Processing speed mediates the relationship between DDR1 and psychosocial functioning in euthymic patients with bipolar disorder presenting psychotic symptoms.

The DDR1 locus is associated with the diagnosis of schizophrenia and with processing speed in patients with schizophrenia and first-episode psychosis. Here, we investigated whether DDR1 variants are associated with bipolar disorder (BD) features. First, we performed a case‒control association study comparing DDR1 variants between patients with BD and healthy controls. Second, we performed linear regression analyses to assess the associations of DDR1 variants with neurocognitive domains and psychosocial functioning. Third, we conducted a mediation analysis to explore whether neurocognitive impairment mediated the association between DDR1 variants and psychosocial functioning in patients with BD. Finally, we studied the association between DDR1 variants and white matter microstructure. We did not find any statistically significant associations in the case‒control association study; however, we found that the combined genotypes rs1264323AA-rs2267641AC/CC were associated with worse neurocognitive performance in patients with BD with psychotic symptoms. In addition, the combined genotypes rs1264323AA-rs2267641AC/CC were associated with worse psychosocial functioning through processing speed. We did not find correlations between white matter microstructure abnormalities and the neurocognitive domains associated with the combined genotypes rs1264323AA-rs2267641AC/CC. Overall, the results suggest that DDR1 may be a marker of worse neurocognitive performance and psychosocial functioning in patients with BD, specifically those with psychotic symptoms.

Super chirped rogue waves in optical fibers.

The super rogue wave dynamics in optical fibers are investigated within the framework of a generalized nonlinear Schrödinger equation containing group-velocity dispersion, Kerr and quintic nonlinearity, and self-steepening effect. In terms of the explicit rogue wave solutions up to the third order, we show that, for a rogue wave solution of order n, it can be shaped up as a single super rogue wave state with its peak amplitude 2n+1 times the background level, which results from the superposition of n(n+1)/2 Peregrine solitons. Particularly, we demonstrate that these super rogue waves involve a frequency chirp that is also localized in both time and space. The robustness of the super chirped rogue waves against white-noise perturbations as well as the possibility of generating them in a turbulent field is numerically confirmed, which anticipates their accessibility to experimental observation.

Peregrine Solitons Beyond the Threefold Limit and Their Two-Soliton Interactions.

Within the coupled Fokas-Lenells equations framework, we show explicitly that, in contrast to the expected threefold-amplitude magnification, Peregrine solitons can reach a peak amplitude as high as 5 times the background level. Besides, the interaction of two such anomalous Peregrine solitons can generate a spikelike rogue wave of extremely high peak amplitude, depending on the parameters used. We numerically confirm that the Peregrine soliton beyond the threefold limit can be reproduced from either a deterministic initial profile or a chaotic background field, hence anticipating the feasibility of its experimental observation.

Rogue-wave bullets in a composite (2+1)D nonlinear medium.

We show that nonlinear wave packets localized in two dimensions with characteristic rogue wave profiles can propagate in a third dimension with significant stability. This unique behavior makes these waves analogous to light bullets, with the additional feature that they propagate on a finite background. Bulletlike rogue-wave singlet and triplet are derived analytically from a composite (2+1)D nonlinear wave equation. The latter can be interpreted as the combination of two integrable (1+1)D models expressed in different dimensions, namely, the Hirota equation and the complex modified Korteweg-de Vries equation. Numerical simulations confirm that the generation of rogue-wave bullets can be observed in the presence of spontaneous modulation instability activated by quantum noise.

Watch-hand-like optical rogue waves in three-wave interactions.

We investigate the resonant interaction of three optical pulses of different group velocity in quadratic media and report on the novel watch-hand-like super rogue wave patterns. In addition to having a giant wall-like hump, each rogue-wave hand involves a peak amplitude more than five times its background height. We attribute such peculiar structures to the nonlinear superposition of six Peregrine-type solitons. The robustness has been confirmed by numerical simulations. This stability along with the non-overlapping distribution property may facilitate the experimental diagnostics and observation of these super rogue waves.

