Ala2 Flashcards

Question

Dopamine

Answer 1

D, through D, receptors (all metabotropic) D. and D, probable runction Found throughout the forebrain Involved in complex behaviors, including motor function, reward, higher cognition Dopamine hypothesis- many substances inc dopamine release- dopamine main component of substance abuse Either direct,y or indirectly act on dopamine

Answer 2

As experiencing euphoria- changes how brain reacts to other stimulus Less dopamine released as on a drug-less pleasure dopamine effect are stunted- affected by drug

Answer 3

Chronic drug abuse severely affects NAc Drugs modify neuronal structure Drawings of representative medium spiny neurons from the shell of the nucleus accumbens in rats receiving saline (control), amphetamine, or cocaine injections. The numbers at the lower right side of each cell represent the number of branches, whereas the number by the spine segments represents the number of dendritic spines, per specified unit. Looked at NA Changes in behaviour after stop using More dendrite spine and branches in drugs- changes structure of neurons, might be permanent, never go back what it was

Answer 4

Receives information from VTA NA consists of a ‘core’ and a ‘shell’ mediates emotional relevance to generate motor response. Core- inner, shell- outer Have different unctions She’ll- emotional Core- motor response See if emotionally sig, if yes caause motor response Ealluate emotional sig Core- striatum Dopamine- activates emotional response

Answer 5

Recall: Craving = an insistent search for an activity SUD criterion Studies in rats show repeated exposure to an addictive substance alters NAc receptors to become more responsive to addiction-related stimuli PFC also disrupted Sti,mutate area, more happy rewarded- relieve depression Repeated spore to substance alters receptors of NA- less responsive to non drug stimulated, more responsive to addictive stimulus, pathway changes in many ways PFC- disrupted- not controlling impulses

Answer 6

Hans Breiter ALSO provides evidence that the brain responds to gambling in a similar fashion to the way it responds to drugs of abuse. Using a creative protocol, Breiter had subjects participate in a game of chance in which an arrow was spun on a disk to determine whether they won or lost money. Each play pf game- shown prospects – shown how much won or loss Most ppl counldnt track how much money, couldn’t tell winnings were growing- show changes in dopamine s winning vs not FMR- NA, hypothalamus and amygdala activated- inc activity White= anticipation- hope they win getting high during anticipation- no matter outcome Dec of activity during outcome Amygdala- during bad outcome

Answer 7

Activation of mesocorticolimbic and brain stress systems. Decreased sensitivity to endogenous DA  anhedonia Medications that increase DA  increase shopping, gambling, or sex DA dysregulation is the common thread Impulsivity/compulsivity Between behavioural and substance Dec susceptibility of dopamine- lack of pleasure

Answer 8

DA neuronal firing signals the difference between prediction and actual occurrence of rewards  “reward prediction error” (RPE) hypothesis DA neuronal activity is hypothesized to code the uncertainty associated with rewards (Schultz) Also showed depression after omission of reward or aversion Dopamine- anticipation signal monkeys trained to respond to fruit juice When given randomly- inc in dopamine After time, gave stimulus that predicted juice coming- neurons fire in response to reward coming, no difference when given the juice If reward didn’t come- Dec in firing rate Rewards that we should be receiving- fully predicted- anticipation cue response Random reward- inc dopamine If reward doesn’t come after anticipation- dopamine Dec we modify dopamine based on reward signalling Helps us to learn and associate Response of dopamine neuron- firing depend as prediction Dopamine- prediction error teaching ignal

Answer 9

Drug use is not a random phenomenon: It’s a purposeful attempt to decrease negative states (Khantzian, 1985): Assuage pain Manage psychological problems Manage personality traits and disorders - Decrease stress Drug use is purposeful- take to Dec negative state

Answer 10

Rats have steady flow of nicotine Have pump removed- do they experience withdrawal 8 hr after- biggest symptoms Stimulating nicotine drug dependence Does it like drug or not- given drug in one environment not the other Test them take out divider- let them go to environment they prefer- drug vs non drug area Above 0 liked that environment Below 0 – didn’t like environmentn Nicotine in non ependent mouse- don’t like nicotine If have withdraw- don’t like withdraw environment Wit both nicotine and withdrawal- prefer nicotine and not being in withdrawal Give vehicle before, Block withdraw- Dec dopamine agonist and agonist Inc or Dec activation of dopamine- doesn’t cause withdraw Dopamine receptor balance- cause withdraw- inc or Dec- want see withdraw

Answer 11

Hypothesis: A specific pattern of DA neuronal activity at DA receptors signals the aversive motivational response to withdrawal from chronic nicotine. Wht receptors are important Electrode into neuron and see activity- VTA Electrophysiology: in vivo extracellular single unit recordings of VTA DA neurons in rats. Big does of nicotine inc dopamine

Answer 12

Bursting activity- phasic Vs stable= baseline Further reduced during withdrawal from nicotine Actuate nictorm inc phasic Withdrawal inc tonic Can we block phasic dopamine Only sig for acute nicotine- big aversion – block phasic dopamine- no effect of withdrawal Acute nicotine  Phasic DA activity Nicotine withdrawal  Tonic DA activity Phasic DA  D1Rs Tonic DA  D2Rs (Goto & Grace, 2005) Acute nicotine aversions  D1R ? Nicotine withdrawal aversions  D2R ? Acute nicotine- butting of dopamine Withdrawal- tonic da activity inc

Answer 13

In non modified mice- withdrawal aversion –aversion to withdrawal- notinvolved w d1 receptor Separate effects of acute nicotine and withdrawal that has seperate effects of dopamine, and activates dopamine receptors Aversion blocked by given d1 agonist or agonist Withdrawal aversion- blocked when given d2 agonist or antagonist

Answer 14

-involved in synaptic plasticity and DA neuronal survival Action of BDNF at its receptor, TrkB, is involved in cocaine & opiate addiction  injection of BDNF in NAc potentiates cocaine reward BDNF injection in VTA switches rats to anopiate-dependent state (Vargas-Perez et al., 2009) Role in drug craving & relapse Cant give opamine agonist- inc dopamine and inc shizophrenic symptoms Antagonist less dopamine- Parkinson’s like symptoms Help neuron grow and develop Bdnf- changing dependent vs non independent state Activateing bdnf- incloved in addiction, makes it more rewarding Put bdnf in VTA- inc addiction

Answer 15

Bdnf in the vta makes mice behave as if nicotine dependent- they have never ecieved drug before- makes mice act as if they are dependent on nicotine Switch happen bc of bdnf in VTA- can we switch it back, make them act non dependent

Answer 16

Stress- main motivation to do drug-withdrawal causes stress Lots of dopamine, crf- only in hippocampus Crf unregulated in VTA when in withdrawal or nicotine dependent- no chance in hypothalamus or amygdala, inc of crf – being made in VTA If we prevent it, don’t experience withdrawal. Affect of withdrawal specific to vta Block crf- do u block aversion- only blocks in nondependt Can prevent withdrawal aversion by blocking crf

Answer 17

Allostasis/Balance (Koob & Le Moal) The recruitment of negative reinforcement is mediated by the corticotropin-releasing factor (CRF) brain stress system, driving addiction (rather than DA & reward) Acute reward still involves DA & other NTs Neuroadaptations occur that motivationally oppose the hedonic effects of drugs of abuse Ba=rain wants balance When take drugs- brain wants balance CRF- drives addiction once its been established Once become dependent- neural captions occur- oppose rewarding and Adonis effect NA interacts with amygdala and opamine and crf intereaction VTA drives he crf

Answer 18

2 types of neuroadaptations involved in transition to addiction: Within-system adaptations 2. Between-system adaptations Crf in dopamine neurons, become expressed in dopamine neuron- Dec tonic dopamine activity, stress inc crf, inc dopamine in crf causing relapse and drug abuse 1- change n dopamine eneurons- decrease tonic cacitivut- within dopamoogerci pathway 2- change in brain, inc in crf, Repeated exposure to drug- changes brain and behaviour Drug changes from impulsive to compulsive Inc dopamine bursting active, inc in drug taking behaviour- pose for cement Change to compulsive-driven by neg enforcement- release from stress- driver= release of stress neural adaptive switch

