Schizophrenia

SCHIZOPHRENIA
Schizophrenia Lecture 1 Objectives

To know the diagnostic criteria, prevalence, risk factors, illness course, and major treatments modalities of schizophrenia To understand some of the neuropsychological, neuroanatomic, and neurophysiological abnormalities associated with schizophrenia
To understand both the benefits and limitations of studying a behaviorally-described rather than physiologically-defined disorder
Overview of Todays Lecture

1. 2. 3. 4. Historical Figures Modern Diagnostic Criteria Issues in DiagnosisReliability Heterogeneity in Schizophrenia, Diagnostically Defined Subtypes 6. Epidemiology 7. Clinical Course 8. Psychosocial Effects
Overview of Todays Lecture

9. NeurobiologyNeurodevelopmental, Neurodegenerative or both? Genetics Neuropathology Neuroanatomy Functional brain imaging Neurophysiology and Neuropsychology Neurotransmitters-next week
Historical figures in schizophrenia research

Emil Kraepelin
In 1883, separated schizophrenia (which he called dementia praecox) from bipolar disorder (which he called manicdepressive psychosis) largely on the basis of the clinical course of the syndromes.
Eugene Bleuler
In 1911 coined the term schizophrenia, meaning splitting (or more accurately, fracturing) of the mind. Note this is NOT intended to imply split personalities but rather a split between thought and emotion
Sanders A. Don't confuse schizophrenia with multiple personality. Tex Med. 1993 Mar;89(3):8. PMID: 8451749
Diagnosis of Schizophrenia - I
A. Characteristic symptoms: > 2 of 5 of the following symptoms:
(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
Note: Only one Criterion A symptom is required if bizarre delusions or running commentary voices or voices conversing with each other.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). American Psychiatric Press; 1994 ISBN: 0890420629
Diagnosis of Schizophrenia - II
B. Social/occupational dysfunction. C. Duration: Continuous signs of the disturbance persist for at least 6 months. This 6-month period must include at least 1 month of symptoms (or less if successfully treated) that meet Criterion A (i.e., active-phase symptoms) and may include periods of prodromal or residual symptoms. D. Schizoaffective and Mood Disorder exclusion. E. Substance / general medical condition exclusion. F. No Relationship to a Pervasive Developmental Disorder: If there is a history of Autistic Disorder or another Pervasive Developmental Disorder, the additional diagnosis of Schizophrenia is made only if prominent delusions or hallucinations are also present for at least a month (or less if successfully treated).
Schizophrenia symptoms
Watch Video From Abnormal Psychology, 3rd edition Barlow & Durand
Differential Diagnosis
Mania Depression with psychotic features Personality Disorders Drug induced psychosis Extreme OCD PTSD NOT dual personality Malingering or multiple personality disorders etc.
Schizophrenia is a Behaviorally Defined Disorder

Symptoms are vague and consensus on diagnosis is not always 100% among clinicians Due to this definition, schizophrenia does NOT define a homogenous population Degree of heterogeneity within schizophrenia still hotly debated
Outcome studies of subtypes Differential physiological response
Subtypes
DSM-IV Subtypes - hierarchy in the order of consideration
Catatonic
Catatonic behavior dominates Less common nowadays Medical supportive care, benzodiazepines may help, consider ECT Disorganized speech, behavior, and affect (flat or inappropriate) Delusions and/or auditory hallucinations Not limited to persecutory themes Tends to have a later onset and better course
Disorganized (previously called hebephrenic) Paranoid
Undifferentiated - not above, but Criterion A still met Residual - Criterion A not currently met
Neurodevelopmental vs Neurodegenerative
Neurodevelopmental Risk for illness can be influenced by prenatal events Presence of MPA (minor physical anomalies) in adults with schizophrenia Post-mortem studies reveal markers of aberrant neurodevelopment (abnormal migration) Neurodegenerative Disorder Classic definition and observation of natural course brain changes such as shrinkage occur after onset of illness Early treatment known to alter course of disease Relapse rates reflect influence of external factors
Neurodevelopment
Obstetrical complications and prenatal infections are two potential non-genetic early influences on neurodevelopment Genes influencing neuronal migration and other aspects of brain development are also candidates to explain abnormalities in neurodevelopment in schizophrenia Is schizophrenia neurodevelopmental or neurodegenerative or some combination? Some now view schizophrenia as a progressive neurodevelopmental disorder (DeLisi et al. 1997; Gur et al. 1998; Rapoport et al. 1999)
Kaplan HI, Sadock BJ (eds). Synopsis of Psychiatry, 8th Edition. Lippincott, Williams & Wilkins. 1998, ISBN: 0683303309 Kandel ER, Schwartz JH, Jessell TM (eds). Principles of Neural Science. McGraw-Hill Professional Publishing. 2000, ISBN: 0838577016.
Epidemiology - I
Lifetime prevalence ~1%; male = female
Quick review of incidence (new cases) versus prevalence (all cases)
Right now over 2 million adult Americans have schizophrenia

