{"title":"Victimization of persons with severe mental illness: a pressing global health problem","authors":"M. Swartz, Sayanti Bhattacharya","doi":"10.1002/wps.20393","DOIUrl":"https://doi.org/10.1002/wps.20393","url":null,"abstract":"","PeriodicalId":49357,"journal":{"name":"World Psychiatry","volume":" ","pages":""},"PeriodicalIF":73.3,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/wps.20393","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45284118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Irritability can be defined as increased proneness to anger, relative to peers. Clinically, it manifests as developmentally inappropriate temper outbursts and sullen, grouchy mood; thus, it includes both behavioral and mood components. Related constructs are mood dysregulation, which is broader than irritability, and aggression, which encompasses only behavioral manifestations. Anger proneness has a defined developmental trajectory, peaking in the preschool period and declining thereafter, with a modest increase during adolescence. Irritability is a common reason for mental health evaluation in children, and pediatric irritability is associated with both concurrent and future impairment. In the 1990s, American researchers suggested that pediatric bipolar disorder does not present with distinct manic episodes as in adults, but instead with severe, chronic irritability. However, post-hoc analyses of epidemiological studies found associations between pediatric irritability and risk for subsequent anxiety and depression, but not for bipolar disorder. Similarly, in studies comparing the two dimensions of oppositional defiant disorder (ODD) (i.e., irritability and headstrong behavior), irritability predicts subsequent anxiety and depression, while headstrong behavior predicts attention-deficit/hyperactivity disorder (ADHD) and conduct disorder. Thus, the diagnosis of bipolar disorder should be reserved for youth (and adults) with distinct manic episodes, rather than chronic irritability. Genetically informative studies link irritability and depression. Twin studies document that longitudinal associations between irritability and both anxiety and depression have a genetic component. These studies also find that the heritability of irritability is approximately 40-60%, similar to anxiety or unipolar depression. Irritability is a diagnostic criterion for multiple disorders in youth, including anxiety disorders, major depressive disorder, and ODD. It is also common in youth with ADHD, bipolar disorder, conduct disorder, and autism. However, for children and adolescents, the validity and clinical utility of a diagnostic category characterized primarily by irritability remains an important and unanswered question. Historically, that category has been ODD, which is conceptualized as a disruptive behavior disorder. However, ODD consists of two dimensions, only one of which, irritability, has genetically mediated longitudinal associations with depression and anxiety. Also, severe irritability has significant cross-sectional associations with anxiety disorders. These considerations call into question the appropriateness of combining irritable and headstrong features into one disorder, and of categorizing a diagnosis characterized primarily by irritability as an externalizing, disruptive behavior disorder, rather than as a mood disorder. Given these complexities, it is not surprising that DSM-5 and ICD-11 take different approaches to diagnosing youth whose primar
{"title":"Irritability in children: what we know and what we need to learn","authors":"E. Leibenluft","doi":"10.1002/wps.20397","DOIUrl":"https://doi.org/10.1002/wps.20397","url":null,"abstract":"Irritability can be defined as increased proneness to anger, relative to peers. Clinically, it manifests as developmentally inappropriate temper outbursts and sullen, grouchy mood; thus, it includes both behavioral and mood components. Related constructs are mood dysregulation, which is broader than irritability, and aggression, which encompasses only behavioral manifestations. Anger proneness has a defined developmental trajectory, peaking in the preschool period and declining thereafter, with a modest increase during adolescence. Irritability is a common reason for mental health evaluation in children, and pediatric irritability is associated with both concurrent and future impairment. In the 1990s, American researchers suggested that pediatric bipolar disorder does not present with distinct manic episodes as in adults, but instead with severe, chronic irritability. However, post-hoc analyses of epidemiological studies found associations between pediatric irritability and risk for subsequent anxiety and depression, but not for bipolar disorder. Similarly, in studies comparing the two dimensions of oppositional defiant disorder (ODD) (i.e., irritability and headstrong behavior), irritability predicts subsequent anxiety and depression, while headstrong behavior predicts attention-deficit/hyperactivity disorder (ADHD) and conduct disorder. Thus, the diagnosis of bipolar disorder should be reserved for youth (and adults) with distinct manic episodes, rather than chronic irritability. Genetically informative studies link irritability and depression. Twin studies document that longitudinal associations between irritability and both anxiety and depression have a genetic component. These studies also find that the heritability of irritability is approximately 40-60%, similar to anxiety or unipolar depression. Irritability is a diagnostic criterion for multiple disorders in youth, including anxiety disorders, major depressive disorder, and ODD. It is also common in youth with ADHD, bipolar disorder, conduct disorder, and autism. However, for children and adolescents, the validity and clinical utility of a diagnostic category characterized primarily by irritability remains an important and unanswered question. Historically, that category has been ODD, which is conceptualized as a disruptive behavior disorder. However, ODD consists of two dimensions, only one of which, irritability, has genetically mediated longitudinal associations with depression and anxiety. Also, severe irritability has significant cross-sectional associations with anxiety disorders. These considerations call into question the appropriateness of combining irritable and headstrong features into one disorder, and of categorizing a diagnosis characterized primarily by irritability as an externalizing, disruptive behavior disorder, rather than as a mood disorder. Given these complexities, it is not surprising that DSM-5 and ICD-11 take different approaches to diagnosing youth whose primar","PeriodicalId":49357,"journal":{"name":"World Psychiatry","volume":" ","pages":""},"PeriodicalIF":73.3,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/wps.20397","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48777504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
