Elevated repetitive behaviors are associated with lower diurnal salivary cortisol levels in autism spectrum disorder

Previously, we reported a subgroup of children with autism spectrum disorders (ASD) had consistently high rates of repetitive behaviors (RBs) with abnormal sensory sensitivity. Given evidence of lower cortisol levels in response to stress and associated sensory sensitivity in the ASD population, this pilot study evaluates whether the presence of RBs reflects an underlying pathophysiology related to cortisol regulation. Diurnal salivary cortisol from 21 children with ASD and high versus low occurrence RBs were collected at four time points over three consecutive days. Although a typical decline in salivary cortisol was observed, participants in the high RB group showed 36% lower diurnal salivary cortisol than the low RB group. Age, IQ, RB type, and sleep quality were unrelated to observed differences. These findings suggest that RBs may serve to mitigate distress or that the glucocorticoid system has been down regulated in association with prolonged distress in this sample population.     

伴发糖尿病的抑郁症患者下丘脑-垂体-肾上腺轴功能的对照研究

目的研究共病糖尿病的抑郁症患者下丘脑-垂体-肾上腺轴(HPA)功能的特点及在抑郁患者的糖尿病发生机制中的意义。方法同时诊断有糖尿病的抑郁症患者(病例组,n=35)测定空腹血糖、糖负荷后2小时血糖、进行地塞米松抑制试验,并与正常糖代谢的抑郁症患者(对照组,n=35)对照。结果①病例组抑制前8:00、16:00血浆皮质醇浓度及抑制后8:00血浆皮质醇浓度[分别为(587±268)nmol/L、(382±163)nmol/L、(276±159)nmol/L]显著高于对照组[分别为(463±184)nmol/L、(290±141)nmol/L、(186±114)nmol/L],差异有统计学意义(均P0.05);②病例组地塞米松抑制试验脱抑制率为74.1%,显著高于对照组的45.7%(P0.05);③病例组抑制前8:00、抑制后8:00的血浆皮质醇浓度与空腹血糖值正相关(r=0.388、0.468,均P0.05)。结论伴发糖尿病的抑郁患者与正常糖代谢的抑郁症患者相比,有更为显著的H PA功能异常;H PA轴功能异常可能是抑郁患者中糖尿病发生的重要起病机制之一。     

Family environment is associated with HPA-axis activity in adolescents. The TRAILS study

The purpose of the present study was to investigate the developmental programming part of the theory of biological sensitivity to context using family environmental factors and hypothalamus-pituitary-adrenal (HPA) axis functioning. Specifically, we investigated whether perceived parenting (Rejection and Emotional Warmth) and socio-economic status (SES) predicted basal cortisol levels and the cortisol awakening response (CAR). In a population-based cohort of 1594 adolescents (mean age = 11.08, SD = 0.54) we assessed salivary cortisol, SES and perceived parenting. Perceived parental Emotional Warmth showed an inverse, linear association with basal cortisol levels. In addition, there was a curvilinear relationship between SES and both basal cortisol levels and the CAR. Our findings with regard to basal cortisol levels confirmed our hypothesis: lower basal HPA-axis activity in both high and low SES families compared to intermediate SES families.     

Serum lipid concentrations in Croatian veterans with post-traumatic stress disorder,post-traumatic stress disorder comorbid with major depressive disorder,or major depressive disorder