Note that although prevalence equal among genders (WHO, ECA) , many more men seen clinically and most research has included more male subjects Seen in all cultures at similar frequency (WHO, refutes "myth" concept), though a few geographical pockets of higher prevalence exist Onset usually late adolescence to young adulthood, earlier in males than females Increased chance of being born in the winter or early spring - see reading for update
Kaplan HI, Sadock BJ (eds). Synopsis of Psychiatry, 8th Edition. Lippincott, Williams & Wilkins. 1998, ISBN: 0683303309
Prevalence relative to medical disorders
Prevalence of Selected DSM-IV Axis I Disorders

12 month Major Depression Panic Disorder Social Phobia Lifetime Major Depression Panic Disorder Social Phobia Schizophrenia M 7.7 1.3 6.6 M 12.7 2.0 11.1 1.3 F 12.9 3.2 9.1 F 21.3 5.0 15.5 0.7 Total 10.3 2.3 7.9 Total 17.1 3.5 13.3 1.0
Prevalence Figures: National Comorbidity Survey (NCS; Kessler et al., 1994); ECA, Environmental Catchment Study
Reasons Prevalence rates vary among older epidemiological studies

diagnostic criteria Rural/urban distribution Low SES slightly higher prevalence Age of sample
Epidemiology - II
Increased mortality rate from accidents and natural causes:
life span is shortened by about a decade some under-diagnosis of medical illness is present
~10-15% suicide; ~50% attempt; prominent risks:

early in illness and young age high premorbid function depression the latter two often contributing to demoralization
Illness seems concentrated in urban settings, i.e., it is somewhat correlated with population density in larger cities. Illness seems concentrated in lower socioeconomic classes.
downward drift vs. social causation
Epidemiology - III
High Co-morbidity with Substance Use ~75% nicotine; ~40% alcohol; ~20% marijuana; ~10% cocaine Substance use comorbidity worsens prognosis. ~1/3 or more of homeless population Disabling (over 50% unemployed) Costly for individual and society High number years of productive life lost 2.5% of all health care expenditures 50% of all inpatient psychiatry beds 30% of all hospitalizations $50 billion annual cost to US (direct + indirect)
Nicotine Use in Schizophrenia
Clinical course
Prodrome Acute index episode (~first hospitalization) Relapsing, remitting course
Generally, there are some prodromal signs & symptoms prior to the first acute episode These most commonly appear as attenuated Criterion A symptoms of schizophrenia and social dysfunction They can also be thought of as the symptoms of Cluster A (odd & eccentric) Personality Disorders, e.g., Paranoid, Schizoid, and/or Schizotypal Personality Disorders
Prodrome
Course
Classically, course consists of exacerbations and remissions, though often not to baseline premorbid level of functioning Illness progression often plateaus at 5 10 years after initial diagnosis Antipsychotic medications improve acute and long-term outcome About 1/4 have a good outcome, 1/4 continue to have moderate symptoms, and 1/2 remain significantly impaired with current treatment, these numbers are changing with improved pharmacologic treatments and can be altered with therapy
Symptom Presentation affects course

Positive symptoms of schizophrenia mean something is present which should not be there: Delusions; hallucinations; disorganized speech; grossly disorganized or catatonic behavior Some investigators put the latter two groups into a third category: disorganized Negative symptoms of schizophrenia mean something is missing which should be there: Affective flattening, alogia, avolition Positive symptoms, especially delusions and hallucinations, tend to decrease in severity with time, while negative symptoms tend to increase in severity over the years
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). American Psychiatric Press; 1994 ISBN: 0890420629 Kaplan HI, Sadock BJ (eds). Synopsis of Psychiatry, 8th Edition. Lippincott, Williams & Wilkins. 1998, ISBN: 0683303309
Factors Affecting Relapse
Overview of schizophrenia diagnostic and clinically validated symptoms
Violence
Media distortions and sensationalism contribute to the idea that most schizophrenics are violent, but this is largely untrue. However, after factoring out comorbid disorders well known for increasing violence (e.g., alcoholism, antisocial personality disorder), an elevated risk remains compared to the general population Best predictors are history of previous violence, along with dangerous behavior while hospitalized and hallucinations or delusions involving violence
Kaplan HI, Sadock BJ (eds). Synopsis of Psychiatry, 8th Edition. Lippincott, Williams & Wilkins. 1998, ISBN: 0683303309 Brennan PA, Mednick SA, Hodgins S. Major mental disorders and criminal violence in a Danish birth cohort. Arch Gen Psychiatry. 2000 May;57(5):494-500. PMID: 10807490
Genetics and Family Studies
Source: Gottesman (1991)

