A randomized controlled trial comparing foster care and institutional care for children with signs of reactive attachment disorder.

OBJECTIVE: The authors examined signs of emotionally withdrawn (inhibited type) and indiscriminately social (disinhibited type) reactive attachment disorder in Romanian children enrolled in a randomized trial of foster care compared with institutional care and in a comparison group of never-institutionalized children. METHOD: At baseline and when children were ages 30, 42, and 54 months and 8 years, caregivers were interviewed with the Disturbances of Attachment Interview to assess changes in signs of reactive attachment disorder in three groups of children: those receiving care as usual (including continued institutional care) (N=68); those placed in foster care after institutional care (N=68); and those who were never institutionalized (N=72). The impact of gender, ethnicity, and baseline cognitive ability was also examined. RESULTS: On the Disturbances of Attachment Interview, signs of the inhibited type of reactive attachment disorder decreased after placement in foster care, and scores were indistinguishable from those of never-institutionalized children after 30 months. Signs of the disinhibited type were highest in the usual care group, lower in the foster care group, and lowest in the never-institutionalized group. Early placement in foster care (before age 24 months) was associated with fewer signs of the disinhibited type. Lower baseline cognitive ability was associated with more signs of the inhibited type in the usual care group and more signs of the disinhibited type in both groups. CONCLUSIONS: Signs of the inhibited type of reactive attachment disorder responded quickly to placement in foster care; signs of the disinhibited type showed less robust resolution with foster placement. Lower baseline cognitive ability was linked to signs of reactive attachment disorder.

The anxiolytic-like profile of the nociceptin receptor agonist, endo-8-[bis(2-chlorophenyl)methyl]-3-phenyl-8-azabicyclo[3.2.1]octane-3-carboxamide (SCH 655842): comparison of efficacy and side effects across rodent species.

The endogenous opioid-like peptide, nociceptin, produces anxiolytic-like effects that are mediated via the nociceptin (NOP) receptor. Similarly, synthetic, non-peptide NOP agonists produce robust anxiolytic-like effects although these effects are limited by marked side effects. In the present studies, the effects of a novel NOP receptor agonist, SCH 655842, were examined in rodent models sensitive to anxiolytic drugs and tests measuring potential adverse affects. Oral administration of SCH 655842 produced robust, anxiolytic-like effects in three species, i.e., rat, guinea pig, and mouse. Specifically, SCH 655842 was effective in rat conditioned lick suppression (3-10 mg/kg) and fear-potentiated startle (3-10 mg/kg) tests, a guinea pig pup vocalization test (1-3 mg/kg), as well as in mouse Geller-Seifter (30 mg/kg) and marble burying (30 mg/kg) tests. The anxiolytic-like effect of SCH 655842 in the conditioned lick suppression test was attenuated by the NOP antagonist, J-113397. In mice, SCH 655842 reduced locomotor activity and body temperature at doses similar to the anxiolytic-like dose and these effects were absent in NOP receptor knockout mice. In rats, SCH 655842 did not produce adverse behavioral effects up to doses of 70-100 mg/kg. Pharmacokinetic studies in the rat confirmed dose-related increases in plasma and brain levels of SCH 655842 across a wide oral dose range. Taken together, SCH 655842 may represent a NOP receptor agonist with improved tolerability compared to other members of this class although further studies are necessary to establish whether this extends to higher species.

Characterization of the selective mGluR1 antagonist, JNJ16259685, in rodent models of movement and coordination.

