Research

13 pages, 1879 KiB

Open AccessArticle

The Association between Blood SIRT1 and Ghrelin, Leptin, and Antibody Anti-Hypothalamus: A Comparison in Normal Weight and Anorexia Nervosa

by Andrea Amerio, Andrea Escelsior, Eleonora Martino, Antonella Strangio, Andrea Aguglia, Matteo Marcatili, Benedetta Conio, Samir Giuseppe Sukkar and Daniele Saverino

J. Pers. Med. 2023, 13(6), 928; https://doi.org/10.3390/jpm13060928 - 31 May 2023

Cited by 2 | Viewed by 1058

Abstract

Sirtuin 1 (SIRT1) is a sensor of cell energy availability, regulating metabolic homeostasis as well as leptin and ghrelin, and it could be considered as a potential plasmatic marker. The aim of this study was to assess whether circulating SIRT1 varies consistently with [...] Read more.

Sirtuin 1 (SIRT1) is a sensor of cell energy availability, regulating metabolic homeostasis as well as leptin and ghrelin, and it could be considered as a potential plasmatic marker. The aim of this study was to assess whether circulating SIRT1 varies consistently with leptin, ghrelin, body mass index (BMI), and IgG reactive to hypothalamic antigens in anorexia nervosa (AN). Fifty-four subjects were evaluated: 32 with AN and 22 normal-weight control subjects. Serum levels of SIRT1, leptin, ghrelin, and IgG reactive to hypothalamic antigens were evaluated by ELISA. Results showed that serum SIRT1 is increased in patients with AN, and the amount is decreased in relation to the duration of the illness. SIRT1 concentration approaches the values obtained for the control group, although the difference is still statistically significant. A negative correlation between serum SIRT1 values and leptin or BMI values has been found. On the contrary, a positive correlation between SIRT1 and ghrelin or IgG specific for hypothalamic antigens is reported. These findings suggest that a peripheral evaluation of SIRT1 could be a possible clinical/biochemical parameter related to AN. In addition, we can assume that SIRT1 is related to autoantibody production and may correlate with the intensity/severity of AN. Thus, reducing the production of autoantibodies specific for hypothalamic cells could be a sign of improvement of the clinical condition. Full article

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

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10 pages, 286 KiB

Open AccessCommunication

Association Study of BDNF, SLC6A4, and FTO Genetic Variants with Schizophrenia Spectrum Disorders

by Aneta Bednarova, Viera Habalova, Michaela Krivosova, Matteo Marcatili and Ivan Tkac

J. Pers. Med. 2023, 13(4), 658; https://doi.org/10.3390/jpm13040658 - 12 Apr 2023

Viewed by 1359

Abstract

Schizophrenia spectrum disorders (patients with a diagnosis of schizophrenia, schizotypal, and delusional disorders: F20-F29 according to International Classification of Diseases 10th revision (ICD-10)) are considered highly heritable heterogeneous psychiatric conditions. Their pathophysiology is multifactorial with involved dysregulated serotonergic neurotransmission and synaptic plasticity. The [...] Read more.

Schizophrenia spectrum disorders (patients with a diagnosis of schizophrenia, schizotypal, and delusional disorders: F20-F29 according to International Classification of Diseases 10th revision (ICD-10)) are considered highly heritable heterogeneous psychiatric conditions. Their pathophysiology is multifactorial with involved dysregulated serotonergic neurotransmission and synaptic plasticity. The present study aimed to evaluate the association of SLC6A4 (5-HTTLPR), FTO (rs9939609), and BDNF (rs6265, rs962369) polymorphisms with schizophrenia spectrum disorders in Slovak patients. We analyzed the genotypes of 150 patients with schizophrenia, schizotypal, and delusional disorders and compared them with genotypes from 178 healthy volunteers. We have found a marginally protective effect of LS + SS genotypes of 5-HTTLPR variant of the serotonin transporter SLC6A4 gene against the development of schizophrenia spectrum disorders, but the result failed to remain significant after Bonferroni correction. Similarly, we have not proven any significant association between other selected genetic variants and schizophrenia and related disorders. Studies including a higher number of subjects are warranted to reliably confirm the presence or absence of the studied associations. Full article

