PSY4080 6.0D Schizophrenia 1 Schizophrenia. Schizophrenia 2 Case Study 1 Mike is a 33 year old divorced white male with two children he rarely ever sees

PSY4080 6.0DPSY4080 6.0D SchizophreniaSchizophrenia 11

SchizophreniaSchizophrenia


Case Study 1Case Study 1 Mike is a 33 year old divorced white male Mike is a 33 year old divorced white male with two children he rarely ever sees. He with two children he rarely ever sees. He has a college education and has a degree has a college education and has a degree in computer science.in computer science.

Mike says he knows someone has removed his Mike says he knows someone has removed his brain and replaced it with someone else's.brain and replaced it with someone else's. He believes that this brain is controlling He believes that this brain is controlling him and that he is not responsible for his him and that he is not responsible for his actions.actions.


Case Study 1Case Study 1 He works everyday and has been on his He works everyday and has been on his current job for 15 years.current job for 15 years. He says he has He says he has lots of friends but sometimes he thinks lots of friends but sometimes he thinks its one of them who did this to him.its one of them who did this to him. His His family physician has tried to get him to family physician has tried to get him to see a local psychiatrist but Mike refuses see a local psychiatrist but Mike refuses to go. to go.


Case Study 2Case Study 2 Jack, 24, graduated from high school and got a job Jack, 24, graduated from high school and got a job

working in a video store. After working for about 6 working in a video store. After working for about 6 months Jack began to hear voices that told him he was months Jack began to hear voices that told him he was no good. He also began to believe that his boss was no good. He also began to believe that his boss was planting small videocameras in the returned tapes to planting small videocameras in the returned tapes to catch him making mistakes. Jack became increasingly catch him making mistakes. Jack became increasingly agitated at work, particularly during busy times, and agitated at work, particularly during busy times, and began talking strangely to customers. began talking strangely to customers.

For example one customer asked for a tape to be For example one customer asked for a tape to be reserved and Jack indicated that that tape may not be reserved and Jack indicated that that tape may not be available because it had “surveilance photos of him that available because it had “surveilance photos of him that were being reviewed by the CIA". were being reviewed by the CIA".


Case Study 2Case Study 2 After about a year Jack quit his job one night, yelling at After about a year Jack quit his job one night, yelling at

his boss that he couldn't take the constant abuse of his boss that he couldn't take the constant abuse of being watched by all the TV screens in the store and being watched by all the TV screens in the store and even in his own home.Jack lived with his parents at the even in his own home.Jack lived with his parents at the time. He became increasingly confused and agitated. His time. He became increasingly confused and agitated. His parent took him to the hospital where he was admitted.parent took him to the hospital where he was admitted.


Prevalence, EtiologyPrevalence, Etiology 1% of population for past 30 years (Thaker 1% of population for past 30 years (Thaker

& Carpenter, 2001)& Carpenter, 2001)

1. Some suggestion that the cause may be 1. Some suggestion that the cause may be genetic (Miyamoto et al., 2003)genetic (Miyamoto et al., 2003)

Heritability (twin studies) up to 90%Heritability (twin studies) up to 90% Number of genes have been implicated:Number of genes have been implicated:

Dysbindin (DTNBP1): synaptic plasticity, signal Dysbindin (DTNBP1): synaptic plasticity, signal transductiontransduction

Neuregulin (NRG1): neuronal migration and brain Neuregulin (NRG1): neuronal migration and brain developmentdevelopment

Series of genes related to myelination and/or Series of genes related to myelination and/or oligodendrocyte functionoligodendrocyte function


Prevalence, EtiologyPrevalence, Etiology2. Number of environmental factors2. Number of environmental factors City dwellers (high population density) City dwellers (high population density) Born during late winter or early spring Born during late winter or early spring

(Feb to May)(Feb to May) (Higher) latitude(Higher) latitude Maternal factors: especially inflammatory Maternal factors: especially inflammatory

responses to infection, prenatal responses to infection, prenatal malnutrition, stressmalnutrition, stress

Neonatal factors: Rh incompatibility, Neonatal factors: Rh incompatibility, prematurity, low birthweight, prematurity, low birthweight, complications during deliverycomplications during delivery


SymptomsSymptoms Positive (presence is diagnostic)Positive (presence is diagnostic)1.1. Hallucinations: perceptions of stimuli Hallucinations: perceptions of stimuli

that are not actually presentthat are not actually present2.2. Thought disorders: disorganized, Thought disorders: disorganized,

irrational thinking, poor logic, nonsense irrational thinking, poor logic, nonsense speechspeech

3.3. Delusions: beliefs that are contrary to Delusions: beliefs that are contrary to factfact

persecutionpersecution grandeurgrandeur controlcontrol


SymptomsSymptoms Negative (absence of normal behaviours)Negative (absence of normal behaviours)1.1. Flattened emotional responseFlattened emotional response2.2. Poverty of speechPoverty of speech3.3. Lack of initiative and persistenceLack of initiative and persistence4.4. Anhedonia (inability to experience Anhedonia (inability to experience

pleasure)pleasure)5.5. Social withdrawalSocial withdrawal

These are not specific to schizophreniaThese are not specific to schizophrenia


SymptomsSymptoms Common cognitive impairments: attention, memory and executive Common cognitive impairments: attention, memory and executive

functions (IQ subtests). functions (IQ subtests).

