Structural variation (copy number variation [CNV] including deletion and duplication, translocation, inversion) of chromosomes has been identified in some individuals with autism spectrum disorder (ASD), but the full etiologic role is unknown. We performed genome-wide assessment for structural abnormalities in 427 unrelated ASD cases via single-nucleotide polymorphism microarrays and karyotyping. With microarrays, we discovered 277 unbalanced CNVs in 44% of ASD families not present in 500 controls (and re-examined in another 1152 controls). Karyotyping detected additional balanced changes. Although most variants were inherited, we found a total of 27 cases with de novo alterations, and in three (11%) of these individuals, two or more new variants were observed. De novo CNVs were found in approximately 7% and approximately 2% of idiopathic families having one child, or two or more ASD siblings, respectively. We also detected 13 loci with recurrent/overlapping CNV in unrelated cases, and at these sites, deletions and duplications affecting the same gene(s) in different individuals and sometimes in asymptomatic carriers were also found. Notwithstanding complexities, our results further implicate the SHANK3-NLGN4-NRXN1 postsynaptic density genes and also identify novel loci at DPP6-DPP10-PCDH9 (synapse complex), ANKRD11, DPYD, PTCHD1, 15q24, among others, for a role in ASD susceptibility. Our most compelling result discovered CNV at 16p11.2 (p = 0.002) (with characteristics of a genomic disorder) at approximately 1% frequency. Some of the ASD regions were also common to mental retardation loci. Structural variants were found in sufficiently high frequency influencing ASD to suggest that cytogenetic and microarray analyses be considered in routine clinical workup.

Depressive personality and depressive illness are examined from an evolutionary adaptationist standpoint. It is postulated that the depressive state evolved in relation to social competition, as an unconscious, involuntary losing strategy, enabling the individual to accept defeat in ritual agonistic encounters and to accommodate to what would otherwise be unacceptably low social rank.

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Clomipramine, haloperidol, and placebo were compared with baseline in the treatment of autism, and overall outcome, specific symptoms, and side effects were examined. It was hypothesized that clomipramine would be better tolerated than haloperidol and prove superior on a measure of stereotypy. Individuals with a DSM-IV diagnosis of autistic disorder (mean age, 16.3 years; range, 10-36 years) were randomly assigned, by using a Latin square design, to the following 7-week trials: placebo, clomipramine (mean daily dose, 128.4 mg; range, 100-150 mg), or haloperidol (mean daily dose, 1.3 mg; range, 1-1.5 mg). Data on 36 subjects were analyzed and taken together; the results favored haloperidol. In those patients who were able to complete a full therapeutic trial, clomipramine proved comparable to haloperidol in terms of improvement compared with baseline. However, significantly fewer individuals receiving clomipramine versus haloperidol were able to complete the trial (37.5% vs. 69.7%, respectively) for reasons related to both side effects and efficacy or behavior problems. In the intent-to-treat sample, which is perhaps more clinically relevant, only haloperidol proved superior to baseline on a global measure of autistic symptom severity, as well as specific measures for irritability and hyperactivity. Clomipramine did not seem more effective on a measure of stereotypy, nor was it better tolerated.

Objective: To advance a new evolutionary model that examines the effects of winning and losing on mood and physiological variables. Previous studies have focused on the involuntary defeat strategy in de-escalating conflict. Here, we propose that there also exists an involuntary winning strategy (IWS) that is triggered by success and characterized by euphoria and increased self-confidence. It motivates efforts to challenge, and promotes reconciliation. Method:Previous studies are presented, including data on student athletes, demonstrating the impact of winning and losing on mood. Results:Winning is consistently shown to be related to physiological changes such as increased testosterone and serotonin levels in primates. It reliably leads to mood changes that serve to motivate winners to continue their competitive efforts. Conclusion:When the IWS functions optimally, success leads to success in an adaptive cycle. Over time, the initial differences between the winners and losers of agonistic encounters become magnified in a process known as difference amplification. As a result of assortative mating, the children of people who have entered into an adaptive cycle will inherit traits from both parents that will, in turn, give them an increased competitive advantage. In this manner, difference amplification could have accelerated human evolution by natural selection. Vignettes of clinical interventions are also used to illustrate therapeutic strategies designed to disrupt maladaptive cycles and promote adaptive behaviour.Can J Psychiatry. 2011;56(6):324-332. Clinical Implications• Previous evolutionary theories of mood have focused on negative outcomes, whereas the model put forward in our paper is chiefly concerned with the positive implications of winning. We advocate a stronger focus on optimal functioning and well-being in psychiatry.• An understanding of the IWS model provides a rationale for stressing the importance of successful experiences for children and adults.• The model can account for the rapidity of change as humans evolved from homo erectus to homo sapiens. Limitations• Because the model has so many ramifications, one cannot adequately present the model in a single article.• Because the model should be integrated with other models, it becomes very difficult to test the psychotherapeutic efficacy.

Selective mutism (SM) occurs when a child persistently lacks speech in some social situations but not in others, despite the ability to use and comprehend language. While considered to be related to anxiety, SM is poorly understood and studies of SM children are often based on parent reports. This study developed a unique, non-verbally based assessment protocol for SM children in order to better characterize their clinical profile, language abilities, and learning abilities. A comparison was done with a group of children of similar age, with social phobia (SP) but no SM, to search for characteristics that might distinguish SM from other anxiety disorders. Twenty-three children participated in the study (14 SM and 9 SP). The assessment protocol included standardized anxiety rating scales, cognitive and academic tests, and a speech and language assessment. SM and SP groups showed similar levels of anxiety and academic ability, but the SM group showed some language impairments relative to the SP group. Though requiring replication with a larger sample and nonclinical comparison group, the results suggest that SM children can be assessed by non-verbal means and that their disorder is characterized by anxiety and subtle language impairments.

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