Body mass affects kinetic symmetry and inflammatory markers in adolescent knees during gait.

BACKGROUND: Early-onset osteoarthritis has been attributed to pro-inflammatory factors and biomechanical changes in obesity. However, research has yet to explore whether knee joint moments are asymmetrical in children with obesity and could precede the onset of knee osteoarthritis. The present study compares knee moment asymmetry between adolescents with and without obesity and examines the relationship between asymmetries and inflammatory biomarkers. METHODS: Twenty-eight adolescents (13-16 years) were classified as with (n = 12) or without (n = 16) obesity. Lower extremity kinetics were measured using three-dimensional motion analysis. Bilateral knee joint moments were analyzed in the sagittal, frontal, and transverse planes across stance phase. Kinetic asymmetry was calculated between the right and left sides and represented by the R2 value. Enzyme-linked immunosorbent assays analyzed serum 25-hydroxy vitamin D, interferon gamma, tumor nercrosis factor alpha, interleukin-6, and C-reactive protein levels. Parametric and non-parametric tests determined significant group differences in asymmetries and biomarkers, respectively. Spearman's correlations identified relationships between biomarkers and asymmetries with statistically significant group differences. FINDINGS: Adolescents with obesity had greater sagittal (loading, midstance) and frontal (midstance, pre-swing) plane kinetic knee asymmetry and higher concentrations of interleukin-6 and C-reactive protein. A moderately negative correlation existed between C-reactive protein and sagittal (loading, midstance) plane asymmetry, and also between interleukin-6 and frontal (pre-swing) plane asymmetry. INTERPRETATION: Inflammatory response increases with greater knee joint asymmetry, suggesting knee joint damage and altered joint loading co-exist in adolescents with obesity. Increased risk to joint health may exist in sub-phases where knee joints are improperly loaded.

Polysomnography-guided mandibular distraction osteogenesis in Pierre Robin sequence patients.

STUDY OBJECTIVES: Craniofacial malformations with micrognathia cause high grades of obstructive sleep apnea (OSA) measured by polysomnography (PSG). Mandibular distraction osteogenesis is a novel procedure for upper airway obstruction relief. Our primary objective was to describe the utilization of PSGs to improve obstruction in patients undergoing mandibular distraction. METHODS: This is a retrospective study. Patients with micrognathia and severe upper airway obstruction, presenting with severe OSA diagnosed by PSG, were included from a single tertiary care center between 2015 and 2019. PSGs were done (1) prior to surgery, (2) once the cosmetic goal was achieved (Post-Op 1), and (3) if residual moderate-to-severe OSA was seen, every 2 nights until mild or no OSA was achieved (Post-Op 2). RESULTS: Thirteen patients were included. The median age at surgery was 1.1 months (10 days-3 months). All 13 patients had baseline severe OSA, with a median obstructive apnea-hypopnea index of 33 events/h and a median O2 nadir of 73%. Post-Op 1 PSG was done at a median of 6 days after surgery. Median first postoperative obstructive apnea-hypopnea index in all 13 patients was 6.8 events/h, with a median O2 nadir of 87%. A median additional distraction of 3 mm was needed beyond the traditionally recommended advancement. Long-term follow-up studies at or after 1 year were done in 5 patients, all showing persistent nonsevere OSA. CONCLUSIONS: This is the first case series utilizing PSGs as a guide for mandibular distraction osteogenesis in patients with micrognathia showing the need for jaw overcorrection to achieve resolution of OSA. CITATION: Kochhar R, Modi V, de Silva N, et al. Polysomnography-guided mandibular distraction osteogenesis in Pierre Robin sequence patients. J Clin Sleep Med. 2022;18(7):1749-1755.

Does Parenting Style Affect Adolescent IBD Transition Readiness and Self-Efficacy Scores?

