Psychological Disorders

Question 1

Categorical approach to mental disorders - is it good?

Answer 1

Categorical approach often not very beneficial in mental disorders – causes, symptoms, genetics, etc are highly overlapping between disorders, and often comorbid, and people might full fill all criteria for one or more disorders, or partly fulfill them.

Question 2

The paradox of addiction

Answer 2

the pleasure decrease, and risk increase as addiction progresses. – this applies to pretty much all addictions, from alcohol to gambling to gaming.

Question 3

Antagonist

Answer 3

• Drug that blocks a neurotransmitter

Question 4

Agonist

Answer 4

• Drug that mimics or increases an effect

Question 5

A mixed agonist

Answer 5

An agonist for some effects and an antagonist for others, or an agonist at some doses and an antagonist at others.

Question 6

Drug’s affinity for a receptor

Answer 6

Measure of drug’s tendency to bind to it

• Ranges from strong to weak affinity

Question 7

Drug’s Efficacy

Answer 7

tendency to activate the receptor
• A drug’s effectiveness and side effects vary from one person to another
• Largely because the abundance of each type of receptor varies between individuals

Question 8

Predispositions to substance abuse

Answer 8

• People differ in their predisposition to alcohol or drug abuse – some people will try a drug a few times and quit, others will become addicted.
• Certain aspects of brain function and behavior are present from the start in people with a familial disposition to addiction (regardless if they later become addicts or not)
• Not all individuals develop addiction

Question 9

Genetic Influences on substance abuse

Answer 9

probability of abusing alcohol or other drugs depends on both genetic and environmental influences

parents’ amount of alcohol use correlates with that of both biological and adopted children, although it correlates more strongly with that of the biological children
Children growing up in unstable environments more susceptible to substance abuse (magnified if also having specific gene affecting serotonin synapses)

• Twin studies confirm strong influence of genetics on vulnerability to alcohol/drugs
• Many addiction-linked genes have been identified, each with a small effect
• Genes affect the probability of substance use, but effects vary depending on environment
• Example: People with a gene for producing less acetaldehyde dehydrogenase metabolize acetaldehyde (from alcohol) more slowly
• Those individuals tend to drink less and have fewer problems with alcohol abuse (e.g., China and Japan)  tend to have lower degree/amount of alcohol addiction.

Question 10

Environmental Influences in alchomolism/drug abuse

Answer 10

• Prenatal environment contributes to risk for alcoholism
• Alcoholic mothers during pregnancy  increased probability of child becomes alcoholic, regardless of mother’s alcohol consumption when they grow up.
• Childhood environment is critical
• Careful parenting supervision decreases likelihood of developing impulsive behavior that leads to abuse (even if they have genetic predisposition)
• Alcoholics that develop alcohol problems before age 25 tend to have family history and a genetic predisposition and rapid onset of problems (suggesting early onset alcoholism tend to have a large genetic influence, where later onset might be more due to environmental influence, more likely to respond well to treatment)

Question 11

Behavioral Predictors of Abuse

Answer 11

One’s behavior can be predictor of substance abuse.
- More impulsive, risk taking, sensation seeking, easily bored people had greater chance of becoming addicts
• Research findings
• Sons of alcoholics show less than average intoxication after drinking a moderate amount of alcohol
• Low level of intoxication may influence person to keep drinking
• Probability of developing alcoholism is greater than 60 percent
• Alcohol decreases stress for most people, but more so for sons of alcoholics
• Similar results have been reported for women
• People ”holding their liqour well” is not something to brag about, but something to be worried about. – higher risk of alcoholism

Question 12

Synaptic Mechanisms and the role of dopamine in substance abuse

Answer 12

• Nearly all abused drugs affect several kinds of receptors (most abused drugs increase activity at dopamine and noepinephrine synapses)
• The effects while the drug is in the brain differ from effects that occur during withdrawal, and effects responsible for cravings
• Efforts to alleviate drug abuse must consider a variety of mechanisms

Dopamine:
• James Olds and Peter Milner (1954)
• Stimulating rat brains: missed target and hit septum causing rats to respond favorably
• Discovered that rats would push a lever to produce electrical self-stimulation of the brain
• Nucleus accumbens
• Central to reinforcing experiences of all types, not just drugs (where cell stimulating behavior happened)
• Location where addictive drugs release dopamine or norepinephrine (direct release with stimulants, or indirect through opiods)
• Can happen e.g. with sexual behavior, gambling, even imagining things.

Stimulant drugs such as cocaine and
amphetamine increase or prolong the release of dopamine in the nucleus accumbens - most other abused drugs do increase dopamine release directly or indirectly. For example, nicotine
stimulates neurons that release dopamine, and opiates
inhibit neurons that inhibit dopamine release.

