About this trial

This study, "Psychobiological Follow-up Study of Transition from Prodrome to Early Psychosis", will be conducted in collaboration with the Shanghai Mental Health Center (SMHC) and several data processing sites in the United States. The current study builds on findings from the investigator's previous work that identified several biomarkers in participants at clinical high risk (CHR) for psychosis that may be related to clinical outcomes such as the development of psychosis. This study responds to the critical need to understand links between biomarkers (could be clinical, cognitive, biological or other abnormalities) and later clinical outcomes.

Participants will receive either one of two real interventions or one of two sham (a procedure that looks like the real treatment but is not) interventions, involving either: 1. repetitive transcranial magnetic stimulation (rTMS)1; or 2. mindfulness-based real time fMRI neurofeedback (mb-rt-fMRI-NFB). Both procedures will measure brain capacity for change in CHR individuals, thus paving the way forward for future therapeutic interventions.

The main hypotheses to be addressed by this study are:

1. \- Following real interventions, novel biomarkers will be more effective predictors of clinical outcome than standard biomarkers in participants at CHR for psychosis 2. \- Following real interventions, novel biomarkers will be more effective predictors of clinical outcomes in participants who received the real intervention than in participants who received sham treatments 3. \- The novel interventions will reduce biomarker abnormalities in individuals with CHR relative to their own baselines and relative to healthy controls (HC) 4. \- The sham interventions will will not reduce biomarker abnormalities in individuals with CHR relative to their own baselines or relative to HC

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

Male or female between 15 and 35 years old.

Can understand and sign an informed consent (or assent for minors) document.

No Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition (DSM-5) Alcohol or Drug Dependence in the past 3 months;

No use on the day of assessment, clearly not intoxicated or hung-over.

Disqualifiers

Meet criteria for current or lifetime Axis I psychotic disorder, including affective psychoses and psychosis Not Otherwise Specified (NOS) at the baseline assessment

Impaired intellectual functioning (i.e., Intelligence Quotient (IQ)<70) at baseline.

Past history of or current clinically significant central nervous system disorder that may contribute to prodromal symptoms or confound their assessment.

Traumatic Brain Injury that is rated as 7 or above on the Traumatic Brain Injury screening instrument (signifying a significant brain injury with persistent sequelae) or current concussion that interferes with any assessment measures.

Trial design

Design model

Parallel

Treatments tested in this trial

Mb-rt-fMRI-NFB
Device
The MRI and TMS interventions described below will yield measures of change in the targeted brain regions in post- relative to pre- intervention comparisons. These change measures will be compared relative to changes in the sham/control group and the HC group. Furthermore, they will be compared to HC to assess improvement or normalization of brain function in the targeted brain regions. In addition, the investigators will examine treatment effects on traditional biomarkers that are likely to be impacted by such interventions: ERP, NP and NLP measures. Here, mindfulness meditation practiced during a real-time fMRI NFB session will be used to bring connectivity changes to brain structures involved in positive psychiatric symptoms (e.g. attenuated psychotic symptoms) in order to to reduce them.
Sham mb-rt-fMRI-NFB
Device
Individuals with CHR who are randomly assigned to this arm will receive mb-rt-fMRI-NFB, as do the experimental group, but it will be aimed at a motor cortex location that is not part of the prefrontal neural networks targeted in the experimental group.
rTMS
Device
In previous work, the investigators used a multivariate pattern analysis to identify functional connectivity correlates of negative symptom severity in a schizophrenia (SZ) group. DLPFC-cerebellum hypo-connectivity was strongly correlated with negative symptoms. In a separate SZ cohort, the investigators used rTMS targeting the cerebellum to manipulate this circuit. The rTMS-induced increase in functional connectivity in a cerebellar-midbrain-DLPFC circuit was strongly linked to negative symptom severity reduction. Furthermore, individuals varied in the degree of change in functional connectivity in response to rTMS. This variation strongly predicted variation in post-rTMS symptom severity. The investigators predict that rTMS based intervention, but not sham rTMS, will similarly impact the cerebellar-midbrain-dorsolateral prefrontal cortex (DLPFC) network in the CHR group receiving real but not sham rTMS.
Sham rTMS
Device
Individuals with CHR who are randomly assigned to this arm will receive rTMS, as do the experimental group, but it will be aimed at a motor cortex location that is not part of the prefrontal neural networks targeted in the experimental group.

Treatment groups

300 Participants

are divided into 5 treatment groups

Group A: CHR with mb-rt-fMRI-NFB GroupExperimental treatment 1 intervention

Group B: CHR with sham mb-rt-fMRI-NFB GroupSham comparator 1 intervention

Group C: CHR with rTMS GroupExperimental treatment 1 intervention

Group D: CHR with sham rTMS GroupSham comparator 1 intervention

Group E: Healthy Control GroupNo intervention 0 interventions

Trial outcomes

Primary outcomes

1

mb-rt-fMRI-NFB intervention: functional connectivity

Context-dependent changes in functional connectivity (i.e., coupling) between brain regions will be measured by statistical software programs as Pearson correlation coefficients between brain regions whose activity depends on an interaction between psychological context (the task) and physiological state (the time course of brain activity)

Time frame

1 month, 1 year, 2 years

2

rTMS intervention: functional connectivity

Context-dependent changes in functional connectivity (i.e., coupling) between brain regions will be measured by statistical software programs as Pearson correlation coefficients between brain regions whose activity depends on an interaction between psychological context (the task) and physiological state (the time course of brain activity)

Time frame

1 month, 1 year, 2 years

Secondary outcomes

1

Clinical

Changes in Clinical High Risk clinical function from baseline will measured using the Structured Interview for Psychosis Risk Syndromes, specifically the Scale for Psychosis Risk Symptoms and the Criteria for Psychosis Risk Syndromes

Time frame

1 month, 1 year, 2 years

2

Neuropsychological function: verbal learning

Changes in verbal learning from baseline will be measured in the Clinical High Risk participants using the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery: Hopkins Verbal Learning Test - Revised

Time frame

1 month, 1 year, 2 years

3

Neuropsychological function: visual learning

Changes in visual learning from baseline will be measured in the Clinical High Risk participants using the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery: Brief Visuospatial Memory Test - Revised

Time frame

1 month, 1 year, 2 years

4

Neuropsychological function: visual-spatial / speed of processing

Changes in visual-spatial speed of processing from baseline will be measured in the Clinical High Risk participants using the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery: Trail Making Test

Time frame

1 month, 1 year, 2 years

Mechanisms of Response to Therapeutic Intervention in Clinical High Risk (CHR) for Psychosis

About this trial

Eligibility criteria

Qualifiers

Disqualifiers

Trial design

Treatments tested in this trial

Treatment groups

Trial outcomes

Primary outcomes

Secondary outcomes

Other outcomes

Sponsors and contacts