Heterogeneity of Outcomes and Network Connectivity in Early-Stage Psychosis: A Longitudinal Study

Abstract

Imaging studies in psychotic disorders typically examine cross-sectional relationships between magnetic resonance imaging (MRI) signals and diagnosis or symptoms. We sought to examine changes in network connectivity identified using resting-state functional MRI (fMRI) corresponding to divergent functional recovery trajectories and relapse in early-stage psychosis (ESP). Prior studies have linked schizophrenia to hyperconnectivity in the default mode network (DMN). Given the correlations between the DMN and behavioral impairments in psychosis, we hypothesized that dynamic changes in DMN connectivity reflect the heterogeneity of outcomes in ESP. Longitudinal data were collected from 66 ESP patients and 20 healthy controls. Longitudinal cluster analysis identified subgroups of patients with similar trajectories in terms of symptom severity and functional outcomes. DMN connectivity was measured in a subset of patients (n = 36) longitudinally over 2 scans separated by a mean of 12 months. We then compared connectivity between patients and controls, and among the different outcome trajectory subgroups. Among ESP participants, 4 subgroups were empirically identified corresponding to: “Poor,” “Middle,” “Catch-up,” and “Good” trajectory outcomes in the complete dataset (n = 36), and an independent replication (n = 30). DMN connectivity changes differed significantly between functional subgroups (F3,32 = 6.06, P-FDR corrected = .01); DMN connectivity increased over time in the “Poor” outcome cluster (β = +0.145) but decreased over time in the “Catch-up” cluster (β = −0.212). DMN connectivity is dynamic and correlates with a change in functional status over time in ESP. This approach identifies a brain-based marker that reflects important neurobiological processes required to sustain functional recovery.

Frontal lobe fALFF measured from resting-state fMRI at baseline predicts acute treatment response in first episode psychosis

“…Additionally, we observed increased fALFF in the precuneus/posterior cingulate over the course of treatment in responders; this change was not observed in non-responders. This finding complements two recent studies reporting that increased connectivity of the posterior cingulate was associated with clinical response to antipsychotic treatment in the first episode of illness 53,54 . This brain region is considered the hub of the default mode network, and is critical to the ability to shift between self-oriented processing and (external) task-oriented function mediated by dorsal prefrontal cortex 73,74 .…”

Subfield‐specific longitudinal changes of hippocampal volumes in patients with early‐stage bipolar disorder

“…Previous longitudinal studies on FEP patients have demonstrated a link between good functional recovery and higher IQ, higher socioeconomic status, and lower severity of psychotic symptoms. 49 In addition, different outcome trajectories were linked to dynamic changes in brain functional connectivity in the default mode network, 35 (iii) follow-up patient cohorts had reduced symptomatology in PANSS and YMRS, and less medication usage compared to baseline-only patients, suggestive of higher functioning patients.…”

“…Medication information, including antipsychotics and lithium dosage, was collected at each assessment timepoint. Antipsychotics (96% second‐generation) were converted into chlorpromazine equivalents (CPZE) based on the recommendations of Gardner et al 33 We used a modified Multnomah Community Ability Scale (MCAS) to assess community functioning 34,35 …”

Impact of Substance Use Disorder on Between-Network Brain Connectivity in Early Psychosis

“…Two runs of resting state fMRI sensitive to blood oxygenation level-dependent (BOLD) contrast were collected: 6.2 min (124 time-points), TE/TR/Θ = 30 ms/3000 ms/85°, 3 mm isotropic voxels. A T1-weighted image (1.2 mm iso) was also collected for co-registration 4 …”