Novel genome-wide associations for effort valuation and psychopathology in children and adults.

The Research Domain Criteria (RDoC) initiative was established by the US National Institute of Mental Health as a multilevel, disorder-agnostic framework for analysis of human psychopathology through designated domains and constructs, including the "Positive Valence Systems" domain focused on reward-related behavior. This study investigates the reward valuation subconstruct of "effort" and its association with genetic markers, functional neurobiological pathways, and polygenic risk scores for psychopathology in 1215 children aged 6-12 and their parents (n = 1044). All participants completed the effort expenditure for rewards task (EEfRT), which assesses "effort" according to two quantitative measures: hard-task choice and reward sensitivity. Genetic association analyses were undertaken in MAGMA, utilizing EEfRT outcome variables as genome-wide association studies phenotypes to compute SNP and gene-level associations. Genome-wide association analyses found two distinct genetic loci that were significantly associated with measures of reward sensitivity and a separate genetic locus associated with hard task choice. Gene-set enrichment analysis yielded significant associations between "effort" and multiple gene sets involved in reward processing-related pathways, including dopamine receptor signaling, limbic system and forebrain development, and biological response to cocaine. These results serve to establish "effort" as a relevant construct for understanding reward-related behavior at the genetic level and support the RDoC framework for assessing disorder-agnostic psychopathology.

Trajectories of psychiatric diagnoses and medication usage in youth with 22q11.2 deletion syndrome: a 9-year longitudinal study.

BACKGROUND: Chromosome 22q11.2 deletion syndrome (22q11DS) is associated with high rates of psychiatric disorders, including schizophrenia in up to 30% of individuals with the syndrome. Despite this, we know relatively little about trajectories and predictors of persistence of psychiatric disorders from middle childhood to early adulthood. Accordingly, we followed youth over four timepoints, every 3 years, to assess long-term trajectories of attention-deficit hyperactivity disorder (ADHD), anxiety, mood, and psychosis-spectrum disorders (PSDs), as well as medication usage. METHODS: Eighty-seven youth with 22q11DS and 65 controls between the ages of 9 and 15 years at the first timepoint (T1; mean age 11.88 ± 2.1) were followed for 9 years (mean age of 21.22 ± 2.01 years at T4). Baseline cognitive, clinical, and familial predictors of persistence were identified for each class of psychiatric disorders. RESULTS: Baseline age and parent-rated hyperactivity scores predicted ADHD persistence [area under curve (AUC) = 0.81]. The presence of family conflict predicted persistence of anxiety disorders (ADs) whereas parent ratings of child internalizing symptoms predicted persistence of both anxiety and mood disorders (MDs) (AUC = 0.84 and 0.83, respectively). Baseline prodromal symptoms predicted persistent and emergent PSDs (AUC = 0.83). Parent-reported use of anti-depressants/anxiolytics increased significantly from T1 to T4. CONCLUSIONS: Psychiatric, behavioral, and cognitive functioning during late childhood and early adolescence successfully predicted children with 22q11DS who were at highest risk for persistent psychiatric illness in young adulthood. These findings emphasize the critical importance of early assessments and interventions in youth with 22q11DS.

Effort valuation and psychopathology in children and adults.

BACKGROUND: The Research Domain Criteria initiative was launched by the US National Institute of Mental Health to establish a multi-level framework for understanding psychological constructs relevant to human psychiatric disorders, and identified 'effort valuation/willingness to work' as a clinically useful construct worthy of further study. This construct encompasses the processes by which the cost(s) of obtaining an outcome are calculated, and the tendency to overcome response costs to obtain a reinforcer. The current study aims to examine effort valuation as a correlate of psychopathology in children and adults, and the moderating effects of sex on this relationship. METHODS: Participants were 1215 children aged 6-12 and their parents (n = 1044). All participants completed the Effort Expenditure for Rewards Task as a measure of effort expenditure. Child psychopathology was measured via the Child Behavior Checklist, while adult psychopathology was measured via the Adult Self Report. Additionally, the Social Adjustment Inventory for Children and Adolescents and Injury Behavior Checklist were used to examine child social impairments/problem behaviors. RESULTS: In children, significant interactions between reward sensitivity and sex were observed in association with anxiety and thought problems, specifically at low reward sensitivity levels. In adults, main effects of effort expenditure were seen in drug and alcohol abuse, where higher effort was associated with higher degrees of abuse. CONCLUSIONS: These results establish effort valuation as a relevant psychological construct for understanding psychopathology, but with different profiles of associated psychopathology across sex in children and adults.

