NEUROBIOLOGY OF SCHIZOPHRENIA, MOOD DISORDERS, AND ANXIETY DISORDERS Flashcards


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1

Characteristics of Schizophrenia

Definition

Population %

Earlier onset in F/M?

  • Is characterized by thought disorders that reflect a break between the cognitive and the emotional side of one’s personality
  • Afflicts 1% of the population
  • Emerges in young adults
    • Men have a slightly earlier onset than women

2

Schizophrenia Pathophysiology

What are different causes?

  • Genetic predisposition
    • Likely involvement of several genes located on different chromosomes
  • Prenatal and perinatal vulnerability factors
    • Exposure to:
    • Prenatal infection
    • Prenatal nutritional deficiencies
    • Perinatal complications, such as birth defects and neonatal hypoxia
    • Upbringing in an urban environment
  • Neuroanatomic alterations
  • Enlargements of:
    • Enlargement of lateral and third ventricles; widening of frontocortical fissures and sulci
  • Reduction of:
    • Reduction in the thalamus and temporal lobe areas (e.g., amygdala, hippocampus, and parahippocampal gyrus)- disrupt neurotransmission between the frontal cortex and primary sensory and motor areas
  • Loss of:
    • Loss of cortical tissue
    • Volume loss in the hippocampus
  • Neurotransmitter alterations
    • Alteration of brain dopamine pathways- Dopamine inc.
    • Glutamate hypothesis: Decrease in glutamate receptors

3

Schizophrenia - Positive S/S

  • Positive Symptoms- Psychotic S/S
    • Frequently occur during a psychotic episode when the individual loses touch with reality and experiences something that should be absent
      • Hallucinations: perceptions are experienced without an external stimulation of the sense organ
      • Delusions: false beliefs are persistent
      • Disorganized behavior is exhibited
        • Disorganized speech
        • Disorganized or bizarre behaviors

4

Schizophrenia- Negative & Cognitive S/S

negative symptoms are experienced most of the time
during a 1-month period with some disturbance present over 6
months

  • Negative symptoms
    • Characterized by disruptions in normal emotional states and expressions
  • Negative dimensions- Negative State
    • Affective flattening: near absence of emotional or facial expressions throughout a conversation/situations
    • Anhedonia "D" decrease pleasure/depression
      • inability to feel pleasure
    • Alogia "L" language
      • poverty of speech- speak less often, use fewer words
    • Avolition "L" lack
      • lack of interest in goal-directed behavior/ lack of motivation
  • Cognitive symptoms- Capacity of memory
    • Problems with thought processes
    • Inability to perform daily tasks requiring attention and planning

5

Schizophrenia Treatment

Two categories of medications?

Consequence of first gen medications ?

What type of therapy?

  • Treatment
    • First-generation/conventional antipsychotic medications
      • Block dopamine - D2 blockers
      • Help with positive symptoms
      • May cause tardive dyskinesia after several years of use - tic-like jerky movements, such as smacking the lips or flicking the tongue, unsteady gait, or rocking back and forth when seated
    • Second generation/atypical antipsychotic medications
      • Reduce positive and negative symptoms
      • Block a range of neurotransmitters receptors
    • Psychosocial therapy
    • Cognitive behavioral therapy (CBT)

6

Mood Disorders

What is mood, affective states, depression?

Two categories of mood disorder?

Two types of Bipolar?

  • Mood: is a sustained emotional state
  • Affective states: are brief emotional feelings
  • Depression: states such as sadness become chronic and uncontrollable
  • Categories of mood disorder
    • Unipolar
      • AKA major depression or clinical depression
      • Is the most common mood disorder
      • Woman are more at risk
    • Bipolar
      • Bipolar 1 person has at least one manic episode followed by hypomanic or major depressive episodes
      • Bipolar II the individual experiences one major depressive episode for at least 2 weeks and at least one hypomanic episode for at least 4 days
      • Affects 3%–5% of the population

7

Mood Disorders Pathophysiology

  • Neurochemical dysregulation
    • Deficits in brain norepinephrine, dopamine, and/or serotonin, leading to depression
    • Mania: elevated concentrations of monoamines
  • Neuroendocrine dysregulation
    • Hypothalamic-pituitary-adrenal (HPA) system dysregulation
    • Altered immune and inflammation from cortisol
    • Hypothalamic-pituitary-thyroid (HPT) system dysregulation

8

Mood Disorders Pathophysiology Contd

  • Neuroanatomic and functional abnormalities
    • Widespread decrease in serotonin 5-HT1A receptor subtype
    • Reduction in glial cell numbers in people with unipolar and bipolar disorders
    • Decreased cerebral blood flow and glucose metabolism; some areas may have increased blood flow
    • Elevated cortical levels of glutamate

9

Mood Disorders: Depression S/S

  • Feeling sadness and despair
  • Feelings of worthlessness and guilt
  • Dysphoric mood: unhappy/unsatisfied
  • Reduced interest in pleasurable activities and interpersonal relationships
  • Sleep disturbances
  • Decreased concentration
  • Restlessness and agitation
  • Weight loss or weight gain
  • Suicidal thoughts

10

Mood Disorders: Mania S/S

  • Elevated levels of euphoria, self-esteem
    • Feelings grandiose with extreme levels of energy
  • May show poor judgment in spending money
    • May make poor business commitments
  • May become hypersexual
  • Excessive, rapid, loud, and pressured speech