The aim of this study was to assess eventual differences in serum cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, LDL-C/HDL-C ratio between veterans with combat-related post-traumatic stress disorder (PTSD) only or comorbid with major depressive disorder (MDD), veterans with combat experiences with MDD, and healthy control group. PTSD and/ or MDD were diagnose according to structured clinical interview based on DSM-IV criteria. Additional criteria to diagnose PTSD were Clinician Administered PTSD Scale (CAPS), and to diagnose MDD Montgomery-Asberg Depression Rating Scale (MADRAS). Serum lipid concentrations were determined by using the enzyme-assay method. Veterans with combat-related PTSD as well as veterans with combat-related PTSD comorbid with MDD showed significantly higher concentrations of cholesterol (F=9.858, p<0.01), triglycerides (F=10.112, p<0.01), LDL-C (F=11.145, p<0.01), and LDL-C/HDL-C ratio (F=8.346, p<0.01) vs. veterans with MDD or healthy control group. Contrary healthy control group and veterans with MDD showed significantly higher concentrations of HDL-C (F=8.421, p<0.01), vs. veterans with PTSD or PTSD comorbid with MDD. In conclusion, there are no differences in serum lipid concentrations between veterans with combat-related PTSD and PTSD comorbid with MDD, but they have higher lipid concentrations than veterans with MDD or healthy control subjects.     

Poor sleep the night before an experimental stress task is associated with reduced cortisol reactivity in healthy women

Sleep disruption is a growing problem that may have serious health effects. As stress-induced increases in cortisol are thought to be a key adaptive process it is important to examine how this response is affected by sleep. The current study investigated the association of four sleep parameters (objective/subjectively measured sleep quality and quantity) and subsequent salivary cortisol reactivity (maximal change from baseline) to an experimental stressor in 53 healthy women. Objective actigraphy monitoring and self-report diaries were used to assess sleep. Results revealed that individuals with lower objective sleep quality (wake percentage during sleep) had a blunted response to the experimental stressor. No associations were found between cortisol reactivity and actigraphy-derived sleep quantity, or either of the self-reported sleep variables. Results are discussed with regard to the possible adverse health effects that may result from poor sleep quality and a blunted cortisol response to stress.     

TNF-alpha −308G>A polymorphism is associated with suicide attempts in major depressive disorder

Background

Despite the substantial role of the cytokine network in depression and suicide, few studies have investigated the role of genetic polymorphisms of pro- and anti-inflammatory cytokines in suicide in major depressive disorder (MDD). The aim of this study was to investigate whether tumor necrosis factor-alpha (TNF-alpha) −308G>A, interferon-gamma (IFN-gamma) +874A>T, and interleukin-10 (IL-10) −1082A>G are associated with increased risk for suicide attempts in MDD.

Methods

Among patients with MDD, 204 patients who had attempted suicide and 97 control patients who had not attempted suicide were recruited. A chi-square test was used to identify a possible risk genotype or allele type for suicide. A subsequent multivariate logistic regression analysis was conducted to investigate the influence of a risk genotype or allele type adjusted for other environmental factors. The lethality of the suicide attempt was also tested between genotype and allele types among suicidal patients with MDD.

Results

The GG genotype of the TNF-alpha −308G>A polymorphism was found to significantly increase risk for suicide attempt (adjusted OR=2.630, 95% CI=1.206 to 5.734). IFN-gamma +874A>T and IL-10 −1082A>G were not associated with risk for suicide. Lethality of the suicide attempt was not associated with any of the three cytokine genotypes or allele types.

Limitations

Limitations include a relatively small sample size and a cross-sectional design.

Conclusions

TNF-alpha −308G>A polymorphism is an independent risk factor for suicide attempts in MDD. Future studies should clarify the neural mechanisms by which the GG genotype of TNF-alpha −308G>A influences suicide in MDD.     

Social support and enhanced suppression of adrenocorticotropic hormone and cortisol responses to hypothalamic-pituitary-adrenal function and thyrotropin-releasing hormone tests in patients with major depressive disorder

The results of the thyrotropin-releasing hormone (TRH) stimulation test and the combined dexamethasone/corticotropin-releasing hormone (DEX/CRH) test are believed to correlate with social support status in patients with major depressive disorder. We studied 41 consecutive patients hospitalized for major depressive disorder and tested their responses to DEX/CRH and TRH on hospital days 4–7. ΔMAX TSH and ΔMAX cortisol were measured. Multiple regression analysis found that social support questionnaire (SSQ-A) and SSQ-B scores were significantly related to ΔMAX cortisol and ΔMAX TSH, respectively, at the time of admission. Social support might contribute partially to the TRH and DEX/CRH test results in patients with major depressive disorder.     

