About this trial
In Study 1, investigators will test the ability of each of the seven paradigms to differentiate between schizophrenia (SZ)/schizoaffective disorder (SZA) and matched healthy control subjects (HC) and to predict individual differences in clinical measures of hallucinations and delusions (as well as measures of function). Investigators will also directly compare the tasks in terms of predictive ability and psychometric properties and determine whether the tasks share variance or explain unique variance. This will include determining whether hallucinations and delusions are best explained by separate underlying processes or by a single process. Investigators will also test whether the model-based parameters from these studies are more precise and sensitive than standard behavioral methods for assessing deficits across psychotic disorders and for predicting hallucinations and delusions (Aim 1). Investigators will also validate key model-based parameters against well-characterized neurophysiological measures using electroencephalogram (EEG) (Aim 4). The data from Study 1 will also be used to optimize (e.g., length, floor, and ceiling effects) tasks for Study 2. To generate a sample with sufficient variation in hallucinations and delusions, investigators will recruit the following groups that balance feasibility with clinical relevance: A) healthy controls (HC) \[HC, N=125\]; B) schizophrenia and schizoaffective disorder \[SZ/SZA, N=200\]). For Study 1, investigators will ensure that 40 patients are unmedicated. Investigators anticipate a \~20% screen fail/drop-out rate based on our prior Cognitive Neuroscience Test Reliability and Clinical Applications for Schizophrenia Consortium (CNTRACS) studies. Thus, investigators will run an additional 40 SZ/SZA and 15 HC. All sites have experience recruiting patients in each of these groups as indicated by our past successful studies, and the fact that investigators have been able to recruit patients with significant hallucinations and delusions in all groups. Investigators will also validate key model-based parameters against well-characterized neurophysiological measures using electroencephalogram (EEG) (Aim 4). The data from Study 1 will also be used to optimize (e.g., length, floor, and ceiling effects) tasks for Study 2. To generate a sample with sufficient variation in hallucinations and delusions, investigators will recruit the following groups that balance feasibility with clinical relevance: A) healthy controls (HC) \[HC, N=125\]; B) schizophrenia and schizoaffective disorder \[SZ/SZA, N=200\]). For Study 1, investigators will ensure that 40 patients are unmedicated. Investigators anticipate a \~20% screen fail/drop-out rate based on our prior Cognitive Neuroscience Test Reliability and Clinical Applications for Schizophrenia Consortium (CNTRACS) studies. Thus, investigators will run an additional 40 SZ/SZA and 15 HC. All sites have experience recruiting patients in each of these groups as indicated by our past successful studies, and the fact that investigators have been able to recruit patients with significant hallucinations and delusions in all groups.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
age 18 to 59
no substance disorder in past six months (confirmed with urine drug screens and breathalyzers);
no clinically significant head injury or neurological disease. 4. Wechsler Test of Adult Reading (WTAR) score =16+.
Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) diagnosis of schizophrenia or schizoaffective;
Disqualifiers
Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) Psychosis or Bipolar Disorder diagnosis
Family history of psychosis or bipolar
not in acute exacerbation requiring immediate hospitalization or treatment
self-reported medication non-compliance for at least the four previous weeks 3)never having started medications
Trial design
Single group
Treatments tested in this trial
Motion Perception Task
BehavioralAssesses updating of beliefs from new sensory inputs with prior knowledge via perceiving direction changes in random dot motion stimuli
Sine Wave Speech Task
BehavioralMeasures the degree to which overweighting of prior beliefs impacts processing of sensory inputs (detection of speech).
Volatility Task
BehavioralMeasures the updating of priors about the location of a bag drop from a helicopter when the location changes (prediction errors).
Choice Probabilistic Reversal Task
BehavioralAssesses prior belief updating when feedback about obtaining positive outcomes changes (prediction errors).
Kamin Blocking Task
BehavioralExamines the role of mismatches between learned priors and new information (prediction errors) in belief formation about event causes.
Minnesota Trust Game
BehavioralAssesses the degree to which people distinguish between their priors about others' motivations, such as selfishness and spite, and impersonal chance in one-shot trust game and dictator games.
Dynamic Trust Game
BehavioralAssesses degree to which people learn and update priors about trusting partners from dynamic social feedback (prediction error) in a social exchange game.
Treatment groups
Trial outcomes
Primary outcomes
Motion Perception Task Performance
With 15 degrees of initial or changed direction vs. the probability of failing to update.
Sine Wave Speech Task Performance
Percentage of trials coded as speech or not vs Dprime
Volatility Task Performance
Percent correct bag captures during periods of stability vs. instability - patients worse in both, but particularly impaired in instability vs. Environmental volatility belief parameter
Choice Probabilistic Reversal Performance Task
in-switch rate - higher in patients, particularly paranoid patients vs. prior on volatility belief updating in response to volatility
Sponsors and contacts
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Washington University School of Medicine
Lead sponsor
National Institute of Mental Health (NIMH)
Collaborator
University of Minnesota
Collaborator
University of Chicago
Collaborator
University of California, Irvine
Collaborator
University of Maryland, Baltimore County
Collaborator