Ala2 Flashcards
Drug paradox
Substance Use Disordersaka Drug Addiction
“Paradox”
How can a person develop and maintain a pattern of behaviour that is so obviously destructive to their life?
Big problem
Gambling recently added
Paradox- know its harmful and destructivee but till do it about 10% of population
Downward spiral of addiction
The maladaptive pattern of drug use often leads to the individual desiring more and more of the drug to recreate the first encounter.
As the individual’s life becomes increasingly consumed with the drug, other important aspects of a fully rounded existence are compromised.
Maladaptive pattern
Cigs in own category
Need more drug to reencouunter first drug
Had first experience- enjoyed it- can never recreate initial experience- spend more time using it, not doing things should, become maladaptive
Need more drug to get same effect= tolerance- or same dose doesn’t produce same effect, brain getting used
Withdrawal- main component keeping the, on drug
Features of addictive behavior
Craving = an insistent search for an activity-Distinctive feature of addictions
Tolerance-Decrease in effect as an addiction develops-Drug tolerance is learned-Can be weakened through extinction procedures
Withdrawal-Body’s reaction to absence of the drug after prolonged use-Drug can relieve withdrawal-Negative reinforcement
Craving- disorder criteria, thought to never go away
Crave them eve though they know they shouldn’t
Cant control cravings
Drug tolerance- learned phenomenon
With
Found this when giving heroine to drugs – only learned tolerance in one environment
learning can extinguish tolerance- learn to associate drug with happiness
Withdrawal- reaction to absence of drug. After taking for a while
Physical and psychological- feel cant function – know that taking drig will reduce symptoms- enforces using drug
Negative reinforcement- removing something bad, enforces bad behaviour
Withdrawal,, take drug- behaviour, reduces negative feelings and drug is reinforced- more likely to take
Pos enforcement- take feel goof, add positive emotions, enforces drug
Frug taken to reduce withdrawal- causes craving in other situations- response to any stress= vicious cycle
What is Addiction?Behavioural definition:
A chronically relapsing disorder characterized by:
Compulsion to seek and take drug
Loss of control in limiting intake
Continued use despite consequences
Must be maladaptive to user’s life
Behavioural definition
Four c
Chronic- lasts long time
Compulsion. To take drug- undeniable urge to do drug loss off control- cant stop, loss control in substance
Consequences- partner leaving, no ob debt- continue to use it
Craving- urges cant control
Maladaptive to live- lots of dysfunction
How drug changes from impulsivity to compulsivity
Changes from impulsive to compulsive
Binging- taking lots of dug feel high
Withdrawal or negative mood state
Occupied with ubstance want to take it
Binge again
Causes more desire, tolerance and vicious cycle
Causes addiction
Start with just wanting to do it for fun turns into addiction
Preoccupation with obtaining
-Persistent physical or psychological problem
Taken in larger
amounts than intended
• 3-stage cycle:
Preoccupation/
anticipation
Binge/antoxication
Withdrawal/ negative affect
Persistent desire
Tolerance withdrawal
Social, occupational, or recreational activines compromisea
Spiraling distress
Addiction
Substance Use Disorder: DSM-5 Diagnostic Criteria (APA, 2013)
Diagnosis of substance use disorder is based on a pathological pattern of behaviours related to use of the substance
To assist with organization, criteria can be considered to fit within groupings:Impaired control (1-4)Social impairment (5-7)Risky use (8 & 9)Pharmacological criteria (10 & 11)
The individual has manifested a maladaptive pattern of substance use for at least 12 months that has led to significant impairment or distress.
