Schizophrenia: Class Notes

Question 1

Schizophrenia, History: Kraeplin

Answer 1

SZ consists of a large range of symptoms
o Conceptualized as one disorder, but it is most likely multiple disorders

Emil Kraepelin, 1904
• A student of Wundt’s experimental lab
• Later became the chief psychiatrist in Estonia
• Father of modern European psychiatry

Created an illness classification system
• Which was the first since Hippocrates
• Both believed illness was due to bodily imbalance

First used the term “dementia praecox” to label SZ
• Translated meant an early onset of deteriorating mental functioning
• Used term to distinguish SZ from bipolar – which was previously grouped

Question 2

Schizophrenia, History: Bleuler

Answer 2

Eugen Bleuler, 1911

Noticed dementia praecox occurred at different ages, and some people recovered

Guided by a desire to be like Freud and his tendency to use metaphors

Believed the underlying problem stemmed from “loose associations”
o Which led to a “split mind”
• Hence the name “schizophrenia”

Failed to properly operationalize “loose associations”
o Led to an abstract construct of the disorder in the US

The US followed Bleuler’s definition, while Europe continued to rely on Kraepelin’s more specific definition

**U.S. thus experienced a surge in hospitalizations due to SZ over-diagnosis, and increase in lobotomies

Question 3

Schizophrenia as “Salience Disorder”

Answer 3

Current trend is a push to relabel schizophrenia as “salience disorder”

Salient = ability to focus on appropriate stimuli

Hallucination may reflect the inability to recognize the subjective value of experiences from an internal representation/source

Question 4

Schizophrenia: Onset and Prevalence

Answer 4

In DSM-III, age 34 was the cut off for being able to obtain a diagnosis of SZ

Current DSM does not have a cut off age (but geriatric onset is very rare)

SZ typically develops around puberty

Lifetime prevalence ~ 1%

Some evidence of gender differences
o Men typically demonstrate more severe cases
o It has been argued estrogen serves as a protective factor

Question 5

Risk factors: Age of Father

Answer 5

Possibly due to degeneration of sperm

Similar link with autism

Potentially encourages social deficits

No specific cutoff age, but 40+ is considered at risk
(Similar to mothers 40+ and link to Down Syndrome)

Question 6

Risk Factors: Immigration status; Marriage

Answer 6

Affects more immigrants, but cause vs effect?
o Could be more people with SZ flee their native countries due to persecution

Marriage
• Common for men with antisocial personality disorder to marry women with SZ

Question 7

Risk Factors: Prenatal

Answer 7

Prenatal infection
o Increase in SZ following a flu epidemic

Exposure to a feline virus increases one’s chance

Rhesus (Rh) incompatibility

Blood types of the mother and child are different

Winter month births
o This trend reflects still-born trends

Some propose the same complication that would kill the fetus may lead to an increased chance of SZ

Poor prenatal care
o Malnutrition and maternal stress

Pregnancy and/or birth complications

Question 8

Neurodevelopmental factors

Answer 8

Dormant, prenatal, brain lesions only arise during puberty

Disorganized neuroarchitecture

Neurons of the brain are strung together in irregular patterns

Complicated, impractical, tangle

Question 9

Other Biological Factors

Answer 9

*Note: not all those diagnosed with SZ display these abnormalities

**Abnormalities are not required to diagnosis SZ

Decreased brain volume

Decreased volume of the thalamus
o Thalamus and irregular temporal lobe are linked with hallucinations

Increased ventricles – which is correlated with negative symptoms

Irregularities in the frontal lobe

Question 10

The dopamine hypothesis:

Answer 10

Dopamine mediates the salience of environmental events and internal representations

Increased DA D2 receptors activity

Complicated link though: blocking D2 may increase D1

Drugs that block dopamine help control symptoms in those with SZ
o But current meds only target D2 receptors and only treat the positive symptoms

Question 11

Dopamine Hypothesis: Pathways

Answer 11

4 major dopamine pathway, but 2 key in SZ

• Mesolimbic
• Mesocortical

Nigrostriatal
Tuberoinfundibular

Question 12

Flaws to Dopamine Hypothesis

Answer 12

There is no genetic link to dopamine production

There is no consistent therapeutic effect of regulating dopamine

Question 13

Glutamate Hypothesis

Answer 13

Nearly half of all neurons in the brain and nearly all of them in the cerebral cortex use glutamate