B. Galling, A. Roldán, K. Hagi, L. Rietschel, F. Walyzada, Wei Zheng, Xiao‐Lan Cao, Y. Xiang, M. Zink, J. Kane, J. Nielsen, S. Leucht, C. Correll
Antipsychotic polypharmacy in schizophrenia is much debated, since it is common and costly with unclear evidence for its efficacy and safety. We conducted a systematic literature search and a random effects meta‐analysis of randomized trials comparing augmentation with a second antipsychotic vs. continued antipsychotic monotherapy in schizophrenia. Co‐primary outcomes were total symptom reduction and study‐defined response. Antipsychotic augmentation was superior to monotherapy regarding total symptom reduction (16 studies, N=694, standardized mean difference, SMD=–0.53, 95% CI: −0.87 to −0.19, p=0.002). However, superiority was only apparent in open‐label and low‐quality trials (both p<0.001), but not in double‐blind and high‐quality ones (p=0.120 and 0.226, respectively). Study‐defined response was similar between antipsychotic augmentation and monotherapy (14 studies, N=938, risk ratio = 1.19, 95% CI: 0.99 to 1.42, p=0.061), being clearly non‐significant in double‐blind and high‐quality studies (both p=0.990). Findings were replicated in clozapine and non‐clozapine augmentation studies. No differences emerged regarding all‐cause/specific‐cause discontinuation, global clinical impression, as well as positive, general and depressive symptoms. Negative symptoms improved more with augmentation treatment (18 studies, N=931, SMD=–0.38, 95% CI: −0.63 to −0.13, p<0.003), but only in studies augmenting with aripiprazole (8 studies, N=532, SMD=–0.41, 95% CI: −0.79 to −0.03, p=0.036). Few adverse effect differences emerged: D2 antagonist augmentation was associated with less insomnia (p=0.028), but more prolactin elevation (p=0.015), while aripiprazole augmentation was associated with reduced prolactin levels (p<0.001) and body weight (p=0.030). These data suggest that the common practice of antipsychotic augmentation in schizophrenia lacks double‐blind/high‐quality evidence for efficacy, except for negative symptom reduction with aripiprazole augmentation.
{"title":"Antipsychotic augmentation vs. monotherapy in schizophrenia: systematic review, meta‐analysis and meta‐regression analysis","authors":"B. Galling, A. Roldán, K. Hagi, L. Rietschel, F. Walyzada, Wei Zheng, Xiao‐Lan Cao, Y. Xiang, M. Zink, J. Kane, J. Nielsen, S. Leucht, C. Correll","doi":"10.1002/wps.20387","DOIUrl":"https://doi.org/10.1002/wps.20387","url":null,"abstract":"Antipsychotic polypharmacy in schizophrenia is much debated, since it is common and costly with unclear evidence for its efficacy and safety. We conducted a systematic literature search and a random effects meta‐analysis of randomized trials comparing augmentation with a second antipsychotic vs. continued antipsychotic monotherapy in schizophrenia. Co‐primary outcomes were total symptom reduction and study‐defined response. Antipsychotic augmentation was superior to monotherapy regarding total symptom reduction (16 studies, N=694, standardized mean difference, SMD=–0.53, 95% CI: −0.87 to −0.19, p=0.002). However, superiority was only apparent in open‐label and low‐quality trials (both p<0.001), but not in double‐blind and high‐quality ones (p=0.120 and 0.226, respectively). Study‐defined response was similar between antipsychotic augmentation and monotherapy (14 studies, N=938, risk ratio = 1.19, 95% CI: 0.99 to 1.42, p=0.061), being clearly non‐significant in double‐blind and high‐quality studies (both p=0.990). Findings were replicated in clozapine and non‐clozapine augmentation studies. No differences emerged regarding all‐cause/specific‐cause discontinuation, global clinical impression, as well as positive, general and depressive symptoms. Negative symptoms improved more with augmentation treatment (18 studies, N=931, SMD=–0.38, 95% CI: −0.63 to −0.13, p<0.003), but only in studies augmenting with aripiprazole (8 studies, N=532, SMD=–0.41, 95% CI: −0.79 to −0.03, p=0.036). Few adverse effect differences emerged: D2 antagonist augmentation was associated with less insomnia (p=0.028), but more prolactin elevation (p=0.015), while aripiprazole augmentation was associated with reduced prolactin levels (p<0.001) and body weight (p=0.030). These data suggest that the common practice of antipsychotic augmentation in schizophrenia lacks double‐blind/high‐quality evidence for efficacy, except for negative symptom reduction with aripiprazole augmentation.","PeriodicalId":49357,"journal":{"name":"World Psychiatry","volume":" ","pages":""},"PeriodicalIF":73.3,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/wps.20387","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48173067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
