Schizophrenia. Environmental factors

Июль 31, 2022

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Schizophrenia. Environmental factors

Содержание

3. Environmental factors
4. Age of onset and peak of mental disorders Nat Rev Neurosci (2), & 2008
6. Schizophrenia: inheritance
7. Manhattan plot showing schizophrenia associations S Ripke et al. Nature 1-7 (2014)
8. Subdivision of Symptoms into Three Dimensions Psychotic Delusions Hallucinations Disorganized Disorganized speech Disorganized behavior Inappropriate affect
9. Types of Hallucinations Auditory Visual Tactile Olfactory
10. Types of Delusions Persecutory Grandiose Religious Jealous Somatic
11. DSM-5 Criteria for Schizophrenia: The Basics Characteristic symptoms for one month Social/Occupational Dysfunction Overall Duration >
12. Differential Diagnosis Mood Disorders Nonpsychotic personality disorders Substance-induced psychotic disorders Psychotic disorders due to a general
13. Drugs That May Induce Psychosis Amphetamines Marijuana Hallucinogens Cocaine Cannabis
14. Medical Conditions That May Present with Psychosis Temporal lobe epilepsy Tumor Stroke Trauma Endocrine/metabolic abnormalities Infections
15. The Dopamine Hypothesis Psychosis (schizophrenia?) is due to excessive dopaminergic tone Psychotic symptoms are relieved by
16. Copyright restrictions may apply. Howes, O. D. et al. Arch Gen Psychiatry 2012;0:archgenpsychiatry.2012.169v1-11. Schematic diagram summarizing
19. Brain Regions Showing Replicable Neuropathological Abnormalities Temporolimbic regions Thalamus Prefrontal cortex
20. Neuropil in Frontal Cortex
22. Criterion A: Characteristic Symptoms At least two of the following, each present for a significant portion
23. Gender Differences Males have an earlier age at onset, a poorer premorbid history, more negative symptoms,
24. Important Epidemiolgical Observations Prevalence is not highly variable over time or over geographical areas Found in
25. Bleuler’s Fundamental Symptoms Associations Affective Blunting Avolition Autism Ambivalence Attention
26. Schneider: The Psychotic Experience Interested in pathognomonic symptoms “First Rank Symptoms” (FRS) E.g., voices commenting Voices
27. Characteristic Symptoms Schneider: specific types of delusions and hallucinations Bleuler: fragmented thinking, inability to relate to
28. Criterion B: Social/Occupational Dysfunction For a significant portion of the time since the onset of the
29. Criterion C: Overall Duration Continuous signs of the disturbance persist for at least six months This
30. Criterion D: Schizoaffective and Mood Disorder Exclusion Schizoaffective Disorder and Mood Disorder with Psychotic Features have
31. Criterion E: Substance / General Medical Condition Exclusion The disturbance is not due to the direct
32. DSM 5: Categories of Psychosis Schizophreniform Disorder Schizophrenia Brief Psychotic Disorder Schizoaffective Disorder Delusional Disorder Shared
33. Poor Outcome: Predictors Prominent negative symptoms Early age of onset Insidious onset Poor premorbid adjustment Low
35. Lower Social Class in Schizophrenia Consistently observed in patients Lower social class is a result—not a
36. Genetic Questions Is the disorder familial? Relative contributions of genes and environment Mode of transmission Location
37. Genetic Methods Family history studies Family studies Twin studies Adoption studies Linkage and association studies, candidate
38. Manhattan plot showing schizophrenia associations S Ripke et al. Nature 1-7 (2014)
39. Family History and Family Studies Provide evidence for a modest level of familial transmission Morbid risk
40. Possible Reasons for Lack of Measurable Abnormalities Problems in defining the phenotype No single pathophysiology Due
41. Hippocampal Atrophy in Schizophrenia Patients Controls
42. Thalamic Nuclei
43. A Neurodevelopmental Disorder: Supporting Evidence from Neuropathology Absence of gliosis Abnormal cytoarchitecture Visible markers of neurodevelopmental
44. Classified Images Continuous Discrete
45. MR Studies: Brain Abnormalities Decreased temporal lobe size Decreased frontal lobe size Decreased hippocampal size Decreased
46. A Neurodevelopmental Brain Disease Most brain abnormalities are present at onset: e.g., decrease in total brain
47. Increased Blood Flow in Striatum due to Chronic Dopamine Blockade by Haloperidol
48. Functional Imaging Tools Single Photon Emission Computed Tomography (SPECT) Positron Emission Tomography (PET) Functional Magnetic Resonance
49. Conclusions from PET Studies Schizophrenia is not a disease of a single brain region Areas of
50. The fMR Blood Flow Signal
51. Verbal Fluency Patients Controls
52. The N-Back Task for fMR Probe x x Target Experimental Task (2-Back): Remember the Probe and
53. 2-Back Task in Normals Bilateral dorsolateral frontal Bilateral parietal Anterior cingulate
54. 2-Back Task in Schizophrenia (unmedicated) Blood flow markedly decreased or absent in regions used by normals
55. Sensory Gating A problem in filtering or gating information Leads to the subject experience of being
56. Cognitive Dysmetria A defect in coordinating mental activity Due to disturbed functional connectivity between the cortex
58. Simplified Summary of Various Anatomical Refinements of the Dopamine Hypotheses of Schizophrenia Laruelle, Biol psychiatry 2013;74:80–81
59. Copyright restrictions may apply. Howes, O. D. et al. Arch Gen Psychiatry 2012;0:archgenpsychiatry.2012.169v1-11. Schematic diagram summarizing
60. Multiple hits interact to result in (1) striatal dopamine dysregulation to alter (2) the appraisal of
63. The Essence of Schizophrenia Originally called “dementia praecox” Produces severe incapacity – “dementia” Typically begins in
64. Kraepelin: Course and Outcome Split “dementia praecox” from manic-depressive illness Early onset Marked deterioration Chronic course
65. Fundamental Questions about Schizophrenia What are the characteristic symptoms? What are the boundaries of the concept?
66. Lifetime Prevalence What proportion of the population will develop the disorder at some time during their
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Environmental factors