Decreased glutamate leads to negative and cognitive symptoms of SZ, including sensory processing deficits

Early trials of glutamate agonists seem to yield similar results of antipsychotics

Question 14

Glutamate Hypothesis: NMDA gateway

Answer 14

NMDA(R) (glutamate receptor) antagonists increase negative and cognitive symptoms

Glutamate regulates other neurotransmitters that are affiliated with SZ – NMDA is known as the gateway receptor

Question 15

SZ Categories of Symptoms

Answer 15

Delusions/hallucinations

Negative affect

Disorganized speech/behavior

Hospitalization occurs if the individual is a risk to self or others

*Just having the symptoms does not lead to hospitalization

Question 16

Delusions

Answer 16

Disturbances in content of thought

Fixed and firmly held despite clear contradictory evidence

Erroneous beliefs

Self-reference

Alien control (aka made impulses)

Thought control

thought broadcast

Grandiosity (though it’s more popular in bipolar)

Question 17

Hallucinations

Answer 17

Sensory experiences that seem real but occur in the absence of any external perceptual stimuli

Can occur in any sensory modality (taste, sight, smell, etc.)

~70% of hallucinations involve auditory hallucinations

10-20% are visual hallucinations
• Which are typically distorted images – not clear-cut

Some evidence hallucinations may be the inability to identify thoughts/ideas as internally-generated
• source monitoring errors

Question 18

Difference between hallucinations and illusions

Answer 18

Illusions are caused by real-world stimuli

Hallucinations are typically negative

Question 19

Disorganized Speech

Answer 19

Failure to make sense of speech–despite conforming to semantic and syntactic rules of speech

Includes disturbances in form, not content, of thought

Differs from manic “flight of ideas”
• With flight of ideas, the speech, while confusing, is understandable when broken down

Question 20

Disorganized Behavior

Answer 20

Impairments of goal-directed activity

Occurs in all areas of daily-functioning

Catatonia – frozen

Catatonia Stupor = cannot be physically moved

Question 21

Negative Symptoms

Answer 21

Avolition (loss of motivation)

Anhedonia (loss of interest)

Flat affect

Alogia (aka poverty of speech; using few words and a lack of spontaneity)

**Important to note flat affect is in terms of expression
• Independent of internal feelings

Overall loss or decrease in normally-present behaviors

Question 22

Altered Neurocognitions

Answer 22

Working memory

Attentional functioning

Speech production

Eye tracking

*Degree to which these are dysfunctional are the best predictors of real-life functioning following discharge

Question 23

Expressed Emotions (E. E.)

Answer 23

Expressed emotions (E.E.) of the families which includes

1. Emotionally overinvolved
2. Overly critical
3. Hostile

Increased EE is related to increased rate of relapse following discharge

In such cases, patient is better living alone following discharge

EE can be reduced via psychoeducation

Some argue that EE may not only encourage relapse, but it can encourage SZ’s appearance in the first place

Question 24

Risk Factors: Low SES

Answer 24

*SZ 8x more likely in low SES, possibly due to:

Poor nutrition

Lack of access to appropriate healthcare

Increased stress

Question 25

Schizoaffective Disorder

Answer 25

Includes mood symptoms But the psychotic symptoms are independent of the mood If they are dependent, then it’s bipolar or depression with psychotic features

Question 26

Schizophreniform Disorder

Answer 26

Active symptoms for less than 6 months, with impaired functioning Typically turns into SZ

Question 27

Delusional Disorder

Answer 27

Only well-developed delusional symptoms are present, and the individual is still able to function

Question 28

Shared Psychotic Disorder

Answer 28

When two people share a delusion, not SZ One is typically the alpha and one is the beta (and follows along)

Question 29

Brief Psychotic Disorder

Answer 29

Occurs after a traumatic event and naturally fades away The individual is not likely to have another episode

Question 30

SZ Treatment: History, Dorothea Dix

Answer 30

Dorothea Dix advocated for better treatments Increase in psychiatric institutes in the late 19th century in reaction to her work, but there were few treatments Castration, lobotomy, near-death experiences, hydrotherapy

Question 31

SZ Treatment: 1950's

Answer 31

Real change began in the 1950s Creation of the first psychiatric drug – Thorazine First used to treat allergies Affects the D2 receptors Has many side effects including sedation (like most allergy medication)