11

Treatment for Depression

  • Depression
    • Antidepressants
    • Psychotherapy
    • Combination of both
    • Electroconvulsive therapy (ECT)
    • Deep-brain stimulation
    • Transcranial magnetic stimulation
  • Relapse is likely if medications and therapy are discontinued

12

Treatment for Mania: Bipolar I and II

  • Bipolar I
    • Lithium: first-line of therapy; must watch for toxicity
    • Lithium combined with SSRIs
    • Anticonvulsant agents
    • Atypical antipsychotic medications
    • ECT
    • Psychotherapy
  • Bipolar II
    • Antidepressants alone

13

Anxiety Disorders

How much of the population is affected?

People with anxiety disorders can also develop...?

Different types?

  • Affect 10%–30% of the general population
  • Many individuals with anxiety disorders develop major depression
  • Examples
    • Panic disorder
    • Generalized anxiety disorder
    • Acute stress disorder
    • Agoraphobia
    • Phobia: Social/Specific
    • Obsessive-compulsive disorder
    • Posttraumatic stress disorder (PTSD)

14

Anxiety Disorder:

  • Panic Disorders S/S

What is a complication to Panic Disorder?

  • Exhibits multiple disabling panic attacks and is characterized by intense autonomic arousal:
    • Lightheadedness
    • Difficulty breathing
    • Chest discomfort/Racing Heart
    • Generalized sweating/Chills, or Hot flashes
    • General weakness/Trembling
    • Abdominal distress
  • Complication: Agoraphobia, which is the phobic avoidance of places or situations where escape or help is not readily available
    • Can become homebound

15

Anxiety Disorder:

  • Panic Disorder Patho

What % of relatives does it affect?

Patho/Etiology?

Treatment?

  • Risk is nearly 20% among first-degree relatives

Patho/Etiology

  • pH alterations in the amygdala:
    • Heightened pH sensitivity in the amygdala may play a key role in generating fearful perceptions and activating the cerebral cortex and neural circuits in the temporal lobe and brainstem, which further facilitates the production of panic symptoms
  • Benzodiazepine (BZ) receptors are reduced:
    • increase panic attacks and feelings of anxiety, suggesting that an alteration in inhibitory neuromodulation contributes to panic disorder
      neuromodulation contributes to panic disorder.

Treatment

  • Approximately 80% respond to CBT and/or antidepressant medications
    • SSRIs; benzodiazepines, if nonresponsive

16

Anxiety Disorder:

  • Generalized Anxiety Disorder

Definition & Diagnosis criteria

Patho/Etiology

Treatment

  • Excessive and persistent worrying for at least 6 months
  • Motor disturbances, irritability, and fatigue
  • Six major symptoms of GAD have been identified and include
    restlessness, muscle tension, irritability, being easily fatigued,
    difficulty concentrating, and difficulty sleeping

Patho/Etiology

  • Norepinephrine and Serotonin abnormalities:
    • reduction in A2-adrenergic receptor binding, a decrease in serotonin levels in CSF

Treatment

  • 5-HT (serotonin)/norepinephrine (NE) reuptake inhibitors: venlafaxine
  • Behavioral therapy

17

Anxiety Disorder:

  • Post Traumatic Stress Disorder

Definition

Patho/Etiology

Treatment

  • Exposure to terrifying, life-threatening trauma
  • Intrusive flashbacks and nightmares

Patho/Etiology

  • Amygdala and Prefrontal Cortex affected:
    • exhibit increased activity in the amygdala and diminished activity in prefrontal cortical areas
  • Altered BZ binding:
    • reduced distribution of BZ receptor binding in the prefrontal cortex

amygdala and prefrontal cortex are highly involved in the pathophysiology of PTSD because these brain structures normally play important roles in how fearful memories are stored, retrieved, and extinguished.

Treatment

  • Group or family therapy, CBT
  • First-line treatment for chronic PTSD: SSRIs
  • TCAs, BZs
  • Other (some experimental): Eye Movement Desensitization Reprocessing (EMDR), ketamine, psychedelics

18

Anxiety Disorder:

  • Obsessive-compulsive disorder

Definition (Two core symptoms)

  • two core symptoms of obsessions and compulsions.
  • Obsessions: repetitive, intrusive thoughts
    • Thoughts of contamination, religion, sex
  • Compulsions: involve physical and mental ritualized acts
    • Washing, cleaning, checking, counting, organizing, hoarding, and repeating specific thoughts or prayers

19

Anxiety Disorder:

  • Obsessive-compulsive disorder

Patho/Etiology

Treatment

  • Genetic and environmental risk factors
  • Basal ganglia–frontocortical circuitry abnormalities
  • Lack of serotonin control over the dopamine system

Treatment

    • SSRIs: citalopram, fluvoxamine, paroxetine, and sertraline (first-line), BZs, antipsychotics: haloperidol, risperidone, olanzapine, or quetiapine
    • CBT and response prevention therapy
    • Neurosurgery-lesioning procedure (disconnect basal ganglia from frontal cortex)
    • If uncontrollable: ECT, transcranial magnetic stimulation (TMS), deep brain stimulation (DBS)