mental illness

Mental Illness

Anxiety Disorders

  • Common Anxiety Related Disorders
      - Panic Disorder
      - Agoraphobia
      - Obsessive-Compulsive Disorder (OCD)
      - Generalized Anxiety Disorder (GAD)
      - Specific Phobias
      - Social Phobia
      - Post-Traumatic Stress Disorder (PTSD)

Biological Bases of Anxiety Disorders

  • Fear Response
      - Evoked by a threatening stimulus, known as a stressor
      - Manifested through a stress response
      - The stimulus-response relationship can be strengthened or weakened by experience
      - Stress Mechanism:
        - Corticotropin-Releasing Hormone (CRH) leads to:
          - Adrenocorticotropic Hormone (ACTH)
          - Cortisol

Neuroanatomy of Anxiety

  • Fear Response Mediation
      - Mediated by the Amygdala in response to sensory information
      - Activation Pathway:
        - Amygdala → Hypothalamus → Activation of the stress response involving:
          - HPA (Hypothalamic-Pituitary-Adrenal) activation
          - Activation of the sympathetic nervous system
          - Resulting behaviors such as avoidance
          - Increased vigilance

Anxiolytic Treatments

  • Mechanism of Action
      - Anxiolytics target the GABAA receptor in the amygdala
      - Types of Anxiolytics:
        - GABA
        - Benzodiazepines
        - Ethanol
        - GABA-gated Cl⁻ channel (GABA receptor)

Affective/Mood Disorders

  • Common Mood Episodes
      - Major Depressive Episode (MDE)
      - Manic or Hypomanic Episode

  • Types of Unipolar Disorders
      - Major Depressive Disorder (MDD)
      - Persistent Depressive Disorder (PDD - Dysthymia)

  • Bipolar Disorder Types
      - Bipolar I (Manic-Depression)
      - Bipolar II (Hypomania + Depression)
      - Cyclothymic Disorder (Milder Episodes)

Biological Bases of Affective Disorders

  • The Monoamine Hypothesis
      - Proposes that mood disorders result from insufficient levels of neurotransmitters such as Norepinephrine (NE) or 5-Hydroxytryptamine (5-HT, Serotonin)
      - Monoamine Oxidase (MAO) Inhibitors:
        - Elevate mood by destroying MAO, an enzyme that breaks down catecholamines and serotonin
      - Imipramine:
        - An antidepressant that inhibits the reuptake of serotonin (5-HT) and norepinephrine (NE)
      - Together, these observations contribute to the understanding of the Monoamine hypothesis of mood disorders

Diathesis-Stress Model/Hypothesis

  • Diathesis:
      - A genetic vulnerability that alone cannot initiate the disorder
  • Diathesis-Stress Hypothesis:
      - Individuals with genetic susceptibility who experience stressors early in life may become sensitized, leading to overreactions to mild stressors later in life

Stress and Mood Relationships

  • HPA Axis Review
      - Hypothalamus → Anterior Pituitary Gland → ACTH → Adrenal Gland → CRH → Cortisol
      - Physiological Changes:
        - Support fight-or-flight responses

HPA Axis Regulation

  • Push-Pull Regulation
      - Amygdala activates HPA axis, while the hippocampus exerts regulatory control over cortisol

Treatments for Affective Disorders

  • Electroconvulsive Therapy (ECT)
      - Involves localized electrical stimulation
      - Advantages: Quick relief
      - Adverse Effects: Loss of prior memories, difficulty in storing new information
      - Involved Structures: Temporal lobe

  • Psychotherapy
      - An important component of treatment
      - Involves various approaches

Pharmacological Treatments for Affective Disorders

  • Antidepressants
      - MAO Inhibitors
      - Tricyclics
      - Selective Serotonin Reuptake Inhibitors (SSRIs) such as Fluoxetine (Prozac)
      - All medications elevate monoamine neurotransmission levels and dampen hyperactivity of the HPA axis

Neurotransmitter Activities in Affective Disorders

  • Effects of Antidepressants:
      - Norepinephrine & Serotonin levels increase immediately upon medication intake
      - Suggests limitations of the monoamine hypothesis, implying downstream effects in the HPA axis

Bipolar Disorders Causes

  • Neurotransmitters in Bipolar Disorder
      - Overactivity of norepinephrine is linked to mania
      - No consistent connection found between high serotonin activity and mania; low serotonin may increase vulnerability
      - Norepinephrine Levels/Activities:
        - Low NE correlates with depression
        - High NE correlates with mania

Treatments for Bipolar Disorder

  • Lithium and Other Mood Stabilizers:
      - Valproate (Depakote):
        - Very effective for managing manic episodes, over 60% of patients respond positively
      - Some physicians also prescribe antidepressants for depressive episodes, focusing on downstream effects and neuroprotective protein production to prevent neuron death