–> Dopamine acts as a reinforcer (but I think I decreases over time, behavior is less rewarding, and then they have to do it more to get reward)

BUT! researchers have possibly been overemphasizing the role of dopamine (Drugs that block dopamine synapses do not reduce the reward properties of opiate drugs, and they do not decrease use and not direct relationship between dopamine and pleasentness of drugs)

Question 13

Cravings

Answer 13

people with addictions have trouble breaking any habit, not just a drug habit. - craving can persist long after the behavior has ceased to be rewarding. a similar pattern for people with prefrontal cortex damage: After they have learned a response or a preference, they are slow to update it in response to new information

• Defining feature for addiction = craving!: Insistent search for the activity (addicts can want something without liking it)
• Even after long period of abstinence, cues can trigger a craving
• The brain mechanism of craving differs from the response to the original activity
• Studies in rats show repeated exposure to an addictive substance alters receptors in nucleus accumbens and other areas to become more responsive to the addictive substance
• And Less responsive to other types of reinforcement
• responses to cues associated with the drug (reminders) become sensitized, attracting greater attention. That increased attention is magnified by the fact that other, competing rewards are less intense than before
• Then, during a period of abstinence, the nucleus accumbens synapses responding to drug cues gradually become more and more sensitive, before later declining partly. – consistent with craving increases during the early stage of abstinence, and slightly declines later

increased response to drug cues has been traced to facilitated glutamate synapses in the nucleus accumbens –> a treatment that desensitizes glutamate synapses
in the nucleus accumbens might reduce cravings for certain drugs.

• Exposure to drugs can disrupt activity in PFC, responsible for restraining impulses = one of biological reasons for cravings and seeking behaviors.

Question 14

• Tolerance

Answer 14

• Decrease in effect as an addiction develops
• Drug tolerance is learned, to a large extent
• Can be weakened through extinction procedures

Question 15

• Withdrawal

Answer 15

• Withdrawal
• Body’s reaction to absence of the drug
• One hypothesis is that addictive behavior is an attempt to avoid withdrawal symptoms – but counter evidence! Cocaine addictive but little withdrawal, gambling addictive but no substance withdrawn.
• Modified hypothesis: person with an addiction may use the substance to cope with (di)stress
• Receiving a drug during withdrawal, can create cravings during other types of stressful experience

Question 16

Treatments for substance use disorders - overview

Answer 16

• Some addicts able to decrease use or quit on their own
• Alcoholics or Narcotics Anonymous (or similar group) (groups that individuals use)
• Cognitive-behavioral therapy (allows for controlling patterns of thinking, attitudes, beliefs, around reactions like drug seeking)
• Contingency management includes rewards for remaining drug-free
• Medication—not as common, but some options are available

Question 17

Medications to Combat Alcohol Abuse

Answer 17

• Antabuse (disulfiram)
• Makes it harder to metabolize acedylhyde (or what it was called) = Results in sickness after drinking
• Taking a nausea-inducing drug after drinking, to associate the two—learned aversion
• Approach has not become popular (placebo has similar effects, but EXPECTATION of getting sick might make them abstain when on placebo, could explain it)
• Someone who takes an Antabuse pill and then drinks alcohol anyway becomes ill, and in most cases quits taking Antabuse instead of quitting alcohol.
• Naloxone (Narcan) and naltrexone
• Block opiate receptors and decrease pleasure from alcohol
• Drug effectiveness varies with user’s motivation to quit

Question 18

Medications to Combat Opiate Abuse

Answer 18

• Naloxone (Narcan)
• Opiate antagonist - reverse the effects of an opioid overdose
• Can restore breathing patterns (obstructed in overdose) – you can also do this to unconscious persons
• But will not fix overdoses of other drugs.
• Does not fix addiction, but can save against death (by overdose)
• Methadone as a safer alternative to heroin/morphine/opiates (used to reduce withdrawal ad prevent high from heroin or morphine)
• Similar to heroin and morphine
• Activates same brain receptors and produces same effects
• Can be taken orally, absorbs slowly, and leaves the brain slowly
• “Rush” and withdrawal both reduced.
• Buprenorphine and LAAM
• Similar to methadone
LAAM has the advantage of producing a long-lasting effect
so that the person visits a clinic three times a week instead of
daily. People using any of these drugs live longer and healthier,
on average, than heroin or morphine users, and they are far
more likely to hold a job

All of these drugs don’t end addiction, but can satisfy cravings in a less dangerous way

Question 19

Major Depressive Disorder and Major depression symptoms

Answer 19

Symptoms:
• Person feels sad and helpless most of the day every day for long periods of time
• Person does not enjoy anything and cannot imagine enjoying anything
• Fatigue, feelings of worthlessness, or contemplation of suicide
• Trouble sleeping
• Cognitive problems: low motivation, impaired memory, concentration problems, and impaired sense of smell
• Cannot imagine being happy
• Their nucleus accumbens becomes less responsive to reward

