Alex S. Keuroghlian

Depression, cortisol, and suppressed cell-mediated immunity in metastatic breast cancer.

Cancer treatment is known to have significant immuno-suppressive/dysregulatory effects. Psychological distress and depression, which often accompany cancer diagnosis and treatment, can also suppress or dysregulate endocrine and immune function. Cell-mediated immunity (CMI) is critical for protection against a host of pathogens to which cancer patients may be particularly susceptible. CMI is also important for defense against some tumors. This study explored relationships among depressive symptoms, cortisol secretion, and CMI responses in 72 women with metastatic breast cancer. Depressive symptoms were assessed with the Center for Epidemiologic Studies-Depression Scale (CES-D). Saliva was sampled throughout the day over a 3-day period to obtain a physiologic index of diurnal cortisol concentrations and rhythmicity, which is associated with breast cancer survival time. CMI for specific antigens was measured following intradermal administration of seven commonly encountered antigens (tuberculin, tetanus, diphtheria, Streptococcus, Candida, Trichophyton, and Proteus). Analyses adjusting for relevant medical and treatment variables indicated that women reporting more depressive symptoms showed suppressed immunity as measured by lower average induration size. Women with higher mean diurnal cortisol concentrations also showed suppressed immunity as indicated by a decreased number of antigens to which positive reactions were measured. This study highlights the relationships among depression, stress, and immune function in the context of advanced breast cancer.

Out on the street: a public health and policy agenda for lesbian, gay, bisexual, and transgender youth who are homeless.

A disproportionate number of lesbian, gay, bisexual, and transgender (LGBT) youth experience homelessness each year in the United States. LGBT youth who are homeless have particularly high rates of mental health and substance use problems, suicidal acts, violent victimization, and a range of HIV risk behaviors. Given the intense needs of LGBT youth experiencing homelessness, it is imperative to understand their unique experiences and develop responsive practices and policies. The range and severity of health risks vary across subgroups of all homeless LGBT youth, and because the population is nonhomogeneous, their particular needs must be identified and addressed. Thus, the purpose of this article is to review the causes of homelessness among LGBT youth, discuss the mental health and victimization risks faced by this population, address differences among homeless LGBT subgoups, and recommend effective interventions and best practices. The authors conclude by discussing promising future research and public policy directions.

A Non-Long Terminal Repeat Retrotransposon Family Is Restricted to the Germ Line Micronucleus of the Ciliated Protozoan Tetrahymena thermophila

ABSTRACT The ciliated protozoan Tetrahymena thermophila undergoes extensive programmed DNA rearrangements during the development of a somatic macronucleus from the germ line micronucleus in its sexual cycle. To investigate the relationship between programmed DNA rearrangements and transposable elements, we identified several members of a family of non-long terminal repeat (LTR) retrotransposons (retroposons) in T. thermophila, the first characterized in the ciliated protozoa. This multiple-copy retrotransposon family is restricted to the micronucleus of T. thermophila. The REP (Tetrahymena non-LTR retroposon) elements encode an ORF2 typical of non-LTR elements that contains apurinic/apyrimidinic endonuclease (APE) and reverse transcriptase (RT) domains. Phylogenetic analysis of the RT and APE domains indicates that the element forms a deep-branching clade within the non-LTR retrotransposon family. Northern analysis with a probe to the conserved RT domain indicates that transcripts from the element are small and heterogeneous in length during early macronuclear development. The presence of a repeated transposable element in the genome is consistent with the model that programmed DNA deletion in T. thermophila evolved as a method of eliminating deleterious transposons from the somatic macronucleus.

Substance use and treatment of substance use disorders in a community sample of transgender adults

