Disentangling nature from nurture in examining the interplay between parent-child relationships, ADHD, and early academic attainment.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is highly heritable and is associated with lower educational attainment. ADHD is linked to family adversity, including hostile parenting. Questions remain regarding the role of genetic and environmental factors underlying processes through which ADHD symptoms develop and influence academic attainment. METHOD: This study employed a parent-offspring adoption design (N = 345) to examine the interplay between genetic susceptibility to child attention problems (birth mother ADHD symptoms) and adoptive parent (mother and father) hostility on child lower academic outcomes, via child ADHD symptoms. Questionnaires assessed birth mother ADHD symptoms, adoptive parent (mother and father) hostility to child, early child impulsivity/activation, and child ADHD symptoms. The Woodcock-Johnson test was used to examine child reading and math aptitude. RESULTS: Building on a previous study (Harold et al., 2013, Journal of Child Psychology and Psychiatry, 54(10), 1038-1046), heritable influences were found: birth mother ADHD symptoms predicted child impulsivity/activation. In turn, child impulsivity/activation (4.5 years) evoked maternal and paternal hostility, which was associated with children's ADHD continuity (6 years). Both maternal and paternal hostility (4.5 years) contributed to impairments in math but not reading (7 years), via impacts on ADHD symptoms (6 years). CONCLUSION: Findings highlight the importance of early child behavior dysregulation evoking parent hostility in both mothers and fathers, with maternal and paternal hostility contributing to the continuation of ADHD symptoms and lower levels of later math ability. Early interventions may be important for the promotion of child math skills in those with ADHD symptoms, especially where children have high levels of early behavior dysregulation.

Shared genetic influences do not explain the association between parent-offspring relationship quality and offspring internalizing problems: results from a Children-of-Twins study.

BACKGROUND: Associations between parenting and child outcomes are often interpreted as reflecting causal, social influences. However, such associations may be confounded by genes common to children and their biological parents. To the extent that these shared genes influence behaviours in both generations, a passive genetic mechanism may explain links between them. Here we aim to quantify the relative importance of passive genetic v. social mechanisms in the intergenerational association between parent-offspring relationship quality and offspring internalizing problems in adolescence. METHODS: We used a Children-of-Twins (CoT) design with data from the parent-based Twin and Offspring Study of Sweden (TOSS) sample [909 adult twin pairs and their offspring; offspring mean age 15.75 (2.42) years], and the child-based Swedish Twin Study of CHild and Adolescent Development (TCHAD) sample [1120 adolescent twin pairs; mean age 13.67 (0.47) years]. A composite of parent-report measures (closeness, conflict, disagreements, expressions of affection) indexed parent-offspring relationship quality in TOSS, and offspring self-reported internalizing symptoms were assessed using the Child Behavior Checklist (CBCL) in both samples. RESULTS: A social transmission mechanism explained the intergenerational association [r = 0.21 (0.16-0.25)] in our best-fitting model. A passive genetic transmission pathway was not found to be significant, indicating that parental genetic influences on parent-offspring relationship quality and offspring genetic influences on their internalizing problems were non-overlapping. CONCLUSION: These results indicate that this intergenerational association is a product of social interactions between children and parents, within which bidirectional effects are highly plausible. Results from genetically informative studies of parenting-related effects should be used to help refine early parenting interventions aimed at reducing risk for psychopathology.

Keeping active endogenous retroviral-like elements in check: the epigenetic perspective.

Endogenous retrovirus-like elements, or ERVs, are an abundant component of all eukaryotic genomes. Their transcriptional and retrotranspositional activities have great potential for deleterious effects on gene expression. Consequences of such activity may include germline mutagenesis and cancerous transformation. As a result, mammalian genomes have evolved means of counteracting ERV transcription and mobilization. In this review, we discuss epigenetic mechanisms of ERV and LTR retrotransposon control during mouse development, focusing on involvement of DNA methylation, histone modifications, small RNAs and their interaction with one another. We also address relevance of research performed in the mouse system to human and challenges associated with studying repetitive families. (Part of a multi-author review).