Metabotropic glutamate receptor 1 (mGluR1) antagonists interfere with learning and memory; however, their role in motor function is not well elucidated despite their abundance in brain areas implicated in the control of movement. Here, the effects of mGluR1 antagonism on movement, coordination, and motor learning were investigated. JNJ16259685, a selective mGluR1 antagonist (negative allosteric modulator), was tested in assays of motor skill, and motor learning in rats and mice. JNJ16259685 produced very minimal effects on locomotor activity and posture up to a dose of 30 mg/kg. Motor skill was unaffected for well-learned tasks (up to 30 mg/kg) in rats, but impaired in mice. Both rats and mice rats were profoundly impaired (0.3 mg/kg) in the acquisition of a novel motor skill (rotarod). These results implicate the mGluR1 receptor in the acquisition of novel motor skills. JNJ16259685 dramatically reduced rearing behavior, exploration of a novel environment and lever pressing for a food reward (rat: 0.3 mg/kg; mouse: 1 mg/kg). JNJ16259685 (30 mg/kg) had no effect on reflexive startle responses to loud auditory stimuli or foot shock in mice. Previous groups have proposed that mGluR1 antagonists induce a general reduction in motivation. The effects seen here to reduce exploration and reward are consistent with that hypothesis. Pharmacological inhibition of the mGluR1 receptor has a modest effect on motor function but blocks motor learning and may reduce motivation to perform simple behaviors.

Trauma-focused cognitive-behavioral therapy for posttraumatic stress disorder in three-through six year-old children: a randomized clinical trial.

BACKGROUND: The evidence base for trauma-focused cognitive behavioral therapy (TF-CBT) to treat posttraumatic stress disorder (PTSD) in youth is compelling, but the number of controlled trials in very young children is few and limited to sexual abuse victims. These considerations plus theoretical limitations have led to doubts about the feasibility of TF-CBT techniques in very young children. This study examined the efficacy and feasibility of TF-CBT for treating PTSD in three- through six-year-old children exposed to heterogeneous types of traumas. METHODS: Procedures and feasibilities of the protocol were refined in Phase 1 with 11 children. Then 64 children were randomly assigned in Phase 2 to either 12-session manualized TF-CBT or 12-weeks wait list. RESULTS: In the randomized design the intervention group improved significantly more on symptoms of PTSD, but not on depression, separation anxiety, oppositional defiant, or attention deficit/hyperactivity disorders. After the waiting period, all participants were offered treatment. Effect sizes were large for PTSD, depression, separation anxiety, and oppositional defiant disorders, but not attention-deficit/hyperactivity disorder. At six-month follow-up, the effect size increased for PTSD, while remaining fairly constant for the comorbid disorders. The frequencies with which children were able to understand and complete specific techniques documented the feasibility of TF-CBT across this age span. The majority were minority race (Black/African-American) and without a biological father in the home, in contrast to most prior efficacy studies. CONCLUSIONS: These preliminary findings suggest that TF-CBT is feasible and more effective than a wait list condition for PTSD symptoms, and the effect appears lasting. There may also be benefits for reducing symptoms of several comorbid disorders. Multiple factors may explain the unusually high attrition, and future studies ought to oversample on these demographics to better understand this understudied population.

The Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R): a scale to assist the diagnosis of Autism Spectrum Disorder in adults: an international validation study.

The Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R) is a valid and reliable instrument to assist the diagnosis of adults with Autism Spectrum Disorders (ASD). The 80-question scale was administered to 779 subjects (201 ASD and 578 comparisons). All ASD subjects met inclusion criteria: DSM-IV-TR, ADI/ADOS diagnoses and standardized IQ testing. Mean scores for each of the questions and total mean ASD vs. the comparison groups' scores were significantly different (p < .0001). Concurrent validity with Constantino Social Responsiveness Scale-Adult = 95.59%. Sensitivity = 97%, specificity = 100%, test-retest reliability r = .987. Cronbach alpha coefficients for the subscales and 4 derived factors were good. We conclude that the RAADS-R is a useful adjunct diagnostic tool for adults with ASD.

Growth and associations between auxology, caregiving environment, and cognition in socially deprived Romanian children randomized to foster vs ongoing institutional care.

