Understanding the neurobiology of suicidal behavior.

Our current knowledge about the neurobiology of suicide is still limited. Technical limitations and the complexity of the CNS are major obstacles. However, there is evidence for a hereditary disposition to suicide, which appears to be independent of diagnosis. Clinical, postmortem, genetic, and animal studies suggest that serotonin has a central role. The main regions of interest in the CNS have been the dorsal and median raphe nuclei in the midbrain that host the main serotonergic cell bodies and the prefrontal cortex, particularly the ventral PFC, innervated by the serotonergic system. In vivo and postmortem studies indicate serotonergic hypofunction in suicide and serious suicide attempts. This deficiency in turn can lead to a predisposition to impulsive and aggressive behavior, probably due to a breakdown in the inhibitory function of the ventral prefrontal cortex as a result of less serotonin input. In the context of this predisposition and the development of mental illness or other life stressors, the individual is at risk of acting on suicidal thoughts. Such deficient serotonin input into the PFC may arise as a result of genetic, parenting, head injury, and other effects. Identifying psychiatric, social, and environmental predictors of suicide are studied to improve prediction and prevention of suicide. A better understanding of the neurobiology of suicide can help detect at risk populations and help develop better treatment interventions.     

单、双相抑郁症自杀行为遗传效应的比较研究

目的　探讨单、双相抑郁症患者自杀行为的遗传效应有否差异。方法　对1 1 5例单相抑郁症及1 84例双相抑郁症患者应用家族史法进行研究,用多基因阈值理论进行遗传率的估算。结果　单、双相抑郁症患者自杀危险性均较其一级亲属高;患者一级亲属自杀危险性均较对照组一级亲属高;单相抑郁症患者自杀危险性较双相抑郁症患者高;单相抑郁症患者一级亲属自杀危险性较双相抑郁症患者一级亲属高;单相抑郁症患者自杀行为的加权平均遗传率及标准误较双相抑郁症的高,均有显著性差异。结论　单、双相抑郁症患者自杀行为均有明显的遗传效应;单、双相抑郁症患者自杀行为遗传效应存在差异,更应注意对单相抑郁症患者及一级亲属自杀行为进行监测、预防。     

Bipolar depression and suicidal behavior

Suicide is a frequent and tragic consequence of bipolar depression. The prevention of suicidal behavior (SB) need an assessment of vulnerability traits related related to SB (personal suicide history, impulsive traits...), characteristics of depression (mixed depression, subtype of bipolar disorder...), psychiatric comorbidities and stressors psycho-social. Meanwhile, the characteristics of suicidal behavior (ie: severe or multiple attempts) suggest a diagnosis of bipolar disorder rather than major depressive disorder. In addition to a correct screening of bipolar disorders and assessment of suicidal behavior, the removal of lethal means, networking and treatment of depression reduces the risk of suicidal behavior. Finally, lithium may have a particular interest in subjects at high risk of suicide.     

Habituation in rodents: a review of behavior, neurobiology, and genetics

Habituation to a novel environment in rodents is commonly defined as a change in exploratory or locomotor activity over time (intrasession) or with repeated exposures (intersession). While numerous neuroactive substances are known to influence habituation, neurotransmitters that play particularly important roles are serotonin, acetylcholine, dopamine and glutamate. Although habituation is a complex process, studies over the past two decades have demonstrated that there is a genetic component. At present, although researchers are still attempting to isolate key genes that control habituation, findings in mutant mice have begun to highlight some of the genes that could play a role. The challenge will be in deciphering what genes are directly involved in the process of habituation, what genes indirectly influence habituation through a secondary mechanism, and what genes have no role in habituation but are only affected as part of the downstream cascade.     

Modeling effects on suicidal behavior

Knowledge of suicidal behavior, i.e., psychiatric patients indicating that they have an acquaintance or relative who has attempted or committed suicide, has been cited as a risk factor in the assessment of suicide potential. The authors evaluated psychiatric patients hospitalized for a suicide attempt (N = 30), serious suicidal ideation (N = 26), or other non-suicide-related reasons (N = 20) and also a control group of 18 patients admitted for orthopaedic surgery. Information derived from a structured clinical interview revealed that suicide attempters have fewer suicidal models than individuals in the other patient groups, and they are more interpersonally distant from the models they do know. Depression level was not positively related to the recall and reporting of suicidal models. Measures assessing suicide-related beliefs revealed that suicide attempters rated suicide as an effective solution for problems to a greater extent that did patients in the remaining three groups. The implications of these results for social learning models of suicidal behavior are discussed.     