BACKGROUND Transgender people have elevated substance use prevalence compared with the U.S. general population, however no studies have comprehensively examined the relationship of psychosocial risk factors to substance use and substance use disorder (SUD) treatment among both male-to-female (MTF) and female-to-male (FTM) transgender adults. METHODS Secondary data analysis of a 2013 community-based survey of transgender adults in Massachusetts (N=452) was conducted. Adjusted multivariable logistic regression models were fit to examine the relationship of four risk factor domains with SUD treatment history and recent substance use: (1) demographics; (2) gender-related characteristics; (3) mental health; (4) socio-structural factors. Adjusted Odds Ratios (aOR) and 95% Confidence Intervals (95% CI) were estimated. RESULTS Ten percent of the sample reported lifetime SUD treatment. Factors associated with significant increase in odds of lifetime SUD treatment alongside recent substance use (all p<0.05) were: (1) older age (aOR=1.02; 95% CI=1.01-1.04), higher educational attainment (aOR=3.59; 95% CI=2.35-5.50), low income (aOR=0.58; 95% CI=0.39-0.86); (2) MTF identity (aOR=3.03; 95% CI=1.95-4.67), gender-affirming medical care (aOR=1.99; 95% CI=1.32-3.00); (3) intimate partner violence (aOR=1.68; 95% CI=1.13-2.49), posttraumatic stress disorder (aOR=2.56; 95% CI=1.69-3.88), depression (aOR=2.30; 95% CI=1.58-3.35), mental health treatment (aOR=1.65; 95% CI=1.11-2.45); (4) discrimination (aOR=1.90; 95% CI=1.22-2.95), unstable housing (aOR=1.80; 95% CI=1.21-2.67), and sex work (aOR=2.48; 95% CI=1.24-4.95). CONCLUSIONS Substance use and SUD treatment among transgender adults are associated with demographic, gender-related, mental health, and socio-structural risk factors. Studies are warranted that identify SUD treatment barriers, and integrate SUD treatment with psychosocial and structural interventions for a diverse spectrum of transgender adults.

Interactions of borderline personality disorder and anxiety disorders over 10 years

OBJECTIVE This report examines the relationship of DSM-IV borderline personality disorder (BPD) to anxiety disorders using data on the reciprocal effects of improvement or worsening of BPD and anxiety disorders over the course of 10 years. METHOD We reliably and prospectively assessed borderline patients (n = 164) with DSM-IV-defined co-occurring generalized anxiety disorder (GAD; n = 42), panic disorder with agoraphobia (n = 39), panic disorder without agoraphobia (n= 36), social phobia (n = 48), obsessive-compulsive disorder (OCD; n = 36), and posttraumatic stress disorder (PTSD; n = 88) annually over a period of 10 years between 1997 and 2009. We used proportional hazards regression analyses to assess the effects of monthly improvement or worsening of BPD and anxiety disorders on each others remission and relapse the following month. RESULTS BPD improvement significantly predicted remission of GAD (hazard ratio [HR] = 0.65, P <.05) and PTSD (HR = 0.57, P < .05), whereas BPD worsening significantly predicted social phobia relapse (HR = 1.87, P < .05). The course of anxiety disorders did not predict BPD remission or relapse, except that worsening PTSD significantly predicted BPD relapse (HR = 1.90, P < .05). CONCLUSION BPD negatively affects the course of GAD, social phobia, and PTSD. In contrast, the anxiety disorders, aside from PTSD, had little effect on BPD course. For GAD and social phobia, whose course BPD unidirectionally influences, we suggest prioritizing treatment for BPD, whereas BPD should be treated concurrently with panic disorders, OCD, or PTSD. We discuss state/trait issues in the context of our findings.

The relationship of chronic medical illnesses, poor health-related lifestyle choices, and health care utilization to recovery status in borderline patients over a decade of prospective follow-up

BACKGROUND The interaction of borderline personality disorder (BPD) with physical health has not been well characterized. In this longitudinal study, we investigated the long-term relationship of chronic medical illnesses, health-related lifestyle choices, and health services utilization to recovery status in borderline patients over a decade of prospective follow-up. METHOD 264 borderline patients were interviewed concerning their physical health at 6-year follow-up in a longitudinal study of the course of BPD. This sample was then reinterviewed five times at two-year intervals over the next ten years. We defined recovery from BPD based on a Global Assessment of Functioning score of 61 or higher, which required BPD remission, one close relationship, and full-time competent and consistent work or school attendance. We controlled for potentially confounding effects of time-varying major depressive disorder. RESULTS Never-recovered borderline patients were significantly more likely than ever-recovered borderline patients to have a medical syndrome, obesity, osteoarthritis, diabetes, urinary incontinence, or multiple medical conditions (p<0.0063). They were also significantly more likely to report pack-per-day smoking, weekly alcohol use, no regular exercise, daily sleep medication use, or pain medication overuse (p<0.0083). In addition, never-recovered borderline patients were significantly more likely than ever-recovered borderline patients to undergo a medical emergency room visit, medical hospitalization, X-ray, CT scan, or MRI scan (p<0.0063). CONCLUSIONS Over a decade of prospective follow-up, failure to recover from BPD seems to be associated with a heightened risk of chronic medical illnesses, poor health-related lifestyle choices, and costly health services utilization.

