Co-activation pattern alterations in autism spectrum disorder-A volume-wise hierarchical clustering fMRI study.

INTRODUCTION: There has been a growing effort to characterize the time-varying functional connectivity of resting state (RS) fMRI brain networks (RSNs). Although voxel-wise connectivity studies have examined different sliding window lengths, nonsequential volume-wise approaches have been less common. METHODS: Inspired by earlier co-activation pattern (CAP) studies, we applied hierarchical clustering (HC) to classify the image volumes of the RS-fMRI data on 28 adolescents with autism spectrum disorder (ASD) and their 27 typically developing (TD) controls. We compared the distribution of the ASD and TD groups' volumes in CAPs as well as their voxel-wise means. For simplification purposes, we conducted a group independent component analysis to extract 14 major RSNs. The RSNs' average z-scores enabled us to meaningfully regroup the RSNs and estimate the percentage of voxels within each RSN for which there was a significant group difference. These results were jointly interpreted to find global group-specific patterns. RESULTS: We found similar brain state proportions in 58 CAPs (clustering interval from 2 to 30). However, in many CAPs, the voxel-wise means differed significantly within a matrix of 14 RSNs. The rest-activated default mode-positive and default mode-negative brain state properties vary considerably in both groups over time. This division was seen clearly when the volumes were partitioned into two CAPs and then further examined along the HC dendrogram of the diversifying brain CAPs. The ASD group network activations followed a more heterogeneous distribution and some networks maintained higher baselines; throughout the brain deactivation state, the ASD participants had reduced deactivation in 12/14 networks. During default mode-negative CAPs, the ASD group showed simultaneous visual network and either dorsal attention or default mode network overactivation. CONCLUSION: Nonsequential volume gathering into CAPs and the comparison of voxel-wise signal changes provide a complementary perspective to connectivity and an alternative to sliding window analysis.

How are social-emotional and behavioral competences and problems at age 1 year associated with infant motor development? A general population study.

Based on limitations in previous research evidence, we concluded that more research is needed for deeper understanding of how social-emotional and behavioral (SEB) outcomes among infant-toddler-aged children in the general population are associated with early motor development. In this study, we investigated associations between early competencies and problems, as measured by the Brief Infant-Toddler Social and Emotional Assessment (BITSEA), and the timing of achievement of the main gross and fine motor milestones usually attained during the first year of life in a general population context. The study sample consisted of 515 infants (mean age 12.9 [SD 0.9] months) and their parents (514 mothers, 434 fathers), who were recruited in child health centers in Northern Finland. The infants were divided into two groups, based on their BITSEA screen status, and motor milestone achievement ages were compared across BITSEA screen status No Concern and Of-Concern infants. An Of-Concern screen status on the maternal and paternal Competence scale and Autism spectrum disorder (ASD) item cluster was associated with later infant achievement ages for gross motor milestones. By contrast, infants who were screened to be in the Of-Concern range on the maternal Problem scale achieved gross motor milestones earlier than infants with the corresponding No Concern screen status. No significant associations were found between the paternal Problem scale screen status and infant motor development. In further analyses, the strongest associations were found between an Of-Concern screen status on the paternal Competence scale and ASD item cluster and infant motor development. The findings indicate that the inclusion of infant motor developmental information may assist early identification and the clinical interpretation of parental reports of early SEB problems. Clinical implications of the current findings are discussed in the paper.

PARENTAL REPORTS OF EARLY SOCIOEMOTIONAL AND BEHAVIORAL PROBLEMS: DOES THE FATHER'S VIEW MAKE A DIFFERENCE?

Although both mothers and fathers are essential sources of information to address early socioemotional/behavioral (SEB) problems, there continues to be a dearth of studies considering both parental views. A sample of 208 toddlers (Mage = 19.3 months) was recruited through public child health centers. Both parents of 172 toddlers (76 boys, 96 girls) completed the Child Behavior Checklist (CBCL) 1-5 (T.M. Achenbach & L.A. Rescorla, 2000; Finnish translation by F. Almqvist, ). Correspondence (intraclass correlation coefficients; ICCs) between the maternal and paternal CBCL ratings was good (.64) for the Internalizing and excellent (.76) for the Externalizing and Total Problems scores whereas ICCs varied from .45 for the Withdrawn to .76 for the Sleep Problems and Aggressive Behavior syndrome scores. Regarding discrepancies, mothers consistently reported higher CBCL scale scores than did fathers. Most significant differences between the parental ratings were found on the Aggressive Behavior syndrome, Externalizing, and Total Problems scales. Interparental rating discrepancies increased with elevations in the corresponding CBCL scale scores. Positive correlations were found between maternal, but not paternal, parenting stress and interparental rating discrepancies on the CBCL. The observed differences between maternal and paternal ratings highlight the importance of gathering reports from both parents when assessing early SEB problems. The findings are more profoundly discussed in the article.