Gottesman II. Schizophrenia Genesis : The Origins of Madness. W H Freeman & Co;1990. ISBN: 0716721473
Genetic epidemiology
Family studies
Show increased risk for illness to relatives of probands (schizophrenics) vs. relatives of controls This risk falls off rapidly as the relationship becomes more distant Schizophrenia spectrum, such as schizotypal personality disorder
Twin studies
Show increased diagnostic concordance rate for monozygotic (identical) vs. dizygotic (fraternal) twins; usually a 3-4:1 ratio Heritability estimates are around 80% Monozygotic concordances of 40-50% are strong evidence for the importance of environmental components
Adoption studies
Show increased risk for biological vs. adoptive relatives of patients with schizophrenia
Segregation analyses
Attempt to fit observed families with modes of inheritance, but have not succeeded with schizophrenia
Adoption Studies Finnish and Danish adoption studies

Adoptees born to mothers with schizophrenia have higher rates of schizophrenia themselves, even though not raised with biological mothers (Heston, 1966; Rosenthal et al., 1971)
Take 2 groups adoptees with schizophrenia, adoptees without
Both groups have biological and adopted parents Biological relatives of schizophrenia adoptees have higher rates of schizophrenia than the remaining 3 groups of relatives (Kety et al., 1994)
Kety et al. Provides basis for genetic rather than environmental or chance component Diathesis stress model of schizophrenia Diathesis =genetic vulnerability, Stress=environmental factor or prenatal insult
Neuropathology (postmortem studies)

Limbic system
Decreased size of amygdala, hippocampus, and parahippocampal gyrus Disorganized neurons in hippocampus
Basal ganglia
Decreased number of D2 dopamine receptors
Temporal and frontal lobes

Some evidence for abnormal neuronal migration
Post-Mortem Neuroanatomy
Disturbed connection between thalamus and PFC
Symptoms and Neuropathology

Delusions - most common in neurological diseases bilaterally affecting the temporal lobes or basal ganglia Hallucinations - visual modality is more commonly found in neurological illnesses Individual symptoms, e.g., auditory hallucinations, are now being mapped in various neuroimaging protocols
Chow TW and Cummings JL. Neuropsychiatry: Clinical Assessment and Approach to Diagnosis. In: Sadock BJ and Sadock VA (eds.). Kaplan and Sadocks Comprehensive Textbook of Psychiatry, Seventh Edition. 2000, pp. 221-242.
Descriptions of Disordered Thought

linear - thought follows a coherent theme and is easy to follow. circumstantial - a circuitous route to the answer. Though there may be many superfluous details, the patient eventually reaches the end. tangential - thoughts that are clearly linked to a current thought but proceed in an entirely different direction. loose associations - a thought that has no logical or meaningful connection to another, adjacent thought. Usually you have no idea what the patient just said. thought blocking - inordinately long interruptions in speech during a conversation. flight of ideas - rapid progression through pretty much understandably linked topics. Usually accompanied by rapid speech. clang associations - speech in which the sound of words governs their associations, rather than meaning. E.g., "I took Zyprexa, anti-trexa, anti-transvestite."
Neuroanatomy (CT & MRI)

