Vineland Adaptive Behavior Scales - II profile of young children with Autism Spectrum Disorder

Adaptive behaviour is a crucial area of assessment for individuals with Autism Spectrum Disorder (ASD). This study examined the adaptive behaviour profile of 77 young children with ASD using the Vineland-II, and analysed factors associated with adaptive functioning. Consistent with previous research with the original Vineland a distinct autism profile of Vineland-II age equivalent scores, but not standard scores, was found. Highest scores were in motor skills and lowest scores were in socialisation. The addition of the Autism Diagnostic Observation Schedule (ADOS) calibrated severity score did not contribute significant variance to Vineland-II scores beyond that accounted for by age and nonverbal ability. Limitations, future directions, and implications are discussed.

Developmental origins of psychological vulnerability factors for mental disorders

Premature birth and associated small body size are known to affect health over the life course. Moreover, compelling evidence suggests that birth size throughout its whole range of variation is inversely associated with risk for cardiovascular disease and type 2 diabetes in subsequent life. To explain these findings, the Developmental Origins of Health and Disease (DOHaD) model has been introduced. Within this framework, restricted physical growth is, to a large extent, considered either a product of harmful environmental influences, such as suboptimal nutrition and alterations in the foetal hormonal milieu, or an adaptive reaction to the environment. Whether inverse associations exist between body size at birth and psychological vulnerability factors for mental disorders is poorly known. Thus, the aim of this thesis was to study in three large prospective cohorts whether prenatal and postnatal physical growth, across the whole range of variation, is associated with subsequent temperament/personality traits and psychological symptoms that are considered vulnerability factors for mental disorders. Weight and length at birth in full term infants showed quadratic associations with the temperamental trait of harm avoidance (Study I). The highest scores were characteristic of the smallest individuals, followed by the heaviest/longest. Linear associations between birth size and psychological outcomes were found such that lower weight and thinness at birth predicted more pronounced trait anxiety in late adulthood (Study II); lower birth weight, placental size, and head circumference at 12 months predicted a more pronounced positive schitzotypal trait in women (Study III); and thinness and smaller head circumference at birth associated with symptoms of attention-deficit hyperactivity disorder (ADHD) in children who were born at term (Study IV). These associations occured across the whole variation in birth size and after adjusting for several confounders. With respect to growth after birth, individuals with high trait anxiety scores in late adulthood were lighter in weight and thinner in infancy, and gained weight more rapidly between 7 and 11 years of age, but weighed less and were shorter in late adulthood in relation to weight and height measured at 11 years of age (Study II). These results suggest that a suboptimal prenatal environment reflected in smaller birth size may affect a variety of psychological vulnerability factors for mental disorders, such as the temperamental trait of harm avoidance, trait anxiety, schizotypal traits, and symptoms of ADHD. The smaller the birth size across the whole range of variation, the more pronounced were these psychological vulnerability factors. Moreover, some of these outcomes, such as trait anxiety, were also predicted by patterns of growth after birth. The findings are concordant with the DOHaD model, and emphasise the importance of prenatal factors in the aetiology of not only mental disorders but also their psychological vulnerability factors.

