Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk

We propose a model wherein chronic stress results in glucocorticoid receptor resistance (GCR) that, in turn, results in failure to down-regulate inflammatory response. Here we test the model in two viral-challenge studies. In study 1, we assessed stressful life events, GCR, and control variables including baseline antibody to the challenge virus, age, body mass index (BMI), season, race, sex, education, and virus type in 276 healthy adult volunteers. The volunteers were subsequently quarantined, exposed to one of two rhinoviruses, and followed for 5 d with nasal washes for viral isolation and assessment of signs/symptoms of a common cold. In study 2, we assessed the same control variables and GCR in 79 subjects who were subsequently exposed to a rhinovirus and monitored at baseline and for 5 d after viral challenge for the production of local (in nasal secretions) proinflammatory cytokines (IL-1β, TNF-α, and IL-6). Study 1: After covarying the control variables, those with recent exposure to a long-term threatening stressful experience demonstrated GCR; and those with GCR were at higher risk of subsequently developing a cold. Study 2: With the same controls used in study 1, greater GCR predicted the production of more local proinflammatory cytokines among infected subjects. These data provide support for a model suggesting that prolonged stressors result in GCR, which, in turn, interferes with appropriate regulation of inflammation. Because inflammation plays an important role in the onset and progression of a wide range of diseases, this model may have broad implications for understanding the role of stress in health.     

Associations between oral health-related quality of life and emotional statuses in children and preadolescents

Oral Diseases (2012) 18 , 639–647 Objectives: To evaluate the associations between oral health‐related quality of life (OHRQoL) and emotional statuses in children and preadolescents. Methods: One hundred and forty‐five Brazilian students (8–14 years) were clinically examined for caries, gingivitis, fluorosis, malocclusions, and temporomandibular disorders (TMD). OHRQoL was measured using two global ratings of oral health (OH) and overall well‐being (OWB). The Revised Children’s Manifest Anxiety Scale (R‐CMAS) and Children’s Depression Inventory (CDI) were used to assess anxiety and depression, respectively. Saliva was collected 30 min after waking and at night to determine the diurnal decline in salivary cortisol (DDSC). The results were analyzed using non‐paired t test/one‐way ANOVA, Pearson’s correlation test, and multiple linear regression analyses. Results: 11–14‐year‐old participants had higher CDI scores (P < 0.01) and DDSC concentrations (P < 0.001). Participants with fewer caries and without gingivitis had higher DDSC concentrations (P < 0.05). TMD patients had higher DDSC concentrations and OWB ratings (P < 0.001). Girls had higher Revised Children’s Manifest Anxiety Scale (RCMAS) scores (P < 0.01). There was positive correlation between RCMAS and CDI scores and OWB ratings (P < 0.05). The OH model retained age (β =0.312; P < 0.001) and the OWB model retained TMD (β = 0.271; P < 0.001) and CDI scores (β=0.175; P < 0.05). Conclusions: Children and preadolescents with poor emotional well‐being are more sensitive to the impacts of OH and its effects on OWB.     

Sex dependent influence of a functional polymorphism in steroid 5‐α‐reductase type 2 (SRD5A2) on post‐traumatic stress symptoms

A non‐synonymous, single nucleotide polymorphism (SNP) in the gene coding for steroid 5‐α‐reductase type 2 (SRD5A2) is associated with reduced conversion of testosterone to dihydrotestosterone (DHT). Because SRD5A2 participates in the regulation of testosterone and cortisol metabolism, hormones shown to be dysregulated in patients with PTSD, we examined whether the V89L variant (rs523349) influences risk for post‐traumatic stress disorder (PTSD). Study participants (N = 1,443) were traumatized African‐American patients of low socioeconomic status with high rates of lifetime trauma exposure recruited from the primary care clinics of a large, urban hospital. PTSD symptoms were measured with the post‐traumatic stress symptom scale (PSS). Subjects were genotyped for the V89L variant (rs523349) of SRD5A2. We initially found a significant sex‐dependent effect of genotype in male but not female subjects on symptoms. Associations with PTSD symptoms were confirmed using a separate internal replication sample with identical methods of data analysis, followed by pooled analysis of the combined samples (N = 1,443, sex × genotype interaction P < 0.002; males: n = 536, P < 0.001). These data support the hypothesis that functional variation within SRD5A2 influences, in a sex‐specific way, the severity of post‐traumatic stress symptoms and risk for diagnosis of PTSD. © 2013 Wiley Periodicals, Inc.     

Somatostatin receptors: From signaling to clinical practice

Somatostatin is a peptide with a potent and broad antisecretory action, which makes it an invaluable drug target for the pharmacological management of pituitary adenomas and neuroendocrine tumors. Somatostatin receptors (SSTR1, 2A and B, 3, 4 and 5) belong to the G protein coupled receptor family and have a wide expression pattern in both normal tissues and solid tumors. Investigating the function of each SSTR in several tumor types has provided a wealth of information about the common but also distinct signaling cascades that suppress tumor cell proliferation, survival and angiogenesis. This provided the rationale for developing multireceptor-targeted somatostatin analogs and combination therapies with signaling-targeted agents such as inhibitors of the mammalian (or mechanistic) target of rapamycin (mTOR). The ability of SSTR to internalize and the development of rabiolabeled somatostatin analogs have improved the diagnosis and treatment of neuroendocrine tumors.     

抑郁症患者治疗前后血浆皮质醇水平的变化

目的:探讨抑郁症患者治疗前后血浆皮质醇水平的变化。方法:对160例抑郁症患者给予抗抑郁药治疗6周,分别于治疗前及治疗后进行汉密尔顿抑郁量表(HAMD)、汉密尔顿焦虑量表(HAMA)评估及血浆皮质醇水平检测。结果:本组治疗前后HAMD总分分别为(24.98±5.10)和(7.57±5.61);HAMA总分分别为(20.62±6.90)和(6.21±5.17);血浆皮质醇水平分别为(407.34±144.29)nmol/L和(354.64±137.13)nmol/L。治疗后HAMD总分、HAMA总分及血浆皮质醇水平较治疗前明显下降(P均<0.001);不同性别间血浆皮质醇水平差异无统计学意义(P>0.05);血浆皮质醇变化值与HAMD、HAMA减分率不相关(r=0.084,r=0.049;P均>0.05)。结论:抗抑郁药物治疗可显著降低抑郁症患者血浆皮质醇水平。