OBJECTIVES: To determine effects of improved nurturing compared with institutional care on physical growth and to investigate the association between growth and cognitive development. DESIGN: A randomized controlled trial beginning in infants (mean age, 21.0 months; range, 5-32 months), with follow-up at 30, 42, and 54 months of age. SETTING: Institutionalized and community children in Bucharest, Romania. PARTICIPANTS: One hundred thirty-six healthy institutionalized children from 6 orphanages and 72 typically developing, never-institutionalized children. INTERVENTION: Institutionalized children were randomly assigned to receive foster care or institutional care as usual. OUTCOME MEASURES: Auxology and measures of intelligence over time. RESULTS: Growth in institutionalized children was compromised, particularly in infants weighing less than 2500 g at birth. Mean height and weight, though not head size, increased to near normal within 12 months in foster care. Significant independent predictors for greater catch-up in height and weight included age younger than 12 months at randomization, lower baseline z scores, and higher caregiving quality, particularly caregiver sensitivity and positive regard. Baseline developmental quotient, birth weight, and height catch-up were significant independent predictors of cognitive abilities at follow-up. Each incremental increase of 1 in standardized height scores between baseline and 42 months was associated with a mean increase of 12.6 points (SD, 4.7 points) in verbal IQ (P < .05). CONCLUSIONS: Foster care had a significant effect on growth, particularly with early placement and high-quality care. Growth and IQ in low-birth-weight children are particularly vulnerable to social deprivation. Catch-up growth in height under more nurturing conditions is a useful indicator of caregiving quality and cognitive improvement.

Placement in foster care enhances quality of attachment among young institutionalized children.

This study examined classifications of attachment in 42-month-old Romanian children (N = 169). Institutionalized since birth, children were assessed comprehensively, randomly assigned to care as usual (CAU) or to foster care, and compared to family-reared children. Attachment classifications for children in foster care were markedly different from those in the CAU. Importantly, children placed in foster care before 24 months were more likely to have secure attachments and if placed earlier were less likely to have disorganized or insecure-other attachments. Cognitive status predicted greater likelihood of organized attachment in the CAU and greater likelihood of secure attachment in the foster care and never-institutionalized groups. Foster care is an important intervention to reduce the adverse effects following early deprivation.

Integrating statistical and clinical research elements in intervention-related grant applications: summary from an NIMH workshop.

OBJECTIVE: The authors summarize points for consideration generated in a National Institute of Mental Health (NIMH) workshop convened to provide an opportunity for reviewers from different disciplines-specifically clinical researchers and statisticians-to discuss how their differing and complementary expertise can be well integrated in the review of intervention-related grant applications. METHODS: A 1-day workshop was convened in October, 2004. The workshop featured panel presentations on key topics followed by interactive discussion. This article summarizes the workshop and subsequent discussions, which centered on topics including weighting the statistics/data analysis elements of an application in the assessment of the application's overall merit; the level of statistical sophistication appropriate to different stages of research and for different funding mechanisms; some key considerations in the design and analysis portions of applications; appropriate statistical methods for addressing essential questions posed by an application; and the role of the statistician in the application's development, study conduct, and interpretation and dissemination of results. RESULTS: A number of key elements crucial to the construction and review of grant applications were identified. It was acknowledged that intervention-related studies unavoidably involve trade-offs. Reviewers are helped when applications acknowledge such trade-offs and provide good rationale for their choices. Clear linkage among the design, aims, hypotheses, and data analysis plan and avoidance of disconnections among these elements also strengthens applications. CONCLUSION: The authors identify multiple points to consider when constructing intervention-related grant applications. The points are presented here as questions and do not reflect institute policy or comprise a list of best practices, but rather represent points for consideration.

Institutional rearing and psychiatric disorders in Romanian preschool children.