Answer 19

The prefrontal cortex (PFC) is involved in inhibitory response control; is disrupted by long-term exposure to drugs of abuse  impaired inhibitory control, decision making, emotion, motivation Both DA and amygdala important as well via connections with FC Imaging of drug abusers show PFC abnormalities (hyper- and hypo-activity) -also decreased gray matter in PFC OCD: PFC activation  compulsivity Pfc involved in inhibition no impulse control , damage to Pfc, Dec in signalling, inc singnillang in other areas- impair decision make=inc and intros= poor decision making, loss of control ,emotional 0problems Affects many other areas of brain Amygdala and opamine- connected with Pfc- rats more vulnerable to self administration habit- Dec dopamine activity in NA, PFC Dampening of activity in PFc Abnormal functions, les neurons Directionality problem

Answer 20

In addictive individuals- d2 recepto is less, glucose stabilization is less as well Dec activity associated with low dr2 levels

Answer 21

Volkow 4 clusters of behaviour interconnected in a positive feedback loop DA function & PFC function diminishes with addiction Drugs come to be more effective rewards compared to other stimuli Drug addiction involves problem in information processing- damage in one area effects all the circuit- influencing many functions Pfc- mediates expectations, executive functioning, dopamine diminishes with addiction Impaired response inhibition and salience- drugs payed more attention to, drug is more rewarding then anything Elise PFC- impaired dirong binging and relapse craving= impulsive repsonding, salient drug rewards

Answer 22

The transcription factor ΔFosB is rapidly induced (and accumulates) in the NAc and the dorsal striatum after drug use. -Mice engineered to overexpress ΔFosB show enhanced sensitivity to a variety of drug effects Some proteins regulated by FosB are involved in glutamate transmission  structural plasticity (ex. increased dendritic branching and spine density; LTP)  ΔFosB may play a significant role in the transition from controlled drug use to addiction More delta fosb- more likely to be sensitive drug Changes in neural plasticity Drug related memories stronger ΔFosB modulates gene expression by epigenetic mechanisms: DNA methylation represses transcription (down-regulation of proteins) Histone acetylation promotes transcription (up-regulation of other proteins) Epigenetics effects- changes dna experessiom influx in amount of proteins-changes susceptibility tod rugs

Answer 23

Learn to respond to drug in environment Change environment, tolerance reduced Learn to associate cues to certain environment Take it somewhere else- not have earned tolerance= drug causes stronger efffects- overdose

Answer 24

Rats were given a high dose of heroin 96% of control group died Tolerant rats, given heroin in the same room (ST, yellow) were more likely to survive than in a different room (DT, blue). Same holds true for other drugs Cravings induced in same way- learned cravings Experience cue- don’t have drug- withdrawal bc of associated effect Causes treatment difficulties Tolerance only for one environment In tolerance group- survived in same environment Situational tolerate Alcohol- Dec body temp, develop tolerance to it, not much change A conditioned response to the cues previously paired with drug administration Person conditioned to be more tolerant

Answer 25

Sociocultural influences When consumed in a group setting, drugs may enhance social bonds The user escapes from normal social norms, roles & responsibilities Drug subcultures: Users embrace social rituals surrounding a particular drug and reject conventional norms and lifestyles Drugs can enhance solidarity within an ethnic or peer group Observational learning/Social Learning Theory

Answer 26

Comprehensive (integrative) perspective (Devor, 1994) Substance abuse is a complex and varied disorder that results from the dynamic interaction of genetic and environmental factors over the course of development High incidence of comorbidity reported in the DSM-5 between almost all of the psychological disorders suggests they may have some causal overlaps, be it underlying genetic predispositions and/or environmental pressures.  Substance use disorder is the result of the unique interaction between: primary genetic risk factors with- histor of substance use, genes secondary genetic risk factors with – other disorder genestertiary genetic factors with- small genetic changes external environmental factors- trauma, job loss- interacts with all Leads to epigenetic changes in gene expression and changes in temperament Biopsychosocial model of addiction - includes all the pharmacological, biological, psychological & sociocultural factors that influence addiction risk: Some factors promote likelihood of addiction, others reduce it

Answer 27

Brain is divided Studied and described for only a century Moved from hopelessness and instutionalization to reduction of symptoms Kraepelin, a psychiatrist and researcher, was among the First to attempt to distinguish different forms of mental distress. From among the many mental patients there emerged a group with a cluster of partially overlapping symptoms that he called dementia praecox. Realized schizophrenia is important and changed it from hopelessness. - when recognized it’s a brain disorder Negative symptoms- harder to detect Symptoms of schizophreni- was point of interest for many Ayurveda- describes it as disorder of mind Aretaeus- poor contact with reality and delusions about being poisoned More modern First to distinguish different mental illnesses and symptoms Hallucinations, motor tics, disrpution in thoughts- thought this was a syndrome- dementia= precursor to schizophrenia

Answer 28

Coined the term ‘schizophrenia’ Bleuler categorized the symptoms associated with schizophrenia into fundamental and accessory symptoms. Coined schizophrenia Split mind Characterized symptoms Fundamental- moo and alterations in thoughts Accessory – got most clinical attention delusions hallucinations

Answer 29

Positive symptoms of schizophrenia Negative symptoms of schizophrenia Disorganized (Cognitive) symptoms of schizophrenia Interest success of drugs based on what it is treating- positive= easiest Hallucinations, disorganized thoughts

Answer 30

Positive- there and shouldn’t be Most common- auditory- can involve any perception Delusions false belief, hallucination- false perception Delusions of grandeur- about importance of self Delsusions o percecutions Psychotic= more severe Psychotic episode- delusions and hallucinations and cognitive symptoms Negative= something taken away from them- emotion, speech, lack of motivation and pleasure Seen in many disorders- frontal lobe damage ‘ Cognitive- poor problem solving- frontal lobe Positive= ecsessive dopamine Negative and cognitive- developmental process impairing bran

Answer 31

The DSM5 diagnosis of schizophrenia is based on six diagnostic criteria which encompass a combination of symptoms and clinical features: Criterion A: Characteristic symptoms -At least 2 or more of the following: *Delusions; *hallucinations; *disorganized speech; grossly disorganized or catatonic behaviour; negative symptoms*1 of 2 symptoms must be one of these 2 or more- one has to be- one positive t Criterion B: Dysfunction Criterion C: Persistence of the disturbance for at least 6 months Criterion D: Exclusion of concurrent disorders with psychotic features Criterion E: Exclusion of substance use or other medical conditions Criterion F: Consideration of childhood disorders Have to make sure not due to any other disorder Autism or other childhood disorder- only present if pos symptoms

Answer 32

It is important to distinguish between bizarre delusions and those that are mood congruent, which may reflect a mood disorder rather than schizophrenia spectrum disorder Critique: The diagnosis currently used appears to be reliant on the patient’s presenting symptoms and history as the main indication of the illness. A significant drawback is the subjectivity of the diagnosis: there are no instruments to detect symptoms Dimension of symptoms Have to make sure different from other disorder This method is bad because have to be presenting symptoms and for certain time- may have schizophrenia but not presenting or not long enough Very subjective and no instrument

Answer 33

Schizophrenia is a complex condition characterized by heterogeneity: Individuals with very different family and personal history, varying response to treatment and prognosis, and ability to live independently are given the same diagnosis. Not just genetics Different family history and response to treatment and genetics- given same diagnosis Hard to say how going to affect the- all different

Answer 34

The lifetime risk of developing schizophrenia = ~1% Typically, symptoms first appear between 15-45. Once diagnosed, individuals are less likely to complete their education or maintain a job and more likely to develop additional psychiatric problems, including depression and drug abuse. Approximately 1 in 7 patients experience recovery. Many on schizophrenia- milf symptoms Slow emergence

Answer 35

Phase I (Pre-morbid)-Largely asymptomatic Phase II (Prodromal)-Prodromal “oddness” & onset of subtle negative symptoms (~late teens) Phase III (Active)-Active phase with destructive positive symptoms; treatment and relapse (~21-40 years old) Phase IV (Static / Residual)-Static phase, poor social functioning and prominent negative and cognitive symptoms. (> 45 years-old) Premorbid- some symptoms Prodorml- odd behaviour, neg symptoms- late teen Active- experiencing symptoms Residual- neg, cog symptoms , poor social functioning Men display these earlier and therefore worse and harder to treat Men= early 20, women- late 20 More earlier diagnosed= worse prognosis