Genetic background of bipolar disorder and related cognitive impairments

Bipolar disorder (BP) is a complex psychiatric disorder characterized by episodes of mania and depression. BP affects approximately 1% of the world’s population and shows no difference in lifetime prevalence between males and females. BP arises from complex interactions among genetic, developmental and environmental factors, and it is likely that several predisposing genes are involved in BP. The genetic background of BP is still poorly understood, although intensive and long-lasting research has identified several chromosomal regions and genes involved in susceptibility to BP. This thesis work aims to identify the genetic variants that influence bipolar disorder in the Finnish population by candidate gene and genome-wide linkage analyses in families with many BP cases. In addition to diagnosis-based phenotypes, neuropsychological traits that can be seen as potential endophenotypes or intermediate traits for BP were analyzed. In the first part of the thesis, we examined the role of the allelic variants of the TSNAX/DISC1 gene cluster to psychotic and bipolar spectrum disorders and found association of distinct allelic haplotypes with these two groups of disorders. The haplotype at the 5’ end of the Disrupted-in-Schizophrenia-1 gene (DISC1) was over-transmitted to males with psychotic disorder (p = 0.008; for an extended haplotype p = 0.0007 with both genders), whereas haplotypes at the 3’ end of DISC1 associated with bipolar spectrum disorder (p = 0.0002; for an extended haplotype p = 0.0001). The variants of these haplotypes also showed association with different cognitive traits. The haplotypes at the 5’ end associated with perseverations and auditory attention, while the variants at the 3’ end associated with several cognitive traits including verbal fluency and psychomotor processing speed. Second, in our complete set of BP families with 723 individuals we studied six functional candidate genes from three distinct signalling systems: serotonin-related genes (SLC6A4 and TPH2), BDNF -related genes (BDNF, CREB1 and NTRK2) and one gene related to the inflammation and cytokine system (P2RX7). We replicated association of the functional variant Val66Met of BDNF with BP and better performance in retention. The variants at the 5’ end of SLC6A4 also showed some evidence of association among males (p = 0.004), but the widely studied functional variants did not yield any significant results. A protective four-variant haplotype on P2RX7 showed evidence of association with BP and executive functions: semantic and phonemic fluency (p = 0.006 and p = 0.0003, respectively). Third, we analyzed 23 bipolar families originating from the North-Eastern region of Finland. A genome-wide scan was performed using the 6K single nucleotide polymorphism (SNP) array. We identified susceptibility loci at chromosomes 7q31 with a LOD score of 3.20 and at 9p13.1 with a LOD score of 4.02. We followed up both linkage findings in the complete set of 179 Finnish bipolar families. The finding on chromosome 9p13 was supported (maximum LOD score of 3.02), but the susceptibility gene itself remains unclarified. In the fourth part of the thesis, we wanted to test the role of the allelic variants that have associated with bipolar disorder in recent genome-wide association studies (GWAS). We could confirm findings for the DFNB31, SORCS2, SCL39A3, and DGKH genes. The best signal in this study comes from DFNB31, which remained significant after multiple testing corrections. Two variants of SORCS2 were allelic replications and presented the same signal as the haplotype analysis. However, no association was detected with the PALB2 gene, which was the most significantly associated region in the previous GWAS. Our results indicate that BP is heterogeneous and its genetic background may accordingly vary in different populations. In order to fully understand the allelic heterogeneity that underlies common diseases such as BP, complete genome sequencing for many individuals with and without the disease is required. Identification of the specific risk variants will help us better understand the pathophysiology underlying BP and will lead to the development of treatments with specific biochemical targets. In addition, it will further facilitate the identification of environmental factors that alter risk, which will potentially provide improved occupational, social and psychological advice for individuals with high risk of BP.

Early protein malnutrition disrupts cerebellar development and impairs motor coordination

Maternal malnutrition affects every aspect of fetal development. The present study asked the question whether a low-protein diet of the mother could result in motor deficits in the offspring. Further, to examine whether cerebellar pathology was correlated with motor deficits, several parameters of the postnatal development of the cerebellum were assayed. This is especially important because the development of the cerebellum is unique in that the time scale of development is protracted compared with that of the cortex or hippocampus. The most important result of the study is that animals born to protein-deficient mothers showed significant delays in motor development as assessed by rotarod and gait analysis. These animals also showed reduced cell proliferation and reduced thickness in the external granular layer. There was a reduction in the number of calbindin-positive Purkinje cells (PC) and granular cells in the internal granular layer. However, glial fibrillary acidic protein-positive population including Bergmann glia remained unaffected. We therefore conclude that the development of the granular cell layer and the PC is specifically prone to the effects of protein malnutrition potentially due to their protracted developmental period from approximately embryonic day 11 to 13 until about the third postnatal week.

