Personality Comparison between Lethal and Non-lethal Intimate Partner Violence Perpetrators and Their Victims.

Intimate partner violence against women (IPVAW) and femicide (intimate partner femicide, IPF), as a worldwide phenomenon, cannot be explained in a simple way. From an ecological point of view, there are individual factors contemplated. In the current studies, we consider personality as an individual factor to clarify what differentiates a non-lethal IPVAW situation from a femicide. Study 1 was designed to investigate the accuracy with which trained interviewers judged the personality of a group of IPVAW perpetrators during an interview. The target sample of study 1 was composed of 293 males who after being interviewed completed a measure of personality assessing the "Big Three" model of personality. The interviewers performed fairly accurate judgements about the personality of the target participants. Study 2 shows the differences in personality, using Eysenck's personality model, between the IPF and IPVAW perpetrators and their victims. The total sample study 2 was formed of 551 participants distributed among IPF perpetrators, IPVAW perpetrators, and the victims of both groups. Differences in proportions were observed between both groups of perpetrators as well as between each group and their respective victims. With these findings, we propose personality as a femicide risk factor that should be taken into consideration by police officers and other practitioners when receiving an IPVAW report.

Uncovering the Genetic and Molecular Features of Huntington's Disease in Northern Colombia.

Huntington's disease (HD) is a genetic disorder caused by a CAG trinucleotide expansion in the huntingtin (HTT) gene. Juan de Acosta, Atlántico, a city located on the Caribbean coast of Colombia, is home to the world's second-largest HD pedigree. Here, we include 291 descendants of this pedigree with at least one family member with HD. Blood samples were collected, and genomic DNA was extracted. We quantified the HTT CAG expansion using an amplicon sequencing protocol. The genetic heterogeneity was measured as the ratio of the mosaicism allele's read peak and the slippage ratio of the allele's read peak from our sequence data. The statistical and bioinformatic analyses were performed with a significance threshold of p < 0.05. We found that the average HTT CAG repeat length in all participants was 21.91 (SD = 8.92). Of the 291 participants, 33 (11.3%, 18 females) had a positive molecular diagnosis for HD. Most affected individuals were adults, and the most common primary and secondary alleles were 17/7 (CAG/CCG) and 17/10 (CAG/CCG), respectively. The mosaicism increased with age in the participants with HD, while the slippage analyses revealed differences by the HD allele type only for the secondary allele. The slippage tended to increase with the HTT CAG repeat length in the participants with HD, but the increase was not statistically significant. This study analyzed the genetic and molecular features of 291 participants, including 33 with HD. We found that the mosaicism increased with age in the participants with HD, particularly for the secondary allele. The most common haplotype was 17/7_17/10. The slippage for the secondary allele varied by the HD allele type, but there was no significant difference in the slippage by sex. Our findings offer valuable insights into HD and could have implications for future research and clinical management.

Socio-emotional strengths against psychopathology and suicidal ideation in fear of COVID-19.

Coronavirus disease (COVID-19) has caused a global health crisis. It also leads to different types of psychosocial problems in society as a result of preventive health measures and the disease itself. Among others, psychopathological symptoms and suicide behaviors have increased. The PsicorecurSOS COVID-19 online protocol was designed. At baseline, 1020 Spanish adults were assessed, during confinement, for sociodemographics, fear of COVID-19, anxious-depressive symptoms, covitality, and suicidal ideation. Reliability, descriptive, and frequency analyses were carried out, and the computer tool SPSS PROCESS was used to carry out a conditional process analysis (model 59). A total of 595 participants were included (58.30% response rate from baseline; mean age = 37.18 [SD = 13.30]; 72.44% female). Regarding suicidal ideation, 12% responded differently to "never," 19.3% exceeded the cutoff point on the anxiety scale, and 24% on the depression scale. Moderate mediation analysis explained 27% of the variance in suicidal ideation. In addition, the indirect effect of moderate mediation was significant (b = -.004, SE = .002 with the presence of covitality; and b = .01, SE = .003 absence of covitality). Sex and age did not influence the overall outcome of the model. The data from this study can serve as a starting point for generating social and health treatment initiatives based on self-examination of anxiety-depressive symptoms and increasing socio-emotional skills in order to prevent and alleviate the psychosocial effects of the pandemic.