Frontal dysconnectivity in 22q11.2 deletion syndrome: an atlas-based functional connectivity analysis.

BACKGROUND: 22q11.2 deletion syndrome (22q11DS) is a neurodevelopmental syndrome associated with deficits in cognitive and emotional processing. This syndrome represents one of the highest risk factors for the development of schizophrenia. Previous studies of functional connectivity (FC) in 22q11DS report aberrant connectivity patterns in large-scale networks that are associated with the development of psychotic symptoms. METHODS: In this study, we performed a functional connectivity analysis using the CONN toolbox to test for differential connectivity patterns between 54 individuals with 22q11DS and 30 healthy controls, between the ages of 17-25 years old. We mapped resting-state fMRI data onto 68 atlas-based regions of interest (ROIs) generated by the Desikan-Killany atlas in FreeSurfer, resulting in 2278 ROI-to-ROI connections for which we determined total linear temporal associations between each. Within the group with 22q11DS only, we further tested the association between prodromal symptoms of psychosis and FC. RESULTS: We observed that relative to controls, individuals with 22q11DS displayed increased FC in lobar networks involving the frontal-frontal, frontal-parietal, and frontal-occipital ROIs. In contrast, FC between ROIs in the parietal-temporal and occipital lobes was reduced in the 22q11DS group relative to healthy controls. Moreover, positive psychotic symptoms were positively associated with increased functional connections between the left precuneus and right superior frontal gyrus, as well as reduced functional connectivity between the bilateral pericalcarine. Positive symptoms were negatively associated with increased functional connectivity between the right pericalcarine and right postcentral gyrus. CONCLUSIONS: Our results suggest that functional organization may be altered in 22q11DS, leading to disruption in connectivity between frontal and other lobar substructures, and potentially increasing risk for prodromal psychosis.

Associations between neurodevelopmental genes, neuroanatomy, and ultra high risk symptoms of psychosis in 22q11.2 deletion syndrome.

22q11.2 deletion syndrome is a neurogenetic disorder resulting in the deletion of over 40 genes. Up to 40% of individuals with 22q11.2DS develop schizophrenia, though little is known about the underlying mechanisms. We hypothesized that allelic variation in functional polymorphisms in seven genes unique to the deleted region would affect lobar brain volumes, which would predict risk for psychosis in youth with 22q11.2DS. Participants included 56 individuals (30 males) with 22q11.2DS. Anatomic MR images were collected and processed using Freesurfer. Participants were genotyped for 10 SNPs in the COMT, DGCR8, GNB1L, PIK4CA, PRODH, RTN4R, and ZDHHC8 genes. All subjects were assessed for ultra high risk symptoms of psychosis. Allelic variation of the rs701428 SNP of RTN4R was significantly associated with volumetric differences in gray matter of the lingual gyrus and cuneus of the occipital lobe. Moreover, occipital gray matter volumes were robustly associated with ultra high risk symptoms of psychosis in the presence of the G allele of rs701428. Our results suggest that RTN4R, a relatively under-studied gene at the 22q11 locus, constitutes a susceptibility gene for psychosis in individuals with this syndrome through its alteration of the architecture of the brain. © 2017 Wiley Periodicals, Inc.

Initial Responsiveness to Reward Attainment and Psychopathology in Children and Adults: An RDoC Study.