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

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12 pages, 305 KiB

Open AccessArticle

Association of HTTLPR, BDNF, and FTO Genetic Variants with Completed Suicide in Slovakia

by Aneta Bednarova, Viera Habalova, Silvia Farkasova Iannaccone, Ivan Tkac, Dominika Jarcuskova, Michaela Krivosova, Matteo Marcatili and Natasa Hlavacova

J. Pers. Med. 2023, 13(3), 501; https://doi.org/10.3390/jpm13030501 - 10 Mar 2023

Cited by 2 | Viewed by 1294

Abstract

Since suicide and suicidal behavior are considered highly heritable phenotypes, the identification of genetic markers that can predict suicide risk is a clinically important topic. Several genes studied for possible associations between genetic polymorphisms and suicidal behaviors had mostly inconsistent and contradictory findings. [...] Read more.

Since suicide and suicidal behavior are considered highly heritable phenotypes, the identification of genetic markers that can predict suicide risk is a clinically important topic. Several genes studied for possible associations between genetic polymorphisms and suicidal behaviors had mostly inconsistent and contradictory findings. The aim of this case-control study was to evaluate the associations between completed suicide and polymorphisms in genes BDNF (rs6265, rs962369), SLC6A4 (5-HTTLPR), and FTO (rs9939609) in relation to sex and BMI. We genotyped 119 completed suicide victims and 137 control subjects that were age, sex, and ethnicity matched. A significant association with completed suicide was found for BDNF rs962369. This variant could play a role in completed suicide, as individuals with the CC genotype were more often found among suicides than in control subjects. After sex stratification, the association remained significant only in males. A nominally significant association between the gene variant and BMI was observed for BDNF rs962369 under the overdominant model. Heterozygotes with the TC genotype showed a lower average BMI than homozygotes with TT or CC genotypes. FTO polymorphism (rs9939609) did not affect BMI in the group of Slovak suicide completers, but our findings follow an inverse association between BMI and completed suicide. Full article

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

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15 pages, 2407 KiB

Open AccessArticle

Protein Succinylation and Malonylation as Potential Biomarkers in Schizophrenia

by Bradley Joseph Smith, Caroline Brandão-Teles, Giuliana S. Zuccoli, Guilherme Reis-de-Oliveira, Mariana Fioramonte, Verônica M. Saia-Cereda and Daniel Martins-de-Souza

J. Pers. Med. 2022, 12(9), 1408; https://doi.org/10.3390/jpm12091408 - 30 Aug 2022

Cited by 2 | Viewed by 1928

Abstract

Two protein post-translational modifications, lysine succinylation and malonylation, are implicated in protein regulation, glycolysis, and energy metabolism. The precursors of these modifications, succinyl-CoA and malonyl-CoA, are key players in central metabolic processes. Both modification profiles have been proven to be responsive to metabolic [...] Read more.

Two protein post-translational modifications, lysine succinylation and malonylation, are implicated in protein regulation, glycolysis, and energy metabolism. The precursors of these modifications, succinyl-CoA and malonyl-CoA, are key players in central metabolic processes. Both modification profiles have been proven to be responsive to metabolic stimuli, such as hypoxia. As mitochondrial dysfunction and metabolic dysregulation are implicated in schizophrenia and other psychiatric illnesses, these modification profiles have the potential to reveal yet another layer of protein regulation and can furthermore represent targets for biomarkers that are indicative of disease as well as its progression and treatment. In this work, data from shotgun mass spectrometry-based quantitative proteomics were compiled and analyzed to probe the succinylome and malonylome of postmortem brain tissue from patients with schizophrenia against controls and the human oligodendrocyte precursor cell line MO3.13 with the dizocilpine chemical model for schizophrenia, three antipsychotics, and co-treatments. Several changes in the succinylome and malonylome were seen in these comparisons, revealing these modifications to be a largely under-studied yet important form of protein regulation with broad potential applications. Full article

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

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11 pages, 7581 KiB

Open AccessArticle

Multi-Omics Analysis Reveals Myelin, Presynaptic and Nicotinate Alterations in the Hippocampus of G72/G30 Transgenic Mice

by Michaela D. Filiou, Larysa Teplytska, Markus Nussbaumer, David-M. Otte, Andreas Zimmer and Christoph W. Turck

J. Pers. Med. 2022, 12(2), 244; https://doi.org/10.3390/jpm12020244 - 09 Feb 2022

Cited by 3 | Viewed by 2505

Abstract

The primate-specific G72/G30 gene locus has been associated with major psychiatric disorders, such as schizophrenia and bipolar disorder. We have previously generated transgenic mice which carry the G72/G30 locus and express the longest G72 splice variant (LG72) protein encoded by this locus with [...] Read more.