Do child healthcare professionals and parents recognize social-emotional and behavioral problems in 1-year-old infants?

Growing evidence supports the existence of clinically significant social-emotional/behavioral (SEB) problems among as young as 1-year-old infants. However, a substantial proportion of early SEB problems remain unidentified during contacts with child healthcare professionals. In this study, child healthcare nurse (CHCN; N = 1008) and parental (N = 518) reports about SEB worries were gathered, along with the maternal and paternal Brief Infant-Toddler Social and Emotional Assessment (BITSEA) ratings, for 12-month-old infants randomly recruited through Finnish child health centers. Only 1.4-1.8 % of CHCNs, 3.9 % of mothers, and 3.2 % of fathers reported of being worried about the assessed child's SEB development. When the CHCNs' and parental reports were combined, 7.7 % (33/428) of the infants assessed each by all three adults had one (7.0 %), two (0.7 %) or three (0 %) worry reports. Even the combination of the CHCN's and parental worry reports identified only 7.0-13.8 % of the infants with the maternal and/or paternal BITSEA Problem or Competence rating in the of-concern range. Identified associations across the three informants' worry reports, parental BITSEA ratings and sociodemographic factors are discussed in the paper. Routine and frequent use of developmentally appropriate screening measures, such as the BITSEA, might enhance identification and intervening of early SEB problems in preventive child healthcare by guiding both professionals and parents to pay more attention to substantial aspects of young children's SEB development and encouraging them to discuss possible problems and worries.

Attention and Working Memory in Adolescents with Autism Spectrum Disorder: A Functional MRI Study.

The present study examined attention and memory load-dependent differences in the brain activation and deactivation patterns between adolescents with autism spectrum disorders (ASDs) and typically developing (TD) controls using functional magnetic resonance imaging. Attentional (0-back) and working memory (WM; 2-back) processing and load differences (0 vs. 2-back) were analysed. WM-related areas activated and default mode network deactivated normally in ASDs as a function of task load. ASDs performed the attentional 0-back task similarly to TD controls but showed increased deactivation in cerebellum and right temporal cortical areas and weaker activation in other cerebellar areas. Increasing task load resulted in multiple responses in ASDs compared to TD and in inadequate modulation of brain activity in right insula, primary somatosensory, motor and auditory cortices. The changes during attentional task may reflect compensatory mechanisms enabling normal behavioral performance. The inadequate memory load-dependent modulation of activity suggests diminished compensatory potential in ASD.

Finnish mothers' and fathers' reports of their boys and girls by using the Brief Infant-Toddler Social and Emotional Assessment (BITSEA).

This study investigated maternal and paternal reports about their very young boys and girls on the Brief Infant-Toddler Social and Emotional Assessment (BITSEA). Two samples were recruited through child health centers in Northern Finland. The infant sample consisted of 227 children (112 boys and 115 girls) (mean age 13.0±1.1 months) and the toddler sample consisted of 208 children (94 boys and 114 girls) (mean age 19.3±1.4 months). Among the infants, girls obtained higher paternal competence total scores than boys, whereas among the toddlers, both maternal and paternal competence total scores were higher for girls compared to boys. In the problem total scale, boys were scored higher than girls by mothers, but not by fathers, in both age groups. In the externalizing problem domain, maternal scores were higher for boys compared to girls among both samples, whereas paternal scores were significantly higher for boys than for girls only among the infants. Also maternal internalizing problem scores were higher for boys than for girls among the toddlers. Compared to fathers, mothers perceived more social-emotional competencies in toddler boys and girls, as well as more total, externalizing and dysregulation problems in toddler boys. However, significant differences between the maternal and paternal BITSEA ratings were not found among the infants of either sex. The results suggest that sex differences in the social-emotional/behavior domain may be observed by the parents among children as young as 11 to 24 months of age. Our findings highlight the importance of paying attention to probable sex differences when assessing and treating early social-emotional/behavior problems.

Valence scaling of dynamic facial expressions is altered in high-functioning subjects with autism spectrum disorders: an fMRI study.

FMRI was performed with the dynamic facial expressions fear and happiness. This was done to detect differences in valence processing between 25 subjects with autism spectrum disorders (ASDs) and 27 typically developing controls. Valence scaling was abnormal in ASDs. Positive valence induces lower deactivation and abnormally strong activity in ASD in multiple regions. Negative valence increased deactivation in visual areas in subjects with ASDs. The most marked differences between valences focus on fronto-insular and temporal regions. This supports the idea that subjects with ASDs may have difficulty in passive processing of the salience and mirroring of expressions. When the valence scaling of brain activity fails, in contrast to controls, these areas activate and/or deactivate inappropriately during facial stimuli presented dynamically.

