Biopsychology of Psychiatric Disorders

63 important questions on Biopsychology of Psychiatric Disorders

What are positive symptoms and negative symptoms in schizophrenie?

Positive symptoms are symptoms that represent or excess normal function, they come new.  Example: hallucinations, odd behavior, weird speech.
Negative are loss of normal functions. Example: reduction of speech, motivation, pleasure.

What are the 4 positive and 4 negative symptoms of schizophrenia?

Positive: 
- Delusions
- Hallucinations
- Incoherent speech or thought
- Odd behavior

Negative:
- Affective flattening, loss of emotion
- Reduction of speech
- Reduction of motivation
- Reduction of experiencing pleasure

What was the first anti-schizophrenic drug to be discovered in the 1950s? What was its original purpose?

Chlorpromazine; it reduces agitation and activates emotionally blunt schizophrenics. Its original purpose was to be an antihistamin.
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Although reserpine and chlorpromazine are different drugs, they have two major similar characteristics. What are these?

1. Both drugs are only effective after 2-3 weeks.
2. Both drugs eventually produce Parkinson-like motor effects.

What is the dopamine theory of Schizophrenia?

It describes the link between Parkinson and Schizophrenia - it was discovered that a deficiency in dopamine was a cause of Parkinson, and they know the antipsychotics produces Parkinson effect but decreased symptoms of Schizophrenia - thus the Dopmine theory was born; too much dopamine in schizophrenia?

What are three support pieces for the Dopamine Theory of Schizophrenia?

1. Resperpine depletes the brain of dopamine and other monoamines by making vessels leaky.
2. L-Dopa reversed the hyopactivity after reserpine.
3. Amphetamine and cocaine are dopamine agonists; produce schizophrenic episodes in healthy subjects.

Chlorproazmine works in a different way than reserpine. How does chlorprozamine work? 

Rather than depleting the brain of dopamine, it blocks the dopamine receptors by binding to it.

Haloperidol is a dopamine antagonist and helps in schizophrenia. However, it has a low affinity for receptor binding to Dopamine. How can it work?

There are more than 1 type of dopamine receptor. So far 5 have been identified.

To what sort of receptors bind the two different kinds of drugs?

Phenothiazines: bind to D1 and D2 (chlorprozamine)
Butyrophenones: bind to D2 (haloperidol)

What was the revision of the dopamine theory of schizophrenia?

Hyperactivity specifically at the D2 receptors causes schizophrenia.

What are the definitions for Depression and Mania?

Depression: affedctive disorder characterized by disturbances of mood or emotion.

Mania: characterized by overconfidence, impulsivity, distractibility and high impulsivuty.

There is reactive depression, which is a reaction on a certain event in ones life. What is the other sort of depression?

Endogenous, it has no particular cause.

What are causal factors in affective disorders? (depression/mania - mood disorders)

1. Genetics; higher for bipolar than for unipolar.
2. Stressful experiences.
3. Seasonal affective disorders; winterdepression, more common in northern contries and light-therapy helps.

Stressful experiences, do they commonly create depression?

No, according to Pinel, the evidence is scarse. They rather cause post-traumatic stress disorder.

There are 4 major classes of antidepressant drugs on the market. What four classes are these?

1. Monoamine oxidase inhibitors
2. Tricyclic antidepressants
3. Selective monoanime-reuptake inhibitors
4. Mood stabilizers

How does monoamine oxidase inhibitor help in depression and what is it callled?

Iproniazid inhibits the activity of monoamine oxidase (MAO). 
MAO breaks down monoamine neurotransmitter in the cytoplasm.
If it is inhibited, monoamine can not be broken down and remains longer in the synaps.

What is the dangerous side effect of Ipronazoid?

Tyramine, an amine which is present in cheese, is a blood elevator and is also broken down bij MAO. If this cannot be broken down, such foods must be avoided because the blood pressure can become to high.

Name an antidepressivum that works as a tricyclic antidepressant and explain how it works.

Imipramine. Anticyclic depressants block the reuptake of serotonin and noradrenaline, thereby increasing their levels in the brain. Safer dan MAO.

How do SSRIs work?

SSRIs (selective monoamine reuptake inhibitors) are serotonin agonists - they block the reuptake of serotonin from the synaps.

Why are SSRIs so immensely popular?

SSRIs, like Prozac, Paxil, Zoloft, have very few side effects.
Also, they are effective at treating other diseases.

What is the most common mood stabilizer?

