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Lithium (Li) is the first-line treatment for bipolar disorder (BD) even though only 30 % of BD patients are considered excellent responders. The mechanisms by which Li exerts its action are not clearly understood, but it has been suggested that specific epigenetic mechanisms, such as methylation processes, may play a role. In this regard, DNA methylation patterns can be used to estimate epigenetic age (EpiAge), which is accelerated in BD patients and reversed by Li treatment. Our first aim was to compare the DNA methylation profile in peripheral blood between BD patients categorized as excellent responders to Li (Ex-Rp) and non-responders (N-Rp). Secondly, EpiAge was estimated to detect differential age acceleration between the two groups. A total of 130 differentially methylated positions (DMPs) and 16 differentially methylated regions (DMRs) between Ex-Rp (n = 26) and N-Rp (n = 37) were identified (FDR adjusted p-value < 0.05). We found 122 genes mapping the DMPs and DMRs, nine of which (HOXB6, HOXB3, HOXB-AS3, TENM2, CACNA1B, ANK3, EEF2K, CYP1A1, and SORCS2) had previously been linked to Li response. We found genes related to the GSK3β pathway to be highly represented. Using FUMA, we found enrichment in Gene Ontology Cell Component for the synapse. Gene network analysis highlighted functions related to the cell cycle, nervous system development and function, and gene expression. No significant differences in age acceleration were found between Ex-Rp and N-Rp for any of the epigenetic clocks analysed. Our findings indicate that a specific methylation pattern could determine the response to Li in BD patients. We also found that a significant portion of the differentially methylated genes are closely associated with the GSK3β pathway, reinforcing the role of this system in Li response. Future longitudinal studies with larger samples will help to elucidate the epigenetic mechanisms underlying Li response., Competing Interests: Declaration of competing interest AGP has received CME-related honoraria, or consulting fees unrelated to the present work from Angelini, Janssen-Cilag, Casen Recordati, Rovi, LCN and Lundbeck. EV has received grants and served as consultant, advisor or CME speaker for the following entities: AB-Biotics, AbbVie, Adamed, Angelini, Biogen, Biohaven, Boehringer-Ingelheim, Celon Pharma, Compass, Dainippon Sumitomo Pharma, Ethypharm, Ferrer, Gedeon Richter, GH Research, Glaxo-Smith Kline, HMNC, Idorsia, Janssen, Lundbeck, Medincell, Merck, Novartis, Orion Corporation, Organon, Otsuka, Roche, Rovi, Sage, Sanofi-Aventis, Sunovion, Takeda, and Viatris, outside the submitted work. The rest of authors have nothing to disclose., (Copyright © 2024. Published by Elsevier B.V.)

Background: Deficits in emotional intelligence (EI) were detected in patients with bipolar disorder (BD), but little is known about whether these deficits are already present in patients after presenting a first episode mania (FEM). We sought (i) to compare EI in patients after a FEM, chronic BD and healthy controls (HC); (ii) to examine the effect exerted on EI by socio-demographic, clinical and neurocognitive variables in FEM patients., Methods: The Emotional Intelligence Quotient (EIQ) was calculated with the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). Performance on MSCEIT was compared among the three groups using generalized linear models. In patients after a FEM, the influence of socio-demographic, clinical and neurocognitive variables on the EIQ was examined using a linear regression model., Results: In total, 184 subjects were included (FEM n = 48, euthymic chronic BD type I n = 75, HC n = 61). BD patients performed significantly worse than HC on the EIQ [mean difference (MD) = 10.09, standard error (s.e.) = 3.14, p = 0.004] and on the understanding emotions branch (MD = 7.46, s.e. = 2.53, p = 0.010). FEM patients did not differ from HC and BD on other measures of MSCEIT. In patients after a FEM, EIQ was positively associated with female sex ( β = -0.293, p = 0.034) and verbal memory performance ( β = 0.374, p = 0.008). FEM patients performed worse than HC but better than BD on few neurocognitive domains., Conclusions: Patients after a FEM showed preserved EI, while patients in later stages of BD presented lower EIQ, suggesting that impairments in EI might result from the burden of disease and neurocognitive decline, associated with the chronicity of the illness.

