No association between major depression with and without childhood adversity and the stress hormone copeptin

Background: Adverse childhood experiences (ACE) are associated with an increased risk of major depressive disorder (MDD) and hypothalamic-pituitary-adrenal (HPA) axis dysregulation. Within the HPA axis, corticotropin-releasing hormone and vasopressin (AVP) synergistically stimulate the release of adrenocorticotropic hormone, which promotes cortisol release. The cleavage product copeptin is produced during AVP synthesis and is a surrogate marker of AVP release. Children with ACE and young adults with depressive symptoms have higher levels of copeptin than healthy controls. Objective: To uncover the effects of MDD and ACE on copeptin levels in adult females. Methods: We recruited 94 women (mean age: 34.0 +/- 3.6 years): 23 with MDD and ACE, 24 with MDD without ACE, 22 with ACE without MDD, and 25 healthy controls. ACE was defined as repeated sexual or physical abuse at least once a month over at least one year before the age of 18 years. MDD was defined by the DSM-IV criteria. Copeptin plasma levels were measured with an immunoluminometric assay. Results: The four groups did not differ in demographic variables. We found a significant negative correlation between body mass index (BMI) and copeptin plasma levels (r = -.21; p = .045). Copeptin plasma levels did not differ between the four groups after controlling for BMI. Conclusion: Neither MDD nor ACE was associated with altered plasma copeptin levels. Thus, copeptin does not seem to play a major role in MDD and ACE in adult females

The role of fludrocortisone in cognition and mood in patients with primary adrenal insufficiency (Addison's disease)

BACKGROUND: Primary adrenal insufficiency (AI) requires hormone replacement therapy with fludrocortisone and hydrocortisone stimulating glucocorticoid (GR) and mineralocorticoid receptors (MR). Evidence from animal and human studies shows that MR function is crucial for cognitive function and mood. Regarding patients with AI very little is known about the role of MR in cognitive function and mood. METHODS: Repeated measures within-subject design was used to determine whether cognitive function and mood are related to MR occupation in patients with AI. Intraindividually, patients were examined twice with one week apart: once with fludrocortisone (high MR occupation) and once without fludrocortisone (low MR occupation). All patients kept their stable regimen of hydrocortisone. Assessment of cognitive function included executive function, attention and verbal, visuospatial, and working memory. Additionally, mood and blood pressure were measured. RESULTS: Verbal memory improved significantly during high MR occupation (after fludrocortisone intake) compared to low MR occupation (without fludrocortisone, t(29) = -2.1, p = 0.046). There were trend level differences in the Number-Combination-Test (t(29) = -1.9, p = 0.074) and in the Stroop Interference Task (t(29) = -1.9, p = 0.068). No significant differences in visuospatial and working memory were found. Furthermore, current mood state was better during high MR occupation compared to low MR occupation (t(29) = -2.4, p = 0.023) as was diastolic blood pressure (F(2, 29) = 3.6, p = 0.07). CONCLUSIONS: Cognitive function and mood in patients with AI depend in part on MR occupation. Because the medium effect size indicates a potential clinical significance, further studies should systematically examine which dosages of fludrocortisone are associated with optimal cognitive function and mood in AI patients

Cognitive function in patients with primary adrenal insufficiency (Addison's disease)

Background: Patients with primary adrenal insufficiency (AI) need to replace glucocorticoids and mineralocorticoids that act on glucocorticoid (GR) and mineralocorticoid receptors (MR). Both receptors are highly expressed in the hippocampus and are closely associated with cognitive function, which might be impaired by insufficient or increased GR and MR stimulation. However, little is known about cognitive function in patients with AI. Methods: It was examined whether patients with AI exhibit worse cognitive function compared to sex-, age-, and education-matched controls. Cognitive function (executive function, concentration, verbal memory, visual memory, working memory, and autobiographical memory) was assessed in 30 patients with AI (mean age 52.4 yrs. +/- 14.4, n = 21 women, mean duration of illness 18.2 yrs. +/- 11.1) and 30 matched controls. We also measured depressive symptoms, body mass index (BMI), and blood pressure. Results: Patients with AI showed more depressive symptoms, had a greater BMI and lower systolic blood pressure compared to controls. Adjusted analyses controlling for these variables revealed that patients with AI performed significantly worse in verbal learning (F = 7.8, p = .007). Executive function, concentration, working memory, verbal memory, visuospatial memory, and autobiographical memory did not differ between groups. Conclusions: No clinically relevant cognitive impairment was found in patients with AI compared to matched controls. Even long-term glucocorticoid and mineralocorticoid substitution over almost two decades appears to have only subtle effects on cognition in patients with AI

Suicidal imagery in borderline personality disorder and major depressive disorder

A better understanding of suicidal behavior is important to detect suicidality in at-risk populations such as patients with Borderline Personality Disorder (BPD), Posttraumatic Stress Disorder (PTSD) and Major Depressive Disorder (MDD). Suicidal tendencies are clinically assessed by verbal thoughts rather than specifically asking about mental images. This study examines whether imagery and verbal thoughts about suicide occur and differ between patients with BPD with and without comorbid PTSD compared to patients with MDD (clinical controls). All patient groups experienced suicide-related images. Patients with BPD with comorbid PTSD reported significantly more vivid images than patients with MDD. Severity of suicidal ideation, number of previous suicide attempts and childhood traumata were significantly associated with suicidal imagery across all patient groups. We demonstrate for the first time that suicide-related mental imagery occurs in BPD and is associated with suicidal ideation. This highlight the importance of assessing mental imagery-related to suicide in clinical practice

Forecasting individual risk for long-term Posttraumatic Stress Disorder in emergency medical settings using biomedical data: A machine learning multicenter cohort study

© 2021 The AuthorsThe necessary requirement of a traumatic event preceding the development of Posttraumatic Stress Disorder, theoretically allows for administering preventive and early interventions in the early aftermath of such events. Machine learning models including biomedical data to forecast PTSD outcome after trauma are highly promising for detection of individuals most in need of such interventions. In the current study, machine learning was applied on biomedical data collected within 48 h post-trauma to forecast individual risk for long-term PTSD, using a multinominal approach including the full spectrum of common PTSD symptom courses within one prognostic model for the first time. N = 417 patients (37.2% females; mean age 46.09 ± 15.88) admitted with (suspected) serious injury to two urban Academic Level-1 Trauma Centers were included. Routinely collected biomedical information (endocrine measures, vital signs, pharmacotherapy, demographics, injury and trauma characteristics) upon ED admission and subsequent 48 h was used. Cross-validated multi-nominal classification of longitudinal self-reported symptom severity (IES-R) over 12 months and bimodal classification of clinician-rated PTSD diagnosis (CAPS-IV) at 12 months post-trauma was performed using extreme Gradient Boosting and evaluated on hold-out sets. SHapley Additive exPlanations (SHAP) values were used to explain the derived models in human-interpretable form. Good prediction of longitudinal PTSD symptom trajectories (multiclass AUC = 0.89) and clinician-rated PTSD at 12 months (AUC = 0.89) was achieved. Most relevant prognostic variables to forecast both multinominal and dichotomous PTSD outcomes included acute endocrine and psychophysiological measures and hospital-prescribed pharmacotherapy. Thus, individual risk for long-term PTSD was accurately forecasted from biomedical information routinely collected within 48 h post-trauma. These results facilitate future targeted preventive interventions by enabling future early risk detection and provide further insights into the complex etiology of PTSD

Predicting future risk of PTSD

Data routinely collected in the emergency department after trauma have the potential to predict those at risk of later PTSD, which shows promise for computational psychiatry.Stress-related psychiatric disorders across the life spa