Lower Baseline Cortisol Levels Research Articles

Longitudinal associations of social jetlag with obesity indicators among adolescents - Shanghai adolescent cohort

ObjectiveTo explore the longitudinal association between social-jetlag (SJL) and obesity development among adolescents, sex-difference and related modifying factors in the association. MethodsBased on Shanghai-Adolescent-Cohort during 2017–2021, a total of 609 students were investigated. In grade 6, 7 and 9, the information on SJL was collected using questionnaires, and anthropometric measures were conducted. The fingernail cortisol and progesterone levels in grade 6 (using LC-MS/MS) and body composition in grade 9 (using Inbody-S10) were measured. By the latent-class-mixture-modeling, two trajectories for SJL (high-level vs. low-level) throughout 4 years were developed. The prospective associations of SJL trajectories and weight/fat gains were analyzed by sex and under different (high/moderate/low) cortisol/progesterone stratifications. ResultsIn grades 6–9, 39.00%–44.50 % of adolescents experienced at least 1 h of SJL. Compared with the low-level SJL trajectory, the high-level SJL trajectory was associated with greater differences in body-mass-index Z-scores and waist-to-height ratios across 4 years, higher levels of body-fat-percentage and fat-mass-index in grade 9 (P-values<0.05), and such associations were stronger among girls and under moderate-to-high (vs. low) baseline cortisol and progesterone levels. However, no significant associations among boys were observed. ConclusionsHigh-level SJL in adolescents may be associated with the development of obesity, especially among adolescent girls and under relatively high baseline cortisol and progesterone levels.

Individual differences in behaviour are related to metabolism, stress response, testosterone, and immunity in the subterranean rodent Ctenomys talarum

The growth of personality research has led to the integration of consistent variation of individual behaviour in multidimensional approaches including physiological variables, which are required to continue building a more comprehensive theory about coping strategies. In this study, we used wild-caught males of Ctenomys talarum (tuco-tucos), a solitary subterranean rodent, to assess the relationships among personality traits and several physiological variables, namely stress response, testosterone, immunity, and energy metabolism. Subjects (n = 21) were used in experimental tests assessing behaviour, energy metabolism, testosterone levels, inflammatory cell-mediated and humoral immunity, and stress response to a simulated predator attack. The structural equation model explained a moderate portion of the variance of personality behaviours related to activity (52%), boldness (35%), and socioaversion (30%). More active and bold individuals showed higher oxygen consumption. While those subjects had lower baseline cortisol levels, there was no relationship between cortisol levels of the stress-induced response. Cell-mediated immune response was related to activity levels. Finally, testosterone only affected boldness. Despite some of these relationships diverge in direction to predicted ones, overall they support the existence of coping styles in male C. talarum; and are discussed in the light of current hypotheses and particular behavioural and ecological traits of tuco-tucos.

Association of serum cortisol and cortisone levels and risk of recurrence after endocrine treatment in breast cancer