Increased ventricular brain ratio (VBR) is commonly seen, especially lateral and third ventricular enlargement
Correlation with severity of disease (deficit symptoms, worse premorbid function, more neurological signs) Not diagnostic and large group overlaps Decreased volumes of amygdala, hippocampus, and parahippocampal gyrus
MRI of Identical Twins
Subset of patients drink water to excess & develop hyponatremia Some neurophysiological traits are strongly associated with illness and may be biological markers:
Abnormal smooth pursuit eye movements Deficits in sensorimotor gating of auditory stimuli more later
Neurophysiology and Neuropsychology findings Several nonspecific electroencephalographic (EEG)
Other problems with information processing at higher levels (more like neuropsychology):
Halstead-Reitan and Luria-Nebraska batteries Consistent with bilateral frontal & temporal dysfunction Impairments in sustained and selective attention (e.g., CPT), retention time, & problem-solving (executive functioning, especially sequencing), visual perception (fusiform gyrus?) Some decreased intelligence as measured by IQ tests as a group
Neurotransmitters
Agonists and Antagonists
Drugs that bind with receptors on the post-synaptic (and sometimes pre-synaptic) membrane fall into two groups: Agonists: Bind to receptors and simulate or enhance a neurotransmitter's actions (i.e., opening ion channels and causing EPSPs or IPSPs). Antagonists : Have the opposite effect of agonists by blocking the receptors and inactivating it (usually by taking up the space but without specifically causing the opening of the channel or the operation of the secondary messenger). The neurotransmitter's effect is nullified or diminished.
Neurotransmitter hypotheses of schizophrenia Dopamine

Positive symptoms of schizophrenia attributed to hyperdopaminergic function (more receptors or increased sensitivity, etc) Many meds are dopamine antagonists Dopamine agonists such as amphetamine mimic psychosis
Glutamate
Disorganized thought symptoms of schizophrenia attributed to hypofunctional glutamate system Glutamate antagonists such as PCP and ketamine mimic disorganized thought, may also cause psychosis and negative symptoms?
Neurotransmitters - I
Dopamine hypothesis - strengths:
Substances leading to increased dopaminergic states cause psychosis. Another way of stating this is that L-DOPA, amphetamine, and cocaine are psychotomimetic. Antidopaminergic agents are antipsychotic, and there is a good correlation for classical antipsychotics between their potency and their D2 dopamine receptor binding Pretreatment correlations of plasma homovanillic acid (major dopamine metabolite) with severity of psychotic symptoms and treatment response Antipsychotics work for psychosis due to many other etiologies in addition to schizophrenia Some atypical antipsychotics such as clozapine are not as well correlated with respect to D2 dopamine receptor binding and clinical potency Does not account for negative symptoms of schizophrenia
Dopamine hypothesis - weaknesses:
Neurotransmitters - II
Glutamate in schizophrenia hypothesis - strengths:
Glutamate antagonists (PCP, ketamine) cause psychosis. Another way of stating this is that PCP an ketamine are psychotomimetic. PCP and ketamine cause some thought disorganization as well as positive symptoms, more similar to schizophrenia than dopamine agonists like amphetamine, also smell effects Data from post-mortem studies suggests that receptor systems may be altered in schizophrenia Ketmaine in animals alters gating in manner similar to impairment in schizophrenia (PPI) Current antipsychotics do NOT have glutamatergic activity, although future antipsychotics being developed appear promising (see NIMH web site) In animals appears to increase glucose function in frontal brain regions where schizophrenia seen to cause hypofrontality
Glutamate hypothesis - weaknesses:
Human Brain
Functional brain imaging

(PET, SPECT, rCBF, fMRI)
Failure to increase blood flow to the dorsolateral prefrontal cortex while performing the activation task of the Wisconsin Card Sorting Test Reduced blood flow to the left globus pallidus (an even earlier finding in the course of illness) suggests a problem in the system connecting the basal ganglia to the frontal lobes Correlation with severity of disease present
Wisconsin Card Sorting Task
Subjects are asked to sort each upcoming card on to one of the four piles (they are not directed but may use shape, color or number). They are told correct/incorrect. Whichever category they choose is correct for a given number of categories then is met with an incorrect response. Subjects must switch sets to get a correct response. Failure to switch sets is termed perseveration.
Schizophrenic subjects perseverate relative to normal controls, Green et al, 1992
PET image of twins during WCST
Source: Daniel Weinberger, M.D., E. Fuller Torrey, M.D., Karen Berman, M.D., NIMH Clinical Brain Disorders Branch Division of Intramural Research Programs, NIMH
Human Brain
Dorsolateral pre-frontal Cortex appears to be Associated with poor Schizophrenic performan
GABA
Earlier studies have shown that whatever causes schizophrenia causes the prefrontal cortex area of the brain to reduce in volume. This "shrinkage" apparently causes the neurons at the front of the brain to pack more closely together, but how this abnormality could produce the symptoms of schizophrenia remains a mystery.
Tooney and Chahl are exploring this mystery by investigating how the shrinkage affects GABA neurons.
Treatment
Psychopharmacologic
Classical (= typical = conventional) antipsychotics Atypical antipsychotics Other agents
Psychosocial
Supportive therapy Social skills training Case management Working with families
Classical (typical) antipsychotics - I

