The Role of Social Skills in Predicting Treatment-Recovery in Children with a Social Anxiety Disorder.

The current study investigated the role of social skills and its interaction with social anxiety as predictors of treatment outcome in children with an anxiety disorder either with or without a social anxiety disorder (SoAD). In total, 133 children (aged 8 to 13) with an anxiety disorder received a 10-session cognitive behavioral treatment (FRIENDS program). Pre- to post treatment Reliable Change (RC) and Treatment-Recovery (TR) were assessed from a multi-informant perspective, by including diagnostic information (ADIS C/P), child-reported anxiety symptoms (MASC) and parent-reported internalizing symptoms (CBCL-Int). Social skills were assessed with the parent-rated Social Skills Rating System (assertion, self-control, responsibility). Results showed that 1) parents of children with a SoAD reported significantly less favorable use of assertive and responsible social behavior in their children pre-treatment than parents of children without SoAD, 2) children with higher social skills had a better treatment recovery, and 3) children with anxiety and higher responsible behavior pre-treatment and without a SoAD had a better treatment recovery, but this effect did not show for children with SoAD. In conclusion, better use of social behavior increased the likelihood of treatment recovery but not of reliable change. Further studies on the role of social skills in the treatment of childhood (social) anxiety are needed to investigate the mechanisms by which social skills impact treatment outcome.

Anterior cingulate cortex grey matter volume abnormalities in adolescents with PTSD after childhood sexual abuse.

Adverse childhood experiences (ACE) substantially increase the risk of later psychiatric and somatic pathology. While neurobiological factors are likely to play a mediating role, specific insights are lacking. The scarce neuroimaging studies in traumatised pediatric populations have provided inconsistent results, potentially due to the inclusion of different types of trauma. To further improve our understanding of the neurobiology of pediatric psychotrauma, this study seeks to investigate abnormalities in grey matter volume (GMV) in a homogeneous group of adolescents with posttraumatic stress disorder (PTSD) due to childhood sexual abuse (CSA) and the relationship between GMV and symptom severity. We performed a voxel based morphometry (VBM) analysis in 21 adolescents with CSA-related PTSD and 25 matched non-traumatised, non-clinical adolescents. Hippocampus, amygdala, anterior cingulate cortex (ACC), medial PFC (mPFC) and superior temporal gyrus (STG) were chosen as regions of interest (ROIs). Trauma symptomatology was measured with the Trauma Symptom Checklist for Children (TSCC) and dissociation symptoms with the Adolescent Dissociative Experiences Scale (A-DES). The ROI analysis showed that the CSA-related PTSD group had significant smaller volumes of the dorsal ACC as compared to healthy controls. However, no correlations were found between GMV and scores on the TSCC and A-DES. The smaller ACC volume is partly in line with previous studies in traumatised youth and is a consistent finding in traumatised adults. Taken together our results suggest that the dorsal ACC is implicated in the neurobiological sequelae of CSA, potentially associated with an altered evaluative processing of emotion, but not directly with PTSD severity.

Differential Fairness Decisions and Brain Responses After Expressed Emotions of Others in Boys with Autism Spectrum Disorders.

Little is known about how emotions expressed by others influence social decisions and associated brain responses in autism spectrum disorders (ASD). We investigated the neural mechanisms underlying fairness decisions in response to explicitly expressed emotions of others in boys with ASD and typically developing (TD) boys. Participants with ASD adjusted their allocation behavior in response to the emotions but reacted less unfair than TD controls in response to happiness. We also found reduced brain responses in the precental gyrus in the ASD versus TD group when receiving happy versus angry reactions and autistic traits were positively associated with activity in the postcentral gyrus. These results provide indications for a role of precentral and postcentral gyrus in social-affective difficulties in ASD.

Amygdala habituation to emotional faces in adolescents with internalizing disorders, adolescents with childhood sexual abuse related PTSD and healthy adolescents.

