Eugenia Conti

The first 1000 days of the autistic brain: a systematic review of diffusion imaging studies

There is overwhelming evidence that autism spectrum disorder (ASD) is related to altered brain connectivity. While these alterations are starting to be well characterized in subjects where the clinical picture is fully expressed, less is known on their earlier developmental course. In the present study we systematically reviewed current knowledge on structural connectivity in ASD infants and toddlers. We searched PubMed and Medline databases for all English language papers, published from year 2000, exploring structural connectivity in populations of infants and toddlers whose mean age was below 30 months. Of the 264 papers extracted, four were found to be eligible and were reviewed. Three of the four selected studies reported higher fractional anisotropy values in subjects with ASD compared to controls within commissural fibers, projections fibers, and association fibers, suggesting brain hyper-connectivity in the earliest phases of the disorder. Similar conclusions emerged from the other diffusion parameters assessed. These findings are reversed to what is generally found in studies exploring older patient groups and suggest a developmental course characterized by a shift toward hypo-connectivity starting at a time between two and four years of age.

Are children born after assisted reproductive technology at increased risk of autism spectrum disorders? A systematic review

STUDY QUESTION Are children born after assisted reproductive technology (ART) at increased risk of autism spectrum disorders (ASD)? SUMMARY ANSWER There is no evidence that ART significantly increases the risk of ASD in the offspring. WHAT IS KNOWN ALREADY A few systematic reviews have explored the correlation between assisted conception and ASD with inconclusive results, partly due to the heterogeneity of diagnostic criteria and methodology in the different studies. STUDY DESIGN, SIZE, DURATION Systematic review of 7 observational studies (2 cohort and 5 case-control) encompassing 9216 subjects diagnosed with ASD published since 2000. MATERIALS, SETTING, METHODS Literature searches were conducted to retrieve observational studies on the risk of ASD in ART population. Databases searched included PubMed, EMBASE and PsycINFO. In order to obtain more consistent results, we only included the studies in which (i) subjects with either infantile autism or ASD could be identified according to international classification systems and (ii) the diagnosis was obtained from hospital records. Seven studies matched the inclusion criteria. MAIN RESULTS AND THE ROLE OF CHANCE Four out of seven studies, including the two with the best quality scores, did not show an association between ART and ASD. The two papers supporting an increased risk of autism following ART had the lowest quality scores, due to major methodological limitations. Only one paper showed a protective role of ART. LIMITATIONS, REASONS FOR CAUTION In spite of the strict inclusion criteria applied as to the diagnosis of ASD, the papers selected are heterogeneous in many aspects including study design, definitions of ART, data source and analysed confounders. WIDER IMPLICATIONS OF THE FINDINGS At present, there is no evidence that ART is significantly associated with ASD and hence that current health policies should be modified. The divergent results of some of the studies suggest that further prospective, large and high-quality studies are still needed. STUDY FUNDING/COMPETING INTEREST(S) This work was supported, in part, by the Italian Ministry of Health and by Tuscany Region. The authors have no competing interests to declare. TRIAL REGISTRATION NUMBER N/A.

Reorganization of visual fields after periventricular haemorrhagic infarction: potentials and limitations

Visual functions are often impaired in preterm infants with periventricular haemorrhagic infarction, because of the involvement of the region where the optic radiations are located. In some cases an unexpected sparing of the visual fields has been described, and related to the plasticity of thalamo‐cortical afferents that are supposedly able to bypass the lesion when it occurs in the early third trimester of gestation. We systematically reviewed the literature in the field to determine the limits and potentials of this type of reorganization. We found four studies meeting our criteria, from which we extracted case reports on 19 individuals with intraventricular haemorrhagic infarction. Eleven of the 19 did not have visual field defects, five had a bilateral visual field defect, and the remaining three had a unilateral visual field defect. The involvement of the optic radiations was often associated with normal visual fields as only one of the four individuals with damaged optic radiations showed visual field defects. Conversely, the presence of basal ganglia/thalamus involvement apparently prevented such reorganization, as the only two individuals with unilateral field restriction and available magnetic resonance imaging data both showed abnormalities in those structures. Consistent with this, we report on a further individual in which visual field restriction was associated with abnormal tractography on brain magnetic resonance imaging. Overall, this review supports the existence of effective mechanisms of plastic reorganization that allow a rewiring of geniculo‐calcarine connections with restoration of full field vision but which are hindered by the involvement of the basal ganglia and thalamus.