• Often dramatic (two standard deviations below that of healthy controls)Often dramatic (two standard deviations below that of healthy controls)

Growing evidence that cognitive impairments are a distinct Growing evidence that cognitive impairments are a distinct dimension of illness (dimension of illness (Keefe and Hawkins, 2006)Keefe and Hawkins, 2006)

May be apparent prior to disease onset, especially areas of May be apparent prior to disease onset, especially areas of executive functioning.executive functioning.

Sensory and motor performance deficits as well (“neurological soft Sensory and motor performance deficits as well (“neurological soft signs”)signs”)


DSM-IV CriteriaDSM-IV CriteriaA. A. Characteristic symptomsCharacteristic symptoms: Two or more of the : Two or more of the

following, each present for a significant portion following, each present for a significant portion of time during a 1-month period (or less if of time during a 1-month period (or less if successfully treated):successfully treated):

1) delusions1) delusions2) hallucinations2) hallucinations3) disorganized speech3) disorganized speech4) grossly disorganized or catatonic behaviour4) grossly disorganized or catatonic behaviour5) negative symptoms5) negative symptoms


DSM-IV CriteriaDSM-IV CriteriaB. B. Social/occupational dysfunctionSocial/occupational dysfunction: One or more : One or more

major areas of functioning such as work, major areas of functioning such as work, interpersonal relations, or self-care are markedly interpersonal relations, or self-care are markedly below the level achieved prior to the onset below the level achieved prior to the onset

C. C. DurationDuration: Continuous signs of the disturbance : Continuous signs of the disturbance persist for at least 6 months. persist for at least 6 months.


DSM-IV CriteriaDSM-IV CriteriaD. Must exclude D. Must exclude SchizoaffectiveSchizoaffective or Mood or Mood

DisordersDisordersE. Must exclude substance use or general E. Must exclude substance use or general

medical conditions.medical conditions.F. If there is a history of Pervasive F. If there is a history of Pervasive

Developmental Disorders (PDDs), the Developmental Disorders (PDDs), the additional diagnosis of Schizophrenia is additional diagnosis of Schizophrenia is made only if prominent delusions or made only if prominent delusions or hallucinations are also present for at hallucinations are also present for at least 1 month.least 1 month.


DSM-IV CriteriaDSM-IV CriteriaSubtypesSubtypes vary with primary symptoms: vary with primary symptoms:1.1. Paranoid (delusions or auditory Paranoid (delusions or auditory

hallucinations)hallucinations)2.2. Disorganized (speech or behaviour, flat Disorganized (speech or behaviour, flat

affect)affect)3.3. Catatonic (motoric immobility/stupor or Catatonic (motoric immobility/stupor or

excessive/excitive motor activity)excessive/excitive motor activity)4.4. UndifferentiatedUndifferentiated


DSM-IV CriteriaDSM-IV Criteria Associated diagnoses:Associated diagnoses:1.1. Schizophreniform disorder (less severe in Schizophreniform disorder (less severe in

terms of symptoms and functioning)terms of symptoms and functioning)2.2. Schizoaffective (mood disorder plus Schizoaffective (mood disorder plus

delusions or hallucinations)delusions or hallucinations)3.3. Delusional disorder (delusions alone: Delusional disorder (delusions alone:

erotomanic, grandiose, jealous, erotomanic, grandiose, jealous, persecutory, somatic)persecutory, somatic)

4.4. Brief psychotic disorderBrief psychotic disorder5.5. Shared psychotic disorder (folie a deux)Shared psychotic disorder (folie a deux)


NeuropathologyNeuropathology1. Dopamine Hypothesis1. Dopamine Hypothesis Schizophrenia is caused by overactivity of Schizophrenia is caused by overactivity of dopaminergic synapsesdopaminergic synapses

Mesolimbic pathway: ventral tegmental Mesolimbic pathway: ventral tegmental area, nucleus accumbens, amygdalaarea, nucleus accumbens, amygdala


NeuropathologyNeuropathology Increased dopamine release (Laruelle, et Increased dopamine release (Laruelle, et al., 1996; Brieier et al., 1997)al., 1996; Brieier et al., 1997)• D2 receptor hyperexcitabilityD2 receptor hyperexcitability• DA agonists induce psychotic symptoms in DA agonists induce psychotic symptoms in healthy subjects (cocaine, amphetamine)healthy subjects (cocaine, amphetamine)