• Absence of happiness is a more reliable symptom than increased sadness (MDD often decreased response to happy/rewarding stimuli, but normal reaction to sad stimuli)
• More common in women during the reproductive era - about equal before puberty and after menopause (reason unknown)
• Affects five-six percent of adults with a given year
• 10 percent lifetime prevalence
• Some people suffer long-term depression
• More common to have periodic episodes of depression (separated by normal moods – later episodes are more frequent, and the more episodes you have, the greater the risk of getting another one)

Question 20

Genetics in depression / mood disorders

Answer 20

• Depression has a moderate degree of heritability
• No one gene has been identified as clearly linked to depression (the effect of a gene varies within the environment)
• People with early-onset depression (before age 30) more likely to have relatives with depression as well as relatives with anxiety disorders, neuroticism, ADD, OCD, IBS, and migraine headaches - Early-onset depression also tends to be more severe, more long-lasting, and more associated with suicidal tendencies
• Late onset depression (after age 45) linked to relatives with circulatory problems
 Another reason why it is hard to find a gene linked to depression is that when we talk about depression, we may be combining separate syndromes.

• Hypothesis: the effect of a gene varies with the environment (especially the serotonin transporter)
• Evidence:
• Young adults with the short form of the serotonin transporter gene who experienced stressful experiences had a major increase in probability of developing depression.
• Long-form of gene less susceptible to stressful events; one long and one short-moderate risk
• Short-form may increase depressive reaction to stressful events (confirmed by meta analysis, but some results have been divergent)—especially childhood stress

Question 21

Abnormalities of Hemispheric Dominance in Depression

Answer 21

• Brain activity associated with depression
• Decreased activity in the left prefrontal cortex
• Increased activity in the right prefrontal cortex
• Imbalance stable over the years, despite symptom changes
• It probably represents a predisposition to depression rather than a reaction to it.
• = imbalance in hemispheric dominance for MDD/depression
• People with depression tend to gaze to the left when asked to do a verbal task
• Most people gaze to the right

Question 22

Antidepressant Drugs - overall

Answer 22

• Many drugs used to treat psychiatric disorders discovered by accident
• Categories of antidepressant drugs
• Tricyclics
• Selective serotonin reuptake inhibitors (SSRIs)
• Monoamine oxidase inhibitors (MAOIs)
• Atypical antidepressants

Presynaptic neuron, when we get it activated and sends down AP, NTs released from vesicles to synaptic cleft, received by postsynaptic receptors, act on post synaptic neuron – when antidepressants do: tricyclics prevent presynaptic from reabsorbing NTs, so they remain in cleft for longer time. SSRI’s do the same, but specific to serotonin. SNRIs block reuptake for serotonin and norepinephrine. MAOIs block MAO from metabolizing catecholamines and serotonin.

Many patients now take two or more drugs with different modes of action, although the effectiveness of this approach is uncertain (mentioned for SNRIs, not sure if applies to all meds)

Although antidepressants vary in which neurotransmitter(s) they target—serotonin, dopamine, norepinephrine, or some combination—all appear to be nearly equal in their effectiveness

It is not possible to predict
which drug will work best for a given patient, so it is strictly a trial-and-error process. Switching to a different type of drug (SSRI versus tricyclic, for example) is no more likely to be helpful than switching to a drug of the same type. Most patients eventually show a favorable response to one of the drugs – but can we know if it was an effect of the drug, or just general recovery (which usually happens within a few months)? – we odn’t know, research fails to include adequate control groups.

Question 23

Antidepressant Drugs—Tricyclics

Answer 23

• Tricyclics (such as imipramine; Tofranil)
• Block transporter proteins that reabsorb serotonin, dopamine, and norepinephrine (all catecholamines she said) into the presynaptic neuron after release
• Also block histamine receptors, acetylcholine receptors, and certain sodium channels
• Side-effects include drowsiness (from blocking histamine receptors), dry mouth (from blocking acethylcholine), difficulty urinating, and heart irregularities (from blocking sodium channels)

Question 24

Antidepressant Drugs—SSRIs

Answer 24

• Selective serotonin reuptake inhibitors (SSRIs)
• Block the reuptake of the neurotransmitter serotonin
• Examples: fluoxetine (Prozac), sertraline (Zoloft), fluvoxamine (Luvox), citalopram (Celexa), and paroxetine (Paxil)
• Work in a similar fashion to tricyclics but specific to the neurotransmitter serotonin
• SSRIs produce milder side effects than the tricyclics, but their effectiveness is about the same

Question 25

Antidepressant Drugs – SNRIs

Answer 25

• Serotonin norepinephrine reuptake inhibitors (SNRIs)
• Examples: duloxetine (Cymbalta) and venlafaxine (Effexor)
• Block reuptake of serotonin and norepinephrine
• Unlike other antidepressants, the SNRIs improve certain aspects of memory
Many patients now take two or more drugs with different modes of action, although the effectiveness of this approach is uncertain

Question 26

Antidepressant Drugs – MAOIs

Answer 26

• Monoamine oxidase inhibitors (MAOIs)
• Block the enzyme monoamine oxidase that metabolizes catecholamines and serotonin into inactive forms (if you block that process = more ACTIVE forms)
• Results in more transmitters in the presynaptic terminal available for release
• Usually only prescribed if SSRIs and tricyclics are not effective
• High blood pressure results with some food (People taking MAOIs must avoid foods containing tyramine—including cheese, raisins, and many others— because a combination of tyramine and MAOIs increases blood pressure)
• MAOIs the original antidepressants, but now largely avoided.

