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1.
Mol Psychiatry ; 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38729992

RESUMO

Decedents with no known mental disorder comprise 5-40% of suicides, suggesting that suicide ideation (SI) and behavior may occur in the psychiatrically healthy with important implications for suicide risk screening. Healthy Volunteers (HV) and patients with Major Depressive Disorder (MDD) provided 7 days of Ecological Momentary Assessment (EMA) data about SI and stressors. Longitudinal mixed effects logistic regression models compared HV and patient SI and stressors. Mixed effects linear regression models compared HVs' and patients' SI score change from the previous epoch's SI score when each stressor occurred. HVs (n = 42) reported less frequent (p < 0.001) and less intense SI (p < 0.003) than patients (n = 80), yet did endorse SI and/or SI-related items in 44% of EMA epochs, endorsing SI items in 25% of epochs with non-zero SI scores. For 7 of 8 stressors, patients reported stressors more often than HVs (all p < 0.001) responding to them with increased SI (0.0001 < p < 0.0472). HVs were relatively resilient to stressors, reporting SI increases only in response to neglect (p < 0.0147). Although SI and SAs are documented among psychiatrically healthy individuals, scientific attention to these observations has been scant. Real-time SI measurement showed that HVs' SI was less pronounced than MDD patients', but was endorsed, nonetheless. Patients were more likely to report stressors than HVs, perhaps due to greater sensitivity to the environment, and reported SI in response to stressors, which was less common in HVs. Both MDD patients and HVs most often manifested passive SI (viz, "decreased wish to live"). However, passive SI (viz, "desire for death"), may predict suicide, even absent SI per se (thinking about killing yourself). This study validates the utility of real-time SI assessment, showing that HVs endorse SI items in 11% of epochs, which implies that suicide risk screening focused on those with mental disorders may be too narrow an approach.

2.
Int J Neuropsychopharmacol ; 27(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38573154

RESUMO

OBJECTIVE: We sought to explore relationships of acute dissociative effects of intravenous ketamine with change in depression and suicidal ideation and with plasma metabolite levels in a randomized, midazolam-controlled trial. METHODS: Data from a completed trial in suicidal, depressed participants (n = 40) randomly assigned to ketamine was used to examine relationships between ketamine treatment-emergent dissociative and psychotomimetic symptoms with pre/post-infusion changes in suicidal ideation and depression severity. Nonparametric correlational statistics were used. These methods were also used to explore associations between dissociative or psychotomimetic symptoms and blood levels of ketamine and metabolites in a subset of participants (n = 28) who provided blood samples immediately post-infusion. RESULTS: Neither acute dissociative nor psychotomimetic effects of ketamine were associated with changes in suicidal ideation or depressive symptoms from pre- to post-infusion. Norketamine had a trend-level, moderate inverse correlation with dissociative symptoms on Day 1 post-injection (P = .064; P =.013 removing 1 outlier). Dehydronorketamine correlated with Clinician-Administered Dissociative States Scale scores at 40 minutes (P = .034), 230 minutes (P = .014), and Day 1 (P = .012). CONCLUSION: We did not find evidence that ketamine's acute, transient dissociative, or psychotomimetic effects are associated with its antidepressant or anti-suicidal ideation actions. The correlation of higher plasma norketamine with lower dissociative symptoms on Day 1 post-treatment suggests dissociation may be more an effect of the parent drug.


Assuntos
Antidepressivos , Transtornos Dissociativos , Ketamina , Ketamina/análogos & derivados , Midazolam , Ideação Suicida , Humanos , Ketamina/administração & dosagem , Ketamina/sangue , Ketamina/farmacologia , Masculino , Adulto , Midazolam/administração & dosagem , Midazolam/farmacologia , Midazolam/sangue , Feminino , Antidepressivos/sangue , Antidepressivos/administração & dosagem , Antidepressivos/farmacologia , Transtornos Dissociativos/induzido quimicamente , Transtornos Dissociativos/sangue , Pessoa de Meia-Idade , Adulto Jovem , Método Duplo-Cego
3.
Am J Geriatr Psychiatry ; 32(5): 622-629, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38182486