Answer 36

Once diagnosed- less likely to complete education, get job More likely to develop other symptoms 1 in 7 experience recovery Risk inc when close family have disorder Inc risk 2 %- uncle and aunt Inc as get closer in genetic- more shared genes Not 100% genetic Look for transcription marker Translocation- exchange of dna between chromosomes Found abnormal translocation- of mental disorder in kid Many members had this link- had different disorders Stars= had translocation and had schizophrenia If have translocation- got schizophrenia, but not for everyone- genes don’t tell whole story

Answer 37

Many genes more common in individuals with SCZ Difficult to replicate results Large number of more common genes produce small effects DISC1 (disrupted in schizophrenia 1) gene controls rate of generation of new neurons and dendritic spines in the hippocampus Possibly caused by new gene mutations or microdeletion of chromosome Many genes more common in schizo Common genes- produce common effects, more genes- more likely Impacts nw neurons and dendriti spine, connections in brain- glutamate Probably combination of genetic and environment Epigenetics- effect of environment on expression of genes- doesn’t modify dna What happen to genes in uteri and shortly after

Answer 38

Strong tendency for prevalence to increase with latitude. Further away from equator, colder temp is, greater prevelance of schizophrenia Have greatest rates of infant mortality- prenatal periods susceptible to cold, affect brain in long term- affect critical period of development

Answer 39

Interleukin-8 Levels Were Nearly Twice as High in Mothers of Offspring Who Developed Schizophrenia Pregnancy and after incidence of schizo Looke at blood of moms whose kids got schizo Is there a link bw blood and schizo Looked at inflammation marker- if ik= more inflammation Schizo= higher inflammation, exposed to more illness This was during flu epidemic The offspring of flu exposed mothers were significantly more likely to display schizoprenic symptoms compared with children born at any other time More likely to have schizo symptoms and other disorders Exposed to virus in uteri- higher risk for schizophrenia and other disorders

Answer 40

After flu season- hogher risk for schizophrenia Kids born after flu season- higher risk of schizophrenia Obsevered by many studies

Answer 41

Prenatal and birth environment:-Complications during birth may cause brain dysfunction/damage -Obstetrical and birth complications (e.g., Caesarean section, anoxia at birth)-Season of birth / Prenatal virus exposure (Ex. influenza virus exposure during second trimester)-Vitamin D deficiency External risk factors- nongenetic Complications in birth- have impact on brain development- affect later in life More likely to have deficiency in vitamin d- don’t know the directionality

Answer 42

The finger ridge count consists of the number of ridges which cut or touch a straight line Finger ridges- on finger print appear at end of fourth month of development Abnormalities can depict abnormalities I brain development Number of ridges that touch straight line Ridge count Relationship bw embryonic stress and simpler ridges instead of whirls have more arches . Schizophrenia have less ridges Suggests early disturbance in utero Inc risk of schizo

Answer 43

Adoption studies suggest a genetic role Therefore prenatal environment cannot be discounted Environmental influence, such as family environment, ALSO shown to have a role Immediate genetic relative- have correlation w stress Prob due to prenatal environment Environment influences genetic risk- more dysfunctional family and genetics= way higher risk

Answer 44

A combination of various environmental stressors triggers the onset of the disease in early adulthood if that person is genetically predisposed (vulnerable) Biological vulnerability may be inherited or acquired; can take the form of neuroanatomical or neurochemical abnormalities, or both Support: SES inversely related to rates of schizophrenia Genetic vulnerability combined with stressor in environment leads to disorder Vulnerability- genetics, brain anormalities and stress- lowers SES, dysfunctional family leads to schizo

Answer 45

Pschyiatric and neurological symptoms Have loss of brain tissue- less eye movement Twice as large ventricle- structural change= larger ventricle More empty space- brain loss Loss of neurons Everyone losses some brain matter as age- this loss is heightened in schizophrenia and earlier In temporal and frontal If brain develops differently- inc susceptibilities Ventricles reflect hippocampal differences Hippocampus and amygdala and frontal lobe- smaller Volume reduction is subtle- 4 % smaller on both size 8% reduction of those areas Smaller left hippocampus(right side)- speech, perceptions Degeneration is early in disease process- throughout life

Answer 46

In what ways do the genetic factors express themselves? How does the brain go from normality to the depths of psychosis following the timed orchestrations of genes being expressed? Why is onset later in life if brain abnormality is ealry on Male more severe and a bit earlier

Answer 47

Disruption in synaptic connectivity Hippocampus is disordered More disorganized in more severe cases

Answer 48

Is this because of pruning of neuronal conenctions Teenagers- experience around puberty- have grey matter and white matter loss Extends throughout 20 May not be dying of neuron over year- loss of grey and white matter- coincides with loss of cortical matter Big amount of cell loss This loss greater when have chizophrenia

Answer 49

= Schizophrenia is caused by abnormalities in prenatal or neonatal nervous system development Leaves the developing brain vulnerable to disturbances later in life Result: mild abnormalities of brain anatomy and major abnormalities in behaviour Caused by abnormalities in prenatal and leave developing brain susceptible to experiences- major abnormalities in behaviour- little brain abnoramlities

Answer 50

DLPFC = one of the slowest brain areas to mature -Area shows consistent signs of deficit in SCZ patients This area- slowest brain area to mature Damage prenatally in this area- won’t know till later Early damage- don’t see expression of it till later Seen in monkeys Memory problems, attention problems younger- minor Get worse as get more mature and brain matures

Answer 51

Schizophrenic subjects show deficient activation of the dorsolateral prefrontal cortex (hypofrontality). Frontal lobe issues Less activity

Answer 52

Dopamine involves Thorazine- help delsuiosn Affecting dopamine In schizo- may be excess dopamine in synapses= too much activation Attention learning and memory Pleasure and reward Sleep Motor movement Problem solving Antipsychotic/neuroleptic drugs Category of drugs tend to relieve schizophrenia and similar conditions Primary action is DA receptor antagonism (D2) Ex. Chlorpromazine Drug commonly used to treat schizophrenia Relieves the positive symptoms of most patients These drug- dopamine receptor antagonist- act against dopamine D2 receptor Relieves most pos symptoms Dopamine blocking effect Larger doses= more effect

Answer 53

Schizophrenia results from excess activity at dopamine synapses in certain areas of the brain Research indicates increased activity specifically at the D2 receptor in schizophrenics Primary evidence= drugs- reduce if dopamine antagonist Cant be sole cause Do immediately but effect takes week to work Using these drugs- show schizophrenia Enhance positive symptoms Inc dopamine

Answer 54

Recall: Mesocorticolimbic system Midbrain tegmentum (VTA) DA neurons projecting to the NAc and prefrontal cortex (PFC) Site where drugs that block dopamine synapses produce their effects Antipsychotics also block DA in the Substantia Nigra Result is tardive dyskinesia, characterized by tremors and involuntary movements From VTA to nucleus succumbs to PFC VTA- if dopamine production ] Blocking dopamine recptor in many areas Activity of dopamine- too much- cant follow rational thought sequence May be due to dysfunction in communication to amygdala- emotional responses Schizo= more paranoid- over activity of amygdala- see neutral faces as scary

Answer 55

First Generation Anti-Psychotics Muscle rigidity Slowing of physical movement 3. Loss of physical movement 4. Tremors Also block dopamine in substantial Niggra- moves dopamine to movement area- leads to tremors and involuntary movement Good at reducing psi symptoms- cause issues in movement- inducing Parkinson’s like symptoms Don’t want unwanted side defects Dopamine Antagonists Reduced Institutionalized Patients Reduction in patients in mental institutions- cold be integrated back into fam with antipsychotic

Answer 56

aka Atypical antipsychotics Seldom produce movement problems Have less effect on dopamine D2 receptors More strongly antagonize serotonin type 5-HT2 receptors and dopamine D4 receptors More effective at relieving positive symptoms. Some effect on negative symptoms. More expensive, and do not significantly improve quality of life (over typical drugs) Less effect on d2 receptor Decrease hallucinations- releave pos and some neg symptoms Don’t ave as much movement problems More expensive and don’t immprove quality of life, Dec immune system Atypical antipsychotics also have side effects: Weight gain Immune system impairment On drug inc activity in frontal lobe esp