Question 27

Atypical Antidepressant Drugs

Answer 27

• Miscellaneous group of drugs with antidepressant effects and milder side effects
• Example: bupropion (Wellbutrin)
• Inhibits the reuptake of dopamine and to some extent norepinephrine, but not serotonin
Although antidepressants vary in which neurotransmitter(s) they target—serotonin, dopamine, norepinephrine, or some combination—all appear to be nearly equal in their effectiveness

Question 28

Antidepressant Drugs—New Investigatory Substances

Answer 28

• Ketamine
• Antagonizes NMDA type glutamate receptors (and increases formation of new synapses)
• Produces rapid antidepressant effects in people who don’t respond to other medications
• Not suitable (produces delusions and hallucinations) but hopefully ketamine investigation may lead to something similar that is more safe.
• St. John’s Wort
• Herb often used as a treatment for depression
• Nutritional supplement not regulated by the FDA (purity varies from bottle to bottle)
• Often less expensive than antidepressant drugs + available without prescription.  People can get it easily but often take inappropriate amounts.
• Effectiveness about the same as standard antidepressants
• Increases the production of a liver enzyme that decreases the effectiveness of other medications, e.g. antidepressants, cancer, or AIDS medicine (important, you should always talk with doctor about herbal remedies you are taking)

Question 29

How Are Antidepressants Effective? —Neurotransmitters

Answer 29

• Most people with depression have normal levels of neurotransmitters
• Decreasing serotonin in control groups (e.g. diet without tryptophan) does not provoke depression
• Major theoretical difficulty: Drugs affect neurotransmitters in synapses quickly (minutes to hours)
• But result improving mood often requires weeks

Question 30

How Are Antidepressants Effective? —BDNF

+ New Neurons in the Hippocampus

Answer 30

• People with depression have lower than average brain-derived neurotrophic factor (BDNF): important for synaptic plasticity, learning, and proliferation of new neurons in hippocampus
• As a result of lower BDNF, people with depression show:
• Smaller than average hippocampus
• Impaired learning
• Reduced production of hippocampal neurons
• Prolonged use of antidepressants increases BDNF production (over weeks), consistent with time frame of weeks for behavioral effects

The importance of new learning may explain why
antidepressants don’t elevate the mood of people who are not
depressed: Those people are not burdened with discouraging
thoughts that they need to unlearn (Castrén & Rantamäki, 2010).
However, the formation of new neurons is not the whole explanation
for antidepressant drugs, as the drugs also exert essential
effects on mature hippocampal neurons

• Proliferation of new neurons in the hippocampus is important for antidepressant effects
• Independent of whether BDNF is responsible
• Studies show antidepressants may not be helpful for mild/moderate depression (but study might be bad scientifically, so don’t trust it too much)
Antidepressants have apparently little effect on the suicide rate

Question 31

Alternatives to Antidepressant Drugs (CBT and exercise and supplements)

Answer 31

• Cognitive-Behavioral Therapy
• Shown to be equally effective for all levels of depression
• Especially good for people who had some kind of childhood abuse or neglect.
• Causes increased metabolism in same brain areas as antidepressants
• More likely to reduce relapse months or years later – effects seemingly longer lasting.
On average, people receiving both treatments show more rapid improvement than people receiving either one alone, but the percentage of people showing improvement increases only slightly  If some people responded better to drugs and others to psychotherapy, we should expect the combination to help a much higher percentage of people, since they are exposed to both.

• Exercise has modest antidepressant benefits
• Best as a supplement to other treatments
• Increases bloodflow to brain and other benefits
• Supplements
• Omega-3 fatty acids and B vitamins
• Research has not been conclusive

Question 32

Alternatives to Antidepressant Drugs—Electroconvulsive Therapy (ECT)

Answer 32

• Electrically induced seizure used for the treatment of severe depression
• For patients who have not responded to antidepressant medication or psychotherapy
• Side effects include memory impairment
• Minimized when shock is only to right hemisphere
• Usually impairments don’t last long.
• High risk of relapse without continued treatment (even if given other therapies to prevent that – often people have to return some time after for more persistent effects)
• ECT applied every second days for two weeks.
• Mostly consensual, but sometimes court-ordered for people with high risk of suicide.
• How ECT relieves depression is unknown
• Proliferates neurons in the hippocampus
• Increases BDNF
• Those might be the key (but may not be related to therapeutic effects on the other hand)

