Neural correlates of deceased-related attention during acute grief in suicide-related bereavement.

BACKGROUND: Individuals who have lost a loved one to suicide demonstrate an attentional bias to deceased-related stimuli during early grief. Regulating attention toward reminders of the deceased during acute bereavement may be linked to grief trajectory and pathological grief development. Despite the potential prognostic importance, little is known about underlying neural circuitry correlates of deceased-related grief processing. The current study examines neural substrates of deceased-related attentional processing during acute grief in individuals bereaved by suicide. METHODS: Thirty-seven participants grieving the loss of a first-degree relative or partner to suicide in the prior six months, underwent functional magnetic resonance imaging (fMRI) while performing an emotional Stroop task using words related to the deceased and a living attachment figure, in order to examine neural correlates of deceased-specific attentional processing. Clinical interviews were conducted at baseline. RESULTS: Deceased-related attentional bias was associated with blood oxygen level-dependent (BOLD) activation in a brain network, including dorsolateral prefrontal cortex (dlPFC), ventrolateral prefrontal cortex (vlPFC), orbitofrontal cortex (OFC), and insula. Greater activation of a bilateral prefrontal cluster during deceased-specific attention was negatively correlated with self-reported grief avoidance behaviors. LIMITATIONS: Lack of non-suicide grief control and small sample size. CONCLUSIONS: These data, if confirmed, indicate a neural network specific to deceased-related attention, and that cognitive control regions within this network appear to be related to grief avoidance behaviors during acute bereavement.

Temporal Interactions between Neural Proxies forMemory Recall, Negative Affect, and EmotionRegulation in Major Depression.

Dysfunction in emotion regulation (ER) and autobiographical memory are components of major depressive disorder (MDD). However, little is known about how they mechanistically interact with mood disturbances in real time. Using machine learning-based neural signatures, we can quantify negative affect (NA), ER, and memory continuously to evaluate how these processes dynamically interact in MDD. Unmedicated individuals with MDD (N=45) and healthy volunteers (HV; N=38) completed a negative autobiographical memory functional magnetic resonance imaging task wherein they recalled, distanced from (an ER strategy), and immersed into memories. We used a negative affect signature (PINES) and an emotion regulation signature (ERS) to quantify moment-to-moment NA and ER. We then examined whether memory engagement, indexed by hippocampal activity, predicted subsequent change in PINES and ERS over time. During memory recall and immersion, greater hippocampal activity predicted increased PINES across groups. During distancing, greater hippocampal activity in HVs predicted increased ERS but not PINES. In MDD, greater hippocampal activity predicted increased PINES but not ERS. Findings suggest abnormalities in the real-time relationship between memory, NA, and ER in MDD. During distancing, as predicted, HVs showed an attenuation of the linkage between memory engagement and NA, and they had subsequent increases in ER following memory reactivation. In contrast, MDD was characterized by continued linkage between memory engagement and NA, without subsequent increases in ER. Deficits in engagement of ER and ineffective modulation of NA following negative memory recall may contribute to the mood disturbances in MDD and are potential targets for clinical intervention.

Improving Suicide Prevention Through Evidence-Based Strategies: A Systematic Review.

Objective: The authors sought to identify scalable evidence-based suicide prevention strategies. Methods: A search of PubMed and Google Scholar identi- fied 20,234 articles published between September 2005 and December 2019, of which 97 were randomized controlled trials with suicidal behavior or ideation as primary outcomes or epidemiological studies of limiting access to lethal means, using educational approaches, and the impact of antidepressant treatment. Results: Training primary care physicians in depression rec- ognition and treatment prevents suicide. Educating youths on depression and suicidal behavior, as well as active out- reach to psychiatric patients after discharge or a suicidal crisis, prevents suicidal behavior. Meta-analyses find that antidepressants prevent suicide attempts, but individual randomized controlled trials appear to be underpowered. Ketamine reduces suicidal ideation in hours but is untested for suicidal behavior prevention. Cognitive-behavioral therapy and dialectical behavior therapy prevent suicidal behavior. Active screening for suicidal ideation or behavior is not proven to be better than just screening for depression. Education of gatekeepers about youth suicidal behavior lacks effectiveness. No randomized trials have been reported for gatekeeper training for prevention of adult suicidal behavior. Algorithm-driven electronic health record screening, Internet-based screening, and smartphone passive monitoring to identify high-risk patients are under-studied. Means restriction, including of firearms, prevents suicide but is sporadically employed in the United States, even though firearms are used in half of all U.S. suicides. Conclusions: Training general practitioners warrants wider implementation and testing in other nonpsychiatrist physi- cian settings. Active follow-up of patients after discharge or a suicide-related crisis should be routine, and restricting firearm access by at-risk individuals warrants wider use. Combination approaches in health care systems show promise in reducing suicide in several countries, but evaluating the benefit attributable to each component is essential. Further suicide rate reduction requires evaluating newer approaches, such as electronic health record-derived algorithms, Internet-based screening methods, ketamine's potential benefit for preventing attempts, and passive monitoring of acute suicide risk change.Reprinted from Am J Psychiatry 2021; 178:611-624, with permission from American Psychiatric Association Publishing. Copyright © 2021.