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Age of onset and peak of mental disorders
Nat Rev Neurosci (2),

& 2008

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Schizophrenia: inheritance

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Manhattan plot showing schizophrenia associations
S Ripke et al. Nature 1-7

(2014)

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Subdivision of Symptoms into Three Dimensions
Psychotic
Delusions
Hallucinations
Disorganized
Disorganized speech
Disorganized behavior
Inappropriate affect
Negative
Poverty of speech
Avolition
Affective

Blunting
Anhedonia

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Types of Hallucinations
Auditory
Visual
Tactile
Olfactory

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Types of Delusions
Persecutory
Grandiose
Religious
Jealous
Somatic

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DSM-5 Criteria for Schizophrenia: The Basics
Characteristic symptoms for one month
Social/Occupational Dysfunction
Overall

Duration > 6 months
Not attributable to mood disorder
Not attributable to substance use or general medical condition

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Differential Diagnosis
Mood Disorders
Nonpsychotic personality disorders
Substance-induced psychotic disorders
Psychotic disorders due to a

general medical condition (i.e., “organic” disorders)

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Drugs That May Induce Psychosis
Amphetamines
Marijuana
Hallucinogens
Cocaine
Cannabis

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Medical Conditions That May Present with Psychosis
Temporal lobe epilepsy
Tumor
Stroke
Trauma
Endocrine/metabolic abnormalities
Infections
Multiple Sclerosis
Autoimmune

diseases

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The Dopamine Hypothesis
Psychosis (schizophrenia?) is due to excessive dopaminergic tone
Psychotic symptoms

are relieved by blockade of dopamine receptors with neuroleptic medications

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Copyright restrictions may apply.
Howes, O. D. et al. Arch Gen Psychiatry

2012;0:archgenpsychiatry.2012.169v1-11.

