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INTRODUCTION: Nurse practitioners have the power to assess psychosocial risk and detect and prevent suicide, a problem plaguing rural areas of the United States. Suicide risk assessment can be completed using the Home, Education, Activities, Drug use and abuse, Sexual behavior, and Suicidality and depression (HEADSS) interview instrument. The purpose of this study was to determine if HEADSS is appropriate for guiding suicide risk assessment of rural adolescents. METHOD: High school students in Southwestern Pennsylvania completed qualitative questions from the Child Behavior Checklist and Coping Response Inventory as part of the Intervention to Promote Mental Health in Rural Youth. Qualitative content analysis was performed. RESULTS: Prominent themes identified by participants included academic performance, relationships, dislikes about school, friends, death, mental health, and the future. Several minor themes concerned safety. Most known risk factors for suicide were concerns of participants. DISCUSSION: The expansion of HEADSS to include death and safety should be considered. The modified version -- HEADDSSS -- can be used to guide suicide risk assessment of youth in rural Pennsylvania, ensuring both thoroughness of assessment and safety. [ABSTRACT FROM AUTHOR]

Background: Depression is one of the most commonly diagnosed and persistent psychiatric disorders among women. Women survivors of the suicide of their significant other and women survivors of abuse appear to be two groups who might likely experience depression. However, little research has been done to identify the psychological implications of both situations. Objective: The study sought to compare psychological implications, specifically depression and behavioral manifestations of depression, among female survivors of the suicide of their significant other and female survivors of abuse. Study Design: A descriptive cohort design was used. The Beck Depression Inventory (BDI) was used to measure the presence and behavioral manifestations of depression. Results: The two groups of women did not differ in their overall level of depression. Both groups were moderately to severely depressed. Differences on three BDI items were found: sadness, irritability, and social withdrawal. Conclusions: Researchers have only just begun to explore and report information with respect to women's health in relation to abuse and bereavement. The presence of depression and behavioral manifestations of depression in these two groups of women (survivors of the suicide of their significant other and survivors of abuse) needs to be examined further. Subsequently, psychiatric mental-health interventions may be developed that will impact the outcomes for both groups. [ABSTRACT FROM AUTHOR]

Background: Child sexual abuse (CSA) is a preventable national public health problem that results in adverse health consequences. Research suggests youth experiencing CSA are often of school age. Screening for early detection of health issues is integral to school nurse (SN) practice. Still, there is little evidence that routine screening when CSA is suspected is occurring in schools, despite recommendations that it should be. Lack of confidence and knowledge related to screening and reporting for CSA contribute to a SN's missed opportunity for early intervention., Purpose: The aim of this study was to describe SNs' knowledge and self-efficacy associated with screening for and reporting suspected CSA in school settings., Methods: A descriptive cross-sectional survey design was employed. The Child Abuse Report Intention Scale was sent to over 2,000 members of the National Association of School Nurses., Results: Among SN respondents (N = 123), the main findings showed almost half reported being concerned a youth was experiencing CSA but may have missed identifying it. Self-efficacy and professional responsibility were predictors of SNs' intention to screen as well as knowledge about obvious and serious signs of abuse were predictors of SNs' intention to report in this sample., Implications: An educational partnership between forensic nurse examiners and SNs can facilitate improving SNs' knowledge about nonspecific physical and behavioral indicators of abuse that are not overtly obvious. The development of a screening tool specific for use by SNs can empower their confidence to screen by providing a resource for them to use as a guide when they are uncertain about the evidence., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 International Association of Forensic Nurses.)

