mental illness
Mental Illness Overview
- Definition and general understanding of 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 is evoked by a threatening stimulus referred to as a stressor.
- The fear response is manifested by a stress response:
- The stimulus-response relationship is strengthened or weakened by experience.
- Stress involves a hormonal pathway:
- Corticotropin-releasing hormone (CRH) is released.
- This stimulates the release of adrenocorticotropic hormone (ACTH).
- ACTH leads to the secretion of cortisol, a stress hormone.
Fear Response
- Mediated by the amygdala in the brain.
- Amygdala Role:
- Analyzes sensory information related to threats.
- Connects with the hypothalamus and other brain regions responsible for stress responses:
- Periaqueductal gray - involved in pain modulation and defensive behavior.
- Stress Response Activates:
- Hypothalamic-Pituitary-Adrenal (HPA) Axis
- Sympathetic Nervous System leading to physiological changes including increased vigilance, avoidance behavior, and other stress responses.
Anxiolytics and Neurotransmitter Involvement
- Anxiolytics target the GABAA receptor in the amygdala:
- These include substances like Benzodiazepine and Ethanol that affect GABA-gated Cl⁻ channels (GABA receptors).
Affective/Mood Disorders
Mood Episodes
- Common mood episodes include:
- Major Depressive Episode (MDE)
- Manic or Hypomanic Episode
- DSM-5 Criteria for Disorders:
- Unipolar Disorders:
- Major Depressive Disorder (MDD)
- Persistent Depressive Disorder (PDD) (Dysthymia)
- Bipolar Disorder:
- Bipolar I (manic-depressive)
- Bipolar II (hypomania and depression)
- Cyclothymic Disorder (milder episodes)
Biological Bases of Affective Disorders
- Monoamine Hypothesis:
- Proposes that mood disorders arise from deficiencies in norepinephrine (NE) or serotonin (5-HT) levels.
- Monoamine Oxidase (MAO) Inhibitors:
- Elevate mood by inhibiting the enzyme that breaks down monoamines.
- Imipramine:
- An antidepressant that inhibits the reuptake of serotonin and norepinephrine.
- Collectively support the Monoamine Hypothesis of mood disorders as deficits lead to depression.
Diathesis-Stress Model
- Diathesis: A genetic susceptibility that alone cannot trigger the disorder.
- Diathesis-Stress Hypothesis:
- Suggests that if genetically susceptible individuals face stressors in early life, their systems become sensitized and may overreact to future mild stressors.
- Comprises genetic and non-genetic factors, including the HPA system.
- Glucocorticoid receptors are involved in response mechanisms.
HPA Axis Review
- Components:
- Hypothalamus
- Stress response leading to activation of the anterior pituitary gland, which releases ACTH.
- The adrenal glands respond with CRH and Cortisol, resulting in physiological changes associated with fight-or-flight responses.
Push-Pull Regulation of HPA Axis
- The amygdala (+) and hippocampus (-) interact to regulate the HPA axis and cortisol levels.
Treatments for Affective Disorders
- Electroconvulsive Therapy (ECT):
- Advantages: Provides quick relief for severe cases.
- Adverse Effects: Potential loss of prior memories and difficulties with new memory formation.
- Structures involved include the temporal lobe.
- Psychotherapy:
- Crucial component of affective disorder treatment, employing various therapeutic approaches.
Medications for Affective Disorders
- Antidepressants:
- MAO Inhibitors, Tricyclics, SSRIs (e.g., Fluoxetine: Prozac).
- All of these medications aim to elevate monoamine neurotransmission levels in the brain.
- Help in dampening hyperactivity of the HPA axis.
Norepinephrine & Serotonin Dynamics
- Neurotransmitter levels rise promptly after starting antidepressant medications, indicating limitations of the monoamine hypothesis, suggesting there are downstream effects concerning the HPA axis.
Causes and Treatments of Bipolar Disorders
Biological Bases
- Neurotransmitters:
- Overactivity of norepinephrine correlates with manic episodes.
- Current understanding does not support a direct link between high serotonergic activity and mania but suggests the opposite:
- Low serotonin may enable higher norepinephrine activity.
Treatments for Bipolar Disorder
- Lithium and other Mood Stabilizers:
- Valproate (Depakote): Highly effective for manic episodes with >60% patient improvement.
- Some effectiveness in depressive episodes; may be prescribed with antidepressants.
- Affects second messengers within neurons and boosts neuroprotective protein production to prevent cell death.
Schizophrenia Overview
Description of Schizophrenia
- Defined as a severe mental disorder characterized primarily by:
- Loss of contact with reality.
- Evidence of psychosis.
- Symptoms exist across a continuum.
Types and Spectrum of Psychotic Disorders
- Reference Table 1 as defined in the DSM-5 to categorize different psychotic disorders.
Symptoms of Schizophrenia
- Positive Symptoms:
- Delusions (false beliefs)
- Hallucinations (false perceptions)
- Disorganized speech
- Grossly disorganized or catatonic behavior
- Loosening of associations and thought disorders
- Negative Symptoms:
- Reduced emotional expression
- Poverty of speech (alogia)
- Loss of will and goal-directed behavior
- Social withdrawal
- Memory impairment
Biological Bases of Schizophrenia
- Genetic factors greatly increase the likelihood of developing schizophrenia, estimated at a 50% chance if an identical twin is affected.
- The interplay of genetics and environment is emphasized; genes may heighten susceptibility to environmental triggers.
- Prenatal infections and maternal nutrition are significant environmental factors.
Structural Changes in Schizophrenia
- Imaging shows inconsistent changes in brain structure among those diagnosed, particularly between identical twins.
- Observations include:
- Altered cell morphology and structure
- Changes in connectivity and fiber tracts
- Reduced cortical volume in frontal and temporal regions
Neural Mechanisms and Cognitive Impairments
- Areas impacted in schizophrenia include:
- Ventral Striatum
- Anterior Prefrontal Cortex
- Dorsolateral Prefrontal Cortex (DLPFC)
- Anterior Cingulate
- Temporal Cortex
- Medial Temporal Lobe (including Hippocampus)
The Dopamine Hypothesis
- Suggests psychotic episodes are triggered by dopamine receptor activation.
- Use of amphetamines enhances neurotransmission at catecholamine synapses and induces release of dopamine, causing psychotic symptoms.
Treatments in Schizophrenia
- Effective treatments include drug therapy combined with psychosocial support.
- Conventional neuroleptics (e.g., Chlorpromazine, Haloperidol):
- Act on D2 receptors to decrease positive symptoms but often yield numerous side effects.
- Antipsychotic Drugs:
- Classified into three generations:
- First Generation:
- Examples: Chlorpromazine (Thorazine), Haloperidol (Haldol).
- Second Generation:
- Examples: Clozapine (Clozaril), Risperidone (Risperdal).
- Third Generation:
- Example: Aripiprazole (Abilify).
Side Effects of Treatments
- First-generation antipsychotics have potential for severe movement-related motor problems, including Parkinson's-like symptoms and Tardive dyskinesia.
- Second- and third-generation drugs do not produce these side effects and treat both positive and negative symptoms more comprehensively.
- Risks associated with second-generation drugs include blood disorders and weight gain.
- The effectiveness and low side effect profile of third-generation drugs lead to lower discontinuation rates.
Mechanisms of Action for Antipsychotics
- Antipsychotic medications are believed to be clinically effective due to their interactions with subtypes of dopamine, glutamate, and serotonin receptors:
- First-generation: Block D2 receptors
- Second-generation: Block D4 and D2 receptors
- Third-generation: Stabilize D2 receptors, block serotonin receptors, with some influence on glutamate.