Alcohol abuse, depression, and suicidal behavior in schizophrenia.

Alcohol use was correlated with depression and suicidal behavior in two independent studies of schizophrenic outpatients. Depression alone accounted for over 80% of the explained variance in suicidal behavior in both studies; alcohol use alone and the correlation between depression and alcohol use accounted for only small amounts of variance.     

Clinical aspects of suicidal behavior relevant to genetics

A major hindrance to determining the underlying biology of suicide is the heterogeneity of the phenotype. Not only are there various forms of self-harm and suicidal behaviors but even the finite act of dying by suicide can occur in multiple psychosocial contexts. Of all the different forms of fatal and non-fatal suicidal behaviors, the one that received the most attention is the aggressive impulsive type, which seems to occur in younger people and to cut across nosological entities, although its most classical expression occurs in borderline personality disorder. This focus should not obscure the fact that other forms of suicidal behavior such as those related to demoralization or wounded honor (narcissism) may well have different underlying genetic diatheses.     

抑郁症患者下丘脑-垂体-肾上腺轴功能与自杀行为

目的：了解抑郁症患者自杀行为与下丘脑－垂体－肾上腺（ＨＰＡ）轴的关系。方法：对２５例抑郁症患者行地塞米松抑制试验（ＤＳＴ）,其中伴有自杀行为的１２例,不伴自杀行为的１３例,并进行为期１年的随访。结果：自杀组和无自且的ＤＳＴ脱抑制率无明显差异。血有皮质醇水平与汉密尔顿抑郁量（ＨＡＭＤ）评分有明显相关。随访期间所有受试者均未发生新的自杀行为。结论：抑随症患者的ＨＰＡ轴功能失调与自杀行为有关,但并不增加     

5-Hydroxytryptamine 1A receptors, major depression, and suicidal behavior.

BACKGROUND: Several lines of evidence suggest a clear relationship between serotonin (5-hydroxytryptamine, 5-HT) hypoactivity and suicidal behavior across several psychiatric diagnoses. Few data are available, however, regarding the possible specific role of 5-HT1A receptors in the biology of suicidality. Therefore, the aim of our study was to use a neuroendocrine strategy to test the hypothesis of a role for 5-HT1A receptors in the biology of suicidal behavior. METHODS: Hormonal (adrenocorticotropic hormone [ACTH], cortisol, prolactin [PRL]) and temperature responses after administration of flesinoxan, a highly potent and selective 5-HT1A receptor full agonist, were assessed in 40 inpatients with major depression, divided into two subgroups (20 suicide attempters and 20 nonattempters), compared with 20 normal control subjects matched for gender and age. RESULTS: Compared with nonattempters, suicide attempters exhibited significantly lower PRL (p = .01), cortisol (p = .014), and temperature (p = .0002) responses. Prolactin (p = .007), cortisol (p = .04), and temperature (p = .00003) responses were also decreased in suicide attempters compared with normal control subjects. In contrast, we did not observe any significant differences in hormonal or temperature responses to flesinoxan between depressed patients without a history of suicide attempt and normal control subjects. CONCLUSIONS: The present study tends to confirm the role of 5-HT and more specifically 5-HT1A receptors in the biology of suicidal behavior in major depression.     

Hypothalamic-pituitary-adrenal axis function and suicidal behavior in depression.

Hypothalamic-pituitary-adrenal (HPA) axis function was examined in relation to suicidal behavior in depression. There were no significant differences between depressed patients who had or had not attempted suicide for either cerebrospinal fluid concentrations of corticotropin-releasing hormone, plasma cortisol levels predexamethasone or postdexamethasone, or for urinary-free cortisol outputs. However, depressed patients who had made a violent suicide attempt had significantly higher 4 PM and maximum postdexamethasone plasma cortisol levels, and significantly more of them were cortisol nonsuppressors than patients who had made nonviolent suicide attempts. A 5-year follow-up was carried out. There were no significant differences on indices of HPA function between depressed patients who did or did not reattempt suicide during the follow-up or who had never attempted suicide. These results suggest the possibility that dysregulation of the HPA axis may be a determinant of violent suicidal behavior in depression.     