South Korea has witnessed an unprecedented rise in suicide rates following the 1997 Asian financial crisis. Unfortunately, the rate has not decreased and still remains the highest among the 34 countries which are part of the Organization for Economic Co-operation and Development (OECD). Several researchers have suggested that, in high-income countries, it is no longer the absolute level of one’s socioeconomic status (SES) that is most important for health, but rather inequality or a sense of inequality. A number of studies have been undertaken to examine the relationship of inequality (at the country level) or a sense of inequality (at the individual level) to health. Some of these studies have focused on subjective SES, which measures one’s perception of his/her own position in the social hierarchy. We aimed to examine how both objective and subjective SES are related to mental health problems (suicidal ideation, depressive symptoms and psychological distress) in South Korea, using data from the 2013 Korea Health Panel survey. Subjective SES was measured using the MacArthur scale, a 10rung ladder on which individuals indicate their perceived standing in the social hierarchy. The assessment of suicidal ideation and depression was based on self-report (“yes” versus “no” in the past 12 months). Psychological distress in the past month was assessed using the Korean version of the Brief Encounter Psychosocial Instrument (BEPSI-K). A score 2.4 was defined as “severe stress”. Of the 16,313 respondents aged 19 years or older, the 14,432 who had no missing data were included in this analysis. All data were weighted to represent the structure of the Korean population. Of the 14,432 participants, 5.4% and 7.2% had suicidal ideation and depression, respectively, in the past 12 months, and 13.6% had severe psychological distress in the past month. A clear social gradient was found in the prevalence of these mental health problems, especially when SES was measured subjectively (subjective SES) rather than objectively (income quintile) (p<0.001). Notably, this pattern was more apparent in the case of severe psychological distress. Of those with the lowest subjective SES (i.e., a rating of 1 on the 10-rung ladder), nearly one in three (29.6%) reported the experience of severe psychological distress in the past month, while only 7.2% reported the same experience among those with the highest subjective SES (i.e., a rating 5). The equivalent rates were 19.3% in the lowest income quintile and 10.2% in the highest income quintile. The associations with subjective SES appeared to far outweigh those with conventional measures of SES when considering both in logistic regression models. Subjective SES was the only factor that was consistently associated with any type of mental health problems. For instance, compared to the respondents with the lowest subjective SES (i.e., a rating of 1 on the 10-rung ladder), those with higher subjective SES were much less likely to rep
{"title":"The relationship of subjective social status to mental health in South Korean adults","authors":"Jihyung Hong, Jonghan Yi","doi":"10.1002/wps.20357","DOIUrl":"https://doi.org/10.1002/wps.20357","url":null,"abstract":"South Korea has witnessed an unprecedented rise in suicide rates following the 1997 Asian financial crisis. Unfortunately, the rate has not decreased and still remains the highest among the 34 countries which are part of the Organization for Economic Co-operation and Development (OECD). Several researchers have suggested that, in high-income countries, it is no longer the absolute level of one’s socioeconomic status (SES) that is most important for health, but rather inequality or a sense of inequality. A number of studies have been undertaken to examine the relationship of inequality (at the country level) or a sense of inequality (at the individual level) to health. Some of these studies have focused on subjective SES, which measures one’s perception of his/her own position in the social hierarchy. We aimed to examine how both objective and subjective SES are related to mental health problems (suicidal ideation, depressive symptoms and psychological distress) in South Korea, using data from the 2013 Korea Health Panel survey. Subjective SES was measured using the MacArthur scale, a 10rung ladder on which individuals indicate their perceived standing in the social hierarchy. The assessment of suicidal ideation and depression was based on self-report (“yes” versus “no” in the past 12 months). Psychological distress in the past month was assessed using the Korean version of the Brief Encounter Psychosocial Instrument (BEPSI-K). A score 2.4 was defined as “severe stress”. Of the 16,313 respondents aged 19 years or older, the 14,432 who had no missing data were included in this analysis. All data were weighted to represent the structure of the Korean population. Of the 14,432 participants, 5.4% and 7.2% had suicidal ideation and depression, respectively, in the past 12 months, and 13.6% had severe psychological distress in the past month. A clear social gradient was found in the prevalence of these mental health problems, especially when SES was measured subjectively (subjective SES) rather than objectively (income quintile) (p<0.001). Notably, this pattern was more apparent in the case of severe psychological distress. Of those with the lowest subjective SES (i.e., a rating of 1 on the 10-rung ladder), nearly one in three (29.6%) reported the experience of severe psychological distress in the past month, while only 7.2% reported the same experience among those with the highest subjective SES (i.e., a rating 5). The equivalent rates were 19.3% in the lowest income quintile and 10.2% in the highest income quintile. The associations with subjective SES appeared to far outweigh those with conventional measures of SES when considering both in logistic regression models. Subjective SES was the only factor that was consistently associated with any type of mental health problems. For instance, compared to the respondents with the lowest subjective SES (i.e., a rating of 1 on the 10-rung ladder), those with higher subjective SES were much less likely to rep","PeriodicalId":49357,"journal":{"name":"World Psychiatry","volume":" ","pages":""},"PeriodicalIF":73.3,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/wps.20357","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41856300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The 2030 United Nations Agenda for Sustainable Development seeks to ensure that, over the next 15 years, countries make concerted efforts towards economic, social and environmental development that is sustainable and inclusive. In order to achieve the goal of universal health and well-being (Goal 3), an important target is “to reduce premature mortality from non-communicable diseases (NCD) through prevention and treatment and promote mental health and well-being”. While this goal applies to all, there is a need for making special efforts to the populations that are vulnerable to be left behind. One such population is people with severe mental disorders (SMD). SMD and NCD are related in complex ways. The major modifiable risk factors for NCD, such