Relationship between COVID-related stressors and internalizing symptoms: Gendered neuroendocrine risk profiles.

The COVID-19 pandemic generated significant life stress and increases in internalizing disorders. Moreover, COVID-related stressors disproportionately impacted women, consistent with outcomes showing a gender gap in stress-related disorders. Gender-related stress vulnerability emerges in adolescence alongside gender-specific changes in neuroendocrine signaling. Most research on the neuroendocrinology of stress-related disorders has focused on differences in the hypothalamic-pituitary-adrenal (HPA) axis effector hormone cortisol. More recent studies, however, emphasize dehydroepiandrosterone (DHEA), a neuroprotective and neuroactive hormone released concurrently with cortisol that balances its biobehavioral actions during stress. Notably, women show lower cortisol responses and higher DHEA responses to stress. However, lower cortisol and higher DHEA are associated with internalizing disorders in women, while those associations are opposite in men. Thus, gender-specific factors perhaps result in a neuroendocrine profile that places women at greater risk for stress-related disorders. The current study prospectively examined socially evaluated cold-pressor task (SECPT) induced neuroendocrine responses at age 15 and internalizing symptoms during the COVID-19 pandemic at age 21 in a cohort of 175 primarily Black low-socioeconomic status participants, while controlling for internalizing symptoms at age 15. The association between COVID-related stress and internalizing symptoms was not stronger in women. Lower DHEA-cortisol ratios were associated with a weaker relationship between COVID-related stress and internalizing symptoms in women, while higher ratios were associated with a weaker relationship in men. These findings suggest gender differences in the relationship between DHEA and cortisol and internalizing outcomes during a stressful period, and support differential neuroendocrine protective and risk pathways for young men and women.

Worsening of the Toxic Effects of (±)Cis-4,4'-DMAR Following Its Co-Administration with (±)Trans-4,4'-DMAR: Neuro-Behavioural, Physiological, Immunohistochemical and Metabolic Studies in Mice.

4,4'-Dimethylaminorex (4,4'-DMAR) is a new synthetic stimulant, and only a little information has been made available so far regarding its pharmaco-toxicological effects. The aim of this study was to investigate the effects of the systemic administration of both the single (±)cis (0.1-60 mg/kg) and (±)trans (30 and 60 mg/kg) stereoisomers and their co-administration (e.g., (±)cis at 1, 10 or 60 mg/kg + (±)trans at 30 mg/kg) in mice. Moreover, we investigated the effect of 4,4'-DMAR on the expression of markers of oxidative/nitrosative stress (8-OHdG, iNOS, NT and NOX2), apoptosis (Smac/DIABLO and NF-κB), and heat shock proteins (HSP27, HSP70, HSP90) in the cerebral cortex. Our study demonstrated that the (±)cis stereoisomer dose-dependently induced psychomotor agitation, sweating, salivation, hyperthermia, stimulated aggression, convulsions and death. Conversely, the (±)trans stereoisomer was ineffective whilst the stereoisomers' co-administration resulted in a worsening of the toxic (±)cis stereoisomer effects. This trend of responses was confirmed by immunohistochemical analysis on the cortex. Finally, we investigated the potentially toxic effects of stereoisomer co-administration by studying urinary excretion. The excretion study showed that the (±)trans stereoisomer reduced the metabolism of the (±)cis form and increased its amount in the urine, possibly reflecting its increased plasma levels and, therefore, the worsening of its toxicity.

Growth factors and neurotrophins in patients with stress-related exhaustion disorder.

Growth factors, such as vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF), and neurotrophic factors, including brain-derived neurotophic factor (BDNF), have attracted attention in studies of the biological effects of long-term stress exposure due to their neuroprotective roles. This study investigated whether circulating levels of EGF, VEGF and BDNF were altered in individuals with stress-related exhaustion disorder. Forty patients diagnosed with exhaustion disorder and 40 healthy subjects (50% women) provided fasting blood samples for analysis of EGF, VEGF, and BDNF in plasma. We found significantly lower levels of EGF, VEGF, and BDNF in patients with ED compared to healthy controls. This pattern was seen in both male and female patients. Given the important roles of BDNF and VEGF for brain plasticity and neurogenesis, decreased levels after long-term stress exposure could indicate increased risk of neuronal damage and cognitive impairments in this patient group.