Synonyms for antipsychotics are neuroleptics or major tranquilizers Henri Laborit, an anesthesiologist, discovered that chlorpromazine had a marked calming effect Their introduction in the 1950s was a major revolution in psychiatry Classical antipsychotics are dopamine (D2) receptor antagonists They are most effective for positive symptoms Depot (long acting) forms are available
Classical (typical) antipsychotics - II

They are divided into a high potency and a low potency group. Potency refers to the amount (mg) of drug to give the antipsychotic effect. Examples of high potency antipsychotics include haloperidol (Haldol) and of low potency antipsychotics include chlorpromazine (Thorazine). The high potency group is worse with extrapyramidal symptom (EPS) side effects, and the low potency group is worse with most of the other side effects (anticholinergic, sedation, orthostatic hypotension). A minimum therapeutic trial is 4-6 weeks of adequate dose.
Types of Side Effects

Anticholinergic Effects (moisture)
Dry mouth, blurred vision, constipation, dizziness, drowsiness Usually disappear a few weeks after treatment, also meds to reduce
Extra-Pyramidal Side Effects (motor)

Meds also block brain areas related o muscle control, get movement disorders, (60% of pts) Muscle spasms, cramps in head and neck (dystonia), fidget or pace restlessly (akathisia), tremors and shuffling feet, facial tics/tongue/lip licking/panting/grimacing (tardive dyskinesia) Meds to reduce
Atypical antipsychotics
Atypical antipsychotics are serotonin-dopamine receptor antagonists They are as effective for positive symptoms and more effective for negative symptoms Clozapine is notable in particular:
It is effective in treatment refractory cases It is worse for most non-EPS side effects It has a ~1-2% risk of inducing agranulocytosis
The others (e.g., risperidone) generally produce fewer side effects than classical antipsychotics hear pamphlet
Other agents
Other agents may be added for augmentation purposes to the antipsychotic:
Lithium, valproate, carbamazepine Benzodiazepines
Electroconvulsive therapy (ECT) is used on occasion, especially when the patient is catatonic
Psychosocial
Supportive therapy
This is well supported as an adjunct to medication. (Insightoriented approaches are contraindicated.)
Social skills training

This especially focuses on amelioration of negative symptoms by means of cognitive-behavioral methods.
Case management
This greatly aids in coordination of care and optimization of treatment compliance.
Working with families

Besides education, the primary goal is to reduce high levels of expressed emotion to improve illness course. The National Alliance for Mental Illness (NAMI) is a key support and advocacy group.
Operational Definition of Auditory Filtering

Sensorimotor gating refers to the filtering of auditory information
Sensorimotor gating is typically measured in paired stimulus paradigms. Successful filtering is inferred from a reduced response to the second stimulus of a pair
Normal Auditory Filtering

P50 suppression is the ratio of reduced amplitude to Click 2 compared to Click 1
P50
P50
0 50 100
300
msec
0 50 100
300
msec
Click 1
Click 2
Normal Auditory Filtering

P50 suppression is the ratio of reduced amplitude to Click 2 compared to Click 1
P50 Amplitude
.5 4
P50 Ratio
Click 2 amp (2 V)
Click 1 amp (4 V) Click 1 Click 2
Example of Impaired Auditory Filtering

Schizophrenic patients have been shown to produce less reduction to Click 2 than normal controls
6
P50 Amplitude
4 2 Click Click 2 1
Normal Controls
Schizophrenic Patients
Reduced suppression of P50 to the second click yields a larger P50 ratio in schizophrenic patients than in normal controls
8
Example of Impaired Auditory Filtering

P50 Ratio
Click 2 / Click 1
6
4 2
Normal Controls
Schizophrenic Patients
Significance of P50 Research

N100
P300 P50
Reason 1 P50 occurs early in auditory stimulus processing, so it may impact later processing stages when impaired P50- filtering N100-selective attention
0 50 100
300
msec
P300- evaluation
Significance of P50 Research

Reason 2 Auditory filtering may contribute to sensory overload in schizophrenia
(Braff & Geyer, Archives of Gen. Psychiatry, 47, 1990)
Reason 3 P50 suppression abnormalities are found in well family members P50 is hypothesized as a genetic marker
(Freedman et al., Schizophrenia Bulletin, 13, 1987)
Replication of Impaired P50 Suppression in Schizophrenia

0.7
Click 2/ Click 1
0.6
P50 Ratio
0.5 0.4
0.3 0.2
0.1 0
Normal Control Subjects
Recent-Onset Schizophrenia Patients
Is P50 suppression impacted by type of neuroleptic administered?