The Research Domain Criteria (RDoC) initiative of the National Institute of Mental Health (NIMH) established a dimensional framework for understanding psychiatric constructs. Initial Responsiveness to Reward Attainment (IRRA) was identified as a dimensional construct relevant to several psychiatric disorders. The current study aimed to (1) examine IRRA as a predictor of psychopathology and impairment in children and their parents, and (2) examine the potential effects of sex and ancestry on the relationship between IRRA and psychopathology. Participants included 1127 children ages 6 to 12, and 1018 of their parents. Parents and children completed self-report measures of IRRA. Psychopathology and impairment were measured using self-report for adults, and parent-report and semi-structured interview for children. In adults, IRRA was significantly, but modestly, related to adaptive functioning. In children, IRRA was significantly, but modestly, related to overall, school, spare time, home, and peer functioning. Findings suggest IRRA may be a helpful construct for understanding adaptive functioning in adults and children, however it may be less helpful for understanding specific dimensions of psychopathology. Additionally, ancestry should be taken into consideration when examining how IRRA relates to psychopathology and functioning.

Autistic spectrum disorders in velo-cardio facial syndrome (22q11.2 deletion).

The extent to which the phenotype of children comorbid for velocardiofacial syndrome (VCFS) and autism spectrum disorders (ASD) differs from that of VCFS-only has not been studied. The sample consisted of 41 children (20 females) with VCFS, ranging in age from 6.5 years to 15.8 years. Eight children with VCFS met formal DSM-IV diagnostic criteria for autism based upon the ADI-R. These eight plus an additional nine participants met diagnostic criteria for an autistic spectrum disorder (VCFS + ASD). Ninety-four percent of the children with VCFS + ASD had a co-occurring psychiatric disorder while 60% of children with VCFS had a psychiatric disorder. Children with VCFS + ASD had larger right amygdala volumes. All other neuroanatomic regions of interest were statistically similar between the two groups.

Manic symptoms and behavioral dysregulation in youth with velocardiofacial syndrome (22q11.2 deletion syndrome).

Mania and bipolar disorder have been reported in adolescents and adults with velocardiofacial syndrome (VCFS; also known as 22q11.2 deletion syndrome). Children with VCFS have a high prevalence of attention-deficit/hyperactivity disorder (ADHD), which may constitute a risk factor for the eventual development of bipolar disorder in this population. Therefore, we sought to determine whether children with VCFS exhibit more manic symptoms than community controls that also may have learning disorders and ADHD. The study population consisted of 86 children with VCFS and 36 community controls from ages 9 to 15 years, using measures of Young Mania Rating Scale-Parent Version, Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL), Child Behavior Checklist (CBCL), and Wechsler Intelligence Scale for Children-3rd edition (WISC-III). The results indicate that manic symptoms were not more prevalent in VCFS than in a community sample of children with learning disorders and ADHD. However, after accounting for symptoms of depression and ADHD, we found that manic symptoms in VCFS predicted uniquely to scores on four Child Behavior Checklist (CBCL) subscales, including anxiety, somatization, thought, and conduct problems. In contrast, manic symptoms in controls predicted uniquely to conduct problems only. Accordingly, our findings of severe behavioral impairment in youth with VCFS and manic symptoms suggest that these children may warrant more intensive monitoring and treatment relative to youth with VCFS and ADHD only.

Atypical functional connectivity in resting-state networks of individuals with 22q11.2 deletion syndrome: associations with neurocognitive and psychiatric functioning.

