Biomarkers of Conversion Risk and Treatment Response in Early-Stage Schizophrenia
Overview
- Phase
- Phase 4
- Intervention
- Risperidone
- Conditions
- Schizophrenia Spectrum and Other Psychotic Disorders
- Sponsor
- Weill Medical College of Cornell University
- Enrollment
- 26
- Locations
- 1
- Primary Endpoint
- Change in Biomarkers Reflecting Treatment Response: Medial Prefrontal Cortex (MPFC) Gamma Amino Butyric Acid (GABA)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
Schizophrenia (SZ) is a highly debilitating neuropsychiatric disorder of young adulthood onset and a leading cause of disability worldwide. While treatments delivered at early stages of the disorder may be effective at reducing psychosis or altering the course of the disease, there are currently no biomarkers capable of identifying subjects in early stages of SZ who are likely to respond to treatment and would be good candidates for available proactive, symptomatic or future disease-modifying treatments; or those who would not respond and can be spared unnecessary medication exposure. The lack of these vitally important biomarkers provides a compelling rationale for the present multidisciplinary research project, which aims to develop and validate highly promising noninvasive and objective proton magnetic resonance spectroscopy (1H MRS)-based biomarkers for monitoring treatment response in early stages of SZ. In support of the viability of this overall objective is a large body of data, reported by the applicants and others, that show (a) that levels of glutamate (Glu) and - aminobutyric acid (GABA) - respectively, the major excitatory and inhibitory amino acid neurotransmitter systems - are abnormally elevated in medication-naïve and unmedicated first episode and chronic SZ patients; (b) that the effect of treatment with antipsychotic medications in these populations may be to lower or normalize brain levels of both Glu and GABA. To investigate the potential of these in vivo brain Glu and GABA abnormalities to serve as biomarkers of treatment response in early-stage SZ, the applicants propose to use 1H MRS to measure Glu and GABA levels in the largest cohort of medication-free SZ subjects to date, at baseline and following 4 weeks of antipsychotic treatment.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Patient
Medication-free individuals during first-episode of psychosis who will receive 4 weeks of treatment with risperidone
Intervention: Risperidone
Outcomes
Primary Outcomes
Change in Biomarkers Reflecting Treatment Response: Medial Prefrontal Cortex (MPFC) Gamma Amino Butyric Acid (GABA)
Time Frame: Baseline and 4th week of treatment for patients, baseline only for controls
Medial Prefrontal Cortex (MPFC) GABA levels will be ascertained at baseline and after 4 weeks of treatment using MRI scan with 1H MRS to assess treatment response. This is a measure of GABA levels, over water, in the mPFC. For patients this is a change measure. For control subjects, this is a one time measure. The values can range from 0 to infinity for controls and -infinity to infinity for patients.
Change in Biomarkers of Treatment Response: Dorsal Caudate (DCA) Gamma Amino Butyric Acid (GABA) Levels
Time Frame: Baseline and 4 weeks of treatment for patients, baseline for controls
Dorsal Caudate (DCA) GABA levels will be ascertained at baseline and after 4 weeks of treatment using MRI scan with 1H MRS to assess treatment response. This is a measure of GABA levels, over water, in the dorsal caudate. For patients this is a change measure. For control subjects, this is a one time measure. The values can range from 0 to infinity for controls and -infinity to infinity for patients.
Change in Biomarkers of Treatment Response: Dorsal Caudate (DCA) Glx (Glutamate+Glutamine)
Time Frame: Baseline and 4th week of treatment for patients, baseline only for controls
Dorsal Caudate (DCA) Glx levels will be ascertained at baseline and after 4 weeks of treatment using MRI scan with 1H MRS to assess treatment response. This is a measure of the levels of Glx over water in the dorsal caudate. For patients this is a change measure. For control subjects, this is a one time measure. The values can range from 0 to infinity for controls and -infinity to infinity for patients.
Change in Biomarkers Reflecting Treatment Response: Medial Prefrontal Cortex (MPFC) Glx (Glutamate+Glutamine)
Time Frame: Baseline and 4th week of treatment for patients, baseline for controls
Medial Prefrontal Cortex (MPFC) Glx levels will be ascertained at baseline and after 4 weeks of treatment using MRI scan with 1H MRS to assess treatment response. This is a measure of glx levels, over water, in the mPFC. For patients this is a change measure. For control subjects, this is a one time measure. The values can range from 0 to infinity for controls and -infinity to infinity for patients.
Secondary Outcomes
- Changes in Neurocognitive Performance: MATRICS Consensus Cognitive Battery (MCCB)(Baseline and 4th week of of treatment for patients, baseline only for controls)
- WAMI (Wealth Asset and Income)(Baseline)
- Changes in Clinical Severity: Clinical Global Impression Scale(Baseline and week 4 for patients; for controls this is a baseline measure only)
- Recreational Substances Used by Patients as Recorded by the Substance Use Questionnaire(This measure is administered on Day 1 of the study.)
- Changes in Clinical Symptomatology: Positive and Negative Syndrome Scale (PANSS)(Baseline and week 4 for patients; for controls only baseline)
- Changes in Motor Symptomatology: Abnormal Involuntary Movement Scale (AIMS)(Baseline and week 4)
- Participants' Verbal I.Q (Intelligence Quotient) as Assessed by the WTAR (Wechsler Test of Adult Reading) to Determine Clinical Eligibility(This measure is completed on Day 1 of the study.)
- Participants' Self-Reported Handedness as Recorded by the Edinburgh Handedness Scale (Predominantly Right)(This measure is completed on Day 1 of the study.)
- Changes in Global Functioning: Global Assessment of Functioning (GAF)(Baseline and week 4 for patients; for controls only baseline)