Schizoaffective Disorder, Depressed Type, Schizophrenia, Schizophreniform Disorder
Conditions
Brief summary
This study will identify and evaluate relevant biomarkers and structural brain imaging for understanding potential biological illness related mechanisms in medication-naïve subjects with early psychosis before and after initiation of antipsychotic medication
Detailed description
It is currently unknown whether deterioration early in the course of psychotic illness represents medication toxicity or the natural course of the illness. The study will help clarify this issue in observing 70 schizophrenic patients before and after they are prescribed an antipsychotic via standard of care. In addition, schizophrenia is a heterogeneous disorder and a putative brain-derived neurotrophic factor (BDNF) deficit, while possibly a common pathway, may not fully capture the biological diversity-the supplemental biomarkers will allow us to perform a more comprehensive assessment of factors contributing to clinical course. Taken together analysis of these biomarkers in relation to clinical course and in relation to healthy subjects will inform us about biological mechanisms contributing to illness onset, effects of antipsychotic medication on these mechanisms, and the predictive value of the biomarkers for clinical course. This information will provide the foundation for future early intervention trials targeting biological mechanisms utilizing a personalized medicine approach. The baseline visit for 70 schizophrenic patients and 70 healthy age and gender matched controls consists of structural and functional MRI in addition to a blood draw for biomarkers including BDNF, inflammation markers, DNA, oxidative stress, and folate status and additionally a salivary cortisol sample collection. Biomarkers and imaging will be repeated after 8 weeks of antipsychotic treatment in patients.
Interventions
None listed
Sponsors
NYU Langone Health
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
16 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
1. Male or female 2. Ages 15-40 years 3. Schizophrenia, any subtype or Schizophreniform disorder 4. Sufficient proficiency in English or Spanish to complete assessments (US)
Exclusion criteria
1. Major depression by the Diagnostic and Statistical Manual of Mental Disorders IV criteria 2. Calgary Depression Scale for Schizophrenia (CDSS) score of 7 or greater. 3. Clinical Global Assessment of Severity of Suicidality of 3 (moderate) or greater. 4. Serious suicide attempt within three years 5. Treatment with an antipsychotic or antidepressant within the last six months 6. Active alcohol or other substance abuse or dependence within one month 7. Unstable medical illness
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Biomarkers | Baseline | Compare biomarkers for inflammation, BDNF, oxidative stress, glucocorticoids and folate/methylation status in medication-naïve schizophrenia/schizophreniform subjects and matched healthy controls to identify illness-related factors. |
| Salivary Cortisol Levels | Baseline and week 8 | Compare biomarkers at baseline and after 8 weeks of risperidone treatment in medication-naïve schizophrenia/schizophreniform subjects to identify treatment-related factors. Since Blood and Saliva was only collected from First Episode participants (FEP) at week 8 (not from healthy controls) these results only report the baseline and week 8 biomarker levels for FEP participants who completed week 8. |
| Change in Salivary Cortisol Levels | Baseline and week 8 | Compare salivary cortisol at baseline and after 8 weeks of risperidone treatment in medication-naïve schizophrenia/schizophreniform subjects to identify treatment-related factors. Since Blood and Saliva was only collected from First Episode participants (FEP) at week 8 (not from healthy controls) these results only report the baseline and week 8 biomarker levels for FEP participants who completed week 8. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Left Hippocampal Volumetric Integrity (HVI) | Baseline | Compare hippocampal volume in medication-naïve schizophrenia/schizophreniform subjects and healthy controls and examine whether biomarkers predict differences between groups in baseline hippocampal volume. |
| Cognitive Performance | Baseline, week 8 | Compare cognitive performance on the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) in medication- naïve schizophrenia/schizophreniform subjects and healthy controls and examine whether biomarkers predict differences between groups in baseline cognitive performance. The composite score on the MCCB is calculated by the software using all tests administered. The composite score is a t-score assuming the mean score (50%) is the normative performance of the general population. The composite score ranges from 0-100 with a standard deviation of 10. A score greater than 50 implies a score better than the average population norm and a score less than 50 indicates performance worse than the general population norm. For schizophrenia subjects who complete 8 weeks of antipsychotic treatment, week 8 MATRICS testing results will be used to minimize the effect of psychosis on cognitive performance. |
| Annualized Change in Left Hippocampal Volume Integrity | Baseline, week 8 | Compare hippocampal volume in medication-naïve schizophrenia/schizophreniform subjects before and after 8 weeks treatment with antipsychotic to assess evidence for early neurotoxicity. This outcome measure reports annualized rate of change in Left Hippocampal Volume Integrity (LHVI) because a few participants had a delay in their week 8 visit. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Healthy Controls Age and gender matched healthy controls | 73 |
| Patients Participants diagnosed with Schizophrenia, schizophreniform disorder, or schizoaffective disorder, depressed type that are naive to anti-psychotic treatment. | 79 |
| Total | 152 |
Baseline characteristics
| Characteristic | Healthy Controls | Total | Patients |
|---|---|---|---|
| Age, Continuous | 23.86 years STANDARD_DEVIATION 6.4 | 24.56 years STANDARD_DEVIATION 6.95 | 25.19 years STANDARD_DEVIATION 7.39 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 73 Participants | 147 Participants | 74 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 2 Participants | 2 Participants |
| Region of Enrollment China | 73 participants | 152 participants | 79 participants |
| Sex: Female, Male Female | 40 Participants | 80 Participants | 40 Participants |
| Sex: Female, Male Male | 33 Participants | 72 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 73 | 1 / 79 |
| serious Total, serious adverse events | 0 / 73 | 0 / 79 |
Outcome results
Primary
Biomarkers
Compare biomarkers for inflammation, BDNF, oxidative stress, glucocorticoids and folate/methylation status in medication-naïve schizophrenia/schizophreniform subjects and matched healthy controls to identify illness-related factors.