as physical inactivity, unhealthy diet, tobacco use and harmful use of alcohol, are exacerbated by poor mental health. Mental illness is a risk factor for NCDs; its presence increases the chance that an individual will also suffer from one or more chronic illnesses. In addition, individuals with mental health conditions are less likely to seek help for NCDs, and symptoms may affect adherence to treatment as well as prognosis. The physical health of people with SMD is commonly ignored not only by themselves and people around them, but also by health systems, resulting in crucial physical health disparities and limited access to health services. This impacts the life expectancy of people with SMD. The facts are clear: people with severe mental disorders die, on average, 15 to 20 years earlier than others. These excess and early deaths are not primarily due to suicide, but to physical diseases that occur more frequently, are not prevented adequately, are not identified early enough and are not treated effectively. And this disparity is not confined to some regions and countries, but seems to be a global reality. This state of affairs is not in keeping with the spirit and letter of the Sustainable Development Goals. It should be unacceptable to any country or community. What is needed? While interventions, guidelines and programmes have been developed to address the risk factors for excess mortality in persons with SMD, they will not really make a difference until a variety of challenges to their implementation are tackled, including problems with culture and attitudes of the various stakeholders involved, resources and expertise available, engagement of patients in the programmes, accessibility and feasibility of the interventions, their costeffectiveness, and the fidelity of their application. At the policy level, there is an obvious issue of prioritization. Reducing excess mortality in persons with SMD should become part of the broader health agenda. Top-level integration of various programmes (e.g., mental health and substance abuse, NCD, tobacco cessation, violence prevention, nutrition and physical exercise) should be set as a precedent for making strides in addressing complex, multifactorial health pr
{"title":"Physical health of people with severe mental disorders: leave no one behind","authors":"S. Saxena, M. Maj","doi":"10.1002/wps.20403","DOIUrl":"https://doi.org/10.1002/wps.20403","url":null,"abstract":"The 2030 United Nations Agenda for Sustainable Development seeks to ensure that, over the next 15 years, countries make concerted efforts towards economic, social and environmental development that is sustainable and inclusive. In order to achieve the goal of universal health and well-being (Goal 3), an important target is “to reduce premature mortality from non-communicable diseases (NCD) through prevention and treatment and promote mental health and well-being”. While this goal applies to all, there is a need for making special efforts to the populations that are vulnerable to be left behind. One such population is people with severe mental disorders (SMD). SMD and NCD are related in complex ways. The major modifiable risk factors for NCD, such as physical inactivity, unhealthy diet, tobacco use and harmful use of alcohol, are exacerbated by poor mental health. Mental illness is a risk factor for NCDs; its presence increases the chance that an individual will also suffer from one or more chronic illnesses. In addition, individuals with mental health conditions are less likely to seek help for NCDs, and symptoms may affect adherence to treatment as well as prognosis. The physical health of people with SMD is commonly ignored not only by themselves and people around them, but also by health systems, resulting in crucial physical health disparities and limited access to health services. This impacts the life expectancy of people with SMD. The facts are clear: people with severe mental disorders die, on average, 15 to 20 years earlier than others. These excess and early deaths are not primarily due to suicide, but to physical diseases that occur more frequently, are not prevented adequately, are not identified early enough and are not treated effectively. And this disparity is not confined to some regions and countries, but seems to be a global reality. This state of affairs is not in keeping with the spirit and letter of the Sustainable Development Goals. It should be unacceptable to any country or community. What is needed? While interventions, guidelines and programmes have been developed to address the risk factors for excess mortality in persons with SMD, they will not really make a difference until a variety of challenges to their implementation are tackled, including problems with culture and attitudes of the various stakeholders involved, resources and expertise available, engagement of patients in the programmes, accessibility and feasibility of the interventions, their costeffectiveness, and the fidelity of their application. At the policy level, there is an obvious issue of prioritization. Reducing excess mortality in persons with SMD should become part of the broader health agenda. Top-level integration of various programmes (e.g., mental health and substance abuse, NCD, tobacco cessation, violence prevention, nutrition and physical exercise) should be set as a precedent for making strides in addressing complex, multifactorial health pr","PeriodicalId":49357,"journal":{"name":"World Psychiatry","volume":" ","pages":""},"PeriodicalIF":73.3,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/wps.20403","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49047440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
top of the political agenda, so that patients with severe mental illness get the best services they need, deserve and will utilize. It is imperative that psychiatrists take the lead in identifying the physical health needs of persons with severe mental illness as well as in orienting the public mental health agenda to ensure that cultural norms and values are taken into account when developing and delivering integrated care at all levels. They must work with stakeholders, including service users and their families groups, to ensure that integrated care and services are sensitive to patients’ needs.