Extreme amplitude spikes in a laser model described by the complex Ginzburg-Landau equation.

We have found new dissipative soliton in the laser model described by the complex cubic-quintic Ginzburg-Landau equation. The soliton periodically generates spikes with extreme amplitude and short duration. At certain range of the equation parameters, these extreme spikes appear in pairs of slightly unequal amplitude. The bifurcation diagram of spike amplitude versus dispersion parameter reveals the regions of both regular and chaotic evolution of the maximal amplitudes.

Dark three-sister rogue waves in normally dispersive optical fibers with random birefringence.

We investigate dark rogue wave dynamics in normally dispersive birefringent optical fibers, based on the exact rational solutions of the coupled nonlinear Schrödinger equations. Analytical solutions are derived up to the second order via a nonrecursive Darboux transformation method. Vector dark "three-sister" rogue waves as well as their existence conditions are demonstrated. The robustness against small perturbations is numerically confirmed in spite of the onset of modulational instability, offering the possibility to observe such extreme events in normal optical fibers with random birefringence, or in other Manakov-type vector nonlinear media.

Treatment outcome of patients with comorbid type 1 diabetes and eating disorders.

BACKGROUND: Co-morbidity between Type 1 Diabetes Mellitus (T1DM) and eating disorders (ED) has been previously described; however the effect of this illness on the outcomes for conventional ED treatments has not been previously investigated. This study aims to compare clinical, psychopathological and personality features between two samples of ED individuals: those with comorbid T1DM and those without (No-DM); and to identify differences in treatment outcomes between the groups. METHODS: This study compares treatment outcome, dropouts, ED psychopathology and personality characteristics for 20 individuals with ED and T1DM and 20 ED patients without diabetes, matched for diagnostic and treatment type. RESULTS: The study found higher dropout rates from therapy in individuals with T1DM and worse treatment outcome in spite of having no significant differences in eating disorder psychopathology, although individuals with T1DM report misusing insulin. CONCLUSIONS: The low levels of motivation to change, and insulin abuse in T1DM patients, may suggest that treatment for patients with ED and T1DM should consider the individual's personality and role of insulin abuse when determining the appropriate intervention.

Burnout, Engagement, and Resilience During the COVID-19 Lockdown: Keys to a Model for Teachers' Self-Efficacy.

BACKGROUND: Social isolation measures by the COVID-19 pandemic have impacted teaching work. In an "Emergency Remote Teaching" (ERT) context, it is relevant to investigate the factors that affect teachers' self-efficacy. METHODS: A total of 289 teachers from schools in southern Spain have participated in this study. They have been asked about their levels of burnout, engagement, and resilience. Comparisons were made by groups in accordance with sex, type of center they belonged to, school social context, and educational level in which the teacher taught. Using a Structural Equations Model, the multivariate relationships between the variables related to burnout, engagement, and resilience were described. RESULTS: During the ERT, teachers' self-efficacy was influenced by the 3 factors: burnout-exhaustion and cynicism-engagement, and resilience. During the ERT, the teachers in semi-private and private centers showed greater self-efficacy. In turn, the teachers in childhood and primary education showed a significantly higher level of work engagement than the teachers in compulsory and post-compulsory secondary education. CONCLUSIONS: The results in relation to ERT are discussed in the context of the exceptionality and universal globality of the pandemic phenomenon and the complex self-perception of the social value of the teaching function.

Genetic variants and abnormal processing of pre-miR-182, a circadian clock modulator, in major depression patients with late insomnia.

