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.