Schizophrenia

  • Description of Schizophrenia
      - Severe mental disorder characterized by:
        - Loss of contact with reality
        - Psychosis
        - Symptoms present along a continuum

Types and Spectrum of Schizophrenia

  • Types of Psychotic Disorders
      - Classification based on DSM-5 criteria
      - A comprehensive table of psychotic disorders is available

Symptoms of Schizophrenia

  • Positive Symptoms:
      - Delusions
      - Hallucinations
      - Disorganized Speech
      - Grossly disorganized or catatonic behavior
      - Loosening of associations, thought disorders

  • Negative Symptoms:
      - Reduced emotional expression
      - Poverty of speech (Alogia)
      - Absence of will, goal-directed behavior
      - Social withdrawal
      - Memory impairment

Biological Bases of Schizophrenia

  • Genetic and Environmental Factors
      - 50% likelihood of developing schizophrenia if an identical twin has it
      - Schizophrenia is classified as a genetic disorder

Genetic Vulnerability and Environmental Interaction

  • Environmental Triggers:
      - Factors such as prenatal infections and maternal nutrition contribute to risk
      - Genetics do not determine outcomes in isolation but in conjunction with environmental factors
  • Presentation:
      - Schizophrenia typically manifests in young adulthood, with structural changes possible from early development
      - Relationship with ventricle-to-brain size ratio noted

Brain Imaging and Schizophrenia

  • Imaging Results
      - MRIs show inconsistent changes in brains of individuals with schizophrenia compared with those who do not have the disorder
      - Observations include altered cell morphology, fiber tracts, and connectivity
      - Reduced cortical volume, primarily in frontal and temporal regions

Cognitive Impairments in Schizophrenia

  • Affected Areas
      - Ventral Striatum
      - Anterior Prefrontal Cortex
      - Dorsolateral Prefrontal Cortex (DLPFC)
      - Anterior Cingulate
      - Temporal Cortex
      - Medial Temporal Lobe (Hippocampus)

Dopamine Hypothesis in Schizophrenia

  • Triggering Psychotic Episodes
      - Psychotic episodes are believed to be linked to dopamine receptor activation
      - The effects of amphetamines provide insight as they enhance neurotransmission at catecholamine synapses, potentially leading to psychotic symptoms
  • Treatment Approach
      - Neuroleptics effectively bind to D2 receptors, blocking dopamine to alleviate positive symptoms

Glutamate Hypothesis in Schizophrenia

  • Behavioral Effects of PCP
      - Phencyclidine (PCP), introduced in the 1950s as an anesthetic, inhibits NMDA receptors leading to symptoms that resemble schizophrenia
      - Indicates that schizophrenia involves more than just dopamine activity
      - Glutamate is identified as a fast excitatory neurotransmitter with roles in the NMDA receptor channel

NMDA Receptor Blockage Effects

  • PCP and Schizophrenia
      - Blockage of NMDA receptors by PCP leads to a syndrome mimicking schizophrenia and exacerbating symptoms in those already diagnosed

Glutamate Hypothesis Summary

  • PCP's Role
      - Indicates that blocking NMDA receptors results in both positive and negative symptoms of schizophrenia
      - Enhancing glutamatergic transmission through NMDA (via D-cycloserine) ameliorates symptoms
      - Atypical antipsychotics like clozapine also enhance NMDA channel transmission

Treatments for Schizophrenia

  • Combined Approach:
      - Effective treatment consists of drug therapy alongside psychosocial support
      - Conventional Neuroleptics:
        - Example: Chlorpromazine and Haloperidol, acting at D2 receptors to reduce positive symptoms, yet with various side effects

Classification of Antipsychotic Drugs

  • First-Generation Drugs
      - E.g. Chlorpromazine (Thorazine) and Haloperidol (Haldol)
  • Second-Generation Drugs
      - E.g. Clozapine (Clozaril) and Risperidone (Risperdal)
  • Third-Generation Drugs
      - E.g. Aripiprazole (Abilify)
  • Table of FDA-Approved Antipsychotic Medications:
      - Includes various generic and brand names with dosages outlined for first, second, and third-generation drugs

Side Effects of Antipsychotic Medications

  • First-Generation Side Effects
      - Risk of severe movement-related side effects such as Parkinson-like symptoms and tardive dyskinesia
  • Second and Third Generation Drugs
      - Generally do not produce these side effects
      - Can treat positive and negative symptoms more effectively, though may have adverse effects like blood disorders, weight gain, or diabetes

Efficacy and Mechanism of Antipsychotic Medications

  • Clinical Effectiveness
      - Antipsychotic medications believed to act efficiently on through various dopamine and glutamate receptor subtypes
      - First Generation: Block D2 receptors
      - Second Generation: Block both D4 and D2 receptors
      - Third Generation: Stabilize D2 receptors, blocks serotonin receptors, and some properties targeting glutamate