Active service members and Veterans with a combat-related traumatic brain injury (TBI) are four times more likely to attempt suicide than those without a TBI. TBIs are the signature injuries of the Post-9/11 conflicts and Combat Veterans (i.e., current and former service members who deployed in support of a combat mission) with these injuries are entitled to receive the Purple Heart medal. However, potentially tens of thousands of Combat Veterans did not receive, or were denied the Purple Heart during the first decade of the Global War on Terrorism because a TBI was not documented during the deployment. To our knowledge, this is the first study to explore the meaning of the Purple Heart and examine the impact of the Purple Heart on Army Combat Veterans with a combat-related TBI. Findings from this mixed methods study revealed that not receiving the Purple Heart is associated with increased suicide risk and lower quality of life after a brain injury. Additionally, thwarted belongingness, perceived burdensomeness, and perceived military institutional betrayal are associated with increased suicide risk in Army Combat Veterans with a TBI. This mixed methods study provides important insights into how Army culture is perceived and the power of the Purple Heart among this high-risk group of Combat Veterans.

This integrative review expands on the work of Kramer et al. (2020), by reviewing studies that utilized the Interpersonal Needs Questionnaire (INQ) to examine the interpersonal constructs (thwarted belongingness and perceived burdensomeness) of the Interpersonal Theory of Suicide (ITS) to understand suicidal thoughts and behaviors among service members and Veterans with combat experience. Very few studies (n = 9) in the literature were identified, however important relationships were revealed between combat exposure/experiences, thwarted belongingness, perceived burdensomeness, and suicidal thoughts and behaviors among military samples. Studies also reported risk factors for high levels of thwarted belongingness or perceived burdensomeness in military samples, such as moral injuries, betrayal, and aggression. This review highlights the utility of the INQ to measure ITS constructs among Post-9/11 U.S. Combat Veterans.

Problem: Suicide is a leading cause of death in children. Sexual minority youth are greater than three times more likely to attempt suicide than their cisgender heterosexual peers., Eligibility Criteria: Empirical and theoretical literature were evaluated through the integrative review process using the Whittemore-Knafl integrative review model (2005). Studies were included when they addressed LGBTQ+ youth seeking emergency care for suicidality., Sample: The final sample included a mix of 13 qualitative, quantitative, and mixed methods studies published in peer-review journals between 2011 and 2020. These articles were located in journals found through a database search, including Medline EBSCO, Health Source/Nursing Academic Education, SportDiscus, ERIC EBSCO, Academic Search Elite, Social Services Abstracts, Sociological Abstracts, APA Psych Info, Embase, and CINAHL., Results: Thirteen studies included individuals 5 to 26 years of age; ten studies included individuals > 11 years old. The analysis and synthesis of coded and grouped data resulted in four themes: 1) affirmation/acceptance, 2) strength, 3) approach/intervention, and 4) safety/psychological distress., Conclusions: Research study methods, design, setting, and quality varied. This integrative review has established that youth who identify as LGBTQ+ and are seeking emergency care for suicidality, value: acceptance, safety, strength, and approach/intervention., Implications: There are strong implications for research, healthcare policy, and pediatric nursing practice. Future research is needed to explore the unique values, beliefs, and experiences of youth who identify as LGBTQ+ seeking emergency/crisis care for suicidality., Competing Interests: Declaration of competing interest None., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Lack of preceptors and hands-on training opportunities has long been an impediment to nurses pursuing sexual assault nurse examiner (SANE) practice and certification after completing a SANE didactic course. In addition, nurses in rural and underserved areas often lack the professional support and mentoring needed. To address this gap and increase the number of certified practicing SANEs, the Duquesne University School of Nursing (DUSON) received funding from the Department of Health Resources and Services Administration for a program designed to provide advanced nursing education to increase the number of nurses who are trained and certified as nurse examiners., Approach: The DUSON developed a hands-on clinical preceptor course and other support programming to supplement the existing SANE didactic course training. The goal was to create a comprehensive model that took students from initial SANE training through to certification., Lessons Learned: In the first two- and three-quarter years of the program, 36 nurses achieved certification, and another 116 completed a didactic course and initial hands-on skills training and are preparing for certification. Approximately 41.5% of participants are from rural and/or underserved areas. Challenges included the adaptations required by the COVID-19 pandemic and engagement of nurses once they returned to their home institution to complete additional hours., Conclusions: The DUSON comprehensive model provides a solid pathway for nurses who want to become SANEs, and the structure of the program seems especially conducive for training nurses in rural and underserved areas., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 International Association of Forensic Nurses.)