Adolescent chronic variable social stress influences exploratory behavior and nicotine responses in male, but not female, BALB/cJ mice.

Anxiety disorders and nicotine use are significant contributors to global morbidity and mortality as independent and comorbid diseases. Early-life stress, potentially via stress-induced hypothalamic-pituitary-adrenal axis (HPA) dysregulation, can exacerbate both. However, little is known about the factors that predispose individuals to the development of both anxiety disorders and nicotine use. Here, we examined the relationship between anxiety-like behaviors and nicotine responses following adolescent stress. Adolescent male and female BALB/cJ mice were exposed to either chronic variable social stress (CVSS) or control conditions. CVSS consisted of repeated cycles of social isolation and social reorganization. In adulthood, anxiety-like behavior and social avoidance were measured using the elevated plus-maze (EPM) and social approach-avoidance test, respectively. Nicotine responses were assessed with acute effects on body temperature, corticosterone production, locomotor activity, and voluntary oral nicotine consumption. Adolescent stress had sex-dependent effects on nicotine responses and exploratory behavior, but did not affect anxiety-like behavior or social avoidance in males or females. Adult CVSS males exhibited less exploratory behavior, as indicated by reduced exploratory locomotion in the EPM and social approach-avoidance test, compared to controls. Adolescent stress did not affect nicotine-induced hypothermia in either sex, but CVSS males exhibited augmented nicotine-induced locomotion during late adolescence and voluntarily consumed less nicotine during adulthood. Stress effects on male nicotine-induced locomotion were associated with individual differences in exploratory locomotion in the EPM and social approach-avoidance test. Relative to controls, adult CVSS males and females also exhibited reduced corticosterone levels at baseline and adult male CVSS mice exhibited increased corticosterone levels following an acute nicotine injection. Results suggest that the altered nicotine responses observed in CVSS males may be associated with HPA dysregulation. Taken together, adolescent social stress influences later-life nicotine responses and exploratory behavior. However, there is little evidence of an association between nicotine responses and prototypical anxiety-like behavior or social avoidance in BALB/cJ mice.

Adolescent social stress increases anxiety-like behavior and ethanol consumption in adult male and female C57BL/6J mice.

Exposure to social stress is an important risk factor for comorbid affective disorders and problem alcohol use. To better understand mechanisms involved in social stress-induced affective disorder and alcohol use co-morbidity, we studied the effects of adolescent social stress on anxiety- and depression-like behaviors and binge-like ethanol consumption. Male and female C57BL/6J mice were exposed to chronic variable social stress (CVSS) or control conditions throughout adolescence (postnatal days, PND, 25-59) and then tested for anxiety-like behavior in the elevated plus maze and a novel open field environment, or depression-like behavior using the forced swim test on PND 64-66. Mice were then tested for binge-like ethanol consumption using the Drinking-in-the-Dark model. Male and female mice exposed to adolescent CVSS had increased adult anxiety-like behavior and increased locomotor adaptation to a novel environment. Further, CVSS mice consumed significantly more ethanol, but not saccharin, than controls. Despite group differences in both anxiety-like behavior and ethanol consumption, there was no relationship between these outcomes within individual mice. These data suggest that exposure to adolescent social stress is an important risk factor for later alcohol use and affective behaviors, but that social stress does not necessarily dictate co-morbidity of these outcomes.

Effects of social crowding on emotionality and expression of hippocampal nociceptin/orphanin FQ system transcripts in mice.

The novel nociceptin/orphanin FQ (N/OFQ) system was proposed to be an important component of neural circuits involved in stress-coping behaviour and fear. This study investigated whether variations between the mouse strains in vulnerability to social crowding stress might be linked to different regulation of N/OFQ system transcripts in mice. Three weeks old C57BL/6J (B6), BALB/cByJ (CBy) and 129S2/SvPas (129S2) male mice were housed individually or in crowded (7/cage) conditions and then tested as adults in a battery of anxiety tests (open field, elevated plus-maze and acoustic startle reflex tests). Both 129S2 and B6 mice displayed increased signs of anxiety under crowded housing, while CBy mice tended to show the opposite profile. Analysis of gene expression revealed a 10-fold increase of nociceptin precursor and 4-fold increase of the NOP receptor mRNAs contents in the hippocampus of CBy mice kept in crowded conditions compared to those housed individually. In B6 mice, mRNA level of the peptide precursor remained unchanged, while that of the receptor was increased by 2-fold under crowding compared to individual housing. No significant changes were detected in 129S2 mice. These findings show that social housing may be important environmental stress factor in mice depending on the strain. The possible involvement of central nociceptin mechanisms in behavioural resilience to social crowding stress is discussed.