Female primary and secondary psychopathic variants show distinct endocrine and psychophysiological profiles.

Research with predominantly male samples supports primary and secondary developmental pathways to psychopathy that are phenotypically indistinguishable on aggressive and antisocial behavior. The aim of this study was to examine whether female variants of psychopathy show divergent endocrine (i.e., cortisol, dehydroepiandrosterone [DHEA], testosterone, and their ratios) and psychophysiological (i.e., heart rate variability [HRV]) reactivity to social provocation. We also tested whether variants differed on reactive aggression when performing a competitive reaction time task against the fictitious participant who previously insulted them. Latent profile analyses on 101 undergraduate women oversampled for high psychopathic traits identified a high-anxious, maltreated secondary variant (n=64) and a low-anxious primary variant (n=37). Although variants did not differ on aggression, secondary variants showed higher cortisol, testosterone, cortisol-to-DHEA ratios, and HRV following social provocation relative to primary variants. Findings suggest that the neurobiological mechanisms underpinning aggression in psychopathy may differ between women on primary versus secondary developmental pathways.

Pain and pain syndromes.

The two main categories of pain, nociceptive and neuropathic, are caused by tissue damage and nerve damage respectively. Psychogenic pain is also described in the literature but it is becoming a pejorative term as the concept of central control of pain is now gaining momentum. There is considerable overlap in brain areas that deal with pain and where mood disorders develop. Some neurotransmitters, e.g. serotonin and noradrenaline, are involved in receiving and processing signals and regulate mood as well. It is no coincidence that many drugs used to treat mood disorders are effective when used for pain relief. This article highlights this interplay of neurotransmission and affective/pain symptomatology.

Estimation of salivary cortisol level in post-menopausal women with psychosomatic disorders.

BACKGROUND: Stress is an undesirable or health threatening response of the body, which is brought on by deleterious external influences (stressors). Objective measurement of psychosocial stress helps in assessment of pivotal role of stress in precipitation of multitude of health problems and a solution to the same. Salivary biomarkers are suggested to provide a reliable and non-invasive method for the estimation of these general health problems. Salivary cortisol is such biomarker used as tool in the examination of human physiological stress response. Post-menopausal women show an increase in stress levels and hence suffer with multiple health related problems. Hence the present study aimed to estimate salivary cortisol levels in post-menopausal women with clinically diagnosed psychosomatic disorder/disorders of the head and neck region, so as to establish salivary cortisol as a biochemical indicator of stress. METHODS: Thorough intra-oral and extra-oral examination was performed to check for the presence of psychosomatic disorder of head and neck. Unstimulated saliva was collected from 100 post-menopausal women with and 100 without clinically diagnosed psychosomatic disorder/disorders through 'Spit Technique'. Salivary cortisol was estimated using ELISA method. RESULTS: The results were statistically significant as they showed that the salivary cortisol was in higher levels in post- menopausal women with clinically diagnosed psychosomatic disorder/disorders. CONCLUSION: The geriatric patients feel that they have very little skills or resources to deal with the high levels of stress that they are experiencing and hence suffer from lack of self-worth. The results of this study recommend that stress evaluation should be done on a regular basis for all post- menopausal women. For individuals who do not reveal their psychological distress, salivary analysis of cortisol may be used as an aid to diagnose their situation in conjunction with clinical diagnosis.

Biological and perceived stress in motor functional neurological disorders.