Previous studies in mice have reported five different microRNAs (miRNAs; miR-219-1/132/183/96/182) to be modulators of the endogenous circadian clock and have presented experimental evidence for some of the genes involved in the molecular clock machinery as target sites. Moreover, disruption of circadian rhythms has long been implicated in the pathophysiology of major depression (MD). We investigated these miRNAs and some of their target sites at the sequence and functional levels as possible predisposing factors for susceptibility to MD and related chronobiological subphenotypes. Mutational screening was performed in a sample of 359 MD patients and 341 control individuals. We found a significant association between the T allele of the rs76481776 polymorphism in the pre-miR-182 and late insomnia in MD patients. Previous studies have reported an association between insomnia and CLOCK gene, a predicted miR-182 target site. A significant overexpression of miR-182 was detected by quantitative real-time polymerase chain reaction in cells transfected with the mutated form of the pre-miR-182 when compared with wild-type form. Moreover, a significant reduction in luciferase activity of plasmids with 3' UTR of ADCY6, CLOCK and DSIP genes was shown when transfecting cells with the mutated form of pre-miR-182 compared with cells that did not express miR-182. These data indicate that abnormal processing of pre-miR-182 in patients carrying the T allele of the rs76481776 polymorphism may contribute to the dysregulation of circadian rhythms in MD patients with insomnia, which could influence expression levels of the mature form of miR-182 and might increase downregulation in some of its target genes.

Optical spectra beyond the amplifier bandwidth limitation in dispersion-managed mode-locked fiber lasers.

We investigate the intracavity pulse dynamics inside dispersion-managed mode-locked fiber lasers, and show numerically that for a relatively wide range of parameters, pulse compression dynamics in the passive anomalous fiber can be accompanied by a significant enhancement of the spectral width by a factor close to 3. Varying the average cavity dispersion also reveals chaotic dynamics for certain dispersion ranges. The impact of the implementation of an optical output port to tap optimal pulse features is discussed.

Relationship between Amount, Type, Enjoyment of Physical Activity and Physical Education Performance with Cyberbullying in Adolescents.

(1) Background: Cyberbullying is a social concern in adolescents. The practice of physical activity is a key factor in protection against cyberbullying related to the multiple psychological benefits. Therefore, the study sets out to analyse the relationship between amount, types, enjoyment of physical activity and performance in physical education with cyberbullying. (2) Methods: A sample of 867 adolescents between 12 and 19 years of age from two schools in Andalusia (Spain) was studied. A computer-based questionnaire given in the classroom was used, with two questions about the type of physical activity, one on physical education performance, the Scale of Enjoyment of Physical Activity (PACES) and the Spanish version of the European Cyberbullying Intervention Project Questionnaire (ECIPQ). (3) Results: Clear relationships were found between the practice of physical activity and cybervictimisation. However, less involvement has been observed among girls who practice physical activity in cyberaggression. (4) Conclusions: In relation to the types of physical activity, it seems that practising physical activities that involve competition can help to develop defence mechanisms against cyberaggression, as well as improve values to be less involved in cyberaggression.

Childhood maltreatment interacts with hypothalamic-pituitary-adrenal axis negative feedback and major depression: effects on cognitive performance.

Background: Childhood maltreatment (CM) is associated with impaired hypothalamic-pituitary-adrenal (HPA) axis negative feedback and cognitive dysfunction, resembling those abnormalities linked to major depressive disorder (MDD). Objectives: We aimed to assess the potential modulating effects of MDD diagnosis or HPA axis function in the association between different types of CM and cognitive performance in adulthood. Methods: Sixty-eight MDD patients and 87 healthy controls were recruited. CM was assessed with the Childhood Trauma Questionnaire. We obtained three latent variables for neuropsychological performance (verbal memory, visual memory and executive function/processing speed) after running a confirmatory factor analysis with cognitive tests applied. Dexamethasone suppression test ratio (DSTR) was performed using dexamethasone 0.25 mg. Results: Different types of CM had different effects on cognition, modulated by MDD diagnosis and HPA axis function. Individuals with physical maltreatment and MDD presented with enhanced cognition in certain domains. The DSTR differentially modulated the association between visual memory and physical neglect or sexual abuse. Conclusions: HPA axis-related neurobiological mechanisms leading to cognitive impairment might differ depending upon the type of CM. Our results suggest a need for early assessment and intervention on cognition and resilience mechanisms in individuals exposed to CM to minimize its deleterious and lasting effects.