Schematic diagram summarizing the findings from our meta-analyses of dopamine function in schizophrenia

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Brain Regions Showing Replicable Neuropathological Abnormalities
Temporolimbic regions
Thalamus
Prefrontal cortex

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Neuropil in Frontal Cortex

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Criterion A: Characteristic Symptoms
At least two of the following, each present

for a significant portion of time during a one month period (or less if successfully treated):
(1) delusions
(2) hallucinations
(3) disorganized speech (e.g., frequent derailment or incoherence)
(4) grossly disorganized or catatonic behavior
(5) negative symptoms, I.e., affective flattening, alogia, or avolition

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Gender Differences
Males have an earlier age at onset, a poorer premorbid

history, more negative symptoms, a poorer outcome, and more prominent brain abnormalities as measured in neuroimaging studies
Women have more prominent affective symptoms and a better outcome

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Important Epidemiolgical Observations
Prevalence is not highly variable over time or over

geographical areas
Found in all cultures
More common and/or severe in males than females
Persists in the population despite decreased fertility

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Bleuler’s Fundamental Symptoms
Associations
Affective Blunting
Avolition
Autism
Ambivalence
Attention

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Schneider: The Psychotic Experience
Interested in pathognomonic symptoms
“First Rank Symptoms” (FRS)
E.g., voices

commenting
Voices arguing
Thought insertion
Involve a loss of the sense of autonomy of self, or “ego boundaries”

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Characteristic Symptoms
Schneider: specific types of delusions and hallucinations
Bleuler: fragmented thinking, inability

to relate to external world
Kraepelin: emotional dullness, avolition, loss of inner unity

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Criterion B: Social/Occupational Dysfunction
For a significant portion of the time since

the onset of the disturbance, one or more major areas of functioning such as work, interpersonal relations or self-care is markedly below the level achieved prior to the onset
OR when the onset is in childhood or adolescence, failure to achieve expected level of interpersonal, academic, or occupational achievement

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Criterion C: Overall Duration
Continuous signs of the disturbance persist for at

least six months
This six-month period must include at least one month of symptoms that meet criterion A (i.e., active phase symptoms), and may include periods of prodromal or residual symptoms
During these prodromal or residual period, the signs of the disturbance may be manifested by only negative symptoms or two or more symptoms listed in criterion A present in an attenuated form (e.g. odd beliefs, unusual perceptual experiences)

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Criterion D: Schizoaffective and Mood Disorder Exclusion
Schizoaffective Disorder and Mood Disorder

with Psychotic Features have been ruled out because of either:
No major depressive or manic episodes have occurred concurrently with the active phase symptoms; or
If mood episodes have occurred during active phase symptoms, their total duration has been brief relative to the duration of the active and residual periods

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Criterion E: Substance / General Medical Condition Exclusion
The disturbance is not

due to the direct effects of a substance (e.g., drugs of abuse, medication) or a general medical condition

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DSM 5: Categories of Psychosis
Schizophreniform Disorder
Schizophrenia
Brief Psychotic Disorder
Schizoaffective Disorder
Delusional Disorder
Shared Psychotic

Disorder
Psychotic Disorder due to a General Medical Condition
Substance-Induced Psychotic Disorder
Psychotic Disorder Not Otherwise Specified

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Poor Outcome: Predictors
Prominent negative symptoms
Early age of onset
Insidious onset
Poor premorbid adjustment
Low

educational achievement
Low parental social class
Male gender

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Lower Social Class in Schizophrenia
Consistently observed in patients
Lower social class is

a result—not a cause—of the illness
Social class of parents does not differ from the general population
Lower social class is due to “downward drift,” not to social deprivation, poor nutrition, or inadequate access to health care