Attentional bias during acute grief predicts clinical outcome in suicide-related bereavement.

BACKGROUND: Individuals who have lost a loved one to suicide are at increased risk for developing complicated grief (CG). It is unclear why only a subgroup of bereaved develops pathological forms of grief. Vulnerability may be related to the ability to regulate attention toward reminders of the deceased during the acute phase of grief. Using a longitudinal design, we determined whether loss-related attentional bias during acute grief predicts grief severity one year later. METHODS: Thirty-seven participants grieving a first-degree relative or partner to suicide in the prior 6 months performed an emotional Stroop task using words related to the deceased, a living attachment figure, living non-attachment figure, and color congruent Stroop to quantify related attentional bias during the acute grief period. Clinical interviews were conducted at baseline (N = 37) and one year later (N = 35). RESULTS: Participants showed greater attentional bias to deceased-related word trials compared with living attachment, non-attachment, and congruent trials, controlling for age, time since loss, depression, and psychiatric medication. A greater reduction in grief severity over time was associated with more deceased-related attentional bias at baseline. Self-reported grief avoidance was related to deceased-related attentional bias, with lower avoidance scores associated with greater bias. LIMITATIONS: Lack of non-suicide grief control and small sample size. CONCLUSIONS: Less deceased-related bias following the loss may hinder the transition from acute to integrated grief and result in poorer grief trajectories.

Improving Suicide Prevention Through Evidence-Based Strategies: A Systematic Review.

OBJECTIVE: The authors sought to identify scalable evidence-based suicide prevention strategies. METHODS: A search of PubMed and Google Scholar identified 20,234 articles published between September 2005 and December 2019, of which 97 were randomized controlled trials with suicidal behavior or ideation as primary outcomes or epidemiological studies of limiting access to lethal means, using educational approaches, and the impact of antidepressant treatment. RESULTS: Training primary care physicians in depression recognition and treatment prevents suicide. Educating youths on depression and suicidal behavior, as well as active outreach to psychiatric patients after discharge or a suicidal crisis, prevents suicidal behavior. Meta-analyses find that antidepressants prevent suicide attempts, but individual randomized controlled trials appear to be underpowered. Ketamine reduces suicidal ideation in hours but is untested for suicidal behavior prevention. Cognitive-behavioral therapy and dialectical behavior therapy prevent suicidal behavior. Active screening for suicidal ideation or behavior is not proven to be better than just screening for depression. Education of gatekeepers about youth suicidal behavior lacks effectiveness. No randomized trials have been reported for gatekeeper training for prevention of adult suicidal behavior. Algorithm-driven electronic health record screening, Internet-based screening, and smartphone passive monitoring to identify high-risk patients are understudied. Means restriction, including of firearms, prevents suicide but is sporadically employed in the United States, even though firearms are used in half of all U.S. suicides. CONCLUSIONS: Training general practitioners warrants wider implementation and testing in other nonpsychiatrist physician settings. Active follow-up of patients after discharge or a suicide-related crisis should be routine, and restricting firearm access by at-risk individuals warrants wider use. Combination approaches in health care systems show promise in reducing suicide in several countries, but evaluating the benefit attributable to each component is essential. Further suicide rate reduction requires evaluating newer approaches, such as electronic health record-derived algorithms, Internet-based screening methods, ketamine's potential benefit for preventing attempts, and passive monitoring of acute suicide risk change.

Effects of Protein, Calcium, and pH on Gene Transcription, Cell-Envelope Peptidase Activity of Lactococcus lactis Strains, and the Formation of Bitter Peptides.