{"title":"Excess mortality in severe mental disorder: the need for an integrated approach","authors":"G. Ivbijaro","doi":"10.1002/wps.20382","DOIUrl":"https://doi.org/10.1002/wps.20382","url":null,"abstract":"top of the political agenda, so that patients with severe mental illness get the best services they need, deserve and will utilize. It is imperative that psychiatrists take the lead in identifying the physical health needs of persons with severe mental illness as well as in orienting the public mental health agenda to ensure that cultural norms and values are taken into account when developing and delivering integrated care at all levels. They must work with stakeholders, including service users and their families groups, to ensure that integrated care and services are sensitive to patients’ needs.","PeriodicalId":49357,"journal":{"name":"World Psychiatry","volume":" ","pages":""},"PeriodicalIF":73.3,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/wps.20382","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46122553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
P. Molero, M. Martínez-González, M. Ruíz-Canela, F. Lahortiga, A. Sánchez-Villegas, A. Perez-Cornago, A. Gea
ANCOVA analysis, which included age and education as covariates. The model also remained significant in a follow-up analysis in which participants who identified as AfricanAmerican (N515) were excluded. Carriers of the 5HTTLPR-S’ allele had increased PTSD symptoms compared to individuals homozygous for the L’ allele (IES mean score: L’L’547.3 6 5.3, S559.8 6 4.1). For DISC1, individuals homozygous for the T allele had increased PTSD symptoms compared to A carriers (A545.3 6 2.8, TT561.9 6 7.2). In ANCOVA analysis of symptom sub-factors, 5-HTTLPR and DISC1 selectively influenced intrusion and hypervigilance symptoms, but did not affect avoidance symptoms. PTSD symptom severity (total IES scores) increased by an average of 40% with each risk genotype (none538.4, one5 54.5, two565.6). These data support prior observations of 5-HTTLPR effects on PTSD symptoms in military veterans. Although 5-HTTLPR has been identified as a potential contributor to PTSD susceptibility in civilian-based populations, its effect may be less robust in those populations, due to lower overall level of trauma exposure. The effects of 5-HTTLPR on PTSD in military veterans after deployment to a war zone may be more robust because of a universal and constant exposure to threat, military training, and/or separation from family and home social support. In addition to 5-HTTLPR, genetic variation in DISC1, a gene associated with susceptibility to multiple mental disorders, was found to contribute to PTSD symptom severity. Possessing both DISC1 and 5-HTTLPR risk genotypes resulted in a 1.7fold increase in PTSD symptoms. Although this is the first report of DISC1 S704C TT allele as a risk factor for PTSD, the finding is not surprising, considering that this allele has been identified as a risk factor for major depression. DISC1 variants interfere with a protein complex important for organelle transport and in tethering of mitochondria, interfering with dendritic development and reducing densities of dendritic spines in the frontal cortex, paralleling our recent report of spine density reductions in the frontal cortex in PTSD. This study was powered to screen for candidate genes with relatively large effect sizes on PTSD symptoms in combat veterans, which may be different from sets of genes affecting PTSD in civilian populations. Study of the serotonin system in PTSD is motivated in large part by the therapeutic utility of serotonin uptake inhibitors to treat symptoms of PTSD. Our data provide additional impetus for continued study of this system in PTSD pharmacotherapy. In addition, antipsychotics such as risperidone have been shown to reverse DISC1-related behavioral deficits and pathophysiology in animal models, suggesting the possibility that such agents could be re-examined for use as alternative pharmacotherapies for PTSD. Keith A. Young, Sandra B. Morissette, Robert Jamroz, Eric C. Meyer, Matthew S. Stanford, Li Wan, Nathan A. Kimbrel Central Texas Veterans Health Care System,
ANCOVA分析，包括年龄和教育作为协变量。在排除非裔美国人(N515)的随访分析中，该模型仍然具有重要意义。5HTTLPR-S’等位基因携带者与L’等位基因纯合子个体相比，PTSD症状增加(IES平均评分:L’L 547.3 6 5.3, S559.8 6 4.1)。对于DISC1，与A携带者相比，T等位基因纯合的个体PTSD症状增加(A545.3 6 2.8, TT561.9 6 7.2)。在ANCOVA分析症状亚因素中，5-HTTLPR和DISC1选择性地影响侵入和超警觉症状，但不影响回避症状。每种风险基因型的PTSD症状严重程度(IES总分)平均增加40%(非538.4，一54.5，二565.6)。这些数据支持了先前关于5-HTTLPR对退伍军人PTSD症状影响的观察。尽管5-HTTLPR已被确定为平民人群中创伤后应激障碍易感性的潜在因素，但由于总体创伤暴露水平较低，它在这些人群中的作用可能不那么明显。5-HTTLPR对部署到战区的退伍军人创伤后应激障碍的影响可能更强，因为他们普遍和持续地暴露于威胁、军事训练和/或与家人和家庭社会支持分离。除了5-HTTLPR外，研究还发现，与多种精神障碍易感性相关的基因DISC1的遗传变异与PTSD症状的严重程度有关。同时拥有DISC1和5-HTTLPR风险基因型导致PTSD症状增加1.7倍。虽然这是DISC1 S704C TT等位基因作为PTSD危险因素的首次报道，但考虑到该等位基因已被确定为重度抑郁症的危险因素，这一发现并不令人惊讶。DISC1变异干扰一种对细胞器运输和线粒体拴系很重要的蛋白质复合物，干扰树突发育并降低额叶皮质树突棘的密度，这与我们最近报道的PTSD患者额叶皮质脊柱密度降低的情况相似。本研究旨在筛选对退伍军人创伤后应激障碍症状有较大影响的候选基因，这可能与影响平民人群创伤后应激障碍的一系列基因不同。研究创伤后应激障碍中的血清素系统在很大程度上是由血清素摄取抑制剂治疗创伤后应激障碍症状的治疗效用所推动的。我们的数据为该系统在PTSD药物治疗中的持续研究提供了额外的动力。此外，在动物模型中，利培酮等抗精神病药物已被证明可以逆转disc1相关的行为缺陷和病理生理，这表明这些药物可能会被重新研究作为创伤后应激障碍的替代药物疗法。Keith A. Young, Sandra B. Morissette, Robert Jamroz, Eric C. Meyer, Matthew S. Stanford, Li Wan, Nathan A. Kimbrel中央德州退伍军人医疗保健系统，坦普尔，德克萨斯州，美国;退伍军人事务部visn17退伍军人归国研究卓越中心，美国德克萨斯州韦科;美国德州坦普尔市德州农工大学健康科学中心精神病学与行为科学系;德克萨斯大学圣安东尼奥分校，美国德克萨斯州圣安东尼奥;希望与康复中心，休斯顿，德克萨斯州，美国;达勒姆退伍军人事务医疗中心，美国北卡罗来纳州达勒姆;VA中大西洋精神疾病研究、教育和临床中心，达勒姆，北卡罗来纳州，美国;杜克大学医学中心，美国北卡罗来纳州达勒姆