BACKGROUND: Current models explaining motor functional neurological disorders (FND) integrate both the neurobiological mechanisms underlying symptoms production and the role of psychosocial stressors. Imaging studies have suggested abnormal motor control linked to impaired emotional and stress regulation. However, little is known on the biological stress regulation in FND. Our aim was to study the biological and perceived response to stress in patients with motor FND. METHODS: Sixteen patients with motor FND (DSM-5 criteria) and fifteen healthy controls underwent the Trier Social Stress Test. Hypothalamo-pituitary-adrenal axis (HPA) response was evaluated with salivary cortisol and autonomous sympathetic response with salivary alpha-amylase. Area under the curve was computed to reflect background levels (AUCg) and change over time (AUCi). Life adversities and perceived subjective stress on a visual analog scale (VAS) were correlated with biological responses. RESULTS: FND patients had significantly higher background levels (AUCg) of both stress markers (cortisol and amylase) than controls. The biological response (AUCi) to stress did not differ between groups for both markers but the subjective response showed an interaction effect with patients reporting higher levels of stress than controls. After stress, controls showed a strong correlation between subjective and objective sympathetic values (amylase) but not patients. The number and subjective impact of adverse life events correlated with cortisol AUCg in patients only. CONCLUSION: This study confirms a baseline HPA-axis and sympathetic hyperarousal state in motor FND related to life adversities. During a social stress, dissociation between perceived stress and biological markers was observed in patients only, reflecting a dysregulation of interoception capacity, which might represent an endophenotype of this disorder.

Relaxation - Induced by Vibroacoustic Stimulation via a Body Monochord and via Relaxation Music - Is Associated with a Decrease in Tonic Electrodermal Activity and an Increase of the Salivary Cortisol Level in Patients with Psychosomatic Disorders.

Vibroacoustic stimulation by a Body Monochord can induce relaxation states of various emotional valence. The skin conductance level (SCL) of the tonic electrodermal activity is an indicator of sympathetic arousal of the autonomic nervous system and thus an indicator of the relaxation response. Salivary cortisol is considered to be a stress indicator of the HPA-axis. The effects of the treatment with a Body Monochord and listening to relaxation music (randomized chronological presentation) on SCL and salivary cortisol in relation to the emotional valence of the experience were examined in patients with psychosomatic disorders (N = 42). Salivary cortisol samples were collected immediately before and after the expositions. Subjective experience was measured via self-rating scales. Overall, both the exposure to the Body Monochord as well as the exposure to the relaxation music induced an improvement of patients' mood and caused a highly significant reduction of SCL. A more emotionally positive experience of relaxation correlated with a slightly stronger reduction of the SCL. Both treatment conditions caused a slight increase in salivary cortisol, which was significant after exposure to the first treatment. The increase of salivary cortisol during a relaxation state is contrary to previous findings. It is possible that the relaxation state was experienced as an emotional challenge, due to inner images and uncommon sensations that might have occurred.

Why are women so vulnerable to anxiety, trauma-related and stress-related disorders? The potential role of sex hormones.

Increased prevalence, severity, and burden of anxiety, trauma-related and stress-related disorders in women compared with men has been well documented. Evidence from a variety of fields has emerged suggesting that sex hormones, particularly oestradiol and progesterone, play a significant part in generation of these sex differences. In this Series paper, we aim to integrate the literature reporting on the effects of sex hormones on biological, behavioural, and cognitive pathways, to propose two broad mechanisms by which oestradiol and progesterone influence sex differences in anxiety disorders: augmentation of vulnerability factors associated with anxiety disorder development; and facilitation of the maintenance of anxious symptoms post-development. The implications for future research, along with novel approaches to psychological and pharmacological treatment of anxiety disorders, are also considered.

[Peculiarities of the psychic state and quality of life in patients with duodenal ulcer in the context of chronomedicine].

Most clinicians consider duodenum ulcer as a psychosomatic disease. Objective: To show the interdependence of this condition and mental disorders and their relation to disturbances of melatonin production . Materials and Methods: 15 patients with seasonal DU and 15 healthy subjects of the control group were examined during 3 years using laboratory, endoscopic, and standard psychodiagnostic methods. Results. It was found that all patients with exacerbation of DU experienced enhanced anxiety, reduced background mood, and impaired quality of life based on general health and mental health scoring scales. The circadian rhythm of melatonin production was markedly distorted throughout the observation period but especially during exacerbations of the disease. Conclusions. The results indicate a high degree of correlation between DU and mental disorders caused by impaired production of melatonin. It suggests common etiological mechanisms of DU and psychosomatic symptom complex.