RESUMO

This clinical viewpoint article aims to draw attention to a yet unexplored factor influencing suicidal behavior: age of onset of suicidal behavior. To tackle the substantial heterogeneity among depressed older attempters, we suggest consideration of at least two distinct pathways to suicidal behavior in late life based on when the first suicidal crisis occurred. Specifically, we discuss the current state of research and the rationale behind the suggested early-late-onset categorization of late-life suicidal behavior. We summarize available evidence so far on early-onset and late-onset attempters, and the potential heterogeneity in the interplay of risk/precipitating factors. Certain risk factors for suicide, such as impulsivity and borderline traits, decrease with age, while memory and broader cognitive impairments increase with age. Research indicates that familial/social exposure to suicidal behavior, childhood trauma, impulsivity, maladaptive personality traits, longstanding interpersonal difficulties, and legal problems are found predominantly in attempters experiencing their first suicidal crisis between youth and early midlife. In contrast, dementia prodrome is one of the most promising but understudied candidates for late-onset suicide risk, especially in the context of other risk factors. Moreover, personality traits conferring increased vulnerability to late-onset suicidal behavior (such as high conscientiousness) are not the same as ones classically identified in younger attempters and in older suicide attempters who have early-onset suicidal behavior (such as neuroticism and Cluster B traits). We discuss methodological points about studying age of onset of suicidal behavior, outline clinical implications, share ideas for future directions, and call for research on this understudied topic.


Assuntos
Ideação Suicida , Suicídio , Humanos , Idoso , Adolescente , Tentativa de Suicídio/psicologia , Suicídio/psicologia , Comportamento Impulsivo , Neuroticismo , Fatores de Risco
4.
Mol Psychiatry ; 26(9): 5079-5086, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-32576966

RESUMO

Suicidal behavior (SB) can be impulsive or methodical; violent or not; follow a stressor or no obvious precipitant. This study tested whether childhood trauma, affective lability, and aggressive and impulsive traits predicted greater SI variability. We also assessed whether affective lability, aggressive or impulsive traits explain childhood trauma's effects on SI variability and whether those with highly variable SI respond to stressful events with increases in SI. Finally, we assessed variable SI's trajectory over 2 years. Depressed participants (n = 51) had ecological momentary assessments (EMA) over 7 days at baseline, 3, 6, 12, 18, and 24 months. SI variability was assessed using the square Root of the Mean Square of Successive Deviations. Mixed Effects Models were fit as appropriate. Childhood trauma was associated with subsequent aggression. Physical abuse predicted both aggression and affective lability as well as SI variability, but not impulsivity. In two-predictor models, physical abuse's effect on SI variability was no longer significant, when controlling for the effect of higher aggression and impulsivity. Those with high SI variability exhibited greater increases in SI after stressors compared with those with less variability. We did not find that SI variability changed over time, suggesting it might be trait-like, at least over 2 years. Variable SI predisposes to marked SI increases after stressful events and may be a trait increasing risk for impulsive SB, at least over 2 years.


Assuntos
Ideação Suicida , Suicídio , Agressão , Biomarcadores , Humanos , Comportamento Impulsivo , Fatores de Risco , Tentativa de Suicídio
5.
Int J Neuropsychopharmacol ; 22(5): 329-338, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30927011

