Brain structural deficits and working memory fMRI dysfunction in young adults who were diagnosed with ADHD in adolescence.

When adolescents with ADHD enter adulthood, some no longer meet disorder diagnostic criteria but it is unknown if biological and cognitive abnorma lities persist. We tested the hypothesis that people diagnosed with ADHD during adolescence present residual brain abnormalities both in brain structure and in working memory brain function. 83 young adults (aged 20-24 years) from the Northern Finland 1986 Birth Cohort were classified as diagnosed with ADHD in adolescence (adolescence ADHD, n = 49) or a control group (n = 34). Only one patient had received medication for ADHD. T1-weighted brain scans were acquired and processed in a voxel-based analysis using permutation-based statistics. A sub-sample of both groups (ADHD, n = 21; controls n = 23) also performed a Sternberg working memory task whilst acquiring fMRI data. Areas of structural difference were used as a region of interest to evaluate the implications that structural abnormalities found in the ADHD group might have on working memory function. There was lower grey matter volume bilaterally in adolescence ADHD participants in the caudate (p < 0.05 FWE corrected across the whole brain) at age 20-24. Working memory was poorer in adolescence ADHD participants, with associated failure to show normal load-dependent caudate activation. Young adults diagnosed with ADHD in adolescence have structural and functional deficits in the caudate associated with abnormal working memory function. These findings are not secondary to stimulant treatment, and emphasise the importance of taking a wider perspective on ADHD outcomes than simply whether or not a particular patient meets diagnostic criteria at any given point in time.This work was supported by an Academy of Finland Award to Dr Veijola; a Sigrid Juselius Foundation grant to Dr Moilanen; a Medical Research Council fellowship to Dr Murray (G0701911); a NARSAD, the Brain and Behavior Research Fund independent investigator award to Dr Miettunen; an Oon Khye Beng Ch'Hia Tsio Studentships in Preventative Medicine awarded by Downing College, Cambridge to Dr Roman-Urrestarazu together with a Becas Chile Doctoral Grant awarded by CONICYT, an Academy of Finland grant and Finnish Medical Foundation grant to Dr Kiviniemi, and an award from the Signe and Ane Gyllenberg Foundation, Finland, to Dr Mäki.. The work was partially conducted with the University of Cambridge Behavioural and Clinical Neuroscience Centre, supported by a joint award from the Medical Research Council (G1000183) and Wellcome Trust (093875/Z/10Z).This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s00787-015-0755-

Brain structure in different psychosis risk groups in the Northern Finland 1986 Birth Cohort

We tested the hypothesis that family risk for psychosis (FR) and clinical risk for psychosis (CR) are associated with structural brain abnormalities, with increased deficits in those at both family risk and clinical risk for psychosis (FRCR). The study setting was the Oulu Brain and Mind Study, with subjects drawn from the Northern Finland 1986 Birth Cohort (n = 9479) using register and questionnaire based screening, and interviews using the Structured Interview for Prodromal Symptoms. After this procedure, 172 subjects were included in the study, classified as controls (n = 73) and three risk groups: FR excluding CR (FR, n = 60), CR without FR (CR, n = 26), and individuals at both FR and CR (FRCR, n = 13). T1-weighted brain scans were acquired and processed in a voxel-based analysis using permutation-based statistics. In the comparison between FRCR versus controls, we found lower grey matter volume (GMV) in a cluster (1689 voxels at − 4.00, − 72.00, − 18.00 mm) covering both cerebellar hemispheres and the vermis. This cluster was subsequently used as a mask to extract mean GMV in all four groups: FR had a volume intermediate between controls and FRCR. Within FRCR there was an association between cerebellar cluster brain volume and motor function. These findings are consistent with an evolving pattern of cerebellar deficits in psychosis risk with the most pronounced deficits in those at highest risk of psychosis

Reelin Associated With Restricted and Stereotyped Behavior Based on Principal Component Analysis on Autism Diagnostic Interview-Revised