Question 33

Altered Sleep Patterns in depression

Answer 33

• Disruption of sleep patterns is common in depression (and typically precede mood changes)
• Typically fall asleep but awaken early and are unable to get back to sleep
• Enter REM sleep sooner than normal (higher number of eye movements during rem) – pattern looks like person travelling, with circadian rhythms being screwed up.
• Sleep pattern disruption increases the likelihood of depression later on
• Periodic sleep deprivation sometimes helpful
• Most depressed people have phase-advanced patterns

light therapy: Researchers have now tested bright-light therapy for nonseasonal depression, with results at least as good as those for antidepressant drugs, with quicker benefits (usually within one week), lower cost, and much less risk of side effects

Question 34

Seasonal Affective Disorder

Answer 34

• Form of depression that regularly occurs during a particular season, such as winter
• Most prominent closer to the poles where nights are long in winter (and short in summer)
• Patients with SAD have phase-delayed sleep and temperature rhythms
• Most depressed people have phase-advanced patterns
• Treatment often uses very bright lights
• Used one hour or more daily
• Benefits are unexplained, but substantial
• Presumably this treatment works by resetting the circadian rhythm
• Many people with SAD have a mutation on a gene responsible for regulating circadian rhythms

Question 35

Deep Brain Stimulation (and optogenetic stimulation)

Answer 35

• Physician implants battery powered device into the brain to deliver periodic stimulation
• Targets brain areas that increase activity as a result of antidepressant drugs
• Still in experimental stage
• Encouraging results
• Alternative: optogenetic stimulation
• Can control individual connections rather than all the axons going from one area to another

Question 36

Unipolar VS Bipolar Disorder

Answer 36

• Unipolar disorder (“normal depression”)
• Characterized by alternating states of normality and depression
• Bipolar disorder (formerly manic-depressive disorder)
• Characterized by alternating states of depression and mania
• Mania: restless activity, excitement, laughter, self-confidence, rambling speech, and loss of inhibition

Question 37

Bipolar Disorder (types and characteristics)

Answer 37

• Bipolar disorder I: characterized by full blown episodes of mania
• Bipolar disorder II: characterized by much milder manic phases, called hypomania
• Onset is usually in teenage years or early 20s
• Brain’s use of glucose increases during periods of mania and decreases during periods of depression
Although it is about equally common for men and women, men are more likely to have severe (bipolar I) cases, but women are more likely to get treatment

Bipolar disorder has been linked to many genes, but apparently none of them are specific to bipolar disorder. The same genes also increase the risk of unipolar depression, schizophrenia, and other disorders

Question 38

Treatments for Bipolar Disorder

Answer 38

• First treatment—lithium: a salt that stabilizes mood and prevents relapse in mania or depression – unknown exactly how it works
• The mechanism of effect evidently has something to do with cells in the hippocampus. The hippocampus forms new neurons throughout life, and some of those that form in bipolar patients are hyperexcitable. Lithium relieves bipolar disorder only if it alleviates the hyperexcitability
• The dose must be regulated carefully, as a low dose is ineffective and a high dose is toxic.
• Drugs: (anticonvulsants) valproate (Depakote) and carbamazepine (if ineffective, can be supplemented with antidepressant drugs or antipsychotic drugs – Antidepressan drugs are risky, as they sometimes provoke a switch from depression to mania.)
• Drugs work by:
• Decreasing glutamate activity
• Blocking the synthesis of the brain chemical arachidonic acid, which is produced during brain inflammation
• Consistent sleep pattern and good diet (with omega 3 fatty acids) is also encouraged.

Question 39

Schizophrenia

Answer 39

• Deteriorating ability to function in everyday life for at least six months, paired with at least two of the following symptoms, including at least one of the first three:
1. Hallucinations, that is, false sensory beliefs, incl hearing voices (obs this is just one type of modality, but most common)
2. Delusions: unjustifiable beliefs (e.g. aliens controlling your actions)
3. Disorganized speech
4. Grossly disorganized behavior
5. Weak or absent signs of emotion, speech, and socialization
SCZ can be hard to diagnose – people with SCZ vary a lot – also e.g. “delusions” might be true, someone following you, etc.

