Disinhibition Is an Essential Network Motif Coordinated by GABA Levels and GABA B Receptors.

Network dynamics are crucial for action and sensation. Changes in synaptic physiology lead to the reorganization of local microcircuits. Consequently, the functional state of the network impacts the output signal depending on the firing patterns of its units. Networks exhibit steady states in which neurons show various activities, producing many networks with diverse properties. Transitions between network states determine the output signal generated and its functional results. The temporal dynamics of excitation/inhibition allow a shift between states in an operational network. Therefore, a process capable of modulating the dynamics of excitation/inhibition may be functionally important. This process is known as disinhibition. In this review, we describe the effect of GABA levels and GABAB receptors on tonic inhibition, which causes changes (due to disinhibition) in network dynamics, leading to synchronous functional oscillations.

Long-Range GABAergic Projections of Cortical Origin in Brain Function.

The study of long-range GABAergic projections has traditionally been focused on those with subcortical origin. In the last few years, cortical GABAergic neurons have been shown to not only mediate local inhibition, but also extend long-range axons to remote cortical and subcortical areas. In this review, we delineate the different types of long-range GABAergic neurons (LRGNs) that have been reported to arise from the hippocampus and neocortex, paying attention to the anatomical and functional circuits they form to understand their role in behavior. Although cortical LRGNs are similar to their interneuron and subcortical counterparts, they comprise distinct populations that show specific patterns of cortico-cortical and cortico-fugal connectivity. Functionally, cortical LRGNs likely induce timed disinhibition in target regions to synchronize network activity. Thus, LRGNs are emerging as a new element of cortical output, acting in concert with long-range excitatory projections to shape brain function in health and disease.

Dysfunctional Patterns of Food Intake by Anxiety during Isolation by COVID-19 in Chile, Colombia and Mexico.

The aim of this research was to compare food intake dysfunctional patterns score with the subjective perception of anxiety and sociodemographic characteristics of the participants in isolation by COVID-19 from Chile, Colombia, and Mexico. A cross-sectional research was carried out, with a virtual questionnaire of subjective perception of anxiety and the questionnaire of three 18-item feeding factors. 958 people of both sexes participated (F = 83%, M = 17%), mainly in the 18 to 35 age range. Dysfunctional eating patterns presented high scores in people who perceived anxiety, as well as in participants from Chile. Additionally, it was found that women present greater cognitive restriction and emotional intake, and college students showed greater disinhibition. In conclusion, the scores of the three dysfunctional eating patterns were higher in people with subjective perception of anxiety during social isolation due to COVID-19, and there were also differences according to country, sex, and educational level.

El objetivo de esta investigación fue comparar el puntaje de los patrones disfuncionales de la ingesta con la percepción subjetiva de la ansiedad y características sociodemográficas de los participantes en aislamiento por COVID-19 de Chile, Colombia y México. Se realizó una investigación de tipo transversal, con un cuestionario virtual de percepción subjetiva de la ansiedad y el cuestionario de tres factores de alimentación 18-items. Participaron 958 personas de ambos sexos (F = 83%, M = 17%), principalmente en el rango de edad de 18 35 años. Los patrones disfuncionales de la ingesta presentaron puntajes altos en personas que percibieron ansiedad y en participantes de Chile. Adicionalmente, se encontró que las mujeres presentan mayor restricción cognitiva e ingesta emocional y los estudiantes universitarios mostraron mayor desinhibición. En conclusión, los puntajes de los tres patrones disfuncionales de la ingesta fueron más altos en las personas con percepción subjetiva de ansiedad durante el aislamiento social por COVID-19 y así mismo se presentaron diferencias de acuerdo al país, sexo y nivel educativo.

DSM-5 Pathological Personality Traits Among College Students / Rasgos de Personalidad Patológica según el DSM-5 en una muestra de estudiantes universitarios

Abstract Individuals with personality pathology exhibit significant impairment in intrapersonal and interpersonal functioning that compromise psychological welfare of significant others. However, common pathological personality traits in college students remain unclear. This study aimed to describe pathological personality traits identified in the Diagnostic and Statistical Manual of Mental Disorders (5th ed., DSM-5) Section III alternative model of personality disorder in college students. This is a quantitative, non-experimental, cross-sectional study. Participants were 81 college students from a Colombian University who were administered the Personality Inventory for DSM-5. Findings suggest that women scored significantly higher than men on hostility (z=-2.577; p=0.01; n 2 = 0.082). A medium size effect was found (p> 0.039) through the ( 2 index. The remaining variables did not prove statistically significant differences when controlling the participant gender (p < 0.05). The personality domain that reached the most dysfunctionality was disinhibition (risk taking, impulsivity, rigid perfectionism). Negative affect had the highest mean score and gender differences in facets and domains showed that women scored significantly higher than men on hostility. However, more studies into the pathological personality traits established by the PID-5 is required if the shift to a dimensional model is likely to occur in future editions of the DSM.