Hypothalamus-pituitary-adrenal system regulation and suicidal behavior in depression.

BACKGROUND: One of the most demanding tasks in psychiatry is to protect patients from suicidal attempts. Preventive strategies could be improved by increasing our knowledge on the pathophysiologic disturbances underlying this behavior. More than 70-80% of suicides occur in the context of depressive disorders, in which dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis is one of the most prominent neurobiological findings. So far data on the involvement of the HPA axis in the pathophysiology of suicidal behavior in depressed patients are controversial. METHODS: In this retrospective study, we administered the combined dexamethasone-suppression/CRH stimulation (Dex/CRH) test to 310 patients with a depressive syndrome characterized at admission for acute and past suicidal behavior within the first 10 days after hospitalization. RESULTS: Suicidal behavior in depressed patients, including past and recent suicide attempts as well as suicidal ideation, was associated with a lower adrenocorticotropin and cortisol response in the combined Dex/CRH test, with lowest hormone levels observed in patients with a recent suicide attempt. DISCUSSION: The findings suggest that suicidal behavior may alter HPA axis regulation in depressed patients. Large-scale prospective studies assessing neuroendocrine changes may help to develop predictors for an early identification of patients at risk for committing suicide.     

青少年抑郁症患者自杀行为的影响因素研究

目的 探讨家庭及其他因素对青少年抑郁症患者自杀行为的影响。方法 选取于 2020 年6 月至 2021 年 12 月在荆门市第二人民医院儿童青少年心理科住院的 126 例青少年抑郁症患者进行横断面调查,根据近 6 个月内是否有自杀行为分为自杀组（n=76）及非自杀组（n=50）。采用一般情况调查表、患者健康问卷抑郁症状群量表（PHQ-9）、自杀意念自评量表（SIOSS）、家庭亲密度与适应性评定量表（FACES Ⅱ-CV）对两组患者的一般资料、抑郁程度、自杀意念、家庭分型进行比较。采用 Spearman 相关分析患者自杀行为与一般资料、PHQ-9、SIOSS、FACES Ⅱ-CV 评分的相关性。采用二元 Logistic 回归模型对患者自杀行为的影响因素进行分析。结果 自杀组饮酒者占 40.8%（31/76）,有精神疾病家族史者占 27.6%（21/76）,分别高于非自杀组的 20.0%（10/50）、12.0%（6/50）,差异有统计学意义（P＜ 0.05）。自杀组患者 PHQ-9 评分、SIOSS 总分、绝望因子评分及睡眠因子评分高于非自杀组［19.0（15.0,21.8）分比 15.0（10.8,19.0）分、15.0（14.0,16.8）分比 13.0（11.0,15.0）分、12.0（10.3,12.0）分比 10.0（7.8,12.0）分、3.0（2.0,3.0）分比 2.0（1.0,3.0）分］,家庭亲密度评分低于非自杀组［50.5（43.3,57.0）分比 57.5（48.8,65.5）分］,差异均有统计学意义（P＜ 0.05）。自杀组患者中极端型家庭占 67.1%（51/76）,高于非自杀组的 44.0%（22/50）,差异有统计学意义（P＜ 0.05）。患者自杀行为与家庭亲密度呈负相关（r=-0.224,P＜0.05）,与 PHQ-9 评分、SIOSS 总分、绝望因子评分、睡眠因子评分、饮酒、有精神疾病家族史呈正相关（r=0.346、0.373、0.361、0.324、0.206、0.217、0.186;P＜ 0.05）。二元 Logistic 回归分析显示,饮酒（OR=3.066,95%CI=1.184～7.941）、家 庭 适 应 性 高（OR=1.126,95%CI=1.034～1.227）、PHQ-9 评 分 高（OR=1.197,95%CI=1.087～1.317）是青少年抑郁症患者自杀行为的危险因素（P＜ 0.05）,家庭亲密度高是自杀行为的保护因素（OR=0.878,95%CI=0.813～0.948）。结论 青少年抑郁症患者自杀行为发生率较高,家庭分型更多见于“僵硬 - 松散”的极端型家庭,有饮酒行为、严重抑郁、家庭关系不良者更容易自杀     