Calcium- and protein-rich fermented milk products, such as concentrated yoghurts and fresh cheeses, may contain undesired bitter peptides, which are generated by the proteolytic cleavage of casein. Up to now, it is not clear whether this process is caused by endogenous milk enzymes, such as plasmin and cathepsin D, or whether proteolytic enzymes from applied starter cultures, such as the lactococcal cell-envelope peptidase PrtP, are involved. A sensory analysis of fresh cheese products made from milk concentrates fermented with prtP-negative and -positive Lactococcus lactis strains revealed bitterness in the products fermented with prtP-positive L. lactis strains. Two prtP-positive strains, LTH 7122 and LTH 7123, were selected to investigate the effect of increased calcium concentrations (additional 5 mM and 50 mM CaCl2) at neutral (pH 6.6) and acidic (pH 5.5) pH-values on the transcription of the prtP gene and its corresponding PrtP peptidase activity in milk citrate broth (MCB). For both strains, it was shown that prtP transcription was upregulated only under slightly elevated calcium conditions (5 mM CaCl2) after 5 h of growth. In concordance with these findings, PrtP peptidase activity also increased. When higher concentrations of calcium were used (50 mM), prtP expression of both strains decreased strongly by more than 50%. Moreover, PrtP peptidase activity of strain LTH 7123 decreased by 15%, but enzymatic activity of strain LTH 7122 increased slightly during growth under elevated calcium concentrations (50 mM CaCl2). Fermentations of reconstituted casein medium with 3.4% (w/v) and 8.5% (w/v) protein and different calcium concentrations using strain LTH 7122 revealed no clear relationship between prtP transcription and calcium or protein concentration. However, an increase in PrtP peptidase activity under elevated protein and calcium conditions was observed. The activity increase was accompanied by increased levels of bitter peptides derived from different casein fractions. These findings could be a possible explanation for the bitterness in fermented milk concentrates that was detected by a trained bitter panel.

Genotoxicity testing of sulfur dioxide (SO2) in a mouse bone marrow micronucleus test complemented with hematological endpoints.

Sulfur dioxide (SO2) is a non-flammable, non-explosive, colorless gas. It is a ubiquitous environmental pollutant and an important chemical intermediate in several industrial processes. The toxicological properties of SO2, including its genotoxic potential, have been studied extensively. The majority of the available in vitro data indicate a lack of genotoxicity of SO2, while for sulfite salts some positive results have been reported. However, recent in vivo studies, using Kunming albino mice, have pointed to in vivo clastogenicity of SO2. To re-evaluate these positive findings, a bone-marrow micronucleus test according to OECD Guideline No. 474 was performed. NMRI mice (m/f) were exposed by inhalation via whole-body exposure to 0 (clean air), 2.7, 8, 27, or 80mg/m3 (0, 1, 3, 10, or 30ppm) SO2 for 4h/day on 7 consecutive days. Animals were sacrificed 24h after start of the last exposure, and blood samples (for complementing hematology) and bone marrow smears (for analysis of micronuclei) were prepared. Under the conditions used, exposure to SO2 caused no acute toxicity, mortality, or reduction in body weight. Compared with the clean-air controls, hematological parameters such as hematocrit, hemoglobin, erythrocyte/platelet/total leukocyte counts, differential white blood cell counts, and indicators of blood formation (reticulocyte counts, ratio of polychromatic to normochromatic erythrocytes in the bone marrow) remained unchanged by SO2 treatment. Unlike the previously reported studies on micronucleus formation, SO2 did not induce micronuclei in polychromatic erythrocytes of the bone marrow, whereas the positive control cyclophosphamide (60mg/kg body weight) was quite effective in this respect. Interestingly, SO2 treatment significantly enhanced malondialdehyde levels in erythrocyte lysates (TBARS method), indicating SO2-mediated oxidative stress, but also demonstrating systemic availability of the inhaled SO2. In conclusion, the present study could not reproduce the genotoxicity findings of the previously reported studies. SO2 is thus considered non-genotoxic in polychromatic erythrocytes in the bone marrow of NMRI mice under the conditions and in the concentrations used.

Suicidal subtypes, stress responsivity and impulsive aggression.