{"title":"Cardiovascular risk and incidence of depression in young and older adults: evidence from the SUN cohort study","authors":"P. Molero, M. Martínez-González, M. Ruíz-Canela, F. Lahortiga, A. Sánchez-Villegas, A. Perez-Cornago, A. Gea","doi":"10.1002/wps.20390","DOIUrl":"https://doi.org/10.1002/wps.20390","url":null,"abstract":"ANCOVA analysis, which included age and education as covariates. The model also remained significant in a follow-up analysis in which participants who identified as AfricanAmerican (N515) were excluded. Carriers of the 5HTTLPR-S’ allele had increased PTSD symptoms compared to individuals homozygous for the L’ allele (IES mean score: L’L’547.3 6 5.3, S559.8 6 4.1). For DISC1, individuals homozygous for the T allele had increased PTSD symptoms compared to A carriers (A545.3 6 2.8, TT561.9 6 7.2). In ANCOVA analysis of symptom sub-factors, 5-HTTLPR and DISC1 selectively influenced intrusion and hypervigilance symptoms, but did not affect avoidance symptoms. PTSD symptom severity (total IES scores) increased by an average of 40% with each risk genotype (none538.4, one5 54.5, two565.6). These data support prior observations of 5-HTTLPR effects on PTSD symptoms in military veterans. Although 5-HTTLPR has been identified as a potential contributor to PTSD susceptibility in civilian-based populations, its effect may be less robust in those populations, due to lower overall level of trauma exposure. The effects of 5-HTTLPR on PTSD in military veterans after deployment to a war zone may be more robust because of a universal and constant exposure to threat, military training, and/or separation from family and home social support. In addition to 5-HTTLPR, genetic variation in DISC1, a gene associated with susceptibility to multiple mental disorders, was found to contribute to PTSD symptom severity. Possessing both DISC1 and 5-HTTLPR risk genotypes resulted in a 1.7fold increase in PTSD symptoms. Although this is the first report of DISC1 S704C TT allele as a risk factor for PTSD, the finding is not surprising, considering that this allele has been identified as a risk factor for major depression. DISC1 variants interfere with a protein complex important for organelle transport and in tethering of mitochondria, interfering with dendritic development and reducing densities of dendritic spines in the frontal cortex, paralleling our recent report of spine density reductions in the frontal cortex in PTSD. This study was powered to screen for candidate genes with relatively large effect sizes on PTSD symptoms in combat veterans, which may be different from sets of genes affecting PTSD in civilian populations. Study of the serotonin system in PTSD is motivated in large part by the therapeutic utility of serotonin uptake inhibitors to treat symptoms of PTSD. Our data provide additional impetus for continued study of this system in PTSD pharmacotherapy. In addition, antipsychotics such as risperidone have been shown to reverse DISC1-related behavioral deficits and pathophysiology in animal models, suggesting the possibility that such agents could be re-examined for use as alternative pharmacotherapies for PTSD. Keith A. Young, Sandra B. Morissette, Robert Jamroz, Eric C. Meyer, Matthew S. Stanford, Li Wan, Nathan A. Kimbrel Central Texas Veterans Health Care System, ","PeriodicalId":49357,"journal":{"name":"World Psychiatry","volume":" ","pages":""},"PeriodicalIF":73.3,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/wps.20390","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42701745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
onists have been tested in ASD associated with fragile X syndrome, and showed promise in a subgroup of patients. GABAergic agents, such as the GABA-B receptor agonist arbaclofen (STX209), have shown some effect on irritability and social withdrawal in ASD children. The peptide hormone oxytocin is important in social cognition and behavior. In ASD adults, acute intravenous administration of oxytocin reduced repetitive behaviors and improved accuracy of recognizing emotions in speech over time. Intranasal administration improved social cognition in children, adolescents and adults with ASD. A vasopressin 1a receptor antagonist had some effect on speech recognition of emotions such as fear and lust in high-functioning ASD adults. Insulin-like growth factor 1 (IGF-1) is important in central nervous system maturation, development and connectivity, that are perturbed in ASD. Studies in Shank-3 deficient mice that model Phelan-McDermid syndrome (PMS), which may be associated with some cases of ASD, indicated that IGF-1 may reverse structural changes in ionotropic glutamate receptors, functional synaptic plasticity changes, and excitation/inhibition imbalance. A clinical trial with recombinant human IGF-1 in PMS children showed improvement in social impairment and restricted behaviors. Agents modulating the immune system have been tested in ASD. The immune response induced by the whipworm Trichuris suis ova has shown benefit on the repetitive behavior domain in adult ASD. Immunosuppressive and protein synthesis inhibiting drugs such as the mTOR inhibitor rapamycin have been shown to improve social deficits in some forms of ASD. The alpha-7 nicotinic acetylcholine receptor (nACR) gene is associated with autism and ADHD. nACR drugs tested in clinical trials include mecamylamine, transdermally administered nicotine, and donepezil. Some alpha-7 nACR antagonists such as galantamine have shown promise in animal models and clinical trials. Drugs modulating the cannabinoid system, such as cannabidiol, have been found effective in childhood epilepsy, and may be worth studying in ASD due to their anti-anxiety, antiepileptic, immunomodulating and cognitive-enhancing effects and good safety. Interestingly, social reward and oxytocin induce release of endocannabinoids in nucleus accumbens. In ASD animal models, cannabidiol has some impact on social deficits, repetitive behaviors and irritability. Complementary and alternative medicine (CAM) treatments have been tested in ASD. However, they are not strictly regulated and have not been studied in large-scale clinical trials. Therefore, their safety and efficacy is not well determined. CAM treatments may complement rather than replace proven therapies for ASD. Melatonin may be used for sleep disorders, omega-3 fatty acids for reducing repetitive behaviors and improving sociability. Vitamin B12 supplements are believed to protect against the oxidative damage in ASD. Curcumin, an active ingredient of turmeric, may be bene