Metabolic reprogramming in breast cancer involves changes in steroid hormone synthesis and metabolism. Alterations in estrogen levels in both breast tissue and blood may influence carcinogenesis, breast cancer growth, and response to therapy. Our aim was to examine whether serum steroid hormone concentrations could predict the risk of recurrence and treatment-related fatigue in patients with breast cancer. This study included 66 postmenopausal patients with estrogen receptor-positive breast cancer who underwent surgery, radiotherapy, and adjuvant endocrine treatment. Serum samples were collected at six different time points [before the start of radiotherapy (as baseline), immediately after radiotherapy, and then 3, 6, 12 months, and 7–12 years after radiotherapy]. Serum concentrations of eight steroid hormones (cortisol, cortisone, 17α-hydroxyprogesterone, 17β-estradiol, estrone, androstenedione, testosterone, and progesterone) were measured using a liquid chromatography–tandem mass spectrometry-based method. Breast cancer recurrence was defined as clinically proven relapse/metastatic breast cancer or breast cancer-related death. Fatigue was assessed with the QLQ-C30 questionnaire. Serum steroid hormone concentrations measured before and immediately after radiotherapy differed between relapse and relapse-free patients [(accuracy 68.1%, p = 0.02, and 63.2%, p = 0.03, respectively, partial least squares discriminant analysis (PLS-DA)]. Baseline cortisol levels were lower in patients who relapsed than in those who did not (p < 0.05). The Kaplan–Meier analysis showed that patients with high baseline concentrations of cortisol (≥ median) had a significantly lower risk of breast cancer recurrence than patients with low cortisol levels (<median) (p = 0.02). During follow-up, there was a decrease in cortisol and cortisone concentrations in relapse-free patients, whereas these steroid hormones increased in patients who relapsed. In addition, steroid hormone concentrations immediately after radiotherapy were associated with treatment-related fatigue (accuracy of 62.7%, p = 0.03, PLS-DA). However, baseline steroid hormone levels did not predict fatigue at 1 year or at 7–12 years. In conclusion, breast cancer patients with low baseline cortisol levels were more likely to experience recurrence. During follow-up, cortisol and cortisone levels decreased in relapse-free patients but increased in patients with recurrence. Thus, cortisol and cortisone may act as potential biomarkers indicating individual risk of recurrence.

Acute stress responses of autonomous nervous system, HPA axis, and inflammatory system in posttraumatic stress disorder

Posttraumatic stress disorder (PTSD) does not only have direct consequences for well-being, but it also comes with a significant risk for severe somatic health consequences. A number of previous studies have pointed to alterations in stress systems in traumatized persons, as well as the inflammatory system, which might be important links in the pathway between trauma, PTSD, and health consequences. The aim of this study was to investigate acute stress responses in PTSD patients compared with healthy controls. Twenty-seven PTSD patients and 15 controls were exposed to the Trier Social Stress Test (TSST), and we measured salivary cortisol, salivary alpha-amylase (sAA), plasma interleukin-6 (IL-6), as well as heart rate and heart rate variability (HRV) at different time points before, during and after the stress test. Results revealed similar stress responses between patients and controls, but lower baseline cortisol levels and higher IL-6 baseline levels in PTSD patients. Increases in sAA stress responses were significantly lower in patients, while sAA concentrations were higher in the PTSD group during intervention. HRV was markedly decreased in patients and showed a significantly blunted acute stress response with a slower recovery after TSST. These results confirm previous findings of marked stress system dysregulations in PTSD and add to the literature on acute stress reactivity in PTSD which appears to show stress system-specific changes. Overall, these results have implications for our understanding of potential risk and resilience factors in the response to trauma.

Shyness, hormones, and quality of life among adults with schizophrenia

Objective: Although individual differences in personality are known to influence quality of life in individuals with schizophrenia, relatively few studies have attempted to identify putative links underlying this relation.Methods: Here, we examined associations among temperamental shyness, hormones (ie baseline salivary cortisol and testosterone), and quality of life (QoL) measured in 42 stable outpatient adults with schizophrenia.Results: We found that baseline cortisol, but not testosterone, moderated the relation between shyness and QoL (ß = 1.09, p = 0.004). Among individuals with relatively low baseline cortisol, higher shyness was associated with lower Intrapsychic Foundations QoL. Individuals with relatively higher baseline cortisol reported similar QoL scores irrespective of level of shyness.Conclusion: These preliminary results suggest that relatively lower baseline cortisol may be helpful to understanding the relation between temperament and Intrapsychic Foundations QoL in schizophrenia. The present findings are consistent with previous studies implicating relatively lower baseline cortisol levels in nonclinical samples of people who are shy and the negative downstream effects resulting from HPA axis dysregulation, and extends these prior findings to people with schizophrenia who are also shy.

Does litter size affect emotionality, spatial learning and memory in piglets?