While prominent models of suicidal behavior emphasize the hypothalamic- pituitary-adrenal (HPA) axis dysregulation, studies examining its role have yielded contradictory results. One possible explanation is that suicide attempters are a heterogeneous group and HPA axis dysregulation plays a more important role only in a subset of suicidal individuals. HPA axis dysregulation also plays a role in impulsivity and aggression. We hypothesize subgroups of attempters, based on levels of impulsivity and aggression, will differ in HPA axis dysregulation. We examined baseline cortisol, total cortisol output, and cortisol reactivity in mood disordered suicide attempters (N = 35) and non-attempters (N = 37) during the Trier Social Stress Test. Suicide attempters were divided into four subgroups: low aggression/low impulsivity, high aggression/low impulsivity, low aggression/high impulsivity, and high aggression/high impulsivity. As hypothesized, attempters and non-attempters did not differ in any cortisol measures while stress response differed based on impulsivity/aggression levels in suicide attempters, and when compared to non-attempters. Specifically, attempters with high impulsive aggression had a more pronounced cortisol response compared with other groups. This is the first study to examine the relationship between cortisol response and suicidal behavior in impulsive aggressive subgroups of attempters. These findings may help to identify a stress responsive suicidal subtype of individuals.

Attentional Bias to Reminders of the Deceased as Compared With a Living Attachment in Grieving.

BACKGROUND: Grieving individuals demonstrate attentional bias toward reminders of the deceased versus neutral stimuli. We sought to assess bias toward reminders of the deceased versus a living attachment figure and to evaluate similarities and differences in the neural correlates of deceased- and living-related attention. We also sought to identify grief process variables associated with deceased-related attentional bias. METHODS: Twenty-five subjects grieving the death of a first-degree relative or partner within 14 months performed an emotional Stroop task, using words related to a deceased or a living attachment figure, and a standard Stroop task, to identify general selective attention, during functional magnetic resonance imaging. Subjects rated word sadness, complicated grief symptoms, depression severity, attachment style, emotional pain, nonacceptance, yearning, and intrusions. RESULTS: We identified an attentional bias to deceased-related versus living-related words, independent of age, depression severity/history, loss type, word sadness, medication use, and time since loss. Attentional bias correlated with complicated grief severity and intrusive thinking. A conjunction analysis identified joint activation in the fusiform gyrus, posterior cingulate, and temporal parietal junction across living- and deceased-related attention versus general selective attention. Insecure-avoidant attachment style correlated with decreased engagement of this network in deceased-related attention. CONCLUSIONS: We have demonstrated an attentional bias to reminders of the deceased versus a living attachment in grieving. Overlapping neural circuits related to living- and deceased-related attention suggest that the bereaved employ similar processes in attending to the deceased as they do in attending to the living. Deceased-related attentional bias appears to be linked primarily to intrusive thinking about the loss.

Prevention of Firearm Suicide in the United States: What Works and What Is Possible.

OBJECTIVE: About 21,000 suicides in the United States in 2014 involved a firearm. The authors reviewed evidence from around the world regarding the relationship between firearm ownership rates and firearm suicide rates and the potential effectiveness of policy-based strategies for preventing firearm suicides in the United States. METHOD: Relevant publications were identified by searches of PubMed, PsycINFO, MEDLINE, and Google Scholar from 1980 to September 2015, using the search terms suicide AND firearms OR guns. Excluding duplicates, 1,687 results were found, 60 of which were selected for inclusion; these sources yielded an additional 10 studies, for a total of 70 studies. RESULTS: Case-control and ecological studies investigating geographic and temporal variations in firearm ownership and firearm suicide rates indicate that greater firearm availability is associated with higher firearm suicide rates. Time-series analyses, mostly from other countries, show that legislation reducing firearm ownership lowers firearm suicide rates. Because the Second Amendment curtails legislation broadly restricting firearm access in the United States, the emphasis is shifted to restricting access for those at risk of harming themselves or others. Most suicides involve guns purchased years earlier. Targeted initiatives like gun violence restraining orders, smart gun technology, and gun safety education campaigns potentially reduce access to already purchased firearms by suicidal individuals. Such measures are too new to have evidence of effectiveness. CONCLUSIONS: Broadly reducing availability and access to firearms has lowered firearm suicide rates in other countries but does not appear feasible in the United States. Approaches restricting access of at-risk individuals to already purchased firearms by engaging the public and major stakeholders require urgent implementation and outcome evaluation for firearm suicide prevention.