Randomized controlled trial of parent-enhanced CBT compared with individual CBT for obsessive-compulsive disorder in young people

Objective: Obsessive-compulsive disorder (OCD) in young people can be effectively treated with Cognitive Behavior Therapy (CBT). Practice guidelines in the United Kingdom recommend that CBT be delivered with parental or family involvement; however, there is no evidence from randomized trials that this enhances effectiveness. The aim of this trial was to assess if CBT with high parental involvement was more effective than CBT with low parental involvement (individual CBT) in reducing symptoms of OCD. Method: Fifty young people ages 12–17 years with OCD were randomly allocated to individual CBT or parent-enhanced CBT. In parent-enhanced CBT parents attended all treatment sessions; in individual CBT, parents attended only Sessions 1, 7, and the final session. Participants received up to 14 sessions of CBT. Data were analyzed using intent-to-treat and per-protocol methods. The primary outcome measure was the Children’s Yale-Brown Obsessive Compulsion Scale (Scahill et al., 1997). Results: Both forms of CBT significantly reduced symptoms of OCD and anxiety. Change in OCD symptoms was maintained at 6 months. Per-protocol analysis suggested that parent-enhanced CBT may be associated with significantly larger reductions in anxiety symptoms. Conclusions: High and low parental involvement in CBT for OCD in young people were both effective, and there was no evidence that 1 method of delivery was superior on the primary outcome measure. However, this study was small. Future trials should be adequately powered and examine interactions with the age of the young person and comorbid anxiety disorders.

Expression of the Rap1 guanine nucleotide exchange factor, MR-GEF, is altered in individuals with bipolar disorder

In the rodent forebrain GABAergic neurons are generated from progenitor cells that express the transcription factors Dlx1 and Dlx2. The Rap-1 guanine nucleotide exchange factor, MR-GEF, is turned on by many of these developing GABAergic neurons. Expression of both Dlx1/2 and MR-GEF is retained in both adult mouse and human forebrain where, in human, decreased Dlx1 expression has been associated with psychosis. Using in situ hybridization studies we show that MR-GEF expression is significantly down-regulated in the forebrain of Dlx1/2 double mutant mice suggesting that MR-GEF and Dlx1/2 form part of a common signalling pathway during GABAergic neuronal development. We therefore compared MR-GEF expression by in situ hybridization in individuals with major psychiatric disorders (schizophrenia, bipolar disorder, major depression) and control individuals. We observed a significant positive correlation between layers II and IV of the dorso-lateral prefrontal cortex (DLPFC) in the percentage of MR-GEF expressing neurons in individuals with bipolar disorder, but not in individuals with schizophrenia, major depressive disorder or in controls. Since MR-GEF encodes a Rap1 GEF able to activate G-protein signalling, we suggest that changes in MR-GEF expression could potentially influence neurotransmission.

Emotional reasoning and anxiety sensitivity: associations with social anxiety disorder in childhood

Background Two specific cognitive constructs that have been implicated in the development and maintenance of anxiety symptoms are anxiety sensitivity and emotional reasoning, both of which relate to the experience and meaning of physical symptoms of arousal or anxiety. The interpretation of physical symptoms has been particularly implicated in theories of social anxiety disorder, where internal physical symptoms are hypothesized to influence the individual's appraisals of the self as a social object. Method The current study compared 75 children on measures of anxiety sensitivity and emotional reasoning: 25 with social anxiety disorder, 25 with other anxiety disorders, and 25 nonanxious children (aged 7–12 years). Results Children with social anxiety disorder reported higher levels of anxiety sensitivity and were more likely than both other groups to view ambiguous situations as anxiety provoking, whether physical information was present or not. There were no group differences in the extent to which physical information altered children's interpretation of hypothetical scenarios. Limitations This study is the first to investigate emotional reasoning in clinically anxious children and therefore replication is needed. In addition, those in both anxious groups commonly had comorbid conditions and, consequently, specific conclusions about social anxiety disorder need to be treated with caution. Conclusion The findings highlight cognitive characteristics that may be particularly pertinent in the context of social anxiety disorder in childhood and which may be potential targets for treatment. Furthermore, the findings suggest that strategies to modify these particular cognitive constructs may not be necessary in treatments of some other childhood anxiety disorders.

