Moderation of antipsychotic-induced weight gain by energy balance gene variants in the RUPP autism network risperidone studies.

Second-generation antipsychotic exposure, in both children and adults, carries significant risk for excessive weight gain that varies widely across individuals. We queried common variation in key energy balance genes (FTO, MC4R, LEP, CNR1, FAAH) for their association with weight gain during the initial 8 weeks in the two NIMH Research Units on Pediatric Psychopharmacology Autism Network trials (N=225) of risperidone for treatment of irritability in children/adolescents aged 4-17 years with autism spectrum disorders. Variants in the cannabinoid receptor (CNR)-1 promoter (P=1.0 × 10(-6)), CNR1 (P=9.6 × 10(-5)) and the leptin (LEP) promoter (P=1.4 × 10(-4)) conferred robust-independent risks for weight gain. A model combining these three variants was highly significant (P=1.3 × 10(-9)) with a 0.85 effect size between lowest and highest risk groups. All results survived correction for multiple testing and were not dependent on dose, plasma level or ethnicity. We found no evidence for association with a reported functional variant in the endocannabinoid metabolic enzyme, fatty acid amide hydrolase, whereas body mass index-associated single-nucleotide polymorphisms in FTO and MC4R showed only trend associations. These data suggest a substantial genetic contribution of common variants in energy balance regulatory genes to individual antipsychotic-associated weight gain in children and adolescents, which supersedes findings from prior adult studies. The effects are robust enough to be detected after only 8 weeks and are more prominent in this largely treatment naive population. This study highlights compelling directions for further exploration of the pharmacogenetic basis of this concerning multifactorial adverse event

Auditory temporal processing in healthy aging: a magnetoencephalographic study

<p>Abstract</p> <p>Background</p> <p>Impaired speech perception is one of the major sequelae of aging. In addition to peripheral hearing loss, central deficits of auditory processing are supposed to contribute to the deterioration of speech perception in older individuals. To test the hypothesis that auditory temporal processing is compromised in aging, auditory evoked magnetic fields were recorded during stimulation with sequences of 4 rapidly recurring speech sounds in 28 healthy individuals aged 20 – 78 years.</p> <p>Results</p> <p>The decrement of the N1m amplitude during rapid auditory stimulation was not significantly different between older and younger adults. The amplitudes of the middle-latency P1m wave and of the long-latency N1m, however, were significantly larger in older than in younger participants.</p> <p>Conclusion</p> <p>The results of the present study do not provide evidence for the hypothesis that auditory temporal processing, as measured by the decrement (short-term habituation) of the major auditory evoked component, the N1m wave, is impaired in aging. The differences between these magnetoencephalographic findings and previously published behavioral data might be explained by differences in the experimental setting between the present study and previous behavioral studies, in terms of speech rate, attention, and masking noise. Significantly larger amplitudes of the P1m and N1m waves suggest that the cortical processing of individual sounds differs between younger and older individuals. This result adds to the growing evidence that brain functions, such as sensory processing, motor control and cognitive processing, can change during healthy aging, presumably due to experience-dependent neuroplastic mechanisms.</p

Advances in understanding and treating ADHD

Attention deficit hyperactivity disorder (ADHD) is a neurocognitive behavioral developmental disorder most commonly seen in childhood and adolescence, which often extends to the adult years. Relative to a decade ago, there has been extensive research into understanding the factors underlying ADHD, leading to far more treatment options available for both adolescents and adults with this disorder. Novel stimulant formulations have made it possible to tailor treatment to the duration of efficacy required by patients, and to help mitigate the potential for abuse, misuse and diversion. Several new non-stimulant options have also emerged in the past few years. Among these, cognitive behavioral interventions have proven popular in the treatment of adult ADHD, especially within the adult population who cannot or will not use medications, along with the many medication-treated patients who continue to show residual disability

Moderation of antipsychotic-induced weight gain by energy balance gene variants in the RUPP autism network risperidone studies.