The COVID-19 pandemic and the lockdown restrictions could have adverse consequences for patients with severe mental disorders (SMD). Here, we aim to compare the early psychological impact (depression, anxiety, and stress responses, intrusive and avoidant thoughts, and coping strategies) on people with SMD (n = 125) compared with two control groups: common mental disorders (CMD, n = 250) and healthy controls (HC, n = 250). An anonymous online questionnaire using a snowball sampling method was conducted from March 19-26, 2020 and included sociodemographic and clinical data along with the DASS-21 and IES scales. We performed descriptive and bivariate analyses and multinomial and linear regression models. People with SMD had higher anxiety, stress, and depression responses than HC, but lower scores than CMD in all domains. Most people with SMD (87.2%) were able to enjoy free time, although control groups had higher percentages. After controlling for confounding factors, anxiety was the only significant psychological domain with lower scores in HC than people with SMD (OR = 0.721; 95% CI: 0.579-0.898). In the SMD group, higher anxiety was associated with being single (beta = 0.144), having COVID-19 symptoms (beta = 0.146), and a higher score on the stress subscale of DASS-21 (beta = 0.538); whereas being able to enjoy free time was a protective factor (beta = -0.244). Our results showed that patients with SMD reacted to the pandemic and the lockdown restrictions with higher anxiety levels than the general public, and suggesting this domain could be a criterion for early intervention strategies and closer follow-up., Competing Interests: Declaration of competing interest The authors declare no conflict of interest for the submitted work., (Copyright © 2020 Elsevier B.V. All rights reserved.)

It has recently been suggested that alterations of the layers of the retina could be a biomarker of specific mental disorders since they originate in the same embryonic layer as the brain and both are interconnected through the optic nerve. The purpose of this article is to offer a systematic review of the literature and a thematic synthesis on the current state of the alterations of the retina layers identified by optical coherence tomography in patients with schizophrenia, bipolar disorder and major depression. For this purpose, we performed a bibliographic search, a systematic review of the studies and a thematic synthesis of the reported findings. Patients with schizophrenia have more abnormal findings followed by patients with bipolar disorder, with very few findings in depression. The nerve fiber layer is the retinal layer with more abnormal findings both in schizophrenia and in bipolar disorder, while no study in major depression found alterations in it. Of the clinical parameters, the duration of the illness correlates significantly and inversely with the thickness of the different layers in all disorders. When interpreting these data, it is necessary to take into account the limitations and differences of the studies, especially the mean length of the disorders. Given that this was very different among the 3 disorders (more than doubled in the case of schizophrenia respect to major depression), the differences in the results found could be due more to the effect of the length of illness than to the disorder itself. In summary, optical coherence tomography findings are promising, since they could provide biomarkers of neurodegeneration and/or neuroprogression of both schizophrenia and bipolar disorder., (Copyright © 2019 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: The age at onset of bipolar disorder (BD) has significant implications for severity, duration of affective episodes, response to treatment, and psychiatric comorbidities. It has been suggested that early-onset BD (EO-BD) could represent a clinically distinct subtype with probable genetic risk factors different from those of late-onset BD (LO-BD). To date, several genes have been associated with BD risk but few studies have investigated the genetic differences between EO-BD and LO-BD. The aim of this study was to evaluate if variants of the gene coding for myo-inositol monophosphatase (IMPA2) are linked to age at onset of BD., Method: 235 bipolar patients were recruited and assessed. The final sample consisting of 192 euthymic individuals, was compared according to the age at onset. Polymorphisms were genotyped in the IMPA2 gene (rs669838, rs1020294, rs1250171, and rs630110). Early-onset was defined by the appearance of a first affective episode before the age of 18., Results: The analyses showed that in the genotype distribution rs1020294 (p = .01) and rs1250171 (p = .01) were associated with the age at onset. The significant effect remained only in the rs1020294 SNP in which G carriers were more likely to debut later compared to patients presenting the AA genotype (p = .002; OR = 9.57, CI95%[2.37-38.64]). The results also showed that EO-BD tended to experience more alcohol misuse (p = .003; OR = .197, CI95%[.07-.58]) compared to LO-BD., Conclusions: Our results provide evidence for genetic differences between EO-BD and LO-BD at the IMPA2 gene as well as clinical differences between subgroups with therapeutic implications., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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Background: Functional recovery remains a core clinical objective for patients with bipolar disorder (BD). Sociodemographic, clinical, and neurocognitive variables are associated with long‐term functional impairment, yet the impact of sex differences is unclear. Functional remediation (FR) is a validated intervention aimed at achieving functional recovery in BD. The present study assessed the effect of sex differences of FR on psychosocial functioning at post‐treatment (6‐months) and 12‐month follow‐up (FUP). To the best of our knowledge, this is the first study to explore the role of sex as a factor in the efficacy of FR. Methods: 157 participants with BD were randomly assigned to either FR (N = 77) or treatment as usual group (80). Clinical, sociodemographic, neuropsychological, and functional data were obtained using a comprehensive assessment battery. Sex differences were explored via a general linear model (GLM) for repeated measures to compare the effect of sex on the intervention over time (6 months and FUP). Results: Results demonstrated that FR benefits both sexes, males (p = 0.001; d' = 0.88) and females (p = 0.04; d' = 0.57), at 6 months suggesting a generalized functional improvement. Conversely, at 12‐month FUP sex differences were observed only in males (p = 0.005; d' = 0.68). Conclusions: FR is a beneficial intervention for males and females after treatment, suggesting that there are no relevant distinct needs. Females may benefit from ongoing psychosocial functioning booster sessions after the intervention to maintain original improvements. Future research exploring sex differences could help to identify strategies to offer personalized FR intervention approaches in individuals with BD. [ABSTRACT FROM AUTHOR]