The primate-specific G72/G30 gene locus has been associated with major psychiatric disorders, such as schizophrenia and bipolar disorder. We have previously generated transgenic mice which carry the G72/G30 locus and express the longest G72 splice variant (LG72) protein encoded by this locus with schizophrenia-related symptoms. Here, we used a multi-omics approach, including quantitative proteomics and metabolomics to investigate molecular alterations in the hippocampus of G72/G30 transgenic (G72Tg) mice. Our proteomics analysis revealed decreased expression of myelin-related proteins and NAD-dependent protein deacetylase sirtuin-2 (Sirt2) as well as increased expression of the scaffolding presynaptic proteins bassoon (Bsn) and piccolo (Pclo) and the cytoskeletal protein plectin (Plec1) in G72Tg compared to wild-type (WT) mice. Metabolomics analysis indicated decreased levels of nicotinate in G72Tg compared to WT hippocampi. Decreased hippocampal protein expression for selected proteins, namely myelin oligodentrocyte glycoprotein (Mog), Cldn11 and myelin proteolipid protein (Plp), was confirmed with Western blot in a larger population of G72Tg and WT mice. The identified molecular pathway alterations shed light on the hippocampal function of LG72 protein in the context of neuropsychiatric phenotypes. Full article

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

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14 pages, 1413 KiB

Open AccessArticle

Investigating the Role of Leukocyte Telomere Length in Treatment-Resistant Depression and in Response to Electroconvulsive Therapy

by Claudia Pisanu, Erika Vitali, Anna Meloni, Donatella Congiu, Giovanni Severino, Raffaella Ardau, Caterina Chillotti, Luigi Trabucchi, Marco Bortolomasi, Massimo Gennarelli, Alessandra Minelli and Alessio Squassina

J. Pers. Med. 2021, 11(11), 1100; https://doi.org/10.3390/jpm11111100 - 27 Oct 2021

Cited by 3 | Viewed by 2446

Abstract

Psychiatric disorders seem to be characterized by premature cell senescence. However, controversial results have also been reported. In addition, the relationship between accelerated aging and treatment-resistance has scarcely been investigated. In the current study, we measured leukocyte telomere length (LTL) in 148 patients [...] Read more.

Psychiatric disorders seem to be characterized by premature cell senescence. However, controversial results have also been reported. In addition, the relationship between accelerated aging and treatment-resistance has scarcely been investigated. In the current study, we measured leukocyte telomere length (LTL) in 148 patients with treatment-resistant depression (TRD, 125 with major depressive disorder, MDD, and 23 with bipolar disorder, BD) treated with electroconvulsive therapy (ECT) and analyzed whether LTL was associated with different response profiles. We also compared LTL between patients with TRD and 335 non-psychiatric controls. For 107 patients for which genome-wide association data were available, we evaluated whether a significant overlap among genetic variants or genes associated with LTL and with response to ECT could be observed. LTL was negatively correlated with age (Spearman’s correlation coefficient = −0.25, p < 0.0001) and significantly shorter in patients with treatment-resistant MDD (Quade’s F = 35.18, p < 0.0001) or BD (Quade’s F = 20.84, p < 0.0001) compared to controls. Conversely, baseline LTL was not associated with response to ECT or remission. We did not detect any significant overlap between genetic variants or genes associated with LTL and response to ECT. Our results support previous findings suggesting premature cell senescence in patients with severe psychiatric disorders and suggest that LTL could not be a predictive biomarker of response to ECT. Full article

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

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Review

Jump to: Research, Other

19 pages, 359 KiB

Open AccessReview

Cortisol and the Dexamethasone Suppression Test as a Biomarker for Melancholic Depression: A Narrative Review

by Martin M. Schumacher and Jacopo Santambrogio

J. Pers. Med. 2023, 13(5), 837; https://doi.org/10.3390/jpm13050837 - 16 May 2023

Cited by 1 | Viewed by 2437

Abstract

The dexamethasone suppression test (DST) assesses the functionality of the HPA axis and can be regarded as the first potential biomarker in psychiatry. In 1981, a group of researchers at the University of Michigan published a groundbreaking paper regarding its use for diagnosing [...] Read more.