Question 32

SZ Treatment: 1960's

Answer 32

Development of Haldol The Community Mental Health Act – in an attempt to move treatment to the community * Released many patients from hospitals without building community health centers * Patients were now on the streets

Question 33

SZ Treatment: Haldol

Answer 33

Still a high dosage medication but lacked the sedating effects of Thorazine Had many extrapyramidal symptoms (EPS) Long term use: risk of tardive dyskinesia

Question 34

SZ Treatment: Haldol EPS

Answer 34

EPS=movement disorders and tardive-like symptoms Blocked dopamine receptors throughout the brain, thereby mimicking the symptoms of Parkinson’s Increase in acetylcholine and norepinephrine : Muscle rigidity Slowed movements Resting tremors Dystonia (muscles locked) Akathisia (inability to sit still) To deal with the side effects, additional drugs were administered to reduce the EPS Lower ACH and remove the cholinergic effects Add beta-blocker to decrease norepinephrine and remove akathisia

Question 35

SZ Treatment: Tardive dyskinesia

Answer 35

Includes spasmodic, gross, motor-movements Not due to EPS, but rather due to long-term usage of 1st generation antipsychotics Due to years of chronic dopamine depletion, new, more sensitive, dopamine receptors are created *More sensitive receptors = more easily fired

Question 36

SZ Treatment: Late 1980s, early 1990s – development of 2nd generation antipsychotics

Answer 36

2nd generation antipsychotics aka “atypicals” Atypicals have, generally, less severe side effects, but are no more efficient that 1st generation antipsychotics Less restrictive on the dopamine systems Controls the system just enough and then releases hold to reduce symptoms Clozapine-- "first and best" according to Serper

Question 37

SZ Treatment: Psychological Approaches

Answer 37

In conjunction with medication: Family therapy Case management • Supervisor is in contact 24 hours a day • Known as the Assertive Community Model (ACT) Social skills Treatment • Difficult to generalize skills however Cognitive remediation • Attempt to increase attention and memory by treating the brain like a muscle Cognitive behavioral therapy • For delusions and psychosis Other forms of individual treatment

Question 38

DA Theory in SZ: L-Dopa

Answer 38

L-dopa and D-amphetamine can cause psychosis-like state in healthy humans and exacerbate symptoms of schizophrenia

Question 39

DA Theory in SZ: postmortem studies

Answer 39

Postmortem studies showed abnormalities in DA indexed in SZ *Though data always confounded by drugs

Question 40

DA Theory in SZ: Neuroimaging Studies

Answer 40

SZ patients when psychotic demonstrate: Heightened synthesis of DA Heightened DA release in response to an impulse Heightened level of synaptic DA

Question 41

DA Theory in SZ: DA Deficiency

Answer 41

SZ = DA deficiency disorder Inadequate stimulation of the dopamine D1 receptors Administration of a D2 antagonist--(blocks DA auto receptors) results in: * Increased DA release * Increased stimulation of D1 receptors Antipsychotic drugs increased the metabolism of DA when administered to animals

Question 42

DA Theory in SZ: Amphetamines

Answer 42

Amphetamine increases synaptic monoamine levels and can induce psychotic symptoms Reserpine – effective for treating psychosis – blocks the reuptake of DA and other monoamines Clinical effectiveness of antipsychotic drugs was directly related to their affinity for DA receptors *Proposal: excess in dopaminergic neurotransmission

Question 43

DA Theory in SZ: Abnormal regulation of the DA system

Answer 43

DA mediates the salience of environmental events and internal representations * e.g. pleasure, reward, reinforcement, prediction error A dysregulated hyperdopaminergic state leads to stimulus-independent DA release This leads to an aberrant assignment of salience to one's experience

Question 44

DA Theory in SZ: Prominence

Answer 44

DA model has been the leading neurochemical hypothesis of SZ for the last 40 years **Current medications functioned primarily to block DA D2 receptors

Question 45

Glutamate Theory in SZ

Answer 45

NMDA (Glutamate receptors) agonists produce negative and cognitive symptoms of SZ Induce neuropsychological and sensory processing deficits Dysregulation of brain DA systems through changes in Glu mechanisms results in positive symptoms of SZ Currently no approved medication for negative and cognitive symptoms NMDA receptors appear to be a potential site for therapeutic intervention in SZ

Question 46

SZ and affect

Answer 46

Deficits in affective EXPRESSION define the disorder *Not deficits in affective experience Lack of affect is poor prognostic indicator The more affect an individual has, generally, the easier it is to treat the disease e.g. paranoia is highly treatable due to affective component Sometimes delusion is grandiose, but person is not grandiose, lacks self-esteem *this is more likely SZ than manic

