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M1 macrophages enter a glycolytic state when endogenous nitric oxide (NO) reprograms mitochondrial metabolism by limiting aconitase 2 and pyruvate dehydrogenase (PDH) activity. Here, we provide evidence that NO targets the PDH complex by using lipoate to generate nitroxyl (HNO). PDH E2-associated lipoate is modified in NO-rich macrophages while the PDH E3 enzyme, also known as dihydrolipoamide dehydrogenase (DLD), is irreversibly inhibited. Mechanistically, we show that lipoate facilitates NO-mediated production of HNO, which interacts with thiols forming irreversible modifications including sulfinamide. In addition, we reveal a macrophage signature of proteins with reduction-resistant modifications, including in DLD, and identify potential HNO targets. Consistently, DLD enzyme is modified in an HNO-dependent manner at Cys477 and Cys484, and molecular modeling and mutagenesis show these modifications impair the formation of DLD homodimers. In conclusion, our work demonstrates that HNO is produced physiologically. Moreover, the production of HNO is dependent on the lipoate-rich PDH complex facilitating irreversible modifications that are critical to NO-dependent metabolic rewiring. Nitric oxide has been shown to target mitochondrial aconitase 2 and pyruvate dehydrogenase to reprogramme macrophage metabolism. Here, the authors extend these findings to show that lipoate is used to generate nitroxyl in this process. [ABSTRACT FROM AUTHOR]

Acne vulgaris can be associated with hyperpigmentation, particularly in individuals with skin of color. This acne-induced macular hyperpigmentation (AMH), also called postinflammatory hyperpigmentation, is often long lasting and negatively impacts quality of life. Large-scale, randomized, controlled clinical trials with regard to the treatment of acne and AMH are lacking. For this reason, evidence-based treatment recommendations cannot be made. However, AMH is a common condition, and it is important for clinicians to have guidance on management strategies. The authors, a group of 10 board-certified dermatologists, conducted a modified Delphi consensus process to reach a consensus on first-line therapy for AMH and determine whether therapeutic choices change in different patient subgroups. We reached a consensus that most patients with acne and AMH should receive early and efficacious acne treatment with a topical retinoid and benzoyl peroxide. Therapies aimed at addressing AMH—including hydroquinone, azelaic acid, chemical peel, or antioxidants—may also be considered for enhancing the effect of the treatment regimen on acne and pigmentation. Chemical peels may be used as adjunctive or second-line therapy. This article details the results of the Delphi process, reviews relevant literature for providing recommendations for AMH, and discusses appropriate treatment options. [ABSTRACT FROM AUTHOR]

This article summarizes Canadian research in "dual diagnosis" spanning the past 20 years and places this research within a historical and policy context. Canadian researchers have made important contributions with regard to understanding inpatient and outpatient mental health services, families, autism, specific disorders and behaviors, aboriginal mental health, forensics, and emergencies. In this article, we aim to summarize several of these contributions. Following a summary of recent research findings, we offer some suggestions and directions for future research in our country.

Carers of individuals with an intellectual disability are often responsible for managing their children's psychiatric crises when they arise. The purpose of this study was to examine the experiences of families using crisis and short-term transitional supports from the perspectives of families and of crisis and transitional support staff. Three focus groups were conducted. Families and staff were asked to discuss their positive experiences and challenges when accessing and utilizing crisis and transitional support services. Families and staff spoke about their positive experiences with crisis and transitional supports, the staff characteristics that enabled these positive experiences, the challenges they encountered with crisis and transitional support services as well as the general service system, and the impact that these service limitations had on families. Findings highlight the importance of understanding family needs in order to help them address crises before, during, and after they occur. (Contains 1 table and 1 footnote.)

It is well-established that parents of individuals with autism spectrum disorder (ASD) experience significant stress in their caregiving role, and research findings indicate that chronic stressors can act as a precipitant to crisis. In the present study, we examined the experience of crisis in families of individuals with ASD from early childhood to adulthood. One hundred and fifty-seven comments provided by family members in response to an online survey were coded using grounded theory methods. We explored three components of crisis drawn from the comments: "antecedents" (precipitating events and the context of crisis), "behaviors" (the nature of crisis), and "consequences" (outcomes and reactions to crisis). Similarities and differences in the crisis experiences among varying age groups are discussed, as well as implications for practice and future research.