Adolescents with internalizing disorders and adolescents with childhood sexual abuse related post-traumatic stress disorder (CSA-related PTSD) show a large overlap in symptomatology. In addition, brain research indicated hyper-responsiveness and sustained activation instead of habituation of amygdala activation to emotional faces in both groups. Little is known, however, about whether the same patterns of amygdala habituation are present in these two groups. The current study examined habituation patterns of amygdala activity to emotional faces (fearful, happy and neutral) in adolescents with a DSM-IV depressive and/or anxiety disorder (N=25), adolescents with CSA-related PTSD (N=19) and healthy controls (N=26). Behaviourally, the adolescents from the internalizing and CSA-related PTSD group reported more anxiety to fearful and neutral faces than adolescents from the control group and adolescents from the CSA-related PTSD group reacted slower compared to the internalizing group. At the whole brain level, there was a significant interaction between time and group within the left amygdala. Follow-up ROI analysis showed elevated initial activity in the amygdala and rapid habituation in the CSA-related PTSD group compared to the internalizing group. These findings suggest that habituation patterns of amygdala activation provide additional information on problems with emotional face processing. Furthermore, the results suggest there are differences in the underlying neurobiological mechanisms related to emotional face processing for adolescents with internalizing disorders and adolescents with CSA-related PTSD. Possibly CSA-related PTSD is characterized by a stronger primary emotional response driven by the amygdala.

Different brain responses during empathy in autism spectrum disorders versus conduct disorder and callous-unemotional traits.

BACKGROUND: Deficits in empathy are reported in autism spectrum disorders (ASD) and also underlie antisocial behavior of individuals with conduct disorder and callous-unemotional traits (CD/CU+). Many studies suggest that individuals with ASD are typically impaired in cognitive aspects of empathy, and individuals with CD/CU+ typically in affective aspects. In the current study, we compared the neural correlates of cognitive and affective aspects of empathy between youth with ASD and youth with CD/CU+. METHODS: Functional magnetic resonance imaging (fMRI) was used to assess boys with ASD (N = 23), boys with CD/CU+ (N = 23), and typically developing (TD) boys (N = 33), aged 15-19 years. Angry and fearful faces were presented and participants were asked to either infer the emotional state from the face (other-task; emotion recognition) or to judge their own emotional response to the face (self-task; emotional resonance). RESULTS: During emotion recognition, boys with ASD showed reduced responses compared to the other groups in the ventromedial prefrontal cortex (vmPFC). During emotional resonance, the CD/CU+ and ASD groups showed reduced amygdala responses compared to the TD controls, boys with ASD showed reduced responses in bilateral hippocampus, and the CD/CU+ boys showed reduced responses in the inferior frontal gyrus (IFG) and anterior insula (AI). CONCLUSION: Results suggest differential abnormal brain responses associated with specific aspects of empathic functioning in ASD and CD/CU+. Decreased amygdala responses in ASD and CD/CU+ might point to impaired emotion processing in both disorders, whereas reduced vmPFC responses suggest problems in processing cognitive aspects of empathy in ASD. Reduced IFG/AI responses, finally, suggest decreased emotional resonance in CD/CU+.

Abnormalities of white matter integrity in the corpus callosum of adolescents with PTSD after childhood sexual abuse: a DTI study.

This study seeks to determine whether white matter integrity in the brain differs between adolescents with post-traumatic stress disorder (PTSD) due to childhood sexual abuse (CSA) and matched healthy adolescents and whether there is a relationship between white matter integrity and symptom severity in the patient group. Using 3T diffusion tensor imaging, we examined fractional anisotropy (FA) in a group of adolescents with CSA-related PTSD (n = 20) and matched healthy controls (n = 20), in a region of interest consisting of the bilateral uncinate fasciculus (UF), the genu, splenium and body of the corpus callosum (CC), and the bilateral cingulum. In addition, we performed an exploratory whole brain analysis. Trauma symptomatology was measured with the Trauma Symptom Checklist for Children (TSCC) to enable correlational analyses between FA differences and trauma symptomatology. The PTSD group had significantly lower FA values in the genu, midbody and splenium of the CC in comparison with controls (p < 0.05, tfce corrected). Post hoc analyses of the eigenvalues of the DTI scan showed increased radial and mean diffusivity in the patient group. In addition, we found a significant negative correlation between scores on the anger subscale of the TSCC and FA values in the left body of the CC in patients (p < 0.05). Adolescents with CSA-related PTSD show decreased FA in the CC, with abnormalities in the integrity of the left body of the CC being related to anger symptoms. These findings suggest that early trauma exposure affects the development of the CC, which may play a role in the pathophysiology of PTSD in adolescents.