Resumen Las personas con patologías de la personalidad exhiben un deterioro significativo en el funcionamiento inter-intrapersonal que compromete el bienestar psicológico de los más cercanos. Sin embargo, los rasgos de personalidad patológica más comunes en estudiantes universitarios aún no son muy claros. Este estudio busca describir los rasgos de personalidad patológica identificados en el manual diagnóstico y estadístico de trastornos mentales (DSM-5), en estudiantes universitarios. Este es un estudio cuantitativo, transversal, no experimental. Los participantes fueron 81 estudiantes del programa de psicología de una Universidad Colombiana quienes fueron evaluados por medio del Inventario de personalidad para el DSM-5. Los hallazgos sugieren que las mujeres tuvieron puntuaciones significativamente más altas que los hombres en hostilidad (z=-2.577; p=0.01; n 2 = 0.082). Se encontró un tamaño del efecto medio (p> 0.039) por medio del índice ( 2 . En las demás variables no se encontraron diferencias estadísticamente significativas en cuanto al género (p < 0.05). Inhibición presentó el grado más alto de disfuncionalidad. Afecto negativo obtuvo la puntuación promedio más alta y las diferencias de género muestran que las mujeres tienden a ser más hostiles que los hombres. Sin embargo, son necesarios más estudios sobre los rasgos de personalidad patológica propuestos por el Inventario de personalidad para el DSM-5 si a futuro se propone un modelo dimensional.

Amnestic and non-amnestic symptoms of dementia: An international study of Alzheimer's disease in people with Down's syndrome.

The presence of age-related neuropathology characteristic of Alzheimer's disease (AD) in people with Down syndrome (DS) is well-established. However, the early symptoms of dementia may be atypical and appear related to dysfunction of prefrontal circuitry. OBJECTIVE: To characterize the initial informant reported age-related neuropsychiatric symptoms of dementia in people with DS, and their relationship to AD and frontal lobe function. METHODS: Non-amnestic informant reported symptoms (disinhibition, apathy, and executive dysfunction) and amnestic symptoms from the CAMDEX-DS informant interview were analyzed in a cross-sectional cohort of 162 participants with DS over 30 years of age, divided into three groups: stable cognition, prodromal dementia, and AD. To investigate age-related symptoms prior to evidence of prodromal dementia we stratified the stable cognition group by age. RESULTS: Amnestic and non-amnestic symptoms were present before evidence of informant-reported cognitive decline. In those who received the diagnosis of AD, symptoms tended to be more marked. Memory impairments were more marked in the prodromal dementia than the stable cognition group (OR = 35.07; P < .001), as was executive dysfunction (OR = 7.16; P < .001). Disinhibition was greater in the AD than in the prodromal dementia group (OR = 3.54; P = .04). Apathy was more pronounced in the AD than in the stable cognition group (OR = 34.18; P < .001). CONCLUSION: Premorbid amnestic and non-amnestic symptoms as reported by informants increase with the progression to AD. For the formal diagnosis of AD in DS this progression of symptoms needs to be taken into account. An understanding of the unique clinical presentation of DS in AD should inform treatment options.

Blockade of spinal α5-GABAA receptors differentially reduces reserpine-induced fibromyalgia-type pain in female rats.

The role of spinal α5 subunit-containing GABAA (α5-GABAA) receptors in chronic pain is controversial. The purpose of this study was to investigate the participation of spinal α5-GABAA receptors in the reserpine-induced pain model. Reserpine administration induced tactile allodynia and muscle hyperalgesia in female and male rats. Intrathecal injection of L-655,708 and TB 21007 (7 days after the last reserpine injection) decreased tactile allodynia and, at a lesser extent, muscle hyperalgesia in female rats. The effects of these drugs produced a lower antiallodynic and antihyperalgesic effect in male than in female rats. Contrariwise, these drugs produced tactile allodynia and muscle hyperalgesia in naïve rats and these effects were lower in naïve male than female rats. Intrathecal L-838,417 prevented or reversed L-655,708-induced antiallodynia in reserpine-treated female rats. Repeated treatment with α5-GABAA receptor small interfering RNA (siRNA), but not scramble siRNA, reduced reserpine-induced allodynia in female rats. Accordingly, α5-GABAA receptor siRNA induced nociceptive hypersensitivity in naïve female rats. Reserpine enhanced α5-GABAA receptors expression in spinal cord and dorsal root ganglia (DRG), while it increased CD11b (OX-42) and glial fibrillary acidic protein (GFAP) fluorescence intensity in the lumbar spinal cord. In contrast, reserpine diminished K+-Cl- co-transporter 2 (KCC2) protein in the lumbar spinal cord. Data suggest that spinal α5-GABAA receptors play a sex-dependent proallodynic effect in reserpine-treated rats. In contrast, these receptors have a sex-dependent antiallodynic role in naïve rats.

