Inherited anxiety-related parent-infant dyads alter LHPA activity.

The pathogenesis of post-traumatic stress disorder (PTSD) is incompletely understood. We hypothesize that disruptions in mother-child relations may be a key contributor to development of PTSD. A normal and healthy separation-individuation process requires adaptations of self- and interactive contingency in both the mother and her child, especially in early childhood development. Anxious mothers are prone to overprotection, which may hinder the individuation process in their children. We examined long-term stress hormones and other stress markers in subjects three generations removed from the Holocaust, to assess the long-term consequences of inherited behavioral and physiological responses to prior stress and trauma. Jewish subjects who recalled overprotective parental behavior had higher hairsteroid-concentrations and dampened limbic-hypothalamic-pituitary-adrenal (LHPA) axis reactivity compared to German and Russian-German subjects with overprotective parents. We suggest that altered LHPA axis activity in maternally overprotected Jewish subjects may indicate a transmitted pathomechanism of "frustrated individuation" resulting from cross-generational anti-Semitic experiences. Thus measurements of hairsteroid-concentrations and parenting practices may have clinical value for diagnosis of PTSD. We propose that this apparent inherited adaptivity of LHPA axis activity could promote higher individual stress resistance, albeit with risk of an allostatic overload.

Tumor necrosis factor alpha-induced apoptosis in human neuronal cells: protection by the antioxidant N-acetylcysteine and the genes bcl-2 and crmA.

Tumor necrosis factor alpha (TNF-alpha) is a candidate human immunodeficiency virus type 1-induced neurotoxin that contributes to the pathogenesis of AIDS dementia complex. We report here on the effects of exogenous TNF-alpha on SK-N-MC human neuroblastoma cells differentiated to a neuronal phenotype with retinoic acid, TNF-alpha caused a dose-dependent loss of viability and a corresponding increase in apoptosis in differentiated SK-N-MC cells but not in undifferentiated cultures. Importantly, intracellular signalling via TNF receptors, as measured by activation of the transcription factor NF-kappa B, was unaltered by retinoic acid treatment. Finally, overexpression of bcl-2 or crmA conferred resistance to apoptosis mediated by TNF-alpha, as did the addition of the antioxidant N-acetylcysteine. These results suggest that TNF-alpha induces apoptosis in neuronal cells by a pathway that involves formation of reactive oxygen intermediates and which can be blocked by specific genetic interventions.

Treatment of depressive symptoms in human immunodeficiency virus-positive patients.

BACKGROUND: This randomized clinical trial compared 16-week interventions with interpersonal psychotherapy, cognitive behavioral therapy, supportive psychotherapy, and supportive psychotherapy with imipramine for human immunodeficiency virus (HIV)-positive patients with depressive symptoms. METHODS: Subjects (N = 101; 85 male, 16 female) with known HIV seropositivity for at least 6 months were randomized to 16 weeks of treatment. Inclusion criteria were 24-item Hamilton Depression Rating Scale score of 15 or higher, clinical judgment of depression, and physical health sufficient to attend outpatient sessions. Therapists were trained in manualized therapies specific for HIV-positive patients. Treatment adherence was monitored. RESULTS: Subjects randomized to interpersonal psychotherapy (n = 24) and supportive psychotherapy with imipramine (n = 26) had significantly greater improvement on depressive measures than those receiving supportive psychotherapy (n = 24) or cognitive behavioral therapy (n = 27). Similar results appeared in the completer subsample. CONCLUSIONS: Depressive symptoms appear treatable in HIV-positive patients. Interpersonal psychotherapy may have particular advantages as a psychotherapy for patients who have experienced the significant life events of HIV infection.

Adjunctive therapies for HIV-1 associated neurologic disease.

In the past decade we have seen a milder phenotype and decreased incidence of HIV-1 associated dementia (HAD), largely due to the widespread use of combination chemotherapy to reduce viral burden. However, the prevalence of neurologic disease in people living with HIV-1 has actually increased, raising significant concerns that new therapeutic strategies, directed at restoring neuronal and glial homeostasis and signaling in the central nervous system (CNS), as opposed to directly interfering with the life cycle of HIV-1, must be developed. In this review, we focus briefly on previous Phase 1 clinical trials for adjunctive (i.e., chemotherapeutic agents that do not have a primary antiretroviral mechanism of action) therapy in patients with HAD, followed by an overview of key molecular events in the neuropathogenesis of HAD, and then discuss in more detail our rationale for investigating the effects of therapeutic agents that restore impaired mitochondrial bioenergetics in the CNS. Specifically, we focus on agents that either work in part through K-ATP channels, present in both mitochondria and plasma membranes, and agents that work to weakly uncouple the respiratory capacity of the electron transport chain in mitochondria from ATP production. We propose these agents may be complementary to currently available antiretroviral agents and may significantly improve the capacity of CNS infected with HIV-1 to meet increased bioenergetic demands involved in normal synaptic communication.