Adult Attachment Interview differentiates adolescents with Childhood Sexual Abuse from those with clinical depression and non-clinical controls.

Although attachment representation is considered to be disturbed in traumatized adolescents, it is not known whether this is specific for trauma, as comparative studies with other clinical groups are lacking. Therefore, attachment representation was studied by means of the Adult Attachment Interview in adolescents with Childhood Sexual Abuse (CSA) (N = 21), clinical depression (N = 28) and non-clinical controls (N = 28). Coherence of mind and unresolved loss or trauma, as well as the disorganized attachment classification differentiated the CSA group from the clinical depression group and controls, over and above age, IQ, and psychiatric symptomatology. In the current era of sustained criticism on criteria-based classification, this may well carry substantial clinical relevance. If attachment is a general risk or vulnerability factor underlying specific psychopathology, this may guide diagnostic assessment as well as treatment.

Amygdala activation during emotional face processing in adolescents with affective disorders: the role of underlying depression and anxiety symptoms.

Depressive and anxiety disorders are often first diagnosed during adolescence and it is known that they persist into adulthood. Previous studies often tried to dissociate depressive and anxiety disorders, but high comorbidity makes this difficult and maybe even impossible. The goal of this study was to use neuroimaging to test what the unique contribution is of depression and anxiety symptomatology on emotional processing and amygdala activation, and to compare the results with a healthy control group. We included 25 adolescents with depressive and/or anxiety disorders and 26 healthy adolescents. Participants performed an emotional face processing task while in the MRI scanner. We were particularly interested in the relation between depression/anxiety symptomatology and patterns of amygdala activation. There were no significant differences in activation patterns between the control group and the clinical group on whole brain level and ROI level. However, we found that dimensional scores on an anxiety but not a depression subscale significantly predicted brain activation in the right amygdala when processing fearful, happy and neutral faces. These results suggest that anxiety symptoms are a better predictor for differentiating activation patterns in the amygdala than depression symptoms. Although the current study includes a relatively large sample of treatment naïve adolescents with depression/anxiety disorders, results might be influenced by differences between studies in recruitment strategies or methodology. Future research should include larger samples with a more equal distribution of adolescents with a clinical diagnosis of depression and/or anxiety. To conclude, this study shows that abnormal amygdala responses to emotional faces in depression and anxiety seems to be more dependent on anxiety symptoms than on depression symptoms, and thereby highlights the need for more research to better characterize clinical groups in future studies.

Aberrant resting-state functional connectivity in limbic and salience networks in treatment--naïve clinically depressed adolescents.

BACKGROUND: Depression is prevalent and typically has its onset in adolescence. Resting-state fMRI could help create a better understanding of the underlying neurobiological mechanisms during this critical period. In this study, resting-state functional connectivity (RSFC) is examined using seed regions-of-interest (ROIs) associated with three networks: the limbic network, the default mode network (DMN) and the salience network. METHODS: Twenty-six treatment-naïve, clinically depressed adolescents of whom 18 had comorbid anxiety, and 26 pair-wise matched healthy controls underwent resting-state fMRI. The three networks were investigated using a seed-based ROI approach with seeds in the bilateral amygdala (limbic network), bilateral dorsal anterior cingulate cortex (dACC; salience network) and bilateral posterior cingulate cortex (default mode network). RESULTS: Compared to healthy controls, clinically depressed adolescents showed increased RSFC of the left amygdala with right parietal cortical areas, and decreased right amygdala RSFC with left frontal cortical areas including the ACC, as well as with right occipito-parietal areas. The bilateral dACC showed decreased RSFC with the right middle frontal gyrus, frontal pole, and inferior frontal gyrus in clinically depressed adolescents. No abnormalities in DMN RSFC were found, and differences in RSFC did not correlate with clinical measures. CONCLUSIONS: The aberrant RSFC of the amygdala network and the dACC network may be related to altered emotion processing and regulation in depressed adolescents. Our results provide new insights into RSFC in clinically depressed adolescents and future models on adolescent depression may include abnormalities in the connectivity of salience network.

