Mental illness

• Drug


  Carried to the blood vessels of the central nervous system
• Blood-brain barrier

  • Protective filter that makes it difficult for many potentially dangerous bloodborne chemicals to pass from blood vessels of the CNS into the space CNS neurons and glia
• Mechanism of psychoactive drugs

  1. Act diffusely on neural membranes through the CNS

  2. Bind to particular synaptic receptors, influencing the synthesis, transport, deactivation of particular neurotransmitters

  3. Influence the chain of chemical reactions elicited in postsynaptic neurons by the activation of their receptors
• Metabolism and elimination of drugs

  1. Terminated by enzymes synthesized by liver

  2. Liver enzymes stimulate the conversion of active drugs to nonactive forms
• Tolerance


  • Cross tolerance - one drug can produce tolerance to other drugs that act by the same mechanism
  • Drug tolerance often develops to some effects of a drug but not to others
  • Drug sensitization - increasing sensitivity to a drug
  • Metabolic tolerance - results from changes that reduce the amount of the drug getting to its sites of action
  • Functional tolerance - result from changes that reduce the reactivity of the sites of action to the drug
• Withdrawal syndrome


  • Sudden elimination can trigger an adverse physiological reaction
  • The effects of drug withdrawal are virtually always opposite to the initial effects of the drug
  • Produced by elimination of the drug from the body
• Contingent drug tolerance


  Tolerance develops only to drug effects that are actually experienced
• Conditioned drug tolerance


  • Tolerance effects are maximally expressed only when a drug is administered in the same situation in which it has previously been administered
  • Conditioned compensatory responses increasingly counteract the unconditional effects of the drug and produce situationally specific tolerance
• Exteroceptive stimuli


  Conditional stimuli that are public, external
• Interoceptive stimuli


  Conditional stimuli that are internal, private
• Drug sensitization

  • Tolerance develops to many drug effects, sometimes the opposite occurs
  • Can be situationally specific
  • Elicited by drug-predictive cues in the absence of the drug
• Physical-dependence perspective of addiction

  Physical dependence traps addicted individuals in a vicious circle of drug taking and withdrawal symptoms
• Positive-incentive perspective of addiction


  The primary factor in most cases of addiction is the craving for the positive effects of the drug
• Intracranial self-stimulation (ICSS)


  • Rats, humans, and many other species will administer brief bursts of weak electrical stimulation to specific sites in their own brains
  • Pleasure centers - brain sites capable of mediating the phenomenon
• Mesotelencephalic dopamine system

  • Important role in intracranial self-stimulation
  • System of dopaminergic neurons that projects from the mesencephalon-midbrain into various regions of the telencephalon
  • Neurons that compose the midbrain dopamine system have cell bodies in the substantia nigra and the ventral tegmental area
  • Mesocorticolimbic pathway - component of the mesotelencephalic dopamine system
• Nucleus accumbens and dopamine

  • Critical to experience of reward and pleasure
  • Self-administer addictive drugs to nucleus accumbens
  • Lead to conditioned place-preferences
  • Reinforcers release dopamine in nucleus accumbens
• Drug self-administration paradigm

  Nonhuman animals press a lever to inject drugs into themselves through implanted cannulas
• Conditioned place-preference paradigm


  Nonhuman animals repeatedly receive a drug in one compartment of a two-compartment box
• Experiments showed that dopamine played an important role in the rewarding effects of addictive drugs and natural reinforcers
• Schizophrenia


  • Means "the splitting of psychic functions"
  • Severe psychiatric disorder
• Positive symptoms of schizophrenia


  • Delusions
  • Hallucinations
  • Inappropriate affect
  • Disorganized speech or thought
  • Odd behavior
• Negative symptoms of schizophrenia

  • Affective flattening - diminished emotional expression
  • Avolition - reduction or absence of motivation
  • Catatonia - Remaining motionless, often in awkward positions for long periods
• Genetics, family studies, and adopted children in schizophrenia