Answer 57

Name Nigrostriatal Location of Cell Bodies Substantia Nigra (caudate nucleus & putamen) Location of Terminal Buttons Striatum Behavioural Effects Movement Mesolimbic Ventral tegmental area Amygdala & Nucleus accumbens Reward pos symptoms Mesocortical Ventral tegmental area Prefrontal cortex Short-term memory, problem-solving cog and neg Explain link bw overactivity of dopamine and pos symptoms- caused by disorganized attentional processes linked to PFC Nigrostriatal= movement Mesolimbic and mesocortical- frontal lobe Pos= hyperactivity Neg and cognitive= dysfunction in these areas

Answer 58

Glutamate hypothesis of Schizophrenia: Schizophrenia is caused by deficient activity at glutamate synapses, especially in the prefrontal cortex In many brain areas, dopamine inhibits glutamate release Alternately, glutamate stimulates neurons (Ex. VTA GABA) that inhibit dopamine release  Increased dopamine thus produces the same effects as decreased glutamate Define it in glutamate synapses in PFC Simulate dompamin- inhibiting glutamate Stimulates neurons Inc dopmaine- and Dec glutamate- produce same effects Dopamine hypothesis also supports glutamate hypothesis Less glutamate and receptors Interacts with dopamine Define it in glutamate synapses in PFC Simulate dompamin- inhibiting glutamate Stimulates neurons Inc dopmaine- and Dec glutamate- produce same effects Dopamine hypothesis also supports glutamate hypothesis Less glutamate and receptors Interacts with dopamine Phencyclidine (PCP): Blocks Glutamate NMDA Rs PCP administration produces psychosis PCP does not produce psychosis in pre-adolescents & produces a much more severe psychosis in people with a schizophrenic history. BUT, no antipsychotics directly stimulate glutamate activity. Why? PCP- blocks glutamate and receptors- produces psychosis- pos and neg symptoms Only produces it in adolescent and stronger effect for schizo- history No drugs do this- rlly bad for rest of brain- excytosicity- kill brain cells Too much glutamate not goof- too risky

Answer 59

Mood continuum Normal variation expected  Severity and duration of mood changes required for diagnosis much stronger than normal variation.  Cause must also be considered Mood= continuum- variations in mood Dsm moved from categorical- yes or no and moved to dimension- vary in severity of emotions- its on a continuum Have normal variation Normal mood= middle, go up and down Distinguish normal mood vs disorder is severity of mood fluctuations- how severe and how long Diagnosed- symptoms for a certain time(duration is important) Not considered disorder until extended time Also look at cause- what brought it on – circumstances

Answer 60

Part A: Specific symptoms, at least 5 of the following 9, present during the same 2-week period, not due to another medical condition: Depressed mood most of the day, nearly every day, as indicated by either subjective report or observation made by others. Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day. *At least 1 of the 5 symptoms MUST be 1 or 2. 9 specific symptoms- #1 or two or both must be present At least 5 in 2 week period – for most days Once experience more likely to happen and time often Inc 1- depressed mood most of day- done subjectively- report feeling sadness or one observes their depressed mood 2- not getting same nejoyement- not interested in activities used too 3. Significant weight change (5%); or change in appetite nearly every day. 4. Insomnia or hypersomnia 5. Change in activity 6. Fatigue or loss of energy 7. Feelings of worthlessness or excessive or inappropriate guilt (may be delusional) 8. Concentration: diminished ability to think or concentrate, or indecisiveness 9. Suicidality Ppl think those who are depressed show it They smile less at funny things Absence of happiness- not getting joy= more noticeable than sadness 2- 5% change within month, change in appetite- different portrayal of symptoms in children- not meeting milestones 5- slow or restless- decrease in speech 6- related to insomnia or hypersomnia- tasks= too much to handle 7- feeling of worthlessness with no route I reality- dwell on past experiences 8- cant focus, indecisive, cant make small decisions

Answer 61

Part B: The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. The episode is not attributable to the physiological effects of a substance or to another medical condition. If use of a substance (ex. Cocaine) is related to depression, then it would be diagnosed as ‘cocaine-induced depressive disorder’ People mourning a recent death can be diagnosed with depression if symptoms meet criteria for depression Part b- distress to person- is it causing impairment, stress Depressive episode not du to substance or other condition Substance induced depressive disorder Previous dsm- didn’t consider grief Experiencing this is difficult Focus on duration and severity

Answer 62

After age 14, MDD more common in women When it occurs in children, likely to persist a long time Affects 5% of adults (within a year) ~20% lifetime prevalence Canadian Report on Mental Illness (2010 Underlying cause for discrepancy- unclear- may be responsiveness to stress and how one deals with stress, hormonal differences Need to do research on both male and female If have in childhood often persists Ealrier and more fewuent episode left untreated= more vulnerable for more episodes Women more diagnosed- could be diagnostic issue- women go to help more

Answer 63

Argument: Depression is a normal, adaptive function of the system Paul Andrews: The Bright Side of Depression (?) An evolutionary theory of depressive behaviour -Mind becomes more analytical and focused, helps us solve problems  Adaptive benefit of feeling depressed Depression in all life styles- could be because modern conditions is so different from ancestors- leads to depression- one explanation= prob not enough Depression is more than disorder- ppl naturally show it and is normal and adaptive- helps a to ruminate and solve problems- afasptive to solve issues Depression is similar to a fever ppl w a fever experience impairment and distress- but not a disorder Having a fever is adaptive- strengthens immune system Depression- causes stress and impairment

Answer 64

Distress and impairment is usually found in depressed individuals trouble performing daily activities can’t concentrate socially isolate themselves lethargic loss of pleasure Andrews: MDD is not necessarily any more of a disorder than a fever Is an adaptive behaviour Depression- psych painful, cant focus, lethargic, loss of pleasure doesn’t mean an episode of depression is a disorder

Answer 65

So what could be so useful about depression? Depressed people tend to ruminate. Have difficulty thinking of anything else. Studies have shown that this style of thinking is highly analytical! Depressed people dwell on a complex problem, breaking it down into smaller components, which are considered one at a time. Very productive analytic style Depression is a normal adaptive function of system and lives in a continuum- depression is adaptive- sate of mind which brings distress and helps to solve problems- mind becomes analytical, logical- solve problems which triggered episode- focus on this= better solve depression and help solve problems Breaking the problem into components- some ppl do problems better when depressed

Answer 66

Depressed and non depressed students identified people’s emotions from pictures of eyes Students classified as mild to moderately depressed were better at recognizing emotion in pictures of people’s eyes. Mildly depressed- better able to detect emotions in pictures of ppl eye Unstersanding emotions- detect emotion then figure out what uis happening Depressed= better to detect emotions but interpret more negatively

Answer 67

Other MDD symptoms that may help with problem solving: Social isolation helps the depressed person avoid situations that would require thinking about other things.-can ruminate adaptively The inability to derive pleasure from sex could also be seen as a way of avoiding distraction. Loss of appetite promotes analytical thinking and focus. Chewing and talking interferes w brain unctioning Score lower on cognitive tasks- focused on own problems

Answer 68

Depression has a moderate degree of heritability, but no one gene has been identified as clearly linked to depression People with early-onset depression (before age 30) are more likely to have relatives with MDD & other disorders Late onset depression (after age 45) linked to relatives with circulatory problems Hypothesis: the effect of a gene varies with the environment (G X E) Passed on from parent to child Genes related to psych functioning- make it more easy to get depression Gene change with enviroment One allele-copy of gene 5htt-serotonin transporter Short allele- associated with depression- binder region is shorter Gene components same- binding region- shorter- causing less transporters Serotonin transporter- transport serotonin back up- recylcle into neuron Having different allele- less transporters- more vulnerable to depression More mRNA in long allele 2 long alleles 2 short alleles- more vulnerable- changes in serotonin recycling- get stressed-more vulnerable to depression One of both Large meta-analysis showing that there is a stronger interaction with the environment (GxE effect) with the S allele Meta analysis- stronger interaction with environment with shorter allele- more vulnerable to environment

