CH 18: Biopsychology of Psychiatric Disorders Flashcards
Describe the POSITIVE symptoms of Schizophrenia & provide specific examples of each (5).
Positive Symptoms = symptoms that seem to represent an excess of typical function, i.e)
- Delusions - of being controlled, persecution
- Hallucinations - imaginary, critical voices
- Inappropriate Affect - failure to react appropriately to emotion or +/- events
- Disorganized Speech/thought - illogical thinking, belief in supernatural
- Odd Behaviour - difficulty performing everyday tasks
Describe the NEGATIVE symptoms of Schizophrenia & provide specific examples of each (3).
Negative Symptoms = symptoms that seem to represent a reduction/loss of typical function, i.e.)
- Affective Flattening - diminished emotional expression
- Avolition - reduced motivation
- Catatonia - motionless, awkward positioning for long periods of time
Describe the causal factors implicated in the development of Schizophrenia.
- ^Genetic factor
- Many genes linked to schizo, but no single gene causes it
- But concordance rate of schizophrenia in monozygotic twins is «100%
- -> Suggests a diff in experience have significant effect in development schizophrenia
- ie) maternal stress, socioeconomic factors, childhood adversity
- -> Alters typical course of neurodevelopment
- -> Leads to schizo in those w/ genetic susceptibility
Define ANTIPSYCHOTIC DRUG.
- Meant to treat certain symptoms of schizophrenia & bipolar disorders
List the 2 widely prescribed antipsychotic drugs.
- Chlorpromazine
2. Reserpine
Describe the discovery of CHLORPROMAZINE.
- Chlorpromazine:
- 1st used as antihistamine - counteracts swelling & had calming effect on some patients
- Antagonizes transmission at synapses by binding to dopamine receptors
- -> Chlorpromazine = receptor blocker = binds to dopamine w/o activating it
- Doesn’t cure schizo, but reduces severity of its symptoms
- -> Agitated patients were calmed, & emotionally blunted patients were activated by it
Describe the discovery of RESERPINE.
- Resperine:
- Antagonizes transmission at synapses by depleting brain of dopamine
- No longer used to treat schizo bc produce dangerous decline in bp & the doses needed for successful treatment
Describe the similarities b/w Chlorpromazine & Reserpine (3).
- Their antipsychotic effect manifested after 2-3 weeks of meds
- Antipsychotic effect ass. w/ motor effects similar to PD (ie. muscular rigidity)
- -> Suggests that both drugs act through the same mechanisms, one related to PD - Both antagonize transmission at dopamine synapses - but in different ways!
Describe the DOPAMINE THEORY OF SCHIZOPHRENIA.
Dopamine Theory of Schizophrenia:
= Schizophrenia is caused by too much dopamine & that antipsychotic drugs exert their effects by decreasing dopamine levels
see pg 478-479 for details
List evidence of support for the Dopamine Theory of Schizophrenia (2).
Support:
1. Reserpine (antipsychotic drug) depletes dopamine in brain by breaking down the synaptic vesicles in which the NTs are stored
- Drugs like cocaine (which trigger schizo-like episodes) ^extracellular levels of dopamine in brain
Describe ATYPICAL ANTIPSYCHOTICS.
Atypical Antipsychotics:
= Drugs effective against schizophrenia but DON’T bind strongly to D2 receptors
- Discredits dopamine theory
- see pg 479 for details
List 3 important notes RE: Atypical Antipsychotics
- Some D2 receptor antagonists have no antipsychotic actions
- Drugs that ^effects of glycerine or block effects of glutamate are proving to be effective treatments of schizophrenia
- There’s growing appreciation for the role of glutamatergic dysregulation in development of schizophrenia
Describe PSYCHEDELIC DRUGS.
Psychedelic Drugs:
= Drugs whose primary action is to alter perception, emotion & cognition
- ie) LSD, hallucinogens
Describe the conclusions made from research on its use in human brain (2).
