Week 6: Psychopathology Flashcards
Affective Disorders
Disorders of the mood; profound alternation of mood
Mania or depression
Depressed Mood
Increase or decrease in activity
changes in sleep (insomnia or hypersomnia)
suicidal ideation or thoughts of death
Mania
Feelings of gradiosity
Periods of excessive talking
Decreased need for sleep
Risky behavior
Area 25
Prefrontal cortex just below the genu of the corpus callosum
Activity (positive or negative) is mostly in this area
VTA to Nucleus Accumbens
A major player in reinforcement - changes in reinforcement (bad things seeming worse, good things seeming not as good) is characteristic of affective disorders
Iproniazid
Euphoria in TB patients - then used an antidepressant
Enhances MA functioning
Reserprine
Depression in hypertensive patients
Affects the vesicles and their ability to package NT to decrease MA functioning
Amphetamines CNS Actions
- Hampers reuptake of MA’s
- Enhances the release of MA’s
- Directly stimulates the postsynaptic receptors
Raphe Nuclei
huge arousal system
NE increases arousal
Locus Ceoruleus
5HT decreases arousal
Medications for Affective Disorders
- TCA’s
- MAO-I’s
- SSRI’s
- NSRI’s
- SNRI’s
- Other
TCA’s
Hamper reuptake of NE and 5HT, some do one better than the other
desipramine - blocks reuptake of NE better than 5HT
imipriamine - blocks reuptake of 5HT better than NE
MAO-I’s
global effect of MA’s
parnate
SSRI’s
Zoloft, Prozac
SNRI’s
Effexor = Pristiq
NSRI
Strattera
Others
Wellbutrin(Anti-depressant)/Zyban(quit smoking) - blocks reuptake of DA and NE
Remeron - Histamine receptor antagonist
Monoamine theory of Affective Disorders
affective disorders are the result of either underactive monoamine system in the brain or the levels of monoamine NT molecules in the brain are too low
Shortcomings of the MA Theory of Affective Disorders
Failst o explain why there is a 10-14 day delay of the onset of taking medication to the onset of clinical improvement
Beta Andrenergic Theory of Affective Disorders
Beta Andrenergic receptors are too active and the down regulation of these receptors (which takes 10 - 14 days) helps to treat depression
The down regulation comes with medication that block the reuptake of NE, and also with a variety that do not directly alter NE
Hypericum / St. John’s Wort
Helps mild-moderate depression
Inhibits MA’s
Inhibits the reuptake of 5HT, NE
Alternatives to Drug Intervention
- Electro-shock therapy
- Transcortical Magnetic Stimulation (TMS)
- Deep Brain Stimulation
- Vagus Nerve Stimulation
ETC
Current is sent through the patient’s brain
immediately down regulation beta andrenergic receptors
enhances 5HT sensitivity
95% response rate, but also a high relapse rate if nothing else is used.
TMS
Generates a strong magnetic field over the brain to change behavior, typically depression
data is not entirely convincing
Deep Brain Stimulation (DBS)
Drop electrodes into area 25 to down regulate activity and depression can be relieved
Some show improvement, some show none
Vagus Nerve
The relief may be due to its upstream pathway - including the locus ceoruleus, which deals with reward and pleasure
Treatment for Mania
Lithium
Side effects of Lithium
relief of manic symptoms mental dullness decreased memory and concentration headache fatigue
Effects of Lithium on brain functioning
decrease brain calcium levels enhances reuptake of NE and 5HT reduces release of NE Alters Na+K+ATPase Pump Prevents recycling of IP3 in G-protein system
Depression and Cortisol
Higher levels of ACTH in depressed patients may raise cortisol levels
May be result of hifh CTRH horomone in the hypothalamus
The feedback look to decrease cortisol may not be working properly (glucorticoid and dexamethasone)
Anxiety Disorders
Panic Disorder
Generalized Anxiety Disorder
Post-Traumatic Stress Disorder
Obsessive Compulsive Disorder
Anxiety Disorders
Panic Disorder
GAD
OCD
Drugs for Panic and GAD’s
first line: Benzo’s
-ativan, Xanax
SSRI
- BuSpar
Second line: antipsychotics
Drugs for OCD
Antidepressant: clomipramine
Motor involvement in OCD
The basal Ganglia (Caudate, Putamen, Globus Pallidus)
NT used by Basal Ganglia
- interneurons in the caudate use ACh
- Interneruons in putamen use GABA
- Striatal projections to globus pallidus use enkepahin and GABA
- pars compacta input to the striatum use DA
- cerebral cortical input uses glu
- output from globus pallidus to substantia nigra uses GABA and substance P
- input from raphe to the striatum uses 5HT
Psychoses
- hallucinations
- delusions
- disturbances of thought, languages and communication
- disturbances of emotion
Negative signs of Psychoses
absence of normal social and interpersonal behaviors
Positive signs of Psychoses
abnormal behavior
Anatomical differences in brains of psychotics
- reduction in blood flow to the globus pallidus (left side)
- frontal cortex does not respond vigorously
- the cortex of the medial temporal lobe is thinner and the antereior portion of the hippocampus is smaller
- lateral and third ventricles are larger (meaning there is less tissue there)
Areas that are prominent in Negative sign of psychoses
hippocampus, prefrontal cortex, basal ganglia
Hallocinogenic loop
Cortex -> basal ganglia -> substania nigra -> thalamus -> Cortex
Categories of Antipsychotics
- First generation antipsychotics - typical antipsychotics
- second generation - atypical antipsychotics
- third generation - abilify
Typical antipsychotics include
Thorazine
Prolixin
Haldol
Actions of antipsychotic drugs
they block DA
Typically induce a tranqulized state without loss of consciousness
Actions of antipsychotic drugs on the PNS
- they block ACh receptors
2. block alpha adrenergic receptors
Symptoms of Psychoses that respond well to medication
hallucinations acute delusions hostility flat affect general withdrawal
Effects of blocking Alpha Adrenergic recepotrs
increased heart rate
mild decrease in blood pressure
postoral hypertension
mild hypothermia
Effects of blocking muscarinic receptors
memory difficulties, confusion, delirium
DA systems
- Nigro-striatal DA pathway
- meso-limbic and meso-cortical systems
- tubero-infundiular sustem
DA Theory of Schizophrenia
Overactive or too much DA
D2 Receptors
principle site of action for phenothiazines and butyrophenones
Located in cerebral cortex, limbic structures, striatum (motor area)
D3, D4 receptors
limbic areas and cerebral cortex, NOT motor areas
Clozapine - Atypical blocks D3, D4 weakly blocks D2
Adverse Behavioral Effects of Antipsychotics
- Acute Dystonia - sustained muscle contractions
- Akathesia - compulsion to move
- Parkinson syndrome - very similar to Parkinson’s disease, but will recede with stopping on meds.
- Tardice Dyskinesia - late-onset motor disorder
Challenges to DA Theory
DA may not be causal pathway
5HT - Clozaprine, Risperidone, Zyprexa, Abilify
Glu has been suggested - DA may be secondary to Glu, Glu may be secondary to 5HT
