Psychological Disorders

Substance Abuse and Addiction

• Most commonly abused drugs are derived from plants (e.g., nicotine in tobacco).
• Agonist: A drug that mimics or increases an effect.
• Antagonist: A drug that blocks a neurotransmitter (example: Narcan on opioid receptors).
• Drug's Affinity for a Receptor: Measure of drug's tendency to bind to it; ranges from strong to weak.
• Efficacy: Tendency to activate the receptor.
• A drug’s effectiveness and side effects vary from one person to another due to the abundance of each type of receptor varying between individuals.

Environmental Influences on Addiction

• Prenatal environment contributes to the risk for alcoholism later in life.
• Childhood environment is critical; careful parenting supervision decreases the likelihood of developing impulsive behavior that leads to abuse.
• Alcoholics who develop problems before age 25 tend to have a family history, genetic predisposition, and rapid onset of problems.
• Drinking alcohol increases GABA, which then blocks Glutamate.

Behavioral Predictors of Abuse

• Sons of alcoholics show less than average intoxication after drinking a moderate amount of alcohol.
  • Low level of intoxication may influence a person to keep drinking.
  • The probability of developing alcoholism is greater than 60% in sons of alcoholics.
• Alcohol decreases stress for most people, but more so for sons of alcoholics.

Synaptic Mechanisms of Drug Abuse

• Nearly all abused drugs affect several kinds of receptors.
• 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.

The Role of Dopamine

• Nucleus Accumbens: Central to reinforcing experiences of all types.
  • The location where addictive drugs release dopamine or norepinephrine.
• Other experiences that release dopamine in the Nucleus Accumbens (via activation):
  • Sexual excitement
  • Music
  • Taste of sugar
  • Imagining something pleasant
  • Habitual gambling and video game playing

Tolerance and Withdrawal

• Tolerance: Decrease in effect as an addiction develops.
  • Drug tolerance is learned, to a large extent.
• Withdrawal: Body’s reaction to the absence of the drug.
  • One hypothesis: Addictive behavior is an attempt to avoid withdrawal symptoms.

Treatments for Addiction

• Some addicts can decrease use or quit on their own.
• Alcoholics Anonymous (or similar group).
• Cognitive-behavioral therapy (CBT).
  • Contingency management includes rewards for remaining drug-free.
• Medication—not as common, but some options are available.

Medications for Alcohol Abuse

• Antabuse (Disulfiram):
  • Results in sickness after drinking, creating a learned aversion.
• Acamprosate (Campral®):
  • Helps rebalance chemicals in the brain that may be changed by drinking too much.
• Opioid receptor antagonist Naltrexone (Narcan):
  • Reduces alcoholism by blocking opioid receptors and prevents opioids from activating these receptors.

Narcan and Opioid Overdose

• Naloxone and naltrexone (Narcan) rapidly block an opioid overdose by blocking opiate receptors (via Cranial Nerve 10), helping the individual to breathe.
• Drug effectiveness varies with the user’s motivation to quit.

Medications for Opiate Abuse

• Methadone:
  • A safer alternative used to treat Opioid Use Disorder (OUD).
  • Activates the same brain receptors as heroin and morphine, producing the same effects.
  • Can be taken orally, absorbs slowly, and leaves the brain slowly.
  • "Rush" and withdrawal are both reduced.
• Buprenorphine and LAAM:
  • Similar to methadone.

Major Depressive Disorder

• Absence of happiness is a more reliable symptom than increased sadness.
• More common in women during the reproductive era (e.g., postpartum depression).
• More common to have periodic episodes of depression.
• Possible cause: Decreased levels of the neurotransmitter Serotonin (5-HT).

Genetics of Depression

• Hypothesis: The effect of a gene varies with the environment to develop depression in the individual.
• Evidence: Young adults with the short form of the serotonin transporter gene who experienced stressful experiences had a major increase in the probability of developing depression.

Brain Activity and Depression

• Brain activity associated with depression:
  • Decreased activity in the left prefrontal cortex.
  • Increased activity in the right prefrontal cortex.
• People with depression tend to gaze to the left when asked to do a verbal task; most people gaze to the right.