RESUMO

BACKGROUND: Abnormalities in the hypothalamic-pituitary-adrenal axis, serotonergic system, and stress response have been linked to the pathogenesis of major depressive disorder. State-dependent hyper-reactivity of the hypothalamic-pituitary-adrenal axis is seen in major depressive disorder, and higher binding to the serotonin 1A receptor is observed as a trait in both currently depressed and remitted untreated major depressive disorder. Here, we sought to examine whether a relationship exists between cortisol secretion in response to a stressor and serotonin 1A receptor binding throughout the brain, both in healthy controls and participants with major depressive disorder. METHODS: Research participants included 42 medication-free, depressed subjects and 31 healthy volunteers. Participants were exposed to either an acute, physical stressor (radial artery catheter insertion) or a psychological stressor (Trier Social Stress Test). Levels of serotonin 1A receptor binding on positron emission tomography with [11C]WAY-100635 were also obtained from all participants. The relationship between [11C]WAY-100635 binding and cortisol was examined using mixed linear effects models with group (major depressive disorder vs control), cortisol, brain region, and their interactions as fixed effects and subject as a random effect. RESULTS: We found a positive correlation between post-stress cortisol measures and serotonin 1A receptor ligand binding levels across multiple cortical and subcortical regions, independent of diagnosis and with both types of stress. The relationship between [11C]WAY-100635 binding and cortisol was homogenous across all a priori brain regions. In contrast, resting cortisol levels were negatively correlated with serotonin 1A receptor ligand binding levels independently of diagnosis, except in the RN. There was no significant difference in cortisol between major depressive disorder participants and healthy volunteers with either stressor. Similarly, there was no correlation between cortisol and depression severity in either stressor group. CONCLUSIONS: This study suggests that there may be a common underlying mechanism that links abnormalities in the serotonin system and hypothalamic-pituitary-adrenal axis hyper-reactivity to stress. Future studies need to determine how hypothalamic-pituitary-adrenal axis dysfunction affects mood to increase the risk of suicide in major depression.


Assuntos
Encéfalo/metabolismo , Transtorno Depressivo Maior/metabolismo , Hidrocortisona/metabolismo , Receptor 5-HT1A de Serotonina/metabolismo , Estresse Fisiológico/fisiologia , Estresse Psicológico/metabolismo , Adolescente , Adulto , Idoso , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Radioisótopos de Carbono , Cateterismo , Transtorno Depressivo Maior/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor Processual/diagnóstico por imagem , Dor Processual/metabolismo , Piperazinas , Tomografia por Emissão de Pósitrons , Piridinas , Compostos Radiofarmacêuticos , Descanso , Estresse Psicológico/diagnóstico por imagem , Adulto Jovem
6.
J Nerv Ment Dis ; 204(11): 845-850, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26894320

RESUMO

We aimed to examine the relationship between religion and suicide attempt and ideation. Three hundred twenty-one depressed patients were recruited from mood-disorder research studies at the New York State Psychiatric Institute. Participants were interviewed using the Structured Clinical Interview for DSM Disorders, Columbia University Suicide History form, Scale for Suicide Ideation, and Reasons for Living Inventory. Participants were asked about their religious affiliation, importance of religion, and religious service attendance. We found that past suicide attempts were more common among depressed patients with a religious affiliation (odds ratio, 2.25; p = 0.007). Suicide ideation was greater among depressed patients who considered religion more important (coefficient, 1.18; p = 0.026) and those who attended services more frequently (coefficient, 1.99; p = 0.001). We conclude that the relationship between religion and suicide risk factors is complex and can vary among different patient populations. Physicians should seek deeper understanding of the role of religion in an individual patient's life in order to understand the person's suicide risk factors more fully.


Assuntos
Depressão/psicologia , Entrevista Psicológica , Religião e Psicologia , Ideação Suicida , Tentativa de Suicídio/psicologia , Adulto , Depressão/diagnóstico , Depressão/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Religião , Fatores de Risco , Tentativa de Suicídio/prevenção & controle
8.
Int J Neuropsychopharmacol ; 17(3): 383-91, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24300434