- Study effects of psychedelic drugs in human brain
- -> Conclusions:
1. Effects of classic hallucinogens (ie. LSD) mimic the (+) symptoms of schizophrenia (ie. hallucinations) by acting as agonists of certain SEROTONIN receptors
- Dissociative hallucinogens mimic the (-) symptoms of schizophrenia by acting as antagonists of GLUTAMATE receptors
Describe research on SCHIZOPHRENIA-RELATED GENES.
- Learned the important roles certain genes play in developing schizophrenia
> ie) Various schizo-relate genes shown to: - Disrupt neural proliferation & migration
- Synaptic prying during neurodevelopment
- Myelination
- Transmission at glutamatergic & GABAergic synapses
** Some genes that ^ susceptibility to schizophrenia are also linked to other psychiatric & neurological disorders**
Describe research on BRAIN STRUCTURE CHANGES ass. w/ SCHIZOPHRENIA.
- Neuro-imaging techniques (ie. MRIs)
- Hippocamps, amygdla, thalamus & nucleus accumbens = significantly smaller in schizo
- Schizo-related V reductions develop in both grey & white matter
- -> Consistently observed in temporal lobes
- -> May be due to reduced neuron size & reduced dendritic & axonal arborization
List 4 important conclusions from research on schizophrenia.
- Individuals not diagnosed w/ schizophrenia but at risk of schizophrenia (ie. bc close relative) display V reductions in some parts of brain
- Extensive brain changes already exist when patients 1st seek medical treatment & receive 1st brain scans
- Subsequent brain scans reveal that the brain changes continue to develop after initial diagnosis
- Alterations to different areas of brain develop at different rates
Define CLINICAL DEPRESSION.
- Depression that’s so severe that it’s difficult for patient to meet essential requirements of daily life
- aka Major Depressive Disorder
Distinguish the difference b/w REACTIVE Depression & ENDOGENOUS Depression.
- Reactive Depression = triggered via obvious (-) experience
- Endogenous Depression = triggered via no apparent cause
Describe the causal factors implicated in the development of Major Depressive Disorder (3).
- Genetic factors, experience (ie. stress, trauma)
- SAD = Seasonal Affective Disorder
- Depression timed during winter months
- -> Suggest depression triggered by reduced sunlight - Peripartum Depression
= intense sustained depression experienced by some women during pregnancy, after giving birth, or both
List 3 major classes of antidepressant drugs.
- Monoamine Oxidase Inhibitors
- Tricyclic Antidepressants
- Selective-Monoamine-Reuptake Inhibitors
- Atypical Antidepressants
- NMDA-Receptor Antagonists
Describe MONOAMINE OXIDASE INHIBITORS - include an example.
- Monoamine Oxidase Inhibitors:
- ^levels of monoamines (ie. norepinephrine, serotonin) by inhibiting activity of monoamine oxidase (MAO)
- Has dangerous side effect = cheese effect
- -> ^risk of stroke bc ^bp when eat cheese
- ie) Iproniazid = 1st antidepressant drug
Describe TRICYCLIC ANTIDEPRESSANTS - include an example.
- Tricyclic Antidepressants:
- Blocks re-uptake of both serotonin & norepinephrine
- -> ^levels in brain
- Safer alternative than MAO inhibitors
- ie) Imipramine = 1st tricyclic antidepressant
Describe SELECTIVE MONOAMINE-REUPTAKE INHIBITORS.
- Selective-Monoamine-Reuptake Inhibitors:
= Serotonin agonists
- Exerts agonistic effects by blocking the re-uptake of serotonin from synapses
- Fewer side effects than Tricyclics &; MAO inhibitors
- Acts against wide range of psych disorders in add. to depression
- ie) Fluoxetine (aka Prozact) = 1st SSRI developed
- Similar class of drugs = SNRIs = Selective Norepinephrine Re-uptake Inhibitors
- -> as effective as SSRIs in treating depression
Describe ATYPICAL ANTIDEPRESSANTS - include an example.
- Atypical Antidepressants:
- A catch-all class for antidepressant drugs that didn’t fit into the above categories
- Each of the drugs in this class has its own unique mechanism of action
- see pg 483 for details
Describe NMDA-RECEPTOR ANTAGONISTS - include an example.