8 V
P50 Amplitude
Click 1 Click 2
6
4 2 0
Fluphenazine Decanoate (n = 5)
Risperidone (n = 17)
Attentional Manipulations Differentially Alter P50 Suppression within Schizophrenia

Disorganized schizophrenic patients improve P50 suppression with attention directed to Click 1
Paranoid schizophrenic patients exhibit impaired P50 suppression with attentional manipulations compared to suppression levels in a passive task
Passive Task
1.6
Click 2 / Click 1
P50 Suppression varies with Attentional Manipulations in Schizophrenia

Intensity Task
1.6 1.6
Number Task
1.2
0.8 0.4 0.0 NC DS PS US
1.2
0.8 0.4 0.0 NC DS PS US
1.2
0.8 0.4 0.0 NC DS PS US
White=Controls, Green=Disorganized Pts, Gold=Paranoid Pts, Blue=Und
2 1.5 1.0 0.5
Anxiety Manipulation Differentially Alters P50 Suppression within Schizophrenia Oral MA Task Passive Task 2
1.5 1.0 0.5 0 NC DS PS US NC DS PS US
White=Controls, Gold=Disorganized Pts, Green=Paranoid Pts, Blue=Undi
Preliminary Conclusions
Diagnostic subtypes of schizophrenic patients appear to exhibit distinct patterns of alteration to P50 suppression during anxiety manipulations
These results support the position that biological heterogeneity exists within schizophrenia

Schizophrenia

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Schizophrenia

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SCHIZOPHRENIA

Schizophrenia Lecture 1 Objectives

Overview of Todays Lecture

Overview of Todays Lecture

Historical figures in schizophrenia research

Schizophrenia is a Behaviorally Defined Disorder

Disorganized (previously called hebephrenic) Paranoid

Right now over 2 million adult Americans have schizophrenia

Prevalence relative to medical disorders

Prevalence of Selected DSM-IV Axis I Disorders

Reasons Prevalence rates vary among older epidemiological studies

~10-15% suicide; ~50% attempt; prominent risks:

Nicotine Use in Schizophrenia

Symptom Presentation affects course

Factors Affecting Relapse

Overview of schizophrenia diagnostic and clinically validated symptoms

Genetics and Family Studies

Source: Gottesman (1991)

Adoption Studies Finnish and Danish adoption studies

Neuropathology (postmortem studies)

Temporal and frontal lobes

Symptoms and Neuropathology

Descriptions of Disordered Thought

Neuroanatomy (CT & MRI)

MRI of Identical Twins

Neurophysiology and Neuropsychology findings Several nonspecific electroencephalographic (EEG)

Neurotransmitter hypotheses of schizophrenia Dopamine

Dopamine hypothesis - weaknesses:

Glutamate hypothesis - weaknesses:

Functional brain imaging

Wisconsin Card Sorting Task

PET image of twins during WCST

Classical (typical) antipsychotics - I

Classical (typical) antipsychotics - II

Types of Side Effects

Extra-Pyramidal Side Effects (motor)

Social skills training

Working with families

Operational Definition of Auditory Filtering

Normal Auditory Filtering

Normal Auditory Filtering

Click 1 amp (4 V) Click 1 Click 2

Example of Impaired Auditory Filtering

Example of Impaired Auditory Filtering

Significance of P50 Research

Significance of P50 Research

Replication of Impaired P50 Suppression in Schizophrenia

Normal Control Subjects

Recent-Onset Schizophrenia Patients

Is P50 suppression impacted by type of neuroleptic administered?

Attentional Manipulations Differentially Alter P50 Suppression within Schizophrenia

P50 Suppression varies with Attentional Manipulations in Schizophrenia

White=Controls, Green=Disorganized Pts, Gold=Paranoid Pts, Blue=Und

2 1.5 1.0 0.5

White=Controls, Gold=Disorganized Pts, Green=Paranoid Pts, Blue=Undi

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