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

A pocket of very high suicide rates in a non-violent, egalitarian and cooperative population of South-East Asia

Background Extremely high rates of suicide localized within subgroups of populations where suicide is rare have been reported. We investigated this intriguing observation in a population of South-East Asia, where local culture should theoretically be preventative of suicide. Method A team including an anthropologist and a psychiatrist surveyed all cases of suicide that had occurred over 10 years in four isolated regions. A psychological autopsy was carried out comparing each suicide case with two matched control cases. Results In a region of 1192 inhabitants, 16 suicides occurred, leading to an annual suicide rate of 134/100000 which is 10 times the rate in the USA or Canada. By contrast, three ethnically similar distant communities showed low to null rates. The gender ratio was three males to one female and two-thirds of cases were aged below 35 years. Methods of suicide were poisoning and hanging and motives mainly included interpersonal discord. The pattern of developmental and clinical risk factors was somewhat different from Western countries, showing no childhood maltreatment, only one case of alcohol/substance abuse and impulsive-aggressive personality but elevated rates of social anxiety. Suicide cases had very high frequencies of second-degree biological relatives who committed suicide. Conclusions Our study confirms a persistent phenomenon of high suicide rates restricted to a subgroup of a pre-industrialized population. We hypothesized this might be explained by isolation and endogamy, which may have promoted the selection/amplification of genetic vulnerability factors, or a contagion effect. These findings shed light on suicide from both a singular and a universal perspective, suggesting that particular local conditions may significantly modulate the rate of this complex behavio

Association between hypovitaminosis D and cognitive inhibition impairment during major depression episode

BACKGROUND: Major depressive episode (MDE) has been associated with cognitive functioning alteration and hypovitaminosis D (hypoVD), but the relationship between hypoVD, depression, and cognition is not well understood. We aimed to compare patient with MDE with or without hypoVD in regard of cognitive functioning. METHODS: 91 patients (38.5 years old, 65.9% female) with MDE were included in a cross-sectional study and were evaluated with a complete cognitive battery. None of the participants were medicated at the time of the inclusion. Serum 25-hydroxyvitamin D was measured using LC-MS/MS method, and hypovitaminosis was defined as 25OHD < 50nmol/L. Covariates were gender, season of dosage, first MDE onset, age, body mass index and depression severity RESULTS: Patients with hypoVD demonstrated a higher stroop intereference index time underscoring that means low cognitive inhibition ability. Mutiple logistic regression confirmed that hypoVD was significantly associated with high stroop interference time index after controlling by gender, season of dosage, first MDE onset, age, body mass index and depression severity. CONCLUSION: Our results suggest that patient with MDE having hypoVD may be more prone to cognitive impairment

Deficit of cognitive inhibition in depressed elderly: a neurocognitive marker of suicidal risk

BACKGROUND: Cognitive deficits, in relation to ventral and dorsal prefrontal cortex dysfunctions, have been associated with a higher risk of suicidal acts in young adult patients. Although a public health concern, much less is known about the neurocognitive basis of suicidal behavior in elderly. Here, we aimed at assessing alterations in cognitive inhibition, a suspected major mechanism of the suicidal vulnerability, in suicidal depressed elderly.METHODS: We compared 20 currently depressed patients, aged 65 and older who recently attempted suicide to 20 elderly subjects with a current depression but no personal history of suicide attempt and 20 elderly controls. Using an extensive neuropsychological battery, we particularly examined different aspects of cognitive inhibition: access to relevant information (using the Reading with distraction task), suppression of no longer relevant information (Trail Making Test, Rule Shift Cards), and restraint of cognitive resources to relevant information (Stroop test, Hayling Sentence Completion test, Go/No-Go). RESULTS: After adjustment for age, intensity of depression, Mini-Mental State Examination score and speed of information processing, suicidal depressed elderly showed significant impairments in all 3 domains of cognitive inhibition in comparison to both control groups. LIMITATIONS: Our results need replication in a larger sample size. CONCLUSIONS: Our study suggests that the inability to inhibit neutral information access to working memory, restrain and delete irrelevant information may impair the patient\u27s capacity to respond adequately to stressful situations subsequently leading to an increased risk of suicidal behavior during late-life depression. Interventions may be developed to specifically target cognitive impairment in the prevention of suicide in depressed elderly