Average litter size has steadily increased over the past decades in the pig farming industry. Large litters are associated with an increase of piglets born with a lower birth weight and reduced overall piglet viability. The aim of our study was to investigate whether litter size affects emotionality, learning and memory in pigs. Ten piglets from large litters (≥18 piglets) were compared with ten piglets from small litters (≤13 piglets). Piglets from two different suppliers, using different breeds, (hereafter called: Source) were tested. Effects were determined of Litter size and Source on birth weights and growth rates, on emotionality of the piglets measured in an open field test (OFT) at 5 weeks of age, and on effects of OFT-induced stress as indicated by salivary cortisol. The effects of Litter size and Source on spatial learning and memory in a holeboard task were assessed between 9 and 14 weeks of age. Small litter piglets from Source 1 grew faster than large litter piglets from the same source. This effect of Litter size was not found in piglets from Source 2. In the OFT, no effects of Litter size on behaviours were found. However, piglets from Source 1 had lower baseline cortisol levels, made more escape attempts and showed higher locomotor activity during the OFT than piglets from Source 2. During the acquisition phase of the holeboard task, piglets from Source 2 learned the reference memory component faster and reached a higher overall working memory level in the reversal phase than piglets from Source 1. Our results show that Source (i.e. supplier and/or breed) influenced performance in behavioural tasks, and that the occurrence of litter size effects was supplier or breed dependent.

Further evidence of low baseline cortisol levels in suicide attempters

BackgroundMany, but not all studies of suicide attempters' cortisol response to stress-either social stress or pharmacological challenge-report an exaggerated response. Recent studies of resting baseline cortisol in past suicide attempters, however, have found lower baseline levels. MethodsIn this study, baseline salivary cortisols were obtained prior to a stress procedure from adults with lifetime diagnoses of a mood disorder (N=69), 31.9% of whom had made a prior suicide attempt. Data were collected during the piloting of this stress procedure, at various times of day and with/without an additional confederate in the room. ResultsAdjusting for procedural, demographic and clinical variables that affect salivary cortisol levels-including time of day of sampling, order of procedure with respect to other assessments, past alcohol abuse, current medication use, and bipolar diagnosis-past suicide attempters had lower baseline cortisol levels compared to non-attempters. LimitationsThis is a pilot study with modest sample sizes using statistical, rather than experimental control of numerous variables affecting salivary cortisol levels. ConclusionsResults confirm previous studies. Low baseline cortisol levels have been associated with childhood adversity and externalizing disorders, suggesting a potential role in reducing inhibitions for risky and dangerous behaviors. Further research is needed to more fully characterize these associations and their role in suicidal behavior risk.

Maternal stress and plural breeding with communal care affect development of the endocrine stress response in a wild rodent

Maternal stress can significantly affect offspring fitness. In laboratory rodents, chronically stressed mothers provide poor maternal care, resulting in pups with hyperactive stress responses. These hyperactive stress responses are characterized by high glucocorticoid levels in response to stressors plus poor negative feedback, which can ultimately lead to decreased fitness. In degus (Octodon degus) and other plural breeding rodents that exhibit communal care, however, maternal care from multiple females may buffer the negative impact on pups born to less parental mothers. We used wild, free-living degus to test this hypothesis. After parturition, we manipulated maternal stress by implanting cortisol pellets in 0%, 50–75%, or 100% of adult females within each social group. We then sampled pups for baseline and stress-induced cortisol, negative feedback efficacy, and adrenal sensitivity. From groups where all mothers were implanted with cortisol, pups had lower baseline cortisol levels and male pups additionally had weaker negative feedback compared to 0% or 50–75% implanted groups. Contrary to expectations, stress-induced cortisol did not differ between treatment groups. These data suggest that maternal stress impacts some aspects of the pup stress response, potentially through decreased maternal care, but that presence of unstressed mothers may mitigate some of these effects. Therefore, one benefit of plural breeding with communal care may be to buffer post-natal stress.