Antecedentes: El maltrato infantil (MI) se asocia con una alteración en la retroalimentación negativa del eje hipotalámico-hipofisario-adrenal (HHA) y disfunción cognitiva, que se asemejan a las anomalías vinculadas al trastorno depresivo mayor (TDM).Objetivos: Nuestro objetivo fue evaluar los posibles efectos moduladores del diagnóstico de TDM y de la función del eje HHA en la asociación entre diferentes tipos de MI y el rendimiento cognitivo en la edad adulta.Métodos: Se reclutaron 68 pacientes con TDM y 87 controles sanos. El MI se evaluó con el Cuestionario de trauma infantil. Se obtuvieron tres variables latentes para el rendimiento neuropsicológico (memoria verbal, memoria visual y función ejecutiva/velocidad de procesamiento) tras realizar un análisis factorial confirmatorio con las pruebas cognitivas aplicadas. La ratio de supresión de cortisol en el test de supresión con dexametasona (DSTR) se realizó usando dexametasona 0,25 mg.Resultados: Los diferentes tipos de MI tuvieron diferentes efectos sobre la cognición, modulados por el diagnóstico de TDM y la función del eje HHA. Los individuos con maltrato físico y TDM presentaron una cognición mejorada en ciertos dominios. El DSTR moduló diferencialmente la asociación entre memoria visual y negligencia física o abuso sexual.Conclusiones: Los mecanismos neurobiológicos relacionados con el eje HHA que conducen al deterioro cognitivo pueden diferir según el tipo de MI. Nuestros resultados sugieren la necesidad de una evaluación e intervención tempranas sobre la cognición y los mecanismos de resiliencia en individuos expuestos a MI para minimizar sus efectos nocivos y duraderos.

Resequencing and association analysis of arylalkylamine N-acetyltransferase (AANAT) gene and its contribution to major depression susceptibility.

Circadian rhythms disruptions, including abnormalities of circadian phase position and melatonin secretion, have been described in major depression (MD). Arylalkylamine N-acetyltransferase (AANAT) is a key enzyme of the melatonin pathway involved in circadian oscillations of melatonin levels. We assessed the contribution of AANAT gene variability to susceptibility to MD considering common and rare genetic variations through a sequential sequencing and single nucleotide polymorphism (SNP)-based genotyping approach in a sample of 445 unrelated patients with MD (257 unipolar MD, 188 bipolar depression) and 440 community-based screened control subjects. We identified 17 sequence changes, thirteen of which represented novel sequence variations. We did not observe an over-representation of patients carrying rare variants compared with the healthy controls. Common variants (MAF > 2%) were included in a case-control association analysis that showed significant association after multiple testing correction of two SNPs located in the promoter region of AANAT with MD: rs3760138 (P = 0.00006) and rs4238989 (P = 0.005). Multimarker analysis found significant associations between two three-marker protective haplotypes and a susceptibility three-marker haplotype containing the rare alleles of rs3760138-rs4238989-rs8150 and MD. We present evidence of the association of genetic variability in the AANAT gene with susceptibility to MD. Our results support the hypothesis that the melatonin-signaling pathway and circadian clock mechanisms may contribute to the pathophysiology of MD.

Hypothalamic-pituitary-adrenal axis-related genes and cognition in major mood disorders and schizophrenia: a systematic review.