Competing Interests: The authors declare no conflict of interest.

Abstract: As a growing profession, forensic nursing requires research to establish best practice guidelines leading to evidence-based practice. In addition, forensic nursing quality improvement projects are necessary to evaluate and improve practices and policies. The purpose of this article is to provide step-by-step guidelines on research and quality improvement projects to encourage all forensic nurses to actively contribute to and utilize research in practice. Research will expand our forensic nursing science and knowledge base. Ultimately, forensic nursing research will benefit our patients and communities by establishing enhanced, evidence-based care., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 International Association of Forensic Nurses.)

The constructed theory of forensic nursing care is a middle-range nursing theory developed from the integrated practice model for forensic nursing science, a conceptual framework. Theory evolution was achieved following a critique of the conceptual framework and through inductive and deductive reasoning. A review of nursing theory growth and significance of middle-range theories is presented as background information in understanding the importance of this emerging forensic nursing middle-range theory. The philosophical and theoretical foundations of forensic nursing are bolstered with the addition of three nursing theories, two healthcare models and one social theory. Links are made between theory components and the current state of forensic nursing. Assumptions and concepts are clearly defined. The middle-range theory provides three testable propositions to frame forensic nursing practice, education, and research. Research conducted on the propositions will expand the forensic nursing scientific base leading to enhanced evidence-based practice. A pictorial model illustrates the propositions as relational statements. The constructed theory of forensic nursing care affirms the focus of forensic nursing care is on the nurse-patient relationship and improved health outcomes. Additional results of forensic nursing care are improved forensic science and criminal justice system outcomes.

Following sexual assaults, victims are advised to seek health care services with forensic evidence collected and packaged in sexual assault kits (SAKs). This large ( N = 1,874), retrospective study examined rates of SAK submissions by law enforcement to the state crime laboratory for analysis from 2010 to 2013 at four sites in a Western state in the United States with established sexual assault nurse examiner (SANE) programs. Variables of legal and extralegal characteristics in sexual assault cases were explored through generalized estimating equations (GEE) modeling to determine what factors statistically predicted SAK submissions. For submitted SAKs, the length of time between the dates of assault and dates of submission was categorized, and bivariate and multivariate analyses were calculated to discover legal and extralegal characteristics affecting time of submission. The study sites represented 40% of the state's law enforcement agencies and 65% of the state's population. Out of the 1,874 SAKs in the study, only 38.2% were submitted by law enforcement to the state crime laboratory for analysis. When SAK submissions were examined based on time between assaults and submission dates, 22.8% were submitted within a year of the assault and 15.4% were submitted more than a year after the assault following media and community pressure for law enforcement agencies to submit SAKs in storage. Significant variability of SAK submission rates and the time submitted from the assault dates were found between the sites. Site location was found to be the main determinant of whether or not SAKs were submitted. The lack of SAK submissions for analysis results in justice denied for victims and raises public safety concerns. The finding that the location in which the sexual assault occurred was the primary factor on SAK submissions represents an inequity of justice.

Stigma and discrimination toward overweight and obese people pose consequences to their psychological and physical health. In the United States, overweight and obesity and affects over 34% of the population. This frequently ignored public health issue often sees overweight and obese individuals blamed for their weight, thereby justifying the bias. During a post-sexual-assault examination, sexual assault nurse examiners and other forensic examiners must be cognizant of the specific issues and challenges related to the care of these victims. Forensic nurses may need to refine their techniques such as positioning overweight and obese patients on an appropriate-sized table, obtaining equipment for better visualization, and requiring assistance during the examination (e.g., lifting the victim's pendulous skin folds for assessment and evidence collection). Moreover, they may need to recognize and reflect on their own weight related biases. Addressing these important issues may lead to decreasing stigmatization during examinations, thereby providing quality care to victims of sexual assault, regardless of their weight.