Mu and delta opioid receptor knockout mice show increased colonic sensitivity.

BACKGROUND: Opiates act through opioid receptors to diminish pain. Here, we investigated whether mu (MOR) and delta (DOR) receptor endogenous activity assessed in the whole mouse body or in particular at peripheral receptors on primary nociceptive neurons, control colonic pain. METHODS: We compared global MOR and DOR receptor knockout (KO) mice, mice with a conditional deletion of MOR and DOR in Nav1.8-positive nociceptive primary afferent neurons (cKO), and control floxed mice of both genders for visceral sensitivity. Visceromotor responses to colorectal distension (CRD) and macroscopic colon scores were recorded on naïve mice and mice with acute colitis induced by 3% dextran sodium sulphate (DSS) for 5 days. Transcript expression for opioid genes and cytokines was measured by quantitative RT-PCR. RESULTS: Naïve MOR and DOR global KO mice show increased visceral sensitivity that was not observed in cKO mice. MOR and preproenkephalin (Penk) were the most expressed opioid genes in colon. MOR KO mice had augmented kappa opioid receptor and Tumour-Necrosis-Factor-α and diminished Penk transcript levels while DOR, preprodynorphin and Interleukin-1ß were unchanged. Global MOR KO females had a thicker colon than floxed females. No alteration was detected in DOR mutant animals. A 5-day DSS treatment led to comparable hypersensitivity in the different mouse lines. CONCLUSION: Our results suggest that mu and delta opioid receptor global endogenous activity but not activity at the peripheral Nav1.8 neurons contribute to visceral sensitivity in naïve mice, and that endogenous MOR and DOR tones were insufficient to elicit analgesia after 5-day DSS-induced colitis. SIGNIFICANCE: Knockout mice for mu and delta opioid receptor have augmented colon sensitivity in the CRD assay. It shows endogenous mu and delta opioid analgesia that may be explored as potential targets for alleviating chronic intestinal pain.

Auditory and visual prepulse inhibition in mice: parametric analysis and strain comparisons.

Prepulse inhibition (PPI) is a multimodal phenomenon where the prepulse and the startling stimulus can be presented in either the same or the different sensory modalities. The aim of the present study was to characterize intramodal and cross-modal PPI in mice. We first examined the effects of varying prepulse intensity and prepulse duration on auditory and visual PPI in three inbred mouse strains C57BL/6J, 129S2 and BALB/cByJ mice. Increasing the intensity (5-15 dB above the background) and the duration (1-25 milliseconds) of the acoustic prepulse increased auditory PPI, and maximum level of inhibition was reached with each prepulse intensity at specific prepulse duration (between 5 and 15 milliseconds). Varying the intensity (30-300 lux) and the duration (1-25 milliseconds) of the light flashes had similar impact on visual PPI level (optimal durations between 1 and 10 milliseconds). There were also marked strain differences in PPI performances, with 129S2 and BALB/cByJ mice displaying the highest and the lowest scores of auditory PPI, respectively. In contrast, opposite strain ranking was obtained for visual PPI. The temporal expression of PPI was then studied in the same mouse strains using a wide range of interstimulus intervals (2-2000 milliseconds between the prepulse offset and the pulse onset). The time-course of the auditory and the visual PPI were relatively comparable (bell-shaped curve) with optimal lead-times between 10 and 100 milliseconds, but the shape of the temporal function varied between the mouse strains depending on the prepulse modality. These findings demonstrate that PPI has many physiological and genetic determinants that vary greatly across temporal and intensity domain, as well as stimulus modality.