BACKGROUND: 22q11.2 deletion syndrome (22q11DS) is a neurogenetic condition associated with deficits in neuropsychological functioning and psychiatric disorders. This deletion confers a high risk for the development of psychosis, as approximately 30-45 % of individuals develop psychosis in adulthood. Previous reports of resting-state functional magnetic resonance imaging (rs-fMRI) functional connectivity patterns in 22q11DS have demonstrated that atypical connectivity is associated with both the emergence and severity of psychotic symptoms. However, due to sample overlap and large age ranges of samples spanning multiple critical periods of brain maturation, more independent studies with samples within the window of time when psychotic symptoms have been shown to emerge (ages 17-26) are needed. Resting-state networks (RSNs) in 22q11DS during this stage of brain development may thus provide insight into the dynamic changes in functional integration that influence the incidence of prodromal symptoms and neurocognitive deficits characteristic of this syndrome. METHODS: Independent component analysis (ICA) was performed to identify RSNs in a combined sample of 55 individuals with 22q11DS (27 males; age range 17-26) and 29 controls (17 males; age range 17-23, consisting of 8 siblings without the deletion and 21 typically developed individuals) from two research sites. We conducted a full factorial analysis to determine group differences between 22q11DS and controls. A Poisson regression analysis was conducted in the 22q11DS group to determine relationships of rs-fMRI network connectivity with psychiatric symptoms based on factors of the 18-item Brief Psychiatric Rating Scale. Nonparametric Spearman correlations were performed to test associations between within-network functional connectivity (FC) and performance on measures of verbal memory (California Verbal Learning Test) and executive function (Behavior Rating Inventory of Executive Function Adult version) in 22q11DS. RESULTS: Between-group network connectivity analyses revealed significant differences in 9 RSNs. Decreased network FC in 22q11DS was observed in the following networks: high-level visual processing network (HLVPN), low-level visual processing network (LLVPN), visual/precuneus network, left frontal-parietal network (LFPN), right frontal-parietal network (RFPN), and self-referential network (SRN). In contrast, greater network FC in 22q11DS was observed in subclusters of the LLVPN, visual/precuneus network, limbic network (LN), default mode network (DMN), and visuospatial processing network (VSPN). Increased functional connectivity of the right cuneus (visual/precuneus network) and right superior parietal lobule (DMN) in 22q11DS was positively associated with both thought disturbance and disorganization factors of the Brief Psychiatric Rating Scale (BPRS). Decreased functional connectivity in the left posterior cingulate (LLVPN) was associated with higher thought disturbance scores in 22q11DS. No associations with our neurocognitive measures passed correction for multiple comparisons (Bonferroni-corrected p ≤ 0.0014). CONCLUSIONS: Our findings suggest that atypical network connectivity within RSNs may be indicative of increased risk for developing psychosis and supports the utility of RSNs as biomarkers of prodromal symptoms in 22q11DS.

The impact of terrorism on children and adolescents: terror in the skies, terror on television.

Terrorist attacks and their aftermath have had a powerful impact on children and their families. Media and television exposure of terrorist events throughout the world has increased during the past few years. There is increasing concern about the effects of this exposure on children who witness these violent images. To develop a proactive and strategic response to reactions of fear, clinicians, educators, and policy makers must understand the psychologic effects of media coverage of terrorism on children. Previous research has focused on media coverage of criminal violence and war. Recent studies have examined the effect of remote exposure of terrorist attacks and have shown a significant clinical impact on children and families.

Behavioral and Psychiatric Phenotypes in 22q11.2 Deletion Syndrome.

22q11.2 Deletion syndrome (22q11.2DS) is a chromosomal microdeletion that affects approximately 40 to 50 genes and affects various organs and systems throughout the body. Detection is typically achieved by fluorescence in situ hybridization after diagnosis of one of the major features of the deletion or via chromosomal microarray or noninvasive prenatal testing. The physical phenotype can include congenital heart defects, palatal and pharyngeal anomalies, hypocalcemia/hypoparathyroidism, skeletal abnormalities, and cranial/brain anomalies, although prevalence rates of all these features are variable. Cognitive function is impaired to some degree in most individuals, with prevalence rates of greater than 90% for motor/speech delays and learning disabilities. Attention, executive function, working memory, visual-spatial abilities, motor skills, and social cognition/social skills are affected. The deletion is also associated with an increased risk for behavioral disorders and psychiatric illness. The early onset of psychiatric symptoms common to 22q11.2DS disrupts the development and quality of life of individuals with the syndrome and is also a potential risk factor for later development of a psychotic disorder. This review discusses prevalence, phenotypic features, and management of psychiatric disorders commonly diagnosed in children and adolescents with 22q11.2DS, including autism spectrum disorders, attention deficit/hyperactivity disorder, anxiety disorders, mood disorders, and schizophrenia/psychotic disorders. Guidelines for the clinical assessment and management of psychiatric disorders in youth with this syndrome are provided, as are treatment guidelines for the use of psychiatric medications.

Childhood reactions to terrorism-induced trauma: a review of the past 10 years.