Tämä artikkeli ei ole avattavissa lehden sivuilta, koska linkit ja DOI vievät väärään artikkeliin samoin PDF sen ohessa. Kustantajalle ilmoitettu ja pyydetty korjausta.Abstract Background: Twin and family studies have indicated a strong genetic component in autism spectrum disorders, and genetic studies have revealed highly heterogeneous risk factors. The range and severity of the symptom presentation also vary in the spectrum. Thus, symptom-based phenotypes are putatively more closely related to the underlying biology of autism than the end-state diagnosis. Methods: We performed principal component analysis on Autism Diagnostic Interview-Revised algorithm for 117 Finnish families and 594 families from the Autism Genetic Research Exchange (AGRE). The resulting continuous component scores were used as quantitative phenotypes in family-based association analysis. In addition, K-means clustering was performed to cluster and visualize the results of the PCA. Unaffected siblings were included in the study. Results: The components were interpreted as Social Component (SC), communication component and Restricted and Stereotyped Behavior Component (RSBC). K-means clustering showed that, especially in SC, the range of the symptom severity was increased by the siblings. The association of neuroligin 1 with SC was increased, compared to a previous study where only the end-state diagnosis was used. In RSBC, the range of the symptom severity of siblings overlapped greatly with that of patients, which could explain why no association of reelin was found in previous studies in which only the end-state diagnosis was used, but a significant association of reelin with RSBC was now found in the Finnish families (Bonferroni-corrected p=0.029 for rs362644). Although, the Finnish sample is isolated and genetically very homogeneous, compared to the heterogeneous background of AGRE families, many single-nucleotide polymorphisms in reelin, showed modest association with RSBC in the AGRE sample, too. Conclusions: This study demonstrates how the quantitative phenotypes can affect the association analyses, and yields further support to the use of siblings in the study of complex neuropsychiatric disorders.Peer reviewe

Brain structure in different psychosis risk groups in the Northern Finland 1986 Birth Cohort

We tested the hypothesis that family risk for psychosis (FR) and clinical risk for psychosis (CR) are associated with structural brain abnormalities, with increased deficits in those at both family risk and clinical risk for psychosis (FRCR). The study setting was the Oulu Brain and Mind Study, with subjects drawn from the Northern Finland 1986 Birth Cohort (n = 9479) using register and questionnaire based screening, and interviews using the Structured Interview for Prodromal Symptoms. After this procedure, 172 subjects were included in the study, classified as controls (n = 73) and three risk groups: FR excluding CR (FR, n = 60), CR without FR (CR, n = 26), and individuals at both FR and CR (FRCR, n = 13). T1-weighted brain scans were acquired and processed in a voxel-based analysis using permutation-based statistics. In the comparison between FRCR versus controls, we found lower grey matter volume (GMV) in a cluster (1689 voxels at − 4.00, − 72.00, − 18.00 mm) covering both cerebellar hemispheres and the vermis. This cluster was subsequently used as a mask to extract mean GMV in all four groups: FR had a volume intermediate between controls and FRCR. Within FRCR there was an association between cerebellar cluster brain volume and motor function. These findings are consistent with an evolving pattern of cerebellar deficits in psychosis risk with the most pronounced deficits in those at highest risk of psychosis

Different vulnerability indicators for psychosis and their neuropsychological characteristics in the Northern Finland 1986 Birth Cohor

This study is one of very few that has investigated the neuropsychological functioning of both familial and clinical high risk subjects for psychosis. Participants (N = 164) were members of the Northern Finland 1986 Birth Cohort in the following four groups: familial risk for psychosis (n = 62), clinical risk for psychosis (n = 20), psychosis (n = 13), and control subjects (n = 69). The neurocognitive performance of these groups was compared across 19 cognitive variables. The two risk groups did not differ significantly from controls, but differed from the psychosis group in fine motor function. Neuropsychological impairments were not evident in a non-help-seeking high-risk sample

Multifactor effects and evidence of potential interaction between complement factor H Y402H and LOC387715 A69S in age-related macular degeneration

Peer reviewe

Characteristics of narrative language in autism spectrum disorder: Evidence from the Finnish

This study examined linguistic and pragmatic aspects of narrative abilities of children with autism spectrum disorder (ASD), which have not been studied thoroughly and not at all in Finnish. Sixteen five- to ten-year-old Finnish high-functioning children with ASD (mean age 7;7 years) and 16 age-matched typically developing children (mean age 7;5 years) participated in this study. Children\u27s picture-based narrations were analyzed for narrative productivity, syntactic complexity, referential accuracy, event content, use of additional and extraneous information, mental state expressions, and narrative comprehension. Several linguistic- and pragmatic-based measures were used in order to gain a comprehensive picture of strengths and weaknesses that children with ASD might show in storytelling. The use of linguistic structure, referential accuracy and mental state expressions was similar between the groups. However, children with ASD showed difficulties in establishing informative story content, making inferences from story events and an ability not to include extraneous information into their stories. Therefore, the problems seen in their narrative language use can be described as being related to pragmatic aspects of narration