Reversibility of cognitive impairment in medical inpatients.

To determine outcomes of patients admitted to the hospital with global cognitive impairment and to identify factors that might predict improvement, we screened all medical ward admissions over a one-month period with Folstein's Mini-Mental State Examination. Of 115 patients, 23 (20%) scored less than 24, indicating that they were cognitively impaired. Nineteen patients survived to discharge and were followed up for three months; three additional patients died in this period. Nine (47%) of the 19 patients significantly improved their Mini-Mental State scores. Five (26%) of the 19 improved to normal. They scored better on the initial Mini-Mental State Examination and lower (less dementia) on Blessed's Dementia Rating Scale. Age, severity and stability of medical illness, presence of neurologic abnormalities, clinical course, extensiveness of medical evaluation, and psychiatric criteria for delirium did not predict improvement.

Psychological responses to serological testing for HIV.

To determine the emotional impact of serological testing for HIV, 218 physically asymptomatic adults were evaluated in a confidential clinical setting 2 weeks before HIV test notification, immediately before and after notification, and 2 and 10 weeks later. All received extensive pre- and post-test counseling. The 179 seronegatives reported one or more HIV risk behaviors: homosexual intercourse (n = 111), heterosexual intercourse with possibly infected partners (n = 62), intravenous drug use (n = 20). Immediately after notification, seronegatives had significant decreases in visual analogue scale (VAS) measures of anxiety, depression, fear of getting AIDS, and fear of having infected others. Reductions were sustained at both follow-up assessments and were complemented by significant reductions on standardized self-reported measures of anxiety (Spielberger State Anxiety Inventory, SAI), depression (Beck Depression Inventory, BDI), and psychiatric symptoms (Brief Symptom Inventory, BSI) as well as by clinical ratings of depression (Hamilton Depression Rating Scale, HDRS). Of 39 seropositives, 35 had homosexual risk behaviors, seven had been intravenous drug users (IVDUs; four of whom were homosexual men), and one was a female partner of an IVDU. Immediately after notification, VAS measures of their anxiety were not significantly increased, and at 10 weeks after notification, their VAS measures of distress and mean scores on BDI, SAI and BSI were significantly lower than at entry. Their HDRS ratings were not significantly increased.

Inconsistent divergence of mitochondrial DNA in the spontaneously hypertensive rat.

We have recently shown that the spontaneously hypertensive rat (SHR) and the Wistar-Kyoto (WKY) rat differ at a frequency of 1 per 62 bases in their nuclear DNA (Hypertension 1992; 19:425-427). Given the origin of these strains this level of divergence was unexpected. To investigate the origin of this nuclear divergence we have examined mitochondrial DNA. Mitochondrial DNA was isolated from SHR and WKY rats, digested with several restriction enzymes, electrophoresed in 1.0% agarose gels, and the fragments visualized with ethidium bromide staining. This approach allowed us to analyze 220 base pairs of mitochondrial DNA. No differences were detected between SHR and WKY rats. Comparison with the King-Holtzman rat strain produced differences at an average of 1 per 52 base pairs. We also examined several SHR and WKY rats from within our colonies and found no differences suggesting intrastrain homogeneity for mitochondrial DNA phenotypes. These data indicate that the SHR and WKY rat share a recent, common maternal ancestor. This result is consistent with the published origins of the SHR and WKY rat strains. Together with the nuclear divergence results, the data suggest that the original Wistar colony from which SHR and WKY rats were derived was probably highly polymorphic for nuclear genes.

Organic mental disorders caused by HIV: update on early diagnosis and treatment.

HIV directly affects the CNS, primarily causing subcortical neuropathology. Dementia as the initial presentation is rare, but organic mental changes that mimic many functional disorders can occur during the course of infection. The mental status examination is not adequately sensitive to detect noncognitive dysfunction, and subjective complaints, neurological signs, reduced T4 lymphocytes, CSF abnormalities, diffuse slowing on ECG, mild cerebral atrophy on brain CT, and nonspecific hyperdensities on brain magnetic resonance imaging do not correlate reliably with early and subtle HIV-induced neuropsychological impairment. Zidovudine (AZT) can delay or reverse mental deficits, and psychostimulants can reduce apathetic withdrawal, but high-potency neuroleptics can cause neuroleptic malignant syndrome.