Minimum of 2 (of 11) criteria must be met:2-3 is a mild substance use disorder diagnosis; 4-5 is moderate; 6+ is severe
Focus on consequence of substance
Has evolved. Lot
Varies In severity
2/11 criteria- mild
Impaired control over substance use (criteria 1-4)
- Using greater amounts or using over a longer time period than intended
- Persistent desire or unsuccessful efforts to cut down or control substance use
- Spending a lot of time obtaining, using, or recovering from using the substance
- Craving
Grouping of criteria
Has 4 criteria
Loss of control using more substance and over longer period of time, don’t have control to stop the self
Desire- though and want to control, want to stop
Tie-s pend time using it, recovering or braiding- in more severe- all they do
Craving- desire for drug, can occur at anytime, usually in similar environment or when stressed
Craving- bug motivator to use substances
Social impairment (criteria 5-7)
- Repeatedly unable to carry out major role obligations at work, school, or home due to substance use
- Continued use despite persistent or recurring social or interpersonal problems caused or made worse by substance use
- Stopping or reducing important social, occupational, or recreational activities due to substance use
Social things tht happen
Not taking car of kid, nor doing things they should
Having relationship problems- fighting with partner, losing friend
7- withdraw from soccer team, don’t do family activities due tos ubbstance use, not functioning as should socially, no doing thing used to
Risky use of the substance (criteria 8 & 9)
- Recurrent use of the substance in physically hazardous situations
- Consistent use of the substance despite acknowledgment of persistent or recurrent physical or psychological difficulties that is/are likely to have been caused or exacerbated by the substance
-key issue is not existence of the problem, but the person’s failure to abstain despite the difficulty it’s causing
8- driving while intoxicated- putting self in serious danger, at work
9- causing physical difficulty, psychological- caused or made worse bus ubstance
Cant stop using substance despite difficulties
Pharmacological criteria (criteria 10 & 11)
- Tolerance
- Withdrawal
-Neither is necessary for diagnosis of substance use disorder
-But, past history of withdrawal associated with a more severe clinical course
-If these symptoms occur during medical treatment, they are not counted
Not necessary but if experience this- associated with more severe disorder
More likely to experience relapse and issues with evrity
If during medical conditions- disorder not diagnosed- in hospital get addicted to morphine
Behavioural addiction
Behavioural addictions- addictions of behaviours- gambling, sex, eating
Gambling- only one in dsm
Are they addictions?
Gambling backed up by animal model
Factors That Influence the Development and Maintenance of Drug Abuse and Addiction
Addiction potential influenced by route of administration
Abused drugs (initially) act as positive reinforcers;
Once dependent on a drug, the drug acts as a negative reinforcer
Faster route of administration- more addictive- get to brain quicker, cause effect faster- more vulnerable to addiction, reaches concentration quicker, euphoria there quick and gone fast- want to take more
Pos enforces- consume feel good strengthen drug behaviour inc likelihood one will do in future ]
Neg- relieve stress, withdrawal- take drug relieve symptoms
Many factors that make drugs addictive
Considering Addiction in the Context of Evolution
Why do people become addicted to something that harms them?
Have you ever felt as if you would do anything for your favourite dessert?
Addictions, including food, are the result of powerful stimulation of the brain.
Self Perceived Fitness (SPFit)
Behaviour that has negative consequences to fitness and reproduction, why does it persist
Survival and reproduction- addiction involves reward, limbic system
Engage in sex- pleasureful, need for reproduction
Food- pleasure and survival
Cravings for food emotions and behaviours are driving motivators, rats feel this way abt sugar- do anything to obtain it
Allows rates to binge eat sugar- deprived of food and gave sugary drink
Then removed sugar from drink- daw withdrawal symptoms- predisposed to get addicted
Drugs produce powerful feelings- activate rewards syste, mimic pleasure
Bc of perception-says we had fitness benefit- associated wit drug and contributes to addictive behavior
Genetics of addiction
50/50
Children of addicts are 8x more likely to develop an addiction
Why would there be an ‘addiction gene’?
Permanent rewiring
BUT genes do not = destiny
50 % genetics, 50% other
Children of addicts- mother abuses drug- 4x more likely to have addiction
May not be an addictive gene- studies trying to find, not one gene- more of them, more likely to develop disorder
Have addiction- brain rewired- never go back to non addictive state
Genes don’t equal destiny, doesn’t mean develop addiction
The Medial Forebrain Bundle (MFB)
Bundle of accounts from PFC to VTA
Releases dopamine
Animals with electrode in MFB- enjoyed it, could stimulate self- motivational and rewarding
Brain reward circuit- amygdala- shits it don
Pfc- executive functions
Stimulate self 10,000 times in 1 hour- huge effect on behaviour, totally focues on simulation, ignore other things- food, water, sex
Neurobiological roots of addiction: The Mesocorticolimbic DA system
Nucleus accumbens
feeling of pleasure
OFC
maintenance of cravings
Stimulating NA- linked to sex and food
Implanting electrode- stimulated same pleasure feeling receives dopamine from VTA
Key role in reward and motivation- damaged= don’t experience pleasure ofc drugs interacts with OFC- maintain e of craving, decision making
Many have more than one addictive behaviour0 this can explain why
The mesocorticolimbic system includes three main components:
Mesolimbic Pathway: This pathway connects the ventral tegmental area (VTA) to the nucleus accumbens, amygdala, and hippocampus. The nucleus accumbens, in particular, is often implicated in the brain’s reward system.
Mesocortical Pathway: This pathway connects the VTA to the prefrontal cortex. The prefrontal cortex is involved in executive functions such as decision-making, planning, and regulating social behavior.
Nigrostriatal Pathway: This pathway connects the substantia nigra to the striatum and is primarily involved in motor control.
These pathways are rich in dopamine, a neurotransmitter associated with pleasure and reward.