Answer 69

Young adults with the short allele (vs long allele) of the serotonin transporter gene (5HTT) who also experienced stressful events had a major increase in the probability of developing depression May be linked with early childhood maltreatment Having stressful event- doesn’t mean will def experience 3 or 4 stressful events= double risk, interacts with enviroment Need experience to express depression Negative delay ever= more vfulnerable

Answer 70

‘Kindling hypothesis’: depressive episodes become more easily triggered over time Kindling can be described as a process which occurs by a lowering of the threshold, or by an increase in spontaneous dysregulation. Twin studies suggest genetic contributions: patients with a high genetic risk were ‘prekindled’ MDD is episodic- don’t usuallyh experience whole life Reccuance is norm Look at patients- more episodes= higher risk for another episode Future episodes predicted by past events More reliable than stressors Kindling- episode is more easily triggered over time, threshold is lower, more senstitves Cant control experience of emotions happe suddenly Hghj genentic risk= more vulnerable to experience episodes, may not be strefful- leads to depressive episode

Answer 71

Altered metabolism in the prefrontal cortex (PFC) in mood disorders. Metabolism is decreased in depressed subjects who are either BD (“Bipolar depressed”) or MDD (“Unipolar depressed”) relative to healthy controls. High activity- back of brain Treatment needs to be tailored to brain- changes in activity Mild brain trauma- enduring effect on brain Need brain rehabilitation Need to look at brain- consider brain Assumptions need to be made- same symptoms= same dysfunction= regulated treatment Altered metabolism in PFC- especially near subgenuial PFC- involved in MDD Glucose metabolim- reduced = reduced cortical area

Answer 72

PET: decreased blood flow and reduced glucose metabolism in the frontal lobes have been associated with depression: Opposite for mania. MRI: cingulate cortex may lose its ability to ‘control’ the emotional processing function of the amygdala -associated with the short allele of the HTT These factors may underlie the tendency of depressed individuals to continuously engage negative information or ruminate about depression-inducing events or information. Not as much activity= less blood flow opposite is true for mania Cingulate cortex- changes activity- decreases, cant control amygdala- PFC doesn’t shut down amygdala= enhanced emotional processing- emotional info- more important- focus after stimulus is gone Depressed- cant let go of neg emotion

Answer 73

Different prefrontal areas apart of limbic amd regulation system Dec neurons in Pfc and Dec volume esp in left hemisphere- emotion Inc activuty in right amygdala Reduced volume in hypothalamus Nucleus succumbuns- lack of motivation, reward

Answer 74

Have PFC- cingulate cortex, DLPFC, OPFC- disturbs circuit- compromised feedback regulation. In circuit Disconnect or changes in activity- hyoactivty- dysregulation in other mood areas DL- hyperactive limbic- doesn’t have stimulation- stimulate emotions, hypothalamus= more depressiom

Answer 75

Certain brain activity is associated with depression Decreased activity in the left prefrontal cortex Increased activity in the right prefrontal cortex This imbalance proves stable over the years, despite symptom changes Ex. People with depression tend to gaze to the left when asked to do a verbal task Most people gaze to the right Change= stable over years Gaze to the left more= changes use of brain areas

Answer 76

If drugs that increase levels of serotonin help treat symptoms, depression must be caused by low levels,…right? SSRI everyone needs different treatment-different damage Serotonin releases- attaches to receptor have uptake and auto receptor- manage serotonin If drugs blocking serotonin transporter- serotonin stays in synapse- help depression

Answer 77

Imipramine - Treatment of schizophrenia Iproniazid - Treatment of tuberculosis Tricyclic antidepressants (named from chemical structure) Used to treat tuberculosis – made ppl happy inhibiting mioanimines which breaks down NT inc duration of synaptic transmission- many side effects- act on many things Imipramine- tricyclic antidepressant- inhibit seton in reuptake now have many- block uptake of serotonin, dopamine

Answer 78

Tricyclics (such as imipramine (Tofranil) Block transporter proteins that reabsorb serotonin, dopamine, and norepinephrine into the presynaptic neuron after release Also block histamine receptors, acetylcholine receptors, and certain sodium channels  Side-effects include drowsiness, dry mouth, difficulty urinating, and heart irregularities Block monanimines Prevent reobsorption

Answer 79

MDD: Is Serotonin low? More serotonin- thought to be serotonin as cause of MDD Have lower levels of 5-Hiaa Eat more tryptophan- dozens make you happier Tryptophan depletion did not immediately increase depression… Serotonin function is not linearly related to the level of depression Tryptophan— not supported Serotonin- not linked to serotonin- depends on neurons instead

Answer 80

Sleep, energy, or appetite may improve within the first 1-2 weeks. Improvement in mood and lack of interest in activities may need up to 6-8 weeks to fully improve. Antidepresent- work immediately Behaviour and symptoms may not improve for weeks

Answer 81

Blood samples indicated that depressed patients had significantly lower plasma concentrations of NE and other principal central nervous system metabolites of NE Modulate norepinephrine Catacomine- depression= bc of low catacomines Depression= less norepinephrine NE neurons are in the pons and medulla of the brainstem Locus coeruleus (LC) in the pons: a dense collection of NE neurons (~12,000 in humans). Fibers run in the dorsal adrenergic bundle, extend to nearly all areas of forebrain. Also cerebellum and spinal cord. Also lateral tegmentalnucleus fibers run in medial forebrain bundle Only one area rich- in pons Fibres- run in bundle- send axons to release norepinephrine – small area supplies all brain Axons run in tract to send norepinephrine through Bain Neurons run in medial bundle too but less

Answer 82

So what’s NE good for anyway? -Vigilance/alertness -Sleep/wake cycles -Reward/reinforcement Stroke of dorsal adrenergic bundle depression -Suggested NE involvement in depression! Alertness vigilance Circadian rhythm Reward and reinforcement Lots of sleep, loss of pleasure Stroke in this area= more likely to experience depression Norepinephrine- key in roles implicated in expression Reboxetine Drug inhibits reuptake More likely to feel better

Answer 83

Serotonin norepinephrine reuptake inhibitors (SNRIs) Examples: duloxetine (Cymbalta) and venlafaxine (Effexor) Block reuptake of serotonin and norepinephrine Block reuptake of serotonin and norepinephrine- more effective

Answer 84

Monoamine theory: Not enough NTs around MAOIs increase their levels at the synapse –block degradation(TCAs, MAOIs) or reuptake (SSRIs, SNRIs) Not enough monoamine and the one tht blocks the enzyme- leave more monoamines in synapse Cause is stressor- something happens Not enough monoamines= degregate recxerptord Take drug= more receptors= more NT Have lots of drugs

Answer 85

Miscellaneous group of drugs with antidepressant effects and milder side effects Examples: Bupropion (Wellbutrin) Inhibits the reuptake of dopamine and to some extent norepinephrine, but not serotonin Have milder effects Wellbutrin- leaves serotonin alone- also helpful for substance abuse

Answer 86

Depressed people have lower than average brain-derived neurotrophic factor (BDNF): important for synaptic plasticity  People with MDD show: Smaller than average hippocampus Impaired learning Reduced production of hippocampal neurons Prolonged use of antidepressants increases BDNF production Some people respond to one drug and not the other The antidepressant- produce effect in hour- takes a while to change- because of synaptic plasticity MDD- have less bdnf- les ihppocampal neurons inc in bdnf w drugs

Answer 87

In adult animals, new neurons are formed continuously from progenitor cells located in the subgranular zone (SGZ) Those neurons differentiate and become incorporated into neuronal circuits in the hippocampus Producing neurons all the time- making stem cells which divide into neurons These neurons incorporated into neuronal circuit is Dentate gurus- new neurons- takes time Time when neurogenesis is forming new neurons- bdnf has been elevated, new neurons forming- takes abt 5 weeks Maybe why depressed ppl have smaller hippocampus- related to neurogenesis

Answer 88

Inc in NT- due to antidepressant= more bdnf= more dendritic spines, more synaptic connection More monoamines

Answer 89

Proliferation of new neurons in the hippocampus is important for antidepressant effects Some studies show antidepressants may not be helpful at all, especially for mild depression Need proliferation of new neurons- for antidepressant to work May not work when one has more damage to brain, more depressed

