Effects of hippotherapy on brain function,BDNF level,and physical fitness in children with ADHD

[Purpose]

The purpose of this study was to examine the effects of hippotherapy on brain function and levels of blood-derived neurotrophic factor (BDNF) in children with attention deficit and/or hyperactivity disorder (ADHD).

[Methods]

The hippotherapy group (HRG) included twenty children with ADHD and the control group (CG) included 19 children. All participants’ physical fitness, fMRI brain scans, and blood BDNF levels were measured at baseline and after 32 weeks of participating in hippotherapy.

[Results]

After 32 weeks of participating in hippotherapy, the body fat of the HRG was significantly decreased (-1.12 ± 4.20%) and the body fat of the CG was increased (2.38 ± 6.35%) (p=0.049). There was no significant difference of physical fitness in both groups (p>0.05). Although there was a higher decrease in the activated insular area in the HRG (-1.59 ± 0.99) than in the CG (-1.14 ± 1.41), there was no significant difference between the two groups (p>0.05) Also, there was a higher increase in the activated cerebellum area in the HRG (1.97 ± 1.45) than in the CG (1.92 ± 1.81). However, there was no significant difference between the two groups (p>0.05). BDNF levels showed an increased tendency in the HRG (166.29 ± 277.52pg) compared to the CG (21.13 ± 686.33pg); otherwise, there was not any significant difference in these blood levels between the two groups (p>0.05). It can be assumed that big individual differences in the level of ADHD in the study participants might not cause any significant results, although there might be positive changes in the brain function of children with ADHD.

[Conclusion]

Therefore, this study suggests that hippotherapy training would need to be modified and developed to increase the efficacy of hippotherapy in children with ADHD.     

Physiological reactivity to infant crying: a behavioral genetic study

In this study, we examined adults' cardiac reactivity to repeated infant cry sounds in a genetically informative design. Three episodes of cry stimuli were presented to a sample of 184 adult twin pairs. Cardiac reactivity increased with each cry episode, indicating that subjects were increasingly sensitized to repeated infant distress signals. Non‐parents showed more cardiac reactivity than parents, and males displayed a larger increase in heart rate (HR) in response to repeated cry sounds than females. Multivariate genetic modeling showed that the genetic component of adults' HR while listening to infant crying was substantial. Genetic factors explained 37–51% of the variance in HR and similar genes influenced HR at baseline and HR reactivity to infant crying. The remaining variance in HR across the cry paradigm was accounted for by unique environmental influences (including measurement error). These results point to genetic and experiential effects on HR reactivity to infant crying that may contribute to the explanation of variance in sensitive and harsh parenting.     

Contribution of LPHN3 to the genetic susceptibility to ADHD in adulthood: a replication study

Attention-deficit/hyperactivity disorder (ADHD) is a common and highly heritable developmental disorder characterized by a persistent impairing pattern of inattention and/or hyperactivity-impulsivity. Using families from a genetic isolate, the Paisa population from Colombia, and five independent datasets from four different populations (United States, Germany, Norway and Spain), a highly consistent association was recently reported between ADHD and the latrophilin 3 (LPHN3) gene, a brain-specific member of the LPHN subfamily of G-protein-coupled receptors that is expressed in ADHD-related regions, such as amygdala, caudate nucleus, cerebellum and cerebral cortex. To replicate the association between LPHN3 and ADHD in adults, we undertook a case-control association study in 334 adult patients with ADHD and 334 controls with 43 single nucleotide polymorphisms (SNPs) covering the LPNH3 gene. Single- and multiple-marker analyses showed additional evidence of association between LPHN3 and combined type ADHD in adulthood [P = 0.0019; df = 1; odds ratio (OR) = 1.82 (1.25-2.70) and P = 5.1e-05; df = 1; OR = 2.25 (1.52-3.34), respectively]. These results further support the LPHN3 contribution to combined type ADHD, and specifically to the persistent form of the disorder, and point at this new neuronal pathway as a common susceptibility factor for ADHD throughout the lifespan.     

