A neuroanatomical dissociation for emotion induced by music

Does feeling an emotion require changes in autonomic responses, as William James proposed? Can feelings and autonomic responses be dissociated? Findings from cognitive neuroscience have identified brain structures that subserve feelings and autonomic response, including those induced by emotional music. In the study reported here, we explored whether feelings and autonomic responses can be dissociated by using music, a stimulus that has a strong capacity to induce emotional experiences. We tested two brain regions predicted to be differentially involved in autonomic responsivity (the ventromedial prefrontal cortex) and feeling (the right somatosensory cortex). Patients with damage to the ventromedial prefrontal cortex were impaired in their ability to generate skin-conductance responses to music, but generated normal judgments of their subjective feelings in response to music. Conversely, patients with damage to the right somatosensory cortex were impaired in their self-rated feelings in response to music, but generated normal skin-conductance responses to music. Control tasks suggested that neither impairment was due to basic defects in hearing the music or in cognitively recognizing the intended emotion of the music. The findings provide evidence for a double dissociation between feeling emotions and autonomic responses to emotions, in response to music stimuli

The role of psychological stress in cancer initiation:clinical relevance and potential molecular mechanisms

The hypothesis that the physiological response to psychological stress influences the initiation of cancer is highly controversial. The link between initiating stressors, the psychological stress response, and disease is plausible considering that the stress response is associated with defined physiological outcomes and molecular mechanisms. In light of this, we review the clinical relevance of psychological stress on the risk of cancer, and we propose potential molecular pathways that may link the stress response to early stages of malignant cell transformation

Comparison of P53 mutation status, primary cytoreductive surgical outcomes, and overall survival in patients with ovarian cancer

Optimal surgical cytoreduction continues to be an important prognostic variable in patients with ovarian cancer independent of p53 mutational status. Among patients with suboptimal cytoreduction a p53 mutation may offer a survival advantage

Diurnal Cortisol and Survival in Epithelial Ovarian Cancer

IntroductionHypothalamic-pituitary-adrenal (HPA) deregulation is commonly observed in cancer patients, but its clinical significance is not well understood. We prospectively examined the association between HPA activity, tumor-associated inflammation, and survival in ovarian cancer patients prior to treatment.Materials and methodsParticipants were 113 women with ovarian cancer who provided salivary cortisol for three days prior to treatment for calculation of cortisol slope, variability, and night cortisol. Cox proportional hazard regression analyses were used to examine associations between cortisol and survival in models adjusting for disease stage, tumor grade, cytoreduction and age. On a subsample of 41 patients with advanced disease ascites fluid was assayed for levels of interleukin-6 (IL-6) and correlated with cortisol variables.ResultsEach cortisol measure was associated with decreased survival time, adjusting for covariates (all p<.041). A one standard deviation increase in night cortisol was associated with a 46% greater likelihood of death. Patients in the high night cortisol group survived an estimated average of 3.3 years compared to 7.3 years for those in the low night cortisol group. Elevated ascites IL-6 was associated with each cortisol measure (all r>36, all p<.017).DiscussionAbnormal cortisol rhythms assessed prior to treatment are associated with decreased survival in ovarian cancer and increased inflammation in the vicinity of the tumor. HPA abnormalities may reflect poor endogenous control of inflammation, dysregulation caused by tumor-associated inflammation, broad circadian disruption, or some combination of these factors. Nocturnal cortisol may have utility as a non-invasive measure of HPA function and/or disease severity

Mitochondria in epithelial ovarian carcinoma exhibit abnormal phenotypes and blunted associations with biobehavioral factors

Malignant tumor cells exhibit mitochondrial alterations and are also influenced by biobehavioral processes, but the intersection of biobehavioral factors and mitochondria in malignant tumors remains unexplored. Here we examined multiple biochemical and molecular markers of mitochondrial content and function in benign tissue and in high-grade epithelial ovarian carcinoma (EOC) in parallel with exploratory analyses of biobehavioral factors. First, analysis of a publicly-available database (n = 1435) showed that gene expression of specific mitochondrial proteins in EOC is associated with survival. Quantifying multiple biochemical and molecular markers of mitochondrial content and function in tissue from 51 patients with benign ovarian masses and 128 patients with high-grade EOC revealed that compared to benign tissue, EOCs exhibit 3.3–8.4-fold higher mitochondrial content and respiratory chain enzymatic activities (P < 0.001) but similar mitochondrial DNA (mtDNA) levels (− 3.1%), documenting abnormal mitochondrial phenotypes in EOC. Mitochondrial respiratory chain activity was also associated with interleukin-6 (IL-6) levels in ascites. In benign tissue, negative biobehavioral factors were inversely correlated with mitochondrial content and respiratory chain activities, whereas positive biobehavioral factors tended to be positively correlated with mitochondrial measures, although effect sizes were small to medium (r = − 0.43 to 0.47). In contrast, serous EOCs showed less pronounced biobehavioral-mitochondrial correlations. These results document abnormal mitochondrial functional phenotypes in EOC and warrant further research on the link between biobehavioral factors and mitochondria in cancer

