Trajectories of Treatment Response as Window Into the Heterogeneity of Psychosis: a Longitudinal Multimodal Imaging Study
| Status: | Recruiting |
|---|---|
| Conditions: | Psychiatric, Psychiatric |
| Therapuetic Areas: | Psychiatry / Psychology |
| Healthy: | No |
| Age Range: | 17 - 35 |
| Updated: | 4/21/2018 |
| Start Date: | April 1, 2018 |
| End Date: | March 31, 2023 |
| Contact: | Kristen Edwards |
| Email: | Ksenetto@uabmc.edu |
| Phone: | 205 996 7171 |
Trajectories of Treatment Response as Window Into the Heterogeneity of Psychosis: a Longitudinal Multimodal Imaging Study in Medication-naïve First Episode Psychosis Patients
Psychosis is a heterogeneous disorder and present treatment only works for a limited number
of patients. In order to identify new therapeutic targets, this study will longitudinally
characterize the underlying pathologies in those with poor treatment response using
complimentary brain imaging modalities.
of patients. In order to identify new therapeutic targets, this study will longitudinally
characterize the underlying pathologies in those with poor treatment response using
complimentary brain imaging modalities.
Schizophrenia is a heterogeneous disorder that likely involves multiple underlying
pathological mechanisms, which has plagued attempts to identify rational therapeutic targets.
All available antipsychotic drugs (APD) are dopamine receptor antagonists, but clinical
response is variable, with a third of patients being partial responders, and a third
non-responders. Arguably, those who respond well to APD have primarily dopaminergic
abnormalities but it is imperative to also characterize the specific underlying pathologies
in those with poor response in order to unravel the heterogeneity of psychosis and
effectively develop new treatments. The investigators propose to longitudinally follow
treatment response to APD for eight months in medication-naïve first episode psychosis (FEP)
subjects using complementary brain imaging techniques.
The investigators have already identified provisional markers for several different
pathophysiological mechanisms underlying psychosis, including abnormalities in glutamate,
brain connectivity, and neurodevelopment that they can track with brain imaging. In addition,
the investigators propose to study the changes that occur in the brain in early compared to
delayed treatment responders and changes that occur over time in response to treatment. By
characterizing treatment trajectories and their relationship to baseline pathophysiologic
alterations, the investigators will further complement their mechanistic understanding of the
heterogeneity of psychosis.
The investigators propose to study 117 well-characterized FEP subjects who are medication
naïve and treat them with the most frequently used APD for 32 weeks. The investigators will
follow a rigorous longitudinal design to capture treatment response whereby those without an
adequate response after 16 weeks of treatment will be switched to another APD for 16 weeks.
All patients will be scanned four times: at baseline and after 6, 16, and 32 weeks of
treatment. The investigators will use (1) proton MR Spectroscopy (MRS), (2) task and resting
state functional MRI and (3) MRI and diffusion weighted imaging (DWI) to measure brain
biochemistry, function and structure. Using several imaging modalities has the potential to
interrogate different neurobiological aspects of treatment response and will offer greater
opportunities for clustering the patterns and combinations of the underlying pathologies in
those with poor response.
Deconstructing the heterogeneity of psychosis has broad implications for the identification
of specific targets for drug development, and to lay the groundwork needed to conduct
therapeutic trials on patients characterized by their specific underlying psychopathology.
pathological mechanisms, which has plagued attempts to identify rational therapeutic targets.
All available antipsychotic drugs (APD) are dopamine receptor antagonists, but clinical
response is variable, with a third of patients being partial responders, and a third
non-responders. Arguably, those who respond well to APD have primarily dopaminergic
abnormalities but it is imperative to also characterize the specific underlying pathologies
in those with poor response in order to unravel the heterogeneity of psychosis and
effectively develop new treatments. The investigators propose to longitudinally follow
treatment response to APD for eight months in medication-naïve first episode psychosis (FEP)
subjects using complementary brain imaging techniques.
The investigators have already identified provisional markers for several different
pathophysiological mechanisms underlying psychosis, including abnormalities in glutamate,
brain connectivity, and neurodevelopment that they can track with brain imaging. In addition,
the investigators propose to study the changes that occur in the brain in early compared to
delayed treatment responders and changes that occur over time in response to treatment. By
characterizing treatment trajectories and their relationship to baseline pathophysiologic
alterations, the investigators will further complement their mechanistic understanding of the
heterogeneity of psychosis.
The investigators propose to study 117 well-characterized FEP subjects who are medication
naïve and treat them with the most frequently used APD for 32 weeks. The investigators will
follow a rigorous longitudinal design to capture treatment response whereby those without an
adequate response after 16 weeks of treatment will be switched to another APD for 16 weeks.
All patients will be scanned four times: at baseline and after 6, 16, and 32 weeks of
treatment. The investigators will use (1) proton MR Spectroscopy (MRS), (2) task and resting
state functional MRI and (3) MRI and diffusion weighted imaging (DWI) to measure brain
biochemistry, function and structure. Using several imaging modalities has the potential to
interrogate different neurobiological aspects of treatment response and will offer greater
opportunities for clustering the patterns and combinations of the underlying pathologies in
those with poor response.
Deconstructing the heterogeneity of psychosis has broad implications for the identification
of specific targets for drug development, and to lay the groundwork needed to conduct
therapeutic trials on patients characterized by their specific underlying psychopathology.
Inclusion Criteria:
- A diagnosis of first episode psychosis
- Never been treated with an antipsychotic medication
- Between the age of 17 and 35
Exclusion Criteria:
- Inability to sign informed consent assessed by the Evaluation to sign - - Consent form
- Poorly controlled acute or chronic medical and neurological conditions
- History of head trauma with loss of consciousness for >2 minutes
- Clinically significant depression, hypomania, or mania
- Active substance abuse or dependence (except for nicotine)
- Suspected substance-induced psychosis
- Treatment with drugs known to affect brain glutamate levels
- Pregnant females
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