The dexamethasone suppression test (DST) assesses the functionality of the HPA axis and can be regarded as the first potential biomarker in psychiatry. In 1981, a group of researchers at the University of Michigan published a groundbreaking paper regarding its use for diagnosing melancholic depression, reporting a diagnostic sensitivity of 67% and a specificity of 95%. While this study generated much enthusiasm and high expectations in the field of biological psychiatry, subsequent studies produced equivocal results, leading to the test being rejected by the American Psychiatric Association. The scientific reasons leading to the rise and fall of the DST are assessed in this review, suggestions are provided as to how the original test can be improved, and its potential applications in clinical psychiatry are discussed. An improved, standardized, and validated version of the DST would be a biologically meaningful and useful biomarker in psychiatry, providing a tool for clinicians caring for depressed patients in the areas of diagnosis, treatment, and prognosis, and predicting the risk of suicide. Additionally, such a test could be a crucial part in the generation of biologically homogenous patient cohorts, necessary for the successful development of new psychotropic medications. Full article

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

11 pages, 1298 KiB

Open AccessReview

Association between Early Phase Serum Lactate Levels and Occurrence of Delayed Neuropsychiatric Sequelae in Adult Patients with Acute Carbon Monoxide Poisoning: A Systematic Review and Meta-Analysis

by Heekyung Lee, Jaehoon Oh, Hyunggoo Kang, Chiwon Ahn, Myeong Namgung, Chan Woong Kim, Wonhee Kim, Young Seo Kim, Hyungoo Shin and Tae Ho Lim

J. Pers. Med. 2022, 12(4), 651; https://doi.org/10.3390/jpm12040651 - 18 Apr 2022

Cited by 1 | Viewed by 2064

Abstract

The primary goal of treating carbon monoxide (CO) poisoning is preventing or minimizing the development of delayed neuropsychiatric sequelae (DNS). Therefore, screening patients with a high probability for the occurrence of DNS at the earliest is essential. However, prognostic tools for predicting DNS [...] Read more.

The primary goal of treating carbon monoxide (CO) poisoning is preventing or minimizing the development of delayed neuropsychiatric sequelae (DNS). Therefore, screening patients with a high probability for the occurrence of DNS at the earliest is essential. However, prognostic tools for predicting DNS are insufficient, and the usefulness of the lactate level as a predictor is unclear. This systematic review and meta-analysis investigated the association between early phase serum lactate levels and the occurrence of DNS in adult patients with acute CO poisoning. Observational studies that included adult patients with CO poisoning and reported initial lactate concentrations were retrieved from the Embase, MEDLINE, Google Scholar and six domestic databases (KoreaMED, KMBASE, KISS, NDSL, KISTi and RISS) in January 2022. Lactate values were collected as continuous variables and analyzed using standardized mean differences (SMD) using a random-effect model. The risk of bias was evaluated using the Quality in Prognosis Studies (QUIPS) tool, and subgroup, sensitivity and meta regression analyses were performed. Eight studies involving a total of 1350 patients were included. The early phase serum lactate concentration was significantly higher in the DNS group than in the non-DNS group in adult patients with acute CO poisoning (8 studies; SMD, 0.31; 95% CI, 0.11–0.50; I² = 44%; p = 0.002). The heterogeneity decreased to I² = 8% in sensitivity analysis (omitting Han2021; 7 studies; SMD, 0.38; 95% CI, 0.23–0.53; I² = 8%; p < 0.001). The risk of bias was assessed as high in five studies. The DNS group was associated with significantly higher lactate concentration than that in the non-DNS group. Full article