- NMDA-Receptor Antagonists:
- Positive effects of antagonizing the glutamate NMDA receptor on depressive disorders
- ie) Ketamine = a dissociative hallucinogen
- -> Single dose rapidly reduces depression
- -> Has undesirable side effects
Describe the various brain differences ass. w/ Major Depressive Disorder (3).
- Consistent reductions in grey matter V in:
- Prefrontal cortex
- Hippocampus
- Amygdala
- Cingulate cortex - White matter reductions in several brain regions (most in frontal cortex)
- Atypical activity in frontal, cingulate & insular cortices, amygdala, thalamus & striatum
List the 2 theories of the biology of Major Depressive Disorder.
- Monoamine Theory of Depression
2. Neuroplasticity Theory of Depression
Describe the MONOAMINE Theory of Depression.
List the evidence of support (2).
Monamine Theory of Depression:
= Depression ass. w/ under-activity as serotonergic & noradrenergic synapses
SUPPORT:
1. Fact that MAO inhibitors, tricyclic antidepressants, SSRIs & SNRIs are all agonists of serotonin, norepinephrine, or both
- ^Norepinephrine & serotonin receptors in brains of dead, depressed ppl w/o pharm. treatment
- -> Implies deficit in monoamine release
- -> When insufficient amount of a NT is released at a synapse, there’s a compensatory ^ in the #receptors for that NT
- -> process = ‘Up-Regulation’
Describe the NEUROPLASTICITY Theory of Depression.
List the evidence of support (2).
Neuropsychology Theory of Depression:
= Depression results from decrease of neuroplastic processes in various brain structures (ie. hippocampus)
–> Leads to neuron loss & other neural pathology
SUPPORT:
- Research showing stress & depression ass. w/ disruption of various neuroplastic processes
- -> ie) decrease in adult hippocampal neurogenesis - Research showing antidepressant treatments ass. w/ enhancement of neuroplastic processes
- -> ie) synthesis of neurotrophins
List 2 forms of treatment for depression that utilize brain stimulation.
- rTMS = Repetitive Transcranial Magnetic Stimulation
2. Deep Brain Stimulation
Describe rTMS.
- Repetitive Transcranial Magnetic Stimulation (rTMS):
= Form of TMS that involves noninvasive delivery of repetitive magnetic pulses at either high frequency or low frequency to specific cortical areas (usually prefrontal cortex)
- HIGH frequency rTMS = stimulate activity w/in those brain regions in which it’s applied
- LOW frequency rTMS n= inhabit activity
Describe Deep Brain Stimulation.
- Deep Brain Stimulation:
= Chronic brain stimulation via implanted electrode
- Tip implanted into area of white matter of anterior cingulate gyrus in medial prefrontal cortex
- Effective for those who don’t respond to other treatments
Describe HYPOMANIA.
- Reduced need for sleep
- High E
- Positive affect
- Talkative
- Energetic
- Impulsive
- Positive
- v confident
Describe MANIA.
- Same features as hypomania but taken to extremes
Additional symptoms:
- Delusions of grandeur
- Overconfidence
- Impulsivity
- Distractibility
Bipolar Disorder type II = bouts of _____ & _____.
- Depression & hypomania
Bipolar Disorder type I = bouts of _____ .
- Mania
Describe the various causal factors that have been identified for bipolar disorders (1).
- ^^^heritable
- Many diff genes in bipolar disorders
- ie) genes that code for particular Ca2+ channels & for particular proteins found at nodes of Ranvier
Describe MOOD STABILIZERS.
Mood Stabilizers:
= Drugs that effectively treat depression or mania w/o ^risk of mania or depression, respectively
- Acts against bouts of mania, some act against depression, & some act against both
–> But they do NOT eliminate all symptoms
- Some have adverse side effects (ie. weight gain, tremor, blurred vision)
Describe LITHIUM.
Lithium
= Simple metallic ion
= 1st drug found to act as mood stabilizer
- Found that lithium rate protected guinea pigs from toxicity of urea
- **Hypo that manic patients have lower levels of lithium than non-manic patients
Describe the brain differences ass. w/ bipolar disorder (3).
