Prefrontal cortex markers of suicidal vulnerability in mood disorders: a model-based structural neuroimaging study with a translational perspective

Open access article. Available from the publisher via doi: 10.1038/tp.2015.1The vulnerability to suicidal behavior has been modeled in deficits in both valuation and cognitive control processes, mediated by ventral and dorsal prefrontal cortices. To uncover potential markers of suicidality based on this model, we measured several brain morphometric parameters using 1.5T magnetic resonance imaging in a large sample and in a specifically designed study. We then tested their classificatory properties. Three groups were compared: euthymic suicide attempters with a past history of mood disorders and suicidal behavior (N=67); patient controls with a past history of mood disorders but not suicidal behavior (N=82); healthy controls without any history of mental disorder (N=82). A hypothesis-driven region-of-interest approach was applied targeting the orbitofrontal cortex (OFC), ventrolateral (VLPFC), dorsal (DPFC) and medial (including anterior cingulate cortex; MPFC) prefrontal cortices. Both voxel-based (SPM8) and surface-based morphometry (Freesurfer) analyses were used to comprehensively evaluate cortical gray matter measure, volume, surface area and thickness. Reduced left VLPFC volume in attempters vs both patient groups was found (P=0.001, surviving multiple comparison correction, Cohen's d=0.65 95% (0.33-0.99) between attempters and healthy controls). In addition, reduced measures in OFC and DPFC, but not MPFC, were found with moderate effect sizes in suicide attempters vs healthy controls (Cohen's d between 0.34 and 0.52). Several of these measures were correlated with suicidal variables. When added to mood disorder history, left VLPFC volume increased within-sample specificity in identifying attempters in a significant but limited way. Our study, therefore, confirms structural prefrontal alterations in individuals with histories of suicide attempts. A future clinical application of these markers will, however, necessitate further research.American Foundation for Suicide PreventionFondation pour la Recherche MédicaleRoyal SocietyProjet Hospitalier de Recherche CliniqueAcadémie Nationale de MédecineInstitut Servie

Mediation effect of anxious attachment on relationship between childhood trauma and suicidal ideation sensitive to psychological pain levels

Introduction: Childhood trauma (CT), depression and psychological pain are known predictors of suicidal ideation. Recent literature additionally highlights the importance of the attachment system.Methods: We aimed to predict suicidal ideation through CT, attachment, and psychological and social pain by using mediation models aiming to predict suicidal ideation through CT (predictor) and attachment (mediator). In the same models, we introduced psychological or social pain as moderator of the relationship between attachment, CT, and suicidal ideation. We included 161 depressed patients and assessed depression, attachment, CT, suicidal ideation, psychological pain, and social pain.Results: We found I) a complete mediating effect of anxious attachment (a2b2 = 0.0035, CI95% = [0.0010; 0.0069]) on the relationship between CT on suicidal ideation, and II) a significant complete conditional mediating effect of anxious attachment and psychological pain (Index of moderated mediation VAS: 0.0014; CI95% = [0.0002; 0.0032]) but not social pain on the relationship between CT and suicidal ideation. Both models were controlled for history of suicidal attempt, depression severity, and sex.Conclusion: Our results suggest a developmental profile of suicidal ideation in mood disorder that is characterized by the presence of CT and insecure attachment, especially anxious attachment, that is sensitive to experiences of psychological pain. Nevertheless, we cannot conclude that avoidantly attached individuals do not present the same mechanism, as they may not disclose those ideas

Understanding the prescription of antidepressants: a Qualitative study among French GPs

<p>Abstract</p> <p>Background</p> <p>One-tenth of France's population is prescribed at least one antidepressant, primarily by General Practitioners. The reasons for this high prescription rate remain unclear. One-third of these prescriptions may not comply with clinical practice guidelines, and 20% are potentially unrelated to any psychiatric condition. Our aim was to explore how GPs declare they use antidepressants in daily practice and understand their reasons for prescribing them.</p> <p>Method</p> <p>Six focus groups including a total of 56 rural and urban GPs, with four interviews were performed. The topic guide focused on reasons for prescribing antidepressants in various primary care situations. Phenomenological analysis was performed by four researchers.</p> <p>Results</p> <p>Antidepressants were seen as useful and not harmful. Personal assessment based on experience and feeling determined the GPs' decisions rather than the use of scales. Twenty-four "non-psychiatric" conditions possibly leading to prescription of antidepressants in primary care were found.</p> <p>Conclusions</p> <p>The GPs reported prescribing antidepressants for a wide range of conditions other than depression. The GPs' decision making process is difficult and complex. They seemed to prefer to focus on their difficulties in diagnosing depression rather than on useless overtreatment. Instead of using the guidelines criteria to detect potential cases of useful prescription, physicians tend to use their own tools based on gut feelings, knowledge of the patient and contextual issues.</p