Early inherited risk for anxiety moderates the association between fathers' child-centered parenting and early social inhibition.

Studies of the role of the early environment in shaping children's risk for anxiety problems have produced mixed results. It is possible that inconsistencies in previous findings result from a lack of consideration of a putative role for inherited influences moderators on the impact of early experiences. Early inherited influences not only contribute to vulnerabilities for anxiety problems throughout the lifespan, but can also modulate the ways that the early environment impacts child outcomes. In the current study, we tested the effects of child-centered parenting behaviors on putative anxiety risk in young children who differed in levels of inherited vulnerability. We tested this using a parent-offspring adoption design and a sample in which risk for anxiety problems and parenting behaviors were assessed in both mothers and fathers. Inherited influences on anxiety problems were assessed as anxiety symptoms in biological parents. Child-centered parenting was observed in adoptive mothers and fathers when children were 9 months old. Social inhibition, an early temperament marker of anxiety risk, was observed at child ages 9 and 18 months. Inherited influences on anxiety problems moderated the link between paternal child-centered parenting during infancy and social inhibition in toddlerhood. For children whose birth parents reported high levels of anxiety symptoms, greater child-centered parenting in adoptive fathers was related to greater social inhibition 9 months later. For children whose birth parents reported low levels of anxiety symptoms, greater child-centered parenting in adoptive fathers was related to less social inhibition across the same period.

Evidence for the involvement of (Cu-ATP)2- in the inhibition of human erythrocyte (Ca2+ + Mg2+)-ATPase by copper.

The effects of copper on the activity of erythrocyte (Ca2+ + Mg2+)-ATPase have been tested on membranes stripped of endogenous calmodulin or recombined with purified calmodulin. The interactions of copper with Ca2+, calmodulin and (Mg-ATP)2- were determined by kinetic studies. The most striking result is the potent competitive inhibition exerted by (Cu-ATP)2- against (Mg-ATP)2- (Ki = 2.8 microM), while free copper gives no characteristic inhibition. Our results also demonstrate that copper does not compete with calcium either on the enzyme or on calmodulin. The fixation of calmodulin on the enzyme is not altered in the presence of copper as shown by the fact that the dissociation constant remains unaffected. It may be speculated that (Cu-ATP)2- is the active form of copper, which could plausibly be at the origin of some of the pathological features of erythrocytes observed in conditions associated with excess copper.

Communicative and other cognitive characteristics of bottlenose dolphins.

Scientists have tried to capture the rich cognitive life of dolphins through field and laboratory studies of their brain anatomy, social lives, communication and perceptual abilities. Encopheliration quotient data sugest a level of intelligence or cognitive processing in the large-brained dolphin that is closer to the human range than are our nearest primate relatives. Field studies indicate a fission-fusion type of social structure, showing social complexity rivaling that found in chimpanzee societies. Notably, cetaceans are the only mammals other than humans that clearly demonstrate vocal learning and parallels in stages of vocal learning have been reported for humans, birds and dolphins. The dolphin's vocal plasticity from infancy through adulthood, in what is probably an 'open' communication system, is likely to be related to their fission-fusion social structure and, specifically, to the fluidity of their short-term associations. However, conflicting evidence exists on the composition and organization of the dolphins whistle repertoire. In general, the level of dolphin performance on complex auditory learning and memory tasks has been compared with that of primates on similar visual tasks; however, dolphins have also demonstrated sophistrcated visual processing abilities. Laboratory studies have also provided suggestive, evidence of minor self-recognition in the dolphin, an ability previously thought to be exclusive to humans humans and apes.

Personal needs, values, and technical preferences in the psychiatric hospital. A replicated study.