Question 47

Eugen Bleuler

Answer 47

Loose Associations Threads that run through consciousness that bind together thoughts, actions and behavior Normals: tightly connected threads SZ: associations loosen or break, causes a split mind Split consciouness Split between thoughts, feelings, behavior -->Schizophrenia

Question 48

SZ: Monothetic Taxonomy

Answer 48

Bleuler's concept of SZ One symptom defines a disorder: loose associations Vaguely defined Anyone with symptom has disorder Anyone with disorder has the symptom *few others: Pedophilia Selective Mutism Also possibly PTSD--traumatic event more criterion, but not alone

Question 49

Bleuler and Kraeplin USA and Europe

Answer 49

SZ dx 1930: 20% in NY and London 1955: 80% NY still 20% London Europe: Kraeplin * dementia praecox dx * narrow definition USA: Bleuler * different construct of SZ * broad definition * translated into Enhligh * expanded Bleuler's definition to ambulatory SZ, process SZ, reactive SZ etc * lot of people lobotomized were probably OCD, Bipolar, BPD--wide net

Question 50

Reserpine

Answer 50

Earliest drug used to treat SZ which was originally designed to control blood pressure Inhibits D2 receptors

Question 51

DA Pathways: Mesolimbic

Answer 51

Affiliated with reward-related cognitions Increased activation = positive symptoms of psychosis

Question 52

DA Pathways: Mesocortical

Answer 52

Affiliated with cognitive control From the midbrain to the frontal cortex Decreased activation = negative symptoms and cognitive deficits

Question 53

DA Pathways: Nigrostriatal

Answer 53

Involved with smooth motor movements Destruction leads to Parkinson’s

Question 54

DA Pathways: Tuberoinfundibular

Answer 54

Linked with the pituitary gland Regulates sex drive

Question 55

Glutamate Hypothesis: NMDA Antagonists

Answer 55

Recreational use of NMDA antagonists increase SZ-like behavior, both positive and negative symptoms eg. angel dust ketamine

Question 56

Glutamate Hypothesis: Genetics

Answer 56

Genes affiliated with SZ impact glutamate More specifically NMDA receptor expression or receptor sites and activation *especially in the frontal cortex Increase in enzymes that break down glutamate in those with SZ Medication-free individuals with SZ display decreased NMDA binding at the hippocampus

Question 57

SZ and Low SES: Social Drift vs. Social Residual

Answer 57

Social drift – the illness causes one to descend in SES ladder Social residual – the illness prevents one from ascending this ladder

Question 58

Tardive dyskinesia

Answer 58

Not due to EPS, but rather due to long-term usage of 1st generation antipsychotics Due to years of chronic dopamine depletion, new, more sensitive, dopamine receptors are created More sensitive = more easily fired Includes spasmodic, gross, motor-movements

Question 59

2nd generation (atypicals) side effects

Answer 59

Obesity Diabetes Metabolic deregulation Zyprexa tends to cause the most weight gain Increase in prolactin release *alterations of sex characteristics and libido Agranulocytosis = deadly allergic reaction o Destroys red blood cells in 1% of those with SZ

Question 60

DA hypothesis: Salience and Delusions

Answer 60

DA mediates the salience of environmental events and internal representations * e.g. pleasure, reward, reinforcement, prediction error A dysregulated hyperdopaminergic state leads to stimulus-independent DA release This leads to an aberrant assignment of salience to one's experience Delusions may be cognitive effort by the patient to make sense of these aberrantly salient experiences

Question 61

DA hypothesis: Salience and Hallucinations

Answer 61

DA mediates the salience of environmental events and internal representations * e.g. pleasure, reward, reinforcement, prediction error A dysregulated hyperdopaminergic state leads to stimulus-independent DA release This leads to an aberrant assignment of salience to one's experience Hallucinations may reflect the direct experience of the aberrant salience of internal representations Antipsychotics dampen the salience of these abnormal experiences If antipsychotic treatment is stopped, the dysregulated neurochemistry returns, and a relapse occurs

Question 62

DSM-5 Changes in SZ

Answer 62

At least 1 of core "positive symptoms" necessary for dx Removal of subtypes (paranoid, disorganized, cationic) *no distinctive pattern of tx response or course