Answer 90

Drysdale et al., 2017. Resting-state connectivity biomarkers define neurophysiological subtypes of depression. Nature Medicine 23, 28-38. fMRI images of 1188 people Identified 4 subtypes of depressed people, with different symptoms and responses to treatment Differences in brain in depressed ppl- had different symptoms, different responses to the drugs 4 biotypes of depression

Answer 91

Found in the nucleus accumbens (reward pathway) & others Transcriptional factor (activator) Low levels in individuals with stress-induced depression at autopsy, and in animal models of social defeat Antidepressant medication shown to increase the expression of this transcription factor Resilient animals have high levels of it Depressed ppl Adonia- lack of pleasure Delta- transcription factor- if its around- transcription is happening Low levels found in stress induced depression also in animal models of social defeit Resilient animals- don’t stop fighting, persevere- high lvls- important in depression and resilience ΔFosB in brain reward circuits mediates resilience to stress and antidepressant responses Delta- High co-occurrence in depression and treatment Socially isolates=more stress= less delta In nucleus succumens Depressed mice- don’t interact w other animals Then inc delta-wanted to be social- acting less depressed Happy mice- when inhibit delta- behave like depressed/socially isolated animals May turn on creb- forms complex- binds w binding protein to activate it Depressed= doesn’t turn on In depressed humans- less delta

Answer 92

Shown to be equally effective for all levels of depression talk therapy Causes increased metabolism in same brain areas as antidepressants More likely to reduce incidence of relapse months or years later Depression occurs in episodes- spontaneous recovery should happen for most Drugs= moderate to severe Talk therapy= all levels Should be doing drugs and therapy- more likely to have LT benefits

Answer 93

Helpful to depressed ppl BrdU- inc bdnf- nerve growth factor Active exercise- inc oxygen- survival and proliferation of neurons After 12 days- rat exercising- more new neurons BrdU- marker for proliferation Exercise- enhance neurons

Answer 94

Electrically induced seizure used for the treatment of severe depression For severe MDD patients who have not responded to antidepressant medication Side effects include memory impairment (amnesia) Minimized when shock is only to right hemisphere Electric convulsive therapy Nothing else works Applied to head every other day for 2 weeks May impair memory for a few months- mimimized when only shock right hemisphere

Answer 95

Physician implants battery powered device into the brain to deliver periodic stimulation Targets brain areas that increase activity as a result of antidepressant drugs *Still in experimental stage Encouraging results Alternative (of the future): optogenetic stimulation Can control individual connections Developed for Parkinson’s Implant battery powered device- deliver periodic stimulation to the brain Optigenetics- control connections of brain Only in animal Inc signalling in areas that lost activity A semi-permanent implant Adjustable Like a pace-maker for the brain Performed in > 150,000 patients with Parkinson’s disease or Essential Tremor DBS for MDD is associated with a > 50% response rate, which is stable over time

Answer 96

The use of an external stimulus to alter (ideally optimize) how the brain functions The progressive ladder of neuromodulation Using external stimulus to change brain function Rtms- magnets- least invasive

Answer 97

Subcallosal Cingulate Cortex (Cg25) In healthy controls, hypermetabolic during sadness, hypometabolic during euthymia Cingulate cortex- healthy= more metabolism in sadness and less in happy = Subgenual cingulate cortex within PFC Area shows increased activation when sad  Chronically activated in some treatment resistant depressives Target for DBS Gained lots of attention Changes in depressed individuals Get sad- should see inc activity here Chronically activated in some treatment resistive depression- always feeling tht way

Answer 98

Subcallosal Cingulate Cortex (Cg25) In healthy controls, hypermetabolic during sadness, hypometabolic during euthymia Recovery from depression correlates with reduced Cg25 metabolism In depression recovery- reduce metabolism her Thought to be switch than can modulate depression

Answer 99

Medial forebrain bundle MDD Subcallosal Cingulate MDD, PTSD Ventral striatum OCD Nucleus Accumbens Alcohol use disorder Different areas targeted depending on disorder Target medial forebrain bundle- many neurons in rewards systm- projects to nucleus succumens

Answer 100

Bold looks and big personalities: Differences in guppy appearance and behaviour is a balance between mate attraction and predation risk. Natural to have fears- many fears survival mechanism- perceive as threat Should have an. Appropriate response- neurobiological response Even babies exhibit fears- not just because of experience= innate fear Heights- acrophobia Survival instincts- fear snakes Learned condition response- more experience= less fear Become accustomed to it Does this make sense- more deaths from car the snakes, evolutionary speaking we should be more afraid of cars now Thought that fears and phobias are adaptive- disorder= maladaptive Natural fears, depression, anxiety- emotions and experiences are adaptive, help us adapt to environment and survive in world Info about fears- come from animal studies For guppies looking bold and colourful is beneficial for sexual attraction= more likely to get mate, more courageous- more likely to find a mate Medium looking ones- stick to group- less likely to get eaten Balance between attracting mate and protection from predators More likely to get eaten= less colourful If we compare anxiety like behaviour in animals, we can see that the most “paranoid” guppies will actually live much longer than those who take risks. Non clourful and non courageous- live longer Flashier and more courageous=die quicker- anxiety can help organism from danger Self preservation- learn from mistakes Couragessnos and colour- related to anxiety

Answer 101

A problem emerges if aspects of emotional and physiological arousal creep into our lives when immediate doom is not obvious. First described by Jacob Da Costa in U.S. Civil War Soldiers. "He rejoined, after a short stay in hospital, his command, and again underwent the exertions of a soldier’s life. He soon noticed that he could not bear them as formerly; he got out of breath, could not keep up with his comrades, was annoyed with dizziness and palpitation, and with pain in the chest; his accoutrements oppressed him, and all this though he appeared well and healthy…. “ (Da Costa 1864) Horror movies play on survival instincts Have internal drive to survive that activates anxiety response Amygdala- responds by activating stress response Something not causing the anxiety- but sense of fear is still there= issue Da costa looked at soldiers- first identified anxiety They couldn’t bear what they used to as well, lose breath, pain in chest- had overactive nervous system- sympathetic nervous system in over drive They were experiencing PTSD- nothing in environment

Answer 102

Thoughts and brain- intertwined Amygdala activated- processes emotional sig- more active= perceive as more tressful Signal sent to hypothalamus Pituitary connected to hypothalamus Hypothalamus- leads to hormonal release Causes release of stress hormone Cry- in amygdala Hypothalamus releases Pituitary releases hormone Adrenal glands reduce cortisol Other areas of hypothalamus- sleep, hunger reproductive hormones Amygdala- hypothalamus- pituitary- adrenal= stress response

Answer 103

Route brain takes to activate sympathetic Hypothalamus- stimulates accelerator nerves- inc breath rate, heart rate, pupils dilate Adrenal cortex- cortisol Hypothalamus leads to all these functions in thus pathways Soldier heart= triggering of fight vs fight pathway in absence of environmental trigger - distinction between fear and anxiety disorder Disorder- psychological factors, not environmental triggers Fear= present, danger Anxiety- worry, psychological in future

Answer 104

Obvious signs- inc HR, sweating, BR- more easy to spot Chronic stress- acne, muscle aches and pains, reproductive system changes, problems with sexual behaviour infertility Immune system lowered Immune system tries to fight cortisol- cant an decreases in function- get more illnesses Long term effects Brain problems- sleep eating concentration

Answer 105

Physiological: changes in the autonomic NS involving respiratory, cardiovascular, & muscular changes in the body. Cognitive: alterations in consciousness & specific thoughts you’re having Behavioural: responses to the consequences of certain emotions. Highly interrelated: Each affects others 3 components pf emotions Before just looked at physical- heart rate, breathing rate, muscle tone- autonomic nervous system functioning Cognitive- thoughts, changes in intention, feelings of hopelessness Behavioural- actions person takes- leave room, pacing Each component is related, affected each other Have physical because of cognitive- vice vera

Answer 106

Adaptive Concerns are realistic, all things considered. Amount of fear is experienced in proportion to the threat Fear response subsides when the threat ends Maladaptive Concerns are unrealistic; source of anxiety either cannot hurt them or very unlikely to occur Amount of fear experienced is out of proportion to the harm the threat could cause Fear response continues or is persistent even after the threat is no longer present; additionally, the person may experience a great deal of anticipatory anxiety Adaptive- beneficial in some way- concerns are validated- more adaptive Amount of fear is different and how severe they feel it is- excessive amounts- often maladaptive- depends on situations Does the fear go away Worry about assignment- finish it, worry goes away- more adaptive anticipatory anxiety- anticipating situation causes anxiety b