BACKGROUND: Transition to adult-centered care requires adolescents with inflammatory bowel disease (IBD) to acquire a set of independent self-management skills. Transition success can be affected by maturity, cognitive development, and many other factors. Our hypothesis was that parenting style would be associated with increased self-efficacy and therefore transitions readiness. METHODS: A prospective cohort survey study of adolescents with IBD and their parents from October 2018 to October 2019 was performed. Participants completed the IBD-Self-Efficacy Scale- Adolescent questionnaire (IBD-SES-A) and the Transition Readiness Assessment Questionnaire (TRAQ). Parents completed the Parent Styles and Dimensions Questionnaire (PSDQ-short form). Demographic and disease information were also collected. RESULTS: Sixty-nine participants were included for full analysis (36 males and 33 females); mean age was 18.2 years, and average age of IBD diagnosis 13 years. Overall, 83% of participants were non-Hispanic Caucasian, and 84% reported parental annual income over USD 100,000. All 69 parents reported an authoritative parenting style. Females have significantly higher TRAQ scores than males (p = 0.0004). TRAQ scores differed significantly between age groups, with 20 to 22 years old having higher scores (p ≤ 0.0001). TRAQ and IBD-SES-A scores did not differ by parental education or parenting style. CONCLUSION: Given the inability to delineate different parenting, this study was unable to demonstrate a protective parenting style associated with better transitions readiness and self-efficacy scores in adolescents with IBD. Within the context of authoritative parenting, we did find that females and older adolescents had higher transition readiness scores. Additional research into psychosocial determinants of transition readiness, and the importance of multidisciplinary management with an integrated team including psychologist and social workers, can help improve IBD transition outcomes.

Simulation-Based Discharge Education Program for Caregivers of Children With Tracheostomies.

OBJECTIVES: To design, implement, and evaluate a simulation-based education (SBE) program for caregivers of children with tracheostomy. METHODS: Self-reported comfort and confidence in knowledge as well as tracheostomy care skills were assessed before and after a single SBE session for 24 consecutively enrolled caregivers of children with tracheostomies aged <21 years who were hospitalized at an academic medical center from August 2018 to September 2019 by using a survey and checklist, respectively. Mean individual and aggregated scores were compared by using a paired samples t-test, and association between instruments was determined with Spearman correlation. RESULTS: Post-SBE, there was a significant improvement in both self-reported comfort and confidence (P < .001) and checklist assessment of most tracheostomy care skills (P < .001). There were no significant correlations between caregivers' self-reported comfort and confidence and skills pre-SBE (ρ = 0.13) or post-SBE (ρ = 0.14). Cronbach's α coefficients for the survey ranged from 0.93 to 0.95 and for the checklist from 0.58 to 0.67. Seventeen percent of caregivers competently completed the entire checklist post-SBE, with most caregivers missing 1 or 2 critical skills such as obturator removal after tracheostomy insertion. CONCLUSIONS: In this pilot study, we demonstrated successful design and implementation of an SBE program for caregivers of children with tracheostomies, revealing improvements in self-reported comfort and confidence as well as in their performance of tracheostomy care skills. Further optimization is needed, and caregivers may benefit from additional SBE sessions to achieve complete skills competency. Future research on the long-term impact of SBE and the peer-to-peer support element of the program is needed.

The Use of Ultrasound-Measured Optic Nerve Sheath Diameter to Predict Ventriculoperitoneal Shunt Failure in Children.

OBJECTIVE: The goal of this study was to assess the accuracy of ultrasound-measured optic nerve sheath diameter (ONSD) as a screen for ventriculoperitoneal shunt failure. METHODS: We prospectively enrolled a convenience sample of children presenting to the ED with suspected shunt failure. The ONSD was measured by ultrasound and compared with computed tomography/magnetic resonance imaging (CT/MRI) and neurosurgical impression. We defined shunt failure on ultrasound as an ONSD greater than 4.0 mm in infants 12 months and younger or greater than 4.5 mm in children older than 12 months. A single emergency radiologist at our institution read all CTs and MRIs for categorical determination of shunt failure. We defined shunt failure based on neurosurgical impression as a decision to admit and perform shunt revision. We report test characteristics and 95% confidence intervals of ONSD as a predictor for shunt failure. RESULTS: We enrolled 32 subjects. The sensitivities of ONSD compared with CT/MRI and neurosurgical impression, 60.0% and 75.0%, respectively, were low. However, the negative predictive values of ONSD compared with CT/MRI and neurosurgical impression were 90.0% and 95.0%, respectively. CONCLUSIONS: Optic nerve sonography may be a useful tool to identify children presenting with suspected ventriculoperitoneal shunt failure who do not require further imaging. This would reduce the use of CT scan and exposure to ionizing radiation in children with suspected shunt malfunction who do not require neurosurgical intervention. Consideration of additional risk factors and a larger sample size may yield stronger results.