• Half of 1 percent affected worldwide (lifetime prevalence)
• More common for men than women, but occurs in all ethnic groups in all parts of the world
• Often develops earlier, and is more severe, in men.
• Many mysteries remain:
• Link to colon cancer (higher), other cancers, rheumatoid arthritis, and allergies (lower chance) & certain autoimmune diseases (increased chance for these in SCZ)
• Characteristic body odor (trans-3-methyl-2-hexenoic acid) + decerased ability to smell the chemical.
• Women having schizophrenic breakdowns & male versus female children (breakdown during pregnancy = usually have female children, if they have it after pregnancy = usually have had male children)
• Deficits in pursuit eye movements (keeping eye on moving target)

Question 40

• Positive symptoms of SCZ

Answer 40

• Behaviors that are present that should be absent

* Examples: hallucinations, delusions, disorganized speech, and disorganized behavior

Question 41

• Negative symptoms of SCZ

Answer 41

• Absent behaviors that should be present (weak emotion, speech, and socialization)
• Usually stable over time and difficult to treat

Question 42

• Cognitive symptoms of SCZ

Answer 42

• Limitations of thought and reasoning common in schizophrenia
• Example: difficulty using and understanding abstract concepts (taking things too literally)
• Hypothesis: due to impairments in attention and working memory (people undergoing a task that is taxing on attention and working memory show similar impairments in incoherent speech as SCZ)

Question 43

Differential Diagnosis of SCZ

Answer 43

• A diagnosis that rules out other conditions with the same symptoms
Conditions that resemble schizophrenia
• Substance abuse
Abuse of amphetamine, methamphetamine,
cocaine, LSD, or phencyclidine (“angel dust”) can
produce hallucinations or delusions.

• Brain damage
Damage or tumors in the temporal or
prefrontal cortex can produce some of the symptoms of
schizophrenia.

• Undetected hearing deficits
Sometimes, someone who is
starting to have trouble hearing thinks that everyone else
is whispering and starts to worry, “They’re whispering
about me!” Delusions of persecution can develop.

• Huntington’s disease
The symptoms of Huntington’s
disease include hallucinations, delusions, and disordered
thinking, as well as motor symptoms.

• Nutritional abnormalities
Niacin deficiency can produce
hallucinations and delusions (Hoffer, 1973), and so can a deficiency of vitamin C or an allergy to milk proteins

Question 44

Genetics of SCZ (and environment)

Answer 44

• Research suggests a genetic component, but does not depend on a single gene
• The more closely you are biologically related to someone with schizophrenia, the greater your own probability of schizophrenia,
• Monozygotic twins have a much higher concordance rate (agreement) than dizygotic twins
• But monozygotic twins only have a 50 percent concordance rate (so not purely genetics, also some role of environment)
• Greater similarity between dizygotic twins than siblings suggest a prenatal/postnatal environmental effect (since both siblings and dizygotic twins would share 50% genetic material)
• Adopted children studies suggest a genetic role
• Prenatal environment of the biological mother cannot be discounted (there is chance of genetic factor, and/or prenatal environment (.g. drinking or smoking, poor diet, complicated pregnancy))
• Environmental influence, such as family environment shown to have a role

Efforts to Locate a Gene
• Many genes more common in individuals with schizophrenia
• Difficult to replicate results
• Large number of more common genes produce small effects
• (important for transmission of glutamate synapses, connections between hippocampus and PFC, brain development)
• One gene often linked to SCZ: DISC1 (disrupted in schizophrenia 1) gene controls rate of generation of new neurons (and dendritic spines) (in hippocampus)
• Possibly caused by new gene mutations or microdeletion of chromosomes
• the hypothesis is that a new mutation or deletion of any of hundreds of genes disrupts brain development and increases the probability of schizophrenia. As fast as natural selection weeds out those mutations or deletions, new ones arise to replace them.
• SCZ likely evolves from combination of genetics and environmental factors.

Question 45

The Neurodevelopmental Hypothesis of SCZ

Answer 45

• Abnormalities occur in prenatal or neonatal nervous system development
• Leaves the developing brain vulnerable to disturbances later in life (even if abnormalities themselves don’t cause SCZ, leaves brain vulnerable in critical periods)
• Result: mild abnormalities of brain anatomy and major abnormalities in behavior
• Evidence for the neurodevelopmental hypothesis
• Several kinds of prenatal or neonatal difficulties are linked to later schizophrenia
• People with schizophrenia have minor brain abnormalities that originate early in life
• Abnormalities of early development could impair behavior in adulthood

Question 46

Prenatal and Neonatal Environment risk factors for SCZ development

Answer 46

Low Risk Factors
• Prenatal environment
• Poor maternal nutrition
• Premature birth or low birth weight
• Complications during delivery
• Also elevated risk if mother experienced extreme stress early in pregnancy, or was ill during pregnancy
• These can all contribute to development of SCZ
• Head injuries in early childhood or acute infection in adolescence also linked to SCZ (but not so much known of causality)
• Mother Rh-negative and baby is Rh-positive (sometimes trigger immunological response (in mother I think), affecting hearing defects, cognitive difficulties, twice the probability of SCZ)
• Season-of-birth effect (people born in winter greater probability of SCZ – maybe due to viral infections (most probable) or nutrition patterns in winter)