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Genetic Questions
Is the disorder familial?
Relative contributions of genes and environment
Mode of

transmission
Location of gene
Function and products of gene
Role of the products in illness mechanisms

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Genetic Methods
Family history studies
Family studies
Twin studies
Adoption studies
Linkage and association studies, candidate

genes
Molecular genetics—functional genomics, proteomics

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Manhattan plot showing schizophrenia associations
S Ripke et al. Nature 1-7

(2014)

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Family History and Family Studies
Provide evidence for a modest level of

familial transmission
Morbid risk for parents: 5.6%
Morbid risk for siblings: 10.1%
Morbid risk for offspring: 12.8%
Second degree relatives: 2.4-4.2%

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Possible Reasons for Lack of Measurable Abnormalities
Problems in defining the

phenotype
No single pathophysiology
Due to reversible neurochemical processes
Not accessible using traditional neuropathology tools
In areas where neuropathologists have not yet looked
Due to abnormalities in connectivity

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Hippocampal Atrophy in Schizophrenia
Patients
Controls

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Thalamic Nuclei

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A Neurodevelopmental Disorder: Supporting Evidence from Neuropathology
Absence of gliosis
Abnormal cytoarchitecture
Visible markers

of neurodevelopmental abnormalities such as cavum septi pellucidi

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Classified Images
Continuous
Discrete

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MR Studies: Brain Abnormalities
Decreased temporal lobe size
Decreased frontal lobe size
Decreased hippocampal

size
Decreased thalamic size
Gyral decreases (superior temporal gyrus, ventral frontal gyri)
General and regional decreases in gray matter volume

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A Neurodevelopmental Brain Disease
Most brain abnormalities are present at onset: e.g.,

decrease in total brain tissue
Occasional evidence of defects in neuronal migration: gray matter heterotopias
Midline abnormalities: cavum septi pellucidi, dysgenesis of the corpus callosum, ventricular enlargement

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Increased Blood Flow in Striatum due to Chronic Dopamine Blockade by

Haloperidol

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Functional Imaging Tools
Single Photon Emission Computed Tomography (SPECT)
Positron Emission Tomography (PET)
Functional

Magnetic Resonance (fMR)

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Conclusions from PET Studies
Schizophrenia is not a disease of a single

brain region
Areas of abnormality vary depending on the task and the nature of current symptoms
Schizophrenia affects distributed circuitry throughout the brain

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The fMR Blood Flow Signal

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Verbal Fluency
Patients
Controls

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The N-Back Task for fMR
Probe
x
x
Target
Experimental Task (2-Back): Remember the Probe and

Monitor for It

Comparison Task: Look for the S

Target

Look for the S

2-Back Task

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2-Back Task in Normals
Bilateral dorsolateral frontal
Bilateral parietal
Anterior cingulate

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2-Back Task in Schizophrenia (unmedicated)
Blood flow markedly decreased or absent in

regions used by normals
Main activation is anterior cingulate

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Sensory Gating
A problem in filtering or gating information
Leads to the subject

experience of being bombarded by stimuli
Explains most symptoms—e.g., confusion of internal and external stimuli would cause delusions and hallucinations
Supported by neurophysiological studies of prepulse inhibition

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Cognitive Dysmetria
A defect in coordinating mental activity
Due to disturbed functional connectivity

between the cortex and subcortical regions (thalamus and cerebellum)
Leads to functional and cognitive misconnections
Explains diversity of symptoms (e.g., misconnecting a perception and its meaning might lead to delusions and hallucinations)
Supported by functional imaging studies

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Simplified Summary of Various Anatomical Refinements of the Dopamine Hypotheses of

Schizophrenia

Laruelle, Biol psychiatry 2013;74:80–81

AST, associative striatum; DA, dopamine; DLPFC, dorsolateral prefrontal cortex; VST, ventral striatum

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Copyright restrictions may apply.
Howes, O. D. et al. Arch Gen Psychiatry

2012;0:archgenpsychiatry.2012.169v1-11.