Reduced anterior cingulate gray matter volume in treatment-naïve clinically depressed adolescents.

Adolescent depression is associated with increased risk for suicidality, social and educational impairment, smoking, substance use, obesity, and depression in adulthood. It is of relevance to further our insight in the neurobiological mechanisms underlying this disorder in the developing brain, as this may be essential to optimize treatment and prevention of adolescent depression and its negative clinical trajectories. The equivocal findings of the limited number of studies on neural abnormalities in depressed youth stress the need for further neurobiological investigation of adolescent depression. We therefore performed a voxel-based morphometry study of the hippocampus, amygdala, superior temporal gyrus, and anterior cingulate cortex (ACC) in 26 treatment-naïve, clinically depressed adolescents and 26 pair-wise matched healthy controls. Additionally, an exploratory whole-brain analysis was performed. Clinically depressed adolescents showed a volume reduction of the bilateral dorsal ACC compared to healthy controls. However, no association was found between gray matter volume of the ACC and clinical severity scores for depression or anxiety. Our finding of a smaller ACC in clinically depressed adolescents is consistent with literature on depressed adults. Future research is needed to investigate if gray matter abnormalities precede or follow clinical depression in adolescents.

How to use the ADI-R for classifying autism spectrum disorders? Psychometric properties of criteria from the literature in 1,204 Dutch children.

The algorithm of the Autism Diagnostic Interview-Revised provides criteria for autism versus non-autism according to DSM-IV. Criteria for the broader autism spectrum disorders are needed. This study investigated the validity of seven sets of criteria from the literature, in 1,204 Dutch children (aged 3-18 years) with and without mental retardation. The original criteria (Rutter et al. in ADI-R Autism Diagnostic Interview Revised. Manual. Western Psychological Services, Los Angeles, 2003) well discriminated ASD from non-ASD in MR. All other criteria (IMGSAC in Am Soc Hum Genet 69:570-581 2001; Sung et al. in Am J Hum Genet 76: 68-81, 2005; Risi et al. in J Am Acad Child Adolesc Psychiatry 45: 1094-1103, 2006) were sensitive at the cost of specificity, bearing the risk of overinclusiveness. In the group without MR, clinicians should decide whether sensitivity or specificity is aimed for, to choose the appropriate criteria. Including the Autism Diagnostic Observation Schedule revised algorithms in the classification, the specificity increases, at the cost of sensitivity. This study adds to a more valid judgment on which criteria to use for specific objectives.

How stable is activation in the amygdala and prefrontal cortex in adolescence? A study of emotional face processing across three measurements.

Prior developmental functional magnetic resonance imaging (fMRI) studies have demonstrated elevated activation patterns in the amygdala and prefrontal cortex (PFC) in response to viewing emotional faces. As adolescence is a time of substantial variability in mood and emotional responsiveness, the stability of activation patterns could be fluctuating over time. In the current study, 27 healthy adolescents (age: 12-19 years) were scanned three times over a period of six months (mean test-retest interval of three months; final samples N=27, N=22, N=18). At each session, participants performed the same emotional faces task. At first measurement the presentation of emotional faces resulted in heightened activation in bilateral amygdala, bilateral lateral PFC and visual areas including the fusiform face area. Average activation did not differ across test-sessions over time, indicating that at the group level activation patterns in this network do not vary significantly over time. However, using the Intraclass Correlation Coefficient (ICC), fMRI reliability demonstrated only fair reliability for PFC (ICC=0.41-0.59) and poor reliability for the amygdala (ICC<0.4). These findings suggest substantial variability of brain activity over time and may have implications for studies investigating the influence of treatment effects on changes in neural levels in adolescents with psychiatric disorders.

The visual rooting reflex in individuals with autism spectrum disorders and co-occurring intellectual disability.