Latent activity rhythm disturbance sub-groups and longitudinal change in depression symptoms among older men

Activity rhythm disturbances and depression often co-occur among older adults. However, little is known about how activity rhythm disturbances themselves co-occur, or how disturbances to multiple aspects of the activity rhythm relate to depression over time. In this study, we performed a Latent Class Analysis to derive sub-groups of older men [total n?=?2933, mean age?=?76.28, standard deviation (SD)?=?5.48] who shared similar patterns of activity rhythm disturbances (defined as extreme values of modeled activity rhythm parameters). We found eight sub-groups with distinct combinations of activity rhythm disturbances: one had all normative activity rhythm parameters (32.09%), one had only lower activity (10.06%), three had earlier activity (totaling 26.96%) and three had later activity (totaling 30.89%). Groups with similar timing were distinguished depending on whether the relative length of the active period was shorter and/or if the activity rhythm had lesser amplitude/robustness. We next examined whether the derived activity rhythm sub-groups were associated with different rates of change in depression symptom levels over an average of 5.5 (0.52 SD) follow-up years. The sub-group with lower activity only had faster increases in depressive symptoms over time (compared with the group with normative rhythm parameters), but this association was accounted for by adjustments for concurrently assessed health status covariates. Independent of these covariates, we found that four activity rhythm disturbance sub-groups experienced faster depressive symptom increases (compared with the normative sub-group): These included all three sub-groups that had later activity timing and one sub-group that had earlier activity timing plus a shorter active period and a dampened rhythm. Low activity rhythm height/robustness with normal timing therefore may mark depression risk that is attributable to co-occurring disease processes; in contrast, having late or combined early/compressed/dampened activity rhythms may independently contribute to depression symptom development. Our findings suggest that activity rhythm-related depression risk is heterogeneous, and may be detected when multiple aspects of rhythm timing are delayed or when early timing is accompanied by compressed/dampened activity rhythms. Future studies should consider how distinct combinations of altered activity rhythm timing and height/robustness develop and conjointly determine health risks. Further research is also needed to determine whether/how activity rhythms can be modified to improve depression outcomes.     

Home-cage activity in heterogeneous stock (HS) mice as a model of baseline activity

Behavioral genetic work in humans indicates that clinical hyperactivity is best viewed as the extreme end of activity levels in the population. However, current animal models of hyperactivity are not studied as quantitative traits as they are either knockout models or inbred strains. Furthermore, these animal models generally demonstrate elevated locomotion in novel environments, but not in their home-cages. This is the opposite of the symptoms seen in the human condition where childhood hyperactivity is generally more pronounced in constant, unstimulating situations. In this study we filmed an outbred population of 44 heterogeneous stock (HS) mice under red light during their active phase, to assess the reliability of individual differences in home-cage behavior and extract an index of home-cage activity (HCA) level. We then compared this measure to locomotor behavior in a novel environment — the open-field. Reliable individual differences in home-cage behaviors such as running, swinging on bars, and burrowing were found, and principal component factor analysis yielded a general activity factor, which accounted for 32% of the variance and correlated 0.90 with a subjective impression of activity level. The correlation between HCA and locomotor activity in the open-field was 0.23, which was non-significant. However, the association with HCA level appeared to increase over the five minutes of the open-field, presumably as the mice habituated. Furthermore, although mice displaying particularly high and low HCA were indistinguishable early in the open-field task, they became significantly differentiated over time. We conclude that home-cage behaviors and the open-field, after habituation, display good face and construct validity, and may provide a good model of baseline activity for quantitative trait loci (QTL) discovery and functional genomics in the HS mice.     

Naturally occurring arrhythmicity in eclosion and activity in Lucilia cuprina: its genetic basis

ABSTRACT. Colonies of wild-type Lucilia cuprina (Wiedemann) (Diptera: Calliphoridae) in our laboratory differed greatly in the degree of rhythmicity of their eclosion when exposed to light/dark cycles, constant darkness or constant light. Among colonies reared in the laboratory for thirty-four to eighty-eight generations and others for more than 360 generations, some were consistently rhythmic, others weakly rhythmic and others arrhythmic.
One colony with arrhythmic eclosion was studied further. Arrhythmicity of eclosion in the colony was found to result from homozygosis of a recessive allele (ary) on chromosome 5. Adults from this colony were arrhythmic in spontaneous flight activity under constant darkness though rhythmic under light/dark cycles.     

