Stress adaptation disorders play a role in rat gestational diabetes with oxidative stress and glucose transporter-4 expression.

Stress adaptation disorder exists in gestational diabetes mellitus (GDM) women, this study was to investigate the impact of stress adaptation disorder on glucose disposal and skeletal muscle glucose transporter4 (GLUT4) expression in GDM rat model. Rats were assigned randomly to Normal control (NC) group and GDM group. We analyzed the levels of corticosterone, epinephrine (E), norepinephrine (NE), malondialdehyde (MDA) and superoxide dismutase (SOD), interleukin-6 (IL-6) and expression of GLUT4 were also detected. Homeostasis model assessment (HOMA-IR) was used to evaluate insulin resistance. Compared with NC group, E, NE and Corticosterone were increased significantly, SOD and MDA were higher and GLUT4 expression was significantly lower in GDM rats. Corticosterone was positively related to MDA, MDA was positively and SOD was negatively related to HOMA-IR in both groups, IL-6 showed significant positive correlations with HOMA-IR. NE and Corticosterone were negative related to GLUT4 in GDM group. Stress hormones (E, NE and Corticosterone), MDA and IL-6 were the risk factors of GDM, SOD was the protective factor of GDM. Changes of stress hormones indicate that stress adaptation disorder exists in GDM rats. Stress adaptation disorder increase oxidative stress injury and inflammation, decrease GLUT4 and lead to incline of glucose uptake, result in hyperglycemia. Gaining an insight into correlations of these changes may be beneficial to maternal and child health and is important for the prevention of glycemia-related diseases.

Tcf4 transgenic female mice display delayed adaptation in an auditory latent inhibition paradigm.

Schizophrenia (SZ) is a severe mental disorder affecting about 1 % of the human population. Patients show severe deficits in cognitive processing often characterized by an improper filtering of environmental stimuli. Independent genome-wide association studies confirmed a number of risk variants for SZ including several associated with the gene encoding the transcription factor 4 (TCF4). TCF4 is widely expressed in the central nervous system of mice and humans and seems to be important for brain development. Transgenic mice overexpressing murine Tcf4 (Tcf4tg) in the adult brain display cognitive impairments and sensorimotor gating disturbances. To address the question of whether increased Tcf4 gene dosage may affect cognitive flexibility in an auditory associative task, we tested latent inhibition (LI) in female Tcf4tg mice. LI is a widely accepted translational endophenotype of SZ and results from a maladaptive delay in switching a response to a previously unconditioned stimulus when this becomes conditioned. Using an Audiobox, we pre-exposed Tcf4tg mice and their wild-type littermates to either a 3- or a 12-kHz tone before conditioning them to a 12-kHz tone. Tcf4tg animals pre-exposed to a 12-kHz tone showed significantly delayed conditioning when the previously unconditioned tone became associated with an air puff. These results support findings that associate TCF4 dysfunction with cognitive inflexibility and improper filtering of sensory stimuli observed in SZ patients.

Replicated linear association between DUF1220 copy number and severity of social impairment in autism.

Sequences encoding DUF1220 protein domains exhibit an exceptional human-specific increase in copy number and have been associated with several phenotypes related to brain size. Autism is a highly heritable and heterogeneous condition characterized behaviorally by social and communicative impairments, and increased repetitive and stereotyped behavior. Given the accelerated brain growth pattern observed in many individuals with autism, and the association between DUF1220 subtype CON1 copy number and brain size, we previously investigated associations between CON1 copy number and autism-related symptoms. We determined that CON1 copy number increase is associated with increasing severity of all three behavioral features of autism. The present study sought to replicate these findings in an independent population (N = 166). Our results demonstrate a replication of the linear relationship between CON1 copy number and the severity of social impairment in individuals with autism as measured by Autism Diagnostic Interview-Revised Social Diagnostic Score, such that with each additional copy of CON1 Social Diagnostic Score increased 0.24 points (SE = 0.11, p = 0.036). We also identified an analogous trend between CON1 copy number and Communicative Diagnostic Score, but did not replicate the relationship between CON1 copy number and Repetitive Behavior Diagnostic Score. Interestingly, these associations appear to be most pronounced in multiplex children. These results, representing the first replication of a gene dosage relationship with the severity of a primary symptom of autism, lend further support to the possibility that the same protein domain family implicated in the evolutionary expansion of the human brain may also be involved in autism severity.