Schematic diagram summarizing the findings from our meta-analyses of dopamine function in schizophrenia

Слайд 60

Multiple hits interact to result in (1) striatal dopamine dysregulation to

alter (2) the appraisal of stimuli and resulting in psychosis, whilst current antipsychotic drugs (3) act downstream of the primary dopaminergic dysregulation.

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The Essence of Schizophrenia
Originally called “dementia praecox”
Produces severe incapacity – “dementia”
Typically

begins in adolescence – “praecox”

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Kraepelin: Course and Outcome
Split “dementia praecox” from manic-depressive illness
Early onset
Marked deterioration
Chronic

course
Diversity of signs and symptoms
Importance of volition and affect

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Fundamental Questions about Schizophrenia
What are the characteristic symptoms?
What are the boundaries

of the concept?
Is the disorder a single illness or multiple disorders?
If multiple, what are the subtypes?

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Lifetime Prevalence
What proportion of the population will develop the disorder at

some time during their lifetime?
Perhaps the most important statistic for schizophrenia because of its inherent chronicity
Prevalence 0.30-0.66% - narrow diagnostic category of schizophrenia
Prevalence 2.3% - schizophrenia and related psychoses (e.g., delusional, catch-all category of NOS)
Prevalence 3.5% - broader category of psychotic disorders including schizophrenia and related disorders, substance-induced psychotic disorders and bipolar disorder

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Schizophrenia. Environmental factors

Содержание

Environmental factors

Age of onset and peak of mental disordersNat Rev Neurosci (2),

Schizophrenia: inheritance

Manhattan plot showing schizophrenia associations S Ripke et al. Nature 1-7

Subdivision of Symptoms into Three DimensionsPsychoticDelusionsHallucinationsDisorganizedDisorganized speechDisorganized behaviorInappropriate affectNegativePoverty of speechAvolitionAffective

Types of HallucinationsAuditoryVisualTactileOlfactory

Types of Delusions PersecutoryGrandioseReligiousJealousSomatic

DSM-5 Criteria for Schizophrenia: The BasicsCharacteristic symptoms for one monthSocial/Occupational DysfunctionOverall

Differential DiagnosisMood DisordersNonpsychotic personality disordersSubstance-induced psychotic disordersPsychotic disorders due to a

Drugs That May Induce PsychosisAmphetaminesMarijuanaHallucinogensCocaineCannabis

Medical Conditions That May Present with PsychosisTemporal lobe epilepsyTumorStrokeTraumaEndocrine/metabolic abnormalitiesInfectionsMultiple SclerosisAutoimmune

The Dopamine HypothesisPsychosis (schizophrenia?) is due to excessive dopaminergic tonePsychotic symptoms

Copyright restrictions may apply.Howes, O. D. et al. Arch Gen Psychiatry

Brain Regions Showing Replicable Neuropathological Abnormalities Temporolimbic regionsThalamusPrefrontal cortex

Neuropil in Frontal Cortex

Criterion A: Characteristic SymptomsAt least two of the following, each present

Gender DifferencesMales have an earlier age at onset, a poorer premorbid

Important Epidemiolgical ObservationsPrevalence is not highly variable over time or over

Bleuler’s Fundamental SymptomsAssociationsAffective BluntingAvolitionAutismAmbivalenceAttention

Schneider: The Psychotic ExperienceInterested in pathognomonic symptoms“First Rank Symptoms” (FRS) E.g., voices

Characteristic SymptomsSchneider: specific types of delusions and hallucinationsBleuler: fragmented thinking, inability

Criterion B: Social/Occupational DysfunctionFor a significant portion of the time since

Criterion C: Overall DurationContinuous signs of the disturbance persist for at

Criterion D: Schizoaffective and Mood Disorder ExclusionSchizoaffective Disorder and Mood Disorder

Criterion E: Substance / General Medical Condition ExclusionThe disturbance is not