Development and genetic differences of complement activity in rabbits*

The ontogeny of haemolytic complement in rabbit serum and the genetic differences of the activity in five strains of adult rabbits were investigated by single radial haemolysis in gel and a microtiter method with purified complement components and the appropriate haemolytic intermediate cells. The haemolytic complement activity was found as early as the 15th day of foetal life, and increased with age reaching approximately adult level by the 120th day of life. Marked strain differences in both total haemolytic activity and C3 levels of adult rabbit sera were observed. The repeatability of haemolytic activity for an individual serum taken at different times was higher than that for C3 levels and no significant correlation between haemolytic activity and C3 level was observed. An inherited complement deficiency, due to the lack of C6, was found in a strain of Angora rabbits. The genetic studies confirmed that this complement defect was transmitted as an autosomal recessive trait.     

A quantitative genetic analysis of tissue-specific catalase activity inMus musculus

Tissue-specific catalase activity in 3-week-old animals from inbred mouse strains 129/ReJ, BALB/c, C3H/HeAnl/Cas-1^b, C3H/HeSnJ, C3H/S, C57BL/6J, and Swiss-Webster was found to be highly variable by analysis of variance (P=0.01). Appropriate crosses were made among strains which were classified as normal (BALB/c, C3H/HeSnJ, C3H/S), hypocatalasemic (129/ReJ, C57BL/6J), and acatalasemic (C3H/HeAnl/Cas-1^b) with respect to blood catalase activity to study the inheritance of the blood, kidney, liver, and lung catalase activity levels in a number of generations (reciprocal F₁'s, F₂, two backcrosses —BC₁ and BC₂— and some RI lines). Segregation analysis and statistical methods which tested different models of inheritance as well as calculations of heritability were used in an effort to assess and evaluate genetic parameters that affect catalase activity. Results indicate that the inheritance of blood catalase activity in the cross involving acatalasemic and normal (BALB/c, C3H/HeSnJ) strains is compatible with the single-locus difference between the parental strains; however, the difference between the acatalasemic and the hypocatalasemic strain (C57BL/6J) would require additional genetic interaction for a satisfactory explanation. A similar pattern of generalization also applies to the inheritance of kidney catalase activity. The segregation pattern for the liver and lung catalase activity in most crosses is significantly different from the expectations of the single locus model. These results are compatible with the concept that a number of genes must affect tissue-specific catalase activity in mice. These may include previously described (e.g., Ce-1 and Ce-2) or novel genetic regulators/modifiers which interact with a single structural gene (Cas-1) or its product to produce the catalase phenotype characteristic of specific tissues in each strain.This investigation was supported by a Natural Sciences and Engineering Research Council of Canada operating grant to S.M.S.     

Male mating activity and genetic aspects in imaginal diapause of Drosophila triauraria

In Drosophila triauraria Bock & Wheeler (Diptera: Drosophilidae) of which females were known to enter reproductive diapause at short daylengths, males also showed reduced mating activity at short daylengths, i.e., males as well as females entered reproductive diapause. The critical daylength for diapause induction did not differ between females and males. Both male and female diapause ended even under short daylengths, but the male diapause was somewhat weaker than the female diapause.The critical daylength and the diapause rate varied geographically in this species. In the cross between diapausing and non-diapausing strains, the critical daylength and the diapause duration inherited in a quantitative manner. On the basis of the present and previous crossing experiments, some models are proposed on the mechanism of diapause induction of this species.

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Résumé Les femelles de D. triauraria Bock & Wheeler (Dipt. Drosophilidae) sont connues pour présenter une diapause reproductrice aux photophases courtes. Les mâles eux aussi ont révélé une activité sexuelle réduite aux photophases courtes, c'est-à-dire qu'ils sont entrés comme les femelles en diapause reproductive. Les photophases critiques pour l'induction de la diapause des mâles et des femelles n'ont pas présenté de différences. Les diapause des mâles et des femelles s'achèvent même sous courtes photophases, mais la diapause mâle était quelque peu plus faible que la diapause femelle.La photophase critique et le taux de diapause ont varié en fonction de l'origine géographique dans l'espèce actuelle. Lors de croisements entre lignées diapausantes et non-diapausantes, la photophase critique et la durée de la diapause ont été héritées quantitativement. A partir de ces expériences et d'expériences précédentes de croisements (Kimura, 1983), quelques modèles de méchnisme d'induction de la diapause de cette espèce sont proposés.

