Heritability of attention problems in children II: longitudinal results from a study of twins age 3 to 12.

this paper we present data of large samples of twin families, with an equal number of girls and boys. The well-known gender difference with boys displaying more OA and AP was observed at each age. Even at the age of 3, boys display more OA problems than girls. Clinical studies have indicated that severe problem behavior can be identified in very young children (see for review, Campbell, 1995; Keenan & Wakschlag, 2000; Shaw, Owens, Giovannelli, & Winslow, 2001) and that the onset of ADHD is during the pre-school period (Barkley, Fisher, Edelbrock, & Smallish, 1990; Table 6 Top part includes percentages of total variances (diagonal) and covariances (off-diagonal) explained by additive genetic, genetic dominance, and unique environmental components based on best fitting models. Percentages for boys and girls are reported below and above diagonal, respectively. Lower part includes correlations calculated for additive genetic, genetic dominance, and unique environmental sources of variance between different ages. Correlations for boys and girls are reported below and above diagonal, respectively Relative proportions of variance and covariance BoysnGirls A% D% E% OA 3 AP 7 AP 10 AP 12 OA 3 AP 7 AP 10 AP 12 OA 3 AP 7 AP 10 AP 12 OA 3 50n41 73 79 75 22n33 17 13 14 28n26 10 8 11 AP 7 59 33n57 50 53 31 39n16 31 28 10 28n27 19 19 AP 10 86 31 41n48 47 6 51 31n25 32 8 18 28n27 21 AP 12 71 24 31 40n54 16 55 45 30n18 13 21 24 30n28 Correlations between different ages BoysnGirls ADE OA 3 AP 7 AP 10 AP 12 OA 3 AP 7 AP 10 AP 12 OA 3 AP 7 AP 10 AP 12 OA 3 1.00 .60 .66 .57 1.00 .30 .16 .20 1.00 .15 .12 .14 AP 7 .57 1.00 .62 .57 .41 1.00 .99 1.00 .15 1.00 .46 .41 AP 10 .68 .56 1.00 .61 .08 .94 1.00 1.00 .11 .42 1.00 .50 AP 12 .49 .42 .53 1.00 .20 .98 .99 1.00 .14 .45 .58 1.00 ..

Increased Activity Imbalance in Fronto-Subcortical Circuits in Adolescents with Major Depression

BACKGROUND: A functional discrepancy exists in adolescents between frontal and subcortical regions due to differential regional maturational trajectories. It remains unknown how this functional discrepancy alters and whether the influence from the subcortical to the frontal system plays a primacy role in medication naïve adolescent with major depressive disorder (MDD). METHODOLOGY/PRINCIPAL FINDINGS: Eighteen MDD and 18 healthy adolescents were enrolled. Depression and anxiety severity was assessed by the Short Mood and Feeling Questionnaire (SMFQ) and Screen for Child Anxiety Related Emotional Disorders (SCARED) respectively. The functional discrepancy was measured by the amplitude of low-frequency fluctuations (ALFF) of resting-state functional MRI signal. Correlation analysis was carried out between ALFF values and SMFQ and SCARED scores. Resting brain activity levels measured by ALFF was higher in the frontal cortex than that in the subcortical system involving mainly (para) limbic-striatal regions in both HC and MDD adolescents. The difference of ALFF values between frontal and subcortical systems was increased in MDD adolescents as compared with the controls. CONCLUSIONS/SIGNIFICANCE: The present study identified an increased imbalance of resting-state brain activity between the frontal cognitive control system and the (para) limbic-striatal emotional processing system in MDD adolescents. The findings may provide insights into the neural correlates of adolescent MDD

Brief report: Comorbid psychiatric disorders of autistic disorder

The behavioral and/or psychiatric symptoms in autistic people as described above have been viewed by many professionals dealing with autistic populations as “associated features of autism” that may result from these individuals' inability to cope with the environmental demands and physical discomfort. Traditionally, in treating individuals with autism, special education intervention including behavioral modifications has been the main emphasis. Such an approach has made some progress in milder and uncomplicated cases of autism. However, if many of these behavioral and/or psychiatric symptoms in those with more severe associated features can be viewed as symptoms of various comorbid psychiatric disorders, there are data suggesting that with an appropriate evaluation, predrug workups, a specific diagnosis, and multiple measures of outcome, pharmacotherapy can be a safe and efficacious adjunct treatment for some symptoms in autistic persons. Nevertheless, the data presented here were obtained mainly from autistic children. A great deal of work remains to be done Future research should put more emphasis on developing agreeable, reliable, and valid diagnostic instruments for identifying comorbid psychiatric disorders in autistic people. Future research should also emphasize employing a randomized double-blind placebo-controlled crossover design, as well as involving multicenters and using uniformed diagnostic criteria to study autistic adolescents and adults.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44613/1/10803_2005_Article_BF02172004.pd

European clinical guidelines for Tourette syndrome and other tic disorders. Part II: pharmacological treatment

To develop a European guideline on pharmacologic treatment of Tourette syndrome (TS) the available literature was thoroughly screened and extensively discussed by a working group of the European Society for the Study of Tourette syndrome (ESSTS). Although there are many more studies on pharmacotherapy of TS than on behavioral treatment options, only a limited number of studies meets rigorous quality criteria. Therefore, we have devised a two-stage approach. First, we present the highest level of evidence by reporting the findings of existing Cochrane reviews in this field. Subsequently, we provide the first comprehensive overview of all reports on pharmacological treatment options for TS through a MEDLINE, PubMed, and EMBASE search for all studies that document the effect of pharmacological treatment of TS and other tic disorders between 1970 and November 2010. We present a summary of the current consensus on pharmacological treatment options for TS in Europe to guide the clinician in daily practice. This summary is, however, rather a status quo of a clinically helpful but merely low evidence guideline, mainly driven by expert experience and opinion, since rigorous experimental studies are scarce

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

A critical analysis of recent data on the long-term outcome of antipsychotic treatment

New studies of long-term outcomes claim to show that taking antipsychotics on a continuous and indefinite basis is the best approach for people diagnosed with a first episode of psychosis or schizophrenia. A 10-year follow-up of a trial of quetiapine maintenance, for example, found a higher proportion of people with a poor composite outcome in the group initially randomised to placebo. However, most people classified as showing poor outcome were rated as having a mild score on a single psychotic symptom; there were no differences in overall symptoms, positive or negative symptoms or level of functioning. Moreover, 16% of participants did not have a follow-up interview and data from the end of the original trial were used instead. A study using a Finnish database suggested that mortality and readmission were higher in people who did not start long-term antipsychotic treatment or who discontinued it as compared with long-term continuous users. However, the analysis did not control for important confounders and is likely to reflect the fact that people who do not comply with treatment are at higher risk of death due to underlying health risks and behaviours. The analysis showed a slightly higher risk of readmission among non-users of antipsychotics compared with long-term users and a more substantial increased risk among people who discontinued treatment. However, follow-up ceased at the first readmission and therefore eventual, long-term outcome was not assessed. Speed of reduction and whether it was done with or without clinical support were also not distinguished