{"title":"Nonmedical use of prescription drugs in adolescents and young adults: not just a Western phenomenon","authors":"S. Martins, L. Ghandour","doi":"10.1002/wps.20350","DOIUrl":"https://doi.org/10.1002/wps.20350","url":null,"abstract":"onists have been tested in ASD associated with fragile X syndrome, and showed promise in a subgroup of patients. GABAergic agents, such as the GABA-B receptor agonist arbaclofen (STX209), have shown some effect on irritability and social withdrawal in ASD children. The peptide hormone oxytocin is important in social cognition and behavior. In ASD adults, acute intravenous administration of oxytocin reduced repetitive behaviors and improved accuracy of recognizing emotions in speech over time. Intranasal administration improved social cognition in children, adolescents and adults with ASD. A vasopressin 1a receptor antagonist had some effect on speech recognition of emotions such as fear and lust in high-functioning ASD adults. Insulin-like growth factor 1 (IGF-1) is important in central nervous system maturation, development and connectivity, that are perturbed in ASD. Studies in Shank-3 deficient mice that model Phelan-McDermid syndrome (PMS), which may be associated with some cases of ASD, indicated that IGF-1 may reverse structural changes in ionotropic glutamate receptors, functional synaptic plasticity changes, and excitation/inhibition imbalance. A clinical trial with recombinant human IGF-1 in PMS children showed improvement in social impairment and restricted behaviors. Agents modulating the immune system have been tested in ASD. The immune response induced by the whipworm Trichuris suis ova has shown benefit on the repetitive behavior domain in adult ASD. Immunosuppressive and protein synthesis inhibiting drugs such as the mTOR inhibitor rapamycin have been shown to improve social deficits in some forms of ASD. The alpha-7 nicotinic acetylcholine receptor (nACR) gene is associated with autism and ADHD. nACR drugs tested in clinical trials include mecamylamine, transdermally administered nicotine, and donepezil. Some alpha-7 nACR antagonists such as galantamine have shown promise in animal models and clinical trials. Drugs modulating the cannabinoid system, such as cannabidiol, have been found effective in childhood epilepsy, and may be worth studying in ASD due to their anti-anxiety, antiepileptic, immunomodulating and cognitive-enhancing effects and good safety. Interestingly, social reward and oxytocin induce release of endocannabinoids in nucleus accumbens. In ASD animal models, cannabidiol has some impact on social deficits, repetitive behaviors and irritability. Complementary and alternative medicine (CAM) treatments have been tested in ASD. However, they are not strictly regulated and have not been studied in large-scale clinical trials. Therefore, their safety and efficacy is not well determined. CAM treatments may complement rather than replace proven therapies for ASD. Melatonin may be used for sleep disorders, omega-3 fatty acids for reducing repetitive behaviors and improving sociability. Vitamin B12 supplements are believed to protect against the oxidative damage in ASD. Curcumin, an active ingredient of turmeric, may be bene","PeriodicalId":49357,"journal":{"name":"World Psychiatry","volume":" ","pages":""},"PeriodicalIF":73.3,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/wps.20350","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45719520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
they may be helpful for DMDD. Data support the use of atypical antipsychotic medication in youth with autism and irritability, and in youth with aggression. However, recent increases in antipsychotic prescriptions may have resulted in part from attempts to treat pediatric irritability, perhaps without adequate exploration of alternative pharmacologic and psychotherapeutic approaches. Selective serotonin reuptake inhibitors (SSRIs) may treat irritability in adults; such an approach in children is supported by the high comorbidity and longitudinal associations among irritability, anxiety and depression. SSRIs are now being tested in youth with DMDD. Psychotherapeutic approaches are likely to be important in the treatment of irritability. Parent training can decrease a child’s aggression and might also decrease irritability. Cognitive behavioral approaches are being tested, as is implicit training designed to alter irritable children’s tendency to view ambiguous faces as angry. In conclusion, the recent focus on irritability has yielded considerable knowledge about its longitudinal course and associations with psychopathology. Ongoing work is aimed at identifying the brain mechanisms mediating irritability and at using that knowledge to inform novel treatment approaches.