Accuracy of Reported Community Diagnosis of Autism Spectrum Disorder.

To compare community diagnoses of Autism Spectrum Disorder (ASD) reported by parents to consensus diagnoses made using standardized tools plus clinical observation. 87 participants (85% male, average age 7.4 years), with reported community diagnosis of ASD were evaluated using the Autism Diagnostic Observation Schedule) (ADOS-2), Differential Ability Scale (DAS-II), and Vineland Adaptive Behavior Scales (VABS-II). Detailed developmental and medical history was obtained from all participants. Diagnosis was based on clinical consensus of at least two expert clinicians, using test results, clinical observations, and parent report. 23% of participants with a reported community diagnosis of ASD were classified as non-spectrum based on our consensus diagnosis. ASD and non-spectrum participants did not differ on age at evaluation and age of first community diagnosis. Non-verbal IQ scores and Adaptive Behavior Composite scores were significantly higher in the non-spectrum group compared to the ASD group (104.5 ± 21.7 vs. 80.1 ± 21.6, p < .01; 71.1 ± 15 versus 79.5 ± 17.6, p < .05, respectively). Participants enrolled with community diagnosis of PDD-NOS were significantly more likely to be classified as non-spectrum on the study consensus diagnosis than Participants with Autism or Asperger (36% versus 9.5%, Odds Ratio = 5.4, p < .05). This study shows suboptimal agreement between community diagnoses of ASD and consensus diagnosis using standardized instruments. These findings are based on limited data, and should be further studied, taking into consideration the influence of DSM 5 diagnostic criteria on ASD prevalence.

Disorganized attachment in infancy: a review of the phenomenon and its implications for clinicians and policy-makers.

Disorganized/Disoriented (D) attachment has seen widespread interest from policy makers, practitioners, and clinicians in recent years. However, some of this interest seems to have been based on some false assumptions that (1) attachment measures can be used as definitive assessments of the individual in forensic/child protection settings and that disorganized attachment (2) reliably indicates child maltreatment, (3) is a strong predictor of pathology, and (4) represents a fixed or static "trait" of the child, impervious to development or help. This paper summarizes the evidence showing that these four assumptions are false and misleading. The paper reviews what is known about disorganized infant attachment and clarifies the implications of the classification for clinical and welfare practice with children. In particular, the difference between disorganized attachment and attachment disorder is examined, and a strong case is made for the value of attachment theory for supportive work with families and for the development and evaluation of evidence-based caregiving interventions.

Child-mother attachments in the face of grandparent HIV.

Child-mother attachment, as observed in the Strange Situation (SSP), was assessed in 61 families affected by HIV and 18 neighborhood comparison families not affected by HIV, but of similar ethnicity and socioeconomic status. Children were aged one to three years at the assessment. Secure attachment was significantly less likely among children in the HIV-affected group than among comparison group children (36% versus 67%). The most common pattern of attachment in the HIV-affected group was disorganized/disoriented, observed in 41% of children (versus 22% of comparison children). Children from families that included a surviving grandparent with HIV showed disorganized attachments more often than children whose grandparents died (53% versus 36%). Child attachment classifications were not associated with families' participation in a family-based, cognitive-behavioral HIV intervention. These results document the inter-generational impact of young mothers' who were growing up with an HIV-infected parent. These findings suggest that families affected by HIV may benefit from interventions that address attachment issues.

The current and ideal state of mental health training: pediatric resident perspectives.