The Broad Autism (Endo)Phenotype: Neurostructural and Neurofunctional Correlates in Parents of Individuals with Autism Spectrum Disorders

Autism Spectrum Disorders (ASD) are a set of neurodevelopmental disorders with an early-onset and a strong genetic component in their pathogenesis. According to genetic and epidemiological data, ASD relatives present personality traits similar to, but not as severe as the defining features of ASD, which have been indicated as the “Broader Autism Phenotype” (BAP). BAP features seem to be more prevalent in first-degree relatives of individuals with ASD than in the general population. Characterizing brain profiles of relatives of autistic probands may help to understand ASD endophenotype. The aim of this review was to provide an up-to-date overview of research findings on the neurostructural and neurofunctional substrates in parents of individuals with ASD (pASD). The primary hypothesis was that, like for the behavioral profile, the pASD express an intermediate neurobiological pattern between ASD individuals and healthy controls. The 13 reviewed studies evaluated structural magnetic resonance imaging (MRI) brain volumes, chemical signals using magnetic resonance spectroscopy (MRS), task-related functional activation by functional magnetic resonance imaging (fMRI), electroencephalography (EEG), or magnetoencephalography (MEG) in pASD.The studies showed that pASD are generally different from healthy controls at a structural and functional level despite often not behaviorally impaired. More atypicalities in neural patterns of pASD seem to be associated with higher scores at BAP assessment. Some of the observed atypicalities are the same of the ASD probands. In addition, the pattern of neural correlates in pASD resembles that of adult individuals with ASD, or it is specific, possibly due to a compensatory mechanism. Future studies should ideally include a group of pASD and HC with their ASD and non-ASD probands respectively. They should subgrouping the pASD according to the BAP scores, considering gender as a possible confounding factor, and correlating these scores to underlying brain structure and function. These types of studies may help to understand the genetic mechanisms involved in the various clinical dimension of ASD.

Lateralization of Brain Networks and Clinical Severity in Toddlers with Autism Spectrum Disorder: A HARDI Diffusion MRI Study

Recent diffusion tensor imaging studies in adolescents and children with Autism Spectrum Disorder (ASD) have reported a loss or an inversion of the typical left–right lateralization in fronto‐temporal regions crucial for sociocommunicative skills. No studies explored atypical lateralization in toddlers and its correlation with clinical severity of ASD. We recruited a cohort of 20 subjects aged 36 months or younger receiving a first clinical diagnosis of ASD (15 males; age range 20–36 months). Patients underwent diffusion MRI (High‐Angular‐Resolution Diffusion Imaging protocol). Data from cortical parcellation were combined with tractography to obtain a connection matrix and diffusion indexes (DI) including mean fractional anisotropy (DFA), number of tracts (DNUM), and total tract length (DTTL). A laterality index was generated for each measure, and then correlated with the Autism Diagnostic Observation Schedule‐Generic (ADOS‐G) total score. Laterality indexes of DFA were significantly correlated with ADOS‐G total scores only in two intrafrontal connected areas (correlation was positive in one case and negative in the other). Laterality indexes of DTTL and DNUM showed significant negative correlations (P < 0.05) in six connected areas, mainly fronto‐temporal. This study provides first evidence of a significant correlation between brain lateralization of diffusion indexes and clinical severity in toddlers with a first diagnosis of ASD. Significant correlations mainly involved regions within the fronto‐temporal circuits, known to be crucial for sociocommunicative skills. It is of interest that all correlations but one were negative, suggesting an inversion of the typical left–right asymmetry in subjects with most severe clinical impairment. Autism Res 2016, 9: 382–392.

