Depression in Somatic Disorders: Is There a Beneficial Effect of Exercise?

Background: The beneficial effects of exercise training on depressive symptoms are well-established. In the past years, more research attention has been drawn to the specific effects of exercise training on depressive symptoms in somatically ill patients. This reviews aims at providing a comprehensive overview of the current findings and evidence of exercise interventions in somatic disorders to improve depressive symptoms. Methods: We systematically searched PubMed and Cochrane databases and extracted meta-analyses from somatically ill patients that underwent exercise interventions and provided information about the outcome of depressive symptoms. Results: Of the 4123 detected publications, 39 were selected for final analysis. Various diseases were included (breast-cancer, prostate cancer, mixed-cancer, cardiovascular disease, coronary heart disease, hemodialysis, fibromyalgia syndrome, acute leukemia, other hematological malignancies, heart failure, HIV, multiple sclerosis, mixed neurological disorders, Parkinson's disease, stroke, ankylosing spondylitis, traumatic brain injury, lupus erythematodes). Most meta-analyses (33/39) found beneficial effects on depressive symptoms, but quality of the included studies as well as duration, intensity, frequency, and type of exercise varied widely. Conclusion: Exercise training has the potential to improve depressive symptoms in patients with somatic disorders. For specific training recommendations, more high quality studies with structured exercise programs and better comparability are needed

Reasons to move — a cross-sectional study to identify factors promoting regular exercise

Regular physical activity can prevent various physical and mental illnesses or improve their prognosis. However, only about half of the German population meets the WHO recommendations for physical activity. The aim of this study was to identify factors that influence engagement in regular exercise and could help increase physical activity levels in the general population. To this end, we conducted a cross-sectional study using questionnaire instruments and self-designed items. The research cohort comprised a sample of online-acquired data from 1,119 mentally healthy individuals. Higher regular exercise was associated with higher both intrinsic and extrinsic motivation, self-efficacy, resilience, internal locus of control, and risk-taking behaviour, as well as higher scores in the personality traits conscientiousness, extraversion, and agreeableness. Higher regular exercise was also linked to lower external locus of control. Whether participants exercised was also related to external circumstances, such as their financial situation, whether family members frequently exercised during childhood or the availability of sports facilities. Furthermore, participants' preferred exercise environment was found to be different from reality. Despite expressing a preference for outdoor and group exercise, most participants reported exercising alone and indoors. People who exercised regularly during childhood stated higher levels of intrinsic as well as extrinsic motivation and resilience. Based on our findings, we suggest that additional low-threshold, low-cost opportunities for physical exercise should be provided in public spaces that lack exercise facilities, as well as in childcare settings with a particular focus on disadvantaged social groups

Disturbed oligodendroglial maturation causes cognitive dysfunction in schizophrenia: a new hypothesis

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

Blood–brain barrier dysfunction and folate and vitamin B12 levels in first-episode schizophrenia-spectrum psychosis: a retrospective chart review

Vitamin deficiency syndromes and blood–brain barrier (BBB) dysfunction are frequent phenomena in psychiatric conditions. We analysed the largest available first-episode schizophrenia-spectrum psychosis (FEP) cohort to date regarding routine cerebrospinal fluid (CSF) and blood parameters to investigate the association between vitamin deficiencies (vitamin B12 and folate) and BBB impairments in FEP. We report a retrospective analysis of clinical data from all inpatients that were admitted to our tertiary care hospital with an ICD-10 diagnosis of a first-episode F2x (schizophrenia-spectrum) between January 1, 2008 and August 1, 2018 and underwent a lumbar puncture, blood-based vitamin status diagnostics and neuroimaging within the clinical routine. 222 FEP patients were included in our analyses. We report an increased CSF/serum albumin quotient (Qalb) as a sign of BBB dysfunction in 17.1% (38/222) of patients. White matter lesions (WML) were present in 29.3% of patients (62/212). 17.6% of patients (39/222) showed either decreased vitamin B12 levels or decreased folate levels. No statistically significant association was found between vitamin deficiencies and altered Qalb. This retrospective analysis contributes to the discussion on the impact of vitamin deficiency syndromes in FEP. Although decreased vitamin B12 or folate levels were found in approximately 17% of our cohort, we found no evidence for significant associations between BBB dysfunction and vitamin deficiencies. To strengthen the evidence regarding the clinical implications of vitamin deficiencies in FEP, prospective studies with standardized measurements of vitamin levels together with follow-up measurements and assessment of symptom severity in addition to CSF diagnostics are needed