Circadian dysregulation, zolpidem dependence, and withdrawal seizure in a resident physician performing shift work.

The abrupt and frequent changes in a rotating workshift schedule can lead to dysregulation of the circadian sleep/wake cycle.1,2 Many shift workers use hypnotic medications to achieve longer-lasting and higher-quality sleep, as well as acceptable work performance.3 The nonbenzodiazepine hypnotic, zolpidem, is the most widely prescribed sleep medication in the United States.4 Zolpidem has frequently been described as a safer, less addictive alternative to benzodiazepines for short-term treatment of insomnia.5 A study comparing zolpidem and triazolam, however, showed that the two drugs have comparable abuse potential.6 Reports have documented zolpidem dependence and withdrawal,5,7 as well as delirium,7 hallucinations,8 and seizure9 upon discontinuation of zolpidem. Zolpidem is nevertheless increasingly being adopted by shift workers to treat dysregulated sleep, for example among United States Air Force crew members and American resident physicians.10–12 The case presented here is the first documented report of zolpidem dependence and withdrawal seizure in the setting of circadian rhythm disturbance from shift work, specifically in a resident physician on a rotating overnight call schedule.

Advancing health equity for lesbian, gay, bisexual and transgender (LGBT) people through sexual health education and LGBT-affirming health care environments

Lesbian, gay, bisexual and transgender (LGBT) people face pervasive health disparities and barriers to high-quality care. Adequate LGBT sexual health education for emerging health professionals is currently lacking. Clinical training programs and healthcare organisations are well poised to start addressing these disparities and affirming LGBT patients through curricula designed to cultivate core competencies in LBGT health as well as health care environments that welcome, include and protect LGBT patients, students and staff. Health education programs can emphasise mastery of basic LGBT concepts and terminology, as well as openness towards and acceptance of LGBT people. Core concepts, language and positive attitudes can be instilled alongside clinical skill in delivering inclusive sexual health care, through novel educational strategies and paradigms for clinical implementation. Caring for the health needs of LGBT patients also involves the creation of health care settings that affirm LGBT communities in a manner that is responsive to culturally specific needs, sensitivities and challenges that vary across the globe.

Voluntary switching between identities in dissociative identity disorder: A functional MRI case study

Patients who suffer from dissociative identity disorder present unique scientific and clinical challenges for psychology and psychiatry. We have been fortunate in working with a patient who—while undergoing functional MRI—can switch rapidly and voluntarily between her main personality (a middle-aged, high-functioning woman) and an alternate personality (a 4–6-year-old girl). A unique task was designed to isolate the processes occurring during the switches between these personalities. Data are from two imaging sessions, conducted months apart, each showing the same activated areas during switches between these personalities. The activated areas include the following: the primary sensory and motor cortex, likely associated with characteristic facial movements made during switching; the nucleus accumbens bilaterally, possibly associated with aspects of reward connected with switching; and prefrontal sites, presumably associated with the executive control involved in the switching of personalities.

Hypnotizability, Posttraumatic Stress, and Depressive Symptoms in Metastatic Breast Cancer

Abstract This study assessed whether high hypnotizability is associated with posttraumatic stress and depressive symptoms in a sample of 124 metastatic breast cancer patients. Hypnotic Induction Profile Scores were dichotomized into low and high categories; posttraumatic intrusion and avoidance symptoms were measured with the Impact of Events Scale (IES); hyperarousal symptoms with items from the Profile of Mood States; and depressive symptoms with the Center for Epidemiologic Studies–Depression Scale. High hypnotizability was significantly related to greater IES total, IES intrusion symptoms, and depressive symptoms. A logistic regression model showed that IES total predicts high hypnotizability after adjusting for depressive symptoms and hyperarousal. The authors relate these results to findings in other clinical populations and discuss implications for the psychosocial treatment of metastatic breast cancer.