- Reductions in grey matter V
- Several specific brain structures smaller in bipolar disorder patients
- ie) medial prefrontal cortex, left anterior cingulate, L superior temporal gyrus, certain prefrontal regions, & hippocampus - Atypical activation in frontal cortex, medial temporal lobe structures & basal ganglia
Describe some of the theories of the etiology of bipolar disorders (4).
- Evidence of hypothalamic-pituitary-adrenal (HPA) axis dysregulation
- Marked disruptions in circadian rhythms in both patients w/ bipolar disorders & their non bipolar disorders
- Atlerations to GABA, glutamate & monamine neurotransmission
- Evidence that BDNF levels lower in bipolar patients when they’re either depressed or manic
Define ANXIETY.
- Chronic fear that persists in absence of any direct threat
Define ANXIETY DISORDER.
- Anxiety that’s so extreme & pervasive that it disrupts normal functioning.
List 4 anxiety disorders.
- Generalized Anxiety Disorder (GAD)
- Specific Phobias
- Agoraphobia
- Panic Disorder
Describe GAD.
- Generalized Anxiety Disorder:
- Stress responses & extreme feelings of anxiety & worry about a large # of different activities/events
Describe Specific Phobias.
- Specific Phobias:
- Strong fear/anxiety about particular objects/situations
Describe Agoraphobia.
- Agoraphobia:
- Pathological fear of public places & open spaces
- ^incapacitating than more specific phobia
Describe Panic Disorder.
- Panic Disorder:
- Recurrent rapid onset attacks of extreme fear & severe symptoms of stress (ie. choking, heart palpations, shortness of breath)
- Panic attacks occur in some cases of GAD, specific phobia, & agoraphobia
Describe the etiological factors that have been implicated in anxiety disorders (3).
- Anxiety disorders triggered by identifiable stressful events
- Anxiety focused on particular objects/situations
- Role of experience in shaping the disorder is apparent - ^^GENETIC component
- Heritable
- ^Concordance rates for monozygotic twins than dizygotic twins
- -> But no specific genes yet linked
List 3 drugs used in the treatment of anxiety disorders.
- Benzodiazepines
- Serotonin Agonists
- Antidepressant Drugs
Describe BENZODIAZEPINES..
- Benzodiazepines:
= Class of GABAA agonists w/ anxiolytic (anti-anxiety), sedative & anticonvulsant properties
- Adverse side effects = sedation, tremor, nausea, withdrawal reaction that includes rebound anxiety
- ^^Addictive
- -> Should be prescribed for short-term use
Describe SEROTONIN AGONISTS.
- Serotonin Agonists:
- Selective agonist effects type of serotonin receptor
- ^specific than benzodiazepines
- -> Produce anxiolytic effects w/o muscle relaxation &sedation
- Side effects = dizziness, nausea, headache, insomnia
Describe ANTIDEPRESSANT DRUGS.
- Antidepressant Drugs:
= Atypical antipsychotics ; anticonvulsants (some of which are effective mood stabilizers) are also effective treatments for certain anxiety disorders
- ie) SSRIs, SNRIs, & anxiolytic drugs
List 3 animal models of anxiety disorders.
- Elevated-Plus-Maze Test
- Defensive-Burying Test
- Risk-Assessment Test
Describe the Elevated-Plus Maze Test.
- Elevated-Plus-Maze Test:
- Rats placed in plus-sign-shaped maze above floor
- -> 2 arms have sides & 2 arms don’t
–> Measure anxiety as proportion of time rats spend in enclosed arms rather than venturing into exposed arms
Describe the Defensive-Burying Test.
- Defensive-Burying Test:
- Rats shocked by wire-wrapped wooden dowel mounted on wall of familiar test chamber
–> Measure anxiety as amount of time rats spend spraying bedding material from floor of chamber at source of shock w/ forward thrusting movements of their head & forepaws
Describe the Risk-Assessment Test.