Hepatoadrenal syndrome in pediatric patients with end-stage liver disease*

Adrenal insufficiency in patients with liver failure, referred to as hepatoadrenal syndrome, is well characterized in adult patients but has not yet been described in children. We present 22 pediatric subjects with end-stage liver disease and adrenal insufficiency, diagnosed using the cosyntropin stimulation test. A retrospective chart review using inpatient records from a pediatric intensive care unit in an academic medical center with a busy pediatric transplant program. Most were infants with anatomical short gut and severe, total parenteral nutrition-induced liver failure awaiting liver transplantation. Many were critically ill; 68% required mechanical ventilation and 59% required vasopressors. None. All patients had low baseline cortisol levels and ten also had an abnormal cosyntropin stimulation test. Cortisol levels at baseline and increments of serum cortisol at 30 and 60 mins post cosyntropin were 9.3 ± 5 μg/dL, 9.3 ± 4 μg/dL, and 10.7 ± 6 μg/dL, respectively, compared to these values in five patients with liver failure and normal adrenal function (21.3 ± 3 μg/dL, 10.5 ± 5 μg/dL, and 12.7 ± 3 μg/dL, respectively). Baseline cortisol levels were higher in patients who required vasopressors (11.1 ± 5 μg/dL) compared to those who did not (6.6 ± 4.3 μg/dL, p = .04), and 60-min increment cortisol levels were lower in nonsurvivors compared to survivors (8.6 ± 4.8 μg/dL vs. 15.1 ± 5.1 μg/dL, p = .002). The severity of adrenal insufficiency did not correlate with the degree of hepatic decompensation. Clinical characteristics, including serum electrolytes and vasopressor requirements, were similar in patients with hepatoadrenal syndrome and patients with liver failure and normal adrenal function. Twelve (55%) of the patients died in the hospital, 11 without receiving a transplant. Hydrocortisone therapy permitted rapid weaning of vasopressor therapy but did not affect survival. Children with end-stage liver disease are at risk for hepatoadrenal syndrome and should have their cortisol levels monitored since clinical manifestations may not be diagnostic.

An endocrinologist's view on relative adrenocortical insufficiency in rheumatoid arthritis

The concept of relative adrenal insufficiency (RAI) has been originally introduced to describe a situation in which critically ill patients, without any prior risk or evidence for adrenal insufficiency, have total serum cortisol levels inadequate for the severity of patients' illness. The concept provided a framework for other disease states, in which higher than normal adrenal function could be expected, such as in chronic inflammation. An intense research in RAI field highlighted some new methodological aspects that significantly improved assessment of adrenal function in chronic illness. Measurement of salivary cortisol may provide additional information on locally available cortisol in target tissues. Low levels of dehydroepiandrosterone (DHEAS) for given age and gender were confirmed as a simple and reliable indicator of decreased adrenal function, even in subjects with normal baseline cortisol or normal corticotropin-stimulated cortisol response. Combined lower DHEAS and lower baseline cortisol levels could be an example of hypocompetence of adrenocortical function, yet clinically not apparent.

Dyadic relationships and operational performance of male and female owners and their male dogs

In the paper we investigate how owner personality, attitude and gender influence dog behavior, dyadic practical functionality and the level of dog salivary cortisol. In three meetings, 12 female and 10 male owners of male dogs answered questionnaires including the Neo-FFI human personality inventory. Their dyadic behavior was video-taped in a number of test situations, and saliva samples were collected. Owners who scored highly in neuroticism (Neo-FFI dimension one) viewed their dogs as social supporters and spent much time with them. Their dogs had low baseline cortisol levels, but such dyads were less successful in the operational task. Owners who scored highly in extroversion (Neo-FFI dimension two) appreciated shared activities with their dogs which had relatively high baseline cortisol values. Dogs that had female owners were less sociable-active (dog personality axis 1) than dogs that had male owners. Therefore, it appears that owner gender and personality influences dyadic interaction style, dog behavior and dyadic practical functionality.