UNLABELLED: PHENOMENON: Mental health (MH) problems are prevalent in the pediatric population, and in a setting of limited resources, pediatricians need to provide MH care in the primary medical home yet are uncomfortable doing so citing a lack of training during residency as one barrier. APPROACH: The purpose of this study is to describe pediatric residents' experiences and perspectives on the current and ideal states of MH training and ideas for curriculum development to bridge this gap. A qualitative study using focus groups of pediatric residents from an urban academic medical center was performed. Audio recordings were transcribed and analyzed using a grounded theory approach. FINDINGS: Twenty-six residents participated in three focus groups, which is when thematic saturation was achieved. The team generated five major themes: capabilities, comfort, organizational capacity, coping, and education. Residents expressed uncertainty at every step of an MH visit. Internal barriers identified included low levels of comfort and negative emotional responses. External barriers included a lack of MH resources and mentorship in MH care, or an inadequate organizational capacity. These internal and external barriers resulted in a lack of perceived capability in handling MH issues. In response, residents reported inadequate coping strategies, such as ignoring MH concerns. To build knowledge and skills, residents prefer educational modalities including didactics, experiential learning through collaborations with MH specialists, and tools built into patient care flow. Insights: Pediatric residency programs need to evolve in order to improve resident training in MH care. The skills and knowledge requested by residents parallel the American Academy of Pediatrics statement on MH competencies. Models of collaborative care provide similar modalities of learning requested by residents. These national efforts have not been operationalized in training programs yet may be useful for curriculum development and dissemination to enhance trainees' MH knowledge and skills to provide optimal MH care for children.

The current and ideal state of mental health training: pediatric program director perspectives.

OBJECTIVE: To assess pediatric residency program director (PD) perceptions of the current state of mental health (MH) training, their receptivity to curricular changes, and perceptions of their residents' knowledge and skills in MH care. METHODS: We performed a cross-sectional study utilizing a Web-based survey of pediatric residency PDs to assess program characteristics, learning modalities PDs currently had or would implement, and their knowledge of the new American Academy of Pediatrics' MH competencies. PDs then ranked their residents' knowledge and skills for 29 MH competencies. Analyses included descriptive statistics and bivariate and multivariate analyses to assess for associations between variables, particularly MH model of care and perceived competence. RESULTS: Ninety-nine PDs (51%) responded. A total of 87% of PDs reported that MH care was taught as part of another rotation, yet PDs were receptive to curricular changes. Only 45% of PDs were aware of the 2009 American Academy of Pediatrics competencies, and PDs infrequently rated their residents' MH skills and knowledge to be above average. Attention-deficit/hyperactivity disorder (ADHD) was an exception: 64% reported above-average ADHD knowledge in diagnoses and 57% in treatment. There was an association between enhanced MH services in continuity clinics and perceived resident systems-based practice (P < .01) and medical knowledge (P = .04). CONCLUSIONS: PDs acknowledged that MH training is not emphasized, leading to deficiencies in their residents' knowledge and skills in MH care. The receptivity of PDs suggests the need for targeted dissemination of national guidelines or curriculum. Integrated models of care may be one way to improve resident competencies, but this deserves further study.

Adolescents' and young adults' perspectives on their emergency care.