Language Deficits as a Preclinical Window into Parkinson's Disease: Evidence from Asymptomatic Parkin and Dardarin Mutation Carriers.

OBJECTIVES: The worldwide spread of Parkinson's disease (PD) calls for sensitive and specific measures enabling its early (or, ideally, preclinical) detection. Here, we use language measures revealing deficits in PD to explore whether similar disturbances are present in asymptomatic individuals at risk for the disease. METHODS: We administered executive, semantic, verb-production, and syntactic tasks to sporadic PD patients, genetic PD patients with PARK2 (parkin) or LRRK2 (dardarin) mutation, asymptomatic first-degree relatives of the latter with similar mutations, and socio-demographically matched controls. Moreover, to detect sui generis language disturbances, we ran analysis of covariance tests using executive functions as covariate. RESULTS: The two clinical groups showed impairments in all measures, most of which survived covariation with executive functions. However, the key finding concerned asymptomatic mutation carriers. While these subjects showed intact executive, semantic, and action-verb production skills, they evinced deficits in a syntactic test with minimal working memory load. CONCLUSIONS: We propose that this sui generis disturbance may constitute a prodromal sign anticipating eventual development of PD. Moreover, our results suggest that mutations on specific genes (PARK2 and LRRK2) compromising basal ganglia functioning may be subtly related to language-processing mechanisms. (JINS, 2017, 23, 150-158).

Theory of Mind in Huntington's Disease: A Systematic Review of 20 Years of Research.

Background: People with Huntington's disease (HD) exhibit neurocognitive alterations throughout the disease, including deficits in social cognitive processes such as Theory of Mind (ToM). Objective: The aim is to identify methodologies and ToM instruments employed in HD, alongside relevant findings, within the scientific literature of the past two decades. Methods: We conducted a comprehensive search for relevant papers in the SCOPUS, PubMed, APA-PsyArticles, Web of Science, Redalyc, and SciELO databases. In the selection process, we specifically focused on studies that included individuals with a confirmed genetic status of HD and investigated ToM functioning in patients with and without motor symptoms. The systematic review followed the PRISMA protocol. Results: A total of 27 papers were selected for this systematic review, covering the period from 2003 to 2023. The findings consistently indicate that ToM is globally affected in patients with manifest motor symptoms. In individuals without motor symptoms, impairments are focused on the affective dimensions of ToM. Conclusions: Based on our analysis, affective ToM could be considered a potential biomarker for HD. Therefore, it is recommended that ToM assessment be included as part of neuropsychological evaluation protocols in clinical settings. Suchinclusion could aid in the identification of early stages of the disease and provide new opportunities for treatment, particularly with emerging drugs like antisense oligomers. The Prospero registration number for this review is CRD42020209769.

Connectivity and molecular profiles of Foxp2- and Dbx1-lineage neurons in the accessory olfactory bulb and medial amygdala.

In terrestrial vertebrates, the olfactory system is divided into main (MOS) and accessory (AOS) components that process both volatile and nonvolatile cues to generate appropriate behavioral responses. While much is known regarding the molecular diversity of neurons that comprise the MOS, less is known about the AOS. Here, focusing on the vomeronasal organ (VNO), the accessory olfactory bulb (AOB), and the medial amygdala (MeA), we reveal that populations of neurons in the AOS can be molecularly subdivided based on their ongoing or prior expression of the transcription factors Foxp2 or Dbx1, which delineate separate populations of GABAergic output neurons in the MeA. We show that a majority of AOB neurons that project directly to the MeA are of the Foxp2 lineage. Using single-neuron patch-clamp electrophysiology, we further reveal that in addition to sex-specific differences across lineage, the frequency of excitatory input to MeA Dbx1- and Foxp2-lineage neurons differs between sexes. Together, this work uncovers a novel molecular diversity of AOS neurons, and lineage and sex differences in patterns of connectivity.

The cognitive structure of time estimation impairments in adults with attention deficit hyperactivity disorder.