Raising a child with an autism spectrum disorder (ASD) has often been associated with higher levels of parenting stress and psychological distress, and a number of studies have examined the role of psychological processes as mediators of the impact of child problem behavior on parent mental health. The current study examined the relations among child problem behavior, parent mental health, psychological acceptance, and parent empowerment. Participants included 228 parents of children diagnosed with ASD, 6-21 years of age. As expected, psychological acceptance and empowerment were negatively related to the severity of parent mental health problems. When acceptance and empowerment were compared with each other through a test of multiple mediation, only psychological acceptance emerged as a significant partial mediator of the path between child problem behavior and parent mental health problems. As child problem behavior increased, parent psychological acceptance decreased, resulting in an increase in parent mental health problems. These findings suggest that for problems that are chronic and difficult to address, psychological acceptance may be an important factor in coping for parents of young people with ASD, in line with the growing literature on positive coping as compared with problem-focused coping. (Contains 2 tables and 1 figure.)

Few studies have investigated bullying experiences among children diagnosed with autism spectrum disorders (ASD); however, preliminary research suggests that children with ASD are at greater risk for being bullied than typically developing peers. The aim of the current study was to build an understanding of bullying experiences among children with ASD based on parent reports by examining rates of various forms of bullying, exploring the association between victimization and mental health problems, and investigating individual and contextual variables as correlates of victimization. Victimization was related to child age, internalizing and externalizing mental health problems, communication difficulties, and number of friends at school, as well as parent mental health problems. Bullying prevention and intervention strategies are discussed.

One of the most salient developmental tasks of adolescence is the entry into romantic relationship, which often involves developing attachments to partners. Adolescents with a history of maltreatment have been found to be at greater risk of insecure attachments to romantic partners than non-maltreated adolescents, and the interaction of maltreatment and insecure attachment style has been linked to dating violence. The current study examined attachment styles and dating violence in child welfare-involved adolescents with borderline-to-mild intellectual disability (n = 40) and with average IQ (n = 116). Despite reporting similar experiences of childhood maltreatment, IQ was found to interact with avoidant attachment style to predict the degree of dating violence victimization and perpetration experienced by youth. It is suggested that an avoidant attachment style is a risk factor for all maltreated youth, and holds a particularly strong effect on youth with lower IQ levels. These findings highlight the need for developmentally appropriate attachment and dating violence interventions for maltreated youth.

Parents of individuals with autism spectrum disorders (ASD) often experience stressors associated with caring for their child. These stressors can cause considerable distress for families, which at times can develop into full blown crisis, and it is important that professionals be able to quickly identify when families are approaching or are in crisis to respond appropriately. The current study presents an initial attempt at measuring the subjective experience of crisis in 164 caregivers of people with ASD through a single item instrument, the Brief Family Distress Scale. The BFDS was negatively correlated with helpful coping mechanisms (family hardiness, and parent empowerment), and positive adjustment (caregiver quality of life and positive parenting experiences), and positively correlated with known stressors (severity of aggressive behavior, negative life events) and problematic coping and outcomes (caregiver burden, worry, mental health problems). As expected, caregivers at Marked levels of distress (approaching or in crisis) were significantly different from caregivers at lower levels of distress in nearly all of the dependent variables. Having a quick way of measuring where families are in terms of distress and crisis can be helpful for researchers and clinicians alike.

Many individuals with intellectual disabilities who live with their families experience mental health problems and ensuing psychiatric emergencies. During periods of crisis, families may require additional services, including going to the emergency department (ED). The goal of this study was to elucidate demographic, clinical, and crisis features associated with ED use in 192 individuals who lived with family and experienced a psychiatric crisis. The presence of psychiatric symptoms; a mild (vs. moderate/severe) level of intellectual disability; a history of behavior problems, psychiatric hospitalization, and ED use; and a recent history of negative life events were related to ED use. Learning about the factors that distinguish groups is needed to make sure we develop proactive community-based resources for such people to prevent visits to the ED from occurring when possible. (Contains 4 tables.)