Heritability and genome-wide analyses of problematic peer relationships during childhood and adolescence.

Peer behaviour plays an important role in the development of social adjustment, though little is known about its genetic architecture. We conducted a twin study combined with a genome-wide complex trait analysis (GCTA) and a genome-wide screen to characterise genetic influences on problematic peer behaviour during childhood and adolescence. This included a series of longitudinal measures (parent-reported Strengths-and-Difficulties Questionnaire) from a UK population-based birth-cohort (ALSPAC, 4-17 years), and a UK twin sample (TEDS, 4-11 years). Longitudinal twin analysis (TEDS; N ≤ 7,366 twin pairs) showed that peer problems in childhood are heritable (4-11 years, 0.60 < twin-h(2) ≤ 0.71) but genetically heterogeneous from age to age (4-11 years, twin-r(g) = 0.30). GCTA (ALSPAC: N ≤ 5,608, TEDS: N ≤ 2,691) provided furthermore little support for the contribution of measured common genetic variants during childhood (4-12 years, 0.02 < GCTA-h(2)(Meta) ≤ 0.11) though these influences become stronger in adolescence (13-17 years, 0.14 < GCTA-h (2)(ALSPAC) ≤ 0.27). A subsequent cross-sectional genome-wide screen in ALSPAC (N ≤ 6,000) focussed on peer problems with the highest GCTA-heritability (10, 13 and 17 years, 0.0002 < GCTA-P ≤ 0.03). Single variant signals (P ≤ 10(-5)) were followed up in TEDS (N ≤ 2835, 9 and 11 years) and, in search for autism quantitative trait loci, explored within two autism samples (AGRE: N Pedigrees = 793; ACC: N Cases = 1,453/N Controls = 7,070). There was, however, no evidence for association in TEDS and little evidence for an overlap with the autistic continuum. In summary, our findings suggest that problematic peer relationships are heritable but genetically complex and heterogeneous from age to age, with an increase in common measurable genetic variation during adolescence.

When do adaptive developmental mechanisms yield maladaptive outcomes?

This article discusses 3 ways in which adaptive developmental mechanisms may produce maladaptive outcomes. First, natural selection may favor risky strategies that enhance fitness on average but which have detrimental consequences for a subset of individuals. Second, mismatch may result when organisms experience environmental change during ontogeny, for instance, because they move from one environment to another. Third, organisms may learn about their environment in order to develop an appropriate phenotype; when cues indicate the environmental state probabilistically, as opposed to deterministically, sampling processes may produce mismatch. For each source of maladaptation, we present a selection of the relevant empirical research and illustrate how models from evolutionary biology can be used to make predictions about maladaptation. We also discuss what data can be collected to test these models in humans. Our goal is to show that evolutionary approaches not only yield insights into adaptive outcomes but can also illuminate the conditions leading to maladaptation. This perspective provides additional nuance to the dialectic between the developmental psychopathology model and evolutionary developmental psychology.

[Stress among public safety and security forces. Genetic and physiopathology]. / Lo stress nelle Forze dell'Ordine. Genetica e fisiopatologia.

Hans Selye used the word "stress" exactly 68 years ago, in hi paper "A syndrome produced by diverse nocuous agents", published in Nature. The syndrome termed as "stress" induces hormonal autonomic responses and, over time, these hormonal changes can lead to ulcers, high blood pressure, arteriosclercosis, arthritis, kidney disease and allergic reactions. The aim of this study is to analyse the General Adaptation Syndrome (GAS), the response of the body to external stimuli, and the current knowledge about biochemistry, physiology and stress genetics. The police forces work is a complex profession, particularly liable to stress disease, as the adverse occurrences of the social life add to the stressing events specifics of callings regarding public order keeping. The results of the present study suggests the advisability of instituting a preventive monitoring for these workers.