NEUR533 - Mental Illness Flashcards
learning outcomes
Biological approach to mental illness
What was the first treatment medication for mental health in 1910?
arsphenamine
What is agoraphobia?
Fear of an open marketplace
Fear of outside, travel, crowds etc
What is OCD associated with?
Obsessions; recurrent intrusive thoughts, ideas or impulses
Compulsions; repetitve behaviours to reduce anxiety
E.g. extreme cleanliness and hand washing, counting
What part in the hypothalamus secretes corticotropin-releasing hormone (CRH)?
Paraventricular nucleus
What hormone does corticotropin-releasing hormone stimulate in the anterior pituitary gland?
adrenocorticotropin hormone (ACTH)
What are the 2 key brain areas that regulate the HPA axis?
Amygdala
Hippocampus
Where does the amygdala project to activate the HPA axis?
Projects to the bed nucleus of the stria terminalis
What does the hippocampus do to suppress HPA axis?
- Negative feedback
- Inhibits CRH release when increased cortisol present
What’s a new target for anxiety disorder drugs?
CRH receptors
Review - serotonin SSRIs
review different types of bipolar
Review the monoamine hypothesis of mood disorders
- Treatment focus on central serotonergic and noradrenergic systems
What is the diathesis-stress hypothesis?
- Genetic predisposition
- Glucocorticoid gene receptor expression regulated by early experiences
- Impacts CRH and HPA axis
- HPA hyperactivity
What changes have they found in the anterior cingulate cortex in depression?
Increased Resting-state metabolic activity
Can be related to increased HPA activity
Treatment of affective disorders - Electroconvulsive therapy (ECT)
How ketamine works on a neuron firing
John Cade inducing lithium treatment for bipolar disorder
Lithium is good for helping to calm mania episodes in bipolar disorder
Deep brain stimulation approach
What area does deep brain stimulation influence?
Anterior cingulate cortex (brodmann’s area 25)
Schizophrenia overview
Genetic relationship of schizophrenia
What are biological differences in the brain with schizophrenia?
- Physical changes
- Larger ventricle to brain size ratio
- Depleted temporal lobe and frontal lobe cortexes
- Reduced myelination
- Excessive catecholamine
- Glutamate hyperexcitability
Whats a neuroleptic drug that is a potent blocker of D2 receptors?
chlorpromazine
- used for amphetamine and cocaine psychoses
What is the main hypothesis triggering psychotic episodes of schizophrenia?
Dopamine hypothesis
Activation of mesocorticolimbic dopamine system
Review schizophrenia and diminished activation of NMDA receptors in the brain
According to Freud, mental illness results when the unconscious and conscious elements of the psyche come into_________.
conflict
A different theory of personality, championed by Harvard University psychologist _______________(1904–1990), is based on the assumption that many behaviors are learned responses to the environment. Behaviorism rejects the notions of underlying conflicts and the unconscious and focuses instead on observable behaviors and their control by the _____________
B. F. Skinner
environment
The disorder general paresis had a progressive course, starting with symptoms of mania—excitement, euphoria, and grandiose delusions—and evolved to cognitive deterioration and, ultimately, paralysis and death. Initially blamed on psychological factors, the cause was eventually traced to infection of the brain with Treponema pallidum, the microorganism that causes ____________.
syphilis
in 1910, German microbiologist Paul Ehrlich had established that the drug _____________ could act as a “magic bullet,” killing the T. pallidum in the blood without damaging its human host.
arsphenamine
The antibiotic____________ (discovered in 1928 by British microbiologist _________ __________) was found to be so effective in killing the microorganism that established brain infections could be completely eradicated. Thus, when penicillin became widely available by the end of World War II, a major psychiatric disorder was virtually eliminated.
penicillin
Alexander Fleming
A form of _______________ (dis- cussed later) has been linked to an autoimmune response triggered by streptococcal pharyngitis (strep throat) in children.
obsessive-compulsive disorder(OCD)
The approach of using genetic information to develop a treatment is sometimes referred to as______________ medicine.
molecular
Frequent panic attacks consisting of discrete periods with the sudden onset of intense apprehension, fearfulness, or terror, often associated with feelings of impending doom… WHAT ANXIETY DISORDER AM I?
Panic disorder
Anxiety about, or the avoidance of, places or situations from which escape might be difficult or embarrassing, or in which help may not be available in the event of a panic attack…WHAT ANXIETY DISORDER AM I?
Agoraphobia
At least 6 months of persistent and excessive anxiety and worry…WHAT ANXIETY DISORDER AM I?
GAD
Clinically significant anxiety provoked by exposure to a specific feared object or situation, often leading to avoidance behavior…WHAT ANXIETY DISORDER AM I?