Answer 107

Anxiety = future oriented Fear = a more primitive emotion; occurs in response to a real or perceived current threat. From an evolutionary perspective, fear is important because of the response it elicits…  fight or flight response, so named because fear either prompts a person to stay and fight or to run away (flee) from a dangerous situation. Anxiety and fear are distinct Both lead to fight vs flight but only fear should Anxiety- shouldn’t be having debilitating fear Fear is normal Anxiety can be pathological Anxiety- on continuum- fear of specific event- more sever Generalized anxiety-broad but less intense- still debilitating Anxiety= very common- phobia is most common What neural pathway and dysfunction is associated with these disorders

Answer 108

“Passengers who survived terrifying Air Transat flight in 2001 help psychologists uncover new clues about post-traumatic stress vulnerability” 30 min- thought were gonna land in Atlantic Ocean She experienced ptsd, her partner did not- what was different 100s of passengers- maneuvered plane to group of island- everyone instructed to prepare for emergency landing- thought were gonna die Landed safe- very few injuries ~50% of passengers experience PTSD Criterion A: Exposure to traumatic event / Stressor Criterion B: Intrusion Symptoms Criterion C: Avoidance Criterion D: Alterations in cognitions & mood Criterion E: Alterations in arousal and reactivity No gender bias Experiencing symptoms years later Criteria a- exposed to traumatic event- death, threatened death, sexual violence, practically anything Criteria b- traumatic event is experienced after it occurred- nightmares, flashbacks, cant stop thinking, symptoms intruding life Cvrietrai c- avoiding any stressful trigger- ppl, palaces, sounds- external reminder of trauma D and E- changes in thoughts or mood and arousal and reactivity- hypervgiliant- easily startled, arousable, memory issues Has to have symptoms persist for more than one month- b,c,d,e- If less= acute Maladaptive, impacting function- social, occupational impairment Can’t be explained by others factor

Answer 109

Not an easy thing to understand what makes one vulnerable to ptsd- not everyone has. MRI before trauma Have ptsd- smaller hippocampus Don’t know temporal precedence- what came first Twin study suggests that developing PTSD- already have smaller hippocampus Vulberabity factor- smaller hippocampus volume 10% avg. difference in hippocampal volume -especially prevalent on Right 10 %- difference in ptsd vs not- especially in right hippocampus Dec right hippocampus volume Is this the result of trauma Looking at memory- conflicting findings- certain memories- enhanced and others suffer because of amnesia of situation. Functional changes in hippocampus- is this the cause What is happening when memories ar enhanced People who had ptsd- vs not

Answer 110

Looked at brain activity while looking at images - their specific trauma - other event - road trip - happy event Told to remember what happened to them- personal experiences Did blocks in mri study- counterbalance- get all conditions in different order In brain AT- flight(specific trauma ) Passengers- more internal details recalled- episodic memories when looking at pics of flights Own episodic memory enhanced- in terms of amount of detail # of details recalled- correlated with medial temporal activity- areas related to emotions and emotional processing And visual areas- imagining Physical size of hippocampus indicates susceptibility to PTSD.- smaller right volume Functional correlates of amygdala indicative of changes in neural response properties to traumatic stimuli.- over activation in amygdala and hippocampus- causes memories The question remains though… What is it about a reduced hippocampus that increases the likelihood of PTSD? Too much stress- shrinks hippocampus- too much stress in brain Over simulation of hippocampus= volume decrease Amygdala and hippocampus- linked, smaller hippocampus= different activity in amygdala

Answer 111

Twin studies show that virtually all anxiety disorders show a moderate level of concordance within family members (4-6X): suggests a genetic role. The estimated heritabilities range from ~25 - 40%. Ppl who have family member w anxiety= 4-6X increase in anxiety likelihood Differences in anxiety disorder

Answer 112

http://www.iflscience.com/health-and-medicine/seven-new-genes-linked-anxiety-disorders/ 7 “new” genes linked to anxiety disorders 6 of which had not been previously linked to them By uncovering these new candidate genes – involved not only in risk, but environmental interplay – there is new hope for better and improved treatment strategies. Biological predisposition to anxiety Looking at genes Genetic risk of anxiety- interacts w environment to lead to expression of disorder Having genes- doesn’t mean get disorder=

Answer 113

The genetic risk for anxiety is suggested to be non-specific; passed on as broader dispositional or temperamental traits. Studies also suggest that anxiety disorders arise from a combination of genetic and environmental factors. G x E  Epigenetic effects Non specific anxiety trait- has to interact w environment to get diagnoses Ex- traumatic stressor- interacts with genes- leads to disorder Example of epigenetics Traumatic experiences- changes expression= leads to disorder

Answer 114

HPA axis dysfunction: Increased secretion of CRF, reduced negative feedback cortisol response  High levels of glucocorticoid Rs in hippocampus- makes it prone to effects if heightened cortisol  Smaller hippocampus? HPA axis- dysfunctional in anxiety disorder Due to inc crf- from adrenal Reduced negative feedback- doesn’t inhibit hormonal release- cortisol keeps being released Cortisol kills neurons- inc vulnerability to further disorder

Answer 115

Anxiety disorders Separation Anxiety Disorder Selective Mutism Specific Phobia Social Anxiety Disorder (Social Obsesssive compulsive Obsessive-Compulsive Disorder Body Dysmorphic Disorder Hoarding Disorder Trichotillomania (Hair-Pulling Trauma and stress related Reactive Attachment Disorder Disinhibited Social Engagement Disorder In dsm- 3 components of anxiety disorders

Answer 116

Obsessions are defined by: Recurrent and persistent unwanted thoughts, urges, or images- obsession Often the person attempts to suppress or ignore such thoughts, impulses, or images or to neutralize them with some other thought or action- compulsion Has obsessions and compulsion Onset is gradual Mire common in young girls Lifetime prevalence- 2-3% Intrusive thoughts, urges, images are aware the compulsions do not make perfect sense- Do compulsion to try and resist thoughts Most common- contamination- germs- try to avoid all contaminations- door knobs, washing hands frequently

Answer 117

Designed to look at type of symptoms and severity On 4 Point scale- looking at time occupied by each obsessive thought- rate how much time they spend on the thought- 4 is most= extreme- most of day Looks at additional info as well- supplied by other ppl- how severe is it

Answer 118

(1) Repetitive behaviours or mental acts in response to an obsession or according to rules that must be applied rigidly. (2) The behaviours or mental acts are aimed at preventing or reducing distress Praying, repeating words,- strict rules Either behaviour or mental act Feel driven to do it to reduce anxiety- response to obseevive thought- may not be connected Ex- washing hands vs germ obsession = linked Counting to reduce sexual thoughts- not linked

Answer 119

Family studies of OCD-affected individuals published since the 1930s provide strong evidence for familial link. Anxiety- innate Extreme anxiety such as ocd- may also be apart of biology Family studies looking at ocd- string evidence for heritability of disorder- among family members- prevelanxe jumps Higher prevelance- looking at ocd features Family and genetic related- is it environmental- parent act in way leading to kid acting certain way Found across cultures

Answer 120

First anatomical localization in 1967 during epilepsy surgery. Stimulation of cingulum led to repetitive behaviours Collection of white matter fibre tracts that allows communication between components of the limbic system Looked at stimulated cingulum- couldn’t t suppress urge to engage in respective behaviours- just had to do it Not single area= belt around brain- tract above corpus collusm- interaction between hemispheres Found in cingulate gyrus connections of white matter and axons connects limbic system together