     

Bipolar disorder risk alleles in adult ADHD patients

Attention-deficit/hyperactivity disorder (ADHD) has an estimated prevalence of 3-5% in adults. Genome-wide association (GWA) studies have not been performed in adults with ADHD and studies in children have so far been inconclusive, possibly because of the small sample sizes. Larger GWA studies have been performed on bipolar disorder (BD) and BD symptoms, and several potential risk genes have been reported. ADHD and BD share many clinical features and comorbidity between these two disorders is common. We therefore wanted to examine whether the reported BD genetic variants in CACNA1C, ANK3, MYO5B, TSPAN8 and ZNF804A loci are associated with ADHD or with scores on the Mood Disorder Questionnaire (MDQ), a commonly used screening instrument for bipolar spectrum disorders. We studied 561 adult Norwegian ADHD patients and 711 controls from the general population. No significant associations or trends were found between any of the single nucleotide polymorphisms (SNPs) studied and ADHD [odds ratios (ORs) ≤ 1.05]. However, a weak association was found between rs1344706 in ZNF804A (OR = 1.25; P = 0.05) and MDQ. In conclusion, it seems unlikely that these six SNPs with strong evidence of association in BD GWA studies are shared risk variants between ADHD and BD.     

Appropriateness of array‐CGH in the ADHD clinics: A comparative study

Attention deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorder with a worldwide prevalence of about 5%. The disorder is characterized by inattentive, hyperactive and impulsive behavior and is often comorbid with other neuropsychiatric conditions. Array comparative genomic hybridization (array‐CGH) testing has been proved to be useful to detect chromosomal aberrations in several neuropsychiatric conditions including autism spectrum disorders (ASD) and intellectual disability (ID). The usefulness of array‐CGH in the ADHD clinics is still debated and no conclusive evidence has been reached to date. We performed array‐CGH in 98 children and adolescents divided in two similarly sized groups according to the clinical diagnosis: (a) one group diagnosed with ADHD as primary diagnosis; (b) the other group in which ADHD was co‐morbid with ASD and/or ID. We detected pathogenetic and likely pathogenetic copy number variants (CNVs) in 12% subjects in which ADHD was co‐morbid with autism and/or intellectual disability and in 8.5% subjects diagnosed with ADHD as primary diagnosis. Detection of CNVs of unknown clinical significance was similar in the two groups being 27% and 32%, respectively. Benign and likely benign CNVs accounted for 61% and 59.5% in the first and second group, respectively. Differences in the diagnostic yield were not statistically significant between the two groups (P > .05). Our data strongly suggest that array‐CGH (a) is a valuable diagnostic tool to detect clinically significant CNVs in individuals with ADHD even in the absence of comorbidity with ASD and/or ID and (b) should be implemented routinely in the ADHD clinics.     

The role of genetic structure in the adaptive divergence of populations experiencing saltwater intrusion due to relative sea‐level rise

Saltwater intrusion into estuaries creates stressful conditions for nektonic species. Previous studies have shown that Gambusia affinis populations with exposure to saline environments develop genetic adaptations for increased survival during salinity stress. Here, we evaluate the genetic structure of G. affinis populations, previously shown to have adaptations for increased salinity tolerance, and determine the impact of selection and gene flow on structure of these populations. We found that gene flow was higher between populations experiencing different salinity regimes within an estuary than between similar marsh types in different estuaries, suggesting the development of saline‐tolerant phenotypes due to local adaptation. There was limited evidence of genetic structure along a salinity gradient, and only some of the genetic variation among sites was correlated with salinity. Our results suggest limited structure, combined with selection to saltwater intrusion, results in phenotypic divergence in spite of a lack of physical barriers to gene flow.     

