disorder, loss of emotions, and memory loss:

• PCP and the related drug ketamine produce little if any psychotic response in preadolescents. Just as the symptoms of schizophrenia usually begin to emerge well after puberty, so do the psychotic effects of PCP and ketamine
• LSD, amphetamine, and cocaine produce temporary schizophrenic symptoms in almost anyone, and the effects are not much worse in people with a history of schizophrenia than anyone else. However, PCP produces severe effects for someone who has recovered from schizophrenia, including a long lasting relapse.

Question 77

Describe the potential role for glycine and for metabotropic glutamate receptors in treating schizophrenia

Answer 77

Because overstimulation of glutamate synapses can kill neurons as in strokes, increasing overall brain glutamate would be risky. However, drugs that stimulate particular kinds of metabotropic glutamate receptors have shown much promise in treating schizophrenia.

The NMDA glutamate receptors has a primary site that is activated by glutamate and a secondary side that is activated by glycine. Glycine by itself does not activate the receptor, but it increases the effectiveness of glutamine. Therefore, an increase in glycine can increase the activity at NMDA synapses without overstimulating glutamate throughout the brain. Although not effective by itself, glycine increases the effect of other antipsychotic drugs, especially with regard to negative symptoms

Question 78

What drugs induce mainly the positive symptoms of schizophrenia? What drug can induce both positive and negative symptoms?

Answer 78

Repeated use of amphetamine, cocaine, or LSD induces positive symptoms, such as hallucinations and delusions. Phencyclidine induces both positive and negative symptoms

Question 79

Why are the effects of antipsychotic drugs equally compatible with the dopamine hypothesis and the glutamine hypothesis of schizophrenia?

Answer 79

Dopamine inhibits glutamate cells in many areas, and glutamate stimulates neurons that inhibit dopamine. Therefore, the effects of increasing dopamine are similar to those of decreasing glutamate

Question 80

Describe one undesired effect of antipsychotic drugs that are used to treat schizophrenia

Answer 80

The drugs that block dopamine synapses produce their benefits by acting on neurons in the mesolimbocortical system, a set of neurons that project from the midbrain tegmentum to the limbic system. These drugs also block dopamine neurons in the mesostriatal system that projects to the basal ganglia.
The effect on the basal ganglia produces tardive dyskinesia, characterized by tremors and other involuntary movements that develop gradually and to varying degrees among different patients. Once this emerges, it can last long after someone quits the drug

Question 81

A movement disorder characterized by tremors and other involuntary movements

Answer 81

Tardive dyskinesia

Question 82

Drugs that alleviate schizophrenia without producing movement problems

Answer 82

Second-generation antipsychotics

The most common of these drugs are clozapine, amisulpride, risperidone, olanzapine, and aripiprazole.

These drugs are more effective than older drugs at treating the negative symptoms of schizophrenia, and they are now used more widely

Question 83

One effect of antipsychotic drugs that treat schizophrenia is tardive dyskinesia. describe the mechanisms of action of the newer drugs that minimize these effects

Answer 83

Second-generation antipsychotics avoid tardive dyskinesia, but they also produce other side effects, including weight gain and impairment of the immune system.

Compared to earlier antipsychotic drugs like haloperidol, these drugs have less effect on dopamine type D2 receptors but more strongly antagonize serotonin type 5-HT2 receptors. They also increase the release of glutamate