Psychiatry 1

CNS Pharmacology

  • Human Brain Composition   - Contains approximately 100 billion nerve cells (neurons).   - Neurons: Specialized cells that receive information through cell extensions called dendrites, integrate signals in the cell body, and send information back out via a single extension called the axon.   - Proper functioning of the nervous system depends on communication between neurons.

Structure of a Neuron

  • Components:   - Cell Body: Contains the nucleus and organelles.   - Dendrites: Multiple extensions that receive signals from other neurons.   - Axon: A single extension that transmits signals to other neurons.   - Terminal Bouton: The end of the axon where neurotransmitter release occurs.

Neurotransmission Process

  • Timeline: The entire process occurs in a few hundred microseconds.

  • Steps Involved:   1. Action potential (AP) travels along presynaptic cells until it reaches synapses.   2. Depolarization opens Ca²⁺ channels at the synaptic membrane, allowing Ca²⁺ influx into the bouton.   3. Increased intracellular Ca²⁺ activates vesicles to dock at the synapse membrane.   4. Neurotransmitters are released into the synaptic cleft.   5. Neurotransmitters bind to neuroreceptors on the postsynaptic neuron, which opens ion channels and initiates another wave of action potential.

Chemical Events at the Level of the Synapse

  • Presynaptic Events:   - Vesicles containing neurotransmitters are released into the synapse.

  • Postsynaptic Events:   - Neurotransmitter binds to postsynaptic receptors.   - Neurotransmitter re-uptake occurs after binding.

Key Neurotransmitters

  • GABA (Gamma-Aminobutyric Acid):   - Inhibitory neurotransmitter widely distributed in the cortex.   - Contributes to motor control, vision, and various cortical functions.   - Plays a role in regulating anxiety.

  • Glutamate:   - Primary excitatory neurotransmitter in the brain.

  • Dopamine (DA):   - Located in several brain regions.   - Important for emotional control and screening stimuli, modulates mood.   - Involved in positive reinforcement and dependency.   - Can induce psychotic symptoms or worsen existing psychotic disorders.

  • Norepinephrine (NE):   - Involved in attentiveness, emotions, sleeping, dreaming, and learning.   - Acts as a hormone, causing blood vessels to contract and heart rate to increase.

  • Serotonin (5HT):   - Regulates various functions like body temperature, sleep, mood, appetite, and pain.

  • Acetylcholine (ACh):   - Widespread excitatory neurotransmitter that triggers muscle contraction and hormonal excretion.   - Involved in wakefulness, attentiveness, aggression, and thirst.

Sleep Disorders

  • Circadian Rhythm:   - Sleep and wakefulness occur in cycles governed by circadian rhythm.   - The suprachiasmatic nucleus, influenced by light-dark input from the retina, controls the circadian clock.

  • Types of Sleep Disorders:   1. Inability to fall asleep, stay asleep, sleep-related breathing/movement disorders, excessive sleepiness.   2. Diagnostic methods include:      - Sleep history      - Sleep schedule adherence      - Quality of sleep assessment

Diagnostic Methods for Sleep Disorders

  • Actigraphy:   - Wrist actigraphy measures muscle movement for objective sleep duration and efficiency.

  • Polysomnography:   - Comprehensive sleep study involving:     - Electroencephalogram (EEG) to measure brain waves.     - Electro-oculogram (EOG) to record eye movements.     - Electromyogram (EMG) for muscle activity.     - ECG and pulse oximetry for assessing arterial oxygen.

Types of Sleep Disorders

  • Circadian Rhythm Disorders:   - Non-24-Hour Sleep-Wake Syndrome:     - Lack of synchronization between internal clock and external environment.     - Typically observed in blind individuals or those with brain lesions.   - Jet Lag: Due to acute shifts in sleep-wake cycle.   - Shift Work Sleep Disorder: Related to irregular work hours.

Treatments for Circadian Rhythm Disorders

  • Behavioral Changes:   - Maintain a home time schedule or adapt to new schedules.

  • Environmental Interventions:   - Use of artificial light and engaging in social activities to improve alignment.

Types of Sleep Disorders Continued

  • Insomnia:   - Defined as difficulty initiating or maintaining sleep, waking too early, experiencing non-restorative sleep.   - Often accompanied by daytime fatigue, impaired concentration, memory issues, irritability.   - Can be acute or chronic.

  • Acute Insomnia:   - Short-term sleep difficulty often resolving with adaptation or resolution of stressors.

  • Chronic Insomnia:   - Persisting for 30 days or more; often related to psychiatric or medical issues (pain, hormonal changes, drug-induced).

Treatments for Insomnia

  • Good Sleep Hygiene Recommendations:   - Establish regular wakeup times.   - Sleep duration adjusted to feel refreshed.   - Maintain a quiet sleeping environment.   - Avoid alcohol and caffeine before sleep.   - Reserve bedroom for sleep only, not for activities like reading or watching TV.

  • Short-Term Use of Sedatives and Hypnotics:   - Medications for sleep induction and maintenance.

Terminology for Medications

  • Sedation:   - Reduction of anxiety; medications termed anxiolytics/sedatives.

  • Hypnosis:   - Induction of sleep; medications termed hypnotics facilitating drowsiness and sleep maintenance.

Other Types of Sleep Disorders

  • Narcolepsy:   - Characterized by excessive daytime sleepiness not resolved by nighttime sleep.   - Chronic neurological disorder due to autoimmune destruction of hypocretin-producing neurons, affecting sleep-wake regulation.