[Features of oxygen utilization by the body of patients with arterial hypertension in the days of magnetic storms depending on the psychosomatic status and treatment options].

During magnetic storms the observed increase in γ-background environment and the reduction of the rate of oxygen utilization by the tissues, but the increase in the number of angina attacks per day to magnetic storms the choleric, in the days of magnetic storms in sanguine, for 3-4 days at a phlegmatic, and 4-5 days in the melancholic especially in groups high anxiety phlegmatic and melancholic. Last-risk group severe arterial hypertension and ischemic heart disease. Antihypertensive therapy based on the blockade of the features of the psychosomatic status, significantly reduced the number of attacks and brought the values of the utilization of oxygen and coefficient of oxygen utilization bu the tissues of all the days to those in healthy individual relevant anxiety and temperament.

Stress and inflammatory biomarkers and symptoms are associated with bioimpedance measures.

BACKGROUND: This large cross-sectional, multi-centre study evaluated the association of body composition measurements by a novel dual frequency bioimpedance device (BIA-ACC) with chronic stress/inflammation biomarkers and the presence of medically unexplained symptoms (MUS). MATERIALS AND METHODS: Participants were adult Caucasians of both sexes and included 10,416 lean subjects with no MUS (Group A), 58,710 lean subjects with MUS (Group B) and 30,445 overweight/obese subjects with no MUS and excessive fat mass (FM) (Group C). RESULTS: Total body extracellular water (ECW) was higher, while intracellular water (ICW) was lower in Group B than both other groups (P < 0.01). Group A had significantly lower FM and higher skeletal mass (SK) and phase angle (PA) than Group B and lower circulating high sensitivity (hs) CRP levels than both other groups. hsCRP was higher in Group C than Group A though (P < 0.01). Salivary cortisol in Group B was lower in the morning and higher in the evening than both other groups (P < 0.001), indicating circadian rhythm obliteration or reversal in this group. ECW correlated positively with serum hsCRP and 8 p.m. salivary cortisol, but negatively with 8 a.m. salivary cortisol, while PA correlated positively with 8 a.m. and negatively with 8 p.m. salivary cortisol and serum hsCRP. Both 8 a.m. and 8 p.m. salivary cortisol and serum hsCRP were associated with the presence of MUS and BIA-ACC measurements, including ECW, ICW, FM, SK and PA. CONCLUSIONS: MUS is an index of chronic stress and inflammation and BIA-ACC may provide a useful, bloodless and rapid tool in the clinical setting, distinguishing patients with chronic stress/inflammation from healthy subjects and monitoring their response to treatment.

Psychological insulin resistance in type 2 diabetes patients regarding oral antidiabetes treatment, subcutaneous insulin injections, or inhaled insulin.

BACKGROUND: "Psychological insulin resistance" (PIR) is an obstacle to insulin treatment in type 2 diabetes, and patients' expectations regarding alternative ways of insulin delivery are poorly understood. SUBJECTS AND METHODS: PIR and beliefs regarding treatment alternatives were analyzed in patients with type 2 diabetes (n=532; mean glycated hemoglobin, 68±12 mmol/mol [8.34±1.5%]) comparing oral antidiabetes treatment, subcutaneous insulin injections, or inhaled insulin. Questionnaires were used to assess barriers to insulin treatment (BIT), generic and diabetes-specific quality of life (Short Form 36 and Problem Areas in Diabetes, German version), diabetes knowledge, locus of control (Questionnaire for the Assessment of Diabetes-Specific Locus of Control, in German), coping styles (Freiburg Questionnaire of Illness Coping, 15-Items Short Form), self-esteem (Rosenberg Self-Esteem Scale, German version), and mental disorders (Patient Health Questionnaire, German version). Patients discussed treatment optimization options with a physician and were asked to make a choice about future diabetes therapy options in a two-step treatment choice scenario. Step 1 included oral antidiabetes drugs or subcutaneous insulin injection (SCI). Step 2 included an additional treatment alternative of inhaled insulin (INH). Subgroups were analyzed according to their treatment choice. RESULTS: Most patients perceived their own diabetes-related behavior as active, problem-focused, internally controlled, and oriented toward their doctors' recommendations, although their diabetes knowledge was limited. In Step 1, rejection of the recommended insulin was 82%, and in Step 2, it was 57%. Fear of hypoglycemia was the most important barrier to insulin treatment. Patients choosing INH (versus SCI) scored higher regarding fear of injection, expected hardship from insulin therapy, and BIT-Sumscore. CONCLUSIONS: The acceptance of insulin is very low in type 2 diabetes patients. The option to inhale insulin increases the acceptability for some but not the majority of patients.