OBJECTIVE: To summarize the literature about the clinical presentation and treatment interventions of childhood reactions to terrorism-induced trauma. METHOD: The literature on children's responses to terrorist activities was reviewed. RESULTS: Over the past 10 years, more research has emerged on the subject of terrorism in children. Many of the effects of terrorism-induced trauma are similar to the effects of natural and man-made trauma. Children's responses include acute stress disorder, posttraumatic stress disorder, anxiety, depression, regressive behaviors, separation problems, sleep difficulties, and behavioral problems. However, several aspects of terrorist attacks result in unique stressors and reactions and pose specific challenges for treatment. The unpredictable, indefinite threat of terrorist events, the profound effect on adults and communities, and the effect of extensive terrorist-related media coverage exacerbates underlying anxieties and contributes to a continuous state of stress and anxiety. Intervention strategies include early community-based interventions, screening of children at risk, triage and referral, and trauma-loss-focused treatment programs. CONCLUSIONS: Advances have been made in the research of childhood reactions to terrorism-induced trauma. Further research is needed to identify children at risk and to determine the long-term impact on children's development. Although the preliminary results of interventions developed to help children are promising, outcome data have not been examined, and further research is needed to evaluate their effectiveness.

Effects of chlordiazepoxide (Librium) during pregnancy and lactation.

The decision to use psychotropic drugs during pregnancy and lactation must depend upon considerations of teratogenicity, effects on fetal and neonatal behavior and development, and a concern for the health and safety of the mother. Pregnancy itself can exacerbate anxiety symptoms, as well as alter the pharmacokinetics of antianxiety drugs; it thus presents a special problem to the clinician treating anxiety disorder in women. Since almost all psychotropic drugs cross the placenta, the use of medications during pregnancy and lactation requires critical attention to the timing of exposure, dosage, duration of use, and fetal susceptibility. Risk to the mother and fetus can be reduced with a number of simple strategies, including monotherapy with the lowest effective, multiple dose of a drug for the shortest period necessary and avoidance of exposure to Benzodiazepines (BZDs) during the first trimester, since this is when the developing fetus is most vulnerable to the toxic effects of most agents. This literature review highlights information from various sources regarding risks for pregnant and lactating mothers to long acting BZDs, especially Chlordiazepoxide.

White matter abnormalities in 22q11.2 deletion syndrome: preliminary associations with the Nogo-66 receptor gene and symptoms of psychosis.

BACKGROUND: This study utilized diffusion tensor imaging (DTI) to analyze white matter tractography in the anterior limb of the internal capsule (ALIC), fornix, and uncinate fasciculus (UF) of individuals with 22q11.2 deletion syndrome and controls. Aberrations in these tracts have been previously associated with schizophrenia. With up to 25% of individuals with 22q11.2DS developing schizophrenia in adulthood, we hypothesized reduction in structural integrity of these tracts, including an association with prodromal symptoms of psychosis. We further predicted an association between allelic variation in a functional polymorphism of the Nogo-66 receptor gene and 22q11.2DS white matter integrity. METHODS: Tractography was conducted using fiber assignment by streamline tracking algorithm in DTI Studio. Subjects were genotyped for the rs701428 SNP of the Nogo-66 receptor gene, and assessed for presence of prodromal symptoms. RESULTS: We found significant group differences between 22q11.2DS and controls in DTI metrics for all three tracts. DTI metrics of ALIC and UF were associated with prodromal symptoms in 22q11.2DS. Further, ALIC DTI metrics were associated with allelic variation of the rs701428 SNP of the Nogo-66 receptor gene in 22q11.2DS. CONCLUSIONS: Alterations in DTI metrics suggest white matter microstructural anomalies of the ALIC, fornix, and UF in 22q11.2DS. Structural differences in ALIC appear to be associated with the Nogo-66 receptor gene, which has been linked to myelin-mediated axonal growth inhibition. Moreover, the association between psychosis symptoms and ALIC and UF metrics suggests that the Nogo-66 receptor gene may represent a susceptibility gene for psychosis through its disruption of white matter microstructure and myelin-associated axonal growth.

Assessment of Suny Upstate Medical University's child telepsychiatry consultation program.

