Associations between aerobic fitness, negative symptoms, cognitive deficits and brain structure in schizophrenia—a cross-sectional study

Maurus, Isabel; Röll, Lukas; Keeser, Daniel; Karali, Temmuz; Papazov, Boris; Hasan, Alkomiet; Schmitt, Aurore; Papazova, Irina; Lembeck, Moritz; Hirjak, Dušan; Thieme, Cristina E.; Münz, Susanne; Seitz, Valentina; Greska, David; Campana, Mattia; Wagner, Elias; Löhrs, Lisa; Pömsl, Johannes; Roeh, Astrid; Malchow, Berend; Keller-Varady, Katriona; Ertl‐Wagner, Birgit; Stöcklein, Sophia; Meyer‐Lindenberg, Andreas; Falkai, Peter

doi:10.1038/s41537-022-00269-1

Cited by 8 publications

(6 citation statements)

References 106 publications

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“… 90 In a multicenter aerobic exercise study in patients with SZ, 91 we detected a positive association of aerobic fitness with right hippocampal volume and white matter volumes in parahippocampal regions. 92 On the subfield level, we found associations between aerobic fitness levels and increases in hippocampal volumes, with the strongest effects for the right CA3 and CA4 head. 93 Furthermore, aerobic fitness in patients with SZ is related to widespread functional connectivity patterns across the whole brain, with the most pronounced links between the temporal lobe, basal ganglia, and cerebellum.…”

Section: Introductionmentioning

confidence: 65%

Disturbed Oligodendroglial Maturation Causes Cognitive Dysfunction in Schizophrenia: A New Hypothesis

Falkai

Rossner

Raabe

et al. 2023

Schizophrenia Bulletin

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Background and Hypothesis Cognitive impairment is a hallmark of schizophrenia, but no effective treatment is available to date. The underlying pathophysiology includes disconnectivity between hippocampal and prefrontal brain regions. Supporting evidence comes from diffusion-weighted imaging studies that suggest abnormal organization of frontotemporal white matter pathways in schizophrenia. Study Design Here, we hypothesize that in schizophrenia, deficient maturation of oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes substantially contributes to abnormal frontotemporal macro- and micro-connectivity and subsequent cognitive deficits. Study Results Our postmortem studies indicate a reduced oligodendrocyte number in the cornu ammonis 4 (CA4) subregion of the hippocampus, and others have reported the same histopathological finding in the dorsolateral prefrontal cortex. Our series of studies on aerobic exercise training showed a volume increase in the hippocampus, specifically in the CA4 region, and improved cognition in individuals with schizophrenia. The cognitive effects were subsequently confirmed by meta-analyses. Cell-specific schizophrenia polygenic risk scores showed that exercise-induced CA4 volume increase significantly correlates with OPCs. From animal models, it is evident that early life stress and oligodendrocyte-related gene variants lead to schizophrenia-related behavior, cognitive deficits, impaired oligodendrocyte maturation, and reduced myelin thickness. Conclusions Based on these findings, we propose that pro-myelinating drugs (e.g., the histamine blocker clemastine) combined with aerobic exercise training may foster the regeneration of myelin plasticity as a basis for restoring frontotemporal connectivity and cognition in schizophrenia.

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Section: Introductionmentioning

confidence: 65%

Disturbed Oligodendroglial Maturation Causes Cognitive Dysfunction in Schizophrenia: A New Hypothesis

Falkai

Rossner

Raabe

et al. 2023

Schizophrenia Bulletin

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“…Indeed, the vast majority of functional studies based their hypotheses on previous structural findings and aimed at shining new light on hippocampal changes consequent to exercise training by looking at its functional connectivity [ 23 , 24 , 27 , 32 ]. Functional connectivity of the hippocampus seemed to increase with the occipital lobe after physical exercise both in ultra-high risks subjects for psychosis [ 24 ] and in attenuated forms of psychosis [ 23 ] compared to control conditions.…”

Section: Resultsmentioning

confidence: 99%

“…Functional MRI Looking at the total number of studies included in this narrative review, a smaller portion of the studies (N = 8) investigated the effect of exercise on functional connections in psychotic patients compared to those dedicated to structural plasticity (Table 2, Figure 2C). Indeed, the vast majority of functional studies based their hypotheses on previous structural findings and aimed at shining new light on hippocampal changes consequent to exercise training by looking at its functional connectivity [23,24,27,32]. Functional connectivity of the hippocampus seemed to increase with the occipital lobe after physical exercise both in ultra-high risks subjects for psychosis [24] and in attenuated forms of psychosis [23] compared to control conditions.…”