OBJECTIVES: The aim of this study was to assess the perspectives of adolescents and young adults seen in the emergency department (ED) on the optimal age for transition from a pediatric ED (PED) to an adult ED (AED) as well as the appropriateness of their assigned ED site. Secondary aims were to determine ED physicians' understanding and assessment of their psychosocial needs, to determine whether subjects had a primary care provider (PCP), as well as to identify resources they felt would improve their ED experience. METHODS: This study used in-person structured interviews on a convenience sample of ED patients aged 15 to 25 years. Data were analyzed with the SPSS for Windows (v15.0) using t tests and uncertainty coefficients. RESULTS: We interviewed 200 subjects; the mean age was 20.5 (SD, 3) years, 65% were female, and 54% were seen in the PED. The subjects reported a mean age of 18.5 years as optimal for transition to an AED (mode, 18; second peak, 21); only 5% chose an age older than 21 years. The AED subjects more likely felt that their site of care was appropriate (Likert scale, 1-3; 2.5 vs 2.2, P < 0.05). HEADSS (Home, Education/Employment, Activity, Drugs, Sexuality, Suicide) topics were rarely addressed in both ED sites. The PED subjects more often identified a PCP (87% vs 68%); there was no difference in notifying their PCP (27% vs 19%). The PED subjects more often desired magazines (83% vs 70%) and entertainment videos (61% vs 34%). CONCLUSIONS: Adolescents and young adults identify the age of 18 years as optimal for transition from a PED to an AED setting. Instituting a standardized HEADSS assessment protocol and offering age-appropriate resources may enhance the emergency experience for this population.

The impact of gestational age on resource utilization after open heart surgery for congenital cardiac disease from birth to 1 year of age.

The impact of gestational age on perioperative morbidity was examined using a novel construct, the resource utilization index (RUI). The medical records of subjects from birth to 1 year of age entered into a pediatric cardiothoracic surgery database from a major academic medical center between 2007 and 2011 were reviewed. The hypothesis tested was that infants born at 37-38 weeks (early-term infants) experience greater resource utilization after open heart surgery than those born at 39 completed weeks and that this association can be observed until 1 year of age. The results support the premise that resource utilization increases linearly with declining gestational age among infants at 0-12 months who undergo cardiac surgery. Five of the six variables comprising the RUI showed statistically significant linear associations with gestational age in the predicted direction. Multivariate linear regression analysis showed that gestational age was a significant predictor of an increased RUI composite. Further investigation is needed to test the concept and to expand on these findings.

Patterns and influence of familial autoimmunity in pediatric systemic lupus erythematosus.

BACKGROUND: A high prevalence of autoimmune disease (AD) has been documented in relatives of adult patients with systemic lupus erythematosus (SLE). However, data on familial inheritance patterns in pediatric SLE patients is scarce. FINDINGS: The charts of 69 patients with pediatric-onset SLE were reviewed retrospectively. The primary aim was to describe the prevalence and types of AD in relatives of children with SLE. The secondary aims were: 1) to compare severity of SLE in children with and without relatives affected by AD, and 2) to evaluate the impact of baseline demographics on severity of SLE in subjects. At diagnosis, 42% of subjects had one or more first, second, or third degree relative(s) with AD; and 32% of subjects had one or more first degree relative(s) with AD. The most common diseases in relatives of children with SLE were SLE (21%) and thyroid disease (15%). Subjects with no family history of AD were more likely to have severe SLE. SLE severity in subjects did not differ by gender. Children presenting with SLE at an earlier age were found to have more severe disease. CONCLUSIONS: This study demonstrated a high prevalence of AD in families of children with SLE, although a family history of AD did not correlate with more severe SLE in subjects. Future larger studies are necessary to elucidate patterns of familial inheritance and baseline patient characteristics that may affect severity of disease in pediatric SLE.

Outcomes 5 years after response to rituximab therapy in children and adults with immune thrombocytopenia.

Treatments for immune thrombocytopenic purpura (ITP) providing durable platelet responses without continued dosing are limited. Whereas complete responses (CRs) to B-cell depletion in ITP usually last for 1 year in adults, partial responses (PRs) are less durable. Comparable data do not exist for children and 5-year outcomes are unavailable. Patients with ITP treated with rituximab who achieved CRs and PRs (platelets > 150 × 10(9)/L or 50-150 × 10(9)/L, respectively) were selected to be assessed for duration of their response; 72 adults whose response lasted at least 1 year and 66 children with response of any duration were included. Patients had baseline platelet counts < 30 × 10(9)/L; 95% had ITP of > 6 months in duration. Adults and children each had initial overall response rates of 57% and similar 5-year estimates of persisting response (21% and 26%, respectively). Children did not relapse after 2 years from initial treatment whereas adults did. Initial CR and prolonged B-cell depletion predicted sustained responses whereas prior splenectomy, age, sex, and duration of ITP did not. No novel or substantial long-term clinical toxicity was observed. In summary, 21% to 26% of adults and children with chronic ITP treated with standard-dose rituximab maintained a treatment-free response for at least 5 years without major toxicity. These results can inform clinical decision-making.