Lithium, a mood stabilizer for bipolar disorder.

How strong is the placebo effect in antidepressants?

Strong, a study in 2008 showed that the placebo was as 82% effective as the anti-depressants in severely depressed individuals.

In what way do affective disorders influence brain damage?

The most consistent evidence is for the amygdala and the cingulate cortex, both of which shrink in depressive patients.

What are the two theories of depression that prominent today?

1. Monoamine Theory of Depression
2 Diathesis Stress Model of Depression.

Explain the Monoamine theory of Depression and its problem.

This theory proposes that depression is associated with underactivity at serotonergic and noradrenergic receptors. Evidence comes from the antidepressants that act on these receptors and that upregulation will occur if depression is untreated (proliferation of monoamine receptors).
The problem is that not everyone responds to MAOs.

Explain the Diathesis-Stress Model of Depression.

It suggests that diathesis (genetic susceptibility) alone is not sufficient to create depression. If stress is added, depression will occur.

Evidence is indirect. Depressed people tend to release more stresshormones, but stories of early abuse etc. is subjective.

Explain the 5 classes of anxiety disorders.

- Generalized anxiety disorders; absence of causal stimulus
- Phobic anxiety disorder; triggered by a specific stimulus (spiders)
- Panis disorders; attacks of extreme fear and stress
- OCD - obsessive thoughts alleviated by compulsive actions
- PTD - pattern of psychological distress following extreme stress

What are two main causes for Anxiety Disorders?

1. Genetic contribution is good evidence for.
2. Life experiences

What aare three categories of drugs commonly used to treat anxiety disorders? How do they work?

1. Benzodiapezines (valium); agonistic reaction via GABAa receptors; also to induce sleep and muscle relaxation.
2. Serotonin agonists; buspirone; specific, reduce anxiety without sedation.
3. Antidepressants; effective because depression and anxiety go toghether often. (comorbid)

What is assumed in anxiety models in animals?

Defensive behavior is triggered by fear and is comparable with anxiety (elevated plus maze test).

Which brain structure is thought to be involved?

The amygdala, althought there is no structural pathology yet identified. There is evidence for over-activity in the amygdala of patients with a phobia when they view that specific object.

How does the drug testing procedure go?

1. Basic research; animals, animal lines.
2. Human clinical trials. 
phase 1; healthy volunteers
phase 2; patients, placebo-control, double blind
phase 3; placebo-control, double-blind, many patients.
3. SELLING TO THE PUBLIC.

What are 2 controversies involved in the development of new Psychotherapeutic drugs?

1. Controversial aspects of the trials. (placebo-need, active placebo's, length)
2. Financial issues. (conflict of interest, orphan drug problem, translational bottleneck).

What are 6 DSM-IV criteria of substance dependence? (also known as drugssss mkaay)

- Tolerance develops
- Dose increases
- Withdrawal symptoms
- Failure cutting down
- Obsessive with substance
- Interference normal life
- Continue despite negative consequences

Is drug abuse an addiction or a dependence?

Dependence is the chosen word, but that decision was a serious mistake. Addiction conveys the appropiate meaning of compulsive drug-taking. Dependence is a more neutral term that could apply to all drugs.

What are three reward mechanisms on which substances exert their effects in the brain?

- endogenous opioids
- endocannabinoids (EC1)
- dopamine mesolimbic DA system

How do addictive drugs work in relation to dopamine?

They release dopamine in the Nucleus Accumbens.

Drugs/substances work on two pathways. What are these?

1. Nigrostriatal pathways; motor control.
2. Mesolimbic pathways; reward system

Hoe lopen de mesocorticolimbische en de nigrostriatale pathways?

1. Mesocorticolimbisch: Projecteren vanuit de ventral tegmental area naar verschillende structuren die onderdeel zijn van limbisch systeem (amygdala, nucleus accumbens, olfactory, septum)

2. Nigrostriatal; Projecteren vanuit de substantia nigra naar het dorsale striatum.

What does mice studies conclude?

Nicotine increases the release of Dopamine.

What is the effect of THC on dopamine release?

THC increases dopamine release.

Do amphetamine and cocaine increase DA release?

Yes. I do cocaaaaaine! 

What are two key methods for measuring drug-produced reinforcement in animals?

1. Drug self-administration through cannulas to the bloodstream; rat likey.

2. Conditioned place-preference; if drug are administered they like to spend more time in that specific compartment; rat likey.


