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8 pages, 1280 KiB

Open AccessArticle

Testosterone/Epitestosterone Ratios—Further Hints to Explain Hyperandrogenemia in Children with Autism

by Benedikt Gasser, Johann Kurz and Markus Mohaupt

Diseases 2021, 9(1), 13; https://doi.org/10.3390/diseases9010013 - 01 Feb 2021

Cited by 2 | Viewed by 2818

Background: Epitestosterone [E] has for a long time been considered as a biologically inactive androgen. However, recently a distinct antiandrogenic activity of this naturally occurring endogenous epimer of Testosterone has been demonstrated. Especially the ratios of testosterone/epitestosterone (T/E) seem to be key as [...] Read more.

Background: Epitestosterone [E] has for a long time been considered as a biologically inactive androgen. However, recently a distinct antiandrogenic activity of this naturally occurring endogenous epimer of Testosterone has been demonstrated. Especially the ratios of testosterone/epitestosterone (T/E) seem to be key as inhibition of epitestosterone on androgen activity was postulated. As in autism, a higher androgen activity was implied. We, therefore, suggested higher levels of T/E ratios of children with autism versus children with typical development. Methods: Urine probes of 22 girls with autism (BMI 18.7 ± 4.3; average age 12.3 ± 3.8 years) and a sample of 51 controls (BMI 17.0 ± 2.6; average age 11.9 ± 4 years), as well as 61 boys with autism (BMI 17.04 ± 2. average age 11.9 ± 2.5 years) and 61 control boys (BMI 17.0 ± 2.6; average age 11.1 ± 3.0 years), were analyzed with gas chromatography mass spectrometry. RESULTS: The average T/E ratio of all boys with autism was 2.5 ± 1.8 versus 2.4 ± 1.3 in boys with typical development, respectively. No significant difference between boys with autism versus boys with typical development could be detected (p = 0.977). In girls with autism, the average T/E ratio was 1.4 ± 0.9 versus 2.0 ± 1.4 in girls with typical development, whereby a significant difference could be detected (p = 0.0285). Further, polynomial analysis of the third degree were conducted, showing a dependence from age with reasonable coefficients of determination (0.075 < R² < 0.22, all samples). Discussion: As encompassing steroid hormone analysis are expensive and work-intensive, we hoped to find an easily applicable biomarker to support diagnostics in autism. However, as a relatively small sample of only 22 girls with autism were analyzed and menstrual cycle and pubertal status were only partly controllable through the matching of BMI and age, the question arises if it was an incidental finding. Nevertheless, one suggestion might be that epitestosterone has the effect of a competitive inhibition on the androgen receptor, which would probably help to explain the higher prevalence of autism in boys as compared to girls. Presumably, as no significant difference was detected in boys, this effect might not be as relevant from a steroid hormone perspective, and other effects such as altered 17/20-hydroxylase activity as previously shown in boys and girls with autism seem to have more relevance. Analysis of larger samples, including plenty of metabolites and enzymatic cascades, as well as the role of backdoor pathway activity of androgen synthesis of girls with autism, are demanded in order to validate current findings of altered steroid hormones in autism. Full article

(This article belongs to the Special Issue Biomarkers in Neuropsychiatric Disorders)

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9 pages, 552 KiB

Open AccessArticle

Hepatitis C Virus Infection Increases Fatigue in Health Care Workers

by Vito Emanuele Catania, Giulia Malaguarnera, Giorgia Fiorenza, Eleonora Margherita Chisari, Anna Rita Lipari, Valentino Gallina, Manuela Pennisi, Giuseppe Lanza and Michele Malaguarnera

Diseases 2020, 8(4), 37; https://doi.org/10.3390/diseases8040037 - 15 Oct 2020

Cited by 2 | Viewed by 2920

Abstract

Fatigue is a common state associated with a weakening or depletion of one’s physical and mental resources, that leads to the inability to continue the individual functioning at a normal level of activity. Frequently, fatigue represents a response to infections, inflammation and autoimmune [...] Read more.