The relationship between blood–brain barrier dysfunction and neurocognitive impairments in first-episode psychosis: findings from a retrospective chart analysis

Background Even before the onset of psychotic symptoms, individuals with schizophrenia display cognitive impairments. Simultaneously, increasing amounts of individuals exhibit dysfunction of the blood–brain barrier (BBB). However, the impact of BBB dysfunction on neurocognitive impairment in people with first-episode psychosis has not yet been investigated. Aims To advance understanding of said relationship, we considered one of the largest first-episode psychosis cohorts with cerebrospinal fluid parameters available, and investigated whether BBB dysfunction is related to working memory, working speed and attention. Method We conducted a retrospective chart review of 121 in-patients diagnosed with a first episode of a schizophrenia spectrum disorder. Patients underwent neurocognitive testing and a lumbar puncture within routine clinical care. To define BBB dysfunction, albumin cerebrospinal fluid/serum quotients, immunoglobulin G ratios and oligoclonal band types were evaluated, and gender-specific differences investigated. Neurocognitive functioning was assessed by the Wechsler Adult Intelligence Scale, Test of Attentional Performance and Repeatable Battery for the Assessment of Neuropsychological Status. We performed simple and multiple linear regression analyses to interpret associations of interest. Results Of those tested, 16% showed an alteration in albumin quotients and 12% had an oligoclonal band type indicating BBB dysfunction. Notably, male patients were more likely to have an increased albumin quotient and a higher immunoglobulin G ratio than female patients. We found no significant association between BBB dysfunction and neurocognitive assessments. Conclusions The hypothesised relationship between BBB and neurocognitive impairments was not detectable in our retrospective cohort. Further cerebrospinal fluid-based studies with a longitudinal assessment of cognitive functioning and disease trajectory are urgently needed

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

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

Higher blood–brain barrier leakage in schizophrenia-spectrum disorders: A comparative dynamic contrast-enhanced magnetic resonance imaging study with healthy controls

Background: Blood-brain barrier (BBB) disruptions are presumed to be implicated in schizophrenia-spectrum disorders (SSDs). Previous studies focused on cerebrospinal fluid (CSF) markers, which are imprecise for detecting subtle BBB disruption. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) enables sensitive investigation of subtle BBB leakage in vivo, yet remains unexplored in SSD research. We hypothesized higher leakage in SSDs compared to healthy controls (HCs), indicating a clinical sub-phenotype. Methods: Forty-one people with SSDs and forty age- and sex-matched HCs were included in this cross-sectional study employing DCE-MRI, clinical characterization, cognitive assessment, blood and CSF analyses. The volume transfer constant Ktrans, calculated using the Patlak method to estimate the contrast agent transfer between blood and extravascular space, was compared between groups to detect differences in BBB leakage. Results: Individuals with SSDs showed higher BBB leakage compared to HCs in a widespread pattern, in brain regions typically affected in SSDs. No significant association was detected between leakage and measures of cognition, symptom severity, peripheral inflammation markers and albumin CSF/serum ratio. Conclusions: This is the first study to date reporting BBB leakage in SSDs compared to HCs in multiple brain regions implicated in the disorder. These findings provide insights into disease mechanisms, highlighting the need for further investigation into the role of the BBB in SSDs