OBJECTIVES: The project assesses the child telepsychiatry services provided by SUNY Upstate psychiatrists to several county mental health clinics in central New York State. METHOD: Data for 45 patients was extracted from pre-consultation forms completed by the referring clinic and postconsultation summaries completed by the Upstate psychiatrists that occurred between July 13, 2009 and May 12, 2010. The study identified characteristics of patients for whom telepsychiatry consultations were sought, why they were sought, and reviewed recommended changes in therapy and medication provided by the telepsychiatry consultant. RESULTS: Analysis of the data showed that there was a large variation in patient characteristics such as age (from age 3 to 17), current living situation, and psychological symptoms. In addition to a family history of mental illness (80%), the most common symptoms were physical aggression (60.0%), defiant/oppositional behavior (57.8%), and attentional problems (55.6%). The most common reason for referral was diagnostic clarification (67%). The child telepsychiatrist recommended a change in medication for most (80.8%) of the patients who were on medications, and to begin medications for most (63.2%) who were not receiving medication at the time of consult. Further, the telepsychiatrist often recommended the addition of family therapy (71.1%) and counseling at school (17.8%). CONCLUSION: The child telepsychiatric program at Upstate seemed effective. It reached a large variety of children with significant mental disorders. The consultants provided diagnostic clarification and recommended modification of treatment for most. However, this assessment is limited as examined as it did not include follow-up information on whether consultant recommendations were followed and, if they were, whether they were effective.

Neuroanatomic predictors to prodromal psychosis in velocardiofacial syndrome (22q11.2 deletion syndrome): a longitudinal study.

BACKGROUND: Up to 30% of young adults with velocardiofacial syndrome (VCFS; 22q11.2 deletion syndrome) develop schizophrenia or psychosis. Identifying the neuroanatomic trajectories that increase risk for psychosis in youth with this genetic disorder is of great interest. METHODS: We acquired high-resolution anatomic magnetic resonance images and measures of psychiatric function on 72 youth with VCFS, 26 unaffected siblings, and 24 age-matched community control subjects at two time points: between late childhood (mean age 11.9 years) and mid-adolescence (mean age 15.1 years). RESULTS: With the exception of cranial gray matter and orbitofrontal prefrontal cortex, neuroanatomic trajectories in youth with VCFS were comparable to unaffected siblings and community control subjects during this developmental window. However, in youth with VCFS, longitudinal decreases in the volumes of cranial gray and white matter, prefrontal cortex, mesial temporal lobe, and cerebellum were associated with increased combined prodromal symptoms at Time 2. In contrast, only decreases in temporal lobe gray matter volumes (p < .002) and verbal IQ (p < .002) predicted specifically to positive prodromal symptoms of psychosis at Time 2. CONCLUSIONS: These findings are in line with studies of non-VCFS individuals at risk for schizophrenia and suggest that early decrements in temporal lobe gray matter may be predictive of increased risk of prodromal psychotic symptoms in youth with VCFS.

Comfort level of pediatricians and family medicine physicians diagnosing and treating child and adolescent psychiatric disorders.

CONTEXT: Twelve to twenty-one percent of children and adolescents have psychiatric disorders with at least mild functional impairment. Pediatricians and family medicine physicians prescribe 85% of psychotropic medications taken by children. However, little is known about the comfort level of these physicians with the diagnosis and treatment of psychiatric disorders in children. OBJECTIVE: To determine the comfort level of physicians in diagnosing and treating psychiatric disorders in children. METHOD: An anonymous survey was sent to pediatricians and family medicine physicians in upstate New York. Of 483 surveys, 200 surveys were returned. OUTCOME MEASURES: To compare differences between pediatricians and family medicine physicians in comfort in diagnosing and prescribing medications for psychiatric disorders. RESULTS: After controlling for age, race, and years since residency, pediatricians were more comfortable in diagnosing (O.R. = 3.05, C.I. = 1.40-6.63) and prescribing stimulants for (O.R. = 4.16, C.I. = 1.96-8.84) Attention Deficit Disorder. Family medicine physicians were more comfortable in diagnosing (O.R. = .28, C.I. = .14-.57) and prescribing medication for (O.R. = .44, C.I. = .22-.87) anxiety and depression. Despite the differences in comfort, there were no differences in the percentage of each group prescribing the different medications. Of those who were comfortable in making the diagnoses, 13%-64% were not comfortable in prescribing medications, although they did prescribe. CONCLUSIONS: Pediatricians and family medicine physicians who prescribe the majority of psychotropic medications for children report disconcerting degrees of discomfort with the diagnosis and treatment of children's psychiatric disorders. The authors discuss the multiple factors that may impact primary care physician's comfort in diagnosing and treating children and adolescents with psychiatric disorders.