Time frame: Baseline
Population: Not all biomarkers were available for analysis for all subjects.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Healthy Controls | Biomarkers | BDNF | 287.37 pg/mL |
| Healthy Controls | Biomarkers | Thioredoxin | 492.33 pg/mL |
| Healthy Controls | Biomarkers | S100B | 130.44 pg/mL |
| Healthy Controls | Biomarkers | C-Reactive Protein | 7610.07 pg/mL |
| Healthy Controls | Biomarkers | Interleukin 1B | 76.77 pg/mL |
| Healthy Controls | Biomarkers | Interleukin 8 | 63.41 pg/mL |
| Healthy Controls | Biomarkers | Tumor Necrosis Factor | 92.03 pg/mL |
| Healthy Controls | Biomarkers | Interferon gamma | 88.96 pg/mL |
| Healthy Controls | Biomarkers | Glutamate | 105.00 pg/mL |
| Healthy Controls | Biomarkers | Aspartate | 102.32 pg/mL |
| Healthy Controls | Biomarkers | Homocysteine | 4.79 pg/mL |
| Healthy Controls | Biomarkers | Lactate | 13.28 pg/mL |
| Patients | Biomarkers | Homocysteine | 4.83 pg/mL |
| Patients | Biomarkers | BDNF | 340.83 pg/mL |
| Patients | Biomarkers | Tumor Necrosis Factor | 93.60 pg/mL |
| Patients | Biomarkers | Thioredoxin | 420.17 pg/mL |
| Patients | Biomarkers | Aspartate | 134.32 pg/mL |
| Patients | Biomarkers | S100B | 125.13 pg/mL |
| Patients | Biomarkers | Interferon gamma | 89.42 pg/mL |
| Patients | Biomarkers | C-Reactive Protein | 7631.41 pg/mL |
| Patients | Biomarkers | Lactate | 15.08 pg/mL |
| Patients | Biomarkers | Interleukin 1B | 68.82 pg/mL |
| Patients | Biomarkers | Glutamate | 111.00 pg/mL |
| Patients | Biomarkers | Interleukin 8 | 71.30 pg/mL |
Primary
Change in Salivary Cortisol Levels
Compare salivary cortisol at baseline and after 8 weeks of risperidone treatment in medication-naïve schizophrenia/schizophreniform subjects to identify treatment-related factors. Since Blood and Saliva was only collected from First Episode participants (FEP) at week 8 (not from healthy controls) these results only report the baseline and week 8 biomarker levels for FEP participants who completed week 8.
Time frame: Baseline and week 8
Population: Analysis was done for first episode subjects who completed both Baseline and Week 8 only.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Healthy Controls | Change in Salivary Cortisol Levels | 7.41 µg/dL |
| Patients | Change in Salivary Cortisol Levels | 4.36 µg/dL |
Primary
Salivary Cortisol Levels
Compare biomarkers for stress (salivary cortisol) in medication-naïve schizophrenia/schizophreniform subjects and matched healthy controls to identify illness-related factors.
Time frame: Baseline
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Healthy Controls | Salivary Cortisol Levels | 4.88 µg/dL |
| Patients | Salivary Cortisol Levels | 6.56 µg/dL |
Primary
Salivary Cortisol Levels
Compare biomarkers at baseline and after 8 weeks of risperidone treatment in medication-naïve schizophrenia/schizophreniform subjects to identify treatment-related factors. Since Blood and Saliva was only collected from First Episode participants (FEP) at week 8 (not from healthy controls) these results only report the baseline and week 8 biomarker levels for FEP participants who completed week 8.
