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      Association Between Neurological Disorders and Death by Suicide in Denmark

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          Abstract

          Is there an association between neurological disorders and a higher risk of death by suicide? In this retrospective cohort study that included 7 300 395 persons in Denmark from 1980 through 2016, there was a significantly higher rate of suicide among those with a diagnosed neurological disorder than all other persons (44.0 per 100 000 person-years vs 20.1 per 100 000 person-years, adjusted incidence rate ratio, 1.8). In Denmark, having a diagnosis of a neurological disorder was associated with a small but statistically significant increased risk of death by suicide. Neurological disorders have been linked to suicide, but the risk across a broad spectrum of neurological disorders remains to be assessed. To examine whether people with neurological disorders die by suicide more often than other people and to assess for temporal associations. Nationwide, retrospective cohort study on all persons 15 years or older living in Denmark, from 1980 through 2016 (N = 7 300 395). Medical contact for head injury, stroke, epilepsy, polyneuropathy, diseases of myoneural junction, Parkinson disease, multiple sclerosis, central nervous system infections, meningitis, encephalitis, amyotrophic lateral sclerosis, Huntington disease, dementia, intellectual disability, and other brain diseases from 1977 through 2016 (n = 1 248 252). Death by suicide during 1980-2016. Adjusted incidence rate ratio (IRRs) were estimated using Poisson regressions, adjusted for sociodemographics, comorbidity, psychiatric diagnoses, and self-harm. Of the more than 7.3 million individuals observed over 161 935 233 person-years (49.1% males), 35 483 died by suicide (median duration of follow-up, 23.6 years; interquartile range, 10.0-37.0 years; mean age, 51.9 years; SD, 17.9 years). Of those, 77.4% were males, and 14.7% (n = 5141) were diagnosed with a neurological disorder, equivalent to a suicide rate of 44.0 per 100 000 person-years compared with 20.1 per 100 000 person-years among individuals not diagnosed with a neurological disorder. People diagnosed with a neurological disorder had an adjusted IRR of 1.8 (95% CI, 1.7-1.8) compared with those not diagnosed. The excess adjusted IRRs were 4.9 (95% CI, 3.5-6.9) for amyotrophic lateral sclerosis, 4.9 (95% CI, 3.1-7.7) for Huntington disease, 2.2 (95% CI, 1.9-2.6) for multiple sclerosis, 1.7 (95% CI, 1.6-1.7) for head injury, 1.3 (95% CI, 1.2-1.3) for stroke, and 1.7 (95% CI, 1.6-1.8) for epilepsy. The association varied according to time since diagnosis with an adjusted IRR for 1 to 3 months of 3.1 (95% CI, 2.7-3.6) and for 10 or more years, 1.5 (95% CI, 1.4 to 1.6, P  < .001). Compared with those who were not diagnosed with a neurological disorder, those with dementia had a lower overall adjusted IRR of 0.8 (95% CI, 0.7-0.9), which was elevated during the first month after diagnosis to 3.0 (95% CI, 1.9-4.6; P  < .001). The absolute risk of suicide for people with Huntington disease was 1.6% (95% CI, 1.0%-2.5%). In Denmark from 1980 through 2016, there was a significantly higher rate of suicide among those with a diagnosed neurological disorder than persons not diagnosed with a neurological disorder. However, the absolute risk difference was small. This population epidemiology study uses Danish registry data to examine associations between neurological disorders and higher suicide rates from 1980 through 2016.

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          Most cited references26

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          The neurobiology of suicide.

          The stress-diathesis model posits that suicide is the result of an interaction between state-dependent (environmental) stressors and a trait-like diathesis or susceptibility to suicidal behaviour, independent of psychiatric disorders. Findings from post-mortem studies of the brain and from genomic and in-vivo neuroimaging studies indicate a biological basis for this diathesis, indicating the importance of neurobiological screening and interventions, in addition to cognitive and mood interventions, in the prevention of suicide. Early-life adversity and epigenetic mechanisms might explain some of the link between suicide risk and brain circuitry and neurochemistry abnormalities. Results from a range of studies using diverse designs and post-mortem and in-vivo techniques show impairments of the serotonin neurotransmitter system and the hypothalamic-pituitary-adrenal axis stress-response system in the diathesis for suicidal behaviour. These impairments manifest as impaired cognitive control of mood, pessimism, reactive aggressive traits, impaired problem solving, over-reactivity to negative social signs, excessive emotional pain, and suicidal ideation, leading to suicidal behaviour. Biomarkers related to the diathesis might help to inform risk-assessment procedures and treatment choice in the prevention of suicide.
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            Pain and suicidality: insights from reward and addiction neuroscience.