We compared the performance of 15 adults with attention deficit hyperactivity disorder (ADHD) and a group of 16 control adults on a temporal bisection task in auditory and visual modalities. The point of subjective equality (PSE) and the difference limen (DL) were computed to analyse performance. The main findings were that (a) individuals with ADHD overestimated the duration of both the auditory and visual stimuli in comparison to the control group, as evidenced by a shift in their mean PSE; (b) individuals with ADHD also showed less precision in their estimates than did the control group as evidenced by flatter psychometric functions; and (c) the degrees of overestimation and imprecision in subjects with ADHD were comparable across modalities. These results, discussed in the framework of the pacemaker-counter clock model of time estimation, suggest that temporal difficulties encountered by ADHD patients might be explained both by an alertness effect at the level of the switch that directs pulses into the accumulator and also by distortions of durations stored in reference memory.

Breaking the cycle of emotional flooding: the protective role of women's emotional intelligence in couple's conflict.

Introduction: One of the most damaging aspects, both for people's well-being and for close relationships, is conflict. Beyond different stressors, the emotions evoked, their regulation and an appropriate conflict resolution strategy will reduce negative consequences. Emotional Intelligence facilitates social relationships, but little applied research has been done on the relationship with couple conflict and emotional flooding, particularly from the perspective of women. Therefore, the present study analyzes the role of Perceived Emotional Intelligence (PEI) and the mediating effect of Positive Conflict Resolution strategies (PCR) in couples' conflicts from women's perspective, examining its effect on Emotional Flooding (EF) and Satisfaction. Methods: Through a cross-sectional design, the relationships between variables were analyzed using group comparisons and means of a structural equation model (SEM) in a sample of 692 women. Results: Significant differences were found between the groups by age, length of relationship, and motherhood. The SEM revealed a good fit. PEI predicted 71.8% of the variance in EF and 35% in Satisfaction through PCR and Conflict.

Women Victims of Intimate Partner Violence and Intimate Partner Homicide: A Typology Based on Victimization Variables.

Intimate partner violence against women (IPVAW) and intimate partner homicide against women (IPHAW) are multidimensional phenomena. The aim of this study was to identify typologies of Spanish IPHAW and IPVAW victims, based on the differences between their characteristics and the determinants of aggression. The sample consisted of 381 cases from the Spanish Integral Monitoring System in Cases of Gender Violence. The instrument used was a semi-structured interview. Results showed differences between IPHAW and IPVAW victims, and latent class analysis suggested a three-profile solution: 1-fatal victims, with low neuroticism, low isolation, and feelings of loneliness, less reconciliation with the aggressor, lower perception of risk and low suicidal ideation; 2-non-fatal victims, with the loss of a loved one and the role of caregiver as stressors, low psychoticism and alcohol abuse, high feelings of loneliness, risk perception, and suicidal ideation; 3-mixed profile, with high neuroticism and psychoticism, alcohol abuse, isolation, and greater reconciliations with the aggressor, and absence of bereavement and caregiver role as stressors. Knowing the differences between IPHAW and IPVAW victims allows the design of more specific instruments for risk assessment and the design of more individualized prevention and treatment programs. This also facilitates police work in identifying victims and deploying more intense protection measures.

La violencia de pareja contra la mujer (violencia de género, VdG) y el homicidio de pareja contra la mujer (feminicidio) son fenómenos multidimensionales. El objetivo de este estudio fue identificar las tipologías de las víctimas españolas de feminicidio y VdG, basado en las diferencias entre sus características y los determinantes de la agresión. La muestra constaba de 381 casos del Sistema Español de Seguimiento Integral de Casos de Violencia de Género. El instrumento utilizado fue una entrevista semiestructurada. Los resultados mostraron diferencias entre las víctimas de VdG y las víctimas de feminicidios y el análisis de clases latentes sugirió tres perfiles: 1-víctimas mortales, con bajo neuroticismo, bajo aislamiento y sentimientos de soledad, menor reconciliación con el agresor, menor percepción de riesgo y baja ideación suicida; 2-víctimas no mortales, con la pérdida de un ser querido y el rol de cuidador como estresores, bajo psicoticismo y abuso de alcohol, sentimientos de soledad elevados, percepción de riesgo e ideación suicida; 3-perfil mixto, con neuroticismo y psicoticismo elevados, abuso de alcohol, aislamiento y una mayor reconciliación con el agresor y ausencia de duelo y del rol de cuidador como estresores. Conocer las diferencias entre víctimas de feminicidio y de VdG permite el diseño de instrumentos más específicos para la evaluación del riesgo y el diseño de programas de prevención y tratamiento más individualizados. También facilita la labor policial en la identificación de las víctimas y el despliegue de medidas de protección más intensas.