The use of mouse models to unravel genetic architecture of physical activity: a review

The discovery of genetic variants that underlie a complex phenotype is challenging. One possible approach to facilitate this endeavor is to identify quantitative trait loci (QTL) that contribute to the phenotype and consequently unravel the candidate genes within these loci. Each proposed candidate locus contains multiple genes and, therefore, further analysis is required to choose plausible candidate genes. One of such methods is to use comparative genomics in order to narrow down the QTL to a region containing only a few genes. We illustrate this strategy by applying it to genetic findings regarding physical activity (PA) in mice and human. Here, we show that PA is a complex phenotype with a strong biological basis and complex genetic architecture. Furthermore, we provide considerations for the translatability of this phenotype between species. Finally, we review studies which point to candidate genetic regions for PA in humans (genetic association and linkage studies) or use mouse models of PA (QTL studies) and we identify candidate genetic regions that overlap between species. On the basis of a large variety of studies in mice and human, statistical analysis reveals that the number of overlapping regions is not higher than expected on a chance level. We conclude that the discovery of new candidate genes for complex phenotypes, such as PA levels, is hampered by various factors, including genetic background differences, phenotype definition and a wide variety of methodological differences between studies .     

A framework for the study of genetic variation in migratory behaviour

Evolutionary change results from selection acting on genetic variation. For migration to be successful, many different aspects of an animal’s physiology and behaviour need to function in a co-coordinated way. Changes in one migratory trait are therefore likely to be accompanied by changes in other migratory and life-history traits. At present, we have some knowledge of the pressures that operate at the various stages of migration, but we know very little about the extent of genetic variation in various aspects of the migratory syndrome. As a consequence, our ability to predict which species is capable of what kind of evolutionary change, and at which rate, is limited. Here, we review how our evolutionary understanding of migration may benefit from taking a quantitative-genetic approach and present a framework for studying the causes of phenotypic variation. We review past research, that has mainly studied single migratory traits in captive birds, and discuss how this work could be extended to study genetic variation in the wild and to account for genetic correlations and correlated selection. In the future, reaction-norm approaches may become very important, as they allow the study of genetic and environmental effects on phenotypic expression within a single framework, as well as of their interactions. We advocate making more use of repeated measurements on single individuals to study the causes of among-individual variation in the wild, as they are easier to obtain than data on relatives and can provide valuable information for identifying and selecting traits. This approach will be particularly informative if it involves systematic testing of individuals under different environmental conditions. We propose extending this research agenda by using optimality models to predict levels of variation and covariation among traits and constraints. This may help us to select traits in which we might expect genetic variation, and to identify the most informative environmental axes. We also recommend an expansion of the passerine model, as this model does not apply to birds, like geese, where cultural transmission of spatio-temporal information is an important determinant of migration patterns and their variation.     

Neurofeedback for Children with ADHD: A Comparison of SCP and Theta/Beta Protocols

Behavioral and cognitive improvements in children with ADHD have been consistently reported after neurofeedback-treatment. However, neurofeedback has not been commonly accepted as a treatment for ADHD. This study addresses previous methodological shortcomings while comparing a neurofeedback-training of Theta-Beta frequencies and training of slow cortical potentials (SCPs). The study aimed at answering (a) whether patients were able to demonstrate learning of cortical self-regulation, (b) if treatment leads to an improvement in cognition and behavior and (c) if the two experimental groups differ in cognitive and behavioral outcome variables. SCP participants were trained to produce positive and negative SCP-shifts while the Theta/Beta participants were trained to suppress Theta (4–8 Hz) while increasing Beta (12–20 Hz). Participants were blind to group assignment. Assessment included potentially confounding variables. Each group was comprised of 19 children with ADHD (aged 8–13 years). The treatment procedure consisted of three phases of 10 sessions each. Both groups were able to intentionally regulate cortical activity and improved in attention and IQ. Parents and teachers reported significant behavioral and cognitive improvements. Clinical effects for both groups remained stable six months after treatment. Groups did not differ in behavioural or cognitive outcome.     

Calibration of ADHD Assessments Across Studies: A Meta-Analysis Tool

When analyzed separately, data from small studies provide only limited information with limited clinical generalizability, due to small sample size, differing assessments, and limited scope. In this methodological paper we outline a theoretical framework for performing meta-analysis of data obtained from disparate studies using disparate tests, based on calibration of the data from such studies and tests into a unified probability scale. We apply this method to combine the data from five studies examining the diagnostic abilities of different assessments of Attention Deficit/Hyperactivity Disorder (ADHD), including behavioral rating scales and EEG assessments. The studies enrolled a total of 111 subjects, 56 ADHD and 55 controls. Each individual study had a small sample focused on a specific age/gender group, for example 8 boys ages 6–10, and generally had insufficient power to detect statistically significant differences. No gender, or age comparisons were possible within any single study. However, when calibrated and combined, the data resulted in a clear separation between ADHD versus non-ADHD groups in males below the age of 16 (p < 0.001), males above the age of 16, (p = 0.015), females below the age of 16, (p = 0.0014), and females above the age of 16, (p = 0.0022).We conclude that if data from various studies using various tests are made comparable, the resulting combined sample size and the increased diversity of the combined sample lead to increased significance of the statistical tests and allow for cross-sectional comparisons, which are not possible within each individual study.     