Sexual Pleasure and Function, Coital Trauma, and Sex Behaviors After Voluntary Medical Male Circumcision Among Men in the Dominican Republic.

BACKGROUND: Voluntary medical male circumcision (VMMC) is effective in decreasing the risk of HIV acquisition. As men resume sexual activity after circumcision, it will be important to study their satisfaction with the procedure, sexual pleasure and function, coital trauma, and risk compensation (RC), which can hamper or facilitate the long-term success of VMMC programs. AIM: To assess men's satisfaction with VMMC, sexual pleasure and function, coital trauma, and RC after VMMC. METHODS: This is a cohort study of circumcised men who presented for follow-up 6 to 24 months after VMMC. Logarithmic binomial regression was performed to explore factors associated with any increase in the number of sex partners after VMMC as a measurement of RC. MAIN OUTCOME MEASURES: (i) Men's satisfaction with their VMMC; (ii) sexual pleasure and function after VMMC; (iii) coital trauma; and (iv) RC. RESULTS: Of 454 circumcised men, 362 (80%) returned for a follow-up visit 6 to 24 months after VMMC. Almost all (98%) were satisfied with the outcome of their VMMC; most (95%) reported that their female partners were satisfied with their circumcision. Two thirds (67%) reported enjoying sex more after VMMC and most were very satisfied or somewhat satisfied (94%) with sexual intercourse after VMMC. Sexual function improved and reported sex-induced coital injuries decreased significantly in most men after VMMC. There was an increase in the proportion of men who reported at least two sexual partners after VMMC compared with baseline. In multivariate analysis, having sex with a woman they met the same day (adjusted relative risk = 1.7, 95% CI = 1.2-2.4) and having at least two sexual partners at baseline (adjusted relative risk = 0.5, 95% CI = 0.3-0.8) were associated with the outcome of any increase in the number of partners after VMMC. CLINICAL IMPLICATIONS: VMMC can be offered to Dominican men for HIV prevention without adversely affecting sexual pleasure or function. The procedure substantially reduces coital trauma. STRENGTHS & LIMITATIONS: This is the first report of long-term overall satisfaction, sexual pleasure/function and sex behaviors in the context of VMMC outside of Africa. Limitations of the study included the reliance on self-reported sex behaviors, the lack of physiologic measurement of penile sensitivity and the lack of follow up data beyond 24 months, which precludes the assessment of longer term RC. CONCLUSION: The study confirmed men's long-term satisfaction with the outcome of their VMMC. VMMC improved sexual pleasure and function for most men and significantly decreased coital injuries. There was mixed evidence of RC. Brito MO, Khosla S, Pananookooln S, et al. Sexual Pleasure and Function, Coital Trauma, and Sex Behaviors After Voluntary Medical Male Circumcision Among Men in the Dominican Republic. J Sex Med 2017;14:526-534.

Relationship Between Eating Behavior and Dietary Intake in Rural Mexican-American Mothers.

We used Spearman's rho correlations and descriptive statistics (α = 0.05) to explore relationships between maternal eating behaviors (disinhibition, cognitive restraint, and susceptibility to hunger) and frequency of consumption of specific food groups (dairy, fruits, vegetables, meats) in a rural Mexican-American population. Analyses were based on the mothers' responses to the Three Factor Eating Questionnaire and Willett's Food Frequency Questionnaire. Cognitive restraint was associated with greater frequency of consumption of vegetables, whereas disinhibition was associated with less frequent consumption of fruit. Susceptibility to hunger may have indirectly influenced the latter by enhancing the level of disinhibition. Mean frequency of consumption of vegetables (1-3 times per month) and fruits (once per week) was less than Healthy People 2020 targets. Additional research is needed to better understand factors contributing to these eating behaviors and patterns. To do so will require developing diet assessment tools that reflect foods typically consumed by this population.

Genetic, psychosocial, and demographic factors associated with social disinhibition in Mexican-origin youth.