OBJECTIVE: There is increasing interest in the relations between adverse early experiences and subsequent psychiatric disorders. Institutional rearing is considered an adverse caregiving environment, but few studies have systematically examined its effects. This study aimed to determine whether removing young children from institutional care and placing them with foster families would reduce psychiatric morbidity at 54 months of age. METHOD: Young children living in institutions in Bucharest were enrolled when they were between 6 and 30 months of age. Following baseline assessment, 136 children were randomly assigned to care as usual (continued institutional care) or to removal and placement in foster care that was created as part of the study. Psychiatric disorders, symptoms, and comorbidity were examined by structured psychiatric interviews of caregivers of 52 children receiving care as usual and 59 children in foster care when the children were 54 months of age. Both groups were compared to 59 typically developing, never-institutionalized Romanian children recruited from pediatric clinics in Bucharest. Foster care was created and supported by social workers in Bucharest who received regular consultation from U.S. clinicians. RESULTS: Children with any history of institutional rearing had more psychiatric disorders than children without such a history (53.2% versus 22.0%). Children removed from institutions and placed in foster families were less likely to have internalizing disorders than children who continued with care as usual (22.0% versus 44.2%). Boys were more symptomatic than girls regardless of their caregiving environment and, unlike girls, had no reduction in total psychiatric symptoms following foster placement. CONCLUSIONS: Institutional rearing was associated with substantial psychiatric morbidity. Removing young children from institutions and placing them in families significantly reduced internalizing disorders, although girls were significantly more responsive to this intervention than boys.

The effects of foster care intervention on socially deprived institutionalized children's attention and positive affect: results from the BEIP study.

BACKGROUND: We examined the effects of a foster care intervention on attention and emotion expression in socially deprived children in Romanian institutions. METHODS: Institutionalized children were randomized to enter foster care or to remain under institutional care. Subsequently, the institutionalized and foster care groups, along with a community-based comparison group, were evaluated on emotion tasks at 30 and 42 months of age. Behaviors reflecting positive and negative affect and attention were coded from videotapes. RESULTS: Data indicated that at both age points, children who received the foster care intervention showed higher levels of attention and positive affect compared to children who remained institutionalized. Compared to the community sample, children in the foster care intervention showed higher levels of attention to the emotion-eliciting tasks at 42 months of age. CONCLUSIONS: The results of this randomized trial demonstrate the impact of a family-based intervention on the development of attention and positive affect.

Duration of ultrasonic vocalizations in the isolated rat pup as a behavioral measure: sensitivity to anxiolytic and antidepressant drugs.

Neo-natal rats emit ultrasonic vocalizations (USVs) when isolated from their mothers and littermates. Clinically effective anxiolytics reliably reduce USVs, making this behavior a useful animal model of the anxiolytic potential of novel pharmacological approaches to the treatment of anxiety. Here, we assess the hypothesis that USV duration (total time spent vocalizing) is a more sensitive measure of anxiolytic and antidepressant efficacy than USV number by testing established and putative anxiolytics in this model. Negative geotaxis and righting reflex latency were measured to assess sedating properties. The benzodiazepines, CDP (1-10 mg/kg) and diazepam (0.3-3 mg/kg), the 5HT(1A) partial agonist, buspirone (0.3-3 mg/kg), and the mGluR5 antagonist, MTEP (1-30 mg/kg), reduced USV duration at lower doses and to a greater magnitude than USV number. The benzodiazepines, unlike buspirone and MTEP, produced measurable sedation, but it was dissociable from reductions in USV duration. The SSRI antidepressants, fluoxetine (1-30 mg/kg) and citalopram (0.3-30 mg/kg), reduced USV duration more than number with no measurable effect on sedation. The tricyclic antidepressants, imipramine (1-10 mg/kg) and amitriptyline (1-30 mg/kg), had no effect dissociable from sedation. These data support USV duration as a more sensitive and useful measure than USV number in the isolated rat pup model.

A scale to assist the diagnosis of autism and Asperger's disorder in adults (RAADS): a pilot study.