Assessment of pediatric residents' communication and interpersonal skills during family-centered rounds.

OBJECTIVES: Residency training programs are required to assess and document residents' competency in communication. Multisource evaluations that include direct resident observations are preferred. Previous studies have often used methods of asking faculty members to evaluate residents on behaviors they did not witness. METHODS: Twenty first year pediatric residents (interns) were evaluated preand post-FCR introduction by a faculty member, a parent, and a nurse after the encounter with the patients and their families during rounds. All participants used the CAT. Mean CAT scores and associations between the evaluator groups were determined. RESULTS: Nurses and faculty were significantly more likely to observe how interns communicated with the parents in the post-FCR period (P < .001). Pre-FCR, compared to parent scores, intern scores were significantly lower (P < .05) and the scores were not correlated (P = .84). Post-FCR, the difference in internparent scores disappeared and their scores were significantly correlated (r18 = 0.73, P < .001). Intern scores did not correlate with faculty and nurse scores. Cronbach a coefficients for the CAT ranged from 0.90 to 0.99. CONCLUSIONS: Family-centered rounds provide more opportunities for direct observation of residents' competence in accordance with Accreditation Council for Graduate Medical Education guidelines. This rounds format also encourages a climate that improves residents' ability to self-assess. Residents' communication skills can be assessed by using the Communication Assessment Tool in an efficient and timely manner, because all evaluators are present at the bedside during family-centered rounds.

Effects of implementing family-centered rounds (FCRs) in a neonatal intensive care unit (NICU).

OBJECTIVES: (1) Evaluate impact of FCR on provider satisfaction and collaboration. (2) Evaluate impact of FCR on parent satisfaction with provider communication. METHODS: Collaboration and Satisfaction about Care Decisions (CSACD) questionnaire was given to staff on 4 patients 2 days a week for 5 weeks prior to and 6 months after implementation of FCR. Parents received a Parents Stress Scale and Neonatal Instrument of Parent Satisfaction before discharge, prior to and 6 months after starting FCR. RESULTS: 278/288 (97%) staff surveys were completed, 142 pre and 136 post. On the CSACD survey NNPs and fellows showed increased (p < 0.05) collaboration and satisfaction post FCR. No group had decreased satisfaction. Twenty-eight of 45 (62%) parent surveys were completed, 12 pre and 16 post. Parents' satisfaction scores increased (p < 0.01) pre vs. post on survey items regarding communication, meeting with physicians, and obtaining information about their infants. CONCLUSIONS: FCR was associated with enhanced collaboration among team members for NNPs and fellows. Parents' satisfaction scores increased post FCR on survey items regarding communication. Since NNPs and fellows are the primary communicators with parents, the increased satisfaction may reflect improved communication due to FCR. This added opportunity for open dialogue may also contribute to the increased parent satisfaction.

The Association between Childhood Overweight and Reflux Esophagitis.

Background. In adults, it has been shown that obesity is associated with gastroesophageal reflux disease (GERD) and GERD-related complications. There are sparse pediatric data demonstrating associations between childhood overweight and GERD. Objective. To investigate the association between childhood overweight and RE. Methods. We performed a retrospective chart review of 230 children (M : F = 114 : 116) who underwent esophagogastroduodenoscopy (EGD) with biopsies between January 2000 and April 2006. Patient demographics, weight, height, clinical indications for the procedure, the prevalence of BMI classification groups, the prevalence of RE and usage of anti-reflux medications were reviewed. For these analyses, the overweight group was defined to include subjects with BMI>/= 85th percentile. The normal weight group was defined to include subjects with BMI 5th to 85th percentile. Results. Among the 230 subjects, 67 (29.1%) had BMI percentiles above the 85th percentile for age and gender. The prevalence of RE in the overweight group did not differ significantly from that in the normal weight group (23.9% versus 24.5%, resp.). Overweight subjects taking anti-reflux medications clearly demonstrated a higher prevalence of biopsy-proven RE compared to overweight subjects not taking anti-reflux medications (34.1% versus 7.7%, P = .009). Conclusions. There was no significant difference in the prevalence of biopsy-proven RE in the overweight group compared to the normal weight group. However, the prevalence of RE was significantly higher in overweight subjects on anti-reflux medications compared to overweight subjects not taking anti-reflux medications. This finding emphasizes the importance of early recognition and treatment of GERD for the overweight pediatric patients with symptoms in conjunction with weight loss program for this population to reduce long-term morbidities associated with GERD.