This study tests the hypothesis that staff and patients try to make their involvement in psychiatric hospitals personally gratifying by fashioning preferences for those specific therapeutic techniques that match or satisfy their personal values and needs. Results of questionnaire data, collected from a total of 397 staff and patients at two psychiatric hospitals at two different times, show two distinctly different combinations of needs, values, and technical preferences. In one, a preference for psychotherapy and somatotherapy correlates highly with a preference or need for structured, cautious, and rule-governed relationships. Underlying these preferences seems to be a common dimension emphasizing a technical attitude towards the psychiatric hospital with true healing provided only by a professional, scientific elite. A second combination shows high correlations between a preference for social therapy and a need for unstructured, open, and trusting relationships. A common dimension underlying these preferences seems to be a moral attitude that stresses the healing power of all human relationships. Treating institutions may be categorized according to whether the technical or moral attitude predominates.

The family meets the hospital. Clinical presentation of a laboratory-based family typology.

This report portrays the distinctive clinical features of four groups of families with psychiatrically hospitalized adolescents. The classification of families into the four groups was made by objective measures of their performance in a standard problem-solving task. Clinicians, blind to this classification, synthesized and described their clinical impressions of these families. There were clear differences among the four groups in family dynamics and in the adolescents' ward behavior. Furthermore, families who experienced themselves as an integrated group became more effectively engaged in a family-oriented inpatient treatment program. Families with noticeable alienation between members did not become effectively engaged in the family-oriented program and may be better candidates for other approaches to inpatient care.

Family process, chronic illness, and death. On the weakness of strong bonds.

Newer techniques for directly measuring social interaction in families permit more informative studies of the family's role in the course of chronic illness. We used laboratory techniques for measuring problem-solving strategies in family groups, supplemented by measures of the family's intelligence and accomplishments as well as its intactness, the latter indicated by measures of duration of marriage and the survival of grandparents. We studied 23 families, each containing an adult patient with end-stage renal disease who was being treated by center-based hemodialysis. In sharp contrast to expectations based on previous data, high scores on the problem-solving variables, as well as the measures of accomplishment and intactness, predicted early death rather than survival. Equally surprising was the finding that noncompliance accounted for most of the association between the family variables and survival.

The family meets the hospital. Predicting the family's perception of the treatment program from its problem solving style.

A family's perception of a treatment program may determine whether ir becomes productively engaged or destructively withdrawn. A theory of family types, in conjunction with a standardized laboratory problem solving procedure, was used to predict the nature of families' shared perceptions of a psychiatric ward. The individual and shared perceptions of thirty families were determined by means of a specially designed Q-sort. Two dimensions of problem solving behavior successfully predicted significant differences between families in their shared perceptions. Configuration, or the family's capacity to derive effective solutions in the laboratory, predicted the subtlety to their perception of the ward. Coordination, or the capacity of family members to dovetail their problem solving effort with one another, predicted the family's sense of comfort and engagement in the ward setting.

The family meets the hospital. A laboratory forecast of the encounter.

Families, like persons, can be considered as unitary cases. Like persons, families can be classified before treatment begins in an effort to predict their responses and thus, to formulate the best treatment program. Although many classification schemes have been proposed in the past, evidence is presented on the first successful use to our knowledge of a family classification scheme to predict a family's response to a family-oriented treatment program. The classification scheme grouped families according to their typical style of adapting to new situations. A family's classification was based on its performance in a standard laboratory problem-solving situation in which its interaction patterns could be measured precisely and objectively. This approach to classification successfully predicted the family's engagement in a family-oriented, inpatient treatment program for adolescents.

Family psychoeducation, social skills training, and maintenance chemotherapy in the aftercare treatment of schizophrenia. II. Two-year effects of a controlled study on relapse and adjustment. Environmental-Personal Indicators in the Course of Schizophrenia (EPICS) Research Group.

We demonstrated earlier that a novel family psychoeducational approach and an individual social skills training approach designed for patients living in high-expressed emotion households each reduced schizophrenic relapse by one-half when compared with medication controls in the 1st year after hospital discharge. The combination of treatments resulted in no relapse. Results have now been obtained after 2 years of continuous treatment. By 24 months, a persistent and significant effect of family intervention on forestalling relapse was observed, but the effect of social skills training was lost late in the 2nd year. There was no additive effect on relapse that accrued to the combination of treatments. Beyond 2 years, however, the effect of family intervention was likely compromised as well. Treatment effects on the adjustment of survivors were circumscribed, due, in part, to study design characteristics. Effects generally favored the social skills-alone condition at 1 year and the family condition or combined family/social skills condition at 2 years.