Family caregivers play an important role in supporting people with intellectual disability (ID) and mental health problems or serious challenging behaviors across the life span. Relevant services for parents of people with ID may vary depending on the age of the child and the severity of mental health problems. Often, individuals with ID experience behavioral crisis, and the purpose of this study is to understand parents' service utilization patterns. Forty mothers of youth and adults with mild ID shared their experiences of crisis and commented on service needs, receipt, and effectiveness as well as on the barriers to service access using an adapted version of the Need for Help Questionnaire (Douma, Dekker, & Koot, 2006). All parents had high levels of service need. Although most parents noted that they received services, many found that service effectiveness was limited. A greater proportion of parents of youth rated the information and mental health care for their child as effective compared with parents of adults. Barriers to service access for parents of youth centered around perceptions of their child's problem behavior, whereas parents of adults focused on perceptions of the service system. Input from caregivers can help identify deficiencies in the system that lead them to crisis and help tailor services to meet their needs. Research is needed to further elucidate different ways of engaging parents of youth and of adults to help them promote mental health in people with ID and prevent behavioral crises from occurring. (Contains 4 tables.)

This study examined predictors of interest in the future provision of clinical services to people with developmental disabilities by Canadian graduate students in psychology. Utilizing a cross-sectional survey, 458 psychology students from clinical, clinical neuropsychology, and counseling psychology programs from across Canada provided information on their interest in working with the population, their formal training experiences within the university, and their experiences outside the university. Formal training in school and informal experiences in the community were significant predictors of students' intention to work with clients with a developmental disability. The implications of these findings for training programs are discussed. (Contains 4 tables.)

Background: Strains on the mental health system and inaccessible services for individuals with intellectual disabilities (ID) often force caregivers to bring individuals with ID to the emergency department (ED) when in psychiatric crisis. The purpose of this study was to understand the experience of caregivers and adults with ID and mental health issues, according to caregivers' perspectives. Method: Focus groups were conducted with one group of unpaid caregivers (i.e. family members) and two groups of paid caregivers (i.e. staff from community agencies) from Ontario, Canada. Results: Caregivers identified a number of issues centering on a lack of services, on respect, on knowledge and on expertise. Diagnostic overshadowing and overmedication were also prevalent concerns. Conclusions: Input from caregivers points to deficiencies in the system that lead them to use the ED when other options have been exhausted. A number of recommendations can be implemented to improve the emergency psychiatric care of adults with ID in the ED.

The Supports Intensity Scale (SIS) is designed as a measure of support needs for individuals with intellectual disability. The current validity study required five experienced clinicians to rank a total of 50 cases as having Low, Medium, or High Support Need based on descriptions that were part of an assessment package for services. These rankings were compared to individuals' SIS scores. The three groups (Low, Medium, High Need) differed in their SIS Support Needs Index scores as well as 6 of the 7 subscale scores. Home Living Activities and Exceptional Behavioral Support Needs emerged as the strongest predictors of group status. These results suggest that the SIS provides valid information regarding the needs of individuals with intellectual disability receiving services. (Contains 3 tables.)

The role of Special Olympics in the lives of mothers of adult athletes was examined. Forty-six mothers participated in a longitudinal study, completing a parenting stress questionnaire, a measure of their child's maladaptive behavior, and a survey of athlete involvement in Special Olympics at two time periods, 42 months apart. Results confirm that involvement in Special Olympics is negatively correlated with mothers' role restriction, isolation, depression, and problems with competence and attachment. Involvement in Special Olympics fully mediated the effect of child social maladjustment on maternal role restriction and depression and partially mediated its effect on maternal problems with competence. Taken together, these findings suggest that Special Olympics can function as a formal support for mothers.

Recent overviews of autism research have yielded a number of suggestions, including: additional research with very young, and with lower functioning samples, and renewed emphasis on appropriate comparison/control groups. We reviewed the abstracts from a major autism conference (IMFAR) from 2004 to 2006 to examine these trends. We found an increase in the proportion of studies with preschool or infant participants. However, there was a decrease in studies using lower functioning samples, and an increase in studies using Mixed samples. The use of control groups generally decreased, and the use of cognitively impaired comparison groups remains low. We also found the use of the more generic term, ASD, versus DSM categories as sample descriptors increasing at IMFAR. The potential impact of these trends on limiting the generalizability of results is discussed. (Contains 8 tables.)