Dual training as clinician-scientist in child and adolescent psychiatry: are we there yet?

Alexis Revet1 · Johannes Hebebrand2 · Sampada Bhide3 · João Caseiro4 · Eugenia Conti5 · Marike Deutz6 · Andra Isac7 · Athanasios Kanellopoulos8 · Tuğba Kalyoncu9 · Katri Maasalo10 · Silvana Markovska‐Simoska11 · Marija Mitkovic‐Voncina12 · Silvia Molteni13 · Mariela Mosheva14 · Susanne Mudra15 · Julia Philipp16 · Cecil Prins‐Aardema17 · Marina Romero Gonzalez18 · Antonín Šebela19 · Jochen Seitz20 · Lise Eilin Stene21 · Nikolina Vrljičak Davidović22 · Ida Wessing23 · Paul Klauser24

A systematic review of structural MRI biomarkers in autism spectrum disorder: A machine learning perspective

Autism Spectrum Disorder (ASD) affects approximately 1% of the population and leads to impairments in social interaction, communication and restricted, repetitive behaviours. Establishing robust neuroimaging biomarkers of ASD using structural magnetic resonance imaging (MRI) is an important step for diagnosing and tailoring treatment, particularly early in life when interventions can have the greatest effect. However currently, there is mixed findings on the structural brain changes associated with autism. Therefore in this systematic review, recent (post‐2007), high‐resolution (3 T) MRI studies investigating brain morphology associated with ASD have been collated to identify robust neuroimaging biomarkers of ASD. A systematic search was conducted on three databases; PubMed, Web of Science and Scopus, resulting in 123 reviewed articles. Patients with ASD were observed to have increased whole brain volume, particularly under 6 years of age. Other consistent changes observed in ASD patients include increased volume in the frontal and temporal lobes, increased cortical thickness in the frontal lobe, increased surface area and cortical gyrification, and increased cerebrospinal fluid volume, as well as reduced cerebellum volume and reduced corpus callosum volume, compared to typically developing controls. Findings were inconsistent regarding the developmental trajectory of brain volume and cortical thinning with age in ASD, as well as potential volume differences in the white matter, hippocampus, amygdala, thalamus and basal ganglia. To elucidate these inconsistencies, future studies should look towards aggregating MRI data from multiple sites or available repositories to avoid underpowered studies, as well as utilising methods which quantify larger‐scale image features to reduce the number of statistical tests performed, and hence risk of false positive findings. Additionally, studies should look to perform a thorough validation strategy, to ensure generalisability of study findings, as well as look to leverage the improved image resolution of 3 T scanning to identify subtle brain changes related to ASD.

Lateralization of Brain Networks and Clinical Severity in Toddlers with Autism Spectrum Disorder

Recent diffusion tensor imaging studies in adolescents and children with Autism Spectrum Disorder (ASD) have reported a loss or an inversion of the typical left–right lateralization in fronto‐temporal regions crucial for sociocommunicative skills. No studies explored atypical lateralization in toddlers and its correlation with clinical severity of ASD. We recruited a cohort of 20 subjects aged 36 months or younger receiving a first clinical diagnosis of ASD (15 males; age range 20–36 months). Patients underwent diffusion MRI (High‐Angular‐Resolution Diffusion Imaging protocol). Data from cortical parcellation were combined with tractography to obtain a connection matrix and diffusion indexes (DI) including mean fractional anisotropy (DFA), number of tracts (DNUM), and total tract length (DTTL). A laterality index was generated for each measure, and then correlated with the Autism Diagnostic Observation Schedule‐Generic (ADOS‐G) total score. Laterality indexes of DFA were significantly correlated with ADOS‐G total scores only in two intrafrontal connected areas (correlation was positive in one case and negative in the other). Laterality indexes of DTTL and DNUM showed significant negative correlations (P < 0.05) in six connected areas, mainly fronto‐temporal. This study provides first evidence of a significant correlation between brain lateralization of diffusion indexes and clinical severity in toddlers with a first diagnosis of ASD. Significant correlations mainly involved regions within the fronto‐temporal circuits, known to be crucial for sociocommunicative skills. It is of interest that all correlations but one were negative, suggesting an inversion of the typical left–right asymmetry in subjects with most severe clinical impairment. Autism Res 2016, 9: 382–392.