Influence of tianeptine on melatonin homeostasis and psychosomatic symptoms in patients with irritable bowel syndrome.

UNLABELLED: Selective serotonin reuptake inhibitors (SSRIs) exert beneficial effect on gastrointestinal tract (GIT), but its mechanism has not been recognized. One of the hypothesis assumes, that fluoxetine increases indirectly melatonin production. For this reason it can be hypothesized, that administration of drugs of opposite effect, for example tianepine (selective serotonin reuptake enhancer (SSRE), can reduce melatonin production resulting in harmful effects as regards GIT. The aim of the study was to confirm or reject this hypothesis. The study included 100 patients, aged 21-58 years, with irritable bowel syndrome (IBS). Basing on the Rome III Criteria patients with constipation-predominant (IBS-C, n=50) and with diarrhoea-predominant (IBS-D, n=50) and 25 health volunteers (control group C) were distinguished. Visual Analog Scale (VAS) and Hamilton Depression Rating Scale (HDRS) were used to determine the severity of somatic and psychic symptoms. The concentration of 6-sultatoxymelatonin (6-HMS) in the urine was measured by ELISA method. In both groups the patients were administrated tianeptine 12.5 mg three times daily or placebo for 8 weeks. After 8 weeks of tianeptine therapy no significant changes were found in urinary 6-HMS excretion both in IBS-C group (9.9±3.2 versus 11.5±3.5 µg/24 h) and in IBS-D group (11.8±3.3 versus 12.2±3.5 µg/24 h). Eight-week tianeptine therapy resulted in significant decrease of somatic and psychic symptoms in both investigated groups. The improvement in the quality of life indices was obtained in 76.5% of IBS-C and in 63.3% of IBS-D patients. CONCLUSIONS: tianeptine does not impair melatonin homeostasis in patients with IB, diminishes IBS symptoms and improves the patients' quality of life.

Effects of mood and rumination on cortisol levels in daily life: an ambulatory assessment study in remitted depressed patients and healthy controls.

The influence of naturally occurring emotional and cognitive experiences on hypothalamic-pituitary-adrenal axis (HPAA) activity is still underinvestigated, particularly in clinical populations. The present study examined effects of mood and rumination on cortisol levels in daily life in remitted depressed patients with recurrent episodes or a chronic precourse (n=31) and healthy controls (n=32). Ambulatory assessment of subjective variables (valence, calmness, energetic-arousal, ruminative self-focus), daily stressors, and saliva cortisol samples was performed five times a day on two consecutive workdays, whereby cortisol was collected 20min after the subjective assessments. In addition, depressive symptoms and trait rumination (brooding, reflection) were measured retrospectively. Multilevel models revealed that remitted depressed patients showed lower cortisol activity compared to healthy controls. Depressive symptoms and trait rumination did not predict HPAA activity, whereas, by controlling for daily stressors, higher daily means of ruminative self-focus and lower daily means of valence, energetic arousal and calmness were associated with higher daily cortisol levels. Separate analyses per group revealed that mean daily ruminative self-focus predicted higher cortisol in both samples. In contrast, lower daily means of calmness, but also of valence and energetic arousal, were significantly linked to higher cortisol output only in healthy controls, but not in the patient sample. These findings indicate that naturally occurring rumination and low mood are associated with increased activation of the HPAA in daily life. Moreover, our data revealed a potentially reduced mood-cortisol coupling in remitted recurrent depression, possibly indicating that during the course of recurrent depression HPAA activation might become less responsive toward subtle emotional experiences in natural contexts.