Association of the cannabinoid receptor gene (CNR1) with ADHD and post-traumatic stress disorder.

Attention deficit hyperactivity disorder (ADHD) is a highly heritable disorder affecting some 5-10% of children and 4-5% of adults. The cannabinoid receptor gene (CNR1) is a positional candidate gene due to its location near an identified ADHD linkage peak on chromosome 6, its role in stress and dopamine regulation, its association with other psychiatric disorders that co-occur with ADHD, and its function in learning and memory. We tested SNP variants at the CNR1 gene in two independent samples-an unselected adolescent sample from Northern Finland, and a family-based sample of trios (an ADHD child and their parents). In addition to using the trios for association study, the parents (with and without ADHD) were used as an additional case/control sample of adults for association tests. ADHD and its co-morbid psychiatric disorders were examined. A significant association was detected for a SNP haplotype (C-G) with ADHD (P = 0.008). A sex by genotype interaction was observed as well with this haplotype posing a greater risk in males than females. An association of an alternative SNP haplotype in this gene was found for post-traumatic stress disorder (PTSD) (P = 0.04 for C-A, and P = 0.01 for C-G). These observations require replication, however, they suggest that the CNR1 gene may be a risk factor for ADHD and possibly PTSD, and that this gene warrants further investigation for a role in neuropsychiatric disorders.

Prevalence and psychiatric comorbidity of attention-deficit/hyperactivity disorder in an adolescent Finnish population.

OBJECTIVE: The purpose of the study was to estimate the prevalence of attention-deficit/hyperactivity disorder (ADHD) and its clinical characteristics in the Northern Finland Birth Cohort 1986. METHOD: A general population Northern Finland Birth Cohort 1986 of 9,432 children followed prospectively from the early fetal period was surveyed at adolescence (ages 16-18) for ADHD behaviors. Among 6,622 respondents to the survey, a subset of 457 likely cases and controls were evaluated for ADHD and other psychiatric disorders. Chi-square and descriptive statistics were used to examine clinical characteristics of ADHD in the subset, and logistic regression was used to estimate prevalence by weighted extrapolation in the larger cohort. RESULTS: The estimated prevalence of ADHD among adolescents in the Northern Finland Birth Cohort 1986 is 8.5% with a male/female ratio of 5.7:1. The distribution of ADHD subtypes among the ADHD adolescents is 28% Combined, 64% Inattentive, and 8% Hyperactive-Impulsive. A lifetime diagnosis of a broadly defined ADHD (probable or definite) had a prevalence of 18.2% with a male/female odds ratio (OR) of 3.2. This lifetime diagnosis of ADHD is significantly associated with anxiety (OR 2.4), mood (OR 2.9), and disruptive behavioral disorders (OR 17.3) in the cohort. CONCLUSIONS: ADHD is a common neurobehavioral disorder among Northern Finnish adolescents and significantly associated with psychiatric comorbidity in adolescence.

Subtypes versus severity differences in attention-deficit/hyperactivity disorder in the Northern Finnish Birth Cohort.

OBJECTIVE: To investigate whether behaviors of inattention, hyperactivity, and impulsivity among adolescents in Northern Finland reflect qualitatively distinct subtypes of ADHD, variants along a single continuum of severity, or of severity differences within subtypes. METHOD: Latent class models, exploratory factor models, and factor mixture models were applied to questionnaire data of ADHD behaviors obtained from the Northern Finland Birth Cohort (NFBC). Latent class models correspond to qualitatively distinct subtypes, factor analysis corresponds to severity differences, and factor mixture analysis allows for both subtypes and severity differences within subtypes. RESULTS: A comparison of the different models shows that models that distinguish between a low scoring majority class (unaffecteds) and a high scoring minority class (affecteds), and allow for two factors (inattentive, hyperactive-impulsive) with severity differences provide the best fit. CONCLUSIONS: The analysis provides support that a high-scoring minority group (8.8% of males and 6.8% of females) likely reflects an ADHD group in the Northern Finland Birth Cohort, whereas the majority of the population falls into a low-scoring group of unaffecteds. Distinct factors composed of items of inattention and hyperactivity-impulsivity are evident for both sexes with considerable variability in severity within each class.

Executive functioning among Finnish adolescents with attention-deficit/hyperactivity disorder.

