Aggressive behavior linked to corticotropin-reactive autoantibodies.

BACKGROUND: Altered stress response is characteristic for subjects with abnormal aggressive and antisocial behavior, but the underlying biological mechanisms are unclear. We hypothesized that autoantibodies (autoAbs) directed against several stress-related neurohormones may exist in aggressive subjects. METHODS: Using enzyme-linked immunosorbent assay, we studied whether autoAbs directed against corticotropin (ACTH), alpha-melanocyte-stimulating hormone (alpha-MSH), oxytocin, and vasopressin are present in serum of male subjects with conduct disorder and prisoners with history of violence. Healthy blood donors served as control subjects. RESULTS: Both conduct disorder and prisoners groups displayed strongly increased levels of ACTH-reactive immunoglobulin G (IgG) and immunoglobulin M (IgM) autoAbs compared with control subjects. Levels of oxytocin-reactive IgM autoAbs were slightly increased in both groups of aggressive subjects, whereas levels of vasopressin-reactive IgG and IgM autoAbs were lower only in conduct disorder. No differences in the levels of alpha-MSH-reactive autoAbs were found between aggressive and control subjects. CONCLUSIONS: High levels of ACTH-reactive autoAbs as well as altered levels of oxytocin- and vasopressin-reactive autoAbs found in aggressive subjects may interfere with the neuroendocrine mechanisms of stress and motivated behavior. Our data suggest a new biological mechanism of human aggressive behavior that involves autoAbs directed against several stress-related neurohormones.     

卒中后抑郁的神经生物学异常

卒中后抑郁是卒中后的常见并发症,严重影响患者神经功能的恢复。文章从发生率、病灶解剖学、病理生理学和神经内分泌特点等方面来阐述卒中后抑郁的神经生物学变化。     

Behavioral,neuroendocrine and physiological indicators of the circadian biology of male and female rabbits

Adult rabbits show robust circadian rhythms of: nursing, food and water intake, hard faeces excretion, locomotion, body temperature, blood and intraocular pressure, corticosteroid secretion, and sleep. Control of several circadian rhythms involves a light‐entrained circadian clock and a food‐entrained oscillator. Nursing periodicity, however, relies on a suckling stimulation threshold. Brain structures regulating this activity include the paraventricular nucleus and preoptic area, as determined by lesions and quantification of cFOS‐ and PER1 clock gene‐immunoreactive proteins. Melatonin synthesis in the rabbit pineal gland shows a diurnal rhythm, with highest values at night and lowest ones during the day. In kits the main zeitgeber is milk intake, which synchronizes locomotor activity, body temperature, and corticosterone secretion. Brain regions involved in these effects include the median preoptic nucleus and several olfactory structures. As models for particular human illnesses rabbits have been valuable for studying glaucoma and cardiovascular disease. Circadian variations in intraocular pressure (main risk factor for glaucoma) have been found, with highest values at night, which depend on sympathetic innervation. Rabbits fed a high fat diet develop cholesterol plaques and high blood pressure, as do humans, and such increased fat intake directly modulates cardiovascular homeostasis and circadian patterns, independently of white adipose tissue accumulation. Rabbits have also been useful to investigate the characteristics of sleep across the day and its modulation by infections, cytokines and other endogenous humoral factors. Rabbit circadian biology warrants deeper investigation of the role of the suprachiasmatic nucleus in regulating most behavioral and physiological rhythms described above.     

A previously uncharacterized role for estrogen receptor beta: defeminization of male brain and behavior

Sex differences in brain and behavior are ubiquitous in sexually reproducing species. One cause of sexual dimorphisms is developmental differences in circulating concentrations of gonadal steroids. Neonatal testes produce androgens; thus, males are exposed to both testosterone and estradiol, whereas females are not exposed to high concentrations of either hormone until puberty. Classically, the development of neural sex differences is initiated by estradiol, which activates two processes in male neonates; masculinization, the development of male-type behaviors, and defeminization, the loss of the ability to display female-type behaviors. Here, we test the hypothesis that defeminization is regulated by estrogen receptor beta (ERbeta). Adult male ERbeta knockout and WT mice were gonadectomized, treated with female priming hormones, and tested for receptive behavior. Indicative of incomplete defeminization, male ERbeta knockout mice showed significantly higher levels of female receptivity as compared with WT littermates. Testes-intact males did not differ in any aspects of their male sexual behavior, regardless of genotype. In olfactory preference tests, males of both genotypes showed equivalent preferences for female-soiled bedding. Based on these results, we hypothesize that ERbeta is involved in defeminization of brain and behavior. This aspect of ERbeta function may lead to developments in our understanding of neural-based sexually dimorphic human behaviors.     