  • The probability of schizophrenia is higher in close biological relatives
  • Concordance rates for schizophrenia are higher in monozygotic twins than in dizygotic twins
  • The risk of schizophrenia is increased by the presence of the disorder in biological parents but not by its presence in adoptive parents
  • Some people inherit a potential for schizophrenia, which may or may not be activated by experience
  • Many genes have been linked to the disorder, but no single gene seems capable of causing schizophrenia by itself
• Factors linked to schizophrenia

  • Birth complications
  • Maternal stress
  • Prenatal infections
  • Socioeconomic factors
  • Urban birth or residing in an urban setting
  • Childhood adversity
• Neurodevelopmental hypothesis of schizophrenia

  Schizophrenia and autism spectrum disorders share many of the same causal factors
• Fetuses whose pregnant mothers suffered in the Nazi-induced Dutch famine of 1944–1945 and the Chinese famine of 1959–1961 were more likely to develop schizophrenia as adults
• Atypical antipsychotics


  • Drugs that are effective against schizophrenia but yet do not bind strongly to D2 receptors
  • Initially claimed to be more effective in the treatment of schizophrenia than the typical (D2-blocking) antipsychotics and without Parkinsonian side effects
  • Some D2 receptor antagonists have no antipsychotic actions
• Drugs that enhance the effects of glycine or block the effects of glutamate


  • Proving to be effective treatments for schizophrenia in preliminary tests
  • There is growing appreciation of the role of glutamatergic dysregulation in the development of schizophrenia
• Psychedelic drug effects


  • Drugs whose primary action is to alter perception, emotion, and cognition
  • One line of research focused on those psychedelic drugs that produce effects similar to the symptoms of psychiatric disorders
  • The other line focused on the feelings of boundlessness, unity, and bliss reported by some users and attempted to use psychedelics in the treatment of psychiatric disorders
• The effects of classical hallucinogens, such as LSD, mimic the positive symptoms of schizophrenia by acting as agonists of particular serotonin receptors
• Dissociative hallucinogens (e.g., ketamine) mimic the negative symptoms of schizophrenia by acting as antagonists of glutamate receptors
• Schizophrenia-related genes


  • The study of schizophrenia-related genes and their effects is still in its early stages, but it has already pointed to several processes that could play important roles in development of the disorder
  • Some genes that increase a person's susceptibility to schizophrenia have also been linked to other psychiatric and neurological disorders
• Brain changes associated with schizophrenia

  • The first generation of studies reported enlarged ventricles and fissures which indicated reduced brain volume
  • The hippocampus, amygdala, thalamus, and nucleus accumbens were found to be significantly smaller in those with schizophrenia
  • Schizophrenia-related volume reductions develop in both gray and white matter, and they are most consistently observed in the temporal lobes
  • Individuals who have not been diagnosed with schizophrenia but are at risk for the disorder display volume reductions in some parts of the brain
  • Extensive brain changes already exist when patients first seek medical treatment and receive their first brain scans
  • Subsequent brain scans reveal that the brain changes continue to develop after the initial diagnosis
  • Alterations to different areas of the brain develop at different rates
• Mood disorders


  • Some people experience deep depression or anhedonia (loss of the capacity to experience pleasure)
  • Clinical depression, major depressive disorder - when condition lasts for 2 weeks or longer
• Types of depression


  • Reactive depression - Depression triggered by an obvious negative experience
  • Endogenous depression - depression with no apparent cause
• Seasonal affective disorder (SAD)

  • Episodes of depression and lethargy typically recur during particular seasons, usually during the winter months
  • Suggested to be triggered by the reduction of sunlight
  • Light therapy can be effective
• Peripartum depression


  Intense, sustained depression experienced by some women during pregnancy, after they give birth, or both
• Classes of antidepressant drugs

  • Monoamine oxidase inhibitors (MAOIs)
  • Tricyclic antidepressants
  • Selective monoamine-reuptake inhibitors (SSRIs and SNRIs)
  • Atypical antidepressants
  • NMDA-receptor antagonists
• Monoamine oxidase inhibitors (MAOIs)

  • Increase the levels of monoamines by inhibiting the activity of monoamine oxidase
  • Some side effects, including the "cheese effect" - risk of stroke caused by surges in blood pressure from consuming tyramine-rich foods
• Tricyclic antidepressants


  Block the reuptake of both serotonin and norepinephrine, thus increasing their levels in the brain