RESUMO

Dopaminergic function is thought to be altered in major depression and, in animal studies, is reduced in omega-3 polyunsaturated fatty acid (PUFA) deficiency states. Therefore we studied PUFAs and resting prolactin, a marker for dopaminergic tone, and cerebrospinal fluid homovanillic acid (HVA), the chief dopamine metabolite. In medication-free adults (n = 23) with DSM-IV major depressive disorder (MDD), we measured plasma phospholipid levels of omega-3 PUFAs docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), the omega-6 PUFA arachidonic acid (AA), and plasma prolactin levels before and after administration of dl-fenfluramine (FEN). In a subset of patients (n = 14), cerebrospinal fluid levels of HVA and the serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), were obtained through lumbar puncture. Baseline prolactin was negatively correlated with omega-3 PUFAs (logDHA, F(1,21) = 20.380, p < 0.001; logEPA, F(1,21) = 10.051, p = 0.005) and positively correlated with logAA:DHA (F(1,21) = 15.263, p = 0.001), a measure of omega-6/omega-3 balance. LogDHA was negatively correlated with CSF HVA (Spearman's ρ = -0.675, p = 0.008) but not 5-HIAA (Spearman's ρ = -0.143, p = 0.626) after controlling for sex and HVA - 5-HIAA correlation. PUFAs did not predict the magnitude of the FEN-stimulated change in prolactin, considered to be a serotonin effect. The robust relationship of omega-3 PUFAs with dopaminergic but not serotonergic indices suggests that omega-6:omega-3 balance may impact depression pathophysiology through effects on the dopaminergic system.


Assuntos
Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/líquido cefalorraquidiano , Ácidos Graxos Insaturados/sangue , Ácido Homovanílico/líquido cefalorraquidiano , Adulto , Idoso , Análise de Variância , Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Feminino , Fenfluramina/uso terapêutico , Humanos , Ácido Hidroxi-Indolacético/líquido cefalorraquidiano , Masculino , Pessoa de Meia-Idade , Prolactina/sangue , Escalas de Graduação Psiquiátrica , Análise de Regressão , Adulto Jovem
9.
J Affect Disord Rep ; 152024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38283689

RESUMO

Emergency department (ED) visits for suicidal ideation or behavior have been increasing in all age groups, particularly younger adults. A rapid-acting treatment to reduce suicidal thinking, adapted for ED use, is needed. Previous studies have shown a single dose of ketamine can improve depression and suicidal ideation within hours. However, most studies used 40 min intravenous infusions which can be impractical in a psychiatric ED. The ER-Ketamine study we describe here is a randomized midazolam-controlled clinical trial (RCT; NCT04640636) testing intramuscular (IM) ketamine's feasibility, safety, and effectiveness to rapidly reduce suicidal ideation and depression in a psychiatric ED. A pre-injection phase involves screening, informed consent, eligibility confirmation, and baseline assessment of suicidal ideation, depression, and comorbidities. The randomized double-blind IM injection is administered in the ED under research staff supervision, vital sign monitoring, pharmacokinetic blood sampling, and clinical assessments. The post-injection phase occurs on a psychiatric inpatient unit with follow-up research assessments through four weeks post-discharge. Outcome measures are feasibility, safety, and effects on suicidal ideation and depression at 24 h post-injection, and through follow-up. The target sample is N = 90 adults in a major depressive episode, assessed by ED clinicians as warranting hospitalization for suicide risk. Here we report design, rationale, and preliminary feasibility and safety for this ongoing study. Demographics of the 53 participants (ages 18 to 65 years) randomized to date suggest a diverse sample tending towards younger adults.

10.
J Psychiatr Res ; 169: 224-230, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38043258

RESUMO

BACKGROUND: Pro-inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α are elevated in response to psychosocial stress; however, less is known about other inflammatory markers. METHODS: We explored response to the Trier Social Stress Test (TSST) of 16 cytokines and growth factors in patients with major depressive disorder (MDD, n = 12) vs. healthy volunteers (HV, n = 16). Outcomes were baseline and post-stress levels estimated by area under the curve (AUCi) and peak change over 3 timepoints. We also explored correlations between biomarkers and clinical characteristics. RESULTS: Baseline concentrations were higher in MDD for platelet-derived growth factor (PDGF)-AB/BB (p = 0.037, d = 0.70), granulocyte-macrophage colony-stimulating factor (GM-CSF, p = 0.033, d = 0.52), and IL-8 (p = 0.046, d = 0.74). After TSST, AUCi was higher in MDD for GM-CSF (p = 0.003, d = 1.21), IL-5 (p = 0.014, d = 1.62), and IL-27 (p = 0.041, d = 0.74). In MDD, depression severity correlated positively with soluble CD40L (sCD40L) for AUCi (Spearman's ρ = 0.76, p = 0.004) and with baseline vascular endothelial growth factor A (VEGFA, r = 0.85, p < 0.001), but negatively with baseline monokine induced by gamma interferon (MIG, aka CXCL9; r = -0.77, p = 0.003). CONCLUSIONS: Effect sizes were robust in this exploratory study, although interpretation of the results must be cautious, given small sample size and multiple comparisons. Differential study of stress-induced biomarkers may have important ramifications for MDD treatment.