Answer 121

-OFC- decision making persistence of intrusive thoughts (obsessions) and the development of repetitive behaviors (compulsions) -ACC -Caudate nucleus- movement Functionakl imaging revieled activity difference Over activation in OFC, ACC and caudate nucleus Bottom brains- left side- more activity Right side- top= symptomatic, bottom= treatment More stimulation in ocd brains These areas- too active Function in OCD: The ACC is involved in cognitive control, error detection, and emotional processing. Abnormalities in the ACC are associated with difficulties in regulating emotions and attention. Role in Obsessions and Compulsions: Dysregulation in the ACC may contribute to the heightened attention to errors and perceived threats, leading to increased anxiety and the need for compulsive rituals to reduce this anxiety. Cortico-Striato-Thalamo-Cortical (CSTC) Circuitry: Interconnected Roles: These brain regions are interconnected and form part of the cortico-striato-thalamo-cortical (CSTC) circuitry, which is implicated in OCD. Dysfunction in this circuitry is thought to contribute to the characteristic symptoms of OCD, including obsessions and compulsions. Imbalance in Circuit Function: In OCD, there may be an imbalance in the functioning of this circuitry, leading to repetitive and ritualistic behaviors as an attempt to relieve anxiety associated with obsessive thoughts. Patients with OCD- looking for metabolic differences- pet scan- looks at functional difference Activity metabolisation is different Rates where higher- during ocd

Answer 122

This illustrates the sensory and emotional recognition of threatening stimuli. Reaction pathway system Normal- natural reaction- see something- danger stimuli- avoid it Key is- have to see it- sensory info- sent through thalamus, visual cortex for processing, temporal lobe- process if it is threat=amygdala First= sensory recognition- perceive through senses – often see Sends pathway through thalamus to primary sensory area for stimulus Visual cortex- once percieved- then react- emotional processing- activity in amygdala and hippocampus- how salient is stimulus- should I react Projects through cingulum from amygdala to OFC- after processing- OFC- helps pay attention

Answer 123

Projects through cingulum from amygdala to OFC- after processing- OFC- helps pay attention Thoughts generated in oFC- sent back through cingulate to moto areas- generate response- how you process Motor response modulated by thalamus- thalamus activity modulated by caudate Caudate activated- have motor response- inhibits hypothalamus to stop focusing Threat removed Response stops. ….ahhhh! Threat is removed- thalamus reduces activity, pathway is reduced No perception of threat decreases attention and pathway Nucleus accumbens- after stressor gone- suppresses OFC and caudate, helps dampen stress response This response= good The thalamus provides sensory input, the amygdala evaluates emotional significance, the OFC contributes to decision-making and context evaluation, the cingulate cortex coordinates responses, and the caudate plays a role in motor control. This complex network allows for adaptive and context-dependent reactions to threats.

Answer 124

In ocd – the decision making- OFC- overactive- cant stop thinking abt threat, actionable response and fight vs flight= also overactive Stimulating threat motor response= compulsions Leading to obsessions and compulsions Over active OFC- failure to inhibit thoughts cotantsly aware of stressful stimulus Keep thinking abt it Because of stimulation of movement pathway= desire to do compulsion takes primary importance over other cognitive tasks Lack of OFC suppression.

Answer 125

One possible theory: Dysfunctional circuitry from nucleus accumbens fails to suppress fronto-striatal circuits. Another aspect Dysfunctional circuitry from Nac- can’t suppress OFC- cant inhibit motor stress pathway Nac and pfc linked- this pathway not having activation- fails to inhibit overactive frontal circuit- motor response

Answer 126

Drugs can modulate activity within fronto-striatal pathways (see right). GABA agonists suppress activity between areas. Serotonin and Dopamine antagonists indirectly reduce excitation of the pathway Calm down activity Gaba agonist- inc functioning at recepto- inc gaba inhibition Inc amount of inhibition within this pathway Serotonin and dopamine component as wel- from NAC These inputs module activity at different areas Blocking those- block some excitability- many side effects- dopamine= movement problems Serotonin= sleep, mood Not modulating In way you want- not as helpful Gaba agonist better- don’t shut everything down- control inhibition more Glutamate- excitatory

Answer 127

Used to treat anxiety and sleep disorder Act on gaba receptor- Benzo bind- excerpt influence over gaba- allosteric effect- inc gaba Inc likelihood gaba will activate and activates stronger gaba Makes it less likely to fire an AP Inc gaba receptor functioning, inc chloride entry, makes it less likely for AP

Answer 128

3 surgical approaches to treat OCD. Two of them involve destroying parts of the frontostriatal circuit! Basal ganglia anterior capsulotomy subcaudate tractotomy Limbic system anterior cingulotomy- Cingular cortex, interior part limbic leukotomy- damage limbic system- some of neurons destroyed In extreme cases- not improving in any way Not a lot of studies 2 involve lesiioning brain- describing connection between caudate nucleus- capsultomy Subcaudate tractomy- destroying connections and tract from caudate Causes change in entire pathway

Answer 129

Stimulate Nucleus Accumbens to turn off Fronto-Striatal activity. Preferable- reversible More expensive Inserted electrodes into nucleus accumbens Stimulate gabaergic area- projections to the frontal cortex- inhibited- reduced symptoms Brain stimulation restores normal activity in obsessive-compulsive disorder Did DBS- normalizes neural activity- control levels Notice that NAc is underactive relative to controls.

Answer 130

DBS reduced the frontal cortex response evoked by symptom-provoking events. DBS- normalizes brain activity in frontal cortex Responsd less tp symptomatic images- don’t get as anxious with stimulation Modulate activit, decrease symptoms Brain stimulation improves OCD symptom score. NAc stimulation ultimately decreases frontostriatal connectivty, thereby reducing symptoms with stimulation Strong pos or relation More the connectivity was devreasesd- reduce symptoms Change n symptoms- linked to ativivty changes

Answer 131

Benzodiazepines bind to a specific site on the GABA-A receptor, which is a type of receptor for GABA. When benzodiazepines bind to the GABA-A receptor, they increase the efficiency of GABA binding to its own binding site on the receptor. This enhances the inhibitory actions of GABA on neurons. Increased Inhibition of Neuronal Activity: GABA, when it binds to its receptor, opens a channel that allows chloride ions to enter the neuron. This influx of chloride ions hyperpolarizes the neuron, making it less likely to generate an action potential and transmit signals. By enhancing GABA's inhibitory actions, benzodiazepines increase this inhibitory effect on neurons, leading to an overall decrease in neuronal activity. Effects on Different Brain Regions: Benzodiazepines have a wide distribution of GABA-A receptors throughout the brain. Therefore, their effects are not limited to a specific region. In the context of anxiety disorders, including OCD, the modulation of GABAergic activity is thought to occur in brain regions involved in emotion regulation and anxiety, such as the amygdala. Potential Anxiolytic Effects: By increasing inhibitory activity in certain brain regions, benzodiazepines may exert anxiolytic effects, reducing excessive neuronal excitability associated with anxiety disorders

Answer 132

The reward prediction error (RPE) model is a concept commonly used in the context of reinforcement learning and neural systems that involve reward processing. In the context of withdrawal, which typically occurs in the context of drug or substance dependence, the RPE model might suggest the following: 1. **Negative Prediction Error during Withdrawal:** - The brain's reward system is calibrated based on predictions of rewards. When someone is dependent on a substance, their brain adapts to the presence of the substance, and it comes to expect the associated rewards. - During withdrawal, when the substance is no longer present, there is a negative prediction error. The brain expected a reward (which was associated with the substance), but it is not received, leading to a dip in the reward prediction. 2. **Increased Sensitivity to Negative Stimuli:** - Withdrawal is often accompanied by negative emotional states, such as anxiety, irritability, and dysphoria. - The RPE model would predict an increased sensitivity to negative stimuli during withdrawal. The absence of the expected reward (from the substance) could lead to a heightened response to negative stimuli, as the brain tries to adapt to the changed environment. 3. **Potential for Altered Learning:** - The RPE model suggests that learning is driven by the discrepancy between predicted and actual rewards. - During withdrawal, the brain might undergo changes in the learning process, recalibrating expectations and associations to adapt to the absence of the substance. 4. **Craving and Motivation:** - The negative prediction error during withdrawal may contribute to increased craving for the substance as the brain seeks to resolve the discrepancy between the expected and actual rewards. - Motivation to seek the substance may be heightened during withdrawal as the brain attempts to restore the expected reward. It's important to note that the RPE model is a theoretical framework used to explain how the brain processes rewards and adapts to changing environments. The specific application to withdrawal can vary depending on the substance, individual differences, and other factors. Additionally, the understanding of these processes is continually evolving as research in neuroscience and addiction progresses.

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