Repositioning of the global epicentre of non-optimal cholesterol

High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world

Repositioning of the global epicentre of non-optimal cholesterol

High blood cholesterol is typically considered a feature of wealthy western countries(1,2). However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world(3) and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health(4,5). However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol-which is a marker of cardiovascular riskchanged from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million-4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.Peer reviewe

Repositioning of the global epicentre of non-optimal cholesterol

High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.</p

Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: a pooled analysis of 1201 population-representative studies with 104 million participants

Background Hypertension can be detected at the primary health-care level and low-cost treatments can effectively control hypertension. We aimed to measure the prevalence of hypertension and progress in its detection, treatment, and control from 1990 to 2019 for 200 countries and territories. Methods We used data from 1990 to 2019 on people aged 30–79 years from population-representative studies with measurement of blood pressure and data on blood pressure treatment. We defined hypertension as having systolic blood pressure 140 mm Hg or greater, diastolic blood pressure 90 mm Hg or greater, or taking medication for hypertension. We applied a Bayesian hierarchical model to estimate the prevalence of hypertension and the proportion of people with hypertension who had a previous diagnosis (detection), who were taking medication for hypertension (treatment), and whose hypertension was controlled to below 140/90 mm Hg (control). The model allowed for trends over time to be non-linear and to vary by age. Findings The number of people aged 30–79 years with hypertension doubled from 1990 to 2019, from 331 (95% credible interval 306–359) million women and 317 (292–344) million men in 1990 to 626 (584–668) million women and 652 (604–698) million men in 2019, despite stable global age-standardised prevalence. In 2019, age-standardised hypertension prevalence was lowest in Canada and Peru for both men and women; in Taiwan, South Korea, Japan, and some countries in western Europe including Switzerland, Spain, and the UK for women; and in several low-income and middle-income countries such as Eritrea, Bangladesh, Ethiopia, and Solomon Islands for men. Hypertension prevalence surpassed 50% for women in two countries and men in nine countries, in central and eastern Europe, central Asia, Oceania, and Latin America. Globally, 59% (55–62) of women and 49% (46–52) of men with hypertension reported a previous diagnosis of hypertension in 2019, and 47% (43–51) of women and 38% (35–41) of men were treated. Control rates among people with hypertension in 2019 were 23% (20–27) for women and 18% (16–21) for men. In 2019, treatment and control rates were highest in South Korea, Canada, and Iceland (treatment >70%; control >50%), followed by the USA, Costa Rica, Germany, Portugal, and Taiwan. Treatment rates were less than 25% for women and less than 20% for men in Nepal, Indonesia, and some countries in sub-Saharan Africa and Oceania. Control rates were below 10% for women and men in these countries and for men in some countries in north Africa, central and south Asia, and eastern Europe. Treatment and control rates have improved in most countries since 1990, but we found little change in most countries in sub-Saharan Africa and Oceania. Improvements were largest in high-income countries, central Europe, and some upper-middle-income and recently high-income countries including Costa Rica, Taiwan, Kazakhstan, South Africa, Brazil, Chile, Turkey, and Iran. Interpretation Improvements in the detection, treatment, and control of hypertension have varied substantially across countries, with some middle-income countries now outperforming most high-income nations. The dual approach of reducing hypertension prevalence through primary prevention and enhancing its treatment and control is achievable not only in high-income countries but also in low-income and middle-income settings

