Clinical neuroscience research最新文献

Introduction: Reports document children with attention deficit hyperactivity disorder (ADHD) and irritability, aggression or mood lability. Whether these additional symptoms represent severe ADHD, juvenile bipolar disorder, or other comorbidities is often unclear and has both diagnostic and treatment implications. We use the Cantwell modifications of the Robins and Guze diagnostic construct to examine the diagnostic validity and treatment implications of children with ADHD and some manic symptoms. Methods: We examined 579 children with ADHD from the multimodal treatment study of children with ADHD (MTA) and compared those with manic symptoms to those without manic symptoms in the domains of clinical phenomenology, demographic factors, psychosocial factors, biological factors, family genetic factors, family environmental factors, natural history, and intervention response. Results: Children with manic symptoms were more symptomatic at baseline and had more comorbidities and psychosocial and family environmental stressors. There were few differences in parental psychopathology and no biological differences. While ADHD children with manic symptoms were more symptomatic at 14 months, most differences were not significant when controlling for baseline symptoms. They were not more likely to have manic-like side effects except for moderate or severe worries. Discussion: Children with ADHD and manic symptoms compared to ADHD children without manic symptoms were more symptomatic and had more comorbidities at baseline. They nonetheless showed no systematic pattern of differences according to the Robins/Guze/Cantwell criteria. Moreover, they improved over time with standard ADHD treatments and were generally not found to have more adverse effects from stimulants.

Despite considerable research, the validity of attention-deficit/hyperactivity disorder (ADHD) remains controversial. This paper summarizes the results of a comprehensive review of the internal and external validity of ADHD as defined in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). Results indicate that for most individuals DSM-IV ADHD is a valid disorder in the sense that it is associated with significant impairment in social, academic, and occupational functioning and increased risk of accidental injury across the life span. Additional research is needed, however, to clarify the diagnostic validity of the hyperactive-impulsive type and the discriminant validity of the combined and inattentive subtypes. Other areas in need of further study include potential modifications to the diagnostic conceptualization of the inattentive subtype, developmental trajectories of the subtypes, and methods to address cross-informant diagnostic inconsistencies. Such research is likely to benefit from an etiologically informed approach to examining heterogeneity both across and within subtypes.

Cantwell [Cantwell DP. Empircism and child psychiatry. In: The 1990 C. Charles Burlingame, M.D., Award Lecture, Hartford, Connecticut: The institute of living; 1990 [1]] recognized age and ethnicity as important factors that should be considered in evaluating the clinical phenomenology of childhood disorders. Here we describe how these factors have been addressed in CHOC-UCI Initiative for the Development of Attention and Readiness (CUIDAR), an early intervention and prevention model for children at risk for diagnosis with Attention-Deficit/Hyperactivity Disorder (ADHD). CUIDAR was developed to address age by focusing on needs of families with young children and ethnicity by focusing on the needs of Hispanic families that speak Spanish. This program provides ‘service before diagnosis’ by removing barriers and offering psychosocial intervention (parent training) before the usual first-line treatment of ADHD (i.e. pharmacological intervention). We present data from the start-up phase of CUIDAR to evaluate differences in ethnic groups on the basis of important measures of effectiveness, such as parental satisfaction, gains in parenting skills, and reductions in child behavior problems. Cantwell [Cantwell DP. Empircism and child psychiatry. In: The 1990 C. Charles Burlingame, M.D., Award Lecture, Hartford, Connecticut: The institute of living; 1990 [1]] also recognized that clinicians often must provide treatment with a great deal of ‘therapeutic enthusiasm’ even though the intervention may be based on inadequate research data, and in this situation he recommended creating an atmosphere in which systematic observations could be made in the existing clinical context even when controlled research was not feasible. The data we report here were accumulated in this fashion during the development of CUIDAR, which was funded by the Children's and Families Commission of Orange County as a service delivery program.

A research program at UC Irvine has investigated the molecular genetic basis of ADHD by focusing on one candidate gene (DRD4) and the highly variable 48 bp VNTR polymorphism in exon 3. Initial studies revealed that the 7R variant is over-represented in ADHD samples, and a subsequent study suggested that the 7R allele is associated with clear excesses in behavior but not with some cognitive deficits thought to be core feature of the disorder. The next phase of this research program showed that (1) the common 7R allele was the product of positive selection, (2) other variation in and around the DRD4 gene is in tight linkage disequilibrium with the 7R allele but not the 4R allele, and (3) more rare 7R variants in the ADHD clinical sample than expected. Based on this program of research, we suggest that the 7R VNTR variant is responsible for the observed association of the DRD4 gene with ADHD, and that a challenge for the future is understanding what other genetic and/or environmental factors influence this association and affect clinical outcome of the disorder.