The psychiatry internship and the development of professional identity.

Advocates of the psychiatry internship believe the experience fosters professinal maturity. The authors examined the maturing process of 10 psychiatry residents during their internship year. Changes in the interns' professional identity including expectations of self and others are described and seen as a goal of the experience. The authors outline danger signals of poor professional development and suggest interventions to help interns resolve conflicts.

Individual psychotherapies for depressed HIV-positive patients.

OBJECTIVE: The authors present preliminary data from two treatment modalities of a randomized clinical trial in which they compared 16-week interventions of interpersonal psychotherapy to supportive psychotherapy. METHOD: HIV-positive patients who were not acutely medically ill and had scores of 15 or higher on the Hamilton Depression Rating Scale were randomly assigned to one of four treatment modalities. They were assessed by the Hamilton scale and Beck Depression Inventory at 8 and 16 weeks. Most subjects who underwent either interpersonal psychotherapy (N = 16) or supportive psychotherapy (N = 16) were male, gay or bisexual, white, and college educated. RESULTS: Results of last-observation-carried-forward and completer analyses showed that scores on the Hamilton scale and Beck Depression Inventory decreased significantly for both treatments. Differential improvement for interpersonal psychotherapy appeared by midtreatment (week 8) and persisted at termination. CONCLUSIONS: This is the first controlled study of individual psychotherapies for depressed HIV-positive patients. Results suggest that a specific antidepressant psychotherapy, interpersonal psychotherapy, has advantages over a supportive therapy.

Simultaneous in situ detection of apoptosis and necrosis in monolayer cultures by TUNEL and trypan blue staining.

A method for simultaneously detecting membrane permeability (characteristic of necrosis) and DNA fragmentation (characteristic of apoptosis) is described. By combining a common dye-exclusion method (Trypan Blue) with a commercially available terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling (TUNEL) labeling kit, we have succeeded in developing a novel methodology for obtaining permanently mounted slides of monolayer cell cultures double-labeled for DNA fragmentation and cell lysis. This method should facilitate in situ studies of cell death by allowing for a more accurate quantification of total toxicity in monolayer cell cultures and perhaps further enhance our understanding of the different mechanisms of cell death as well.

Serosurvey of human immunodeficiency virus, hepatitis B virus, and hepatitis C virus infection among hospital-based surgeons. Serosurvey Study Group.

BACKGROUND: Because occupational blood contact places health-care workers at risk for infection with bloodborne pathogens, we wanted to estimate the prevalence of infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) among hospital-based surgeons and correlate the results with occupational and nonoccupational risk factors. STUDY DESIGN: All surgeons in training or in practice in general surgery, obstetrics and gynecology, or orthopedics at 21 hospitals in moderate to high AIDS incidence areas were eligible to participate in a voluntary, anonymous serosurvey. Serum samples were tested for HIV antibody, for HCV antibody, and for markers of HBV infection: hepatitis B surface antigen, total antibody to hepatitis B core antigen, and antibody to hepatitis B surface antigen. RESULTS: Of 2,887 eligible surgeons, 770 (27 percent) participated in the study. One of 740 surgeons not reporting nonoccupational risk factors was HIV seropositive (0.14 percent, upper limit 95 percent confidence interval [CI] equals 0.64 percent). None of 20 participants reporting nonoccupational HIV risk factors and none of ten not responding to the question on nonoccupational risk factors were HIV positive. Of 129 (17 percent) participants with past or current HBV infection, three (0.4 percent) had chronic HBV infection; all were negative for hepatitis B e antigen. Risk factors for HBV infection included not receiving hepatitis B vaccine (odds ratio [OR] 14.7, 95 percent CI 8.3 to 26.0) and practicing surgery at least ten years (OR 2.2, 95 percent CI 1.3 to 3.8). Seven (0.9 percent) participants had anti-HCV. CONCLUSIONS: Although not necessarily generalizable to all surgeons in moderate to high AIDS incidence areas, these results do not indicate a high rate of previously undetected HIV infection among surgeons who trained or practiced in these areas, or both. Hepatitis B virus posed the highest risk of infection with a bloodborne pathogen, followed by HCV and HIV.

Behavioral and psychological responses to HIV antibody testing.

