3) Schizophrenia

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Emil Kraeplin

Back 1

Two major forms of "insanity"

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Two major forms of insanity

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-Kraeplin
1. manic-depressive insanity: alteration in mood; an episodic course
2. dementia praecox: alteration in thoughts; a progressively deteriorating course into profound dementia

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Manic-depressive insanity

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alteration in mood; EMOTION (depression), EPISODIC (distinct periods of disturbed emotions, otherwise emotionally healthy)

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Dementia praecox

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alteration in thoughts; COGNITION, PROGRESSIVE, eventually vegetative state

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Why did Kraepelin name it dementia praecox?

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to emphasize its characteristic onset in adolescence or young adulthood

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Egen Bleuler

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Renamed dementia praecox- schizophrenia

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Clinical features of Schizophrenia

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Two or more of the following symptoms for a duration of 6 months:
1. delusions (usually paranoid)
2. hallucinations (usually non-paranoid/ disorganized)
3. disorganized speech
4. grossly disorganized or catatonic behavior
5. negative symptoms (usually chronic)

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Types of delusions

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1. persecution (someone is out to get me)
2. reference (see hidden meanings in environment)
3. influence (mental telepathy; can read my thoughts)
4. grandeur (i'm a very important person)
In order of most common

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Positive Symptoms include

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Present in the behavior of the individual
1. delusions
2. hallucinations
3. disorganized thoughts and speech
4. catatonic or grossly disorganized manner
- catatonicity: over abundance mobility, waxy flexibility (can move them easily)
- catatonic immobility- hard to move them
- mind racing: unable to remove thoughts in head

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Most common type of hallucination

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auditory hallucinations

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Negative Symptoms

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CHRONIC- come to dominate pts life
Absences in behavior that should be there in a normal person
1. Anhedonia
2. Autism
3. Avolition, amotivation, apathy
4. Alogia

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Anhedonia

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emotional flatness; lack of emotional response/pleasure

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Autism

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withdrawal or avoidance of social connectedness; poverty of speech

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Avolition, amotivation, apathy

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loss of life-plan
impairment in functional role as wage-earner, student, homemaker; marked lack of initiative, interest, or energy

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Alogia

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absence of logical coherence in ones appraisal of events

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cognitive symptoms*

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1. executive function; abstraction; strategic problem solving; planning (prefrontal cortex)
2. spatial and verbal learning and memory (hippocampus)
3. complex and sustained attention (anterior cingulate gyrus)

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Three subtypes of this disorder

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1. Paranoid
2. Disorganized (Non-paranoid)
3. Negative (Timothy Crow's type II schizophrenia)

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Prevalence

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0.5-1% of the world population

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Equal gender distribution but...

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1. Males have earlier onset
(puberty --> age 30)... making prognosis worse
2. Females more successfully treated until menopause

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Onset

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Onset prior to adolescence is rare. Later onset (after 45) does occur though

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course of the disease

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Some show a continuous deterioration
Most show periodic relapses and remissions- but usually with residual negative symptoms during the periods of remission

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Are there genes that cause schizophrenia?*

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Candidate genes that affect dopamine or glutamate
Candidate genes that affect early development and maturation of the NS

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Multiple contributing factors

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Viral infections- women in their 2nd trimester that developed the flu- greater occurrence of child developing schizophrenia
Maternal health
Older parental age
Birth complications

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Viral infections leading to schizophrenia

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1. higher prevalence of schizophrenia among individuals born in winter months
2. influenze epidemic in Finland; babies born 3 months later had 2X the normal prevalence of schizophrenia

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Maternal health leading to schizophrenia

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diet, stress, exposures to teratogens

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Older paternal age leading to schizophrenia

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4X greater prevalence of schizophrenia if the father is >50

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Birth complications leading to schizophrenia

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Studies of high risk children (born to schizophrenic parents) show differences in birth complications between those who do and do not develop the disease
1. prematurity
2. low birth weight
3. breech presentation, cord complications
4. lower Apgar score
5. anoxia

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Post-mortem and imaging studies of schizophrenic patients' brains reveals:

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1. ventricular enlargement
2. reductions in cortical gray matter volume
3. Reduction in subcortical volumes

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Post mortem brain evaluation: Ventricular enlargement

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1. clearly not unique to schizophrenia
2. not found for all pts

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Post mortem brain evaluations: Reductions in cortical grey matter volume

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1. especially in the frontal lobes (prefrontal cortex) and temporal lobes
2. Findings in the prefrontal cortex are always of special interest bc this area of brain does not reach full maturity until late adolescence/early adulthood, corresponding to the typical time of onset for schizophrenia
Also, the prefrontal cortex coordinates so many of the types of functions that are impaired or aberrant in schizophrenia

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Post mortem brain evaluations: Reduction in subcortical volumes

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1. Hippocampus
2. Thalamus
3. Cerebellum

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Functional Imaging Studies

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- Best results obtained when comparing pts and controls as they perform some task, not with "resting" studies when the subjects are inactive
2. Wisconsin card sorting test in MZ twins: hypofrontality shown in the schizophrenic twin
3. Hypofrontality
4. Lots of contradictory findings- only 60% of studies offered evidence of hypofrontality
5. Andreasen: more likely to find hypofrontality in pts with neg. symptoms

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The average length of hospital stay decreased from 6 months in 1955 to 2 months in 1965... why?