An empirically based 78 question self-rating scale based on DSM-IV-TR and ICD-10 criteria was developed to assist clinicians' diagnosis of adults with autism and Asperger's Disorder-the Ritvo Autism and Asperger's Diagnostic Scale (RAADS). It was standardized on 17 autistic and 20 Asperger's Disorder and 57 comparison subjects. Both autistic and Asperger's groups scored significantly higher than comparison groups with no overlap; sensitivity, specificity, and content validity equaled one. Cronbach's alpha coefficients of internal consistency of three subscales were satisfactory. Gender, age, and diagnostic categories were not significantly associated factors. The RAADS can be administered and scored in less than an hour and may be useful as a clinical scale to assist identification of autism and Asperger's Disorder in adults. The RAADS does not distinguish between autism and Asperger's Disorder.

Clinical evidence that Asperger's disorder is a mild form of autism.

OBJECTIVE: The aim of this study is to obtain clinical evidence to test the hypothesis that Asperger's disorder (AD) is a mild form of autism (AU). METHOD: A 78-item Likert scale (the RAADS) was administered to 25 adults with AD and 19 with AU (ages, 18-65 years) to assess presence, type, and duration of symptoms. RESULTS: The following results were found: (a) subjects with AD and AU have similar symptoms throughout adulthood (responses to 72 of 78 questions were not significantly different); (b) subjects with AD had a significantly fewer total number of symptoms; (c) subjects with AD reported nonsignificantly fewer symptoms in the DSM-IV-TR domains of social interaction and repetitive patterns of behavior; and (d) subjects with AD had significantly fewer symptoms in the communication domain. CONCLUSIONS: The data support the hypothesis that AD is a mild form of AU, and that they share a common etiology and developmental neuropathology. It appears warranted in future diagnostic manuals to incorporate AU and AD into 1 diagnostic category such as, "Autism Spectrum Disorder, (with modifiers, severe, moderate, mild, atypical, and Asperger's type)."

Cognitive recovery in socially deprived young children: the Bucharest Early Intervention Project.

In a randomized controlled trial, we compared abandoned children reared in institutions to abandoned children placed in institutions but then moved to foster care. Young children living in institutions were randomly assigned to continued institutional care or to placement in foster care, and their cognitive development was tracked through 54 months of age. The cognitive outcome of children who remained in the institution was markedly below that of never-institutionalized children and children taken out of the institution and placed into foster care. The improved cognitive outcomes we observed at 42 and 54 months were most marked for the youngest children placed in foster care. These results point to the negative sequelae of early institutionalization, suggest a possible sensitive period in cognitive development, and underscore the advantages of family placements for young abandoned children.

Designing research studies on psychosocial interventions in autism.

To address methodological challenges in research on psychosocial interventions for autism spectrum disorder (ASD), a model was developed for systematically validating and disseminating interventions in a sequence of steps. First, initial efficacy studies are conducted to establish interventions as promising. Next, promising interventions are assembled into a manual, which undergoes pilot-testing. Then, randomized clinical trials test efficacy under controlled conditions. Finally, effectiveness studies evaluate outcomes in community settings. Guidelines for research designs at each step are presented. Based on the model, current priorities in ASD research include (a) preparation for efficacy and effectiveness trials by developing manuals for interventions that have shown promise and (b) initial efficacy studies on interventions for core features of ASD such as social reciprocity.

The discrimination of facial expressions by typically developing infants and toddlers and those experiencing early institutional care.

Early experience likely plays an important role in the development of the ability to discriminate facial expressions of emotion. We posited that compared to children reared with their biological families (n=72), abandoned children being reared in institutions (n=39) should demonstrate impairments in this ability. The visual paired comparison procedure was utilized to assess the abilities of 13- to 30-month-old children to discriminate among multiple pairs of photographs of facial expressions. Both groups exhibited a normative profile of discrimination, with no group differences evident. Such findings suggest that early institutionalization does not affect the ability of 1- to 3-year-olds to discriminate facial expressions of emotion, at least as inferred by the Visual Paired Comparison Procedure.

Young children with developmental delays as young adults: predicting developmental and personal-social outcomes.