Antidepressant Drug Categories

• Many drugs used to treat psychiatric disorders were discovered by accident.
  • Example #1: Imipramine tricyclic was used to treat tuberculosis, then for depression.
  • Example #2: Chlorpromazine decreases psychosis and was thought to be an antihistamine.
• Categories of antidepressant drugs:
  • Monoamine oxidase inhibitors (MAOIs)
  • Selective serotonin reuptake inhibitors (SSRIs)
  • Selective serotonin norepinephrine reuptake inhibitors (SSNRIs)
  • Atypical antidepressants

Antidepressant Drugs—SSRIs

• Selective serotonin reuptake inhibitors (SSRIs):
  • Elevate levels of Serotonin by blocking the reuptake of the neurotransmitter serotonin.
  • Examples: fluoxetine (Prozac), sertraline (Zoloft), fluvoxamine (Luvox), citalopram (Celexa), paroxetine (Paxil).

Antidepressant Drugs – SNRIs

• Serotonin norepinephrine reuptake inhibitors (SNRIs):
  • Examples: duloxetine (Cymbalta) and venlafaxine (Effexor).
  • Block reuptake of serotonin and norepinephrine.
• Improve certain aspects of memory and have few side effects, hence popular versus Tricyclic Antidepressants.

Antidepressant Drugs – NDRIs

• Norepinephrine Dopamine reuptake inhibitors (NDRIs):
  • Examples: Bupropion (Wellbutrin, Zyban, Aplenzin).
  • Block reuptake of norepinephrine and dopamine.
• Primarily used to treat depression.
• Considered to be an atypical antidepressant but often prescribed by primary care doctors.

Antidepressant Drugs – MAOIs

• Monoamine oxidase inhibitors (MAOIs):
  • Block the enzyme monoamine oxidase that metabolizes catecholamines and serotonin into inactive forms.
  • Results in more transmitters in the presynaptic terminal available for release.
• Usually only prescribed if SSRIs and tricyclics are not effective due to many side effects.
  • High blood pressure results with some food.

Antidepressant Drugs—St. John’s Wort

• Herb sometimes used as self-treatment for depression.
• Nutritional supplement not regulated by the FDA.
• Effectiveness about the same as standard antidepressants; however, does not do well with other medications.
• Increases the production of a liver enzyme that decreases the effectiveness of other medications.

How Antidepressants Are Effective - BDNF

• People with depression have lower than average brain-derived neurotrophic factor (BDNF), which is important for synaptic plasticity.
• As a result, people with depression show:
  • Smaller than average hippocampus
  • Impaired learning
  • Reduced production of hippocampal neurons
• Prolonged use of antidepressants increases BDNF production.

Alternatives to Antidepressant Drugs

• Cognitive-Behavioral Therapy
  • Shown to be equally effective for all levels of depression.
  • Causes increased metabolism in the same brain areas as antidepressants.
  • More likely to reduce relapse months or years later.
• Exercise
  • Has modest antidepressant benefits.
  • Best as a supplement to other treatments.
• Supplements
  • Omega-3 fatty acids and B vitamins.
  • Research has not been conclusive.

Alternatives to Antidepressant Drugs—Electroconvulsive Therapy (ECT)

• Electrically induced seizure used for the treatment of severe depression.
  • For patients who have not responded to antidepressant medication.
  • Side effects include memory impairment.
  • Minimized when the shock is only to the right hemisphere.
  • High risk of relapse without continued treatment.
• How ECT relieves depression is unknown.
  • Proliferates neurons in the hippocampus.
  • Increases BDNF.

Alternatives to Antidepressant Drugs—Transcranial Magnetic Stimulation (TMS)

• A non-invasive procedure.
• An alternative to ECT treatment.
• Transcranial magnetic stimulation (TMS) uses magnetic fields to stimulate nerve cells in the brain to improve symptoms of major depression; neurons are temporarily turned off in the process.

Seasonal Affective Disorder (SAD)

• A subtype of Major Depression (and Bipolar Depression) that regularly occurs during a particular season, such as winter.
  • Most prominent closer to the poles.
• Patients with SAD have phase-delayed sleep and temperature rhythms; primarily a winter disorder.
• Treatment often uses very bright lights.
  • Used one hour or more daily.
  • Benefits are unexplained, but substantial.
  • Melatonin treatment.
  • Antidepressant treatments.
• Many people with SAD have a mutation on a gene:
  • The family gene mutation is of gene PER3 responsible for regulating circadian rhythms.
• Often treated with Cognitive-Behavioral Therapy and/or antidepressants, encouraged to be social.