Highlights • Patients with a severe mental disorder suffer a high prevalence of MetS. • High homocysteine and low 25-OH-VD and folate levels are frequent in those patients. • We report an association between MetS and both low 25-OH-VD and high retinol levels. • Inflammation-related biomarkers may help identify patients with a high risk of MetS. • These biomarkers are available to most psychiatrists for routine patient assessment. Abstract There is a scarcity of studies assessing the influence of biomarkers in metabolic syndrome in psychiatric patients. Our aim was to correlate serum or plasma levels of 25-hydroxyvitamin D (25-OH-VD), retinol, vitamin B12 (VB12), folate and homocysteine (Hcy), with the metabolic status, in a sample of 289 outpatients with Schizophrenia or Bipolar Disorder. Logistic regression and multiple linear regressions were performed to assess the ability of biomarkers to predict the presence of MetS, the number of risk factors for MetS, and insulin resistance indexes (HOMA and QUICKI). Regarding the association between biomarkers and the QUICKI index, the model explained 6.8% of the variance, with folate and 25-OH-VD levels contributing significantly to the model. The model predicting the number of MetS risk factors was significant and explained 21.7% of the variance, being 25-OH-VD and retinol the statistically significant factors. As for the impact of biomarkers on MetS, the model was statistically significant, being 25-OH-VD and retinol levels the significant factors. We report for the first time an association between MetS and both low 25-OH-VD and high retinol concentrations. Inflammation-related biomarkers may help identify patients with a high risk of MetS who might benefit from healthy lifestyle counselling and early intervention. [ABSTRACT FROM AUTHOR]

Genome wide association studies (GWAS) has allowed the discovery of some interesting risk variants for schizophrenia (SCZ). However, this high-throughput approach presents some limitations, being the most important the necessity of highly restrictive statistical corrections as well as the loss of statistical power inherent to the use of a Single Nucleotide Polymorphism (SNP) analysis approach. These problems can be partially solved through the use of a polygenic approach. We performed a genotyping study in SCZ using 86 previously associated SNPs identified by GWAS of SCZ, bipolar disorder (BPD) and autistic spectrum disorder (ASD) patients. The sample consisted of 3063 independent cases with DSM-IV-TR diagnosis of SCZ and 2847 independent controls of European origin from Spain. A polygenic score analysis was also used to test the overall effect on the SCZ status. One SNP, rs12290811, located in the ODZ4 gene reached statistical significance (p=1.7×10(-4), Allelic odds ratio=1.21), a value very near to those reported in previous GWAS of BPD patients. In addition, 4 SNPs were close to the significant threshold: rs3850333, in the NRXN1 gene; rs6932590, at MHC; rs2314398, located in an intergenic region on chromosome 2; and rs1006737, in the CACNA1C gene. We also found that 74% of the studied SNPs showed the same tendency (risk or protection alleles) previously reported in the original GWAS (p<0.001). Our data strengthen the polygenic component of susceptibility to SCZ. Our findings show ODZ4 as a risk gene for SCZ, emphasizing the existence of common vulnerability in psychosis. [ABSTRACT FROM AUTHOR]