Second-generation antipsychotic exposure, in both children and adults, carries significant risk for excessive weight gain that varies widely across individuals. We queried common variation in key energy balance genes (FTO, MC4R, LEP, CNR1, FAAH) for their association with weight gain during the initial 8 weeks in the two NIMH Research Units on Pediatric Psychopharmacology Autism Network trials (N=225) of risperidone for treatment of irritability in children/adolescents aged 4-17 years with autism spectrum disorders. Variants in the cannabinoid receptor (CNR)-1 promoter (P=1.0 × 10(-6)), CNR1 (P=9.6 × 10(-5)) and the leptin (LEP) promoter (P=1.4 × 10(-4)) conferred robust-independent risks for weight gain. A model combining these three variants was highly significant (P=1.3 × 10(-9)) with a 0.85 effect size between lowest and highest risk groups. All results survived correction for multiple testing and were not dependent on dose, plasma level or ethnicity. We found no evidence for association with a reported functional variant in the endocannabinoid metabolic enzyme, fatty acid amide hydrolase, whereas body mass index-associated single-nucleotide polymorphisms in FTO and MC4R showed only trend associations. These data suggest a substantial genetic contribution of common variants in energy balance regulatory genes to individual antipsychotic-associated weight gain in children and adolescents, which supersedes findings from prior adult studies. The effects are robust enough to be detected after only 8 weeks and are more prominent in this largely treatment naive population. This study highlights compelling directions for further exploration of the pharmacogenetic basis of this concerning multifactorial adverse event

Análise da eficácia do metilfenidato usando a versão abreviada do questionário de conners em transtorno de déficit de atenção/hiperatividade Analysis of the methylphenidate's efficacy using the abbreviated version Conners' questionnaire in attention deficit hyperactivity disorder

O transtorno de déficit de atenção/hiperatividade (TDAH) é quadro diagnóstico bastante complexo, de início precoce, com evolução crônica que repercute em diversos contextos. Três a 5% das crianças em idade escolar apresentam esse transtorno. O questionário de Conners vem sendo utilizado como instrumento de levantamento epidemiológico para o TDAH. OBJETIVO: Este estudo visa a utilização deste instrumento para a análise da eficácia do tratamento com metilfenidato em crianças com TDAH. MÉTODO: Foram selecionadas 21 crianças do gênero masculino, com TDAH do tipo combinado, idade cronológica entre sete anos completos a 10 anos e 11 meses e todos foram tratados com metilfenidato. A versão abreviada do questionário de Conners para pais e professores foi aplicada em dois momentos: um antes da medicação e outro entre seis a oito meses após o seu início. RESULTADOS: Obteve-se redução na pontuação no questionário de Conners em todas as crianças com TDAH concomitante à melhora clínica. CONCLUSÃO: Observou-se que o questionário de Conners mostrou-se útil não só como auxílio diagnóstico, mas também como um instrumento de avaliação da eficácia do tratamento do TDAH.<br>The attention deficit/hyperactivity disorder (ADHD) is a complex diagnosis. Its installation is precocious, with chronic evolution that impacts on the subject's performance in several contexts. Three to 5% of the school aged children present this disorder. The Conners' questionnaire has been used as an instrument of epidemiological survey for ADHD children. OBJECTIVE: This study aimed to investigate if this instrument could be an useful tool for the analysis of the methylphenidate's treatment efficacy in ADHD's children. METHOD: Twenty-one male children were selected, with ADHD combined type, chronological ages ranging from seven to 10 years and 11 months and all were treated with methylphenidate. The Conners' questionnaire abbreviated version for parents and teachers was applied in two moments, one without medication and another between six to eight months after the beginning of the methylphenidate. RESULTS: Results pointed to a reduction in punctuation in Conners' questionnaire in all children with ADHD concomitant to clinical improvement. CONCLUSION: Conners' questionnaire revealed to be useful not only for diagnosis, but also as an instrument to evaluate the effectiveness of the treatment of ADHD