Fatigue is a common state associated with a weakening or depletion of one’s physical and mental resources, that leads to the inability to continue the individual functioning at a normal level of activity. Frequently, fatigue represents a response to infections, inflammation and autoimmune diseases. The scope of this study was to evaluate the fatigue in healthcare workers with and without hepatitis C virus (HCV) infection. Mental, physical and severity fatigue were evaluated through Krupp, Wessely and Powell fatigue scale. Anti-HCV antibodies, HCV RNA and HCV genotypes were also measured. Physical, mental and severity fatigue were higher in healthcare workers with HCV infection than the healthcare workers without infection (p < 0.01). Our data showed a direct link between fatigue and HCV infection in healthcare workers. Further studies are needed to evaluate HCV antiviral treatments on fatigue severity and on quality of life in healthcare workers Full article

(This article belongs to the Special Issue Biomarkers in Neuropsychiatric Disorders)

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11 pages, 587 KiB

Open AccessArticle

Are Steroid Hormones Dysregulated in Autistic Girls?

by Benedikt Andreas Gasser, Johann Kurz, Bernhard Dick and Markus Georg Mohaupt

Diseases 2020, 8(1), 6; https://doi.org/10.3390/diseases8010006 - 14 Mar 2020

Cited by 11 | Viewed by 5116

Abstract

Evidence of altered cholesterol and steroid hormones in autism is increasing. However, as boys are more often affected, evidence mainly relates to autistic males, whereas evidence for affected autistic girls is sparse. Therefore, a comprehensive gas chromatography mass spectrometry-based steroid hormone metabolite analysis [...] Read more.

Evidence of altered cholesterol and steroid hormones in autism is increasing. However, as boys are more often affected, evidence mainly relates to autistic males, whereas evidence for affected autistic girls is sparse. Therefore, a comprehensive gas chromatography mass spectrometry-based steroid hormone metabolite analysis was conducted from autistic girls. Results show increased levels of several steroid hormones, especially in the class of androgens in autistic girls such as testosterone or androstenediol. The increase of the majority of steroid hormones in autistic girls is probably best explained multifactorially by a higher substrate provision in line with the previously developed cholesterol hypothesis of autism. Full article

(This article belongs to the Special Issue Biomarkers in Neuropsychiatric Disorders)

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12 pages, 1120 KiB

Open AccessArticle

One Single Nucleotide Polymorphism of the TRPM2 Channel Gene Identified as a Risk Factor in Bipolar Disorder Associates With Autism Spectrum Disorder in a Japanese Population

by Naila Al Mahmuda, Shigeru Yokoyama, Toshio Munesue, Kenshi Hayashi, Kunimasa Yagi, Chiharu Tsuji and Haruhiro Higashida

Diseases 2020, 8(1), 4; https://doi.org/10.3390/diseases8010004 - 07 Feb 2020

Cited by 3 | Viewed by 3021

Abstract

The transient receptor potential melastatin 2 (TRPM2) is a non-specific cation channel, resulting in Ca²⁺ influx at warm temperatures from 34 °C to 47 °C, thus including the body temperature range in mammals. TRPM2 channels are activated by β-NAD⁺, ADP-ribose [...] Read more.

The transient receptor potential melastatin 2 (TRPM2) is a non-specific cation channel, resulting in Ca²⁺ influx at warm temperatures from 34 °C to 47 °C, thus including the body temperature range in mammals. TRPM2 channels are activated by β-NAD⁺, ADP-ribose (ADPR), cyclic ADPR, and 2′-deoxyadenosine 5′-diphosphoribose. It has been shown that TRPM2 cation channels and CD38, a type II or type III transmembrane protein with ADP-ribosyl cyclase activity, simultaneously play a role in heat-sensitive and NAD⁺ metabolite-dependent intracellular free Ca²⁺ concentration increases in hypothalamic oxytocinergic neurons. Subsequently, oxytocin (OT) is released to the brain. Impairment of OT release may induce social amnesia, one of the core symptoms of autism spectrum disorder (ASD). The risk of single nucleotide polymorphisms (SNPs) and variants of TRPM2 have been reported in bipolar disorder, but not in ASD. Therefore, it is reasonable to examine whether SNPs or haplotypes in TRPM2 are associated with ASD. Here, we report a case-control study with 147 ASD patients and 150 unselected volunteers at Kanazawa University Hospital in Japan. The sequence-specific primer-polymerase chain reaction method together with fluorescence correlation spectroscopy was applied. Of 14 SNPs examined, one SNP (rs933151) displayed a significant p-value (OR = 0.1798, 95% CI = 0.039, 0.83; Fisher’s exact test; p = 0.0196). The present research data suggest that rs93315, identified as a risk factor for bipolar disorder, is a possible association factor for ASD. Full article

(This article belongs to the Special Issue Biomarkers in Neuropsychiatric Disorders)

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Review

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17 pages, 500 KiB

Open AccessReview

Lymphocytes as a Biomarker of Frailty Syndrome: A Scoping Review

by Rut Navarro-Martínez and Omar Cauli

Diseases 2021, 9(3), 53; https://doi.org/10.3390/diseases9030053 - 13 Jul 2021

Cited by 4 | Viewed by 3162

Abstract

Frailty is a geriatric syndrome characterized by a decrease in physiological reserve and reduced resistance to stress, as a result of an accumulation of multiple deficits in physiological systems. Frailty increases the vulnerability to adverse events and is associated with the aging process. [...] Read more.