Traumatic memories, post-traumatic stress disorder and serum cortisol levels in long-term survivors of the acute respiratory distress syndrome

Survivors of the acute respiratory distress syndrome (ARDS) often report traumatic memories from the intensive care unit (ICU) and display a high incidence of post-traumatic stress disorder (PTSD). As it is known that subjects with PTSD often show sustained reductions in circulating cortisol concentrations, we examined the relationship between serum cortisol, traumatic memories and PTSD in patients after ARDS. We evaluated 33 long-term survivors of ARDS (7.5 ± 2.9 years after discharge from the ICU) for pre-defined categories of traumatic memory from the ICU, hypothalamic–pituitary–adrenocortical axis reactivity to corticotropin and PTSD (by psychiatric interview). During evaluation, patients with multiple traumatic memories had significantly lower basal serum cortisol levels when compared to patients with no or only 1 category of traumatic memory, with no differences in peak cortisol levels after corticotropin stimulation between both subgroups. There was a significant negative correlation between basal cortisol levels and the number of traumatic memories present. PTSD symptom scores correlated with the number of traumatic memories but not with cortisol levels. These findings indicate that lower baseline cortisol levels in long-term survivors of ARDS are associated with an increased incidence of traumatic memories from the ICU, and that more traumatic memories are related to a higher incidence and intensity of PTSD symptoms.

Cytokine Inhibition after Glucocorticoid Exposure in Healthy Men with Low versus High Basal Cortisol Levels

Objective: The balance between glucocorticoid (GC) release and GC sensitivity in target cells is believed to be important to maintain homeostasis in the neuroendocrine control of inflammation. We investigated the impact of in vivo exposure to adrenocorticotropic hormone (ACTH) and dexamethasone (DEX) on GC sensitivity measured in vitro in healthy individuals with high versus low baseline cortisol levels. Methods:136 healthy male volunteers were screened twice and sorted according to their 24-hour urinary free cortisol (UFC) excretion. The 10 individuals with the highest UFC (290 ± 87 nmol/24 h) and the 10 with the lowest UFC (168 ± 34 nmol/24 h) were further tested. Measurements were performed at baseline, after a low dose (0.5 μg/1.73 m²) of ACTH challenge and after 2 weeks’ exposure to DEX (0.1 mg twice daily). GC sensitivity was assessed in vitro as the ability of DEX to inhibit lipopolysaccharide-stimulated production of the cytokines interleukin 1-β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in a whole-blood assay. Results:After exposure to DEX in vivo, inhibition of IL-6 and TNF-α decreased. Also, after DEX in vivo, low-cortisol men showed lower inhibition of IL-1β and IL-6, both compared to the high-cortisol group and their own baseline levels. Conclusion: A downregulation of GC sensitivity in leukocytes after exposure to an exogenous GC seems to occur most strongly in men with low cortisol levels.

Salivary cortisol levels in children of low-income women with high depressive symptomatology

Children (N = 324 boys, 315 girls) between the ages of 2.5 and 6 (mean age = 3.63) were identified in a house to house survey in low-income areas (income <20th percentile nationally) of urban Mexico. The Center for Epidemiologic Studies-Depression Scale was administered to mothers of all children. Salivary cortisol samples were taken in children as a measure of hypothalamic-pituitary-adrenocortical (HPA) system activity at time of arrival (baseline, Time 0), 25 min after arrival (Time 1), and 50 min after arrival (Time 2). Between Time 0 and Time 1, children were administered several cognitive tests. Results of hierarchical linear modeling analyses revealed that higher levels of maternal depressive symptoms were associated with lower baseline cortisol levels in their children (p < .05), while controlling for age, gender, and time since awakening. Higher levels of maternal depressive symptoms were associated with less of an increase in salivary cortisol to the arrival of the experimenters and subsequent cognitive testing (p < .05). All results were moderated by gender, with enhanced cortisol response in girls and no response in boys. These results suggest that among very low-income families, high maternal depressive symptoms are associated with hypoactivity of the HPA system in children, particularly boys.