Schizophrenia

• 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:
  • Hallucinations (hearing voices)
  • Delusions (unjustifiable beliefs)
  • Disorganized speech
  • Grossly disorganized behavior
  • Weak or absent signs of emotion, speech, and socialization

Diagnosis of Schizophrenia

• Positive Symptoms (they add):
  • Behaviors that are present that should be absent.
  • Examples: hallucinations, delusions, disorganized speech, and disorganized behavior.
• Negative Symptoms (they take away):
  • Absent behaviors that should be present (weak emotion, blunting of affect and thought, apathy, poor socialization).
  • Refers to an absence or lack of normal mental function involving thinking, behavior, and perception.
  • Usually stable over time and difficult to treat.
• Cognitive Symptoms:
  • Hypothesis: Due to impairments in attention and working memory.
  • Limitations of thought and reasoning common in schizophrenia.
  • Example: difficulty using and understanding abstract concepts.

Genetics of Schizophrenia

• DISC1 (Disrupted In Schizophrenia 1) Gene:
  • Controls the rate of generation of new neurons.
  • Responsible for proliferation during embryonic and adult neurogenesis, thought to be disrupted in Schizophrenia.
• Possibly caused by new gene mutations or microdeletion of chromosomes.

Prenatal and Neonatal Environment and Schizophrenia

• Season-of-birth effect:
  • Tendency for people born in winter to have a slightly (5–8%) greater probability of developing schizophrenia.
  • More pronounced in latitudes far from the equator.
  • Possible explanation: increased likelihood of viral infection in the mother (e.g., flu virus).
• Result of viral infections in the mother:
  • Increased cytokines in the mother that impairs brain development of the fetus.
  • Fever that slows divisions of fetal neurons.
• Conclusion: A wide variety of genetic and environmental influences can cause schizophrenia.

Mild Brain Abnormalities in Schizophrenia

• Most people with schizophrenia have:
  • Less gray matter and white matter.
  • Larger than average ventricles.
  • Minor abnormalities in subcortical areas.
  • Smaller hippocampus.
  • Deficits of memory and attention consistent with damage to the prefrontal cortex.
• Lateralization differences in people with schizophrenia:
  • The Right Planum Temporale is slightly larger.
    *Planum Temporale = referred to/close to Wernicke's area, is involved in auditory processing and receptive language.
  • Lower than normal activity in left hemisphere.
  • More likely to be left-handed.

Long-Term Course of Schizophrenia

• Schizophrenia was previously thought to be a progressive disorder.
• New studies show varied outcomes of people diagnosed with schizophrenia due to:
  • Poverty, social support, drug abuse, and other factors can influence the outcome.

Antipsychotic Drugs and Dopamine

• Research indicates increased activity specifically at the D2 receptor.
  • Schizophrenics had twice as many D2 receptors occupied as normal.

Early Development and Later Psychopathology

• Most cases of schizophrenia are not diagnosed until age 20 or later.
  • Problems often observed in childhood, though not diagnosed until approximately 12+ yrs/teen.
    *Data is limited.
  • Impulse control, attention, and memory.
• Dorsolateral prefrontal cortex one of the slowest brain areas to mature.
  • This area shows consistent signs of deficit in schizophrenia patients.

Treatments for Schizophrenia

• Antipsychotic/neuroleptic drugs: Category of drugs that tend to relieve schizophrenia and similar conditions.
  • Example: Chlorpromazine (Thorazine).
  • Drug used to treat schizophrenia.
  • Relieves the positive symptoms of most patients.
    *inhibits dopamine at the postsynaptic D2 receptors.

Antipsychotic Drugs and Dopamine Hypothesis

• Dopamine Hypothesis of schizophrenia:
  • Schizophrenia results from excess activity at dopamine synapses in certain areas of the brain.
• Substance-induced psychotic disorder:
  • Hallucinations and delusions resulting from repeated large doses of amphetamines, methamphetamines, or cocaine.
    *Each prolongs activity at dopamine synapses.

The Role of Glutamate in Schizophrenia

• The Glutamate Hypothesis:
  • The problem relates partially to deficient activity at glutamate synapses, especially in the prefrontal cortex.
  • 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. The relationship works both ways.