- Risk-Assessment Test:
- Rats experience single brief exposure to cat then flee to their burrows & freeze
- -> Rats engage in variety of risk-assessment behaviours (ie. scanning surface from mouth of burrow)
–> Measure anxiety as amount of time rats spend in freezing & risk assessment
How were the above tests validated?
- Validated by demonstrating that benzodiazepines reduce the various indices of anxiety used in tests
- -> Whereas non-anxiolytic drugs do not
Describe research findings related to the neural bases of anxiety disorders.
- Overlap in brain structures involved in Major Depressive Disorder & anxiety disorders
- ie) prefrontal cortex, hippocampus & amygdala
- -> But difference in patterns:
- -> Major Depression: shrinkage of these structures
- -> Anxiety Disorders: No significant atrophy
Define TICS.
- repetitive, stereotyped movements or vocalizations
Describe TOURETTE’s DISORDER.
Tourette’s Disorder:
= Disorder of tics
Describe the symptoms of Tourette’s Disorder.
List some common motor tics & verbal tics.
- Begins in early life w/ simple motor tics (ie. eye blinking or head moving)
- ^complex & severe symptoms as patients grows older
- Common complex MOTOR tics = hitting, touching objects, squatting, hopping, twirling
- Common VERBAL tics = inarticulate sounds (ie. barking), repetition of words
- Symptoms reach peak in few years then gradually subside as patient matures
- -> Tics are involuntary but can be temporarily suppressed w/ [ ] & effort by patient
Describe research findings related to the neural bases of Tourette’s Disorder.
Tourette’s patients often have:
- Smaller stratal volumes
- When suppress tics, fMRI activity recorded in both prefrontal cortex ; caudate nuclei
- -> aka decision to suppress tics comes from prefrontal cortex, which initiates the suppression by acting on the caudate nuclei
Describe how Tourette’s Disorder is treated (3).
- Educate patient & fam about nature of syndrome
- Focus treatment on ancillary emotional problems (ie. anxiety & depression)
- Treat tics via ANTIPSYCHOTICS
- Often refused bc adverse side effects (ie. weight gain, fatigue)
- **Blocks tics
- -> Hypo that disorder is related to changes in the cortical-striatal-thalamic cortical circuit bc that circuit relies heavily on dopaminergic signaling
Describe the 3 phases of clinical trials.
PHASE 1: Screening for safety
- Finds maximum safe dose
- Used on healthy, paid volunteers
PHASE 2: Establishing the testing protocol
- Establishing most effective doses & schedules of treatment
PHASE 3: Final testing
- Clear demonstration that drug is therapeutic
Describe the 1st controversial aspect of clinical trials.
- Requirement for double-blind design & placebo controls.
- Sick patients wanting experimental treatment may be given placebo instead
- -> Ineffective for some patients
Describe the 2nd controversial aspect of clinical trials.
- The need for active placebos
- Experimental drugs may produce side effects
- -> Obvious to patient that they’re not in placebo group
- -> ^Contribute to positive effects of the drug
- Active Placebos = control drugs that have no therapeutic effect but produce side effects similar to those produced by the drug under evaluation
Describe the 3rd controversial aspect of clinical trials.
- Length of time required
- Patients desperately seeking new treatments are frustrated by amount of time needed for clinical trials
- -> ie) takes long time to be approved, etc.
Describe the 4th controversial aspect of clinical trials.
- Financial issues
- Drug companies pay scientists, physicians, technicians, etc. $$$ in drug trials
- -> Will suppress any (-) findings bc anxious to gain money back
- -> Rarely profitable
Describe the 5th controversial aspect of clinical trials.
- Targets of psychopharmacology
- Current characteristics of psychiatric disorders are the best they can be given the existing evidence
- -> But it’s clear that most disorders are likely clusters for disorders w/ diff patterns of ass. brain changes
- -> Thus, effective new drugs are likely to benefit only a proportion of those patients who have been given a particular diagnosis
- -> Thus their effectiveness might go unrecognized
Discuss the relative effectiveness of clinical trials.
- Clinical trials = most objective method devised to assess efficacy of a treatment
- Are expensive & slow
- -> But results are trustworthy bc trials carefully monitored/conducted