Shyness is a necessary but not sufficient condition for high salivary cortisol in typically developing 10 year-old children

Previous research has noted both high and low baseline cortisol levels in anxious personality styles. We examined the relations among shyness, baseline salivary cortisol, and resting heart rate in a non-clinical sample of 10-year-old children. As predicted, shyness was positively correlated with baseline salivary cortisol and resting heart rate, replicating and extending earlier work with preschool age children to middle childhood. However, post-hoc analyses revealed that the scatterplot of shyness and salivary cortisol was significantly triangular in shape, indicating that shyness was a necessary, but not sufficient, condition for high salivary cortisol at age 10. For children high in shyness, salivary cortisol levels ranged from low to high; for children low in shyness, salivary cortisol levels were low. This triangular pattern was not found for the association between shyness and resting heart rate, suggesting different roles of neuroendocrine and autonomic measures in relation to shyness. The potential roles of cortisol in the maintenance of shyness developmentally are discussed as are the broader implications for clarifying prior inconsistent results on the relation between temperament and cortisol in humans. The use of triangular data analytic strategies for interpreting relations between psychological variables and identification of risk and protective factors is also discussed.

Serum ghrelin levels are suppressed in hypopituitary patients following insulin‐induced hypoglycaemia irrespective of GH status

Circulating ghrelin is suppressed during insulin-induced hypoglycaemia in healthy subjects, but it is unknown whether this is determined by feedback inhibition from counter-regulatory hormones. We therefore investigated the impact of GH and cortisol on ghrelin secretion during insulin-induced hypoglycaemia. Serum levels of ghrelin, GH, and cortisol were measured in 41 adult patients with suspected hypopituitarism during insulin-induced hypoglycaemia. Based on their peak GH response (cut-off level: 3 microg/l), the patients were divided into a GH-sufficient group (GHS) and a GH-deficient group (GHD). The GHS patients (n = 16) were younger (P < 0.01), had lower baseline cortisol levels [255 +/- 37 vs. 372 +/- 38 nmol/l (P = 0.04)], and tended to have a lower body mass index (P = 0.09) as compared to GHD patients (n = 25). By definition, peak GH (microg/l) was higher in GHS patients [15.0 +/- 1.8 vs. 1.0 +/- 0.2 (P < 0.0001)]. The increase in serum cortisol during the ITT (insulin-tolerance test) was higher and occurred later in GHS patients [Cmax (nmol/l): 561 +/- 41 vs. 412 +/- 50 (P = 0.04); Tmax (minutes): 65 +/- 5 vs. 49 +/- 5 (P = 0.03)]. Serum ghrelin levels changed significantly with time during ITT in both groups (P < 0.0001), characterized by a moderate decline during the initial 50-60 min and a return to baseline after 2 h. No significant differences were recorded in AUCghrelin during the ITT between the two groups. No gender differences in ghrelin levels were recorded. (i) Like in healthy subjects serum ghrelin levels are suppressed during an ITT in patients with suspected hypopituitarism. (ii) The suppression of ghrelin was similar in GHD and GHS subjects and was not determined by cortisol. (iii) We hypothesize that insulin rather than hypoglycaemia accounts for ghrelin suppression during an ITT.

Cortisol levels and adrenal reserve after successful cardiac arrest resuscitation.

The postresuscitation phase after out-of-hospital circulatory arrest shares similarities with severe sepsis. Corticosteroid replacement is beneficial in patients with septic shock and adrenal dysfunction. The goal of this study was to assess baseline cortisol and adrenal reserve of out-of-hospital circulatory arrest patients after recovery of spontaneous circulation. Thirty-three consecutive patients successfully resuscitated after cardiac arrest were prospectively included between March 2002 and June 2003. A serum cortisol assay and a corticotropin test (250 microg i.v.) were done 6 to 36 h after circulatory arrest. A cortisol increase smaller than 9 microg/dL after corticotropin (nonresponders) defined adrenal reserve insufficiency. Response status was compared in the three outcome groups: survival with full neurologic recovery (n = 4), early death from refractory shock (n = 10), or later death from neurologic dysfunction (n = 19). Patients who died of early refractory shock had lower baseline cortisol levels than patients who died of neurologic dysfunction (27 microg/dL [15-47] vs. 52 microg/dL [28-73], respectively; P < 0.01), suggesting an inadequate adrenal response to severe systemic inflammation. Corticotropin response status was not associated with standard severity markers and seemed uninfluenced by therapeutic hypothermia. In conclusion, patients who die of early refractory shock after cardiopulmonary resuscitation may have an inadequate adrenal response to the stress associated with this condition. Thresholds for cortisol levels at baseline and after corticotropin need to be determined in this clinical setting.