Assuntos
Citocinas , Transtorno Depressivo Maior , Humanos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/uso terapêutico , Fator de Necrose Tumoral alfa , Biomarcadores , Estresse Psicológico
11.
J Affect Disord ; 328: 6-12, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36750161

RESUMO

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.


Assuntos
Viés de Atenção , Luto , Suicídio , Humanos , Pesar , Suicídio/psicologia , Atenção/fisiologia
12.
Psychiatry Res ; 326: 115324, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37390599

RESUMO

Time from first DSM4 major depressive episode (MDE) until treatment in the community was compared across racial/ethnic groups. This secondary analysis used structured baseline data from a depression research clinic (N = 260). Chi-square and survival analyses compared rates and delays to antidepressant medication and psychotherapy. Non-Hispanic Black and Hispanic (any race) participants had lower rates of both antidepressant medication and psychotherapy and longer delays to antidepressant medication compared with non-Hispanic White participants. The results underscore the need to reduce these disparities.


Assuntos
Transtorno Depressivo Maior , Disparidades em Assistência à Saúde , Tempo para o Tratamento , Humanos , Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Hispânico ou Latino , Psicoterapia , Grupos Raciais , Estados Unidos , Negro ou Afro-Americano
13.
J Affect Disord ; 341: 8-11, 2023 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-37619654

RESUMO

OBJECTIVE: Our group reported previously a comparable overall antisuicidal effect of lithium and valproate in bipolar patients. We investigated factors associated with higher antisuicidal efficacy of lithium in older individuals. METHODS: The age-related antisuicidal effect of lithium and valproate was compared in ninety-four (n = 94) high-risk bipolar suicide attempters who participated in a 2.5-year randomized, double-blind trial. RESULTS: Age significantly moderated the effect of lithium vs. valproate on the risk of suicide event during the study (z = -1.98, p = 0.049). We found that those who were 42 years or older (above the 75th percentile), and on lithium had significantly lower risk of suicidal behavior than older patients on valproate (>42y) or younger (<42 y) patients on either medication (interaction HR = 0.09, 95%CI: 0.01-0.89, z = -2.07, p = 0.039). This difference in risk differences was not explained away by age-related differences in the proportion of participants with bipolar II disorder (Fisher's test p = 0.020) or higher lethality of past suicide attempts in younger participants (Wilcoxon test p = 0.024); neither was there any correlation with age in the longitudinally measured blood lithium levels (t = 1.04, df = 36, p = 0.307) or valproate levels (t = -0.50, df = 41, p = 0.621). LIMITATIONS: Besides the fact that this is a secondary analysis, a limitation is that the study is not powered to detect suicide deaths or suicide attempts. CONCLUSION: Bipolar patients randomized to lithium and older than 42 years had less suicidal behavior compared to same aged patients on valproate or younger patients (<42 y) on either medication. This effect was independent of clinical and sociodemographic characteristics.


