Katja Jussila

Comorbid Psychiatric Disorders Associated with Asperger Syndrome/High-functioning Autism: A Community- and Clinic-based Study

The present study identifies the prevalence and types of comorbid psychiatric disorders associated with Asperger syndrome (AS)/high-functioning autism (HFA) in a combined community- and clinic-based sample of fifty 9- to 16-year-old subjects using the Schedule for Affective Disorders and Schizophrenia for School-Age Children, Present and Lifetime Version. The level of functioning was estimated using the Children’s Global Assessment Scale. The results support common (prevalence 74%) and often multiple comorbid psychiatric disorders in AS/HFA; behavioral disorders were shown in 44%, anxiety disorders in 42% and tic disorders in 26%. Oppositional defiant disorder, major depressive disorder and anxiety disorders as comorbid conditions indicated significantly lower levels of functioning. To target interventions, routine evaluation of psychiatric comorbidity in subjects with AS/HFA is emphasized.

Autism Spectrum Disorders According to DSM-IV-TR and Comparison With DSM-5 Draft Criteria: An Epidemiological Study

OBJECTIVE The latest definitions of autism spectrum disorders (ASDs) were specified in DSM-IV-TR in 2000. DSM-5 criteria are planned for 2013. Here, we estimated the prevalence of ASDs and autism according to DSM-IV-TR, clarified confusion concerning diagnostic criteria, and evaluated DSM-5 draft criteria for ASD posted by the American Psychiatry Association (APA) in February 2010. METHOD This was an epidemiological study of 5,484 eight-year-old children in Finland, 4,422 (81%) of them rated via the Autism Spectrum Screening Questionnaire by parents and/or teachers, and 110 examined by using a structured interview, semi-structured observation, IQ measurement, school-day observation, and patient records. Diagnoses were assigned according to DSM-IV-TR criteria and DSM-5 draft criteria in children with a full-scale IQ (FSIQ) ≥50. Patient records were evaluated in children with an FSIQ <50 to discover diagnoses of ASDs. RESULTS The prevalence of ASDs was 8.4 in 1,000 and that of autism 4.1 in 1,000 according to DSM-IV-TR. Of the subjects with ASDs and autism, 65% and 61% were high-functioning (FSIQ ≥70), respectively. The prevalence of pervasive developmental disorder not otherwise specified was not estimated because of inconsistency in DSM-IV-TR criteria. DSM-5 draft criteria were shown to be less sensitive in regard to identification of subjects with ASDs, particularly those with Aspergers syndrome and some high-functioning subjects with autism. CONCLUSIONS DSM-IV-TR helps with the definition of ASDs only up to a point. We suggest modifications to five details of DSM-5 draft criteria posted by the APA in February 2010. Completing revision of DSM criteria for ASDs is a challenging task.

Alterations in regional homogeneity of resting-state brain activity in autism spectrum disorders

Measures assessing resting-state brain activity with blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) can reveal cognitive disorders at an early stage. Analysis of regional homogeneity (ReHo) measures the local synchronization of spontaneous fMRI signals and has been successfully utilized in detecting alterations in subjects with attention-deficit hyperactivity disorder (ADHD), depression, schizophrenia, Parkinsons disease and Alzheimers dementia. Resting-state brain activity was investigated in 28 adolescents with autism spectrum disorders (ASD) and 27 typically developing controls being imaged with BOLD fMRI and analyzed with the ReHo method. The hypothesis was that ReHo of resting-state brain activity would be different between ASD subjects and controls in brain areas previously shown to display functional alterations in stimulus or task based fMRI studies. Compared with the controls, the subjects with ASD had significantly decreased ReHo in right superior temporal sulcus region, right inferior and middle frontal gyri, bilateral cerebellar crus I, right insula and right postcentral gyrus. Significantly increased ReHo was discovered in right thalamus, left inferior frontal and anterior subcallosal gyrus and bilateral cerebellar lobule VIII. We conclude that subjects with ASD have right dominant ReHo alterations of resting-state brain activity, i.e., areas known to exhibit abnormal stimulus or task related functionality. Our results demonstrate that there is potential in utilizing the ReHo method in fMRI analyses of ASD.

Multi-informant reports of psychiatric symptoms among high-functioning adolescents with Asperger syndrome or autism

The aim of the study was to examine psychiatric symptoms in high-functioning adolescents with autism spectrum disorders reported by multiple informants. Forty-three 11- to 17-year-old adolescents with Asperger syndrome (AS) or high-functioning autism (HFA) and 217 typically developed adolescents completed the Youth Self-Report (YSR), while their parents completed the Child Behavior Checklist (CBCL). Teachers of adolescents with AS/HFA completed the Teacher Report Form (TRF). The informants reported significantly more psychiatric symptoms, especially withdrawn, anxious/depressed, social and attention problems, in adolescents with AS/HFA than in controls. In contrast to findings in the general population, the psychiatric problems of adolescents with AS/HFA are well acknowledged by multiple informants, including self-reports. However, anxiety and depressive symptoms were more commonly reported by adolescents with AS/HFA and their teachers than their parents, indicating that some emotional distress may be hidden from their parents.