Specific phobias
Clinically significant anxiety provoked by exposure to certain types of social or performance situations, often leading to avoidance behavior…WHAT ANXIETY DISORDER AM I?
social phobia
The symptoms include palpitations, sweating, trembling, shortness of breath, chest pain, nausea, dizziness, tingling sen- sations, and chills or blushing. Most people report an overwhelming fear that they are dying or “going crazy,” and flee from the place where the attack begins, often seeking emergency medical assistance….WHAT ANXIETY DISORDER AM I?
PANIC DISORDER
panic attacks
People with ________________________ have obsessions, which are recurrent, intrusive thoughts, images, ideas, or impulses that the person perceives as being inappropriate, grotesque, or forbidden.
obsessive-compulsive disorder (OCD)
Is the humoral response mediated by the HPA axis?
Yes
the hormone cortisol (a glucocorticoid) is released from the adrenal cortex in response to an elevation in the blood level of _______________________
adrenocorticotropic hormone (ACTH)
ACTH is released by the anterior pituitary gland in response to ___________________________________
corticotropin-releasing hormone (CRH).
CRH is released into the blood of the portal circulation by________________ neurosecretory neurons in the_____________________ nucleus of the hypothalamus.
parvocellular
paraventricular
Re-draw out
CRH is the chemical messenger between the ________________________ of the hypothalamus and the anterior pituitary gland.
paraventricular nucleus
The location of the amygdala and hippocampus.
The CRH neurons of the hypothalamus are regulated by two structures that were introduced in earlier chapters: the__________ and the____________
amygdala
hippocampus
Sensory information enters the_____________ amygdala, where it is processed and relayed to neurons in the __________ nucleus.
basolateral
central
Downstream from the amygdala, The bed nucleus neurons of the _______________ activate the HPA axis and the stress response.
stria terminalis
hippocampal activation____________, rather than____________, CRH release
suppresses
stimulates
Review
The hippocampus contains numerous _______________receptors that respond to the cortisol released from the adrenal gland in response to HPA system activation
glucocorticoid
Thus, the hippocampus normally participates in the feedback regulation of the HPA axis by inhibiting________ release (and the subsequent release of ACTH and cortisol) when circulating________ levels get too high.
CRH
cortisol
Anxiety disor- ders have been related to both___________ of the amygdala and____________ activity of the hippocampus.
hyperactivity
reduced
GABAA receptors are GABA-gated chloride channels that mediate_____ inhibitory postsynaptic potentials
fast
SSRIs are also highly effective for treating other psychiat- ric disorders, notably including______.
OCD
serotonin is released throughout the brain by a diffuse modulatory system originating in the ______ ______of the brain stem
raphe nuclei
The actions of serotonin are mediated by ___________ and are terminated by reup- take, via serotonin transporter proteins, into the axon terminal
GPCRs
SSRI therapeutic effects develop slowly, over a period of______, in response to regular daily dosing. This finding indicates that the immediate rise in extracellular serotonin caused by the SSRI is not responsible for the anxiolytic effect. Rather, the effect appears to be due to an________ of the nervous system to chronically elevated brain serotonin, via some structural or functional change that is not understood.
weeks
adaptation
Affect is the medical term for emotional state or_____; affective disorders are disorders of mood.
mood
It can occur suddenly, often without obvious external cause, and if left untreated, it usually lasts 4–12 months…. WHAT AFFECTIVE DISORDER AM I?
Depression
Another expression of depression, afflicting 2% of the adult population, is called________. Although milder than major depression, dysthymia has a chronic, “smoldering” course, and it seldom disappears spontaneously.
dysthymia
type ____bipolar disorder is also always associated with episodes of major depression.
II
The__________ Hypothesis. The first real indication that depression might result from a problem with the central diffuse modulatory systems came in the ______.
Monoamine
1960s
A drug called________, introduced to control high blood pressure, caused severe depression in about 20% of cases. Reserpine depletes central catecholamines and serotonin by interfering with their loading into synaptic vesicles.
reserpine
Another class of drugs that were introduced to treat tuberculosis caused a marked mood elevation. These drugs inhibit ___________________, the enzyme that destroys catecholamines and serotonin.
monoamine oxidase (MAO)
Another piece of the puzzle fell into place when neuroscientists recognized that the drug___________, introduced some years earlier as an antidepressant, inhibits the reuptake of released serotonin and nor- epinephrine, thus promoting their action in the synaptic cleft.
imipramine
According to this idea, called the monoamine hypothesis of mood disorders, depression is a consequence of a deficit in one of these diffuse modulatory systems
Where is norepinephrine secretied from?
Locus coeruleus
Where is NE secreted to?
Cerebellum
THalamus
Hypothalamus
Neocortex
Injected______ into the brains of animals produces behavioral effects that are similar to those of major depression: insomnia, decreased appetite, decreased inter- est in sex, and, of course, an increased behavioral expression of anxiety.
