Salivary cortisol response to psychosocial stress in patients with first-episode psychosis

AimTo analyze the difference in the salivary cortisol response to psychosocial stress between the patients with the first episode of psychosis (FEP) and the control group.MethodsWe performed a cross-sectional analysis of the baseline measurements of a prospective cohort study conducted from 2015 to 2018 at two Croatian psychiatric hospitals. The study consecutively enrolled 53 patients diagnosed with FEP and 63 healthy controls. The primary outcome was the difference in the changes of salivary cortisol concentration during the stress test. The secondary outcome was the difference in the baseline levels of salivary cortisol between patients with FEP and controls. The tertiary outcome were the correlations of salivary cortisol levels with the results of the Positive and Negative Syndrome Scale for Schizophrenia, Rosenberg Self-Esteem Scale, and the International Personality Item Pool.ResultsPatients with FEP had significantly higher baseline salivary cortisol than controls, but their salivary cortisol increased significantly less during the stress test.ConclusionPatients with FEP respond differently to stressful stimuli than controls, as shown by the increased baseline salivary cortisol and blunted cortisol response, possibly indicating a greater vulnerability to psychosocial stress.

Schizophrenia is one of the most complex psychiatric disorders (1), and in most cases, a long-term condition characterized by alternating periods of acute psychosis and remission. The first episode of psychosis (FEP) is usually preceded by a prodromal phase with non-specific symptoms, followed by psychotic symptoms pertaining to five dimensions: positive, negative, affective, cognitive, and psychomotor. While the pathogenesis is largely unknown, different streams of research consistently show that schizophrenia results from a complex gene-environment interaction (2), in line with the stress-diathesis model of schizophrenia etiology (3). According to this model, genetic and environmental factors lead to vulnerability to schizophrenia (2), and schizophrenia occurs when the vulnerable person experiences “enough” stress (4). For the majority of people, significant distress is associated with major stressors, eg, death in the family, serious illness, or separation (5). However, in persons prone to psychosis significant distress is caused even by minor stressors, also known as daily hassles (6).Response to stress involves the activation of the hypothalamic-pituitary-adrenal axis (HPA): the hypothalamus secretes corticotropin-releasing factor (CRF), which stimulates the secretion of adrenocorticotropic hormone (ACTH) from the front pituitary gland. ACTH then stimulates the release of cortisol from the adrenal gland, causing the cascading effect of several bodily systems (immune, neuroendocrine, inflammatory response to the organism, etc) (7). In the central nervous system, increased cortisol levels can lead to the sensitization of dopaminergic response to stress, which can lead to an excessive dopamine release and psychotic symptoms (6). Indeed, various indicators of altered stress response have been confirmed in the population at risk for psychosis compared with healthy population (8,9).While it has been suggested that persons with schizophrenia show a blunted cortisol response following experimentally induced psychosocial stress (10,11), these findings should be further elucidated considering the heterogeneous research results. Some of these discrepancies may arise from the heterogeneity of the samples and different confounding factors but also from different stress response across illness types and stages (12).Generally, persons with FEP show higher basal cortisol values than the healthy population (8,13,14), a finding that possibly indicates their increased basic HPA hyperactivity, which contributes to their higher vulnerability to stressors. HPA axis hyperactivity indicated by elevated basal cortisol levels in individuals with psychosis is expected to also produce a higher acute elevation of cortisol concentrations in response to acute stressful situation (11). However, studies on FEP are not uniform in their findings (5-7). A small study with eleven medication-naive patients found an attenuated response of cortisol to psychosocial stress (15). Furthermore, Pruessner et al (16) reported significantly lower cortisol levels and systolic blood pressure during the psychosocial stress task in an ultra-high-risk group compared with controls; the lower cortisol levels were associated with higher self-rated stress in the past year. The authors suggested that in these patients attenuated stress response reflects the vulnerability to stressors. A recent study among patients with FEP obtained contrary results, ie, lower salivary cortisol levels at baseline but no difference in the cortisol response during psychosocial stress challenge test compared with healthy controls (17). Another study found no differences in baseline salivary cortisol levels between patients with FEP and controls, but a blunted cortisol response to stressors in FEP, both on and off medication, compared with controls (18). Finally, individuals with schizophrenia have shown lower cortisol levels both in anticipation and after exposure to social stress compared with controls, even though there were no differences in cortisol production rate (19).Of note, people with posttraumatic stress syndrome (20) and those with high anxiety traits (21) showed higher salivary baseline cortisol, but a blunted response to psychosocial stress compared with healthy controls (22), which suggests a deficient acute neuroendocrine stress response.Thus, the aim of our study was to assess the difference in the salivary cortisol response to the psychosocial stress between the patients with FEP and healthy controls. We enrolled only patients with FEP who were homogeneous in age, duration of illness, phase of illness, and with minimal exposure to medication to limit some of the major confounding factors from other studies. We hypothesized that patients with FEP showed higher baseline salivary cortisol levels, which indicates increased basic HPA hyperactivity, and a lower cortisol increase in response to psychosocial stressor compared with HC, as an indicator of an aberrant response to psychosocial stress. Our exploratory aim was to analyze the correlation of other clinical factors, including psychopathology, personality traits, and stressful life events with salivary cortisol levels.     