The rooting reflex has long been studied by neurologists and developmentalists and is defined as an orientation toward tactile stimulation in the perioral region or visual stimulation near the face. Nearly, all previous reports of the visual rooting reflex (VRR) concern its presence in adults with neurological dysfunction. Previously, the VRR was reported to be present in a majority of individuals with autism and absent in control subjects. In the present larger study, we examined the presence of the VRR in 155 individuals with ASD and co-occurring Intellectual Disability (ASD + ID: autism, N = 60; Pervasive Developmental Disorder-Not Otherwise Specified (PDD_NOS), N = 95) and in a contrast group of 65 individuals with ID only. The VRR was present significantly more often in the ASD + ID (43.9%) group than in the ID-only group (24.6%; χ(1)(2)= 7.19; P = 0.007). Individuals with autism displayed a VRR more often (55.0%) than individuals with PDD-NOS (36.8%; χ(1)(2)= 4.92; P = 0.026) and individuals with ID only (24.6%; χ(1)(2)= 12.09; P = 0.001). A positive VRR was associated with lower IQ and adaptive functioning; in the ASD + ID group, ADI-R/ADOS domain scores were significantly higher in the VRR-positive subgroup. The results replicate and extend the finding of an increased occurrence of the VRR in autism. Although some association with IQ was observed, the VRR occurred substantially more often in the autism group compared with an intellectually disabled group, indicating some degree of specificity. Additional studies of infants and children with typical development, ASD and ID are needed to determine the utility of the VRR in ASD risk assessment and to elucidate possible specific behavioral associations.

Standardized ADOS scores: measuring severity of autism spectrum disorders in a Dutch sample.

The validity of the calibrated severity scores on the ADOS as reported by Gotham et al. (J Autism Dev Disord 39: 693-705, 2009), was investigated in an independent sample of 1248 Dutch children with 1455 ADOS administrations (modules 1, 2 and 3). The greater comparability between ADOS administrations at different times, ages and in different modules, as reached by Gotham et al. with the calibrated severity measures, seems to be corroborated by the current study for module 1 and to a lesser extent for module 3. For module 2, the calibrated severity scores need to be further investigated within a sample that resembles Gotham's sample in age and level of verbal functioning.

Validity of the Children's Social Behavior Questionnaire (CSBQ) in children with intellectual disability: comparing the CSBQ with ADI-R, ADOS, and clinical DSM-IV-TR classification.

The Children's Social Behavior Questionnaire (CSBQ) was compared with the Autism Diagnostic Interview-Revised (ADI-R), Autism Diagnostic Observation Schedule (ADOS), and clinical classification in children with mild and moderate intellectual disability (ID), to investigate its criterion related validity. The contribution of the CSBQ to a classification of Autism Spectrum Disorder (ASD) was most specific for the subscales 'contact' and 'stereotyped', with high coherence with all three classification methods. The CSBQ may be used as a signaling, screening, or describing instrument for children with ASD and ID, as it complements other methods by adding unique information about the clinical presentation.

Evaluation of the ADOS revised algorithm: the applicability in 558 Dutch children and adolescents.

The revised ADOS algorithms, proposed by Gotham et al. (J Autism Dev Disord 37:613-627, 2007), were investigated in an independent sample of 558 Dutch children (modules 1, 2 and 3). The revised algorithms lead to better balanced sensitivity and specificity for modules 2 and 3, without losing efficiency of the classification. Including the restricted repetitive behaviour domain in the algorithm contributes to a clinical ASD classification in modules 2 and 3. For module 1, the results indicate less improvement, probably due to the low-functioning population. In most groups, the advantages of the revised algorithms are achieved without losing the strength of the original algorithm.

Developmental trajectories of depressive symptoms from early childhood to late adolescence: gender differences and adult outcome.