Postresuscitation disease after cardiac arrest: a sepsis-like syndrome?

Despite advances in cardiac arrest resuscitation, neurologic impairments and other organ dysfunctions cause considerable mortality and morbidity after restoration of spontaneous cardiac activity. The mechanisms underlying this postresuscitation disease probably involve a whole-body ischemia and reperfusion syndrome that triggers a systemic inflammatory response. Postresuscitation disease is characterized by high levels of circulating cytokines and adhesion molecules, the presence of plasma endotoxin, and dysregulated leukocyte production of cytokines: a profile similar to that seen in severe sepsis. Transient myocardial dysfunction can occur after resuscitation, mainly as a result of myocardial stunning. However, early successful angioplasty is independently associated with better outcomes after cardiac arrest associated with myocardial infarction. Coagulation abnormalities occur consistently after successful resuscitation, and their severity is associated with mortality. For example, plasma protein C and S activities after successful resuscitation are lower in nonsurvivors than in survivors. Low baseline cortisol levels may be associated with an increased risk of fatal early refractory shock after cardiac arrest, suggesting adrenal dysfunction in these patients. Postresuscitation abnormalities after cardiac arrest mimic the immunologic and coagulation disorders observed in severe sepsis. This suggests that therapeutic approaches used recently with success in severe sepsis should be investigated in patients successfully resuscitated after cardiac arrest.

Drs. Harkness and Monroe Reply

TO THE EDITOR: We reviewed with great interest the recent article by Kate L. Harkness, Ph.D., and Scott M. Monroe, Ph.D. (1), demonstrating a strong link between early childhood trauma and endogenous depression, in contrast to prior work linking early adversity with nonendogenous subtypes of depression (2). However, we are skeptical of these new findings in view of critical exclusions in their data collection, including a lack of consideration of atypical depression and overly narrow inclusion criteria. Atypical depression, by definition, is characterized by mood reactivity, hypersomnia, and increased eating, in contrast to the lack of mood reactivity, insomnia, and loss of appetite seen in endogenous depression. Subjects with atypical depression thus provide a natural comparison group for linking particular vulnerability factors with endogenous depressive subtypes. Using this latter approach in a communitybased sample of 653 individuals with major depression, we previously demonstrated a significant association between early childhood physical and/or sexual abuse and atypical but not endogenous symptoms of depression (3). Biological studies also point to a mechanistic link between atypical depression and severe trauma. More specifically, low baseline cortisol levels and hypersensitivity to low doses of dexamethasone have been found in both posttraumatic stress disorder (4) and atypical depression (5, 6), consistent with a hypothalamic-pituitary-adrenal (HPA) axis that is hyperregulated. In contrast, a large body of work has demonstrated hypercortisolemia and resistance to dexamethasone in endogenous depression, consistent with a stress response that is chronically overactivated and hyporegulated (7). This further suggests that severe trauma is more closely linked with atypical than endogenous depressive symptoms. Given these links between atypicality and early trauma, the sampling procedure of Drs. Harkness and Monroe becomes problematic in that individuals with chronic depression and many with a “comorbid exclusionary diagnosis” were excluded from consideration in their study. Chronicity and comorbidity are hallmarks of atypical depression (8–10) and are themselves associated with early trauma; thus, elimination of subjects with these characteristics establishes a significant sampling bias. Another issue relates to the cross-sectional nature of their study, in that many patients with recurrent depression have a fluctuation of neurovegetative symptoms over time; i.e., they may appear endogenously depressed at one point in time, while exhibiting atypical symptoms at other times (11). This is not a trivial point in that we have previously reported that depressed individuals with this fluctuating course have particularly high rates of severe childhood abuse (3). We speculate that several individuals labeled endogenous in the current study would have been designated as fluctuating had this been a consideration, further diluting the authors’ ability to find a putative link between early trauma and nonendogenous symptoms. In sum, it may be that in a heterogeneous group of individuals with major depression, particularly high rates of trauma will be found in those with atypical symptoms, while in a more homogeneous group with nonchronic illness without certain comorbidities, a link with endogenous symptoms will emerge. This is an important consideration in designing and interpreting research linking early trauma with particular depressive subtypes.