Early postnatal exposure to methylphenidate alters stress reactivity and increases hippocampal ectopic granule cells in adult rats.

To mimic clinical treatment with methylphenidate (MPH; Ritalin) for attention deficit/hyperactivity disorder (ADHD), rat pups were injected with MPH (5 mg/kg, i.p.) or placebo twice daily during their nocturnal active phase from postnatal day (PND) 7-35. Thirty-nine days after the last MPH administration (PND 76), four litters of rats experienced stressful conditions during the 2003 New York City blackout. MPH-treated rats that endured the blackout lost more weight and regained it at a slower pace than controls (p<0.05; N=7-11 per group). Furthermore, MPH-treated rats had elevated systolic arterial blood pressure (from 115.6+/-1.2 to 126+/-1.8 mmHg; p<0.05), assessed on PND 130 by tail cuff plethysmography. Immunocytochemical studies of transmitter systems in the brain demonstrated rearrangements of catecholamine and neuropeptide Y fibers in select brain regions at PND 135, which did not differ between blackout and control groups. However, MPH-treated rats that endured the blackout had more ectopic granule cells in the hilus of the dorsal hippocampal dentate gyrus compared to controls at PND 135 (p<0.05; N=6 per group). These findings indicate that early postnatal exposure to high therapeutic doses of MPH can have long lasting effects on the plasticity of select brain regions and can induce changes in the reactivity to stress that persist into adulthood.

Methylphenidate administration to juvenile rats alters brain areas involved in cognition, motivated behaviors, appetite, and stress.

Thousands of children receive methylphenidate (MPH; Ritalin) for attention deficit/hyperactivity disorder (ADHD), yet the long-term neurochemical consequences of MPH treatment are unknown. To mimic clinical Ritalin treatment in children, male rats were injected with MPH (5 mg/kg) or vehicle twice daily from postnatal day 7 (PND7)-PND35. At the end of administration (PND35) or in adulthood (PND135), brain sections from littermate pairs were immunocytochemically labeled for neurotransmitters and cytological markers in 16 regions implicated in MPH effects and/or ADHD etiology. At PND35, the medial prefrontal cortex (mPFC) of rats given MPH showed 55% greater immunoreactivity (-ir) for the catecholamine marker tyrosine hydroxylase (TH), 60% more Nissl-stained cells, and 40% less norepinephrine transporter (NET)-ir density. In hippocampal dentate gyrus, MPH-receiving rats showed a 51% decrease in NET-ir density and a 61% expanded distribution of the new-cell marker PSA-NCAM (polysialylated form of neural cell adhesion molecule). In medial striatum, TH-ir decreased by 21%, and in hypothalamus neuropeptide Y-ir increased by 10% in MPH-exposed rats. At PND135, MPH-exposed rats exhibited decreased anxiety in the elevated plus-maze and a trend for decreased TH-ir in the mPFC. Neither PND35 nor PND135 rats showed major structural differences with MPH exposure. These findings suggest that developmental exposure to high therapeutic doses of MPH has short-term effects on select neurotransmitters in brain regions involved in motivated behaviors, cognition, appetite, and stress. Although the observed neuroanatomical changes largely resolve with time, chronic modulation of young brains with MPH may exert effects on brain neurochemistry that modify some behaviors even in adulthood.