Donald Goff

Pattern separation and pattern completion are opposing yet complementary components of mnemonic processing that heavily rely on the hippocampus. It has been shown that processing within the dentate gyrus (DG) subfield promotes pattern separation while operations within the CA3 subfield are important for pattern completion. Schizophrenia has been associated with anatomical and functional hippocampal abnormalities, including within the DG and CA3. We hypothesized that an impairment in hippocampal circuitry in individuals with first-episode schizophrenia leads to deficits in pattern separation (mnemonic discrimination) and pattern completion (recognition memory), that these deficits contribute to delusions, and that antipsychotic treatment improves circuit functioning. We measured behavioral and neural responses during the identification of new, repeated, and similar stimuli using high-resolution fMRI in 45 medication-free or minimally-treated patients with first-episode schizophrenia and 49 matched controls. We found recognition memory and pattern separation deficits in patients and a negative association between memory performance and the severity of delusions. Neural analyses revealed deficits in both univariate BOLD responses and multivariate patterns in the hippocampus during mnemonic discrimination in patients compared to controls. Importantly, by investigating the association between trial-level neural activity and behavior before and after treatment, we found that antipsychotics normalized DG activity during pattern separation and CA3 activity during pattern completion. Lastly, trial-level cortical responses during …

IntroductionThe clinical course of schizophrenia is often characterized by recurrent relapses. Blood inflammatory markers are altered in acute psychosis, and may be state markers for illness relapse in schizophrenia. Few studies have investigated longitudinal, intra-individual changes in inflammatory markers as a predictor of relapse. In the present study, we explored this association in a relapse prevention trial in patients with schizophrenia.MethodsWe analyzed blood inflammatory markers in 200 subjects, with a mean 11 samples per subject, during the 30 month Preventing Relapse in schizophrenia: Oral Antipsychotics Compared to Injectable: eValuating Efficacy (PROACTIVE) trial. Associations between longitudinal changes in inflammatory markers and relapse were analyzed using a within-subjects design.Results70 (35 %) of subjects relapsed during the study period. There were no significant differences in …

In this issue of the Journal, Cao and colleagues (1) present results of a new method for using functional connectivity to predict antipsychotic medication response. This method combines connectivity measures collected under multiple brain states (resting state and task based) and examines the entire brain connectome. The authors propose that by potentially improving predictive power, their work represents an important step toward precision psychiatry. Many other approaches have been used previously to predict response to antipsychotic medication, including genetics, epigenetics, metabolomics, magnetic resonance spectroscopy measurement of glutamate and other markers, and brain morphometric analysis (2–5). All of these approaches have produced statistically significant findings but have fallen short of ushering in personalized medicine, for several reasons. First, it is not enough to find a statistically …

Objectives Disengagement from treatment is common in first episode schizophrenia (FES) and is associated with poor outcomes. Our aim was to determine whether hippocampal subfield volumes predict disengagement during maintenance treatment of FES. Methods FES patients were recruited from sites in Boston, New York, Shanghai, and Changsha. After stabilization on antipsychotic medication, participants were randomized to add-on citalopram or placebo and followed for 12 months. Demographic, clinical and cognitive factors at baseline were compared between completers and disengagers in addition to volumes of hippocampal subfields. Results Baseline data were available for 95 randomized participants. Disengagers (n = 38, 40%) differed from completers (n = 57, 60%) by race (more likely Black; less likely Asian) and in more alcohol use …

Chronic neck pain (CNP), a global health problem, involves a large amount of psychological and socioeconomic burdens. Not only physical causes but also behavioral disorders such as a fear-avoidance belief (FAB) can associate with the chronicity of neck pain. However, functional brain mechanisms underlying CNP and its related behavioral disorders remain unknown. The aim of the current resting-state functional magnetic resonance imaging (fMRI) study was to explore how the functional brain networks differed between CNP patients and age- and sex-matched healthy, pain-free controls (HCs). We also investigated whether these possible brain network changes in CNP patients were associated with fear avoidance belief (FAB) and the intensity of pain. We analyzed the resting-state fMRI data of 20 CNP patients and 20 HCs. FAB and the intensity of pain were assessed by Tampa Scale for Kinesiophobia (TSK) and Visual Analog Scale (VAS) of pain. The whole brain analysis showed that CNP patients had significant different functional connectivity (FC) compared with HCs, and the right dorsolateral prefrontal cortex (DLPFC) was a core hub of these altered functional networks. Furthermore, general linear model analyses showed that, in CNP patients, the increased FC between the right DLPFC and the right anterior insular cortex (aIC) significantly associated with increased TSK (p = 0.01, statistical significance after Bonferroni correction: p<0.025), and the FC between the right DLPFC and dorsal posterior cingulate cortex had a trend of inverse association with VAS (p = 0.04). Our findings suggest that aberrant FCs between the right DLPFC and …

Background and Hypothesis Microvascular and inflammatory mechanisms have been hypothesized to be involved in the pathophysiology of psychotic spectrum disorders (PSDs). However, data evaluating these hypotheses remain limited. Study Design We applied a three-compartment intravoxel incoherent motion free water imaging (IVIM-FWI) technique that estimates the perfusion fraction (PF), free water fraction (FW), and anisotropic diffusion of tissue (FAt) to examine microvascular and microstructural changes in gray and white matter in 55 young adults with a PSD compared to 37 healthy controls (HCs). Study Results We found significantly increased PF, FW, and FAt in gray matter regions, and significantly increased PF, FW, and decreased FAt in white matter regions in the PSD group versus HC. Furthermore, in patients, but not in the HC group …

Levetiracetam effects on hippocampal blood flow and symptoms in medication-free individuals with nonaffective first episode psychosis (letter) Levetiracetam effects on hippocampal blood flow and symptoms in medication-free individuals with nonaffective first episode psychosis (letter) Schizophr Res. 2023 Aug 30;260:140-142. doi: 10.1016/j.schres.2023.08.018. Online ahead of print. Authors Donald C Goff 1 , Michele Santacatterina 2 , Gillian Capichioni 3 , Fumika Ando 3 , Kamber Hart 3 , Antonio Convit 4 , Henry Rusinek 5 Affiliations 1 Department of Psychiatry, NYU Grossman School of Medicine, New York, NY, United States of America; Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, United States of America. Electronic address: Donald.Goff@nyulangone.org. 2 Department of Population Health, NYU Grossman School of Medicine, New York, NY, United States of America. 3 Department of …

In the current issue of Biological Psychiatry, Sehatpour et al.(1) report the results of a placebo-controlled pilot trial that examined the dose response of D-serine administered with auditory training to assess effects on synaptic plasticity in individuals with schizophrenia. This study followed the National Institute of Mental Health Fast-Fail Trials approach that is intended to evaluate a candidate drug’s target engagement before proceeding to larger clinical trials; establishing target engagement ensures that the novel mechanistic hypothesis is tested. The first step in the Fast-Fail Trials funding mechanism, the R61 pilot trial, uses biomarkers to demonstrate engagement of the molecular target. These studies provide a go/nogo signal based on predefined criteria, but because of small sample sizes, statistical significance may not be achieved and hence reliability of results may not be high. Neuroplasticity, the subject of this …