Frailty is a geriatric syndrome characterized by a decrease in physiological reserve and reduced resistance to stress, as a result of an accumulation of multiple deficits in physiological systems. Frailty increases the vulnerability to adverse events and is associated with the aging process. Several studies show an association between frailty syndrome and altered blood lymphocyte levels, which is therefore potentially useful for monitoring interventions to improve or delay frailty. The main objective of this review is to provide an analysis of the current evidence related to changes in lymphocyte counts and their associations with frailty syndrome. To that end, the literature published in this field until March 2021 was in several databases: PubMed, SCOPUS, and Cochrane. Eighteen studies analyzed the association between lymphocyte counts, lymphocyte subtypes, and frailty syndrome. Eighteen studies were analyzed, and most of them reported associations. Interestingly, the association between frailty syndrome and lower lymphocytes counts appears in different clinical conditions. Further studies are needed to determine the sensitivity of lymphocyte counts and lymphocyte subtypes in the diagnosis and monitoring of frailty syndrome, and for this measure to be used as a biomarker of frailty status. Full article

(This article belongs to the Special Issue Biomarkers in Neuropsychiatric Disorders)

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18 pages, 1466 KiB

Open AccessReview

Cholinergic Modulation of the Immune System in Neuroinflammatory Diseases

by Marcella Reale and Erica Costantini

Diseases 2021, 9(2), 29; https://doi.org/10.3390/diseases9020029 - 12 Apr 2021

Cited by 24 | Viewed by 4430

Abstract

Frequent diseases of the CNS, such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and psychiatric disorders (e.g., schizophrenia), elicit a neuroinflammatory response that contributes to the neurodegenerative disease process itself. The immune and nervous systems use the same mediators, receptors, and cells to [...] Read more.

Frequent diseases of the CNS, such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and psychiatric disorders (e.g., schizophrenia), elicit a neuroinflammatory response that contributes to the neurodegenerative disease process itself. The immune and nervous systems use the same mediators, receptors, and cells to regulate the immune and nervous systems as well as neuro-immune interactions. In various neurodegenerative diseases, peripheral inflammatory mediators and infiltrating immune cells from the periphery cause exacerbation to current injury in the brain. Acetylcholine (ACh) plays a crucial role in the peripheral and central nervous systems, in fact, other than cells of the CNS, the peripheral immune cells also possess a cholinergic system. The findings on peripheral cholinergic signaling, and the activation of the “cholinergic anti-inflammatory pathway” mediated by ACh binding to α7 nAChR as one of the possible mechanisms for controlling inflammation, have restarted interest in cholinergic-mediated pathological processes and in the new potential therapeutic target for neuro-inflammatory-degenerative diseases. Herein, we focus on recent progress in the modulatory mechanisms of the cholinergic anti-inflammatory pathway in neuroinflammatory diseases. Full article

(This article belongs to the Special Issue Biomarkers in Neuropsychiatric Disorders)

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16 pages, 5410 KiB

Open AccessReview

Glycated Hemoglobin (HbA1c) as a Biomarker for Diabetic Foot Peripheral Neuropathy

by Giulia Casadei, Marta Filippini and Lorenzo Brognara

Diseases 2021, 9(1), 16; https://doi.org/10.3390/diseases9010016 - 22 Feb 2021

Cited by 25 | Viewed by 7340

Abstract

Background: Diabetic peripheral neuropathy (DPN) is known to predict foot ulceration, lower-extremity amputation and mortality. Patients with diabetes mellitus have a predisposition toward developing chronic inflammatory demyelinating polyneuropathy, and this may also facilitate the formation of diabetic foot and cutaneous impairment, which are [...] Read more.