Similarities in the phenotype of the auditory neural substrate in children with Asperger syndrome and their parents

Asperger syndrome (AS) is a developmental disorder of brain function characterized by deficits in social interaction including difficulties in understanding emotional expressions. Children with AS share some of the behavioural characteristics with their parents and AS seems to run particularly in the male members of the same families. The aim of the present study was to determine whether similarities could be found between children with AS and their parents at central auditory processing. It was found that in children with AS the sound encoding, as reflected by the exogenous components of event‐related potentials, was similarly abnormal as in both their mothers and fathers. However, their abnormal cortical auditory discrimination, as indexed by the prolonged latency of the mismatch negativity, resembled that of their fathers but not that of their mothers. The present results suggest that complex genetic mechanisms may contribute to auditory abnormalities encountered in children with AS.

Resting state fMRI reveals a default mode dissociation between retrosplenial and medial prefrontal subnetworks in ASD despite motion scrubbing

In resting state functional magnetic resonance imaging (fMRI) studies of autism spectrum disorders (ASDs) decreased frontal-posterior functional connectivity is a persistent finding. However, the picture of the default mode network (DMN) hypoconnectivity remains incomplete. In addition, the functional connectivity analyses have been shown to be susceptible even to subtle motion. DMN hypoconnectivity in ASD has been specifically called for re-evaluation with stringent motion correction, which we aimed to conduct by so-called scrubbing. A rich set of default mode subnetworks can be obtained with high dimensional group independent component analysis (ICA) which can potentially provide more detailed view of the connectivity alterations. We compared the DMN connectivity in high-functioning adolescents with ASDs to typically developing controls using ICA dual-regression with decompositions from typical to high dimensionality. Dual-regression analysis within DMN subnetworks did not reveal alterations but connectivity between anterior and posterior DMN subnetworks was decreased in ASD. The results were very similar with and without motion scrubbing thus indicating the efficacy of the conventional motion correction methods combined with ICA dual-regression. Specific dissociation between DMN subnetworks was revealed on high ICA dimensionality, where networks centered at the medial prefrontal cortex and retrosplenial cortex showed weakened coupling in adolescents with ASDs compared to typically developing control participants. Generally the results speak for disruption in the anterior-posterior DMN interplay on the network level whereas local functional connectivity in DMN seems relatively unaltered.

Psychometric evaluation of social phobia and anxiety inventory for children (SPAI-C) and social anxiety scale for children-revised (SASC-R)

The study evaluated the psychometric properties of Finnish versions of the Social Phobia and Anxiety Inventory for Children (SPAI-C) and the Social Anxiety Scale for Children-Revised (SASC-R). 352 students (M = 12.2 years) participated in the study and completed the SPAI-C and SASC-R. In addition, 68 participants (M = 12.2 years) and their parents were interviewed with the Schedule for Affective Disorders and Schizophrenia for School Aged Children (K-SADS-PL). The SPAI-C was more sensitive for identifying youth meeting criteria for social phobia (SP), whereas the SASC-R demonstrated greater specificity. The youth in this sample had lower mean total scores on the self-report questionnaires than did those in the original validitation studies of the SPAI-C and SASC-R conducted in America. These findings question whether cross-cultural differences in the expression of SP influence the clinical cut-off scores used in translated versions of social anxiety questionnaires.The study evaluated the psychometric properties of Finnish versions of the Social Phobia and Anxiety Inventory for Children (SPAI-C) and the Social Anxiety Scale for Children-Revised (SASC-R). 352 students (M = 12.2 years) participated in the study and completed the SPAI-C and SASC-R. In addition, 68 participants (M = 12.2 years) and their parents were interviewed with the Schedule for Affective Disorders and Schizophrenia for School Aged Children (K-SADS-PL). The SPAI-C was more sensitive for identifying youth meeting criteria for social phobia (SP), whereas the SASC-R demonstrated greater specificity. The youth in this sample had lower mean total scores on the self-report questionnaires than did those in the original validitation studies of the SPAI-C and SASC-R conducted in America. These findings question whether cross-cultural differences in the expression of SP influence the clinical cut-off scores used in translated versions of social anxiety questionnaires.

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.

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

Abstract 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.

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

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.