CRH
Recall that the activation of the_____________ glucocorticoid receptors by cortisol normally leads to feedback inhibition of the HPA axis
hippocampal
In depressed patients, this feedback is disrupted, explaining why_____ function is hyperactive. A molecular basis for the diminished hippocampal response to cortisol is a__________ number of glucocorticoid receptors.
HPA
decreased
What regulates glucocorticoid receptor number? In a fascinat- ing parallel with the factors implicated in mood disorders, the answer is genes,____________, and early childhood experience.
monoamines
In rats, it has been shown that the amount of glucocorticoid receptor gene expression is regulated by early sensory experience. Rats that received a lot of maternal care as pups express______ glucocorticoid receptors in their hippocampus, less CRH in their hypothalamus, and reduced anxiety as adults.
more
Elevations in brain____, and________ feedback inhibition of the HPA system, may make the brain especially vulnerable to depression.
CRH
decreased
Functional brain imaging stud- ies have consistently found_________ resting-state metabolic activity in the anterior cingulate cortex of depressed patients
increased
This region of the brain is considered to be a “node” in an extensive network of interconnected structures that include other regions of the frontal cortex, hippocampus, amygdala, hypothalamus, and brain stem…. WHAT IS IT?
anterior cingulate cortex
aCC
one temporal lobe structure affected by ECT is the___________, which we have seen is involved in regulating CRH and the HPA axis.
hippocampus
Antidepressant drugs include (1) tricyclic compounds (named for their chemical structure), such as imip- ramine, which among other actions, block the reuptake of both norepineph- rine and serotonin by transporters; (2) SSRIs, such as fluoxetine, which act only on serotonin terminals; (3) NE- and 5-HT-selective reuptake in- hibitors, such as venlafaxine; and (4) MAO inhibitors, such as phenelzine, which reduce the enzymatic degradation of serotonin and norepinephrine
Who discovered that lithium is highly effective in stabilizing the mood of patients with bipolar disorder, by preventing not only the recurrence of mania but also the episodes of depression
Australian psychiatrist John Cade
Lithium biochemical influence
Lithium affects neurons in many ways. In solution, it is a monovalent cation that passes freely through neuronal sodium channels. Inside the neuron, lithium prevents the normal turnover of phosphatidyl inositol ______, a precursor for important second messenger molecules that are generated in response to activation of some G-protein-coupled neurotransmitter receptors
(PIP2)
Lithium also interferes with the actions of ______ ______, essential for the generation of the second messenger cyclic-AMP, and glycogen synthase kinase, a critical enzyme in cel- lular energy metabolism.
adenylyl cyclase
This approach to treat depression was pioneered by Helen Mayberg, a neurologist…. what type of stimulation am I?
Deep Brain
Mayberg and a team of neu- rosurgeons at the University of Toronto found that electrical stimulation of a circumscribed region of the _____ ________cortex, comprising Brodmann’s area 25, could produce immediate relief from depression.
anterior cingulate
The name, introduced in 1911 by Swiss psychiatrist Eugen Bleuler, roughly means “divided mind,” because of his observation that many patients seemed to oscillate between normal and abnormal states…. what disorder am I?
schizophrenia
The symptoms of schizophrenia fall into two categories: positive and negative.________ symptoms reflect the presence of abnormal thoughts and behaviors, such as:
* Delusions
* Hallucinations
* Disorganized speech
* Grossly disorganized or catatonic behavior
Positive
______symptoms reflect the absence of responses that are normally present. These symptoms include:
* Reduced expression of emotion
* Poverty of speech
* Difficulty in initiating goal-directed behavior * Memory impairment
Negative
In some cases,_______________- is accompanied by peculiarities of voluntary movement, such as immobility and stupor (catatonia), bizarre posturing and grimacing, and senseless, parrot-like repetition of words or phrases.
schizophrenia
the brains of schizophrenics have, on average, a significantly_________ ventricle-to-brain-size ratio than people who do not have the disorder.
larger
schizophrenics often have defects in the_______ sheaths surrounding axons in their cerebral cortex
myelin
In Schizophrenia Changes in synapses and sev- eral neurotransmitter systems have also been implicated. As we’ll see next, particular attention has focused on alterations in chemical synaptic transmission mediated by_________ and glutamate.
dopamine
In the 1950s, researchers discovered that the drug chlorpromazine, initially developed as an antihistamine, could prevent the positive symptoms in schizophrenia. Chlorpromazine and other reduced antipsychotic drugs, collectively called neuroleptic drugs, were later found to be potent blockers of dopamine receptors, specifically the_____ receptor.
D2
The Glutamate Hypothesis. Another indication that there is more to schizophrenia than dopamine comes from the behavioral effects of phen- cyclidine (PCP) and__________.
ketamine
PCP and ketamine act by___________ NMDA receptors
inhibiting