Civic Engagement and Personality: Associations with the Big Five and the Dark Triad.

Several studies have analyzed the relationship between general personality traits and attitudes and behaviors, indicating that a person is more committed to the community. After raising the question of whether malevolent traits might also be related, the aim was to analyze the relationship between civic engagement and personality, delving into the contribution of the Dark Triad (narcissism, Machiavellianism, and psychopathy) and controlling for the association with the Big Five. The Civic Engagement Questionnaire, the Short Dark Triad, and the Big Five Inventory-10 were administered to 1175 Spanish students (convenience sampling). After performing statistical analyses using SPSS statistical software, it was obtained that the three Dark Triad traits explained 11% of the total explained variance of civic engagement, while 19% was reached when the Big Five were included. Narcissism and openness were the factors most strongly associated with engagement. The positive relationship between narcissism and general personality traits could explain why narcissistic people have more favorable attitudes. Furthermore, people with narcissistic traits may display these attitudes for their own benefit. This study provides further evidence of how the narcissistic personality trait differs from the other two malevolent traits. Given that these traits are also associated with maladaptive behaviors, knowing all their characteristics could facilitate the design of prevention programs aimed at reducing such maladaptive behaviors.

Tissue plasminogen activator induces microglial inflammation via a noncatalytic molecular mechanism involving activation of mitogen-activated protein kinases and Akt signaling pathways and AnnexinA2 and Galectin-1 receptors.

Inflammatory responses mediated by glial cells play a critical role in many pathological situations related to neurodegeneration such as Alzheimer's disease. Tissue plasminogen activator (tPA) is a serine protease which best-known function is fibrinolysis, but it is also involved in many other physiological and pathological events as microglial activation. Here, we found that tPA is required for Aß-mediated microglial inflammatory response and tumor necrosis factor-α release. We further investigated the molecular mechanism responsible for tPA-mediated microglial activation. We found that tPA induces a catalytic-independent rapid and sustained activation of extracellular signal-regulated kinase (ERK)1/2, Jun N-terminal kinase (JNK), Akt, and p38 signaling pathways. Inhibition of ERK1/2 and JNK resulted in a strong inhibition of microglial activation, whereas Akt inhibition led to increased inflammatory response, suggesting specific functions for each signaling pathway in the regulation of microglial activation. Furthermore, we demonstrated that AnnexinA2 and Galectin-1 receptors are involved in tPA signaling and inflammatory response in glial cells. This study provides new evidences supporting that tPA plays a cytokine-like role in glial activation by triggering receptor-mediated intracellular signaling circuits and opens new therapeutic strategies for the treatment of neurological disorders in which neuroinflammation plays a pathogenic role.

Same Personality, New Ways to Abuse: How Dark Tetrad Personalities Are Connected With Cyber Intimate Partner Violence.

New technologies bring new forms of intimate partner violence (IPV) or abuse, such as cyber intimate partner violence (C-IPV). This is a contemporary issue with different consequences from in-person IPV. C-IPV is a complex phenomenon triggered by a number of factors, including personality traits such as the Dark Tetrad, composed of four "malevolent" qualities: subclinical narcissism, Machiavellianism, subclinical psychopathy, and everyday sadism. The Dark Tetrad plays an important role in predicting the perpetration or victimization of the resulting pervasive behaviors. Although the correlations between in-person IPV and the Dark Tetrad have been studied before, to our knowledge this investigation is the first to look at the links between these four dark personality traits and C-IPV. With a sample of 1,189 participants, we measured C-IPV victimization and perpetration rates and compared the results with the Dark Tetrad profiles of the respondents. To analyze these correlations, we conducted bivariate analysis and structural equation modeling. The analysis yielded positive relations of psychopathy and narcissism with cyber controlling behaviors. Psychopathy was found to be strongly related with direct cyber aggression behaviors; sadism was mainly related with C-IPV victimization in both controlling and direct aggression, and, finally and interestingly, Machiavellianism presented negative correlations with direct cyber aggression. Remarkable is that joining sadistic personalities increased vulnerability to victimization from C-IPV direct aggression, as well as more psychopathic traits and an increased probability of perpetration. These combinations may create dangerous situations. In conclusion, we found that both C-IPV perpetrators and victims present higher scores in the dark personality traits and gender-based differences than in-person IPV actors.