Background and Purpose: Self-employed nurse practitioners (NPs) have been part of the American health care landscape since the 1970s, owning practices throughout the United States. The purpose of this study was to explore and measure the 2 characteristics of job satisfaction and empowerment in self-employed NPs practicing within the 50 states and District of Columbia and to explore factors that influence these characteristics., Methods: A convergent parallel design, mixed methods study, using a survey and semistructured interviews, was completed. The survey included the Misener Job Satisfaction Survey and Conditions of Work Effectiveness Questionnaire II., Conclusions: Self-employed NPs are satisfied and empowered. The more empowered, the higher their level of job satisfaction. Over 40% practiced with full practice authority in a rural location, and 50% had over 10 years of experience as both an RN and NP. Their experience in private practice was explored further in the interviews., Implications for Practice: This study identifies barriers to job satisfaction and empowerment in self-employed NPs, including physician oversight and lack of business management education. Continuing work to remove restricted and reduced state regulatory environments and to provide education on business management may increase the number of NPs in private practice, expanding access to health care in the United States.

The use of probiotics in the hospital setting is largely understudied and highly controversial. Probiotics are living organisms that, when taken internally, can produce an immunomodulating effect and improve the gastrointestinal (GI) mucosal barrier. Although used for centuries by healthy individuals for GI health, their use in the hospital setting is now gaining wide attention for the prevention of infectious complications such as antibiotic-associated diarrhea, Clostridium difficile infections, multiple-organ dysfunction syndrome, and ventilator-associated pneumonia. However, current understanding of the efficacy of probiotics in the acute care setting is confounded by the inconsistencies in the literature with regard to the strain of probiotic being studied, optimal dosage, and timing and duration of dosing, which make the formulation of clinical practice guidelines difficult. Although the safety of probiotics has been confirmed when used for the prevention and treatment of certain diseases, practitioners remain hesitant to administer them to their patients, citing the lack of high-quality studies clearly demonstrating efficacy and safety. Infection is a cause of late death in trauma patients, but only recently has research been conducted on the use of probiotics specifically for the prevention of hospital-acquired infections in trauma patients. In the face of such limited but promising research, is it reasonable to use probiotics for the prevention of infection in hospitalized trauma patients and improve outcomes? Use of the "precautionary principle" may be useful in this instance.

Health priorities of women after incarceration remain poorly understood, constraining development of interventions targeted at their health during that time. We explored the experience of health and health care after incarceration in a focused ethnography of 28 women who had been released from prison or jail within the past year and were living in community corrections facilities. The women's outlook on health was rooted in a newfound core optimism, but this was constrained by their pressing health-related issues; stress and uncertainty; and the pressures of the criminal justice system. These external forces threatened to cause collapse of women's core optimism. Findings support interventions that capitalize on women's optimism and address barriers specific to criminal justice contexts. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

This retrospective study of medical examiner records from three counties reported on 252 persons who killed 302 victims before killing themselves and reviews the Tarasoff ruling that set the standard for duty to warn and/or protect third parties whose lives are threatened by a patient. The three sites varied significantly for the perpetrator in terms of race, employment, cause of death, and motive. Female offenders killed more children under the age of 10 and adolescents than did male offenders. Evidence of premeditation included suicide notes and weapon brought to the crime scene, while strangulation indicated a spontaneous domestic homicide. Implications for practice are discussed including the importance of evaluating violent thoughts, fantasies, and behaviors in acute emergency settings and recommendations include second opinion consultation for Tarasoff-type cases and psychological autopsy review for completed homicide-suicide cases.

