Chapter 16: Schizophrenia, Affective Disorders, Anxiety Disorders, And OCD Flashcards
Schizophrenia
Serious mental disorder characterized by disordered thoughts, delusions, hallucinations, and bizarre behaviors
Schizophrenia: Positive Symptoms
Presence of unusual behaviors, in excess of typical functioning
- Thought disorders - Delusions - Hallucinations
Thought Disorders
Disorganized, irrational thinking
Delusions
Believe that is clearly contradiction to reality (persecution, grandeur, and control)
Hallucinations
Perception of nonexistent object or events
Schizophrenia: Negative Symptoms
Absence or decrease in some typical behaviors
- Social withdrawal, lack of affect, anhedonia, and reduced motivation
Schizophrenia: Cognitive Symptoms
Cognitive deficits
- Difficulty sustaining attention, low psychomotor speed, deficits in learning and memory, poor abstract thinking, poor problem solving
Genetic Factors of Schizophrenia
- Heritability plays a role, but no “schizophrenia gene”
- Evidence of susceptibility to develop schizophrenia, but triggered by other factors
- Higher rate in monochorionic monozygotic twins
Schizophrenia Mutations
Mutations of DISC1 gene increases likelihood of schizophrenia and other mental disorders
Schizophrenia Paternal Age
Children of older fathers are more likely to develop schizophrenia
- Increased likelihood of mutations in chromosome of cells that produce sperms (mutations in spermatocyte)
Schizophrenia Epigenetic
- Rare mutations of epigenetic factors may predispose people to schizophrenia
- Methylation leads to suppression of gene
- DNA is wound more tightly
Epidemiology
Study of distribution and causes of diseases in populations
Environmental Factors of Schizophrenia
- Season of birth
- Viral epidemics
- Vitamin D deficiency
- Population density
- Prenatal stress
- Substance abuse
Seasonality Effect
Increased incident of schizophrenia in people born during late winter and early spring
Dopamine hypothesis
Positive symptoms of schizophrenia are caused by hyperactivity of dopaminergic synapses in the mesolimbic pathway
- Drugs acting as agonists produce and reinforce positive symptoms - brain may contain more dopamine receptors
D2 receptors and Schizophrenia
Increased in people with schizophrenia, but not main reason for schizophrenia
Chlorpromazine
DA-R blocker antipsychotic drug
Mesolimbic Dopamine Pathway and Schizophrenia
- Drugs acting as agonists produce and reinforce positive symptoms
- Some studies show those diagnosed with schizophrenia release excessive dopamine; brains may contain more dopamine receptors
- Certain thoughts are hijacking the mesolimbic system
- More DA
Consequences of Long-Term Drug Treatment of Schizophrenia
- Early drugs used for treatment had side effects
- Parkinson’s-like symptoms
- Tardive dyskinesia
Tardive Dyskinesia
Opposite of Parkinson’s
- involuntary movements of face and neck - Supersensitivity of D2 receptors in caudate nucleus
Supersensitivity
Caused by damage to afferent axons or long-term blockage of NT release
Hypofrontality
Decreased activity of PFC (especially DLPFC)
- believed to be responsible for negative symptoms - may also be responsible for hyperactivity in the mesolimbic pathways related to positive symptoms
Atypical Antipsychotics
Unlike original antipsychotics, they increase DAergic activity in PFC and reduce it in mesolimbic system
- Aripiprazole
Clozapine
Blocks D4-R in NAc
Aripiprazole
Acts as a partial agonist at DA-R
- Increase DA activity in PFC (low DA) - Decrease DA activity in mesolimbic system (high DA)
Glutamate hypothesis
Decreased Glu activity (resulting in hypofrontality) may contribute to negative and positive symptoms
- Chronic low doses of Glu antagonist drugs produces negative and cognitive symptoms - PCP and ketamine (indirect NMDA antagonists)
Developmental Changes Theories in Schizophrenia
- Abnormalities (suppressed DISC1 expression) in pyramidal neurons of the PFC are primary cause of process that leads to schizophrenia
- Abnormalities in the striatal DA system are primary causes of process that leads to schizophrenia
- result of inhibitory GABAergic transmission in DLPFC
Affective Disorders
- Characterized by disorder feelings
- Two main types
- Bipolar disorder
- Major depressive disorder (MDD)
Bipolar Disorder
Cyclical periods of mania and depression
Major Depressive Disorder (MDD)
Unremitting depression or period of depression that don’t alternate with period of trauma
Genetic factors of Affective disorders
- Heritability suggests genetic anomalies
- RORA, GRM8, and RORB genes all have associations with affective disorders
Antidepressants
- MAO inhibitors
- Tricyclic antidepressants
- Selective serotonin reuptake inhibitors (SSRIs)
- Serotonin and norepinephrine reuptake inhibitors (SNRIs)
- Ketamine
- Lithium
MAO Inhibitors
5-HT and catecholamines DA, Epi, and NE
Tricyclic Antidepressants
Inhibit reuptake of 5-HT and NE
Selective Serotonin Reuptake Inhibitors (SSRIs)
Prozac, Celexa, and Paxil
Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs)
- Antagonist action on NAergic transporters
- Milnacipran, duloxetine, and venlafaxine
Therapeutic Lag
Period of time between beginning antidepressant treatment and experiencing therapeutic effects
- autoreceptor densensitization
Ketamine
For treatment resistant depression