Dark tetrad personality traits also play a role in bullying victimization.

Bullying refers to physical and/or psychological mistreatment or abuse by one individual or group toward another individual or group. Bullying is widespread in our society and carries considerable negative consequences. This phenomenon is caused by multiple factors, which include personality. Much more attention has been paid to the study of the perpetrators' negative personality traits than the victims. Several studies have examined the relationship between these traits-the Dark Triad or Dark Tetrad-and being a victim of bullying (or mobbing) in adults, especially in the workplace. However, only two studies have been located that have studied these relationships in adolescents. Therefore, this study aimed to analyze the relationship between being a victim of bullying and the ark Tetrad traits, delving into the specific contribution of Machiavellianism, narcissism, psychopathy, and sadism in victims of bullying in Spanish adolescents. A cross-sectional study was carried out by administering the Short Dark Triad, the Assessment of Sadistic Personality, and the Peer Bullying Questionnaire to 393 adolescents aged 12-18 years (M = 14.18; SD = 2.52; 53.7% male). The Dark Tetrad traits predicted the victimization variables in the seven models analyzed, with the verbal abuse model being the model with the largest contribution. Of the four dark traits, sadism stands out as the trait with the highest specific contribution. Our results indicate, despite not implying a causal relationship, that those people with high scores in the Dark Tetrad traits tend to be more victimized by bullying. Knowing the personality traits of the bullying perpetrators and their victims, practitioners will have a complete picture of the personality variables that play a role in preventing bullying and its associated victimization.

Effects of the Action for Neutralization of Bullying Program on Bullying in Spanish Schoolchildren.

Bullying can have serious physical and emotional consequences. In recent years, interest in this phenomenon has been growing, becoming a public health problem in the first world. The aim of this study was to evaluate the effects of the Action for Neutralization of Bullying Program (ANA) in Spanish children. This study used a quasi-experimental design that included a pre-test evaluation, 2 months of intervention, a post-test, and 3 months of follow-up. A sample of 330 children aged 7-12 years (M = 9.27; SD = 1.09) from third to sixth grade participated in the study. One hundred and fifty-nine were girls (48.2%). The program consisted of eight group sessions in which empathy, assertiveness, communication skills, conflict resolution, and group cohesion were worked on. The results showed statistically significant reductions in verbal abuse behaviors (t = 4.76, p < 0.001), direct social exclusion (t = 3.53, p < 0.001), threats (t = 2.04, p = 0.042), aggression with objects (t = 3.21, p < 0.001), and physical abuse (t = 4.41, p < 0.001). The differences were not statistically significant for indirect social exclusion behaviors (t = 1.86, p = 0.065) or cyberbullying (t = 0.31, p = 0.756). The effects in the reduction of the bullying behaviors decreased after the implementation of the program, achieving even greater reduction in victimization behaviors after 3 months than immediately after the end of the program. These results indicate that the ANA program is effective in reducing bullying behaviors in a group of children. Implications for practice and future research are discussed.

Neuroticism Is Associated with Tau Pathology in Cognitively Unimpaired Individuals with Autosomal Dominant Alzheimer's Disease.