Pennsylvania's response to adolescent suicide is its Student Assistance Program (SAP). SAP has been funded for 27 years although no statewide outcome studies using case-level data have been conducted. This study used logistic regression to examine drug-/alcohol-related behaviors and suspensions of suicidal students who participated in SAP. Of the 46 services, 10 best predicted (p<.01) that these undesirable outcomes would cease. Although no study subjects died by suicide, 42 of 374,626 referred students did die by suicide. Suicidal students who did not participate had double the rate of suicide of suicidal participants of SAP. Students referred for other reasons also killed themselves. Further work must be done to assess all referred students for suicide risk, examine educational outcomes, monitor substance-related crimes and overdoses, and examine school-related factors postmortem. Evidence from this study can be used by researchers to plan future studies and by Pennsylvania's school nurses when planning services.

Objective(s): This study examined the health status of women with a recent history of incarceration and explored if/how women were accessing health care resources at the time immediately following release., Design and Sample: This mixed methods study utilized two phases: (1) a quantitative survey; and (2) qualitative interviewing. Thirty-four women (18 years of age and older, released from incarceration in the last 12 months) participated in the quantitative phase; 11 of those completed the qualitative interviews., Measures: In phase 1, data were collected on demographics, health history, health status, and health-promoting behaviors. In the second phase, semi-structured interviews were used., Results: Women in the study reported below average health status compared with the general population. The major health issues identified by participants included specific health problems affected by incarceration, mental health needs, routine health promotion and maintenance, recovery from substance abuse as a major health concern, and social and environmental barriers to care., Conclusions: Women leaving jail or prison have significant and complex health care needs. This period of transition appears to be an opportune time to offer support, services, and other health-promoting interventions., (© 2013 Wiley Periodicals, Inc.)

Background: A 30° head-of-bed elevation is recommended for most critically ill patients. Measuring intrabladder pressure with the patient in this position is controversial., Objective: To assess the feasibility of measuring intrabladder pressure with a 30° head-of-bed elevation., Methods: A prospective, randomized, and experimental study. Patients had intrabladder pressure measured first while positioned supine with a 30° head-of-bed elevation and 25 mL of saline instilled into the bladder and again after the patients were randomly repositioned to supine without any head-of-bed elevation (flat) or with a 30° head-of-bed elevation while supine or in right lateral or left lateral position with either 25, 50, or 200 mL of saline instilled into the patient's bladder., Results: Intrabladder pressures measured with the patient in all 3 head-of-bed elevated positions were higher than pressures measured with patients supine and flat after instillation of 25 mL of saline into the bladder, but intrabladder pressure did not differ between the 30° head-of-bed elevated positions and the supine and flat positions when 50 or 200 mL of saline was instilled into the bladder. Two-way analysis of variance showed a significant interaction between volume of saline instilled (P = .05), patient's position (P = .007), and bladder instill volume and position interaction (P = .004)., Conclusion: It is feasible to measure intrabladder pressure with a 30° head-of-bed elevation, and that position could be an alternative to supine positioning of patients for measurement of intrabladder pressure.

Background: The reliability of intrabladder pressure measurements obtained in nonsupine patients is unknown., Objectives: To investigate the reliability of measurements of intrabladder pressure obtained with 30 degrees head-of-bed elevation., Methods: With patients supine, 30 degrees head-of-bed elevation, and instillation of 0 and 25 mL physiological saline, intrabladder pressure was measured in 10 patients: twice by one nurse to assess intraobserver reliability and once by a different nurse to assess interobserver reliability. Data were analyzed by using paired t tests, Pearson correlation, and Bland-Altman analysis., Results: For intraobserver reliability, measurements obtained with no instillation (mean difference, -1.8; 95% confidence interval [CI], -4.9 to 1.3; P = .22) and with instillation of 25 mL (mean difference, -0.6; 95% CI, -1.8 to 0.6; P = .28) did not differ significantly. Pearson r values were 0.74 and 0.81, respectively. Estimated Bland-Altman bias and limits of agreements were -1.8 and -10.3 to 6.7 mm Hg and -0.6 and -3.82 to 2.62 mm Hg, respectively. For interobserver reliability, measurements obtained with no instillation (mean difference, 1.0; 95% CI, -2.2 to 4.2; P = .49) and with instillation of 25 mL (mean difference, -0.7; 95% CI, -2.45 to 1.05; P = .39) did not differ significantly. Pearson r values were 0.78 and 0.82, respectively. Estimated Bland-Altman bias and limits of agreement were 1.0 and -7.76 to 9.76 mm Hg and -0.7 and -5.5 to 4.0 mm Hg, respectively., Conclusions: Reliability of intrabladder pressure measurements obtained with 30 degrees head-of-bed elevation is strong.