BACKGROUND: Limited information is available on gender differences and young-adult poor outcome in children and adolescents following distinct developmental trajectories of depressive symptoms. METHODS: Parent information on depressive symptoms of 4- to 18-year-olds from an ongoing Dutch community-based longitudinal multiple-cohort study (N = 2,076) was used to estimate trajectories from semi-parametric mixture models. The identified trajectories were used to predict depressive problems, general mental health problems, referral to mental health care, and educational attainment in young adulthood. RESULTS: In both genders six distinct developmental trajectories were identified. Gender differences existed not only in level, but also in shape and timing of onset of depressive problems. Only in girls was a chronic trajectory of early childhood-onset depression identified. In both boys and girls a group with increasing levels of depressive symptoms was identified that reached a high level around adolescence, although boys showed an earlier onset. Two decreasing trajectories were found in boys, one reaching normative levels of depressive symptoms around late childhood and one around mid-adolescence, while none was found for girls. Individuals who followed elevated trajectories during their whole childhood or starting at adolescence had significantly more depressive and other mental health problems in young adulthood compared to those who followed normative trajectories. Boys in these elevated trajectories showed lower educational attainment, while girls were more likely to have been referred to mental health care. CONCLUSIONS: This study shows the value of estimating growth-mixture models separately for boys and girls. Girls with early childhood or adolescence-onset depressive problems and boys with depressive problems during childhood or starting in adolescence are especially at risk for poor outcome as young adults and should be considered candidates for intervention.

Predictors of future depression in early and late adolescence.

BACKGROUND: This study examined whether the possibility to predict future DSM-IV depressive disorder can be increased with recurrent screening for depression in community adolescents, compared to single screening in early or in late adolescence. In addition, it examined which depressive symptoms in early and late adolescence predicted future depressive disorder most accurately. METHODS: Participants from an ongoing longitudinal cohort study were assessed when they were aged between 10 and 15 (early adolescence), and between 14 and 19 (late adolescence), and were followed until they were 20-25 (young adulthood). The Child Behavior Checklist (CBCL) and Youth Self-Report (YSR) were used to screen for depression in early and late adolescence, and CIDI/DSM-IV diagnoses of depressive disorder were used as the outcome measure during follow-up. RESULTS: Recurrent screening only slightly improved the prediction of future depression, and cognitive and physical symptoms in late adolescence predicted future depression accurately in boys. Sleeping problems in early adolescence predicted future depression in girls. LIMITATIONS: The main limitation was the retrospective recall of the age of onset of a depressive disorder. CONCLUSIONS: Recurrent screening for depression did not predict future depressive disorder better than single screening in late adolescence. However, depressive symptoms like sleeping problems predicted future depression quite accurately in adolescent boys and girls. This indicates that it may be useful to screen adolescents for the presence of such symptoms, for instance in school settings, to predict which adolescents are at risk to develop DSM-IV depressive disorder in early adulthood.

Autonomic reactivity in clinically referred children attention-deficit/hyperactivity disorder versus anxiety disorder.

This study examined whether children with attention-deficit/hyperactivity disorder (ADHD) have lower autonomic nervous system (ANS) activity and show less stress reactivity than children with an anxiety disorder. It also explored whether such a difference was accounted for by comorbid oppositional defiant disorder (ODD) or conduct disorder (CD) in some of the ADHD children. Forty-three referred children performed a stress task, during which skin conductance (SCL) and heart rate (HR) levels were measured. Results showed that the ADHD group had similar SCL responses as the anxiety disorder group, but showed less HR reactivity immediately after the stress task. The ADHD with ODD/CD group had a slightly higher HR level than the pure ADHD group, but showed similar SCL and HR reactivity and recovery. It was concluded that ADHD children have less HR reactivity immediately after stress than children with an anxiety disorder, which was not accounted for by comorbid ODD/CD symptoms, and which may be related to a stronger parasympathetic than sympathetic activation.

No distinctions between different types of anxiety symptoms in pre-adolescents from the general population.

Studies aimed at anxiety symptoms in children from the general population samples often make distinctions between symptoms of Separation Anxiety, Social Phobia, Panic Disorder, and Generalized Anxiety Disorder. Given the high comorbidity rates between these disorders, the usefulness of such distinctions is questionable. The present study was conducted to investigate which homogenous subgroups of children aged 10-12 years can be identified, according to the presence and frequencies of different types of anxiety. A general population sample of 2210 children was assessed with the RCADS, a self-report questionnaire. Latent class analysis did not yield classes of children with symptoms of one anxiety disorder, without symptoms of another anxiety disorder. Instead, five classes of children were identified that differed in the frequency of anxiety symptoms, irrespective of the type of anxiety. Results indicate that, in a general population sample, it may not be useful to discern children with different types of anxiety symptoms.