Hippocampal Memory Circuits in Delusions

NYU Langone Health212 enrolled

Overview

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.

Study Type

OBSERVATIONAL

Enrollment

212

Conditions

Psychosis

Interventions

Eligibility

Sex: ALLMin age: 16 YearsMax age: 35 Years

Medical Language ↔ Plain English

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).

Locations (3)

New York Langone Health

New York, New York, United States

Shanghai Mental Health Center

Shanghai, China

Suzhou Guangji Hospital

Suzhou, China

Outcomes

Primary Outcomes

The difference in CA1 activation between a mismatch and an intact trial in FEP subjects after 8 weeks of antipsychotic treatment and the correlation of this change with change in delusions as measured by the Psyrats-D total score.

Time frame: 8 Weeks

Change in hippocampus-to-VTA (hip-VTA) IFC and hip-to-lateral occipital complex (hip-LO) IFC, from pre- to post- encoding during the encoding-plasticity paradigm, between FEP and HC.

Time frame: 8 Weeks

Change in (a) hip-VTA IFC and (b) hip-LO IFC, from pre- to post- encoding during the encoding-plasticity paradigm

Time frame: 8 Weeks

correlation of change (a) hip-VTA IFC and (b) hip-LO IFC with change in delusional severity measured by the Psyrats-D total score.

Time frame: 8 Weeks