DSM 5: Categories of PsychosisSchizophreniform DisorderSchizophreniaBrief Psychotic DisorderSchizoaffective DisorderDelusional DisorderShared Psychotic

Poor Outcome: PredictorsProminent negative symptomsEarly age of onsetInsidious onsetPoor premorbid adjustmentLow

Lower Social Class in SchizophreniaConsistently observed in patientsLower social class is

Genetic QuestionsIs the disorder familial?Relative contributions of genes and environmentMode of

Genetic MethodsFamily history studiesFamily studiesTwin studiesAdoption studiesLinkage and association studies, candidate

Manhattan plot showing schizophrenia associations S Ripke et al. Nature 1-7

Family History and Family StudiesProvide evidence for a modest level of

Possible Reasons for Lack of Measurable Abnormalities Problems in defining the

Hippocampal Atrophy in SchizophreniaPatientsControls

Thalamic Nuclei

A Neurodevelopmental Disorder: Supporting Evidence from NeuropathologyAbsence of gliosisAbnormal cytoarchitectureVisible markers

Classified ImagesContinuousDiscrete

MR Studies: Brain AbnormalitiesDecreased temporal lobe sizeDecreased frontal lobe sizeDecreased hippocampal

A Neurodevelopmental Brain DiseaseMost brain abnormalities are present at onset: e.g.,

Increased Blood Flow in Striatum due to Chronic Dopamine Blockade by

Functional Imaging ToolsSingle Photon Emission Computed Tomography (SPECT)Positron Emission Tomography (PET)Functional

Conclusions from PET StudiesSchizophrenia is not a disease of a single

The fMR Blood Flow Signal

Verbal FluencyPatientsControls

The N-Back Task for fMRProbexxTargetExperimental Task (2-Back): Remember the Probe and

2-Back Task in NormalsBilateral dorsolateral frontalBilateral parietalAnterior cingulate

2-Back Task in Schizophrenia (unmedicated)Blood flow markedly decreased or absent in

Sensory GatingA problem in filtering or gating informationLeads to the subject

Cognitive DysmetriaA defect in coordinating mental activityDue to disturbed functional connectivity

Simplified Summary of Various Anatomical Refinements of the Dopamine Hypotheses of

Copyright restrictions may apply.Howes, O. D. et al. Arch Gen Psychiatry

Multiple hits interact to result in (1) striatal dopamine dysregulation to

The Essence of SchizophreniaOriginally called “dementia praecox”Produces severe incapacity – “dementia”Typically

Kraepelin: Course and OutcomeSplit “dementia praecox” from manic-depressive illnessEarly onsetMarked deteriorationChronic

Fundamental Questions about SchizophreniaWhat are the characteristic symptoms?What are the boundaries

Lifetime PrevalenceWhat proportion of the population will develop the disorder at

Похожие презентации

Age of onset and peak of mental disorders
Nat Rev Neurosci (2),

Manhattan plot showing schizophrenia associations
S Ripke et al. Nature 1-7

Subdivision of Symptoms into Three Dimensions
Psychotic
Delusions
Hallucinations
Disorganized
Disorganized speech
Disorganized behavior
Inappropriate affect
Negative
Poverty of speech
Avolition
Affective

Types of Hallucinations
Auditory
Visual
Tactile
Olfactory

Types of Delusions
Persecutory
Grandiose
Religious
Jealous
Somatic

DSM-5 Criteria for Schizophrenia: The Basics
Characteristic symptoms for one month
Social/Occupational Dysfunction
Overall

Differential Diagnosis
Mood Disorders
Nonpsychotic personality disorders
Substance-induced psychotic disorders
Psychotic disorders due to a

Drugs That May Induce Psychosis
Amphetamines
Marijuana
Hallucinogens
Cocaine
Cannabis

Medical Conditions That May Present with Psychosis
Temporal lobe epilepsy
Tumor
Stroke
Trauma
Endocrine/metabolic abnormalities
Infections
Multiple Sclerosis
Autoimmune

