ABSTRACT
To better characterize hippocampal pathophysiology in schizophrenia, we conducted a longitudinal study evaluating hippocampal functional connectivity during resting state, using seeds prescribed in its anterior and posterior regions. We enrolled 34 unmedicated patients with schizophrenia or schizoaffective disorder (SZ) and 34 matched healthy controls. SZ were scanned while off medication, then were treated with risperidone for 6 weeks and re-scanned (n = 22). Group differences in connectivity, as well as changes in connectivity over time, were assessed on the group's participant level functional connectivity maps. We found significant dysconnectivity with anterior and posterior hippocampal seeds in unmedicated SZ. Baseline connectivity between the hippocampus and anterior cingulate cortex, caudate nucleus, auditory cortex and calcarine sulcus in SZ predicted subsequent response to antipsychotic medications. These same regions demonstrated changes over the 6-week treatment trial that were correlated with symptomatic improvement. Our findings implicate several neural networks relevant to clinical improvement with antipsychotic medications.
Subject(s)
Antipsychotic Agents/pharmacology , Caudate Nucleus/physiopathology , Cerebral Cortex/physiopathology , Connectome/methods , Hippocampus/physiopathology , Nerve Net/physiopathology , Outcome Assessment, Health Care , Psychotic Disorders/physiopathology , Schizophrenia/physiopathology , Adult , Antipsychotic Agents/administration & dosage , Caudate Nucleus/drug effects , Cerebral Cortex/drug effects , Female , Hippocampus/drug effects , Humans , Longitudinal Studies , Magnetic Resonance Imaging , Male , Nerve Net/drug effects , Psychotic Disorders/drug therapy , Risperidone/administration & dosage , Risperidone/pharmacology , Schizophrenia/drug therapyABSTRACT
Understanding the role of the pancreatic extracellular matrix (ECM) in supporting islet survival and function drives the pursuit to create biomaterials that imitate and restore the pancreatic ECM microenvironment. To create an ECM mimic holding bioinductive cues for ß-cells, self-assembled peptide amphiphiles (PAs) inscribed with four selected ECM-derived cell adhesive ligands are synthesized. After 7 days, compared to control groups cultured on biologically inert substrates, MIN6 ß-cells cultured on PAs functionalized with YIGSR and RGDS cell adhesive ligands exhibit elevated insulin secretion in responses to glucose and also form ß-cell clusters. These findings suggest that the self-assembled PA nanomatrix may be utilized to improve pancreatic islet transplantation for treating type 1 diabetes.
