Exam 4, Lec 4: Schizophrenia Anxiety Depression

Positive symptoms of Schizophrenia

Symptoms that include delusions, hallucinations, disorganized speech, paranoia, and grossly disorganized behavior.

Negative symptoms of schizophrenia

Symptoms characterized by decreased motivation, diminished emotional recognition and expression (flat affect), social withdrawal, and poverty of speech.

Cognitive deficits in schizophrenia

Impairments in executive function, attention, working memory, episodic memory, and language comprehension.

Two-hit hypothesis of schizophrenia

A theory suggesting that schizophrenia arises from a combination of genetic heredity and environmental risk factors.

Genetic heredity in schizophrenia

Approximately 80-85% of the risk for developing schizophrenia is attributed to genetic factors, involving around 50-100 susceptibility genes like Neuregulin 1 (NRG1), Dirupted-in-Schizophrenia 1 (DISC1), and Dystrobrevin Binding Protein 1 (DTNBP1).

Environmental risk factors for schizophrenia

Include gestational and birth complications

• (Oxygen Deprivation, Drug Use, Viral Infections during second trimester, Severe Malnutrition, Birth during late winter-early spring months),

childhood stressors

• (Exposure to toxins, Family climate, Socioeconomic Status),

adolescent cannabis use which contribute to the development of schizophrenia.

• Functional polymorphism in COMT gene increases risk of developing psychosis

Abnormalities in Brain Structure

Abnormalities in prefrontal cortex and auditory regions (Broca’s Wernicke’s Areas)

Thinned Cortex in temporal regions

Enlarged Ventricles

Cerebral atrophy in the temporal lobe, hippocampus, parahippocampal gyrus, and amygdala

Abnormal dendrites/disorganization in prefrontal cortex, hippocampus and entorhinal cortex

Lower blood flow in the prefrontal cortex affecting executive function

Original Dopamine Hypothesis

Elevating dopamine can produce schizophrenia-like positive symptoms

Increasing dopamine levels in individuals with schizophrenia can worsen symptoms

Blocking dopamine activity in schizophrenias can reduce symptoms (antipsychotics)

Revised Dopamine Hypothesis

Positive Symptoms

• Excess subcortical dopamine (hyperstimulation of D2 receptors in mesolimbic pathway)

Negative Symptoms and Cognitive Impairments

• Deficit in prefrontal dopamine (hypostimulation of D1 receptors in mesocortical pathway)

• Associated with defects in a subset of GABAergic interneurons

Treatment: Dopamine Antagonists

Chloropromazine and derivatives

Gradually effective over times

Side effects can affect drug compliance

• Parkinsonian like symptoms(tremors, akinesia, muscle rigidty)

• Tardive dyskinesia (Affecting 15-20%) leading to involuntary, purposeless movements

• Mostly irreversible; thought to be due to postsynaptic DA receptor super sensitization

Chlorpromazine and Haloperidol

An antipsychotic medication that reduces positive symptoms by blocking dopamine receptors.

Second Generation: Neuroleptics

Atypical antipsychotics (clozapine, risperidone, olanzapine)

Fewer motor side effects and more effective in reducing negative symptoms

Abilify (Aripiprazole)

A third-generation antipsychotic that acts as a partial agonist at the D2 receptor, stabilizing dopamine levels in different areas of the brain.

Fear

Cognitive Appraisal:

Physiologic Arousal:

Behaviors:

Cognitive Appraisal: Recognizing and remembering real threats

Physiologic Arousal: Signals danger, enchances alertness, prepares body for action

Behaviors: Flight/fight Freezing

Anxiety Disorders (Emotional and Physical Symptoms)

Emotional Symptoms: Irrational and ecessive fear or worry, panic, feelings of dread, difficult concentrating, irritability, restlessness, tension, or jumpiness

Physical Symptoms (During panic attacks): Pounding heart, sweating, shortness of breath, choking sensations, muscle tension, headaches, fatigue, Insomnia

Fear Brain Circuits

Increased Activity in locus Ceruleus (Norepinephrine)

Decreased Activity in Dorsal Raphe Nucleus (Serotonin)

Increased Amygdala Activity (Processes sensory information and assigns emotional valence)

Hyperactive Hypothalamus (Autonomic Response)

Anxiolytics

Drugs that relieve anxiety, including benzodiazepines that enhance GABA receptor activity.

Benzodiazepines

Sedative-Hypnotics (CNS Depressants)

Quickly relieve psychological and physical symptoms of anxiety and assist with insomnia

Tolerance can develop; risk of dependence and withdrawal

Benzodiazepines and GABA Receptors

Enhance activity of GABA receptors

Indirect GABA agonists that increase GABA binding and effect

No effect in absence of GABA, making them safer than barbiturates

Monoamine theory of depression

The idea that clinical depression is associated with blunted brain monoamine systems, particularly serotonin (5-HT) and norepinephrine (NE).

Monoamine Theory

Reserpine depletion of monoamines leads to depression in some individuals

Antidepressants generally increase monoamine levels

Low levels of serotonin in the ventricular fluid of suicide victims

Decreased cortex activity in depression, esp. prefrontal cortex

Reserpine

A drug that depletes serotonin and norepinephrine, used to treat high blood pressure, found to induce depression in some patients.

Limitations of Monoamine Theory

Antidepressants take weeks to show effects despite immediate monoamine increases

Lowering monoamines doesn’t consistently lead to depression

Elevating monoamines doesnt reliably improve symptoms

Brain Changes Associated with Depression

Decreased brain volumes in hippocampus, amygdala, and cortex

impaired HPA function linked to stress

Neurotrophic support and neurogenesis issues leading to cell survival concerns

Depression Brain Activity

Overall decreases in brain activity in depressed patients

Genetic factors of depression

Genetic predisposition to depression indicated by high concordance rates among identical twins related to the serotonin transporter gene.

Environmental Factors of Depression

Stress can exacerbate existing conditions but may not directly cause depression

Gene and Environment Interaction Depression: Diagram of Interplay

Illustrates how genetic predisposition can interact with environmental factors to influence mental health outcomes

Neuronal connectivity in depression

Changes in the connectivity and activity of neurons and brain regions implicated in depression, affecting neurotransmitter systems.

Symptoms of panic attack

Discrete period of intense fear or discomfort with symptoms such as palpitations, sweating, trembling, and a sense of impending doom.

Fear response components

Include cognitive appraisal, physiological arousal, and behaviors such as fight, flight, or freezing.

Cerebral atrophy in schizophrenia

Structural brain changes including thinning of the cortex in temporal regions and enlarged ventricles associated with the disorder.

GABA receptors role in anxiety

GABA receptors mediate inhibitory neurotransmission that helps in reducing anxiety when enhanced by benzoacids.

Negative symptoms of schizophrenia

Symptoms that reflect a loss or decrease of normal functions, like emotional expression and social engagement.

Hyperactive hypothalamus

Increased activity of the hypothalamus associated with autonomic responses in anxiety.