Drug reward & Dopamine
-Drugs of abuse activate different parts of the DA pathway
-Most act to increase DA in some way
Drugs activate it differently
DA- system main component in reward and motivation
Activates other NT
Gaba- less gaba less inhibition- more Dopamine
The role of Dopamine in drug seeking behaviour
DAT deficient mice still self-administered cocaine and preferred the location associated with cocaine use
Value of dopamine in addictive behaviour
Mouse with no dopamine vs regular mice
Still do administer drug to themselves with no dopamine- choose cocaine environemneyt
Dopamine important but not only thing
Drugs and behavior
Recall: Drug mechanisms
Antagonist
Drug that blocks a neurotransmitter’s actions at its receptors
Agonist
Drug that mimics or increases an effect of a neurotransmitter at receptors
Drug have different effect based on how it affects receptor
Antagonist- block it
Agonist inc activity- act like NT
Drug effects
Drug mechanisms:
Affinity: Measure of drug’s tendency to bind to a receptor
Efficacy: tendency to activate the receptor
A drug’s effectiveness and side effects vary from one person to another
Abundance of each type of receptor varies between individuals
Affinity range sting to weak- strong if bind to it
High efficacy- high effect, activates drug strongly
How do drugs interact with our brain’s communication systems
When a neurotransmitter binds to a receptor, it activates a change.
Bind to receptor avitbate change- open or close channel or other effects
How do Drugs like alcohol, heroin, and nicotine indirectly excite the dopamine-containing neurons
Presynaptic influences on activity
Transmitter Production
Transmitter Release.
3. Transmitter Clearance
Affect the key (Neurotransmission)
Transmitter clearance—drugs called reuptake inhibitors can block reuptake of transmitter, while others allow the transmitter to accumulate by blocking enzymes
Drug neural signalling- affects many
Amount produced, amount released
Indirectly influence it via transmitter release
Affect precursors, enzymes, proteins, reuptake
Clearance of neurotransmitter, block transporter that bring NT back – remains in synapse for longer
How is the action of drugs complex
A single receptor can be influenced in a number of different ways.
Gaba receptor- chloride Chanel- activates it causing more positive
Alcohol facilitates activity at gaba receptors, inc inhibition
Benzodiazepine- bond to different area of receptor- modulate how much is going in and out
3 ways to infkunce receptors
Consuming drugs- activating receptors not usually activated
Glutamate
AMA. kainate. and INMDA receptors lionotronic mcluk’s metabotropic glutamate receptors
GABA, (ionotropic)
GABA; (metabotropic)
Glutamate is the most abundant of all neurotransmitters and the
most important excitatory transmitter.
Glulamate recepiors are crucial for excitalory signals, and NMDA receptors are especially implicated in learning and
GABA receptors mediate most of the brain’s inhibitory activity, balancing the excitatory actions of glutamate. GABA, receptors are inhibitory in many brain regions, reducing excitability
and preventing seizure clivily
GABA, receptors are also inhibitory, by a different mechanism.
Dopamine
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
How Chronic drug abuse severely affects nucleus accumbens
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
How Drugs modify neuronal structure
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
What is the Role of the NAc
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
Drug Cravings
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
Functional Imaging of Neural Responses to Expectancy and Experience of Monetary Gains and Losses
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
Common themes of drugs
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
DA as a teaching signal
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
Drug Addiction as Self-Medication
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
Nicotine addiction in rats
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
aversive motivational response to withdrawal from chronic nicotine.
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
Phasic vs tonic DA activity
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
D2R nicotine withdrawal D1R acute nicotine
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
BDNF
-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
Neurobiological switch
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
The CRF brain stress system
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
The Brain Needs Balance
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
2 types of neuroadaptations involved in transition to addiction:
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
Executive Function (PFC) Theories of Addiction
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
Relationship between striatal D2 receptor binding and OFC glucose metabolism
In addictive individuals- d2 recepto is less, glucose stabilization is less as well
Dec activity associated with low dr2 levels
Impaired Response Inhibition and Salience Attribution (I-RISA)
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
Molecular theory of addiction
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
Learned drug tolerance
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
Situational-Specificity of Tolerance
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
Sociocultural influences drug addictions
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
Developmental-Genetic Model
Substance abuse
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
Emil Kraepelin
(Late 19th century)
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
E.P. Bleuler
Swiss Psychiatrist (20th Century)
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
Diagnostic criteria of schizophrenia
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
Schizophrenia symptoms
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
Diagnosing Schizophrenia
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
Differential Diagnosis
Of schizophrenia
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
Same diagnosis, different presentation
Schizophrenia
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
Schizophrenia
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
Stages of schizophrenia
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
Genetic risk schizophrenia
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
Schizophrenia Gene’
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
Schizophrenia Prevalence and Latitude by Continent
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
