Psychological Disorders

Drug Mechanisms

Antagonist – drug that blocks a neurotransmitter (inhibits), decreases activity at a synapse (low affinity, low efficacy)

Agonist – drug that increases effects (facilitates), increases activity at a synapse (high affinity, high efficacy)

Mixed agonist-antagonist – agonist for some effects or doses and antagonist for others

Affinity – tendency of a drug to bind to a receptor (varies from strong to weak)

Efficacy – drug’s tendency to activate/ stimulate the receptor

Genetic Influences

Parental alcohol use correlates with that of biological (stronger) and adopted children

Unstable environment – increased if having a gene affecting serotonin synapses

(influences predisposition of abuse):

Ethyl alcohol -> acetaldehyde (toxic) -> + enzyme acetaldehyde dehydrogenase = acetic acid (used for energy)

Environmental Influences

Prenatal environment : Pregnant drinking alcohol = child likely to develop alcoholism, same in rats

Careful parental supervision – child less likely to have impulse problems, even if have genes or antisocial behavior

People with early-onset alcoholism – usually family history of alcoholism, genetic predisposition, rapid onset of the problem

Late onset – life difficulties, usually no history of alcoholism in family, respond better to treatment

Synaptic Mechanisms

Drugs affect synapses differently at diff. stages – when its in the brain, during withdrawal and effects responsible for cravings

The Role of Dopamine

Cocaine, amphetamine, sexual excitement – increase or prolong the release of dopamine in nucleus accumbens

Alcohol, marijuana, nicotine – non-stimulants increase dopamine release but not much. The amount of produced dopamine doesn’t correlate with pleasure or probability of addiction.

Cravings - insistent search for the activity/ substance. Even after a long period of abstinence cues can trigger a craving

Tolerance – decrease in effect of the drug; its learned and can be weakened through extinction procedures

Withdrawal – body’s reaction to the absence of drugs. Addictive behavior might be a way to avoid withdrawal symptoms or to cope with stress.

Medications to combat alcohol use

· Antabuse (disulfiram) – antagonizes the enzyme that metabolizes acetaldehyde = sickness after drinking; nausea-inducing drug to associate the two-learned aversion.

· Naloxone and naltrexone – block opiate receptors and decrease pleasure from alcohol

Methadone – similar to heroin and morphine, activates the same brain receptors and produces the same effects; it can be taken orally and it gradually enters the blood and brain avoiding the ‘rush’ which disrupts behavior

Buprenorphine and levomethadyl acetate (LAAM) – long-lasting effects so people don’t have to go to the clinic daily but 3 times a week. People using them live longer and healthier that heroin/morphine users and can hold a job.

Major Depressive Disorder

– extremely low mood for weeks, .

– nucleus accumbens less responsive to reward

– Feelings of worthlessness, sadness, suicidal thoughts, trouble sleeping. Low motivation, problems with attention, memory and impaired sense of smell

– Depression more common in women during reproductive era

– Report less number of pleasant experiences, reacted normally to sad/ frightening images but rarely smiled at comedies/ pleasant pictures

Genetics

Twin studies & adopted children show moderate heritability for depression

Increased activity of immune system: arise from injury, stressful experience, poor diet, etc

Different genes for depression found – different genetic variations in diff populations

Depression could be an evolutionary adaptation – conserving energy after defeat of some sort or valid purpose for ancestors after physical injury

Early onset depression (before 30 yo):

· likely to have relatives with depression, anxiety disorders, neuroticism, attention-deficit disorder, alcohol or marijuana abuse, obsessive-compulsive disorder, bulimia, migraine and irritable bowel syndrome.

· More severe, long-lasting and more associated with suicidal tendencies

Late onset depression (especially after 45-50) – likely to have relatives with circulatory problems

Two long alleles= stressful events slightly increased risk.

One short one long gene = intermediate risk.

Simply inheriting the gene was not enough to lead to depression, but the genes' interaction with stressful life events increased one's likelihood of developing depression.

Serotonin transporter gene – a protein that regulates the ability of axons to reabsorb serotonin after its release;

Abnormalities of Hemispheric Dominance

People without depression – happy mood = increased activity in the left prefrontal cortex

Depressed people – higher activity in the right prefrontal cortex; the imbalance is stable over years despite changes in symptoms of depression (probably a predisposition not a reaction)

Antidepressant Drugs

Iproniazid – first antidepressant drug, it was firstly used to treat tuberculosis then they found out it works for depression

Chlorpromazine – used for different purposes then noticed to treat schizophrenia

Types of antidepressants

Tricyclics – block the transporter protein that reabsorb serotonin, dopamine and norepinephrine into the presynaptic neuron.

Tricyclics also block histamine and acetylcholine receptors, and certain sodium channels

Blocking histamine = drowsiness blocking acetylcholine = dry mouth,

trouble urinating

Serotonin reuptake into presynaptic neuron – serotonin transporter protein open to the outside of the neuron. Then it picks the molecule and flips position to the inside (tricyclics and SSRI lock the protein in position on the left):

SSRI – selective serotonin reuptake inhibitors; similar to tricyclics but specific to neurotransmitter serotonin.

1. Fluoxetine (Prozac)

2. Sertraline (Zoloft)

3. Fluvoxamine (Luvox)

4. Citalopram (Celexa)

5. Paroxetine (Paxil/ Seroxat)

SNRI – serotonin norepinephrine reuptake inhibitors; block serotonin and norepinephrine reuptake. Improve memory, many patients take two or more drugs with different mode of action

1. Duloxetine (Cymbalta)

2. Venlafaxine (Effexor)

MAOIs – monoamine oxidase inhibitors; they block the enzyme monoamine oxidase.

(MAO): presynaptic enzyme that metabolizes catecholamines (dopamine, norepinephrine) and serotonin into inactive chemicals .

How are antidepressants effective?

Drugs affect neurotransmitters in synapses quickly (minutes to hours).

People with depression have lower brain-derived neurotrophic factor (BDNF) - important for synaptic plasticity.

People with depression show:

Smaller hippocampus, impaired learning, reduced production of hippocampal neurons

Prolonged use of antidepressants increases BDNF production.

Cognitive-behavioral therapy – equal effects for all levels of depression; increased metabolism in the same brain areas as antidepressants; reduces relapse into depression which is more likely after antidepressants.

Electroconvulsive Therapy (ECT) - electrically induced seizure used for treatment of severe depression.

Dissociative identity disorder – multiple personality disorder.

Schizophrenia – emotional expression unconnected with current experiences; deterioration in everyday functioning for at least 6 months, delusions (illogical beliefs), hallucinations (false sensory experience), disorganized speech (rambling / incoherent), grossly disorganized behavior, weak emotional expression, speech and socialization.

Positive symptoms – behaviors that are present that should be absent: delusions, hallucinations, disorganized speech and behavior

Negative symptoms – behaviors that are absent that should be present f. ex. Weak emotional expression, speech, socialization; stable over time and difficult to treat.

Causes of schizophrenia:Genetics, Prenatal and Neonatal Environment,Mild Brain Abnormalities.

Microdeletion – deletion of a small part of a chromosome, more common among ppl with schizophrenia

For adopted children the disorder is more common in biological relatives than the adopting ones.

prenatal influence – women with schizophrenia often abuse drugs, alcohol, eat a poor diet and have complications during pregnancy and delivery.

environmental influences – higher probability for schizophrenia if a mother has the disease and the child is in a dysfunctional adopting family.

Prenatal or neonatal influences – genetic, environmental or both – produce abnormalities in the developing brain; vulnerability to disturbances at critical periods in childhood and adolescence such.