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

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Other

Jump to: Research, Review

19 pages, 811 KiB

Open AccessEditor’s ChoiceSystematic Review

Investigating the Role of Maintenance TMS Protocols for Major Depression: Systematic Review and Future Perspectives for Personalized Interventions

by Giacomo d’Andrea, Gianluca Mancusi, Maria Chiara Santovito, Carlotta Marrangone, Fabrizio Martino, Mario Santorelli, Andrea Miuli, Francesco Di Carlo, Maria Salvina Signorelli, Massimo Clerici, Mauro Pettorruso and Giovanni Martinotti

J. Pers. Med. 2023, 13(4), 697; https://doi.org/10.3390/jpm13040697 - 21 Apr 2023

Cited by 6 | Viewed by 2683

Abstract

Repetitive Transcranial Magnetic Stimulation (rTMS) has been approved by the FDA as an effective intervention for Treatment-Resistant Depression (TRD). However, there is little evidence about maintenance protocol necessity. The aim of this systematic review is to identify, characterize, and evaluate the current maintenance [...] Read more.

Repetitive Transcranial Magnetic Stimulation (rTMS) has been approved by the FDA as an effective intervention for Treatment-Resistant Depression (TRD). However, there is little evidence about maintenance protocol necessity. The aim of this systematic review is to identify, characterize, and evaluate the current maintenance TMS protocols for MDD and TRD patients who have received acute treatment. A literature search was conducted following the PRISMA guidelines of 2015 on PubMed, Scopus, and Web of Science databases for publications up to March 2022. Fourteen articles were included. High protocol heterogeneity was observed. Most studies highlighted significant efficacy of maintenance protocols in decreasing relapse risk, suggesting that administering two or fewer stimulations per month is ineffective in sustaining an antidepressant effect or in reducing the risk of relapse in responder patients. The risk of relapse was most pronounced after five months from the acute treatment. Maintenance TMS appears to be a resourceful strategy to maintain acute antidepressant treatment effects, significantly reducing relapse risk. The ease of administering and the ability to monitor treatment adherence should be considered when evaluating the future use of maintenance TMS protocols. Further studies are needed to clarify the clinical relevance of overlapping acute TMS effects with maintenance protocols and to evaluate their long-term effectiveness. Full article

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

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12 pages, 1118 KiB

Open AccessCase Report

Depressive Pseudodementia with Reversible AD-like Brain Hypometabolism: A Case Report and a Review of the Literature

by Federico Emanuele Pozzi, Daniele Licciardo, Monica Musarra, Lorenzo Jonghi-Lavarini, Cinzia Crivellaro, Gianpaolo Basso, Ildebrando Appollonio and Carlo Ferrarese

J. Pers. Med. 2022, 12(10), 1665; https://doi.org/10.3390/jpm12101665 - 06 Oct 2022

Cited by 2 | Viewed by 2583

Abstract

Recent European guidelines recommend using brain FDG-PET to differentiate between Alzheimer’s disease (AD) and depressive pseudodementia (DP), with specific hypometabolism patterns across the former group, and typically normal or frontal hypometabolism in the latter. We report the case of a 74 years-old man [...] Read more.

Recent European guidelines recommend using brain FDG-PET to differentiate between Alzheimer’s disease (AD) and depressive pseudodementia (DP), with specific hypometabolism patterns across the former group, and typically normal or frontal hypometabolism in the latter. We report the case of a 74 years-old man with DP (MMSE 16/30), whose FDG-PET visual rating and semiquantitative analysis closely mimicked the typical AD pattern, showing severe hypometabolism in bilateral precuneus, parietal and temporal lobes, and sparing frontal areas, suggesting the diagnosis of moderate AD. Shortly after starting antidepressant polytherapy, he underwent formal NPS testing, which revealed moderate impairment of episodic memory and mild impairment on executive and visuospatial tests, judged consistent with neurodegenerative dementia and concomitant depression. Over the following two years, he improved dramatically: repeated NPS assessment did not show significant deficits, and FDG-PET showed restoration of cerebral metabolism. The confirmation of PET findings via semiquantitative analysis, and their reversion to normality with antidepressant treatment, proved the non-neurodegenerative origin of the initial AD-like FDG-PET abnormalities. We review similar cases and provide a comprehensive analysis of their implications, concluding that reversible FDG-PET widespread hypometabolism might represent a biomarker of pseudodementia. Therefore, we suggest caution when interpreting FDG-PET scans of depressed patients with cognitive impairment. Full article

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

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