OBJECTIVE: The present study examined cognitive functioning in a population sample of adolescents with and without attention-deficit/hyperactivity disorder (ADHD) from the Northern Finland Birth Cohort 1986. METHOD: The sample consisted of 457 adolescents ages 16 to 18 who were assessed using a battery of cognitive tasks. Performance according to diagnostic group (control, behavior disorder, and ADHD) and sex was compared. Then, the effect of executive function deficit (EFD) was assessed by diagnostic group status on behavioral and cognitive measures. RESULTS: When compared to non-ADHD groups, adolescents with ADHD exhibited deficits on almost all of the cognitive measures. The behavior disorder group obtained scores that were generally intermediate between the ADHD and control groups, but exhibited deficits in intelligence and executive function similar to the ADHD group. Approximately half the ADHD sample had EFD; however, the type and presence of EFDs were not differentially related to cognitive performance as a function of diagnosis. CONCLUSIONS: These findings indicate that EFDs are more frequent in ADHD than control or behavior disorder groups. EFDs are a general risk factor for poor cognitive functioning across multiple domains, irrespective of diagnostic status.

ADHD symptoms and subtypes: relationship between childhood and adolescent symptoms.

OBJECTIVE: To study attention-deficit/hyperactivity disorder (ADHD) symptoms and DSM-IV subtypes in childhood and adolescence. METHOD: A total of 457 adolescents ages 16 to 18 years from the Northern Finland Birth Cohort 1986 participated in an epidemiological survey for ADHD. After assessment with a diagnostic interview those with current or childhood ADHD were classified using DSM-IV criteria. Childhood diagnosis of ADHD was set according to retrospective recall. The characteristics and relationships in ADHD symptomatology in childhood and adolescence were studied in relation to behavioral problems and parental history of attentional problems. RESULTS: ADHD was reported more commonly in childhood than in adolescence and variations in subtype classification occurred. Those with childhood and adolescent diagnosis had endorsed specific inattentive symptoms more commonly, had greater comorbid major depression and/or oppositional defiant disorder, and had fathers with more reported attentional problems than those with only childhood diagnosis. In childhood, ADHD subtypes differed along symptom severity, but by adolescence these differences were no longer significant. CONCLUSIONS: The persistence of ADHD from childhood to adolescence may be common. Specific inattentive symptoms, certain psychiatric comorbidity, and family history of attention problems (fathers specifically) contribute to the risk of persistent ADHD. ADHD subtype differences reflect symptom severity differences in childhood that are negligible by adolescence.

ADHD candidate gene study in a population-based birth cohort: association with DBH and DRD2.

OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) is a common childhood-onset disorder with a significant impact on public health. Although a genetic contribution to risk is evident, predisposing genetic determinants remain largely unknown despite extensive research. So far, the most promising candidate genes have been those involved in dopamine and serotonin pathways. This study tests a series of allelic variants within such candidate genes to determine their potential influence on ADHD susceptibility. METHOD: We used a population sample ascertained from a birth cohort of a subpopulation of Finland, characterized by founder effect and isolation, thus minimizing genetic heterogeneity. The subjects were systematically ascertained using DSM-IV diagnostic criteria for ADHD from the Northern Finland Birth Cohort 1986 of more than 9,000 individuals, resulting in the study sample of 188 ADHD cases and 166 controls. We genotyped markers in 13 candidate genes, including critical components of dopamine and serotonin pathways. RESULTS: We report evidence for association of ADHD with allelic variants of the dopamine beta-hydroxylase (DBH) and dopamine receptor D2 (DRD2) genes. CONCLUSIONS: Our study supports the involvement of the dopamine pathway in the etiology of ADHD; specifically the genes DBH and DRD2 deserve more attention in further studies.

How long do the consequences of parental preference last: A study of twins from pregnancy to young adulthood.

We analyzed depressive and psychosomatic symptoms in relation to parental preference in 419 twins at the age of 22 to 30 years. Depressiveness was elicited with Children's Depression Inventory and reported as a total score and three subscales (low self-confidence, anhedonia and sadness) based on factor analysis as reported in a previous epidemiological study conducted in Finland. Items assessing nervous complaints and somatic symptoms were adapted from Finnish studies of juvenile health habits. Twins reported the preference in two directions: experienced parental preference towards either twin, and twin's own preference towards either parent. About half of the twins were from pairs where both twins experienced having been equally close to both parents, while about 30% were from 'equal and mother's' pair, where one twin evaluated having been preferred by the mother and the co-twin evaluated having been equally close to both parents. According to the twins' own preference, about one third of the twin pairs were 'both equal', one third 'both mother's' and one third 'equal and mother's'. Those male twins who were equally close to both parents (experienced parental preference) had least total depressiveness, while females in the intermediate situation had the highest self-confidence and least anhedonia and nervousness. According to twins' own preference, twins who felt equally close to both parents had the least depressiveness and anhedonia. The intermediate position seems to be the best alternative, as these twins had the least symptoms.