Background: Chiari I malformation (CMI) is diagnosed by rigid radiographic criteria along with appropriate clinical symptomatology. The aim of this study was to investigate the dimensions of the posterior cranial fossa in patients without significant tonsillar descent but with symptoms comparable to CMI., Methods: Twenty-two patients with signs and symptoms comparable to CMI but without accepted radiographic criteria of tonsillar descent > 3-5 mm were referred to our clinic for evaluation. A history and physical examination were performed on all patients. In reviewing their MRI scans, nine morphometric measurements were recorded. The measurements were compared to measurements from a cohort of twenty-five individuals with cranial neuralgias from our practice., Results: For patients with Chiari-like symptomatology, the following statistically significant abnormalities were identified: reduced length of the clivus, reduced length of basisphenoid, reduced length of basiocciput, and increased angle of the tentorium. Multiple morphometric studies have demonstrated similar findings in CMI., Conclusion: The current classification of CMI is likely too restrictive. Preliminary morphologic data suggests that a subgroup of patients exists with tonsillar descent less than 3 mm below the foramen magnum but with congenitally hypoplastic posterior fossa causing symptomatology consistent with CMI.

Purpose: To provide clinicians with guidelines for the assessment, evaluation, diagnosis, and management of comorbid depression and anxiety in the primary care setting., Data Sources: Research-based articles in the medical and psychiatric literature, literature reviews by experts in the field, and DSM-IV-TR., Conclusions: Comorbid anxiety and depression occurs at a high rate in primary care, and is costly to both the individual and to society. These patients most often present in primary care settings, have more severe symptoms, and require more health care resources. The presentation of depression and anxiety together pose complicated diagnostic and treatment challenges, leading to inadequate diagnosis and treatment resulting in unnecessary patient distress and increased utilization of health care services., Implications for Practice: This article is a review of comorbid depression and anxiety with a focus upon societal and patient significance and impact, under recognition and under treatment, diagnostic challenges, medical comorbidity, treatment considerations, and educational strategies. Effective assessment, evaluation, diagnosis and treatment can lead to better treatment outcomes and improved quality of life in primary care patients.

This study evaluates the effects of two group interventions, the Bereavement Group Postvention (BGP) and the Social Group Postvention (SGP), on the bereavement outcomes in widowed survivors of suicide. The goals were to determine if the group interventions would significantly decrease levels of depression, psychological distress, and grief, as well as significantly increase the level of social adjustment among widowed survivors of suicide. Sixty widowed survivors of suicide were randomized to either the BGP or SGP intervention for 1-1/2 hour weekly sessions over an 8-week period. Study participants were recruited through various media and community referrals and initiated telephone contact with the study investigators. Statistically significant changes were found on all measures when the SGP and the BGP were combined for analyses on posttreatment assessments at 3 to 5 days after completion of the group intervention, and 6 months and 12 months after the intervention. Participants experienced a significant reduction in overall depression, psychological distress, and grief, as well as an increase in social adjustment. Further research with tighter controls of confounding variables as well as the inclusion of a no-treatment control group is indicated.