Pilot randomized clinical trial of an SSRI vs bupropion: effects on suicidal behavior, ideation, and mood in major depression

Randomized controlled trials in depressed patients selected for elevated suicidal risk are rare. The resultant lack of data leaves uncertainty about treatment in this population. This study compared a serotonin reuptake inhibitor with a noradrenergic/dopaminergic antidepressant in major depression with elevated suicidal risk factors. We conducted a double-blind, randomized, clinical pilot trial of paroxetine (N=36) or bupropion (N=38) in DSM IV major depression with a suicide attempt history or current suicidal ideation. The effects during acute (8 weeks) and continuation treatment (up to 16 weeks) were measured. Main outcomes were suicidal behavior and ideation. The secondary outcome was modified 17-item Hamilton Depression Rating Scale score subtracting the suicide item (mHDRS-17). Treatment was not associated with time to a suicidal event and no treatment main effect or treatment × time interaction on suicidal ideation or mHDRS-17 was found. Exploratory model selection showed modest advantages for paroxetine on: (1) mHDRS-17 (p=0.02); and (2) in a separate model adjusted for baseline depression, for suicidal ideation measured with the Beck Scale for Suicidal Ideation (p=0.03), with benefit increasing with baseline severity. Depressed patients with greater baseline suicidal ideation treated with paroxetine compared with bupropion appeared to experience greater acute improvement in suicidal ideation, after adjusting for global depression. Given the lack of evidence-based pharmacotherapy guidelines for suicidal, depressed patients-an important public health population-this preliminary finding merits further study.     

Clinical determinants of suicidal ideation and behavior in geriatric depression

BACKGROUND: The aim of this study was to find clinical characteristics that can identify elderly patients with depression at risk for suicidal ideation and to determine their prognosis. METHOD: Suicidal ideation, past suicidal behavior, severity of depression, cognitive impairment, medical burden, disability, and social support were studied in 354 patients with depression aged 61 to 93 years. The patients had in-person evaluations every 6 months and telephone evaluations for a mean of 1.8 years (SD, 2.2). RESULTS: During the index episode, suicidal ideation was predicted by previous suicide attempts with serious intent (odds ratio [OR], 2.82; 95% confidence interval [CI], 1.37-5.80), severity of depression (OR, 1.09; 95% CI, 1.03-1.16), and poor social support (OR, 1.77; 95% CI, 1.18-2.65). Suicide attempts during the year prior to entry were reported by patients with a severe index episode (OR, 1.05; 95% CI, 1.00-1.11), impaired instrumental activities of daily living (OR, 0.78; 95% CI, 0.67-0.93), and limited impairment in activities of daily living (OR, 1.53; 95% CI, 1.10-2.14). At the initial evaluation, severity of depression, previous attempts, and seriousness of suicidal intent during previous attempts predicted the course of suicidal ideation (concordance correlation, 0.78). During follow-up, contemporaneous severity of depression was the most important determinant of suicidal ideation over time (concordance correlation, 0.88). CONCLUSIONS: Elderly individuals with severe depression, history of suicide attempts with serious intent, and poor social support are most likely to have suicidal ideation and should be targeted for appropriate interventions. Severity of depression is the strongest predictor of the course of suicidal ideation.     

低血清胆固醇与女性抑郁症的自杀行为

目的　本文对女性抑郁症患者的血清胆固醇水平与自杀行为的关系进行了探讨。方法　对 116例样本进行血清胆固醇水平测定 ,其中抑郁症伴自杀行为的 40例 ,抑郁症不伴自杀行为的 3 6例 ,正常人 40例。结果　抑郁症伴有自杀行为组血清胆固醇水平明显低于无自杀行为组和正常对照组。血清胆固醇水平与自杀的严重程度呈明显相关。结论　我们认为低血清胆固醇水平可增加女性抑郁症自杀的风险。推测低血清胆固醇导致的自杀行为可能与中枢 5 羟色胺 ( 5 HT)功能降低有关。