{"title":"Are there new advances in the pharmacotherapy of autism spectrum disorders?","authors":"E. Hollander, G. Uzunova","doi":"10.1002/wps.20398","DOIUrl":"https://doi.org/10.1002/wps.20398","url":null,"abstract":"they may be helpful for DMDD. Data support the use of atypical antipsychotic medication in youth with autism and irritability, and in youth with aggression. However, recent increases in antipsychotic prescriptions may have resulted in part from attempts to treat pediatric irritability, perhaps without adequate exploration of alternative pharmacologic and psychotherapeutic approaches. Selective serotonin reuptake inhibitors (SSRIs) may treat irritability in adults; such an approach in children is supported by the high comorbidity and longitudinal associations among irritability, anxiety and depression. SSRIs are now being tested in youth with DMDD. Psychotherapeutic approaches are likely to be important in the treatment of irritability. Parent training can decrease a child’s aggression and might also decrease irritability. Cognitive behavioral approaches are being tested, as is implicit training designed to alter irritable children’s tendency to view ambiguous faces as angry. In conclusion, the recent focus on irritability has yielded considerable knowledge about its longitudinal course and associations with psychopathology. Ongoing work is aimed at identifying the brain mechanisms mediating irritability and at using that knowledge to inform novel treatment approaches.","PeriodicalId":49357,"journal":{"name":"World Psychiatry","volume":" ","pages":""},"PeriodicalIF":73.3,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/wps.20398","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45200646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nancy H. Liu, G. Daumit, T. Dua, R. Aquila, F. Charlson, P. Cuijpers, B. Druss, Kenneth J. Dudek, M. Freeman, Chiyo Fujii, W. Gaebel, U. Hegerl, I. Levav, T. Munk Laursen, Hong Ma, M. Maj, María Elena Medina‐Mora, M. Nordentoft, D. Prabhakaran, K. Pratt, M. Prince, T. Rangaswamy, D. Shiers, E. Susser, G. Thornicroft, K. Wahlbeck, Abe Fekadu Wassie, H. Whiteford, S. Saxena
Excess mortality in persons with severe mental disorders (SMD) is a major public health challenge that warrants action. The number and scope of truly tested interventions in this area remain limited, and strategies for implementation and scaling up of programmes with a strong evidence base are scarce. Furthermore, the majority of available interventions focus on a single or an otherwise limited number of risk factors. Here we present a multilevel model highlighting risk factors for excess mortality in persons with SMD at the individual, health system and socio‐environmental levels. Informed by that model, we describe a comprehensive framework that may be useful for designing, implementing and evaluating interventions and programmes to reduce excess mortality in persons with SMD. This framework includes individual‐focused, health system‐focused, and community level and policy‐focused interventions. Incorporating lessons learned from the multilevel model of risk and the comprehensive intervention framework, we identify priorities for clinical practice, policy and research agendas.
{"title":"Excess mortality in persons with severe mental disorders: a multilevel intervention framework and priorities for clinical practice, policy and research agendas","authors":"Nancy H. Liu, G. Daumit, T. Dua, R. Aquila, F. Charlson, P. Cuijpers, B. Druss, Kenneth J. Dudek, M. Freeman, Chiyo Fujii, W. Gaebel, U. Hegerl, I. Levav, T. Munk Laursen, Hong Ma, M. Maj, María Elena Medina‐Mora, M. Nordentoft, D. Prabhakaran, K. Pratt, M. Prince, T. Rangaswamy, D. Shiers, E. Susser, G. Thornicroft, K. Wahlbeck, Abe Fekadu Wassie, H. Whiteford, S. Saxena","doi":"10.1002/wps.20384","DOIUrl":"https://doi.org/10.1002/wps.20384","url":null,"abstract":"Excess mortality in persons with severe mental disorders (SMD) is a major public health challenge that warrants action. The number and scope of truly tested interventions in this area remain limited, and strategies for implementation and scaling up of programmes with a strong evidence base are scarce. Furthermore, the majority of available interventions focus on a single or an otherwise limited number of risk factors. Here we present a multilevel model highlighting risk factors for excess mortality in persons with SMD at the individual, health system and socio‐environmental levels. Informed by that model, we describe a comprehensive framework that may be useful for designing, implementing and evaluating interventions and programmes to reduce excess mortality in persons with SMD. This framework includes individual‐focused, health system‐focused, and community level and policy‐focused interventions. Incorporating lessons learned from the multilevel model of risk and the comprehensive intervention framework, we identify priorities for clinical practice, policy and research agendas.","PeriodicalId":49357,"journal":{"name":"World Psychiatry","volume":" ","pages":""},"PeriodicalIF":73.3,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/wps.20384","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46665407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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