Abuse of women by their intimate partner is a staggering national problem. Abused women have a higher number of medically unexplained somatic symptoms, more functional disability, a lower self-rating of general health, and higher health care utilization when compared to nonabused women. The authors' purpose in this study was to examine differences in occurrences of negative life experiences, level of depression, and T-cell function between abused and nonabused women. The sample consisted of abused women (n = 12) and nonabused women (n = 12). Hypotheses tested were (1) abused women will have more negative life experiences than nonabused women, (2) abused women will have higher levels of depression than nonabused women, and (3) abused women will have reduced T-cell function compared to nonabused women. A cross-sectional cohort design was used to compare differences in negative life experiences, levels of depression, and T-cell function. Independent sample t-tests were performed comparing the abused versus nonabused women on the dependent measures. Significant differences were found between the groups for negative life experiences (LES; t = 2.29, p < 0.05), level of depression (BDI; t = 3.48, p < 0.01), and T-cell function (TMR; t = -5.62, p < 0.01). These findings are descriptive and do not establish causal links. However, this is an inquiry into the psychological and biobehavioral responses of women experiencing abuse and their potential health problems. The study shows that abused women reported more negative life experiences, experienced higher levels of depression, and experienced lower T-cell function when compared with nonabused women.

Of heuristic value in understanding the neurochemistry of major depression is whether the hypothalamo-pituitary-adrenocortical (HPA) axis hyperactivity that occurs in this illness can be related to putative neurotransmitter dysfunction(s). Cholinergic neurotransmission stimulates hypothalamic corticotropin releasing hormone (CRH) and arginine vasopressin (AVP) secretion, both of which stimulate pituitary corticotropin (ACTH) secretion, but whether the HPA axis in humans is activated only by doses of cholinergic agonists that produce noxious side effects remains controversial. To test the hypothesis of increased cholinergic sensitivity in major depression, physostigmine (PHYSO), a reversible cholinesterase inhibitor, was administered to patients and control subjects at a dose that elevated plasma ACTH, cortisol, and AVP concentrations but produced few or no side effects. Exogenous AVP also was administered to determine if it would augment the effect of low-dose PHYSO on the HPA axis. Twelve premenopausal or estrogen-replaced female major depressives, 12 individually matched female control subjects, eight male major depressives, and eight matched male control subjects underwent four test sessions 5-7 days apart: PHYSO (8 microg/kg IV), AVP (0.08 U/kg IM), PHYSO + AVP, and saline control. Serial blood samples were taken before and after pharmacologic challenge and analyzed for ACTH1-39, cortisol, and AVP. Estradiol and testosterone were also measured at each test session. PHYSO (8 microg/kg) significantly increased plasma ACTH, cortisol, and AVP, while producing no side effects in approximately half the subjects and predominantly mild side effects in the other half. These hormone increases following PHYSO occurred primarily in the female depressives and the male control subjects and were not significantly related to the presence or absence of side effects. The greater the ACTH and AVP responses to PHYSO, the stronger their correlation, suggesting that AVP may have been acting as a secretagogue for ACTH. Administered AVP significantly increased the secretion of ACTH in the patients and control subjects to a similar degree, and AVP given after PHYSO did not augment the HPA axis response to a greater degree in the depressives than in the control subjects. Plasma estradiol and testosterone were within the normal range for all four groups of subjects and were not significantly related to their HPA axis hormone responses. The study results support the hypothesis of heightened cholinergic sensitivity in premenopausal female, but not in male, patients with major depression. The low dose of PHYSO used may represent a useful paradigm for central cholinergic stimulation of the HPA axis.