BACKGROUND: Greater neuroticism has been associated with higher risk for Alzheimer's disease (AD) dementia. However, the directionality of this association is unclear. We examined whether personality traits differ between cognitively-unimpaired carriers of autosomal-dominant AD (ADAD) and non-carriers, and are associated with in vivo AD pathology. OBJECTIVE: To determine whether personality traits differ between cognitively unimpaired ADAD mutation carriers and non-carriers, and whether the traits are related to age and AD biomarkers. METHODS: A total of 33 cognitively-unimpaired Presenilin-1 E280A mutation carriers and 41 non-carriers (ages 27-46) completed neuropsychological testing and the NEO Five-Factor Personality Inventory. A subsample (n = 46; 20 carriers) also underwent tau and amyloid PET imaging. RESULTS: Carriers reported higher neuroticism relative to non-carriers, although this difference was not significant after controlling for sex. Neuroticism was positively correlated with entorhinal tau levels only in carriers, but not with amyloid levels. CONCLUSION: The finding of higher neuroticism in carriers and the association of this trait with tau pathology in preclinical stages of AD highlights the importance of including personality measures in the evaluation of individuals at increased risk for cognitive impairment and dementia. Further research is needed to characterize the mechanisms of these relationships.

ADGRL3, FGF1 and DRD4: Linkage and Association with Working Memory and Perceptual Organization Candidate Endophenotypes in ADHD.

Attention deficit hyperactivity disorder (ADHD) is a highly heritable neurobehavioral disorder that affects children worldwide, with detrimental long-term consequences in affected individuals. ADHD-affected patients display visual-motor and visuospatial abilities and skills that depart from those exhibited by non-affected individuals and struggle with perceptual organization, which might partially explain impulsive responses. Endophenotypes (quantifiable or dimensional constructs that are closely related to the root cause of the disease) might provide a more powerful and objective framework for dissecting the underlying neurobiology of ADHD than that of categories offered by the syndromic classification. In here, we explore the potential presence of the linkage and association of single-nucleotide polymorphisms (SNPs), harbored in genes implicated in the etiology of ADHD (ADGRL3, DRD4, and FGF1), with cognitive endophenotypes related to working memory and perceptual organization in 113 nuclear families. These families were ascertained from a geographical area of the Caribbean coast, in the north of Colombia, where the community is characterized by its ethnic diversity and differential gene pool. We found a significant association and linkage of markers ADGRL3-rs1565902, DRD4-rs916457 and FGF1-rs2282794 to neuropsychological tasks outlining working memory and perceptual organization such as performance in the digits forward and backward, arithmetic, similarities, the completion of figures and the assembly of objects. Our results provide strong support to understand ADHD as a combination of working memory and perceptual organization deficits and highlight the importance of the genetic background shaping the neurobiology, clinical complexity, and physiopathology of ADHD. Further, this study supplements new information regarding an ethnically diverse community with a vast African American contribution, where ADHD studies are scarce.

Impulsive and Omission Errors: Potential Temporal Processing Endophenotypes in ADHD.

Temporal processing (TP) is associated with functions such as perception, verbal skills, temporal perspective, and future planning, and is intercorrelated with working memory, attention, and inhibitory control, which are highly impaired in individuals with attention deficit hyperactivity disorder (ADHD). Here we evaluate TP measures as potential endophenotypes in Caribbean families ascertained from probands affected by ADHD. A total of 232 individuals were recruited and clinically evaluated using an extensive battery of neuropsychological tasks and reaction time (RT)-based task paradigms. Further, the heritability (genetic variance underpinning phenotype) was estimated as a measure of the genetics apportionment. A predictive framework for ADHD diagnosis was derived using these tasks. We found that individuals with ADHD differed from controls in neuropsychological tasks assessing mental control, visual-verbal memory, verbal fluency, verbal, and semantic fluency. In addition, TP measures such as RT, errors, and variability were also affected in individuals with ADHD. Moreover, we determined that only omission and commission errors had significant heritability. In conclusion, we have disentangled omission and commission errors as possible TP endophenotypes in ADHD, which can be suitable to assess the neurobiological and genetic basis of ADHD. A predictive model using these endophenotypes led to remarkable sensitivity, specificity, precision and classification rate for ADHD diagnosis, and may be a useful tool for patients' diagnosis, follow-up, and longitudinal assessment in the clinical setting.

Sex-Specific Social Behavior and Amygdala Proteomic Deficits in Foxp2 +/- Mutant Mice.