• Increased postsynaptic response to dopamine Increased postsynaptic response to dopamine release (Kestler, Walker, & Vega, 2001)release (Kestler, Walker, & Vega, 2001)

Presynaptic DA abnormalityPresynaptic DA abnormality• Dysfunction in storage and metabolism at the Dysfunction in storage and metabolism at the axon terminal (hyper-responsiveness)axon terminal (hyper-responsiveness)

Prolonged activation of postsynaptic Prolonged activation of postsynaptic receptorsreceptors


NeuropathologyNeuropathology2. The Serotonergic Hypothesis2. The Serotonergic Hypothesis Serotonergic hyper-excitability can also produce Serotonergic hyper-excitability can also produce

hallucinations (I.e. LSD)hallucinations (I.e. LSD) 5-HT 2A and 1A receptor subtypes appear to be the 5-HT 2A and 1A receptor subtypes appear to be the

one of the sites of action of atypical one of the sites of action of atypical antipsychoticsantipsychotics

Serotonergic pathways in pre-frontal cortex may be Serotonergic pathways in pre-frontal cortex may be disrupted or impaired in schizophrenicsdisrupted or impaired in schizophrenicsThere is likely a disruption of all monoamine There is likely a disruption of all monoamine pathways in the mesolimbic/mesocortical pathwaypathways in the mesolimbic/mesocortical pathway


NeuropathologyNeuropathology3. Brain Abnormalities shown postmortem, or 3. Brain Abnormalities shown postmortem, or with CT, PET, MRIwith CT, PET, MRI

Not related to loss of tissue, rather to Not related to loss of tissue, rather to disrupted developmental processes (neuron disrupted developmental processes (neuron size, increased cellular packing density)size, increased cellular packing density)

Reduction (bilateral) in the size of the Reduction (bilateral) in the size of the hippocampushippocampus

Enlargement of the ventricles (non-Enlargement of the ventricles (non-specific to schizophrenia)specific to schizophrenia)

Reduced brain volume overallReduced brain volume overall


NeuropathologyNeuropathology4. A neurodevelopmental disorder?4. A neurodevelopmental disorder? Abnormalities of early brain development Abnormalities of early brain development increase risk for subsequent clinical increase risk for subsequent clinical symptomssymptoms

Established correlation between Established correlation between developmental pathology developmental pathology (precursory/prodromal symptoms) and adult (precursory/prodromal symptoms) and adult psychosispsychosis

Schizophrenia may degenerative, with Schizophrenia may degenerative, with worsening of function over timeworsening of function over time

Association between first-episode psychosis Association between first-episode psychosis and structural brain changesand structural brain changes


NeuropathologyNeuropathology4. A neurodevelopmental disorder?4. A neurodevelopmental disorder? Seems to be associated with some physical Seems to be associated with some physical dysmorphisms (Schiffman et al., 2002)dysmorphisms (Schiffman et al., 2002)• head circumference too large or smallhead circumference too large or small• two or more hair whorls (cowlicks)two or more hair whorls (cowlicks)• wide-set eyeswide-set eyes• low-set or asymmetrical earslow-set or asymmetrical ears• high palate high palate • curved fifth finger, single crease in palmcurved fifth finger, single crease in palm


NeuropathologyNeuropathology Recent research suggests that some neural Recent research suggests that some neural degeneration may occur in adolescents with degeneration may occur in adolescents with early-onset schizophreniaearly-onset schizophrenia

Thompson et al (2001) - loss of cortical Thompson et al (2001) - loss of cortical gray matter volumne starting in parietal gray matter volumne starting in parietal lobes and progressing through temporal and lobes and progressing through temporal and frontal lobesfrontal lobes• May be related to prenatal influences being May be related to prenatal influences being activated by pubertal hormones, or stresses activated by pubertal hormones, or stresses associated with adolescence.associated with adolescence.


NeuropathologyNeuropathology4. Different symptoms caused by separate 4. Different symptoms caused by separate pathways.pathways.

PositivePositive symptoms are caused by hyperactivity symptoms are caused by hyperactivity of DA synapses in nucleus accumbens (Carr & of DA synapses in nucleus accumbens (Carr & Sesack, 2000).Sesack, 2000).

NegativeNegative symptoms are caused by brain symptoms are caused by brain abnormalities, particularly loss of frontal abnormalities, particularly loss of frontal neuronsneurons• Hypo-excitability of (dorsolateral) prefrontal Hypo-excitability of (dorsolateral) prefrontal cortexcortex

• Reduction of inhibitionReduction of inhibition• Associated with less activation of the frontal Associated with less activation of the frontal lobes on PET (Taylor, 1996)lobes on PET (Taylor, 1996)

Documents

PSY4080 6.0D Schizophrenia 1 Schizophrenia. Schizophrenia 2 Case Study 1 Mike is a 33 year old divorced white male with two children he rarely ever sees