Schizophrenia: Class Notes Flashcards
Schizophrenia, History: Kraeplin
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
Schizophrenia, History: Bleuler
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
Schizophrenia as “Salience Disorder”
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
Schizophrenia: Onset and Prevalence
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
Risk factors: Age of Father
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)
Risk Factors: Immigration status; Marriage
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
Risk Factors: Prenatal
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
Neurodevelopmental factors
Dormant, prenatal, brain lesions only arise during puberty
Disorganized neuroarchitecture
Neurons of the brain are strung together in irregular patterns
Complicated, impractical, tangle
Other Biological Factors
*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
The dopamine hypothesis:
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
Dopamine Hypothesis: Pathways
4 major dopamine pathway, but 2 key in SZ
- Mesolimbic
- Mesocortical
Nigrostriatal
Tuberoinfundibular
Flaws to Dopamine Hypothesis
There is no genetic link to dopamine production
There is no consistent therapeutic effect of regulating dopamine
Glutamate Hypothesis
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
Glutamate Hypothesis: NMDA gateway
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
SZ Categories of Symptoms
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
Delusions
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)
Hallucinations
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
Difference between hallucinations and illusions
Illusions are caused by real-world stimuli
Hallucinations are typically negative
Disorganized Speech
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
Disorganized Behavior
Impairments of goal-directed activity
Occurs in all areas of daily-functioning
Catatonia – frozen
Catatonia Stupor = cannot be physically moved
Negative Symptoms
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
Altered Neurocognitions
Working memory
Attentional functioning
Speech production
Eye tracking
*Degree to which these are dysfunctional are the best predictors of real-life functioning following discharge
Expressed Emotions (E. E.)
Expressed emotions (E.E.) of the families which includes
- Emotionally overinvolved
- Overly critical
- 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
Risk Factors: Low SES
*SZ 8x more likely in low SES, possibly due to:
Poor nutrition
Lack of access to appropriate healthcare
Increased stress
Schizoaffective Disorder
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
Schizophreniform Disorder
Active symptoms for less than 6 months, with impaired functioning
Typically turns into SZ
Delusional Disorder
Only well-developed delusional symptoms are present, and the individual is still able to function
Shared Psychotic Disorder
When two people share a delusion, not SZ
One is typically the alpha and one is the beta (and follows along)
Brief Psychotic Disorder
Occurs after a traumatic event and naturally fades away
The individual is not likely to have another episode
SZ Treatment: History, Dorothea Dix
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
SZ Treatment: 1950’s
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)
SZ Treatment: 1960’s
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
SZ Treatment: Haldol
Still a high dosage medication but lacked the sedating effects of Thorazine
Had many extrapyramidal symptoms (EPS)
Long term use: risk of tardive dyskinesia
SZ Treatment: Haldol EPS
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
SZ Treatment: Tardive dyskinesia
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
SZ Treatment: Late 1980s, early 1990s – development of 2nd generation antipsychotics
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
SZ Treatment: Psychological Approaches
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
DA Theory in SZ: L-Dopa
L-dopa and D-amphetamine can cause psychosis-like state in healthy humans and exacerbate symptoms of schizophrenia
DA Theory in SZ: postmortem studies
Postmortem studies showed abnormalities in DA indexed in SZ
*Though data always confounded by drugs
DA Theory in SZ: Neuroimaging Studies
SZ patients when psychotic demonstrate:
Heightened synthesis of DA
Heightened DA release in response to an impulse
Heightened level of synaptic DA
DA Theory in SZ: DA Deficiency
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
DA Theory in SZ: Amphetamines
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
DA Theory in SZ: Abnormal regulation of the DA system
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
DA Theory in SZ: Prominence
DA model has been the leading neurochemical hypothesis of SZ for the last 40 years
**Current medications functioned primarily to block DA D2 receptors
Glutamate Theory in SZ
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
SZ and affect
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
Eugen Bleuler
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
SZ: Monothetic Taxonomy
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
Bleuler and Kraeplin USA and Europe
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
Reserpine
Earliest drug used to treat SZ which was originally designed to control blood pressure
Inhibits D2 receptors
DA Pathways: Mesolimbic
Affiliated with reward-related cognitions
Increased activation = positive symptoms of psychosis
DA Pathways: Mesocortical
Affiliated with cognitive control
From the midbrain to the frontal cortex
Decreased activation = negative symptoms and cognitive deficits
DA Pathways: Nigrostriatal
Involved with smooth motor movements
Destruction leads to Parkinson’s
DA Pathways: Tuberoinfundibular
Linked with the pituitary gland
Regulates sex drive
Glutamate Hypothesis: NMDA Antagonists
Recreational use of NMDA antagonists increase SZ-like behavior, both positive and negative symptoms
eg.
angel dust
ketamine
Glutamate Hypothesis: Genetics
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
SZ and Low SES: Social Drift vs. Social Residual
Social drift – the illness causes one to descend in SES ladder
Social residual – the illness prevents one from ascending this ladder
Tardive dyskinesia
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
2nd generation (atypicals) side effects
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
DA hypothesis: Salience and Delusions
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
DA hypothesis: Salience and Hallucinations
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
DSM-5 Changes in SZ
At least 1 of core “positive symptoms” necessary for dx
Removal of subtypes (paranoid, disorganized, cationic)
*no distinctive pattern of tx response or course