[Perimenopausal disorders: the aging, psychological and social predictors of their occurrence].

Perimenopausal disorders are one of important problems of medico-biological, psychosocial and socio-cultural life of women entered the perimenopausal period (climacteric). The women of perimenopausal age within the biopsychosocial approach were surveyed, thus the basic group of the surveyed was made by 416 women at the age of 42-55 years with implications of a climacteric syndrome, and the control group was made by 138 women with a normal current the perimenopausal period. The revealed psychosomatic disorders have a multifactorial (biopsychosocial) genesis in more than 70% of women of different age groups with perimenopausal disorders. The analysis of pathogenetic conditions of formation perimenopausal disorders in women has shown interrelation of hereditary, perinatal, psychological and family-social factors.

Posttraumatic oxytocin dysregulation: is it a link among posttraumatic self disorders, posttraumatic stress disorder, and pelvic visceral dysregulation conditions in women?

This article explicates a theory that oxytocin, a sexually dimorphic neurotransmitter and paracrine hormone, is a plausible mechanism linking early relational trauma with posttraumatic self disorders (e.g., dissociation, somatization, and interpersonal sensitivity), posttraumatic stress disorder, and pelvic visceral dysregulation disorders (e.g., irritable bowel syndrome, chronic pelvic pain, interstitial cystitis, and hyperemesis gravidarum). This posttraumatic oxytocin dysregulation disorders theory is consistent with the historical and contemporary literature. It integrates attention to psychological and physical comorbidities and could account for the increased incidence of these disorders among females. Specific propositions are explored in data from studies of traumatic stress and women's health.

Levels of salivary stress markers in patients with anxiety about halitosis.

OBJECTIVE: To investigate the relationship between salivary stress markers and mental stress states in patients complaining of oral malodour. The utility of the salivary stress markers in assessment of mental conditions of those patients was also investigated. DESIGN: The study population included 74 patients, aged 20-59 years, who complained of oral malodour and were referred to the Breath Odor Clinic at Tokushima University Hospital. Patients were classified into two groups, genuine halitosis (GH) and psychosomatic halitosis (PH), according to the results of organoleptic rating measurement. All patients were subjected to examination by the Cornell Medical Index (CMI) Health Questionnaire. Resting saliva was collected and levels of salivary IgA, cortisol and chromogranin A were determined by ELISA. Twenty-three volunteers not complaining of halitosis were included as the control group. Kruskal-Wallis test and Mann-Whitney's U-test were used for statistical analysis. RESULTS: A significant increase was observed in the concentrations of salivary cortisol in the PH group as compared with GH and control groups (p<0.05). Concentrations of IgA and chromogranin A in saliva were not significantly different among the three groups. In addition, higher salivary cortisol concentrations were found in CMI scale III and IV (tendency towards neurosis) than in scale I and II (normal) (p<0.05). Since salivary cortisol reflects a status of chronic stress condition, psychosomatic halitosis might be closely related to this state of chronic stress. CONCLUSIONS: Determination of cortisol levels in saliva may provide useful information for evaluating the mental status of patients complaining of halitosis.

[The role of melatonin in the development of psychosomatic diseases].

Relationship between psychic and somatic disorders is currently a most widely discussed problem. The published results of relevant research reflect controversial views of internists and psychiatrists. The aim of this paper is to elucidate common mechanisms underlying some psychosomatic diseases based on the chronobiological approach with special reference to abnormal production of melatonin (main rhythm-controlling hormone) resulting in the disturbance of biological rhythms (desynchronosis). Different scenarios of development of psychosomatic disorders are considered using models of irritated bowel syndrome and ulcer disease.