Intermediate Risk Factors
living in a crowded city is a risk factor, presumably for environmental reasons. Another intermediate
risk factor is prenatal or childhood infection with the parasite Toxoplasma gondii.
• Childhood information/infections
• Toxoplasma gondii can infect humans, and lead to memory impairments and delusions and hallucinations (reproduces in cats – people with SCZ more likely to have had a pet cat during childhood)
• Conclusion
• Wide variety of genetic and environmental influences can cause schizophrenia

Question 47

Mild Brain Abnormalities in SCZ

Answer 47

• Most people with schizophrenia have:
• Less gray matter and white matter
• Grey matter reduced especially in the hippocampus, amygdala, and thalamus
• Larger than average ventricles
• Minor abnormalities in subcortical areas
• Smaller hippocampus
• Areas of increased metabolism, followed by atrophy
• Deficits of memory and attention consistent with damage to the prefrontal cortex
• Abnormalities visible in the blood vessels of the retina imply less than average blood flow to the brain
• brain volume is only about 5 percent smaller than average, and many people show little or no anatomical abnormality
• The brain areas with consistent signs of abnormality include some that mature slowly, such as the dorsolateral prefrontal cortex
• Lateralization differences in people with schizophrenia
• Right planum temporale slightly larger
• Lower than normal activity in left hemisphere
• More likely to be left-handed

Question 48

Early Development and Later Psychopathology in SCZ + Long-Term Course

Answer 48

• Most cases of schizophrenia are not diagnosed until age 20 or later, but neurodevelopmental hypothesis says most “causes” occur in early development.
• Problems often observed in childhood
• Impulse control, attention, and memory
• movement abnormalities during infancy
• These relatively minor problems developed into more serious problems later
• Dorsolateral prefrontal cortex one of the slowest brain areas to mature
• Area shows consistent signs of deficit in schizophrenia patients
• Less prominent signs in childhood (when area hasn’t fully matured) = more prominent signs later (when SCZ is often diagnosed later)

Long term course:
people diagnosed with schizophrenia vary in their outcome.
Up to one-fourth show a serious disorder
throughout life and possibly deteriorate, perhaps due to
poverty, lack of social support, drug abuse, and poor care.
Another group, perhaps 10 to 20 percent of all cases, recover
from a first episode and do well from then on. The others—
the majority—have one or more remissions and one or more
relapses.

In schizophrenia, some studies report that a few brain areas deteriorate
over age more than normally, bu most of the abnormality
of both brain and behavior is present at the time of first
diagnosis, with some further impairment in the next couple of years.
Further deterioration could also be from e.g. drug use rather than SCZ.

Question 49

Treatments for Schizophrenia - Antipsychotic Drugs and Dopamine

Answer 49

• Chlorpromazine (Thorazine)
• (first) Drug used to treat schizophrenia
• Relieves the positive symptoms of most patients
• Other Antipsychotic/neuroleptic drugs
• Category of drugs tend to relieve schizophrenia and similar conditions
• Work by blocking dopamine synapses
• Two chemical families of antipsychotic drugs used to treat schizophrenia
• Phenothiazines: includes chlorpromazine
• Butyrophenones: includes halperidol (Haldol)

Behavioral benefits of any of these drugs develop gradually over weeks. Symptoms may or may not return after cessation of treatment.

• Both drugs block dopamine synapses

2nd generation antipsychotics (incl clauzopine): can relieve symptoms, but do not produce movement disorders like haladol can. – strong effects on D4 and serotonin receptors.
- Better at relieving positive AND negative symptoms, but don’t improve quality of life more than any other antipsychotic drug.

Question 50

• Dopamine hypothesis of schizophrenia

Answer 50

• Schizophrenia results from excess activity at dopamine synapses in certain areas of the brain
• Evidence from drugs that alleviate symptoms by blocking dopamine synapses
• Substance-induced psychotic disorder
• Hallucinations and delusions resulting from repeated large doses of amphetamines, methamphetamines, or cocaine, or even LSD
• Each prolongs activity at dopamine synapses
•  further evidence of role of dopamine in SCZ
• Research indicates increased activity specifically at the D2 receptor
• Schizophrenics had twice as many D2 receptors occupied as normal
• But excess dopamine not SOLE cause of SCZ – medications need to build up to work for behavior, but work at synapses immediately. (discrepancy!)

Question 51

Mesolimbocortical System and SCZ (role of dopamine)

Answer 51

• Antipsychotics seem to work well because they block the dopamine synapses through the mesolimbocortical system. (coming from limbic system up to cortical system)
• The mesolimbocortical system
• Set of neurons that project from the midbrain tegmentum to the limbic system and prefrontal cortex
• Site where drugs that block dopamine synapses produce their benefits
• Drugs also block dopamine in the mesostriatal system
• Result is tardive dyskinesia, characterized by tremors and involuntary movements – caused by prolonged blockage of dopamine in basal ganglia

Question 52

The Role of Glutamate in SCZ

Answer 52

The dopamine hypothesis is, at best, incomplete, because about one-third of all patients fail to respond to the drugs that block dopamine
• The glutamate hypothesis: idea of deficient activity at glutamate synapses. (and decreased glutamate release in PFC)
• Problem relates partially to deficient activity at glutamate synapses, especially in the prefrontal cortex (and hippocampus)
• In many brain areas, dopamine inhibits glutamate release
• Alternately, glutamate stimulates neurons that inhibit dopamine release
• Increased dopamine thus produces the same effects as decreased glutamate
• SCZ often have fewer glutamate receptors
It may not just be one NT, but multiple NTs!