Paraneoplastic thrombocytosis in ovarian cancer

&lt;p&gt;Background: The mechanisms of paraneoplastic thrombocytosis in ovarian cancer and the role that platelets play in abetting cancer growth are unclear.&lt;/p&gt; &lt;p&gt;Methods: We analyzed clinical data on 619 patients with epithelial ovarian cancer to test associations between platelet counts and disease outcome. Human samples and mouse models of epithelial ovarian cancer were used to explore the underlying mechanisms of paraneoplastic thrombocytosis. The effects of platelets on tumor growth and angiogenesis were ascertained.&lt;/p&gt; &lt;p&gt;Results: Thrombocytosis was significantly associated with advanced disease and shortened survival. Plasma levels of thrombopoietin and interleukin-6 were significantly elevated in patients who had thrombocytosis as compared with those who did not. In mouse models, increased hepatic thrombopoietin synthesis in response to tumor-derived interleukin-6 was an underlying mechanism of paraneoplastic thrombocytosis. Tumorderived interleukin-6 and hepatic thrombopoietin were also linked to thrombocytosis in patients. Silencing thrombopoietin and interleukin-6 abrogated thrombocytosis in tumor-bearing mice. Anti–interleukin-6 antibody treatment significantly reduced platelet counts in tumor-bearing mice and in patients with epithelial ovarian cancer. In addition, neutralizing interleukin-6 significantly enhanced the therapeutic efficacy of paclitaxel in mouse models of epithelial ovarian cancer. The use of an antiplatelet antibody to halve platelet counts in tumor-bearing mice significantly reduced tumor growth and angiogenesis.&lt;/p&gt; &lt;p&gt;Conclusions: These findings support the existence of a paracrine circuit wherein increased production of thrombopoietic cytokines in tumor and host tissue leads to paraneoplastic thrombocytosis, which fuels tumor growth. We speculate that countering paraneoplastic thrombocytosis either directly or indirectly by targeting these cytokines may have therapeutic potential. &lt;/p&gt

SSRI use and clinical outcomes in epithelial ovarian cancer

Selective serotonin reuptake inhibitor (SSRI) use is common among ovarian cancer patients. We examined the effect of SSRIs on survival and progression in ovarian cancer patients and effects of 5-HT on ovarian cancer cell (OCC) proliferation. Ovarian cancer patients from a 6-site study between 1994 and 2010 were included. Cox proportional hazards models were used for multivariate analysis. SSRI use was associated with decreased time to disease recurrence (HR 1.3, CI 1.0-1.6, p=0.03), but not overall survival (HR 1.1, CI 0.9-1.3, p=0.56). Compared to normal ovarian cells, most OCCs had elevated 5-HT2A receptor mRNA expression (up to 1600 fold greater expression). Clonogenic survival increased in cells treated with 10 uM (1.6 fold, p<0.001) and 20uM (1.9 fold, p=0.018) 5-HT. Mice receiving 5-HT injections had increases in tumor weight (p=0.07) and nodules (p=0.08) with increased Ki67 expression. Injections with sertraline doubled mean tumor weight in mice (p=0.16). 5-HT and sertraline both increased Ki67 expression in mouse tumors (p < 0.001). Patients using SSRIs had significantly decreased time to disease progression. It is possible that SSRIs alter serotonin levels in the tumor microenvironment, resulting in activation of proliferation pathways. Further characterization of serotonergic pathways in ovarian cancer is recommended to demonstrate safety of these medications

Depressive symptoms and cortisol variability prior to surgery for suspected endometrial cancer

Endometrial cancer (EC) is the most common type of gynecologic cancer affecting women; however, very little research has examined relationships between psychological factors and hypothalamic-pituitary-adrenal (HPA) axis dysregulation in this population. The current study examined relations between depressive/anxious symptoms and salivary cortisol diurnal rhythm and variability in women undergoing surgery for suspected endometrial cancer. Depressive and anxious symptoms were measured prior to surgery using the Structured Interview Guide for the Hamilton Depression Inventory (SIGH-AD). Saliva was collected four times a day for the three days prior to surgery and then assayed by ELISA to obtain cortisol concentrations. Cortisol slopes and intraindividual variability were then calculated across subjects. Relations between depressive/anxious symptoms and cortisol indices were examined using multilevel modeling and linear regression analyses. Participants were 82 women with nonmetastatic endometrial cancer. Anxious symptoms were not associated with either cortisol slope or intraindividual variability, and depressive symptoms were unrelated to cortisol slope. However, after controlling for presence of poorer prognosis cancer subtypes, greater depressive symptoms (excluding symptoms possibly/definitely due to health/treatment factors) in the week preceding surgery were significantly related to greater cortisol intraindividual variability (β=.214; p<.05). These results suggest that depressive symptoms prior to surgery for suspected endometrial cancer are related to greater cortisol intraindividual variability, which is suggestive of more erratic HPA axis arousal. Future research should examine whether mood symptoms may be associated with compromised health outcomes via erratic HPA axis arousal in this population