Minor structural abnormalities in the infant face disrupt neural processing: a unique window into early caregiving responses

Infant faces elicit early, specific activity in the orbitofrontal cortex (OFC), a key cortical region for reward and affective processing. A test of the causal relationship between infant facial configuration and OFC activity is provided by naturally occurring disruptions to the face structure. One such disruption is cleft lip, a small change to one facial feature, shown to disrupt parenting. Using magnetoencephalography, we investigated neural responses to infant faces with cleft lip compared with typical infant and adult faces. We found activity in the right OFC at 140 ms in response to typical infant faces but diminished activity to infant faces with cleft lip or adult faces. Activity in the right fusiform face area was of similar magnitude for typical adult and infant faces but was significantly lower for infant faces with cleft lip. This is the first evidence that a minor change to the infant face can disrupt neural activity potentially implicated in caregiving.

Substitutional and orientational disorder in organic crystals: a symmetry-adapted ensemble model

Modelling of disorder in organic crystals is highly desirable since it would allow thermodynamic stabilities and other disorder-sensitive properties to be estimated for such systems. Two disordered organic molecular systems are modeled using a symmetry-adapted ensemble approach, in which the disordered system is treated as an ensemble of the configurations of a supercell with respect to substitution of one disorder component for another. Computation time is kept manageable by performing calculations only on the symmetrically inequivalent configurations. Calculations are presented on a substitutionally disordered system, the dichloro/dibromobenzene solid solution, and on an orientationally disordered system, eniluracil, and the resultant free energies, disorder patterns, and system properties are discussed. The results are found to be in agreement with experiment following manual removal of physically implausible configurations from ensemble averages, highlighting the dangers of a completely automated approach to organic crystal thermodynamics which ignores the barriers to equilibration once the crystal has been formed.

Examining vulnerability to involuntary memories in schizophrenia comorbid with post-traumatic stress disorder

The current study explored whether individuals diagnosed with schizophrenia and a high level of PTSD symptoms experience more frequent neutral intrusive memories than individuals diagnosed with schizophrenia with low level PTSD symptoms. Results supported a vulnerability to neutral intrusive memories within the comorbid group, which did not seem to be related to psychotic symptom severity. It is possible that a subgroup of psychotic individuals’ process information in a manner that make them susceptible to frequent intrusive memories, characteristic of a PTSD presentation. A longitudinal study is required to specify the development of this vulnerability so as to inform future interventions.

Disorder-specific functional abnormalities during temporal discounting in youth with Attention Deficit Hyperactivity Disorder (ADHD), Autism and comorbid ADHD and Autism

Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) are often comorbid and share cognitive abnormalities in temporal foresight. A key question is whether shared cognitive phenotypes are based on common or different underlying pathophysiologies and whether comorbid patients have additive neurofunctional deficits, resemble one of the disorders or have a different pathophysiology. We compared age- and IQ-matched boys with non-comorbid ADHD (18), non-comorbid ASD (15), comorbid ADHD and ASD (13) and healthy controls (18) using functional magnetic resonance imaging (fMRI) during a temporal discounting task. Only the ASD and the comorbid groups discounted delayed rewards more steeply. The fMRI data showed both shared and disorder-specific abnormalities in the three groups relative to controls in their brain-behaviour associations. The comorbid group showed both unique and more severe brain-discounting associations than controls and the non-comorbid patient groups in temporal discounting areas of ventromedial and lateral prefrontal cortex, ventral striatum and anterior cingulate, suggesting that comorbidity is neither an endophenocopy of the two pure disorders nor an additive pathology.

Abnormal functional activation and maturation of fronto-striato-temporal and cerebellar regions during sustained attention in autism spectrum disorder

Objective Sustained attention problems are common in people with autism spectrum disorder (ASD) and may have significant implications for the diagnosis and management of ASD and associated comorbidities. Furthermore, ASD has been associated with atypical structural brain development. The authors used functional MRI to investigate the functional brain maturation of attention between childhood and adulthood in people with ASD. Method Using a parametrically modulated sustained attention/vigilance task, the authors examined brain activation and its linear correlation with age between childhood and adulthood in 46 healthy male adolescents and adults (ages 11–35 years) with ASD and 44 age- and IQ-matched typically developing comparison subjects. Results Relative to the comparison group, the ASD group had significantly poorer task performance and significantly lower activation in inferior prefrontal cortical, medial prefrontal cortical, striato-thalamic, and lateral cerebellar regions. A conjunction analysis of this analysis with group differences in brain-age correlations showed that the comparison group, but not the ASD group, had significantly progressively increased activation with age in these regions between childhood and adulthood, suggesting abnormal functional brain maturation in ASD. Several regions that showed both abnormal activation and functional maturation were associated with poorer task performance and clinical measures of ASD and inattention. Conclusions The results provide first evidence that abnormalities in sustained attention networks in individuals with ASD are associated with underlying abnormalities in the functional brain maturation of these networks between late childhood and adulthood.