            Suicidality is exceedingly prevalent in pain patients. Although the pathophysiology of this link remains unclear, it may be potentially related to the partial congruence of physical and emotional pain systems. The latter system's role in suicide is also conspicuous during setbacks and losses sustained in the context of social attachments. Here we propose a model based on the neural pathways mediating reward and anti-reward (i.e., allostatic adjustment to recurrent activation of the reward circuitry); both are relevant etiologic factors in pain, suicide and social attachments. A comprehensive literature search on neurobiology of pain and suicidality was performed. The collected articles were critically reviewed and relevant data were extracted and summarized within four key areas: (1) physical and emotional pain, (2) emotional pain and social attachments, (3) pain- and suicide-related alterations of the reward and anti-reward circuits as compared to addiction, which is the premier probe for dysfunction of these circuits and (4) mechanistically informed treatments of co-occurring pain and suicidality. Pain-, stress- and analgesic drugs-induced opponent and proponent states of the mesolimbic dopaminergic pathways may render reward and anti-reward systems vulnerable to sensitization, cross-sensitization and aberrant learning of contents and contexts associated with suicidal acts and behaviors. These findings suggest that pain patients exhibit alterations in the brain circuits mediating reward (depressed function) and anti-reward (sensitized function) that may affect their proclivity for suicide and support pain and suicidality classification among other "reward deficiency syndromes" and a new proposal for "enhanced anti-reward syndromes". We suggest that interventions aimed at restoring the balance between the reward and anti-reward networks in patients with chronic pain may help decreasing their suicide risk. Published by Elsevier Ltd.
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              Suicide risk in primary care patients with major physical diseases: a case-control study.

              Most previous studies have examined suicide risk in relation to a single physical disease. To estimate relative risk across a range of physical diseases, to assess the confounding effect of clinical depression and effect modification by sex and age, and to examine physical illness multimorbidity. Nested case-control study. Family practices in England (n = 224) [corrected] registered with the General Practice Research Database from January 1, 2001, through December 31, 2008. The case-control data were drawn from approximately 4.7 [corrected] million complete patient records, with complete linkage to national mortality records. A total of 873 adult suicide cases and 17 460 living controls matched on age and sex were studied. The reference group for relative risk estimation consisted of people without any of the specific physical illnesses examined. Suicide and open verdicts. Among all patients, coronary heart disease, stroke, chronic obstructive pulmonary disease, and osteoporosis were linked with elevated suicide risk, and, with the exception of osteoporosis, the increase was explained by clinical depression. The only significantly elevated risk in men was with osteoporosis. Female effect sizes were greater, with 2- or 3-fold higher risk found among women diagnosed as having cancer, coronary heart disease, stroke, chronic obstructive pulmonary disease, and osteoporosis. In women with cancer and coronary heart disease, a significant elevation persisted after adjustment for depression. Overall, heightened risk was confined to physically ill women younger than 50 years and to older women with multiple physical diseases. Our findings indicate that clinical depression is a strong confounder of increased suicide risk among physically ill people. They also demonstrate an independent elevation in risk linked with certain diagnoses, particularly among women. Health care professionals working across all medical specialties should be vigilant for signs of undetected psychological symptoms.
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                Author and article information

                Journal
                JAMA
                JAMA
                American Medical Association (AMA)
                0098-7484
                February 04 2020
                February 04 2020
                : 323
                : 5
                : 444
                Affiliations
                [1 ]Danish Research Institute for Suicide Prevention, Mental Health Centre Copenhagen, Copenhagen, Denmark
                [2 ]Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
                [3 ]Focused Research Unit, Department of Psychiatry, University Hospital of the Region of Southern Denmark, Aabenraa
                [4 ]Center of Mental Health Research, Australian National University, Canberra, Australia
                [5 ]MS-Clinic of Southern Jutland (Sønderborg, Esbjerg, Kolding), Hospital of Southern Jutland, Sønderborg, Denmark
                [6 ]Department of Neurology, Hospital of Southern Jutland, Sønderborg, Denmark
                [7 ]Department of Regional Health Research, University of Southern Denmark, Odense
                [8 ]Focused Research Unit, Center Sønderjylland, Hospital of Southern Jutland, Aabenraa, Denmark
                [9 ]Center for the Study and Prevention of Suicide, University of Rochester Medical Center, Rochester, New York
                [10 ]Section of Biostatistics, University of Copenhagen, Copenhagen, Denmark
                [11 ]Centre for Suicide Research, University of Oxford, Oxford, United Kingdom
                [12 ]Oxford Health NHS Foundation Trust, Warnerford Hospital, Oxford, United Kingdom
                [13 ]Copenhagen Research Center for Mental Health, Mental Health Centre Copenhagen, Copenhagen, Denmark
                [14 ]Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
                Article
                10.1001/jama.2019.21834
                7042859
                32016308
                d15f62b1-b7fe-4845-bd42-5ea25c3b019f
                © 2020
                History

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