Cognitive inhibition and quality of life in schizophrenia: A pilot study

AbstractAim To compare cognitive inhibition and quality of life in patients with schizophrenia and healthy controls. Methods Ten patients with schizophrenia were compared to 10 healthy controls, matched for age, sex, and educational level. Cognitive inhibition was examined by: 1) access to relevant information (Reading with distraction task), 2) suppression of no longer relevant information (Trail Making Test), and 3) restraint of cognitive resources to relevant information (Stroop Test, Hayling Sentence Completion Test, Go/No-Go Test). Montgomery Asberg Depression Rating Scale, Positive and Negative Syndrome Scale, and Schizophrenia-Quality of Life scale (S-QoL) were also used. Results Patients with schizophrenia showed a significant impairment in the suppression function of cognitive inhibition only, in comparison to the control group. Their access and restraint functions of cognitive inhibition were preserved. No relationship between quality of life and cognitive inhibition was found in patients with schizophrenia. Conclusions During the stabilization phase of schizophrenia, the ability to inhibit neutral information access to working memory, and to restrain and suppress irrelevant information may not impair the patient\u27s capacity to respond adequately to stressful situations, and thus would do not impact their quality of life

Increased functional coupling of the mu opioid receptor in the anterior insula of depressed individuals

The mu opioid receptor (MOR) is a G protein-coupled receptor that plays an essential role in reward and hedonic processes, and that has been implicated in disorders such as depression and addiction. Over the last decade, several brain imaging studies in depressed patients have consistently found that dysregulation of MOR function occurs in particular in the anterior insular cortex, an important brain site for the perception of internal states and emotional regulation. To investigate molecular mechanisms that may underlie these effects, here we assessed genetic polymorphisms, expression, and functional G-protein coupling of MOR in a large post-mortem cohort (N = 95) composed of depressed individuals who died by suicide, and healthy controls. Results indicated that depression, but not comorbid substance use disorder or acute opiate consumption, was associated with increased MOR activity. This effect was partly explained by a specific increase in expression of the inhibitory alpha G-protein subunit GNAI2. Consistent with previous neuroimaging studies, our findings support the notion that enhanced endogenous opioidergic tone in the anterior insula may buffer negative affective states in depressed individuals, a mechanism that could potentially contribute to the antidepressant efficacy of emerging opioid-based medications.journal articleresearch support, non-u.s. gov't2021 042021 02 02importe

The neuroscience of suicidal behaviors: what can we expect from endophenotype strategies?

Vulnerability to suicidal behavior (SB) is likely mediated by an underlying genetic predisposition interacting with environmental and probable epigenetic factors throughout the lifespan to modify the function of neuronal circuits, thus rendering an individual more likely to engage in a suicidal act. Improving our understanding of the neuroscience underlying SBs, both attempts and completions, at all developmental stages is crucial for more effective preventive treatments and for better identification of vulnerable individuals. Recent studies have characterized SB using an endophenotype strategy, which aims to identify quantitative measures that reflect genetically influenced stable changes in brain function. In addition to aiding in the functional characterization of susceptibility genes, endophenotypic research strategies may have a wider impact in determining vulnerability to SB, as well as the translation of human findings to animal models, and vice versa. Endophenotypes associated with vulnerability to SB include impulsive/aggressive personality traits and disadvantageous decision making. Deficits in realistic risk evaluation represent key processes in vulnerability to SB. Serotonin dysfunction, indicated by neuroendocrine responses and neuroimaging, is also strongly implicated as a potential endophenotype and is linked with impulsive aggression and disadvantageous decision making. Specific endophenotypes may represent heritable markers for the identification of vulnerable patients and may be relevant targets for successful suicide prevention and treatments