Family psychoeducation, social skills training, and maintenance chemotherapy in the aftercare treatment of schizophrenia. I. One-year effects of a controlled study on relapse and expressed emotion.

Relapse rates averaging 41% in the first year after discharge among schizophrenic patients receiving maintenance neuroleptic treatment led to the development of two disorder-relevant treatments: a patient-centered behavioral treatment and a psychoeducational family treatment. Following hospital admission, 103 patients residing in high expressed emotion (EE) households who met Research Diagnostic Criteria for schizophrenia or schizoaffective disorder were randomly assigned to a two-year aftercare study of family treatment and medication, social skills training and medication, their combination, or a drug-treated condition. First-year relapse rates among those exposed to treatment demonstrate a main effect for family treatment (19%), a main effect for social skills training (20%), and an additive effect for the combined conditions (0%) relative to controls (41%). Effects are explained, in part, by the absence of relapse in any household that changed from high to low EE. Only the combination of treatment sustains a remission in households that remain high in EE. Continuing study, however, suggests a delay of relapse rather than prevention.

Genetic questions for environmental studies. Differential parenting and psychopathology in adolescence.

BACKGROUND: Recent genetic evidence suggests that the most important environmental influences on normal and pathologic development are those that are not shared by siblings in the same family. We sought to determine the relationship between differences in parenting styles and depressive symptoms and antisocial behavior in adolescence, and to compare the influence of these nonshared experiences with genetic influences. METHODS: We studied 708 families with at least two same-sexed adolescent siblings who were monozygotic twins (93 families), dizygotic twins (99 families), ordinary siblings (95 families), full siblings in step families (181 families), half siblings in step families (110 families), and genetically unrelated siblings in step families (130 families). Data on parenting style were collected by questionnaire and by video recording of interaction between parents and children. RESULTS: Almost 60% of variance in adolescent antisocial behavior and 37% of variance in depressive symptoms could be accounted for by conflictual and negative parental behavior directed specifically at the adolescent. In contrast, when a parent directed harsh, aggressive, explosive, and inconsistent parenting toward the sibling, we found less psychopathologic outcome in the adolescent. CONCLUSIONS: Parenting behavior directed specifically at each child in the family is a major correlate of symptoms in adolescents. Furthermore, harsh parental behavior directed at a sibling may have protective effects for adolescents, a phenomenon we call the "siblin barricade."

Role of adrenal steroidogenesis in etiology of hypertension in the spontaneously hypertensive rat.

We measured peripheral adrenal steroid levels in spontaneously hypertensive rats (SHR), killed by nitrogen suffocation, at different ages during the development of hypertension. SHR became hypertensive by 8 weeks of age. Circulating plasma aldosterone (Aldo) levels of SHR gradually declined with age compared to their male Wistar-Kyoto (WKY) normotensive controls. On the other hand, corticosterone (B) concentrations rose relatively as the rats grew older, however, they were significantly lower in SHR at 16 weeks of age. Deoxycorticosterone (DOC) levels were significantly lower at 8 weeks and 18-hydroxy-11-deoxycorticosterone (18-OH-DOC) were lower at 16 weeks of age. Steroid ratios at age 4 weeks showed significantly higher B to 18-OH-DOC and lower B to DOC, 18-OH-DOC to Aldo, and 18-OH-DOC to DOC values in SHR. Furthermore, the B to 18-OH-DOC ratio remained significantly higher at 12 weeks and the B to DOC ratio remained lower at 16 weeks. These data imply the possibility of the secretion of an unknown steroid(s) and the existence of another, fourth pathway of Aldo biosynthesis in young SHR. Thus, major alterations of adrenal steroidogenesis exist in young SHR which may be causative in the development of hypertension. After the onset of hypertension, steroidogenesis tends to return to normal, by which time, however, SHR may have developed metacorticoid hypertension.