TPH1 218A/C polymorphism is associated with major depressive disorder and its treatment response

The association between the tryptophan hydroxylase 1 (TPH1) 218A/C polymorphism and (1) severity of major depressive disorder (MDD) and (2) response to treatment was studied. There were three study populations, the first consisting of 119 treatment-resistant MDD inpatients treated with electro-convulsive therapy (ECT), and the second of 98 MDD open care patients treated with selective serotonin reuptake inhibitors (SSRI). In addition, there was a control population of 395 healthy blood donors. The first aim of the study was to compare the genotypes of the patient with those of the healthy controls and between patient populations. The second aim was to compare the genotypes of MDD patients achieving remission with basic SSRI treatment (MADRS < 8) with the genotypes of non-responders to ECT (defined as MADRS > 15). TPH1 218A/C polymorphism was associated with the risk of MDD. CC genotype was significantly more common in patients (including both ECT and SSRI treated patients) than in controls (38.2% and 26.8% respectively; p = 0.008), and its frequency was significantly higher in more severe forms of depression, i.e. in ECT treated patients compared with SSRI treated patients (42.0% and 33.7%, p = 0.026). CC genotype was also associated with lower probability of achieving remission. It was significantly more frequent among ECT non-responders than among SSRI remitters (53.1% and 23.3%, p = 0.049). In this Finnish population TPH1 218A/C polymorphism was associated with the risk of MDD and treatment response; CC genotype was associated with the increased risk of MDD and lower probability of responding treatment. Further studies with larger samples will be required to confirm the results.     

Tryptophan hydroxylase 2 gene is associated with major depressive disorder in a female Chinese population

Background

Previous candidate gene studies of major depressive disorder (MDD) have provided inconclusive evidence of association for genes with strong biological rationale for MDD. In this study, we aimed to investigate the association of tryptophan hydroxylase 2 gene with MDD and its treatment response in the Chinese Han population.

Methods

Three hundred and sixty eight depressed patients who met DSM-IV criteria for major depressive disorder were recruited for the study. 371 normal controls were recruited from local community. Patients and normal controls were genotyped for TPH2 (rs4290270 and rs7305115) variants by polymerase chain reaction. Male and female subjects were analyzed separately.

Results

No differences were found in the frequencies of the single alleles and genotypes of the tested polymorphisms between MDD patients and normal group. The frequency of the A-A haplotype was significantly higher in female MDD compared to healthy female controls (P < 0.05). No significant association with treatment response was discovered in haplotype and single-marker analysis.

Limitations

This study lacks a placebo control and we cannot definitively exclude the possibility that some patients in the responder group responded to the placebo effect alone.

Conclusion

The result suggests that TPH2 gene may have a gender dependent effect on susceptibility to MDD but not with its treatment response in Chinese Han population. Further studies are needed to replicate the association that we observed.     

Treatment response for acute depression is not associated with number of previous episodes: Lack of evidence for a clinical staging model for major depressive disorder

Mental illness has been observed to follow a neuroprogressive course, commencing with prodrome, then onset, recurrence and finally chronic illness. In bipolar disorder and schizophrenia responsiveness to treatment mirrors these stages of illness progression, with greater response to treatment in the earlier stages of illness and greater treatment resistance in chronic late stage illness. Using data from 5627 participants in 15 controlled trials of duloxetine, comparator arm (paroxetine, venlafaxine, escitalopram) or placebo for the treatment of an acute depressive episode, the relationship between treatment response and number of previous depressive episodes was determined. Data was dichotomised for comparisons between participants who had >3 previous episodes (n=1697) or ≤3 previous episodes (n=3930), and additionally for no previous episodes (n=1381) or at least one previous episode (n=4246). Analyses were conducted by study arm for each clinical trial, and results were then pooled. There was no significant difference between treatment response and number of previous depressive episodes. This unexpected finding suggests that treatments to reduce symptoms of depression during acute illness do not lose efficacy for patients with a longer history of illness.