Treatment resistant depression
MDD whose symptoms aren’t relieved after trials of different treatment methods
Lithium
- For bipolar
- Taken as LiCO4
- positive response within 1-2 weeks
- side effects: hand tremors, weight gain, excessive urine production, and thirst
- Eliminates mania
- increased gray matter= neural.glial growth
Electroconvulsive Therapy
Involves brief electrical shock used to induce a seizure
- used to treat mania and depression - decreased brain activity and increased seizure threshold - rapid effects - risk of cognitive impairment or memory loss
Vagus Nerve Stimulation
- Indirect form of brain stimulation, but doesn’t induce seizures
- Used for treatment-resistant depression
Transcranial Magnetic Stimulation
- TMS provides similar benefits to ECT without risk of cognitive impairments or memory loss
- Used to treat depression
Deep Brain Stimulation
- useful for treatment-resistant depression
- implanted electrodes under subgenual anterior cingulate cortex
Subgenual ACC
Focal point in regulation of mood
Depressed patients show hyperactivity of […] along with decreased activity in […]
Depressed patients show hyperactivity of subgenual ACC along with decreased activity in DLPFC. VLPFC, VMPFC, and orbitofrontal cortex
Monoamine Hypothesis
Depression is caused by insufficient activity of monoaminergic neurons
- roles of norepinephrine and 5-HT
Tryptophan Depletion Procedure
Procedure involved low-Trp diet and Trp-free amino acid “cocktail” that lowers brain Trp and decrease synthesis of 5-HT
- Depletion of Trp in brain causes recurrence of depressive symptoms - 5-HT plays a role in mood, although exact nature is unknown
5-HT transporter and depression
- stressful life events increase probability of depression for those with 1-2 copies of short alleles for 5-HTT promoter
- less likely to respond to treatment
Neurogenesis and Depression
- Stress and depression are associated with reduced hippocampal neurogenesis (dentate gyrus)
- Antidepressant treatment increases hippocampal neurogenesis in lab animals
Exercise and Neurogenesis
Increased blood volume in dentate gyrus leads to neurogenesis
Circadian Rhythms and Depression
- Sleep disturbances
- Sleep deprivation can reduce depression in some people
- Seasonal affective disorder
Seasonal Affective Disorder
Mood disorder characterized by depression, lethargy, sleep disturbances, and craving for carbs during winter season when days are short
- can be treated by phototherapy - genetic basis: allele of gene responsible for production of melanopsin
Phototherapy
Treatment of SAD by daily exposure to bright light
Sleep and Depression
Reduced sleep latency, reduced REM latency, lack of slow-wave sleep, and general fragmentation of sleep
Anxiety Disorders
- Characterized by unrealistic, unfounded fear and anxiety
- Most common psychiatric disorder
- Overactive ANS
- Panic disorder
- Generalized anxiety disorder
- Social anxiety disorder
Panic Disorder
Episodic attacks of acute anxiety
- Anticipatory Anxiety - Agoraphobia
Anticipatory Anxiety
Fear of having panic attack
Agoraphobia
Fear of being away from home or other protected places
Generalized Anxiety Disorder
Excessive anxiety and worry serious enough to cause disruption of person’s life
Social Anxiety Disorder
Excessive fear of being exposed to scrutiny of other people that leads to avoidance of social situations in which person is called on to perform
Anxiety and Genetic Factors
- Genes for BDNF protein likely play a role
Anxiety Biology
- Increased activation of amygdala
- Decreased of VLPFC
BDNF
Neuronal survival and differentiation during development and LYP
Amygdala and vmPFC: Anxiety
Adolescents with generalized anxiety disorder show increased activation amygdala and decreased activation of vmPFC
- vmPFC-role in extinction and inhibition of fear and anxiety
Anxiety Pharmacological Treatment
- Benzodiazepines
- SSRIs
Benzodiazepines: Anxiety
- Bind to GABAa-R
- Fast acting; often used for emergency treatment
- Less appropriate for long-term treatment
SSRIs: Anxiety
- Preferred treatment option
- Used in conjunction with cognitive behavior therapy
Obsessive-Compulsive Disorder
- Individuals experience unwanted thoughts and uncontrollable behaviors
- Commonly begin in young adulthood
- Four categories: counting, checking, cleaning, and avoidance
Obsession
Unwanted thought or idea with which person is preoccupied
- also seen in schizophrenia
Compulsion
Feeling that one is obliged to perform a behavior
OCD Genetics
Heredity plays a role
OCD Environment
- Brain damage at birth, encephalitis, and head trauma
- Group A b-hemolytic infection
- Autoimmune disorder
Brain changes OCD
- Damage to the basal ganglia, cingulate gyrus or PFC
- There was an increase in size to the basal ganglia for those with b-hemolytic streptococcus
- Increased activity of frontal lobe and caudate nucleus in those with OCD
OCD Drug Therapies
Serotonergic agonists such as clomipramine, fluoxetine, and fluvoxamine used for treating OCD
- Clomipramine also used for three other compulsions - Symptoms relieved by increasing the activity of serotonergic pathways with inhibitory role in behaviors
Deep Brain Stimulation: OCD
DBS in basal ganglia or subthalamic nucleus
Serotonin can be seen in 3 different compulsions
Trichotillomania, onychophagia, and actual lick dermatitis