A population genetic study in the Ochamchir region, Abkhazia, SSR

The reported longevity of residents of the Soviet Socialist Republic of the Caucasus has focused considerable attention on this population. However, little is known of the genetic composition of this population. With this in mind, several village populations of the Ochamchir Region, Abkhazia, SSR, were typed for 37 discrete genetic blood groups, erythrocyte and plasma protein loci. Gene and haplotype frequencies calculated for the polymorphic markers were determined and the results used in an analysis of intervillage heterogeneity and genetic distance analysis comparing the Abkhazians to European and Asian reference populations. The Abkhazians are approximately equal distance from European and West Asian populations in a genetic sense, and this is consistent with their geographical location. In addition to the usual genetic polymorphisms, rare electrophoretic variants were encountered at the lactate dehydrogenase A and phosphohexose isomerase loci. These results suggest that the population of the Ochamchir Region is relatively homogeneous and not distinctly different from its geographical neighbors.     

Combined Psychophysiological Assessment of ADHD: A Pilot Study of Bayesian Probability Approach Illustrated by Appraisal of ADHD in Female College Students

Manifestations of ADHD are observed at both psychological and physiological levels and assessed via various psychometric, EEG, and imaging tests. However, no test is 100% accurate in its assessment of ADHD. This study introduces a stochastic assessment combining psychometric tests with previously reported (Consistency Index) and newly developed (Alpha Blockade Index) EEG-based physiological markers of ADHD. The assessment utilizes classical Bayesian inference to refine after each step the probability of ADHD of each individual. In a pilot study involving six college females with ADHD and six matched controls, the assessment achieved correct classification for all ADHD and non-ADHD participants. In comparison, the classification of ADHD versus non-ADHD participants was < 85% for any one of the tests separately. The procedure significantly improved the score separation between ADHD versus non-ADHD groups. The final average probabilities for ADHD were 76% for the ADHD group and 8% for the control group. These probabilities correlated (r = .87) with the Brown ADD scale and (r = .84) with the ADHD-Symptom Inventory used for the screening of the participants. We conclude that, although each separate test was not completely accurate, a combination of several tests classified correctly all ADHD and all non-ADHD participants. The application of the proposed assessment is not limited to the specific tests used in this study--the assessment represents a general paradigm capable of accommodating a variety of ADHD tests into a single diagnostic assessment.     

血清微量元素与多动症患儿行为症状的相关性研究

目的:探讨多动症(ADHD)患儿血清中微量元素水平与患儿行为症状的相关性。方法:以原子吸收光谱仪检测6~14岁80名ADHD患儿及72名正常儿童血清中的铁(Fe)、锌(Zn)、铜(Cu)、钙(Ca)、镁(Mg)、镉(Cd)、铅(Pb)等微量元素的含量,应用Conner氏量表评价患儿行为症状,分析血清微量元素与行为症状评分的相关性。结果:ADHD患儿血清中Zn水平明显低于正常儿童、Pb水平明显高于正常儿童,差异均有统计学意义(P0.05);Fe、Ca略低于正常儿童,Cu、Cd略高于正常儿童,但差异均无统计学意义(P0.05)。ADHD患儿品行问题、学习问题、冲动-多动、焦虑指数较正常儿童相比有显著差异(P0.05);经Pearson相关分析,ADHD患儿血清Zn与学习问题、冲动-多动、多动指数呈负相关(P0.05),血清Pb与患儿冲动-多动、多动指数呈正相关(P0.05)。结论:ADHD患儿血清中Zn与Pb异常表达,与行为症状密切相关。在治疗ADHD患儿过程中,可以通过检测这些指标进行针对性或预防性治疗,有一定的指导价值。