The five-item Brief-Symptom Rating Scale as a suicide ideation screening instrument for psychiatric inpatients and community residents

<p>Abstract</p> <p>Background</p> <p>An efficient screening instrument which can be used in diverse settings to predict suicide in different populations is vital. The aim of this study was to use the five-item Brief Symptom Rating Scale (BSRS-5) as a screening instrument for the prediction of suicide ideation in psychiatric, community and general medical settings.</p> <p>Methods</p> <p>Five hundred and one psychiatric, 1,040 community and 969 general medical participants were recruited. The community participants completed a structured telephone interview, and the other two groups completed the self-report BSRS-5 questionnaire.</p> <p>Results</p> <p>The logistic regression analysis showed that the predictors of suicide ideation for the psychiatric group were depression, hostility and inferiority (<it>p </it>< 0.001, <it>p </it>= 0.016, <it>p </it>= 0.011), for the community group, inferiority, hostility and insomnia (<it>p </it>< 0.001, <it>p </it>< 0.001, <it>p </it>= 0.003), and for the general medical group, inferiority, hostility, depression and insomnia (<it>p </it>< 0.001, <it>p </it>= 0.001, <it>p </it>= 0.020, <it>p </it>= 0.008). The structural equation model showed the same symptom domains that predicted suicide ideation for all three groups. The receiver operating characteristic curve using the significant symptom domains from logistic regression showed that for the psychiatric group, the optimal cut-off point was 4/5 for the total of the significant dimensions (positive predictive value [PPV] = 78.01%, negative predictive value [NPV] = 79.05%), for the community group, 7/8 (PPV = 68.75%, NPV = 96.09%), and for the general medical group, 12/13 (PPV = 92.86%, NPV = 88.48%).</p> <p>Conclusion</p> <p>The BSRS-5 is an efficient tool for the screening of suicide ideation-prone psychiatric inpatients, general medical patients, and community residents. Understanding the discriminative symptom domains for different groups and the relationship between them can help health care professionals in their preventative programs and clinical treatment.</p

Decreased cerebral blood flow in the limbic and prefrontal cortex using SPECT imaging in a cohort of completed suicides

Suicide has a high comorbidity with impulsivity and depression, and finding imaging biomarkers indicative of patients at high risk for suicidal behavior is invaluable to the clinician. Using single-photon emission computed tomography (SPECT) imaging, we have previously reported regional cerebral blood flow (rCBF) decreases in the medial prefrontal cortex, ventral tegmental area and subgenual cingulate cortex (Brodmann area 25 (BA 25)), a region found to be hypoperfused with treatment-resistant depression. From 2007 to 2010, we have extended our analysis to include nine additional completed suicides. In all, 27 healthy, age- and gender-matched subjects from a previously acquired healthy brain study served as controls to our 21 completed suicides. All 21 suicides had been previously diagnosed with depression according to Diagnostic and Statistical Manual of Mental Disorder-IV criterion. Voxel-by-voxel analyses were performed using statistical parametric mapping to compare the differences in technetium-99m hexamethylpropylene amine oxime brain uptake between the groups. Factor analysis of the data identified the top 10 regions of hypoperfusion in the suicidal group, including the bilateral superior frontal lobes, the right precuneus, the rolandic operculum, postcentral gyrus, left caudate and insular cortex. We also demonstrate more focal decreases in rCBF in the subgenual cingulate cortex (BA 25) in 18 subjects, supporting our previous hypothesis that hypoperfusion of BA 25 may be a risk factor for suicide in depressed patients. This work suggests that SPECT might be useful in predicting risk for suicide completion in subjects with depression or treatment-resistant depression. Further investigation of this work is necessary to better understand the predictive value of this finding