Hypothalamic-pituitary-adrenal (HPA) axis dysregulation and cognitive deficits are two well-characterized endophenotypes present in different serious mental illnesses (SMIs), including major depressive disorder, bipolar disorder and schizophrenia. Our aim was to study the influence of genetic and epigenetic variations in HPA axis-related genes on cognitive performance in clinical samples, including patients with major mood disorders and schizophrenia. A systematic search was performed using PubMed (Medline), PsycINFO and Scopus databases. The systematic review identified 12 studies dealing with HPA-related genes and cognition in samples including patients with SMIs, focusing on single nucleotide polymorphism (SNP) variants, while no studies analysing epigenetic variations were found. The results suggest different and specific effects on the cognitive performance of SNP variants in the HPA axis-related genes studied, as well as interactions with traumatic experiences. There was high heterogeneity in the studied samples, genes analysed, and cognitive tasks evaluated. The relationship between HPA-related genes and cognition in SMIs is still largely unknown, and further studies including larger samples and epigenetic variations are needed.

BDNF genetic variants and methylation: effects on cognition in major depressive disorder.

Brain-derived neurotrophic factor (BDNF) gene regulation has been linked to the pathophysiology of major depressive disorder (MDD). MDD patients show cognitive deficits, and altered BDNF regulation has a relevant role in neurocognitive functions. Our goal was to explore the association between BDNF genetic and epigenetic variations with neurocognitive performance in a group of MDD patients and healthy controls considering possible modulating factors. The sample included 134 subjects, 64 MDD patients, and 70 healthy controls. Clinical data, childhood maltreatment, and neurocognitive performance were assessed in all participants. Eleven single nucleotide polymorphisms (SNPs) and two promoter regions in the BDNF gene were selected for genotype and methylation analysis. The role of interactions between BDNF genetic and epigenetic variations with MDD diagnosis, sex, and Childhood Trauma Questionnaire (CTQ) scores was also explored. We observed significant associations between neurocognitive performance and two BDNF SNPs (rs908867 and rs925946), an effect that was significantly mediated by methylation values at specific promoter I sites. We identified significant associations between neurocognitive results and methylation status as well as its interactions with MDD diagnosis, sex, and CTQ scores. Our results support the hypothesis that BDNF gene SNPs and methylation status, as well as their interactions with modulating factors, can influence cognition. Further studies are required to confirm the effect of BDNF variations and cognitive function in larger samples.

FKBP5 polymorphisms and hypothalamic-pituitary-adrenal axis negative feedback in major depression and obsessive-compulsive disorder.

Major depressive disorder (MDD) and obsessive-compulsive disorder (OCD) have both been linked to abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis. Polymorphisms in the genes involved in HPA axis activity, such as FKBP5, and their interactions with childhood trauma have been associated with stress-related mental disorders. Our goal was to study the role of FKBP5 genetic variants in HPA axis negative feedback regulation as a possible risk factor for different mental disorders such as MDD and OCD, while controlling for childhood trauma, anxiety and depressive symptoms. The sample included 266 participants divided into three groups: 1) MDD (n = 89 [n = 73 melancholic; n = 3 atypical]), 2) OCD (n = 51; 39% with comorbid MDD [n = 13 melancholic; n = 7 atypical]) and 3) healthy controls (n = 126). Childhood trauma, trait anxiety and depressive symptoms were assessed. HPA negative feedback was analyzed using the dexamethasone suppression test ratio (DSTR) after administration of 0.25 mg of dexamethasone. Twelve SNPs in the FKBP5 gene were selected for genotyping. Multiple linear regressions, after adjusting for the covariates considered, showed a reduced DSTR in individuals with the rs9470079-A variant that was significant after correction for multiple testing. Childhood trauma did not moderate the association between the rs9470079 and DSTR. Our results support the evidence that FKBP5 genetic variation could lead to abnormal HPA axis negative feedback independent of diagnosis. Therefore, this association can be identified as a transdiagnostic feature, offering an interesting opportunity to identify patients with higher stress vulnerability. Further studies focusing on the influence of FKBP5 on measurable biological endophenotypes are needed.

Hypothalamic-pituitary-adrenal axis activity in the comorbidity between obsessive-compulsive disorder and major depression.