Lateralization of Brain Networks and Clinical Severity in Toddlers with Autism Spectrum Disorder: A HARDI Diffusion MRI Study: Brain tracts lateralization in ASD toddlers

Recent diffusion tensor imaging studies in adolescents and children with Autism Spectrum Disorder (ASD) have reported a loss or an inversion of the typical left–right lateralization in fronto‐temporal regions crucial for sociocommunicative skills. No studies explored atypical lateralization in toddlers and its correlation with clinical severity of ASD. We recruited a cohort of 20 subjects aged 36 months or younger receiving a first clinical diagnosis of ASD (15 males; age range 20–36 months). Patients underwent diffusion MRI (High‐Angular‐Resolution Diffusion Imaging protocol). Data from cortical parcellation were combined with tractography to obtain a connection matrix and diffusion indexes (DI) including mean fractional anisotropy (DFA), number of tracts (DNUM), and total tract length (DTTL). A laterality index was generated for each measure, and then correlated with the Autism Diagnostic Observation Schedule‐Generic (ADOS‐G) total score. Laterality indexes of DFA were significantly correlated with ADOS‐G total scores only in two intrafrontal connected areas (correlation was positive in one case and negative in the other). Laterality indexes of DTTL and DNUM showed significant negative correlations (P < 0.05) in six connected areas, mainly fronto‐temporal. This study provides first evidence of a significant correlation between brain lateralization of diffusion indexes and clinical severity in toddlers with a first diagnosis of ASD. Significant correlations mainly involved regions within the fronto‐temporal circuits, known to be crucial for sociocommunicative skills. It is of interest that all correlations but one were negative, suggesting an inversion of the typical left–right asymmetry in subjects with most severe clinical impairment. Autism Res 2016, 9: 382–392.

Wiring the preterm brain: contribution of new meta‐analytic approaches

Increasingly clinicians are turning to synthesized sources of literature to gain an understanding of the state of the research evidence in relevant areas of clinical practice. While quantitative meta-analyses and systematic reviews have become prolific in health care literature, qualitative syntheses are only beginning to emerge. The paper by Livingstone and Field highlights the value of qualitative synthesis for providing a greater depth of understanding of the complex issues that characterize clinical practice in pediatric rehabilitation and developmental medicine. By engaging in a systematic process for identification of relevant literature, and evaluation and synthesis of results, Livingstone and Field have provided a useful summary of the state of evidence regarding subjective child and family experiences with power mobility. Quantitative research conducted with children with mobility impairments suggests that power mobility can increase self-initiated movement and enhance overall child development. Information about the subjective experience of families provides complementary depth of understanding, which also offers important insights that inform clinical practice. Through families’ stories, we are reminded of the importance of ensuring a good fit between mobility methods and environments so that children with mobility impairments can participate in activities that are meaningful to them and develop social relationships with their peers. Participation in self-selected activities is an important contributor to quality of life; an important outcome that clinicians aim to achieve through interactions with families. Maximizing participation for children with mobility impairments may require consideration of different mobility methods in different environments. Even children who are able to walk with assistive devices in most settings may benefit from alternative methods of mobility to ensure they can travel independently for longer distances or navigate challenging environments. From a clinical perspective, family-centered service involves working collaboratively with children and families to address outcomes that are important to them. Family perspectives can also inform the outcomes measured in clinical studies. This synthesis offers insight into the impacts of effective mobility – specifically, power mobility – that are meaningful to children and families. Future research in this area could examine the effects of power mobility on identified outcomes that have not been adequately explored in previous research. These include the impact of effective mobility on meaningful participation in self-selected activities, confidence, and self-esteem; and how power mobility, or effective mobility in general, affects the quality of social relationships. The effectiveness of various interventions in reducing barriers to power mobility use could also be evaluated.