Associations between performance on the Rey-Osterrieth Complex Figure and regional brain volumes in children with and without velocardiofacial syndrome.

Ninety-two children with velocardiofacial syndrome (VCFS), a genetic disorder caused by a microdeletion of chromosome 22q11.2 and an age, race, and gender-ratio comparable sample of 59 control participants were included in the project. Participants received an MRI as well as a comprehensive neuropsychological battery; the primary outcome measure in the current report is the Rey-Osterrieth Complex Figure (ROCF). Children with VCFS performed less well on the ROCF and have lower whole brain volume compared to controls. After controlling for whole brain volume differences, children with VCFS have bilaterally less parietal lobe gray and white matter yet more frontal lobe white matter. Brain-behavior relationships include: (a) for both groups, parietal volumes (both gray and white matter) predicted ROCF Copy Organization performance and frontal volumes (both gray and white matter) predicted ROCF Copy Accuracy performance; (b) for controls, frontal white matter also predicted ROCF Copy Organization performance; (c) ROCF Recall Organization performance was best predicted by frontal gray matter volume only in our controls; ROCF Recall Accuracy performance was best predicted by frontal gray matter volume in both groups; and (d) in children with VCFS, performance on the ROCF-Copy Structural Elements Accuracy scale was predicted by right hemisphere white matter volume. Our hypotheses were also retested using IQ-matched and whole brain volume-matched subsamples. Identical results were obtained in these analyses. Assumptions about the organization of and the localization of the brain structures that subserve specific cognitive functions in the typically developing brain may not apply in the abnormally developing brain.

Comparing phenotypes in patients with idiopathic autism to patients with velocardiofacial syndrome (22q11 DS) with and without autism.

At least three research groups have reported that autism is diagnosed in up to 20% of children with velocardiofacial syndrome (VCFS). However the degree of phenotypic overlap between VCFS-affected children with autism and those with idiopathic autism has not been established. The purpose of this study was to define and differentiate the behavioral phenotype of autism in samples of children with either (VCFS) or idiopathic autism. Five groups of children ages 5-15 were included in the between-group design. Parent report of autism behaviors (based on the Autism Diagnostic Interview-Revised, ADI-R) were compared between children with VCFS, children with VCFS and autism (VCFS + autism), siblings of the children with VCFS, a community control group, and a group of children with idiopathic autism. Autism diagnoses were based according to the ADI-R. Parental responses to the ADI-R indicated that relative to children with VCFS-only, children with idiopathic autism and children with VCFS + autism exhibited less make believe play and more rituals, motor stereotypies and repetitive use of objects. However several other core autism behaviors, including difficulties sharing attention, deficits in gestural communication and initiating conversation, and presence of circumscribed interests, appear to be phenotypic VCFS behaviors, characterizing children with VCFS regardless of an autism diagnosis. Accordingly, the autism phenotype in VCFS differs to some extent from that of idiopathic autism. Several features of idiopathic autism are spared in VCFS, and other features appear to be a function of the VCFS phenotype independent of autism. These findings carry implications for clinicians who diagnose and treat VCFS or autism, and for researchers who study genotype-phenotype associations in autism.

School refusal in children and adolescents.

School refusal is a problem that is stressful for children, families, and school personnel. Failing to attend school has significant short- and long-term effects on children's social, emotional, and educational development. School refusal often is associated with comorbid psychiatric disorders such as anxiety and depression. It is important to identify problems early and provide appropriate interventions to prevent further difficulties. Assessment and management of school refusal require a collaborative approach that includes the family physician, school staff, parents, and a mental health professional. Because children often present with physical symptoms, evaluation by a physician is important to rule out any underlying medical problems. Treatments include educational-support therapy, cognitive behavior therapy, parent-teacher interventions, and pharmacotherapy. Family physicians may provide psychoeducational support for the child and parents, monitor medications, and help with referral to more intensive psychotherapy.