Electric field and temperature dependence of the local structural disorder in the lead-free ferroelectric Na0.5Bi0.5TiO3: An EXAFS study

The complex nature of the structural disorder in the lead-free ferroelectric Na1/2Bi1/2TiO3 has a profound impact on the perceived global structure and polar properties. In this paper, we have investigated the effect of electric field and temperature on the local structure around theBi and Ti atoms using extended x-ray absorption fine structure. Detailed analysis revealed that poling brings about a noticeable change in the bond distances associated with the Bi-coordination sphere, whereas the Ti coordination remains unaffected. We also observed discontinuity in the Bi-O bond lengths across the depolarization temperature of the poled specimen. These results establish that the disappearance of the monoclinic-like (Cc) global distortion, along with the drastic suppression of the short-ranged in-phase octahedral tilt after poling B. N. Rao et al., Phys. Rev. B 88, 224103 (2013)] is a result of the readjustment of theA-O bonds by the electric field, so as to be in conformity with the rhombohedral R3c structure.

Novelty and Habituation: the Driving Forces in Early Stage Learning for Developmental Robotics

Meng, Q., & Lee, M. (2005). Novelty and Habituation: the Driving Forces in Early Stage Learning for Developmental Robotics. Wermter, S., Palm, G., & Elshaw, M. (Eds.), In: Biomimetic Neural Learning for Intelligent Robots: Intelligent Systems, Cognitive Robotics, and Neuroscience. (pp. 315-332). (Lecture Notes in Computer Science). Springer Berlin Heidelberg.

Growth of Motor Coordination in Early Robot Learning

M. H. Lee and Q. Meng, Growth of Motor Coordination in Early Robot Learning, IJCAI-05, 2005.

Novelty and Habituation: the Driving Forces in Early Stage Learning for Developmental Robotics

Q. Meng and M. H. Lee, Novelty and Habituation: the Driving Forces in Early Stage Learning for Developmental Robotics, AI-Workshop on NeuroBotics, University of Ulm, Germany. September 2004.

Developmental Learning for Autonomous Robots

M.H. Lee, Q. Meng and F. Chao, 'Developmental Learning for Autonomous Robots', Robotics and Autonomous Systems, 55(9), pp 750-759, 2007.

Staged development of Robot Motor Coordination

M.H. Lee and Q. Meng, 'Staged development of Robot Motor Coordination', IEEE International Conference on Systems, Man and Cybernetics, (IEEE SMC 05), Hawaii, USA, v3, 2917-2922, 2005.

Mutations in NGLY1 cause an inherited disorder of the endoplasmic reticulum-associated degradation pathway.

PURPOSE: The endoplasmic reticulum-associated degradation pathway is responsible for the translocation of misfolded proteins across the endoplasmic reticulum membrane into the cytosol for subsequent degradation by the proteasome. To define the phenotype associated with a novel inherited disorder of cytosolic endoplasmic reticulum-associated degradation pathway dysfunction, we studied a series of eight patients with deficiency of N-glycanase 1. METHODS: Whole-genome, whole-exome, or standard Sanger sequencing techniques were employed. Retrospective chart reviews were performed in order to obtain clinical data. RESULTS: All patients had global developmental delay, a movement disorder, and hypotonia. Other common findings included hypolacrima or alacrima (7/8), elevated liver transaminases (6/7), microcephaly (6/8), diminished reflexes (6/8), hepatocyte cytoplasmic storage material or vacuolization (5/6), and seizures (4/8). The nonsense mutation c.1201A>T (p.R401X) was the most common deleterious allele. CONCLUSION: NGLY1 deficiency is a novel autosomal recessive disorder of the endoplasmic reticulum-associated degradation pathway associated with neurological dysfunction, abnormal tear production, and liver disease. The majority of patients detected to date carry a specific nonsense mutation that appears to be associated with severe disease. The phenotypic spectrum is likely to enlarge as cases with a broader range of mutations are detected.

The impact of the developmental timing of trauma exposure on PTSD symptoms and psychosocial functioning among older adults.