Assuntos
Transtorno Bipolar , Idoso , Humanos , Fatores Etários , Transtorno Bipolar/tratamento farmacológico , Lítio , Ideação Suicida , Ácido Valproico/farmacologia , Adulto , Pessoa de Meia-Idade
14.
J Affect Disord ; 325: 695-700, 2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36681306

RESUMO

BACKGROUND: Insecure attachment is associated with mental health morbidity. We explored associations between parent and offspring attachment style in a longitudinal study of families with a depressed parent. METHODS: Parents (N = 169) with a DSM-IV mood disorder and their adult offspring (N = 267), completed the Adult Attachment Questionnaire at one or more time points during up to 9.7 years of follow-up. Linear mixed effects models explored associations between parent and offspring anxious and avoidant attachment scores. Residualized models accounted for parent and offspring depression severity. RESULTS: Avoidant attachment scores were associated between parents and offspring with (p = .034) and without (p = .012) adjustment for baseline age and sex of parent and offspring. Depressed father-offspring relationships showed more avoidant attachment in offspring compared to depressed mother-offspring pairs (p = .010). After accounting for depression severity, parent average residualized avoidant attachment scores did not significantly correlate with those of offspring (unadjusted p = .052; adjusted p = .085), though the effect sizes did not change substantially, and 75 % of the correlation was retained. Parent-son relationships exhibited stronger avoidant attachment correlations compared to parent-daughter pairs (p = .048). LIMITATIONS: Small sub-sample of fathers, parent and offspring assessments not always completed at the same time, and use of a self-report attachment style instrument. CONCLUSIONS: Familial transmission of insecure avoidant attachment, a risk factor for negative mental health outcomes, merits research as a potential treatment target. In this preliminary study, its transmission to offspring seemed mostly independent of depression. Depressed fathers and their sons may deserve focus to reduce insecure avoidant attachment and improve clinical course.


Assuntos
Transtornos do Humor , Pais , Adulto , Humanos , Estudos Longitudinais , Pais/psicologia , Relações Pai-Filho , Saúde Mental , Apego ao Objeto
15.
Nutrients ; 15(21)2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37960195

RESUMO

Neurocognitive deficits are implicated in major depressive disorder (MDD) and suicidal behavior, and cognitive function may be affected by blood levels of polyunsaturated fatty acids (PUFAs). Neuroprotective functions have been described for omega-3 (n-3) PUFAs, while omega-6 (n-6) PUFAs exhibit broadly opposing activities. Both classes of PUFAs are linked to MDD and suicidal behavior. However, few studies have investigated the relationships between PUFAs and neurocognitive function with respect to MDD or suicidal behavior. Among participants with MDD (n = 45) and healthy volunteers (HV, n = 30) we assessed performance on tasks of attentional capacity and executive function and its relationship to plasma phospholipid PUFA levels, expressed as a percentage of total plasma phospholipids, for eicosapentaenoic acid (EPA%), docosahexaenoic acid (DHA%), and arachidonic acid (AA%). Regression models tested the correlations between PUFA levels and task performance in three groups: MDD with a history of suicide attempt (SA, n = 20), MDD with no attempts (NA, n = 25), and HV. Interaction testing indicated a significant positive correlation of EPA% with continuous performance test scores in the NA group (F = 4.883, df = 2,72, p = 0.01), a measure of sustained attention. The AA% correlated negatively with performance on two executive function tasks, object alternation (beta = -3.97, z-score = -2.67, p = 0.008) and the Wisconsin card sort (beta = 0.80, t-score = -2.16, df = 69, p = 0.035), after adjustment for group and age, with no group effects. Our findings suggest a role for PUFA imbalance in attentional functioning and executive performance; however, no MDD-specific effect was observed.


Assuntos
Transtorno Depressivo Maior , Ácidos Graxos Ômega-3 , Humanos , Fosfolipídeos , Ácidos Graxos Insaturados , Ácido Eicosapentaenoico , Ácidos Docosa-Hexaenoicos
16.
Eur Neuropsychopharmacol ; 70: 1-13, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36780841

