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.

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.

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.

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.

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.

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.

A new SLC12A3 founder mutation (p. Val647Met) in Gitelman's syndrome patients of Roma ancestry / Una nueva mutación fundadora en SLC12A3 (p. Val647Met) en pacientes con síndrome de Gitelman de etnia gitana

Background: Gitelman's syndrome (GS) is an autosomal recessive disorder caused by mutations in the SLC12A3 gene. GS is characterized by hypokalaemic metabolic alkalosis, hypomagnesemia and hypocalciuria. Most of the reported patients of Roma ancestry are homozygous for an SLC12A3 intron 9 frameshifting mutation (c.1180+1G>T). Some forms of Bartter's syndrome result from mutations in the CLNCKB gene and clinically overlap with GS. Objectives: To characterize a second SLC12A3 mutation in Roma patients negative for the intron 9 variant. Methods: SLC12A3 and CLNCKB genes were analyzed by next-generation sequencing in two Spanish and Greek gypsy patients who were negative for the intron 9 splicing mutation. Sanger sequencing was performed to confirm the putative mutations in patients and family members. Results: We identified a missense variant (p.Val647Met, c.1939G>A) in both cases, and both were homozygous for Met. This mutation was also found in three additional patients; two homozygous and one heterozygous compound with the intron 9 splicing mutation. This new SLC12A3 mutation seems to be characteristic of gipsy GS patients and was linked to the same haplotype in all cases, supporting a founder origin. All the patients showed biochemical features characteristic of GS. Conclusion: We report a second founder mutation among GS patients of Roma ethnic background. The direct screening of this mutation would facilitate the characterization of patients who are negative for the more common intron 9 +1G>T mutation (AU)

Antecedentes: El síndrome de Gitelman (SG) es un trastorno autosómico recesivo causado por las mutaciones en el gen SLC12A3.El SG se caracteriza por una alcalosis metabólica hipopotasémica, hipomagnesemia e hipocalciuria. La mayoría de los pacientes de etnia gitana notificados son homocigotos para la mutación con desplazamiento del marco de lectura del intrón 9 de SLC12A3 (c.1180+1G>T). Algunas formas del síndrome de Bartter proceden de las mutaciones del gen CLNCKB y se solapan clínicamente con el SG. Objetivos: Determinar las características de una segunda mutación en SLC12A3 en pacientes de etnia gitana con resultados negativos en la variante intrón 9. Métodos: Se analizaron los genes SLC12A3 y CLNCKB mediante secuenciación de nueva generación en 2 pacientes -uno español y otro griego- de etnia gitana con resultados negativos en la mutación de empalme del intrón 9. Se llevó a cabo una secuenciación de Sanger para confirmar las supuestas mutaciones en los pacientes y sus familiares. Resultados: Se identificó una variante con cambio de sentido (p.Val647Met, c.1939G>A) en ambos casos, y ambos eran homocigotos con respecto a Met. También se observó esta mutación en 3 pacientes adicionales, 2 homocigotos y uno heterocigoto compuesto con la mutación del intrón 9. Esta nueva mutación del SLC12A3 parece ser característica de los pacientes con SG de etnia gitana y se relacionó con el mismo haplotipo en todos los casos, lo que indica un origen fundador. Todos los pacientes presentaron rasgos bioquímicos propios del SG. Conclusión: Informamos de una segunda mutación fundadora en los pacientes con SG de etnia gitana. El cribado genético directo de esta mutación facilitará la determinación de las características de los pacientes con resultados negativos en la mutación del intrón 9+1G>T, que es más frecuente (AU)

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.

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.

Emotional intelligence in non-psychotic first-degree relatives of people with schizophrenia.

UNLABELLED: Subtle social cognitive deficits in unaffected relatives of schizophrenia patients have received increasing attention over the last few years, supporting their potential endophenotypic role for this disorder. The current study assessed non-psychotic first-degree relatives' performance on a multidimensional measure of emotional intelligence (EI): the Mayer-Salovey-Caruso Emotional Intelligence Test 2.0 (MSCEIT). Endorsed by the National Institute of Mental Health, the MSCEIT is a valid and reliable instrument for detecting emotion-processing deficits among schizophrenia patients and people high in schizotypy. METHOD: Thirty-seven first-degree relatives, 37 schizophrenia outpatients and 37 healthy controls completed the MSCEIT, which comprises eight subscales aimed to assess the four branches of EI: Identifying, Facilitating, Understanding and Managing Emotions. Potential associations with cognitive function and schizotypy levels, measured with the Schizotypal Personality Questionnaire-Brief, were further evaluated. RESULTS: Relatives had significantly lower MSCEIT total scores than controls and also significantly lower scores on the Identifying emotions branch. Nevertheless, schizophrenia patients still had the poorest global EI performance. The strongest positive correlations were found in relatives and controls with measures of executive function, processing speed and general intelligence. A higher level of schizotypy correlated significantly with lower MSCEIT scores among controls, but not among relatives. CONCLUSIONS: Contrary to expectations in the general population, the current study observed subtle EI impairment in non-psychotic first-degree relatives of schizophrenia patients. These findings support the hypothesis that these EI deficiencies may be potential endophenotypes located between the clinical phenotype and the genetic predisposition for schizophrenia.

The CORE system for sub-typing melancholic depression: Adaptation and psychometric properties of the Spanish version.

We report the development procedure for a Spanish version of the CORE measure for subtyping melancholic depression and its psychometric properties. The sample comprised two subsets of depressive patients: 117 in-patients clinically assessed after admission and before discharge; and 34 in- and out-patients who were video-recorded, with each recording being rated by independent raters and re-rated six months later. The internal consistency of the Spanish version of the CORE was high, with Cronbach's alpha coefficient of 0.93 for the total CORE score. High intra-class correlation coefficient for the total score (0.96) and the three subscales (around 0.8) indicate high inter-rater reliability. Baseline and six-month ratings of video-recordings showed high test-retest reliability. Regarding construct validity, the correlation between the CORE and the Newcastle endogeneity scale scores was 0.64. A ROC curve generated an optimal cut-off of 10 to predict the definition of endogeneity/melancholia based on the Newcastle score >=6 and the DSM-IV-TR definition of melancholia. The comparison between the CORE scores at admission and at discharge revealed large differences, indicating demonstrable sensitivity to change. The Spanish version of the CORE system is a reliable and valid instrument for sub-typing depression in terms of melancholic versus non-melancholic sub-types.

Extreme soliton pulsations in dissipative systems.

We have found a strongly pulsating regime of dissipative solitons in the laser model described by the complex cubic-quintic Ginzburg-Landau equation. The pulse energy within each period of pulsations may change more than two orders of magnitude. The soliton spectra in this regime also experience large variations. Period doubling phenomena and chaotic behaviors are observed in the boundaries of existence of these pulsating solutions.

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.

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.

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.

Coexisting rogue waves within the (2+1)-component long-wave-short-wave resonance.

The coexistence of two different types of fundamental rogue waves is unveiled, based on the coupled equations describing the (2+1)-component long-wave-short-wave resonance. For a wide range of asymptotic background fields, each family of three rogue wave components can be triggered by using a slight deterministic alteration to the otherwise identical background field. The ability to trigger markedly different rogue wave profiles from similar initial conditions is confirmed by numerical simulations. This remarkable feature, which is absent in the scalar nonlinear Schrödinger equation, is attributed to the specific three-wave interaction process and may be universal for a variety of multicomponent wave dynamics spanning from oceanography to nonlinear optics.