psychopathology

Schizophrenia

  • Prevalence: Schizophrenia affects approximately 1% of the population.
    • Key symptom: Impaired logical thought.

Positive Symptoms of Schizophrenia

  • Definition: Positive symptoms represent abnormal behaviors that are gained and include:
    • Hallucinations: Perception of something that isn’t present.
    • Delusions: Firmly held false beliefs that contradict reality.
    • Excited motor behavior: Increased agitation or movement.
  • Characteristics:
    • Generally acute in onset.
    • More likely to respond to antipsychotic medications.

Negative Symptoms of Schizophrenia

  • Definition: Negative symptoms are characterized by a loss of functions and include:
    • Slow thought and speech: Reduced responsiveness and communication.
    • Emotional and social withdrawal: Decreased engagement and interaction with others.
    • Blunted affect: Diminished emotional expression.
  • Cognitive Symptoms:
    • Disorganized thoughts, difficulty in concentrating, and challenges in following instructions.

Heritability of Schizophrenia

  • Genetic factors play a role in schizophrenia susceptibility.
    • Population statistics indicate varying risks based on familial connections:
    • General population: 1%
    • Spouses: 1%
    • First cousins: 2%
    • Uncles/Aunts: 2%
    • Nephews/Nieces: 4%
    • Grandchildren: 5%
    • Half-siblings: 6%
    • Children: 13%
    • Siblings: 9%
    • Siblings with one parent who has schizophrenia: 17%
    • Dizygotic twins: 17%
    • Parents: 6%
    • Monozygotic twins: 48%

Brain Imaging and Schizophrenia

  • MRI studies show discordant twins (one with schizophrenia, one without) have different ventricle-to-brain volume ratios.
    • Findings:
    • Patients with schizophrenia exhibit larger ventricles, indicating reduced brain volume.

Causes of Schizophrenia

  • Schizophrenia arises from a combination of genetic vulnerabilities and environmental exposures.
    • The illness is likely to develop if a genetic threshold is exceeded by environmental stressors.
    • Environmental factors can upregulate or downregulate gene function and expression.

Environmental Factors

  • Some potential environmental triggers include:
    • Infectious agents (e.g., high influenza exposure during pregnancy).
    • This can lead to increased birth rates of individuals with schizophrenia during high-flu years.

Brain Structure and Schizophrenia

  • Hippocampus and Amygdala:
    • These regions may be smaller in some individuals with schizophrenia.
    • Pyramidal neurons in the hippocampus are often disorganized.
    • Some individuals show a deficiency in Reelin, crucial for cell migration in the brain, correlating with symptoms.

Neurological Changes in Schizophrenia

  • Accelerated Loss of Gray Matter:
    • In adolescents diagnosed with schizophrenia, there is notable underactivity in the temporal and frontal lobes.
    • Linked to accelerated aging and neuron loss, characterized as hypofrontality.

Dopamine Hypothesis

  • Definition: Schizophrenia is associated with excess synaptic dopamine or increased postsynaptic sensitivity to dopamine.
    • Evidence supporting this includes:
    • Neuroleptics are dopamine antagonists.
    • Chronic amphetamine usage can induce a schizophrenia-like syndrome.
    • Treatment with L-dopa in Parkinson's can lead to psychotic symptoms.
    • Increased D2 receptor levels are noted in the auditory thalamus of affected individuals.

Antipsychotic Drug Mechanisms

  • All current antipsychotic medications modulate the function of the dopamine D2 receptor.
  • Dosages required to block these receptors vary significantly among different antipsychotics.

Limitations of Dopamine Hypothesis

  • Key issues include:
    • Many schizophrenics exhibit normal dopamine metabolite levels.
    • Drugs rapidly block dopamine receptors yet delay symptom relief.
    • Not all positive symptoms respond to dopamine receptor antagonists.

Atypical Antipsychotics

  • Examples include Risperidone and Abilify that block both serotonin (5-HT2) and D2 receptors.
  • Some may also increase dopamine levels in the frontal cortex.

Glutamate Hypothesis of Schizophrenia

  • The role of glutamate receptors (particularly NMDA) is crucial.
    • PCP (Phencyclidine) is an NMDA antagonist and mimics acute schizophrenia symptoms through prolonged NMDA underactivation.
    • Atypical antipsychotics may enhance glutamate signaling by downregulating the glutamate transporter gene.

Endocannabinoid System and Schizophrenia

  • Overactivity of endocannabinoids (EC) occurs in schizophrenia.
    • Elevated levels of endocannabinoids, particularly affecting CB1 receptors, inhibit other neurotransmitters.
    • THC exposure in at-risk individuals can precipitate psychosis; worsening symptoms in diagnosed patients.

Other Mental Disorders

Depression

  • Common mood disorder characterized by:
    • Sad mood: Persistent feelings of sadness.
    • Feelings of worthlessness or guilt: Self-criticism and low self-esteem.
    • Loss of interest in pleasurable activities: Anhedonia.
    • Appetite changes: Either increase or decrease in appetite; significant weight change.
    • Sleep pattern alterations: Insomnia or hypersomnia.
    • Suicidal ideation: Thoughts of self-harm or suicidal plans.