Animal studies indicate that central cholinergic neurotransmission stimulates CRH secretion, but several human studies suggest that the hypothalamo-pituitary-adrenal cortical (HPA) axis may be activated only by doses of cholinergic agonists that produce noxious side effects and, by inference, a nonspecific stress response. Physostigmine (PHYSO), a reversible cholinesterase inhibitor, was administered to normal women and men at a dose that elevated plasma ACTH1-39, cortisol, and arginine vasopressin (AVP) concentrations but produced few or no side effects. Exogenous AVP also was administered alone and following PHYSO, to determine if it would augment the effect of PHYSO on the HPA axis. Fourteen normal women and 14 normal men matched to the women on age and race underwent four test sessions 5 to 7 days apart: PHYSO (8 micrograms/kg i.v.), AVP (0.08 U/kg i.m.), PHYSO plus AVP, and saline control. Serial blood samples taken before and after pharmacologic challenge were analyzed for ACTH1-39, cortisol, and AVP. PHYSO and AVP administration produced no side effects in about half the subjects and mild side effects in the other half, with no significant female-male differences overall. There also were no significant female-male differences in ACTH1-39 or cortisol responses to AVP. In contrast, the men had significantly greater ACTH1-39 responses to PHYSO administration than did the women. The endogenous AVP response to PHYSO also was significantly greater in the men than in the women, and the ACTH1-39 and AVP responses to PHYSO were significantly correlated in the men (both = +0.70) but not in the women. None of the hormone responses was significantly correlated with the presence or absence of side effects in either group of subjects. These results indicate a greater sensitivity of the HPA axis to low-dose PHYSO in normal men than in normal women, which likely is mediated by increased secretion of AVP. The lack of difference in side effects between the two groups of subjects and the lack of significant correlations between presence or absence of side effects and hormone responses in either group suggest that the increased hormone responses in the men were due to increased responsivity of central cholinergic systems and not to a nonspecific stress response.

To determine the relationship of pretreatment hypothalamic-pituitary-adrenal cortical (HPA) axis measures in major depressives to the occurrence of relapse following discontinuation of successful treatment, we compared pretreatment demographic, clinical, and HPA axis measures in 35 patients with DSM-III-R primary major depression divided into two groups. One group (n = 26) required continuing treatment to hold their symptoms in abeyance, and the other group (n = 9) had been successfully tapered off medication, remained in remission, and had been medication-free for at least 1 month. The major features that differentiated the 26 patients who required continuing medication to abate their symptoms from the 9 patients who were successfully discontinued from treatment were trends toward a longer duration of episode prior to initial study and increased baseline corticotropin (ACTH) 1-39, and significantly higher baseline cortisol and cortisol response to ACTH 1-24, in the former group. These results suggest that measures of HPA axis hyperactivity, along with longer duration of the index depressive episode, may predict the need for continuing medication for patients to remain in remission.

We previously reported a trend toward a higher mean nocturnal serum melatonin (MEL) concentration, based on 30-min blood sampling over 24 h, in 23 female definite endogenous depressive compared to 23 matched normal female control subjects, and no significant difference in 15 male depressives compared to their controls (Rubin et al., 1992). In both groups of patients vs. their controls, there also were trends toward an earlier MEL rise time, by about 30 min, and a later MEL peak time, by about 90 min. Because the offset of MEL secretion was not estimated in that study, the total duration of MEL secretion could not be determined. To further delineate the nocturnal MEL secretion curve, we modeled the MEL data by a linear-Beta model, a four-parameter adaptation of the Beta function. One parameter accounted-for baseline (diurnal) MEL concentration, two accounted for the shapes of the ascending and descending phases of the nocturnal secretion curve, and the fourth accounted for the area under the curve. The model permitted estimation of the start, peak, and end times of nocturnal MEL secretion. There again was a trend toward a higher mean nocturnal MEL concentration in the female depressives compared to their matched controls. There were no significant patient-control differences in secretion onset or peak times in either the women or the men except for nocturnal MEL offset time: the female patients had a trend toward a later offset time, by about 40 min, than their controls; this difference was not present in the men. With women and men analyzed together, the difference in nocturnal MEL offset time between patients and controls just reached significance (P < 0.05). The linear-Beta model appears to satisfactorily fit the MEL data and provides estimators of the onset, peak, and offset times of the activation phase of MEL secretion. This model may be applicable to more severely skewed 24-h hormone secretion curves, such as ACTH and cortisol.