Childhood Trauma and Depression

Back to table of contents Previous article Next article Letter to the EditorFull AccessChildhood Trauma and DepressionROBERT D. LEVITAN, M.D., M.Sc., F.R.C.P.C., and SAGAR V. PARIKH, M.D., F.R.C.P.C., ROBERT D. LEVITANSearch for more papers by this author, M.D., M.Sc., F.R.C.P.C., and SAGAR V. PARIKHSearch for more papers by this author, M.D., F.R.C.P.C., Toronto, Ont., CanadaPublished Online:1 Jun 2003https://doi.org/10.1176/appi.ajp.160.6.1188AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: We reviewed with great interest the recent article by Kate L. Harkness, Ph.D., and Scott M. Monroe, Ph.D. (1), demonstrating a strong link between early childhood trauma and endogenous depression, in contrast to prior work linking early adversity with nonendogenous subtypes of depression (2). However, we are skeptical of these new findings in view of critical exclusions in their data collection, including a lack of consideration of atypical depression and overly narrow inclusion criteria.Atypical depression, by definition, is characterized by mood reactivity, hypersomnia, and increased eating, in contrast to the lack of mood reactivity, insomnia, and loss of appetite seen in endogenous depression. Subjects with atypical depression thus provide a natural comparison group for linking particular vulnerability factors with endogenous depressive subtypes. Using this latter approach in a community-based sample of 653 individuals with major depression, we previously demonstrated a significant association between early childhood physical and/or sexual abuse and atypical but not endogenous symptoms of depression (3). Biological studies also point to a mechanistic link between atypical depression and severe trauma. More specifically, low baseline cortisol levels and hypersensitivity to low doses of dexamethasone have been found in both posttraumatic stress disorder (4) and atypical depression (5, 6), consistent with a hypothalamic-pituitary-adrenal (HPA) axis that is hyperregulated. In contrast, a large body of work has demonstrated hypercortisolemia and resistance to dexamethasone in endogenous depression, consistent with a stress response that is chronically overactivated and hyporegulated (7). This further suggests that severe trauma is more closely linked with atypical than endogenous depressive symptoms.Given these links between atypicality and early trauma, the sampling procedure of Drs. Harkness and Monroe becomes problematic in that individuals with chronic depression and many with a “comorbid exclusionary diagnosis” were excluded from consideration in their study. Chronicity and comorbidity are hallmarks of atypical depression (8–10) and are themselves associated with early trauma; thus, elimination of subjects with these characteristics establishes a significant sampling bias.Another issue relates to the cross-sectional nature of their study, in that many patients with recurrent depression have a fluctuation of neurovegetative symptoms over time; i.e., they may appear endogenously depressed at one point in time, while exhibiting atypical symptoms at other times (11). This is not a trivial point in that we have previously reported that depressed individuals with this fluctuating course have particularly high rates of severe childhood abuse (3). We speculate that several individuals labeled endogenous in the current study would have been designated as fluctuating had this been a consideration, further diluting the authors’ ability to find a putative link between early trauma and nonendogenous symptoms.In sum, it may be that in a heterogeneous group of individuals with major depression, particularly high rates of trauma will be found in those with atypical symptoms, while in a more homogeneous group with nonchronic illness without certain comorbidities, a link with endogenous symptoms will emerge. This is an important consideration in designing and interpreting research linking early trauma with particular depressive subtypes.