Lithium augmentation increases post-dexamethasone cortisol in the dexamethasone suppression test in unipolar major depression

Although considerable evidence exists on the efficacy of lithium as an augmenting agent in refractory depression, the underlying neurobiology of this phenomenon is unknown. In patients with major depression, changes of the hypothalamic-pituitary-adrenocortical (HPA) system have been detected by means of the dexamethasone suppression test (DST), when administered during treatment with tricyclic antidepressants. We investigated whether the DST also reveals alterations of the HPA system during lithium augmentation. We also sought to identify whether response to lithium augmentation can be predicted with the DST. Twenty-five patients with unipolar major depression, who did not respond to an adequate antidepressant monotherapy of at least 4 weeks, were measured for basal (pre-dexamethasone, 0800h) cortisol and ACTH levels and were administered the DST the day before initiation of lithium augmentation treatment. The same neuroendocrine procedures were repeated after 3 to 4 weeks. Criteria of response to lithium augmentation, defined as a reduction of the Hamilton Depression Rating Scale (HDRS17) score by > or =50% and an end point score of 9 or less, were determined by weekly HDRS ratings. The DST revealed a statistically significant increase of the post-dexamethasone cortisol values (P = 0.021) and an increase in the post-dexamethasone ACTH values (P = 0.051) during lithium augmentation as compared to pre-treatment baseline evaluations. The pre-dexamethasone hormone values were unchanged. The number of non-suppressors at baseline was one and increased to three at follow-up. Results of DST did not predict response to lithium augmentation, which occurred in 40% of subjects. Results suggest that lithium augmentation increases HPA system activity, as indicated by the increase of post-dexamethasone cortisol and ACTH levels measured by the DST. This is in contrast to the established decline of HPA system activity during treatment with tricyclic antidepressants.     

生长激素和胰岛素样生长因子-Ⅰ对生殖的影响

除促性腺激素释放素和促性腺激素外,生长激素/胰岛素样生长因子-Ⅰ也影响着动物和人类垂体及性腺的功能.生长激素受体基因被敲除的雌鼠卵泡发育、排卵率、性成熟、对信息素信号的产生与应答和黄体的功能等都受到损伤;胰岛素样生长因子-Ⅰ缺乏和生长激素受体被敲除的雄鼠青春期延迟,精子发生和间质细胞的功能受到影响,神经内分泌-性腺功能减弱.这些小鼠的生殖力受到影响,可能是由垂体腺或性腺的功能低下引起.同样,人类Laron综合征(原发性生长激素不敏感综合征)的部分患者青春期延迟也是由于生长激素抵抗引起的.可见生长激素和胰岛素样生长因子-Ⅰ在青春期、生育期、垂体腺和性腺内分泌功能上起着重要的作用.     

Steroid hormones and maternal experience interact to induce glial plasticity in the cingulate cortex

Neocortical plasticity is not usually associated with changes in reproductive function. However, we have shown a six to 10-fold increase in the number of astrocytes labeled with glial fibrillary acidic protein (GFAP) and astrocytic basic fibroblast growth factor or FGF-2 (bFGF) in the cingulate cortex area 2 (Cg2) in postpartum rats, indicative of changes in connectivity in this area. In the present studies, we investigated the necessary and sufficient stimuli for these changes to occur. We show that 3 h of maternal experience combined with a hormonal treatment that mimics late pregnancy induces the astrocytic changes in Cg2 in virgin rats. The extent of these changes was similar to those of postpartum females. Sensitized virgin females did not show any astrocytic changes after 3 h of maternal behavior, suggesting that a similar amount of maternal experience alone is not sufficient to increase astrocytic bFGF- and GFAP-immunoreactivity in Cg2. Consistent with these data, eliminating early maternal experience by removing pups immediately postpartum abolishes the increased bFGF and GFAP protein expression in the cingulate cortex. These results suggest that maternal experience and hormonal state interact to produce astrocytic remodeling in the Cg2. The current results are consistent with a role for the cingulate cortex in maternal responsivity as suggested by early lesion studies in rats and more recent imaging studies in humans.     

急性脑出血患者下丘脑垂体激素变化的研究

目的:探讨急性脑出血患者发生脑内脏综合征的高危因素。方法:以电化学发光法测定37例急性期脑出血患者、24例脑梗死患者血清卵泡刺激素(FSH)、促甲状腺激素(TSH)、促肾上腺皮质激素(ACTH)水平的变化,并与30名健康体检者作对照。分析血清FSH、TSH、ACTH水平与脑出血患者病情程度、出血量、出血是否破入脑室或是否有脑中线结构移位的相关性。结果:脑出血组和脑梗死组的血清FSH、TSH水平均较对照组为低,且脑出血组低于脑梗死组(P均<0.01);脑出血和脑梗死组的血ACTH水平均较对照组高,且脑出血组高于脑梗死组(P均<0.01)。脑出血的病情越重、出血量越大、出血破入脑室或有脑中线结构移位时,患者血清FSH、TSH水平越低,ACTH水平越高。结论:在脑出血的危急状态下,机体可能发生类似于休克时血流重新分布的神经内分泌功能重新组合。     

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.