The present study examined the impact of the developmental timing of trauma exposure on posttraumatic stress disorder (PTSD) symptoms and psychosocial functioning in a large sample of community-dwelling older adults (N = 1,995). Specifically, we investigated whether the negative consequences of exposure to traumatic events were greater for traumas experienced during childhood, adolescence, young adulthood, midlife, or older adulthood. Each of these developmental periods is characterized by age-related changes in cognitive and social processes that may influence psychological adjustment following trauma exposure. Results revealed that older adults who experienced their currently most distressing traumatic event during childhood exhibited more severe symptoms of PTSD and lower subjective happiness compared with older adults who experienced their most distressing trauma after the transition to adulthood. Similar findings emerged for measures of social support and coping ability. The differential effects of childhood compared with later life traumas were not fully explained by differences in cumulative trauma exposure or by differences in the objective and subjective characteristics of the events. Our findings demonstrate the enduring nature of traumatic events encountered early in the life course and underscore the importance of examining the developmental context of trauma exposure in investigations of the long-term consequences of traumatic experiences.

Coordination and movement pathology: models of structure and function

Here we consider the role of abstract models in advancing our understanding of movement pathology. Models of movement coordination and control provide the frameworks necessary for the design and interpretation of studies of acquired and developmental disorders. These models do not however provide the resolution necessary to reveal the nature of the functional impairments that characterise specific movement pathologies. In addition, they do not provide a mapping between the structural bases of various pathologies and the associated disorders of movement. Current and prospective approaches to the study and treatment of movement disorders are discussed. It is argued that the appreciation of structure-function relationships, to which these approaches give rise, represents a challenge to current models of interlimb coordination, and a stimulus for their continued development. (C) 2002 Elsevier Science B.V. All rights reserved.

Movement-related potentials in high-functioning autism and Asperger's disorder

Autism and Asperger's disorder (AD) are neurodevelopmental conditions that affect cognitive and social-communicative function. Using a movement-related potential (MRP) paradigm, we investigated the clinical and neurobiological issue of 'disorder separateness' versus 'disorder variance' in autism and AD. This paradigm has been used to assess basal ganglia/supplementary motor functioning in Parkinson's disease. Three groups (high functioning autism [HFA]: 16 males, 1 female; mean age 12y 5mo [SD 4y 4mo]; AD: 11 males, 2 females; mean age 13y 5mo [SD 3y 8mo]; comparison group: 13 males, 8 females; mean age 13y 10mo, [SD 3y 11 mo]) completed a cued motor task during electroencephalogram recording of MRPs. The HFA group showed reduced peak amplitude at Cz, indicating less activity over the supplementary motor area during movement preparation. Although an overall significant between-group effect was found for early slope and peak amplitude, subanalysis revealed that the group with AD did not differ significantly from either group. However, it is suggested that autism and AD may be dissociated on the basis of brain-behaviour correlations of IQ with specific neurobiological measures. The overlap between MRP traces for autism and Parkinson's disease suggests that the neurobiological wiring of motor functioning in autism may bypass the supplementary motor area/primary motor cortex pathway.

Experiences of parents during diagnosis and forward planning for children with Autism Spectrum Disorder.

Background For families of children diagnosed with autism spectrum disorder (ASD) getting a diagnosis is a traumatic experience on which future care and education plans for the child depend. In this paper parental experiences of diagnosis and forward planning for children with ASD are reported. Method This paper is part of a large cross-sectional study conducted in Northern Ireland and the Republic of Ireland that assessed the needs and experiences of parents of children diagnosed with ASD. Questionnaires were designed and completed by 95 parents, reporting on 100 children, as well as 67 multi-disciplinary professionals. Results Findings confirm that diagnostic and planning processes are extremely stressful for parents, that statutory diagnosis takes a long time, that care and education plans do not include full parental participation, and that reviews of plans do not consistently include intervention data. Conclusion Policy and practice implications of these findings are important for future revisions of diagnostic tools and manuals.