We report on a 20-year follow-up of 30 children with developmental delays identified at age 3. Our purpose was to assess the relationship of early indicators of delay to cognitive and personal-social status in young adulthood. Predictors were Developmental and Personal-Social factors derived from standardized tests and parent questionnaires administered when the children were 3 and 6 to 7. Outcome measures in young adulthood included standardized and project-developed questionnaires and interviews with young adults and parents. Findings indicate that prediction varies relative to the outcome assessed. Developmental status at 6 to 7 was a strong predictor of developmental status in young adulthood. However, personal-social outcomes were generally not predicted by Personal-Social factors in the early years.

Ambulatory blood pressure and family history of hypertension in healthy men and women.

BACKGROUND: Family history of hypertension is a primary predictor of high blood pressure (BP). This study attempted to determine whether there is a gradual increase in BP between individuals with two hypertensive parents, one hypertensive parent, and normotensive parents and whether this increase is apparent with both ambulatory and casual BP assessments in men as well as in women. METHODS: A total of 220 healthy men and women, aged 22 to 50 years, completed two 24-h ambulatory BP sessions (one work day and one off work day). Based on family history information obtained from parents, three groups were formed: subjects with two hypertensive parents, one hypertensive parent, and normotensive parents. Work and off work days did not differ; analyses were based on mean values of the 2 days. RESULTS: Men with two hypertensive parents had higher daytime and night-time ambulatory BP than men with normotensive parents. Those with one hypertensive parent had intermediate BP levels. Ambulatory BP was not associated with family history in women. Also, men with one or two hypertensive parents had higher ambulatory BP than women with hypertensive parents, whereas offspring of normotensive parents exhibited no sex differences in BP. CONCLUSIONS: Elevated systolic and diastolic BP throughout the day and night seems to characterize men with two hypertensive parents. In evaluating the relationship between family history of hypertension and BP, it is important to use ambulatory BP measures, differentiate between individuals with one and with two hypertensive parents, and focus on gender differences in BP.

Diet quality affects the playground activities of Kenyan children.

The present study examined the effects of a school breakfast program on the activity level, emotional state, and social interactions of a group of Kenyan schoolchildren on the playground. Five hundred forty children in rural Kenya participated in the study. The first standard (grade) classes were randomly assigned to groups provided for 21 months with school breakfasts of equivalent caloric value while families with children in the control group were given a goat at the end of the study. The study aimed to determine whether enhanced caloric intake or diet quality influenced the children's behavior on the school playground. The results indicate that supplemented children were more active and showed more leadership behavior and initiative than did non-supplemented children. In addition, children given meat showed fewer periods of low activity and more leadership behaviors and initiative than did children provided entirely with vegetable source foods. These results support our previous findings from naturalistic studies in the same community that both diet quantity and quality are important for children's development.

Ambulatory blood pressure and the brain: a 5-year follow-up.

OBJECTIVE: To determine if initial values of casual and ambulatory systolic blood pressure (SBP) predict white matter hyperintensities, insular subcortex hyperintensities, and brain atrophy 5 years later in a group of healthy elderly individuals. METHODS: The authors studied 155 healthy men and women, aged 55 to 79 years. Two 24-hour ambulatory blood pressure (BP) sessions assessed BP level and variability during waking and sleep. Hyperintensities and total brain volume were quantified by MRI. Procedures were repeated 5 years later in 78% (121) of subjects. RESULTS: Hyperintensities and brain atrophy increased over time, with greater increases among older subjects. The presence of increased BP level and variability initially and again 5 years later had negative consequences for the brain. Independent of age, the greater the initial SBP, the greater the likelihood that individuals would have severe white matter hyperintensities after 5 years. Also, elevated casual SBP was associated with severe insular subcortex hyperintensities and greater SBP sleep variability with increased brain atrophy. CONCLUSIONS: Among healthy elderly individuals whose initial, average, casual blood pressure (BP) was relatively low (116.9/71.1 mm Hg), small increases in casual and 24-hour ambulatory BP measures were associated with greater brain atrophy and subcortical lesions after 5 years.