RESUMO

We examined relationships between the serotonin system and stress in major depression and suicidal behavior. Twenty-five medication-free depressed participants (13 suicide attempters) underwent same-day [11C]DASB and [11C]CUMI-101 positron emission tomography (PET) imaging. Binding potential (BPND) to the serotonin transporter (5-HTT) and serotonin 1A (5-HT1A) receptor, respectively, was quantified using the NRU 5-HT atlas, reflecting distinct spatial distributions of multiple serotonin targets. Ecological momentary assessment (EMA) measured current stress over one week proximal to imaging. EMA stress did not differ between attempters and non-attempters. In all depressed participants, 5-HTT and 5-HT1A BPND were unrelated to EMA stress. There were region-specific effects of 5-HTT (p=0.002) and 5-HT1A BPND (p=0.03) in attempters vs. nonattempters. In attempters, region-specific associations between 5-HTT (p=0.03) and 5-HT1A (p=0.005) BPND and EMA stress emerged. While no post-hoc 5-HTT BPND correlations were significant, 5-HT1A BPND correlated positively with EMA stress in attempters in 9/10 regions (p-values<0.007), including the entire cortex except the largely occipital region 5. Brodmann-based regional analyses found diminished effects for 5-HTT and subcortically localized positive corrrelations between 5-HT1A and EMA stress, in attempters only. Given comparable depression severity and childhood and current stress between attempters and nonattempters, lower 5-HTT binding in attempters vs. nonattempters may suggest a biological risk marker. Localized lower 5-HTT and widespread higher 5-HT1A binding with stress among attempters specifically may suggest that a serotonergic phenotype might be a key determinant of risk or resiliency for suicidal behavior.


Assuntos
Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/metabolismo , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Ideação Suicida , Serotonina/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Depressão , Avaliação Momentânea Ecológica , Biomarcadores/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Receptor 5-HT1A de Serotonina/metabolismo
17.
Brain Behav Immun ; 25(6): 1272-8, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21605657

RESUMO

BACKGROUND: Inflammation has been linked to depression and suicide risk. One inflammatory process that has been minimally investigated in this regard is cytokine-stimulated production of kynurenine (KYN) from tryptophan (TRP). Recent data suggest that KYN increases in cerebrospinal fluid (CSF) are associated with depressive symptoms secondary to immune activation. KYN may alter dopaminergic and glutamatergic tone, thereby contributing to increased arousal, agitation and impulsivity - important risk factors in suicide. We hypothesized that patients with major depressive disorder (MDD) and a history of suicide attempt would have higher levels of KYN than depressed nonattempters, who in turn would have higher levels than healthy volunteers. METHODS: Plasma KYN, TRP, and neopterin were assayed by high performance liquid chromatography in three groups: healthy volunteers (n=31) and patients with MDD with (n=14) and without (n=16) history of suicide attempt. Analysis of variance tested for group differences in KYN levels. RESULTS: KYN levels differed across groups (F=4.03, df=(2,58), and p=0.023): a priori planned contrasts showed that KYN was higher in the MDD suicide attempter subgroup compared with MDD non-attempters (t=2.105, df=58, and p=0.040), who did not differ from healthy volunteers (t=0.418, df=58, and p=0.677). In post hoc testing, KYN but not TRP was associated with attempt status, and only suicide attempters exhibited a positive correlation of the cytokine activation marker neopterin with the KYN:TRP ratio, suggesting that KYN production may be influenced by inflammatory processes among suicide attempters. CONCLUSION: These preliminary results suggest that KYN and related molecular pathways may be implicated in the pathophysiology of suicidal behavior.


Assuntos
Transtorno Depressivo Maior/sangue , Cinurenina/sangue , Tentativa de Suicídio , Adolescente , Adulto , Idoso , Antidepressivos/uso terapêutico , Citocinas/fisiologia , Transtorno Depressivo Maior/tratamento farmacológico , Cloridrato de Duloxetina , Feminino , Humanos , Hypericum , Comportamento Impulsivo , Inflamação , Cinurenina/biossíntese , Masculino , Pessoa de Meia-Idade , Neopterina/sangue , Fitoterapia , Recidiva , Serotonina/metabolismo , Fumar/epidemiologia , Tiofenos/uso terapêutico , Triptofano/sangue , Adulto Jovem
18.
Front Psychiatry ; 12: 602976, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33897480