If we look at alcohol and addiction, there are two stages divided in two sorts of use. What are these?

Impulsive stage: Use and Heavy Use

Compulsive stage: Early dependence, late dependence (neuro-adapted state)

What is tolerance for a drug?

Increasingly large doses of drugs must be taken to achieve a particular effect. Drugs can also be sensitized.

How does drug tolerance work as a mechanism?

- Less drug is getting to the site of action.
- Decreased response at the site of action, fewer receptors, less binding, receptors are less responsive.

What does environment have to do with drug tolerance?

In the environment where the drug is usually taken, the maximal tolerance effects are the highest. Most tolerance.

What are conditioned compensatory responses?

a conditional response that opposes, rather than being the same as, the unconditional response. It functions to reduce the strength of the unconditional response, as in drug tolerance

What happens in drug tolerance and how do withdrawal effects occur?

1. Tolerance: Person takes addictive drug. Shows effects of tolerance. Must increase dose to get the same effect.

2. Person stops taking drugs. Withdrawal effects, opposite to the primary effects of drug occur.

What is the cause of drug tolerance?

Not the drug itself (see rat treadmill experient). 
Not the history of a drug (see rat centrifuge treadmill).

Tolerance occurs because we make conditionary compensatory responses in anticipation of getting a drug, these responses counter the durf effect, thus tolerance increases.

What are the withdrawal drug effects of alcohol, amphetamine and heroin?

Alcohol: Increased activity.
Amphetamine: Decreased activity, depression.
Heroin: Intense pain.

In overall withdrawal effects, the body can only function normally with the drug.

What are other characterisitcs of drug tolerance and conditioning?

1. Overdose occurs more often in unfamiliar surroundings.
2. Conditioning can be exteroceptive (external stimuli) or interoceptive (internal stimuli in the body self).

Give a simple neural model for instrumental conditioning.

1. Stimulus is shown.
2. Neural circuit detects particular stimulus. Perceptual system.
3. Neural circuit that controls particular behavior; motor system, reacts.
4. Behavior is shown.
5. Stimulus is reinforced, reinforcement system strengthens the connection between perceptual and motor system.

Which two neural circuits are involved in reinforcement?

1. Ventral Tegmental Area; group of neurons in midbrain whose axons from mesolimbic and mesocortical systems are important in reinforcement.

2. Nucleus Accumbens; nucleus of basal forebrain near septum that receives dopamine from neurons of VTA and is perhaps involved in reinforcement and attention.

Which brain structure is involved in conditioning of drug related stimuli?

Amygdala.

What is the difference between the a-process and the b-process when looking to the amount of time when a drug is used on a hedonic scale?

1. In the a-process there is a release of dopamine, primary effect is intense and hedonic value is high.

2. In the b-process, there is a intensity of after-reaction, hedonic value is low and CRF is released. CRF is involved in mood changes and subsequent addiction.

After a while, if a drug if frequently used, it is more used to reduce the .... effects than to exert the hedonic value.

Affective after reaction, hedonic value gets really low then.

Name two things that can influence drug dependence.

1. Isolation.
2. Non-dominant position (rats).

Cocaine, Amphetamine and Ecstasy are three drugs that work on DA-receptors. How do they work?

1. Cocaine: binds with and deactivated dopamine transporter proteins. Dopamine reuptake is blocked. DOPAMINE AGONIST.

2. Amphetamine: inhibits reuptake of dopamine, stimulate the release of dopamine from terminal buttons.

3. Ecstasy: serotonin releaser, acts on serotonin reuptake transporter.

How does nicotine work on the brain?

1. Stimulates nicotinic acetylcholine receptors.
2. Increases activity of dopaminergic neurons of the mesolimbic system, therefore dopamine is released in NAC.

What happens in drug use if MCH receptors are blocked?

Decreased effectiveness of cocaine-cues and alcohol intake in animal behavior. MCH are found in for example NAC on neurons that also contain DA receptors. So blocking this decreases intake!

What is the role of orexin in drug addiction?

Orexinergic neurons are activated if a subject is presented with an addictive drug or associated stimuli.
If orexin is injected in VTA, drug seeking is reinstated if previously extinguished.

What is the current view of brain structures that mediate addiction?

1. Prefrontral lobes, amygdala and mesocorticolimbic pathway; initial drug taking.

2. Craving and compulsive drug use: Dorsal striatum and hypothalamic stress circuits.

3. Relapse: prefrontal cortex, amygdala, hypothalamic stress circuits.

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