'Normal' vs. Clinical Depression

  • Normal Depression:
    • Reaction to life events, described as feeling 'blue'.
    • Few symptoms and short duration (hours to days).
    • Little to no impairment in functioning.
  • Clinical Depression:
    • Mood described as 'black', characterized by many symptoms and a long duration (weeks to months).
    • Significant impairment in daily functioning, can be debilitating.

Neurobiology of Depression

  • Increased activity in the emotional orbitofrontal cortex and amygdala; decreased in attention and language areas.
  • Monoamine hypothesis: Proposes the cause of depression is reduced activity of norepinephrine and serotonin at synapses.

Treatment Modalities for Depression

  • Antidepressants operate by:
    • Inhibiting reuptake of serotonin (5-HT) or norepinephrine (NE).
    • Binding to presynaptic 5-HT or NE autoreceptors to enhance neurotransmitter release.
    • Inhibiting monoamine oxidase, reducing neurotransmitter breakdown.

Efficacy of Antidepressants

  • Approximately 60% response rate seen in primary care settings.
  • Overactive serotonin autoreceptors can impair release and contribute to depression; autoreceptor activity declines after weeks of SSRI treatment, increasing serotonin release and neuronal activity.

Electroconvulsive Therapy (ECT)

  • Early findings indicated that seizure induction could alleviate depression.
  • ECT parallels this effect by raising monoamine levels and is particularly used for severe depression associated with suicidal ideation.
  • Short-term remission rate: 87%; long-term remission rate: 43%.

Brain Stimulation Treatments

  • Transcranial Magnetic Stimulation (TMS): Non-invasive stimulation that produces effects resembling traditional ECT.
  • Deep brain stimulation: Targets the anterior cingulate gyrus and median forebrain bundle, also showing immediate therapeutic effects.
  • Vagus nerve stimulation: Gradual relief for depression symptoms.

Types of Antidepressants

  • SSRI (Selective Serotonin Reuptake Inhibitors): First choice due to fewer severe side effects.
  • SNRI (Selective Norepinephrine Reuptake Inhibitors)
  • TCA (Tricyclics)
  • MAO Inhibitors: Known to be effective but involve dietary restrictions and risk of hypertensive crisis.

Hypothalamic-Pituitary-Adrenal Axis in Depression

  • The stress response involves complex interactions between the hypothalamus, pituitary gland, and adrenal glands, impacting cortisol levels.
  • Cortisol levels can be significantly elevated in individuals with primary psychiatric disorders compared to normal controls.

Stress and Depression

  • Neurotransmitter systems (glutamate and NMDA receptors) are impacted by stress.
  • Exposure to stress contributes to synaptic dysconnectivity and diminishes overall neuronal function.

Ketamine in Depression

  • Efficacy as an alternative treatment for severe depression; it shows a quick upsurge in glutamate, restoring synaptic function.
    • Comparison with ECT shows efficacy in symptom relief.

Sleep Patterns in Depression

  • Individuals with depression often have reduced and fragmented slow-wave sleep and enter REM sleep rapidly, often with increased REM prevalence.

Bipolar Disorder

  • Characteristics: Fluctuation between depressive and manic states.
  • Symptoms of mania include:
    • Excess energy: Increased confidence and grandiosity.
    • Reduced need for sleep: Patients may engage in hypersexual behavior or substance abuse.

Bipolar Disorder and Genetics

  • Research suggests the involvement of specific genes (e.g., Clock gene) in the predisposition to bipolar disorder.

Cyclothymia

  • A milder form of bipolar disorder, characterized by cycling between mild depression and hypomania.

Anxiety Disorders

  • Phobic Disorders: Involves intense, irrational fear of specific objects or situations.
  • Panic Disorder: Characterized by recurrent panic attacks marked by extreme fearfulness.
  • Generalized Anxiety Disorder: Persistent and excessive worry about various aspects of life.
  • Obsessive-Compulsive Disorder (OCD): Defined by recurrent intrusive thoughts (obsessions) and compulsive behaviors (compulsions) such as hand-washing.

Treatment for Anxiety Disorders

  • Antidepressants help by reducing serotonin autoreceptor sensitivity.
  • Benzodiazepines are commonly utilized for treating acute anxiety symptoms.

Neurobiology of Anxiety Disorders

  • Patients with OCD exhibit increased activity in the orbitofrontal cortex and caudate nuclei.
  • Surgery to disconnect the orbitofrontal cortex from the anterior cingulate cortex can lead to significant long-lasting improvements.

Tourette’s Syndrome

  • Related to OCD, characterized by motor and phonic tics.
  • Activation of the basal ganglia during tics is a prominent feature.

Historical Treatments in Psychiatry

  • Frontal Lobotomy: Performed on various psychiatric disorders to induce remission but often resulted in severe personality changes.
  • The technique used tools to create lobotomies that altered brain functioning, usually causing irreversible changes.