Time frame: Baseline and week 8
Population: Analysis was done for first episode participants who completed both Baseline and Week 8 only.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Healthy Controls | Salivary Cortisol Levels | Tumor necrosis factor | 93.60 pg/mL |
| Healthy Controls | Salivary Cortisol Levels | Interleukin 1B | 68.81 pg/mL |
| Healthy Controls | Salivary Cortisol Levels | Aspartate | 3.71 pg/mL |
| Healthy Controls | Salivary Cortisol Levels | Lactate | 4.49 pg/mL |
| Healthy Controls | Salivary Cortisol Levels | Homocysteine | 4.78 pg/mL |
| Healthy Controls | Salivary Cortisol Levels | Interleukin 8 | 74.34 pg/mL |
| Healthy Controls | Salivary Cortisol Levels | BDNF | 465.98 pg/mL |
| Healthy Controls | Salivary Cortisol Levels | C-reactive protein | 7541.41 pg/mL |
| Healthy Controls | Salivary Cortisol Levels | Thioredoxin | 417.50 pg/mL |
| Healthy Controls | Salivary Cortisol Levels | Interferon gamma | 95.26 pg/mL |
| Healthy Controls | Salivary Cortisol Levels | S100B | 154.63 pg/mL |
| Healthy Controls | Salivary Cortisol Levels | Glutamate | 5.21 pg/mL |
| Patients | Salivary Cortisol Levels | S100B | 111.39 pg/mL |
| Patients | Salivary Cortisol Levels | Glutamate | 5.29 pg/mL |
| Patients | Salivary Cortisol Levels | C-reactive protein | 7627.60 pg/mL |
| Patients | Salivary Cortisol Levels | Interleukin 1B | 57.01 pg/mL |
| Patients | Salivary Cortisol Levels | Interleukin 8 | 65.79 pg/mL |
| Patients | Salivary Cortisol Levels | Interferon gamma | 98.14 pg/mL |
| Patients | Salivary Cortisol Levels | Tumor necrosis factor | 89.45 pg/mL |
| Patients | Salivary Cortisol Levels | Lactate | 3.95 pg/mL |
| Patients | Salivary Cortisol Levels | Homocysteine | 5.02 pg/mL |
| Patients | Salivary Cortisol Levels | BDNF | 356.20 pg/mL |
| Patients | Salivary Cortisol Levels | Thioredoxin | 405.33 pg/mL |
| Patients | Salivary Cortisol Levels | Aspartate | 4.75 pg/mL |
Secondary
Annualized Change in Left Hippocampal Volume Integrity
Compare hippocampal volume in medication-naïve schizophrenia/schizophreniform subjects before and after 8 weeks treatment with antipsychotic to assess evidence for early neurotoxicity. This outcome measure reports annualized rate of change in Left Hippocampal Volume Integrity (LHVI) because a few participants had a delay in their week 8 visit.
Time frame: Baseline, week 8
Population: This analysis includes participants that completed both baseline and week 8 visits.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Healthy Controls | Annualized Change in Left Hippocampal Volume Integrity | 0.004535 Percentage of standard hippocampal vol. |
| Patients | Annualized Change in Left Hippocampal Volume Integrity | -0.03027 Percentage of standard hippocampal vol. |
Secondary
Cognitive Performance
Compare cognitive performance on the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) in medication- naïve schizophrenia/schizophreniform subjects and healthy controls and examine whether biomarkers predict differences between groups in baseline cognitive performance. The composite score on the MCCB is calculated by the software using all tests administered. The composite score is a t-score assuming the mean score (50%) is the normative performance of the general population. The composite score ranges from 0-100 with a standard deviation of 10. A score greater than 50 implies a score better than the average population norm and a score less than 50 indicates performance worse than the general population norm. For schizophrenia subjects who complete 8 weeks of antipsychotic treatment, week 8 MATRICS testing results will be used to minimize the effect of psychosis on cognitive performance.
Time frame: Baseline, week 8
Population: Data provided only for subjects who completed assessments at both time points.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Healthy Controls | Cognitive Performance | Baseline MCCB Composite Score | 47.50 units on a scale |
| Healthy Controls | Cognitive Performance | Week 8 MCCB Composite Score | 49.50 units on a scale |
| Patients | Cognitive Performance | Baseline MCCB Composite Score | 34 units on a scale |
| Patients | Cognitive Performance | Week 8 MCCB Composite Score | 42.50 units on a scale |
Secondary
Left Hippocampal Volumetric Integrity (HVI)
Compare hippocampal volume in medication-naïve schizophrenia/schizophreniform subjects and healthy controls and examine whether biomarkers predict differences between groups in baseline hippocampal volume.
Time frame: Baseline
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Healthy Controls | Left Hippocampal Volumetric Integrity (HVI) | .9512 % of hippocampal volumetric integrity |
| Patients | Left Hippocampal Volumetric Integrity (HVI) | .9275 % of hippocampal volumetric integrity |