Social communication deficits: specific associations with Social Anxiety Disorder

Background Social communication deficits are prevalent amongst children with anxiety disorders; however whether they are over-represented specifically among children with Social Anxiety Disorder has not been examined. This study set out to examine social communication deficits among children with Social Anxiety Disorder in comparison to children with other forms of anxiety disorder. Methods Parents of 404 children with a diagnosed anxiety disorder completed the Social Communication Questionnaire (SCQ; Rutter, M., Bailey, A., Lord, C., 2003. The Social Communication Questionnaire – Manual. Western Psychological Services, Los Angeles, CA). Children with a diagnosis of Social Anxiety Disorder (n=262) and anxious children without Social Anxiety Disorder (n=142) were compared on SCQ total and subscale scores and the frequency of participants scoring above clinical cut-offs. Results Children with Social Anxiety Disorder scored significantly higher than anxious children without Social Anxiety Disorder on the SCQ total (t(352)=4.85, p<.001, d=.55, r=.27), Reciprocal Social Interaction (t(351)=4.73, p<.001, d=.55, r=.27), communication (t(344)=3.62, p<.001, d=.43, r=.21) and repetitive, restrictive and stereotyped behaviors subscales (t(353)=3.15, p=.002, d=.37, r=.18). Furthermore, children with Social Anxiety Disorder were three times more likely to score above clinical cut-offs. Limitations The participants were a relatively affluent group of predominantly non-minority status. The social communication difficulties measure relied on parental report which could be influenced by extraneous factors. Conclusions Treatments for Social Anxiety Disorder may benefit from a specific focus on developing social communication skills. Future research using objective assessments of underlying social communication skills is required.

The experience of friendship, victimization and bullying in children with an autism spectrum disorder: associations with child characteristics and school placement

Children with an autism spectrum disorder (ASD) may be vulnerable to social isolation and bullying. We measured the friendship, fighting/bullying and victimization experiences of 10–12-year-old children with an ASD (N = 100) using parent, teacher and child self-report. Parent and teacher reports were compared to an IQ-matched group of children with special educational needs (SEN) without ASD (N = 80) and UK population data. Parents and teachers reported a lower prevalence of friendships compared to population norms and to children with SEN without an ASD. Parents but not teachers reported higher levels of victimization than the SEN group. Half of the children with an ASD reported having friendships that involved mutuality. By teacher report children with an ASD who were less socially impaired in mainstream school experienced higher levels of victimization than more socially impaired children; whereas for more socially impaired children victimization did not vary by school placement. Strategies are required to support and improve the social interaction skills of children with an ASD, to enable them to develop and maintain meaningful peer friendships and avoid victimization.

Autonomic arousal in childhood anxiety disorders: associations with state anxiety and social anxiety disorder

Background Psychophysiological theories suggest that individuals with anxiety disorders may evidence inflexibility in their autonomic activity at rest and when responding to stressors. In addition, theories of social anxiety disorder, in particular, highlight the importance of physical symptoms. Research on autonomic activity in childhood (social) anxiety disorders, however, is scarce and has produced inconsistent findings, possibly because of methodological limitations. Method The present study aimed to account for limitations of previous studies and measured respiratory sinus arrhythmia (RSA) and heart rate (HR) using Actiheart heart rate monitors and software (Version 4) during rest and in response to a social and a non-social stressor in 60 anxious (30 socially anxious and 30 ‘other’ anxious), and 30 nonanxious sex-and age-matched 7–12 year olds. In addition, the effect of state anxiety during the tasks was explored. Results No group differences at rest or in response to stress were found. Importantly, however, with increases in state anxiety, all children, regardless of their anxiety diagnoses showed less autonomic responding (i.e., less change in HR and RSA from baseline in response to task) and took longer to recover once the stressor had passed. Limitations This study focused primarily on parasympathetic arousal and lacked measures of sympathetic arousal. Conclusion The findings suggest that childhood anxiety disorders may not be characterized by inflexible autonomic responding, and that previous findings to the contrary may have been the result of differences in subjective anxiety between anxious and nonanxious groups during the tasks, rather than a function of chronic autonomic dysregulation.