Background: Diabetic peripheral neuropathy (DPN) is known to predict foot ulceration, lower-extremity amputation and mortality. Patients with diabetes mellitus have a predisposition toward developing chronic inflammatory demyelinating polyneuropathy, and this may also facilitate the formation of diabetic foot and cutaneous impairment, which are considered one of the most serious impairments of diabetes mellitus, with a prevalence of 4–10% in this population. Biomarkers research provides opportunities for the early diagnosis of these complications for specific treatments useful to prevent amputation and, therefore, physical inability and mental disturbance. The recent literature has suggested that glycemic levels may be a novel factor in the pathogenesis of diabetic foot complications and is an important mediator of axonal dysfunction. The aim of this systematic literary review is to determine whether hemoglobin A1c (HbA1c) is a positive predictor for diabetic foot peripheral neuropathy and its complications, such as foot cutaneous impairments. There is a lack of consensus regarding the effect of glycemic variability on diabetic foot peripheral neuropathy, unlike other complications such as retinopathy, nephropathy or micro/macrovascular pathology. Methods: Relevant articles were searched in the Medline database using PubMed and Scopus and relevant keywords. The primary search terms used were “glycated hemoglobin” OR “HbA1c” AND “diabetic neuropathies” AND “Foot”. Results: A number of articles (336) were initially identified while searching the scientific literature regarding this topic, and 32 articles were selected and included in this review. Conclusions: This review highlights the role of HbA1c in diabetic foot peripheral neuropathy. Biomarkers play an important role in the decision-making process, and HbA1c levels are extensively used for diabetic foot clinical outcomes and settings, but biomarker research in diabetic foot peripheral neuropathy is in its infancy and will require careful attention to a number of factors and associations, since the consequences of DPN also include neurological alterations. HbA1c is an accurate and easy-to-administer test and can be an effective biomarker in establishing the diagnosis of diabetes, but future research should focus on standardizing the HbA1c level and selecting which DPN value and its correlated complications, such as foot cutaneous impairments, are the most informative. Full article

(This article belongs to the Special Issue Biomarkers in Neuropsychiatric Disorders)

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19 pages, 708 KiB

Open AccessReview

Depression and Obesity: Analysis of Common Biomarkers

by Walter Milano, Paola Ambrosio, Francesca Carizzone, Valeria De Biasio, Walter Di Munzio, Maria Gabriella Foia and Anna Capasso

Diseases 2020, 8(2), 23; https://doi.org/10.3390/diseases8020023 - 14 Jun 2020

Cited by 40 | Viewed by 7636

Abstract

Depression and obesity are very common pathologies. Both cause significant problems of both morbidity and mortality and have decisive impacts not only on the health and well-being of patients, but also on socioeconomic and health expenditure aspects. Many epidemiological studies, clinical studies and [...] Read more.

Depression and obesity are very common pathologies. Both cause significant problems of both morbidity and mortality and have decisive impacts not only on the health and well-being of patients, but also on socioeconomic and health expenditure aspects. Many epidemiological studies, clinical studies and meta-analyses support the association between mood disorders and obesity in relationships to different conditions such as the severity of depression, the severity of obesity, gender, socioeconomic status, genetic susceptibility, environmental influences and adverse experiences of childhood. Currently, both depression and obesity are considered pathologies with a high-inflammatory impact; it is believed that several overlapping factors, such as the activation of the cortico-adrenal axis, the exaggerated and prolonged response of the innate immune system and proinflammatory cytokines to stress factors and pathogens—as well as alterations of the intestinal microbiota which promote intestinal permeability—can favor the expression of an increasingly proinflammatory phenotype that can be considered a key and common phenomenon between these two widespread pathologies. The purpose of this literature review is to evaluate the common and interacting mechanisms between depression and obesity. Full article

(This article belongs to the Special Issue Biomarkers in Neuropsychiatric Disorders)

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9 pages, 1125 KiB

Open AccessReview

Effects of Physical Activity on Brain Energy Biomarkers in Alzheimer’s Diseases

by Khadijeh Ebrahimi, Morteza Jourkesh, Saeed Sadigh-Eteghad, Stephen R Stannard, Conrad P. Earnest, Roger Ramsbottom, Jose Antonio and Khan H. Navin

Diseases 2020, 8(2), 18; https://doi.org/10.3390/diseases8020018 - 08 Jun 2020

Cited by 2 | Viewed by 4986

Abstract

The prevalence of dementia has substantially increased worldwide. Currently, there is no cure for dementia or Alzheimer’s disease (AD), and care for affected patients is financially and psychologically costly. Of late, more attention has been given to preventive interventions—in particular, physical activity/exercise. In [...] Read more.

The prevalence of dementia has substantially increased worldwide. Currently, there is no cure for dementia or Alzheimer’s disease (AD), and care for affected patients is financially and psychologically costly. Of late, more attention has been given to preventive interventions—in particular, physical activity/exercise. In this review, examine the risk factors associated with AD and the effects physical activity may play in the prevention of the degenerative process of this disease, loss of memory and cognitive performance in the elderly. To date, research has shown that physical activity, especially aerobic exercise, has a protective effect on cognitive function and memory in the elderly and Alzheimer’s patients. In comparison with aerobic exercise, several strength training studies have also shown positive effects, and the rare studies that compare the two different modalities show no difference. Full article

(This article belongs to the Special Issue Biomarkers in Neuropsychiatric Disorders)

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