PCP:
• Further support for the glutamate hypothesis comes from the effects of phencyclidine (PCP; “angel dust”), a drug that inhibits the NMDA glutamate receptors
• At larger doses, it produces both positive and negative symptoms of schizophrenia (at low doses it produces e.g. slurred speech and intoxication). PCP is an interesting model for understanding schizophrenia:
• PCP (and ketamine) produce little psychotic response in preadolescents. The symptoms of schizophrenia usually emerge after puberty as do the psychotic effects of PCP.
• PCP produces a relapse for someone who has recovered from schizophrenia.
• Should we just inject glutamate? No, risk over overstimulation. Glyceine receptors instead maybe, but no drugs currently focused on increasing glutamate.
• But some experimental compounds, e.g. aminoacidglycene (not antipsychotic on its own, but increase effects of other antipsychotics)

Question 53

Autism Spectrum Disorders (ASD)

Answer 53

• Includes autism and what was called Asperger’s syndrome in the past – we just call it autism for simplicity.
• Includes people with varying degrees of difficulty (spectrum disorder)
• Ranges from relatively mild to severe
• Once rarely diagnosed
• More commonly diagnosed today
• Much more common (four times) in boys than in girls, but tends to be more severe in girls.

Autism Spectrum Disorder Characteristics
• Deficits in social and emotional exchange
• Deficits in nonverbal communication
• Examples: gestures, facial expressions
• Repetitive movements / other stereotyped behaviors
• Resistant to change in routine
• Unusually weak or strong responses to stimuli (e.g. indifference to pain, or panic reaction to sound)
• Infants with autism make a normal amount of eye contact at two months
• Eye contact declines over time

Most people with autism have additional problems, such as epilepsy, anxiety, poor coordination, or deficits in attention or sleep (Bourgeron, 2015). Many have abnormalities in the cerebellum, resulting in clumsiness and impaired voluntary eye movements (Fatemi et al., 2012). Some have autistic symptoms secondary to brain tumors or other serious medical disorders (Sztainberg & Zoghbi, 2016). All of these symptoms vary substantially from one person to another.

In addition to the deficits characteristic of autism, certain
strengths occur, too. Many develop narrow skills at
which they excel.

Question 54

Causes of ASD

Answer 54

• Genetics and other causes
• Many genes linked to autism, but no one gene is found in a high percentage of people with autism
• Dozens of very rare genes can cause autism, but combined the identified genes account for only about 5 percent of cases
• Many cases may result from mutations and microdeletions in one or more genes (incl topoamarase genes, for replication of DNA and RNA)
• Although the number of possible mutations relevant to autism is large, their effects converge onto just a few chemical pathways that affect the early development of the brain

Prenatal environment can also contribute to autism. The risk of autism increases if the mother is exposed during pregnancy to large amounts of pesticides, solvents, perfumes, or air pollutants. Prenatal environments often similar for pregnancies occurring close together in time  higher chance of getting second autistic child after short delay compared to longer delay.
• Some mothers of children with autism have antibodies that attack certain brain proteins
• Studies in monkeys have confirmed this is a contributing factor
• Identifying these antibodies might allow us to intervene pharmacologically to prevent ASD.
• Prenatal nutrition
• Adequate amounts of folic acid (vitamin B9) during pregnancy halves the risk of having an autistic child

Children with autism have brain abnormalities that vary
from one to another. A feature often noted is a large head. At
age one year, the mean head size for autistic children is 10 percent
greater than average. For the next several years, much
of the cerebral cortex is larger than average. Some connections
within the brain are stronger than average, whereas others
are weaker than average. By young adulthood, the brain
size is only about 1 percent greater than average
= brain development is abnormal, but unsure how it affects symptoms.

Question 55

Treatments for ASD

Answer 55

• No medical treatment for central problems of decreased social behavior and communication
• Risperidone sometimes reduces stereotyped behaviors
• Has serious side effects
- In rare cases autism is due to mutation of a gene whose effects could be reversed chemically – at least in theory.
• Behavioral treatments focus on attention and social aspects and reinforcing favorable behaviors
• Treatments for stereotyped behaviors include reinforcing other behaviors or competing behaviors.
• Not much research is available to evaluate the success of this approach (therapists and parents say it works, ASD people say it doesn’t)

huge number of fad treatments have arisen, including special diets, chelation, music, and therapeutic touch (can trick desperate parenst)