Hormone therapy in epithelial ovarian cancer

Although epidemiologic studies, animal experiments and receptor studies have shown that not only normal ovaries but also many malignant ovarian tumors can be considered as endocrine related and hormone dependent, the place of hormonal therapy in the management of patients with ovarian cancer remains unsettled. Most trials of hormonal treatment in ovarian cancer have been retrospective, involved only limited numbers of patients, and lacked important patient-related data and information pertaining to tumor characteristics. In addition, a variety of hormonal preparations with different degrees of potency and in different dosages were included in these studies. A literature review shows that response to hormonal therapy even in a preterminal setting, is modest, with about 8% objective response but almost no side effects. In a similar patient setting, more toxic therapeutic agents do not yield a better response. The place of hormonal therapy in the management of patients with epithelial ovarian cancer needs more thorough evaluation in well-designed randomized trials.     

A prospective study of the use of fine-needle aspiration cytology and core biopsy in the diagnosis of breast cancer

A prospective study was carried out on 143 consecutive patients with palpable lumps larger than 2 cm in size which were clinically suspicious of carcinoma. One hundred and five lumps proved to be malignant and 38 were benign. Of the 105 patients with malignancy, confirmation was made in 95 by fine-needle aspiration cytology (FNAC) with a sensitivity of 90.4% and 100 by core biopsy with a sensitivity of 95.2%. The sensitivity of core biopsies increased with the number of cores taken (one core, 76.2%; two cores, 80.9%, three cores, 89.2%; four cores, 95.2%). The combined sensitivity of FNAC and core biopsies was 100%, and so are complementary in the accurate diagnosis of breast cancer. Patients presenting to the breast clinic with a solid suspicious breast lump larger than 2 cm can benefit from FNAC and a minimum of four core biopsies to improve diagnosis.     

Techniques in occluding the aorta during endovascular repair of ruptured abdominal aortic aneurysms

Among various methods to achieve rapid occlusion of the aorta during endovascular repair for ruptured abdominal aortic aneurysm, particular emphasis is placed on two techniques that have been incorporated into our endovascular repair practice. The sheath-over-balloon technique (the Loan SOB technique) facilitates hemodynamic stability by transfemoral endovascular placement of an aortic occlusion balloon catheter to the infrarenal abdominal aorta. The balloon-ahead-of-graft technique (the Hornsby BAG technique) allows suprarenal hemodynamic control using a stent-graft system with a built-in balloon. The two techniques are simple, quick, and effective in achieving hemodynamic stability.     

Effect of nitrous oxide and methionine treatments on hepatic S-adenosylmethionine and methylation reactions in the rat

Nitrous oxide administration to experimental animals leads to significant alterations in the hepatic folate pathway. This pathway is closely linked to the metabolism of methionine and S-adenosylmethionine (AdoMet), two compounds that play a central role in biologically important methylation reactions. This study was carried out to assess whether nitrous oxide administration to animals can affect the metabolism of AdoMet and the AdoMet-dependent methylation reactions. Exposure of rats to a mixture of nitrous oxide and oxygen (50:50) for 2 hr reduced hepatic AdoMet levels. However, when methionine was administered to these rats, hepatic AdoMet rapidly increased to levels that were significantly higher than those observed in air-exposed animals. Concomitant with this increase, there was a significant and marked increase in the rate of methylation of phospholipids and carboxymethylation of proteins. Thus, nitrous oxide, in addition to its inhibitory effect on 5-methyltetrahydrofolate:homocysteine methyltransferase (methionine synthase, EC 2.1.1.13) activity, possesses another effect. It increases the rate of conversion of exogenously administered methionine into AdoMet with a subsequent increase in the rate of methylation of key cellular constituents.