Comorbid conditions in children with attention deficit hyperactivity disorder (ADHD) are frequent and can affect treatment response and life course. From the multimodal treatment study of ADHD (MTA), we examined the persistence or development of conditions other than ADHD, e.g. oppositional defiant disorder (ODD), conduct disorder (CD), anxiety, depression, and learning disorder (LD) in 576 children, age 7–9 years, diagnosed rigorously with ADHD, who were randomly assigned to four different treatments for 14 months. The treatment groups were medication management alone (MedMgt), behavioral treatment alone (Beh), the combination (Comb), and community comparison routine care (CC). For the sample as a whole, we found significant decreases from baseline to 14 months in diagnoses of ODD, CD, and anxiety disorder but not LD or mood disorder. The CC group developed significantly more new ODD and retained more baseline ODD than the Comb or MedMgt groups. There were no significant treatment group differences for specific other conditions. Only the Comb group was significantly better than the CC group in reducing total number of disorders and impairment at 14 months in subjects with multiple conditions at baseline. Well-titrated and monitored stimulant medication can decrease ODD and possibly prevent future CD. Combined treatment may be required for the most disturbed children with ADHD who have multiple disorders and severe impairment.

This paper will review the evidence that the human mu opioid receptor gene influences risk for addictions. The structure of the gene will be delineated. Animal model work will be summarized briefly, indicating what drug addictions might be influenced by the mu opioid receptor gene. Finally, human genetic studies will be examined.

Alcoholism is a major public health problem, and a devastating disorder for affected individuals, their families, and society. We have made great gains in the past 25 years in understanding and treating alcoholism. A recent and important treatment advance is the use of pharmacotherapies that improve treatment response for many patients beyond what they obtain from counseling. We have gained a better understanding of the neurobiology associated with alcoholism, pharmacological treatments can be targeted to numerous pathways affected by chronic and excessive alcohol drinking. Consequently, an increased number of investigational studies of new compounds that are meant to reduce alcohol craving and drinking have emerged in the literature. There are three medications that have been approved in the United States (US) by the Food and Drug Administration (FDA) for the treatment of alcohol dependence: disulfiram, naltrexone, and acamprosate. Many more are being used in Canada, Europe, Australia and other parts of the world for treating alcohol dependence. Studies have also examined best practices in prescribing medications. For example, it has been empirically demonstrated that patient non-adherence to treatment diminishes the treatment's value. In turn, we can improve treatment response if we proactively provide patients with strategies to help them take their medications and attend their counseling visits. Other important advances related to pharmacotherapy are that alcoholic subgroups differentially respond to specific pharmacotherapies, and combining two pharmacotherapies that address different neurobiological systems simultaneously to treat alcohol dependence may prove more beneficial than a single medication in some patient groups.

The discovery that botanical cannabinoids such as delta-9 tetrahydrocannabinol exert some of their effect through binding specific cannabinoid receptor sites has led to the discovery of an endocannabinoid signaling system, which in turn has spurred research into the mechanisms of action and addiction potential of cannabis on the one hand, while opening the possibility of developing novel therapeutic agents on the other. This paper reviews current understanding of CB1, CB2, and other possible cannabinoid receptors, their arachidonic acid derived ligands (e.g. anandamide; 2 arachidonoyl glycerol), and their possible physiological roles. CB1 is heavily represented in the central nervous system, but is found in other tissues as well; CB2 tends to be localized to immune cells. Activation of the endocannabinoid system can result in enhanced or dampened activity in various neural circuits depending on their own state of activation. This suggests that one function of the endocannabinoid system may be to maintain steady state. The therapeutic action of botanical cannabis or of synthetic molecules that are agonists, antagonists, or which may otherwise modify endocannabinoid metabolism and activity indicates they may have promise as neuroprotectants, and may be of value in the treatment of certain types of pain, epilepsy, spasticity, eating disorders, inflammation, and possibly blood pressure control.