RESUMO

There is a public health need for improved suicide risk assessment tools. This pilot methodology study compared the assay sensitivity of computerized adaptive tests (CAT) of depression and suicidal ideation vs. traditional ratings in a randomized trial subgroup. The last 20 persons to enroll in a published ketamine trial in suicidal depression were studied. This subgroup received traditional and CAT ratings at baseline, 24 h post-infusion and follow-up week 2, 4, and 6: Hamilton Depression Rating Scale, Beck Depression Inventory, and Beck Scale for Suicidal Ideation vs. the CAT-Depression Inventory and CAT-Suicide Scale. Results showed larger effect sizes (ES) for CAT compared with traditional clinician-rated and self-report scales. Coefficients of variation for baseline measurements were lower for CAT compared with traditional scales. This is the first study to show that CAT may have greater assay sensitivity for treatment effects, particularly for suicidal ideation, compared with traditional clinician-rated and non-adaptive self-rated scales in a randomized trial. The findings suggest CAT can enable quick long-term follow-up assessments via cellphone, tablet, or computer while minimizing response bias due to repeated measurement of the same symptom items. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT01700829.

19.
Arch Suicide Res ; 25(3): 690-703, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32290789

RESUMO

In 2008, the Department of Veterans Affairs mandated that clinicians oversee the construction of a Suicide Safety Plan for every patient who is identified as "high risk" for suicide. While the Suicide Safety Plan is a mandated "best practice," there are currently no recommended guidelines for its augmentation in a group setting. To address this gap, a novel group intervention, "Project Life Force," (PLF; a 10-session manualized psychotherapy), was developed and piloted. Results indicate high feasibility and acceptability. Exploratory analysis revealed statistically significant decreases in suicidal thoughts/behaviors, depression, and hopelessness. Feedback from Veterans and PLF therapists is also discussed. Despite some limitations (e.g. small sample size) exploratory results suggest that PLF may be a promising treatment for Veterans with suicidal symptomology.


Assuntos
Prevenção do Suicídio , Veteranos , Humanos , Ideação Suicida
20.
Contemp Clin Trials ; 100: 106224, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33220488

RESUMO

BACKGROUND: The treatment of suicidal patients often suffers owing to a lack of integrated care and standardized approaches for identifying and reducing risk. The National Strategy for Suicide Prevention endorsed the Zero Suicide (ZS) model, a multi-component, system-wide approach to identify, engage, and treat suicidal patients. The ZS model is a framework for suicide prevention in healthcare systems with the aspirational goal of eliminating suicide in healthcare. While the approach is widely endorsed, it has yet to be evaluated in a systematic manner. This trial evaluates two ZS implementation strategies statewide in specialty mental health clinics. METHODS/STUDY DESIGN: This trial is the first large-scale implementation of the ZS model in mental health clinics using the Assess, Intervene, and Monitor for Suicide Prevention (A-I-M) clinical model. Using a hybrid effectiveness-implementation type 1 design, we are testing the effectiveness of ZS implementation in 186 mental health clinics in 95 agencies in New York State. Agencies are randomly assigned to either: "Basic Implementation" (BI; a large group didactic learning collaboratives) or "Enhanced Implementation" (EI; participatory small group learning collaboratives; enhanced consultation for site champions). Primary outcomes include suicidal behaviors, hospitalizations and Emergency Department visits; implementation outcomes include protocol adoption, protocol fidelity and barriers/facilitators to implementation. DISCUSSION: This project has the potential to have a significant public health impact by determining the effectiveness of the ZS model in mental health clinics, a setting where suicide attempts and suicides occur at a higher rate than any other healthcare setting. It will also provide guidance on the implementation level required to achieve uptake and sustainability of ZS. TRIAL REGISTRATION: N/A.


Assuntos
Pacientes Ambulatoriais , Psiquiatria , Atenção à Saúde , Humanos , Ideação Suicida , Tentativa de Suicídio
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