Section: Exercise Effects On Functional Plasticity In Psychosismentioning

confidence: 99%

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

et al. 2023

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Recently, genuine motor abnormalities have been recognized as prodromal and predictive signs of psychosis onset and progression. Therefore, physical exercise could represent a potentially relevant clinical tool in promoting the reshaping of neural connections in motor circuitry. The aim of this review is to provide an overview of the literature on neuroimaging findings as a result of physical treatment in psychosis cohorts. Twenty-one studies, all research articles, were included and discussed in this narrative review. Here, we first outlined how the psychotic brain is susceptible to structural plastic changes after aerobic physical training in pathognomic brain areas (i.e., temporal, hippocampal and parahippocampal regions). Secondly, we focused on functional changes, both region-specific and in terms of connections, to gain insights into the involvement of distant but inter-related neural regions in the plastic process occurring after treatment. Third, we attempted to bridge neural plastic changes occurring after physical interventions with clinical and cognitive outcomes of psychotic patients in order to assess the relevance of such neural reshaping in the psychiatric rehabilitation field. In conclusion, we suggest that the current state of the art is presenting physical intervention as effective in promoting neural changes for patients with psychosis; it is not only useful at the onset of the pathology but also in improving the course of the illness and its functional outcome. However, more evidence is needed to improve our knowledge of the efficacy of physical exercise in plastically reorganizing the psychotic brain in the long term, especially within regions lacking specific investigations, such as motor circuitry.

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“…Analysis of covariance was performed to compare the changes in variables from baseline to 24 weeks, adjusted by the baseline levels, between groups. Partial correlation analysis 16 , 18 , 26 , 29 , 86 was performed to examine the relationships of cognitive performance to alterations in the whole-brain GMV and IL-6 level and between the latter, with adjustment for age, education level, schizophrenia duration, total PANSS score, and antipsychotic agent dosage (chlorpromazine equivalent).…”

Section: Methodsmentioning

confidence: 99%

Low-dose lithium adjunct to atypical antipsychotic treatment nearly improved cognitive impairment, deteriorated the gray-matter volume, and decreased the interleukin-6 level in drug-naive patients with first schizophrenia symptoms: a follow-up pilot study

Zhuo,

Hu,

Chen

et al. 2023

Schizophr

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This study was conducted to investigate the effects of long-term low-dose lithium adjunct to antipsychotic agent use on the cognitive performance, whole-brain gray-matter volume (GMV), and interleukin-6 (IL-6) level in drug-naive patients with first-episode schizophrenia, and to examine relationships among these factors. In this double-blind randomized controlled study, 50 drug-naive patients with first-episode schizophrenia each took low-dose (250 mg/day) lithium and placebo (of the same shape and taste) adjunct to antipsychotic agents (mean, 644.70 ± 105.58 and 677.00 ± 143.33 mg/day chlorpromazine equivalent, respectively) for 24 weeks. At baseline and after treatment completion, the MATRICS Consensus Cognitive Battery (MCCB) was used to assess cognitive performance, 3-T magnetic resonance imaging was performed to assess structural brain alterations, and serum IL-6 levels were quantified by immunoassay. Treatment effects were assessed within and between patient groups. Relationships among cognitive performance, whole-brain GMVs, and the IL-6 level were investigated by partial correlation analysis. Relative to baseline, patients in the lithium group showed improved working memory, verbal learning, processing speed, and reasoning/problem solving after 24 weeks of treatment; those in the placebo group showed only improved working memory and verbal learning. The composite MCCB score did not differ significantly between groups. The whole-brain GMV reduction was significantly lesser in the lithium group than in the placebo group (0.46% vs. 1.03%; P < 0.001). The GMV and IL-6 reduction ratios correlated with each other in both groups (r = −0.17, P = 0.025). In the lithium group, the whole-brain GMV reduction ratio correlated with the working memory improvement ratio (r = −0.15, P = 0.030) and processing speed (r = −0.14, P = 0.036); the IL-6 reduction ratio correlated with the working memory (r = −0.21, P = 0.043) and verbal learning (r = −0.30, P = 0.031) improvement ratios. In the placebo group, the whole-brain GMV reduction ratio correlated only with the working memory improvement ratio (r = −0.24, P = 0.019); the IL-6 reduction ratio correlated with the working memory (r = −0.17, P = 0.022) and verbal learning (r = −0.15, P = 0.011) improvement ratios. Both treatments implemented in this study nearly improved the cognitive performance of patients with schizophrenia; relative to placebo, low-dose lithium had slightly greater effects on several aspects of cognition. The patterns of correlation among GMV reduction, IL-6 reduction, and cognitive performance improvement differed between groups.

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Associations between aerobic fitness, negative symptoms, cognitive deficits and brain structure in schizophrenia—a cross-sectional study

Cited by 8 publications

References 106 publications

Disturbed Oligodendroglial Maturation Causes Cognitive Dysfunction in Schizophrenia: A New Hypothesis

Disturbed Oligodendroglial Maturation Causes Cognitive Dysfunction in Schizophrenia: A New Hypothesis

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

Low-dose lithium adjunct to atypical antipsychotic treatment nearly improved cognitive impairment, deteriorated the gray-matter volume, and decreased the interleukin-6 level in drug-naive patients with first schizophrenia symptoms: a follow-up pilot study

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