The Dopamine Hypothesis
Psychosis (schizophrenia?) is due to excessive dopaminergic tone
Psychotic symptoms

Copyright restrictions may apply.
Howes, O. D. et al. Arch Gen Psychiatry

Brain Regions Showing Replicable Neuropathological Abnormalities
Temporolimbic regions
Thalamus
Prefrontal cortex

Criterion A: Characteristic Symptoms
At least two of the following, each present

Gender Differences
Males have an earlier age at onset, a poorer premorbid

Important Epidemiolgical Observations
Prevalence is not highly variable over time or over

Bleuler’s Fundamental Symptoms
Associations
Affective Blunting
Avolition
Autism
Ambivalence
Attention

Schneider: The Psychotic Experience
Interested in pathognomonic symptoms
“First Rank Symptoms” (FRS)
E.g., voices

Characteristic Symptoms
Schneider: specific types of delusions and hallucinations
Bleuler: fragmented thinking, inability

Criterion B: Social/Occupational Dysfunction
For a significant portion of the time since

Criterion C: Overall Duration
Continuous signs of the disturbance persist for at

Criterion D: Schizoaffective and Mood Disorder Exclusion
Schizoaffective Disorder and Mood Disorder

Criterion E: Substance / General Medical Condition Exclusion
The disturbance is not

DSM 5: Categories of Psychosis
Schizophreniform Disorder
Schizophrenia
Brief Psychotic Disorder
Schizoaffective Disorder
Delusional Disorder
Shared Psychotic

Poor Outcome: Predictors
Prominent negative symptoms
Early age of onset
Insidious onset
Poor premorbid adjustment
Low

Lower Social Class in Schizophrenia
Consistently observed in patients
Lower social class is

Genetic Questions
Is the disorder familial?
Relative contributions of genes and environment
Mode of

Genetic Methods
Family history studies
Family studies
Twin studies
Adoption studies
Linkage and association studies, candidate

Manhattan plot showing schizophrenia associations
S Ripke et al. Nature 1-7

Family History and Family Studies
Provide evidence for a modest level of

Possible Reasons for Lack of Measurable Abnormalities
Problems in defining the

Hippocampal Atrophy in Schizophrenia
Patients
Controls

A Neurodevelopmental Disorder: Supporting Evidence from Neuropathology
Absence of gliosis
Abnormal cytoarchitecture
Visible markers

Classified Images
Continuous
Discrete

MR Studies: Brain Abnormalities
Decreased temporal lobe size
Decreased frontal lobe size
Decreased hippocampal

A Neurodevelopmental Brain Disease
Most brain abnormalities are present at onset: e.g.,

Functional Imaging Tools
Single Photon Emission Computed Tomography (SPECT)
Positron Emission Tomography (PET)
Functional

Conclusions from PET Studies
Schizophrenia is not a disease of a single

Verbal Fluency
Patients
Controls

The N-Back Task for fMR
Probe
x
x
Target
Experimental Task (2-Back): Remember the Probe and

2-Back Task in Normals
Bilateral dorsolateral frontal
Bilateral parietal
Anterior cingulate

2-Back Task in Schizophrenia (unmedicated)
Blood flow markedly decreased or absent in

Sensory Gating
A problem in filtering or gating information
Leads to the subject

Cognitive Dysmetria
A defect in coordinating mental activity
Due to disturbed functional connectivity

Copyright restrictions may apply.
Howes, O. D. et al. Arch Gen Psychiatry

The Essence of Schizophrenia
Originally called “dementia praecox”
Produces severe incapacity – “dementia”
Typically

Kraepelin: Course and Outcome
Split “dementia praecox” from manic-depressive illness
Early onset
Marked deterioration
Chronic

Fundamental Questions about Schizophrenia
What are the characteristic symptoms?
What are the boundaries

Lifetime Prevalence
What proportion of the population will develop the disorder at