Hippocampal Memory Circuits in Delusions

NCT ID: NCT03822910

Last Updated: 2024-04-30

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 212 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-07-13
• Study Completion Date: 2023-08-12

Brief Summary

This study will investigate dentate gyrus (DG) and hippocampal CA3 sub field function, using the pattern separation paradigm, as reflected by the difference in brain activation in response to same-as-previously- seen (OLD) vs. similar-to-previously-seen (SIM) objects in first episode psychosis (FEP) subjects before and after anti psychotic treatment and in matched healthy controls (HC). The current study uses three novel high-resolution task-based and post-encoding resting fMRI measures to probe hippocampal circuitry in delusions. It will also study CA1 function, using a sequential associative mismatch paradigm, as reflected by activation of CA1 in response to mismatching information compared to memory of that stimulus in FEP subjects before and after antipsychotic treatment and in matched HC. Finally, this study will evaluate plasticity of hippocampal intrinsic functional connectivity (IFC) in response to memory consolidation, using an encoding-plasticity paradigm, in FEP subjects before and after anti psychotic treatment and in matched HC. For each of the three imaging projects, a total of 50 FEP subjects and 50 matched healthy controls (HC) will be studied; hence, 300 subjects will be studied over 5 years. Within each paradigm, medication-naive FEP subjects will be studied at baseline and 8 weeks after starting anti psychotic medication. HC participants will be studied at baseline and 8 weeks later but will not receive any treatment.

Conditions

Psychosis

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Healthy Controls

Matched Healthy Controls

Pattern Separation Paradigm

Intervention Type: DIAGNOSTIC_TEST

Will be used to investigate dentate gyrus (DG) and hippocampal CA3 subfield as reflected by the difference in brain activation in response to same as previously seen (OLD) vs similar to previously seen (SIM) objects in first episode (FEP) subjects before and after treatment.

Sequential Associative Mismatch Paradigm

Intervention Type: DIAGNOSTIC_TEST

used to reflect activation of CA1 in response to mismatching information compared to memory of the stimulus in FEP subjects before and after antipsychotic treatment and in matched Healthy Control (HC).

Encoding Plasticity Paradigm

Intervention Type: DIAGNOSTIC_TEST

Used to evaluate plasticity of hippocampal Intrinsic Functional Connectivity (IFC) in response to memory consolidation in FEP subjects before and after antipsychotic treatment and in matched HC.

Firt Episode Psychosis (FEP)

subjects before and after antipsychotic treatment

Pattern Separation Paradigm

Intervention Type: DIAGNOSTIC_TEST

Will be used to investigate dentate gyrus (DG) and hippocampal CA3 subfield as reflected by the difference in brain activation in response to same as previously seen (OLD) vs similar to previously seen (SIM) objects in first episode (FEP) subjects before and after treatment.

Sequential Associative Mismatch Paradigm

Intervention Type: DIAGNOSTIC_TEST

used to reflect activation of CA1 in response to mismatching information compared to memory of the stimulus in FEP subjects before and after antipsychotic treatment and in matched Healthy Control (HC).

Encoding Plasticity Paradigm

Intervention Type: DIAGNOSTIC_TEST

Used to evaluate plasticity of hippocampal Intrinsic Functional Connectivity (IFC) in response to memory consolidation in FEP subjects before and after antipsychotic treatment and in matched HC.

Interventions

Pattern Separation Paradigm

Will be used to investigate dentate gyrus (DG) and hippocampal CA3 subfield as reflected by the difference in brain activation in response to same as previously seen (OLD) vs similar to previously seen (SIM) objects in first episode (FEP) subjects before and after treatment.

Intervention Type: DIAGNOSTIC_TEST

Sequential Associative Mismatch Paradigm

used to reflect activation of CA1 in response to mismatching information compared to memory of the stimulus in FEP subjects before and after antipsychotic treatment and in matched Healthy Control (HC).

Intervention Type: DIAGNOSTIC_TEST

Encoding Plasticity Paradigm

Used to evaluate plasticity of hippocampal Intrinsic Functional Connectivity (IFC) in response to memory consolidation in FEP subjects before and after antipsychotic treatment and in matched HC.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• Males and females 16 to 35 years of age, inclusive, at the time of informed consent
• Right-handed
• Must have experienced a first episode of non-affective psychosis over the past five years
• Must exhibit a persistence of delusions for at least 4 days per week for at least 4 weeks in the absence of psychotomimetic substance use or other potential organic etiologies, including epilepsy or significant head trauma.
• Must score at least a 2 (mild to moderate) on the "Amount of preoccupation with delusions" and "Conviction" items on the Psychotic Symptom Rating Scale (PSYRATS).

Exclusion Criteria

• Diagnosis of major mood disorder or other Axis I disorder other than Schizophrenia, Schizoaffective Disorder or Schizophreniform Disorder.
• Significant medical or neurological illness by history or physical exam including seizure disorder, history of loss of consciousness related to head trauma or developmental disorder including mental retardation.
• Metal implants, pacemaker, or other metal in the body or medicinal patch.
• History of claustrophobia.
• Currently taking any anti psychotic medication (within 4 weeks).

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

NYU Langone Health

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Donald Goff, MD

Role: PRINCIPAL_INVESTIGATOR

NYU Langone Health

Locations

New York Langone Health

New York, New York, United States

Shanghai Mental Health Center

Shanghai, , China

Suzhou Guangji Hospital

Suzhou, , China

Countries

United States; China

Other Identifiers

18-00656

Identifier Type: -

Identifier Source: org_study_id