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1. The community mental health movement with its emphasis on prevention, early detection, crisis intervention, brief hospitalization and easy return to a community, and the availability of community-based support resources to allow the pt to receive psychological care.
2. Antipsychotic drugs

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The more ___ symptoms you have the better off you are.

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Positive
b/c of drugs

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Drugs to treat schizophrenia:

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1. Barbituits
2. Organic drugs (Reserpine)

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The Doctrine of Signs

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Signs will let you know which plants should be useful to cure/relieve symptoms of what disease.
1. snake root must be good for snake bite (raises bp)
2. antihypertenisive effects of rauwolfia serpentina (lowers bp)- reserpine was isolated from Rauwolfia serpentina

Front 37

Nathan Klein

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Demonstrates the antipsychotic properties of reserpine

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Reserpine

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The first antipsychotic drug- an organic drub
Depressive side effects in approximately 25% of all psychotic pts treated
Quickly replaced when the synthetic antipsychotic drugs such as chlorpromazine became available a few years later

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Effect of Reserpine with the CNS

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1. Interference w/ the storage of catecholamine neurotrasmitters (dopamine/NE) in synaptic vessicles
2. Thus, making these NT more subject to degradation by MAO
3. Thus, in effect, lowering the level of catecholamines in the brain

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Amphetamine Psychosis

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- close similarity to an acute paranoid from of schizophrenia

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Amphetamine and acute paranoid schizophrenic pts.

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Greater exaccerbates symptoms and pts with this form of schizophrenia rarely abuse amphetamines

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Amphetamine and chronic schizophrenic pts.

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Amphetamine has little effect on persons with chronic schizophrenia and abuse of amphetamines does occur

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Psychotomimetric drugs and schizophrenic pts

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(LSD, mescaline, peyote)
Readily induced with antipsychotic drugs and pts are more inclined to use these drugs

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The schizophrenic-like symptoms resulting from an amphetamine psychosis can be treated with _______?

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antipsychotic drugs

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Amphetamine is sometimes referred to as an ________

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"indirect agonist"
- acts in the CNS by inhibiting the re-uptake of catecholamines and by permitting these neurotransmitters to be released into the synapse spontaneously, without the benefit of an AP

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Henri Laborit

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Discovery of Chlorpromazine
when searching for an antihistamine drug to diminish pre-surgical stress and thus allow less anesthesia to be used during major surgery

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Phenothiazines

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Block dopamine and noradrenergic receptors
ex:Thorazine

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Butyrophenones

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Haloperidol (Haldol): exlusively block dopamine

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The catecholamine hypothesis of schizophrenia becomes the dopamine hypothesis

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1. All of these drugs were histamine (H1) antagonists - thus sedating
2. block dopamine receptors in the brain; their clinical potency is correlated with their binding affinity for these receptors
3. these drugs often exacerbate Parkinsonian symptoms for patients with PD
4. Schizophrenic pts on execessive dosages of these antipsychotic drugs will show Parkinsonian symptoms due to blocking of dopamine receptors in the striatum
6. Effective blockade of 60-65% of D2 receptors required to treat psychotic symptoms

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The dopamine theory of schizophrenia

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-presynaptic vs post synaptic?
- Post-synaptic problem
bc
1. homovanillic acid levels in schizophrenic pts are normal- even though those pts are most responsive to antipsychotic drugs
2. prolactin secretion levels are normal in unmedicated acute and chronic schizophrenics

Front 51

Rule of thirds

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1/3 will get well
1/3 will spend sometime in hospital/ sometime at home (relapses)
1/3 will chronic schizophrenic- spend life in ward

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Atypical antipsychotic drugs:

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Clozapine (Clozaril)

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Crow's distinction between Type 1 and Type II Schizophrenia

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Type 1 (good prognosis)
- positive symptoms
- good response to antipsychotics
- normal ventricular size
- over-active DA systems
Type II (poor prognosis)
- Negative symptoms
- poor response to antipsychotics
- enlarged ventricular size; "hypofrontality"
- normal or inactive DA systems

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Paranoid and Disorganized typically lead to chronic (Kraeplin) but Crowe says otherwise...

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No, these are distinct types (type I vs type II)
There are pts. with type II that are young

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Kindling

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ex: epilesy- get rid of seizures, control the disease
Manic Depressive disorder: get control of behavior issues, the more episodes the more likely to get worse in future (less time inbtwn episodes, coming on more spontaneously)

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DA= Ach

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fine

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Ach > DA

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Akinesa
PD

difficulty in calling forth movements, freezing

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DA > Ach

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Dyskinesa
HD