Fitness is positively associated with hippocampal formation subfield volumes in schizophrenia: a multiparametric magnetic resonance imaging study

Abstract

Hippocampal formation (HF) volume loss is a well-established finding in schizophrenia, with select subfields, such as the cornu ammonis and dentate gyrus, being particularly vulnerable. These morphologic alterations are related to functional abnormalities and cognitive deficits, which are at the core of the insufficient recovery frequently seen in this illness. To counteract HF volume decline, exercise to improve aerobic fitness is considered as a promising intervention. However, the effects of aerobic fitness levels on HF subfields are not yet established in individuals with schizophrenia. Therefore, our study investigated potential associations between aerobic fitness and HF subfield structure, functional connectivity, and related cognitive impact in a multiparametric research design. In this cross-sectional study, 53 participants diagnosed with schizophrenia (33 men, 20 women; mean [SD] age, 37.4 [11.8] years) underwent brain structural and functional magnetic resonance imaging and assessments of aerobic fitness and verbal memory. Multivariate multiple linear regressions were performed to determine whether aerobic fitness was associated with HF subfield volumes and functional connections. In addition, we explored whether identified associations mediated verbal memory functioning. Significant positive associations between aerobic fitness levels and volumes were demonstrated for most HF subfields, with the strongest associations for the cornu ammonis, dentate gyrus, and subiculum. No significant associations were found for HF functional connectivity or mediation effects on verbal memory. Aerobic fitness may mitigate HF volume loss, especially in the subfields most affected in schizophrenia. This finding should be further investigated in longitudinal studies. Clinical Trials Registration: The study on which the manuscript is based was registered in the International Clinical Trials Database, ClinicalTrials.gov (NCT number: NCT03466112 ) and in the German Clinical Trials Register (DRKS-ID: DRKS00009804).

Effects of aerobic exercise on hippocampal formation volume in people with schizophrenia – a systematic review and meta-analysis with original data from a randomized-controlled trial

“…Correspondingly, the different areas of the CA have been shown to be particularly responsive to aerobic fitness changes and aerobic exercise (48,49). At the same time, the CA area is supposed to be specifically prone to volume loss in schizophrenia (29,82).…”

“…Aerobic fitness and exercise are related to increases in the volume of the HF and its subfields, especially in CA3, CA4 and DG, leading to improvements in short-term memory, working memory and general functioning in patients with schizophrenia (44)(45)(46)(47)(48)(49)(50). However, evidence is heterogeneous with comparable examinations contradicting these findings (51)(52)(53)(54)(55).…”

Hippocampal Subfield Volumes in Amateur Marathon Runners

“…The volumes of hippocampal subfields were obtained using FreeSurfer software (version 6.0, http://surfer.nmr.mgh.harvard.edu/ , RRID:SCR_001847), which is widely used for healthy adults ( 17 , 48 ) and patients with neuropsychiatric disorder ( 49 , 50 ). FreeSurfer interrogates contrast differences between substructures using previously defined in vivo and ex vivo hippocampal atlases to determine substructure characteristics ( 50 ).…”

The Effect of Physical Exercise on People with Psychosis: A Qualitative Critical Review of Neuroimaging Findings

“…Therefore, the utmost investigated brain region is the hippocampus, together with its subfields and the parahippocampal areas. Volumetric studies reported mixed results consequent to aerobic fitness, with evidences for either an increased cortical volume of the hippocampus in schizophrenic patients [25,27,30,35,39] or stable hippocampal grey matter both in clinical high-risk subjects [23,24] and later stages of psychosis [31,36,37]. The same Therefore, the utmost investigated brain region is the hippocampus, together with its subfields and the parahippocampal areas.…”