INTRODUCTION: The genetic heritability for sensation-seeking tendencies ranges from 40 to 60%. Sensation-seeking behaviors typically manifest during adolescence and are associated with alcohol and cigarette experimentation in adolescents. Social disinhibition is an aspect of sensation-seeking that is closely tied to cigarette and alcohol experimentation. METHODS: We examined the contribution of candidate genes to social disinhibition among 1132 Mexican origin youth in Houston, Texas, adjusting for established demographic and psychosocial risk factors. Saliva samples were obtained at baseline in 2005-06, and social disinhibition and other psychosocial data were obtained in 2008-09. Participants were genotyped for 672 functional and tagging SNPs potentially related to sensation-seeking, risk-taking, smoking, and alcohol use. RESULTS: Six SNPs were significantly associated with social disinhibition scores, after controlling for false discovery and adjusting for population stratification and relevant demographic/psychosocial characteristics. Minor alleles for three of the SNPs (rs1998220 on OPRM1; rs9534511 on HTR2A; and rs4938056 on HTR3B) were associated with increased risk of social disinhibition, while minor alleles for the other three SNPs (rs1003921 on KCNC1; rs16116 downstream of NPY; and rs16870286 on LINC00518) exhibited a protective effect. Age, linguistic acculturation, thrill and adventure-seeking, and drug and alcohol-seeking were all significantly positively associated with increased risk of social disinhibition in a multivariable model (P < 0.001). CONCLUSIONS: These results add to our knowledge of genetic risk factors for social disinhibition. Additional research is needed to verify whether these SNPs are associated with social disinhibition among youth of different ethnicities and nationalities, and to elucidate whether and how these SNPs functionally contribute to social disinhibition.

Obesidad, conducta alimentaria e inseguridad alimentaria en adolescentes de la Ciudad de México / Obesity, eating behavior, and food insecurity among adolescents in Mexico City

Introducción. La inseguridad alimentaria se presenta cuando existe disponibilidad limitada de alimentos nutricionalmente adecuados. La desinhibición alimentaria se refiere al consumo excesivo de alimentos en ausencia de hambre. El objetivo de este trabajo fue analizar la relación de la inseguridad alimentaria, la desinhibición alimentaria, el consumo de alimentos y la obesidad en adolescentes de la Ciudad de México. Métodos. Se realizó una encuesta transversal con una muestra de adolescentes de la Ciudad de México (N=543). La variable independiente fue la existencia de inseguridad alimentaria, la cual fue identificada con el U.S. Household Food-Security/Hunger Survey Module. Las variables dependientes fueron el consumo de alimentos, la desinhibición alimentaria (evaluada mediante una escala) y el estado de nutrición (sobrepeso por IMC para edad, obesidad por pliegues tricipital y subescapular y obesidad abdominal mediante la circunferencia de cintura). Para evaluar la existencia de asociaciones se estimaron modelos de regresión logística. Resultados. Los adolescentes que experimentaron inseguridad alimentaria tuvieron mayor probabilidad de presentar una forma de desinhibición alimentaria (hambre ante estímulos), mayor consumo de alimentos de origen animal y mayor prevalencia de obesidad abdominal. En los modelos de regresión logística se observó que el mayor riesgo de obesidad abdominal observado en los adolescentes con inseguridad alimentaria sin hambre se debía, en parte, a un indicador de desinhibición alimentaria (comer rápido). La inseguridad alimentaria no se relacionó con el sobrepeso y la obesidad. Conclusiones. En esta muestra de adolescentes, la inseguridad alimentaria se relacionó con mayor riesgo de obesidad abdominal. Se requieren más estudios para ahondar y confirmar el posible papel mediador de la desinhibición alimentaria.

Background. Food insecurity is presented when there is a limited availability of food that is nutritionally adequate. Food disinhibition refers to excessive eating in the absence of hunger. We analyzed the relationship among food insecurity, dietary disinhibition, food consumption and obesity in adolescents of Mexico City. Methods. A cross-sectional survey was carried out with a convenience sample (n = 543) of adolescents in Mexico City. Food insecurity was the independent variable and was assessed through the U.S. Household Food-Security/Hunger Survey Module. Food consumption, dietary disinhibition (assessed through an ad hoc inventory), and nutritional status (overweight using body mass index, obesity through triceps and subscapular skinfolds, abdominal obesity by waist circumference) were the dependent variables. Logistic regression models were estimated to assess the existence of associations. Results. Adolescents who experienced food insecurity had a higher probability of reporting an indicator of dietary disinhibition (hunger due to stimuli), higher intake of animal food and higher rate of abdominal obesity. In the logistic regression models it was observed that the higher probability of abdominal obesity among adolescents with food insecurity without hunger was partially due to another indicator of dietary disinhibition (fast eating). Conclusions. In this sample of adolescents, food insecurity was related to higher probability of abdominal obesity. More studies are necessary to explore this problem in depth and confirm the possible mediating role ofdietary disinhibition.