The effect of alkyl substitution on the extraction properties of BTPhen ligands for the partitioning of trivalent minor actinides and lanthanides in spent nuclear fuels

Bis-triazinylphenanthroline ligands (BTPhens), which contain additional alkyl (n-butyl and sec-butyl) groups attached to the triazine rings, have been synthesized, and the effects of this alkyl substitution on their extraction properties with Ln(III) and An(III) cations in simulated nuclear waste solutions have been studied. The speciation of n-butyl-substituted ligand (C4- BTPhen) with some trivalent lanthanide nitrates was elucidated by 1 H-NMR spectroscopic titrations. These experiments have shown that the dominant species in solution were the 1:2 complexes [Ln(III)(BTPhen)2], even at higher Ln(III) concentrations, and the relative stability of 2:1 to 1:1 BTPhen-Ln(III) complexes varied with different lanthanides. As expected, sec-butylsubstituted ligand (sec-C4 BTPhen) showed higher solubility than C4-BTPhen in certain diluents. A greater separation factor (SFAm/Eu = ca. 210) was observed for sec-C4-BTPhen compared to C4-BTPhen (SFAm/Eu = ca. 125) in 1-octanol at 4 M HNO3 solutions. The greater separation factor may be due to the higher solubility of the 2:1 complex for sec-C4-BTPhen at the interface than the 1:1 complex of C4-BTPhen.

Observing interactions between children and adolescents and their parents: the effects of anxiety disorder and age

Parental behaviors, most notably overcontrol, lack of warmth and expressed anxiety, have been implicated in models of the development and maintenance of anxiety disorders in children and young people. Theories of normative development have proposed that different parental responses are required to support emotional development in childhood and adolescence, yet age has not typically been taken into account in studies of parenting and anxiety disorders. In order to identify whether associations between anxiety disorder status and parenting differ in children and adolescents, we compared observed behaviors of parents of children (7–10 years) and adolescents (13–16 years) with and without anxiety disorders (n=120), while they undertook a series of mildly anxiety-provoking tasks. Parents of adolescents showed significantly lower levels of expressed anxiety, intrusiveness and warm engagement than parents of children. Furthermore, offspring age moderated the association between anxiety disorder status and parenting behaviors. Specifically, parents of adolescents with anxiety disorders showed higher intrusiveness and lower warm engagement than parents of non-anxious adolescents. A similar relationship between these parenting behaviors and anxiety disorder status was not observed among parents of children. The findings suggest that theoretical accounts of the role of parental behaviors in anxiety disorders in children and adolescents should distinguish between these different developmental periods. Further experimental research to establish causality, however, would be required before committing additional resources to targeting parenting factors within treatment.

Interpretation and expectations among mothers of children with anxiety disorders: associations with maternal anxiety disorder

Background Models of the development and maintenance of childhood anxiety suggest an important role for parent cognitions: that is, negative expectations of children's coping abilities lead to parenting behaviors that maintain child anxiety. The primary aims of the current study were to (1) compare expectations of child vulnerability and coping among mothers of children with anxiety disorders on the basis of whether or not mothers also had a current anxiety disorder, and (2) examine the degree to which the association between maternal anxiety disorder status and child coping expectations was mediated by how mothers interpreted ambiguous material that referred to their own experience. Methods The association between interpretations of threat, negative emotion, and control was assessed using hypothetical ambiguous scenarios in a sample of 271 anxious and nonanxious mothers of 7- to 12-year-old children with an anxiety disorder. Mothers also rated their expectations when presented with real life challenge tasks. Results There was a significant association between maternal anxiety disorder status and negative expectations of child coping behaviors. Mothers’ self-referent interpretations were found to mediate this relationship. Responses to ambiguous hypothetical scenarios correlated significantly with responses to real life challenge tasks. Conclusions Treatments for childhood anxiety disorders in the context of parental anxiety disorders may benefit from the inclusion of a component to directly address parental cognitions. Some inconsistencies were found when comparing maternal expectations in response to hypothetical scenarios with real life challenges. This should be addressed in future research.