In humans, mutations in the transcription factor encoding gene, FOXP2, are associated with language and Autism Spectrum Disorders (ASD), the latter characterized by deficits in social interactions. However, little is known regarding the function of Foxp2 in male or female social behavior. Our previous studies in mice revealed high expression of Foxp2 within the medial subnucleus of the amygdala (MeA), a limbic brain region highly implicated in innate social behaviors such as mating, aggression, and parental care. Here, using a comprehensive panel of behavioral tests in male and female Foxp2 +/- heterozygous mice, we investigated the role Foxp2 plays in MeA-linked innate social behaviors. We reveal significant deficits in olfactory processing, social interaction, mating, aggressive, and parental behaviors. Interestingly, some of these deficits are displayed in a sex-specific manner. To examine the consequences of Foxp2 loss of function specifically in the MeA, we conducted a proteomic analysis of microdissected MeA tissue. This analyses revealed putative sex differences expression of a host of proteins implicated in neuronal communication, connectivity, and dopamine signaling. Consistent with this, we discovered that MeA Foxp2-lineage cells were responsive to dopamine with differences between males and females. Thus, our findings reveal a central and sex-specific role for Foxp2 in social behavior and MeA function.

Sex Differences in Biophysical Signatures across Molecularly Defined Medial Amygdala Neuronal Subpopulations.

The medial amygdala (MeA) is essential for processing innate social and non-social behaviors, such as territorial aggression and mating, which display in a sex-specific manner. While sex differences in cell numbers and neuronal morphology in the MeA are well established, if and how these differences extend to the biophysical level remain unknown. Our previous studies revealed that expression of the transcription factors, Dbx1 and Foxp2, during embryogenesis defines separate progenitor pools destined to generate different subclasses of MEA inhibitory output neurons. We have also previously shown that Dbx1-lineage and Foxp2-lineage neurons display different responses to innate olfactory cues and in a sex-specific manner. To examine whether these neurons also possess sex-specific biophysical signatures, we conducted a multidimensional analysis of the intrinsic electrophysiological profiles of these transcription factor defined neurons in the male and female MeA. We observed striking differences in the action potential (AP) spiking patterns across lineages, and across sex within each lineage, properties known to be modified by different voltage-gated ion channels. To identify the potential mechanism underlying the observed lineage-specific and sex-specific differences in spiking adaptation, we conducted a phase plot analysis to narrow down putative ion channel candidates. Of these candidates, we found a subset expressed in a lineage-biased and/or sex-biased manner. Thus, our results uncover neuronal subpopulation and sex differences in the biophysical signatures of developmentally defined MeA output neurons, providing a potential physiological substrate for how the male and female MeA may process social and non-social cues that trigger innate behavioral responses.

Mutations in sphingolipid metabolism genes are associated with ADHD.

Attention deficit hyperactivity disorder (ADHD) is the most prevalent neurodevelopmental disorder in children, with genetic factors accounting for 75-80% of the phenotypic variance. Recent studies have suggested that ADHD patients might present with atypical central myelination that can persist into adulthood. Given the essential role of sphingolipids in myelin formation and maintenance, we explored genetic variation in sphingolipid metabolism genes for association with ADHD risk. Whole-exome genotyping was performed in three independent cohorts from disparate regions of the world, for a total of 1520 genotyped subjects. Cohort 1 (MTA (Multimodal Treatment study of children with ADHD) sample, 371 subjects) was analyzed as the discovery cohort, while cohorts 2 (Paisa sample, 298 subjects) and 3 (US sample, 851 subjects) were used for replication. A set of 58 genes was manually curated based on their roles in sphingolipid metabolism. A targeted exploration for association between ADHD and 137 markers encoding for common and rare potentially functional allelic variants in this set of genes was performed in the screening cohort. Single- and multi-locus additive, dominant and recessive linear mixed-effect models were used. During discovery, we found statistically significant associations between ADHD and variants in eight genes (GALC, CERS6, SMPD1, SMPDL3B, CERS2, FADS3, ELOVL5, and CERK). Successful local replication for associations with variants in GALC, SMPD1, and CERS6 was demonstrated in both replication cohorts. Variants rs35785620, rs143078230, rs398607, and rs1805078, associated with ADHD in the discovery or replication cohorts, correspond to missense mutations with predicted deleterious effects. Expression quantitative trait loci analysis revealed an association between rs398607 and increased GALC expression in the cerebellum.