La douleur sociale au centre des conduites suicidaires

International audienceBackgroundIntolerable pain is often reported in suicide notes. Moreover, the frequency of life events preceding a suicidal act is high, especially interpersonal difficulties. Such adversity is the source of psychological or social pain.MethodsWe propose a narrative review to discuss the role of pain in the suicidal process while having a focus on social ties.ResultsUsing Ecological Momentary Assessment in suicide attempters it has been shown that being alone increased suicidal ideation while being with close others significantly reduced this risk. At a neuroanatomical level, suicidal vulnerability is associated with dysfunctional insula activation during social exclusion, a region involved in social and physical pain processing. Social pain elicited by social exclusion or devaluation shares common neurobiological patterns with physical pain. It is also an exemplar of psychological pain. Despite the complexity of its definition, higher psychological pain levels are associated with suicidal ideation and acts. Finally, intense physical pain or chronic pain are strong risk factors of suicidal ideation and act. Interestingly, suicide notes often report the existence of an intolerable pain. Presence of psychological pain and difficulties in communication predict the lethality and seriousness of suicide attempts. Moreover, presence of psychological pain is associated with more impulsive choices in suicidal patients, suggesting that a suicidal act is a means to escape intolerable suffering despite negative long-term consequences (i.e. death). Analgesics are usually used to get relief from pain but are also frequently involved in suicidal overdoses. It has been shown that opioid analgesics are associated with an increased risk of suicide. Higher consumption of opioid analgesics has been shown in suicidal patients in comparison to patients with history of depression but no suicidal act and healthy controls whereas non-suicidal patients were those reporting higher presence of pain in comparison to healthy controls. It may suggest that opioids are being used by suicidal patients to get relief from psychological/social pain rather than from physical pain. Involvement of opioidergic system in suicidal process opens new therapeutic strategies. Recently, the time-limited, short-term use of very low dosages of sublingual buprenorphine (vs. placebo) was associated with decreased suicidal ideation and mental pain in severely suicidal patients without substance abuse. In a randomized controlled trial comparing a 7-week acceptance and commitment therapy (ACT) versus relaxation group, as adjunct to treatment as usual for adult outpatients suffering from a current suicidal behavior disorder, ACT has shown its effectiveness in reducing suicidal ideation and psychological pain. Evidence indicates that maintaining contact either via letter, postcard or telephone with at-risk adults following discharge from care services after a suicide attempt can reduce reattempt risk. Based on these results, a preventive program of recontact for suicide attempters, VIGILANS, has been developed in France in usual care.ConclusionThe approach of the suicidal issue by the angle of pain and social disconnection offers new advances to improve clinical assessment, to identify new biological pathways involved in suicidal risk, and to propose innovative therapeutic and preventive actions.Avec un million de décès dans le monde, le suicide est un problème de santé majeur. Malgré la recherche actuelle, les stratégies thérapeutiques efficaces font encore défaut. Les notes de suicide témoignent souvent de la présence d’une douleur intolérable, qu’elle soit physique et/ou psychologique. Les pathologies somatiques en particulier douloureuses sont reconnues comme facteur de risque suicidaire. En outre, malgré la complexité de sa définition, la douleur psychologique semble centrale dans le processus suicidaire. Enfin, considérer l’exclusion sociale (source de la douleur psychologique) peut aussi aider à comprendre la phénoménologie de l’acte suicidaire. La question du rôle de la douleur dans la survenue d’idées et de comportements suicidaires est donc centrale et ouvre de nouvelles voies de compréhension biologique, notamment à travers le système opioïdergique ou l’étude du fonctionnement cérébral. Après avoir exposé les principales données de la littérature permettant de faire le lien entre phénomène douloureux et conduites suicidaires, nous tenterons d’apporter des arguments montrant que l’approche de la problématique suicidaire par l’angle de la douleur et de la déconnexion sociale permet d’envisager des avancées pour améliorer la qualité de l’évaluation du risque suicidaire, pour développer des stratégies thérapeutiques pharmacologiques ou non aux patients suicidaires et pour proposer des actions de prévention

Suicide in older adults: current perspectives

Ismael Conejero,1,2 Emilie Oli&eacute;,1&ndash;3 Philippe Courtet,1&ndash;3 Raffaella Calati1&ndash;3 1Institut National de la Sant&eacute; Et de la Recherche M&eacute;dicale (INSERM), University of Montpellier, Neuropsychiatry: Epidemiological and Clinical Research, Montpellier, France; 2Department of Emergency Psychiatry and Post-Acute Care, Lapeyronie Hospital, Center Hospitalier Universitairere (CHU) Montpellier, Montpellier, France; 3FondaMental Foundation, Cr&eacute;teil, France Abstract: Suicidal behavior in older adults (65 years old and over) is a major public health issue in many countries. Suicide rates increase during the life course and are as high as 48.7/100,000 among older white men in the USA. Specific health conditions and stress factors increase the complexity of the explanatory model for suicide in older adults. A PubMed literature search was performed to identify most recent and representative studies on suicide risk factors in older adults. The aim of our narrative review was to provide a critical evaluation of recent findings concerning specific risk factors for suicidal thoughts and behaviors among older people: psychiatric and neurocognitive disorders, social exclusion, bereavement, cognitive impairment, decision making and cognitive inhibition, physical illnesses, and physical and psychological pain. We also aimed to approach the problem of euthanasia or physician-assisted suicide in older adults. Our main findings emphasize the need to integrate specific stress factors, such as feelings of social disconnectedness, neurocognitive impairment or decision making, as well as chronic physical illnesses and disability in suicide models and in suicide prevention programs in older adults. Furthermore, the chronic care model should be adapted for the treatment of older people with long-term conditions in order to improve the treatment of depressive disorders and the prevention of suicidal thoughts and acts. Keywords: suicide, attempted suicide, older adults, risk factor