  • Sleep Apnea:   - Central Sleep Apnea: Disorder affecting the brain's respiratory centers.   - Obstructive Sleep Apnea: Results from upper airway obstruction, characterized by snoring, disrupted sleep, excessive daytime sleepiness; caused by relaxation of throat tissue.

Psychosis

  • Definition:   - Not a diagnosis, but a symptom; schizophrenia represents a specific type of psychotic illness.

Schizophrenia

  • Characteristics:   - Exact pathogenesis is unknown; involves neurodevelopmental changes during prenatal/perinatal periods.   - Symptoms include:     - Abnormal social behavior.     - Failure to recognize reality.     - Associated with gray matter loss impacting intelligence, sensory perception, and muscle control.

Stages of Illness in Schizophrenia

  • Stages:   1. Full functioning, odd behavior, subtle negative symptoms.   2. Positive symptoms, remissions, relapses but never returning to full functioning.   3. Prominent negative and cognitive symptoms leading to continuing disability (burnout stage).

Pathological Changes in Schizophrenia

  • Pathological changes believed to occur during the prenatal or perinatal period leading to gray matter loss observable through imaging.

Psychotic Symptoms in Schizophrenia

  • Types:   - Positive Symptoms: Features present that should not exist, such as hallucinations (auditory and visual), and delusions (persecution, grandeur, control).   - Negative Symptoms: Reflect diminishing or loss of emotional and psychological functions (e.g., psychomotor retardation, affective flattening, anhedonia, avolition, alogia, social withdrawal, thought block).   - Cognitive Impairments: Issues with attention, memory, executive functioning, and verbal fluency.   - Mood Symptoms: Dysphoria, hopelessness, potential suicide ideation.

Other Symptoms of Psychosis

  • Unusual Motor Behavior:   - Catatonia: Rigid, immobile position held for a long duration, ignoring external stimuli.   - Incongruous affect: e.g., smiling inappropriately.

Dopamine Hypothesis in Schizophrenia

  • Proposed Mechanism:   - Schizophrenia linked to relative excess dopaminergic activity in specific neuronal tracts.   - Overactive dopamine neurons lead to behavioral agitation, failure to screen stimuli adequately, and disorganization of thought and perception.

Mechanism of Action of Antipsychotics

  • Action:   - Antipsychotic medications block postsynaptic D2 dopamine receptors in the mesolimbic tract.   - Blockade of other dopamine pathways induces side effects rather than therapeutic effects.

Dopamine Pathways

  • Key Pathways:
      - Mesocortical Tract:
        - It plays a critical role in regulating mood, cognition, and various executive functions. Impairments in this pathway are associated with negative symptoms of schizophrenia, such as emotional blunting, anhedonia, and social withdrawal.
      - Mesolimbic Tract:
        - This pathway is crucial for the reward system and behavioral reinforcement. It is associated with the therapeutic effects of antipsychotic medications. An overactivity of dopamine transmission in this tract is linked to positive symptoms of schizophrenia, which include hallucinations, delusions, and thought disorganization.
      - Nigrostriatal Tract:
        - This pathway is essential for the coordination of movement and the regulation of motor function. A deficiency of dopamine in this tract can lead to movement disorders such as Parkinson’s disease and other extrapyramidal symptoms, which manifest as tremors, rigidity, and bradykinesia following antipsychotic treatment.
      - Tuberoinfundibular Tract:
        - This pathway affects the secretion of prolactin from the pituitary gland. When dopamine transmission in this tract is disrupted, it can lead to hyperprolactinemia resulting in side effects such as amenorrhea, gynecomastia, and sexual dysfunction. These effects are significant considerations in the treatment of patients with schizophrenia and bipolar disorder, necessitating regular monitoring of prolactin levels.

Treatments for Schizophrenia

  • Goals:   - Induce remission, prevent recurrences, improve behavioral, cognitive, and psychosocial functions.

  • Interventions:   - Pharmacotherapy:     - Use of typical (older) and atypical (newer) antipsychotics.   - Psychosocial Therapy:     - Education of patient and family.     - Vocational rehabilitation.

Bipolar Disorder

  • Pathogenesis:   - Exact causes unknown; linked to structural brain abnormalities.   - Possible involvements include neurotransmitter and cortisol level dysregulation.

  • Behavioral Characteristics:   - Episodes of depression and episodes of extreme happiness/irritability;   - Extreme shifts in activity and energy levels.

Functioning in Bipolar Patients

  • Patients exhibit a broad spectrum of social functioning ranging from high to low.

  • In contrast, patients with schizophrenia typically exhibit lower functioning levels.

Goals of Therapy for Bipolar Disorder

  • Aim:   - Address manic symptoms.   - Manage depressive symptoms.   - Prevent extremes in mood swings (maintenance therapy).

Symptoms of Bipolar Disorder

  • Mood Spectrum:   - Patients experience shifts between manic and depressive poles.

  • Mania Symptoms:   - Decreased need for sleep and food; rapid pressured speech; inflated self-esteem.   - Episodes alternate between excessive energy and feelings of sadness/hopelessness with possible normal mood interludes.   - Mixed symptomatology can occur (mania with agitation).

  • Psychotic Symptoms:   - Possible occurrence during manic episodes.

Treatments for Bipolar Disorder

  • Psychotherapy Options:   - Cognitive Behavioral Therapy (CBT), Interpersonal Therapy, Family-Focused Therapy.

  • Medication Options:   - Antidepressant drugs.   - Electroconvulsive Therapy (ECT): Involves small electric currents inducing a generalized seizure lasting around 40 seconds, used for severe depression and mania.   - Antipsychotics and Mood Stabilizers: (Lithium and anticonvulsants); especially for patients unresponsive to lithium and those experiencing frequent episodes of mania and depression annually.