Major depressive disorder (MDD) is the most common psychiatric comorbidity in patients with obsessive-compulsive disorder (OCD). Hypothalamic-pituitary-adrenal (HPA) axis abnormalities have been described in both disorders and might play a role in the association between them. We aimed to study the role of HPA axis activity in the comorbidity between OCD and MDD, while controlling for psychopathological dimensions such as anxiety and depressive symptoms. We studied 324 participants belonging to four diagnostic groups: 1) MDD (n = 101), 2) OCD with comorbid MDD (n = 33), 3) OCD without MDD (n = 52), and 4) healthy subjects (n = 138). State anxiety, trait anxiety and depressive symptoms were assessed. Three HPA axis measures were analyzed in saliva: cortisol awakening response (CAR), diurnal cortisol slope (calculated using two formulas: [1] awakening to 11 p.m. [AWE diurnal slope]; [2] considering fixed time points [FTP diurnal slope] from 10 a.m. to 11 p.m.), and dexamethasone suppression test ratio after 0.25 mg of dexamethasone (DSTR). Multiple linear regression analyses were conducted to explore the contribution of clinical diagnosis and symptom dimensions to each HPA axis measure. A more flattened FTP diurnal cortisol slope was observed for OCD patients with comorbid MDD. Regarding the CAR and DSTR, a significant interaction was found between trait anxiety and OCD, as OCD patients with greater trait anxiety showed an increased CAR and reduced cortisol suppression after dexamethasone administration. Our results suggest that trait anxiety plays an important role in the relationship between HPA axis measures and OCD/MDD comorbidity.

Hypothalamic-pituitary-adrenal axis activity and cognition in major depression: The role of remission status.

OBJECTIVES: Neuropsychological deficits and hypothalamic-pituitary-adrenal (HPA) axis dysfunction have been described in major depressive disorder (MDD). We conducted an exploratory study to investigate the role of remission status in the relationship between HPA axis and cognition in MDD. METHODS: Ninety-seven MDD patients (44 remitted, 53 non-remitted) and 97 healthy controls (HC) were evaluated. We measured verbal and visual memory, working memory, processing speed, attention, and executive function. Three HPA axis measures were assessed: cortisol awakening response (CAR), diurnal cortisol slope, and cortisol suppression ratio with 0.25mg of dexamethasone (DSTR). Multiple linear regression analyses were performed to study the relationship between cortisol measures and cognition while controlling for potential confounders. We conducted an overall analysis in all participants to compare both MDD-remitted and MDD non-remitted groups with respect to HC. Another analysis including MDD patients only was used to explore a moderating effect by remission status. RESULTS: MDD patients showed poorer cognitive performance compared with HC, without significant differences between remitters and non-remitters. Cortisol measures did not differ between remitters and non-remitters. Although most HPA axis measures were not associated with cognitive dysfunction, we found significant associations between cognitive performance in MDD-remitters and cortisol measures for visual memory, processing speed and executive function. A significant moderating effect for remission status was found between cortisol diurnal slope (but neither CAR nor DSTR) and performance in processing speed or executive function. CONCLUSIONS: Remission status in MDD appears to moderate the association between some cognitive domains (processing speed and executive function) and HPA axis activity.

Chirped Peregrine solitons in a class of cubic-quintic nonlinear Schrödinger equations.

We shed light on the fundamental form of the Peregrine soliton as well as on its frequency chirping property by virtue of a pertinent cubic-quintic nonlinear Schrödinger equation. An exact generic Peregrine soliton solution is obtained via a simple gauge transformation, which unifies the recently-most-studied fundamental rogue-wave species. We discover that this type of Peregrine soliton, viable for both the focusing and defocusing Kerr nonlinearities, could exhibit an extra doubly localized chirp while keeping the characteristic intensity features of the original Peregrine soliton, hence the term chirped Peregrine soliton. The existence of chirped Peregrine solitons in a self-defocusing nonlinear medium may be attributed to the presence of self-steepening effect when the latter is not balanced out by the third-order dispersion. We numerically confirm the robustness of such chirped Peregrine solitons in spite of the onset of modulation instability.