The development of tests to identify the antibody to human immunodeficiency virus (HIV) has made it possible to diagnose infection with the virus prior to the development of physical symptoms. The introduction of these tests raises questions regarding the effects of informing individuals of their antibody status. These issues include the emotional impact of telling individuals that they have been infected with a fatal virus and the usefulness of antibody testing in promoting behaviors that would reduce the spread of acquired immunodeficiency syndrome (AIDS). Research that has examined changes in psychological distress and in behaviors associated with HIV infection among individuals who have undergone antibody testing is reviewed. Methodological issues encountered in studying behavioral and psychological responses to antibody testing are identified, and directions for future research are offered.

Memory performance among women with parental abuse histories: enhanced directed forgetting or directed remembering?

Performance on a directed forgetting task was assessed in 24 individuals with borderline personality disorder and early life parental abuse, 24 borderline individuals with no history of abuse, and 24 healthy nonclinical controls under conditions of explicit and implicit memory. In the explicit memory condition, individuals with abuse histories showed greater differential recall of "to-be-remembered" versus "to-be-forgotten" material compared to the 2 comparison groups. Implicit memory performance was equivalent for all 3 groups. The enhanced selective memory in the abused group was the result of better recall for "remember" and not poorer recall for "forget" information, indicating that abused individuals have an enhanced ability to sustain attention to designated "remember" information. Because most people with childhood abuse recall their abuse, enhanced remembering of designated events (e.g., information not associated with abuse) may be a coping strategy.

Undermedication for pain on a burn unit.

As the consultation-liaison psychiatrist for a large burn service, the author investigated the undermedication for pain. This phenomenon could not be adequately explained by the staff's insensitivity, by mistaken ideas about analgesics, or by fears of iatrogenic addiction. For both patients and staff, the pain served to maintain self-object differentiation and to provide reassurance that the patient was alive. Developmental observations and psychoanalytic theory support this unconscious need for pain.

Use of a psychodynamic life narrative in the treatment of depression in the physically ill.

Depression, unlike grief, is a maladaptive response to the crisis of illness. This crisis has certain characteristics: (a) psychic disequilibrium with confusion and uncertainty; (b) regression with intensified transferences; and (c) a tendency to examine the trajectory of one's life. This situation makes the patient not only more vulnerable but also more responsive to intervention. These characteristic reactions of illness can be considered in designing a therapeutic maneuver to treat depression. Three cases are used for illustration. In each case a depressed patient was presented a statement that placed his physical illness in the context of his life trajectory and demonstrated the psychodynamic logic of his depression. We call this intervention a "psychodynamic life narrative." The therapeutic effect of such a narrative and the type of patient most likely to benefit from such an intervention are discussed.

Determining resuscitation status: a survey of medical professionals.

Regarding the determination of resuscitation status (RS) and the writing of do-not-resuscitate orders, we compared the recent Presidential Guidelines with the attitudes and perceptions of 143 medical professionals in a major medical center. Seventy-four percent of respondents believed that RS was primarily determined by the physician. Only 1% believed the patient decides and a minority (40%) believed the patient should decide; 61% would want to decide for themselves if they were ill. Most respondents agreed that neither patients nor staff were well-informed about the individual patient's RS. When presented case vignettes requiring a decision about RS, the respondents frequently chose a RS contrary to the wishes of a competent patient. The findings of this survey point to the significant differences between the Presidential Commission's guidelines and the actual attitudes and perceived practices of clinicians.

A resident's rotation in consultation psychiatry. A maturational experience.

The authors emphasize the importance of a consultation psychiatry experience in the maturation of the young psychiatrist by examining some of the processes operational in both community and hospital consultation work, performed by the senior author during his fourth year of residency. Such experiences can provide opportunities for developing psychiatric skills not emphasized elsewhere, including the adoption of an active therapeutic stance, the application of the psychodynamic theory to the consultation system itself, and teaching without the use of jargon. In addition the experience as consultant facilitates the transition from residency to the outside world, not only through attitudinal changes achieved by exposure to less structured settings, a change in the supervisory model, and a solidification of identity as a physician and psychiatrist, but also by providing the resident the opportunity to begin de-cathecting from the training program.

The impact of multiple bereavement in a gay male sample.

The effect of experiencing multiple close losses on a variety of psychological symptoms was examined in a sample of HIV positive and HIV negative gay men over 1 year. Symptoms assessed included depression, intrusive and avoidant thoughts and images, anxiety, and general distress. It was found that on average, experiencing two or more losses in the year prior to the initial interview was associated with significantly higher levels of distress in follow-up assessment over 1 year. Comparisons between subjects with two or fewer losses versus three or more losses produced the largest differences in emotional symptoms. HIV positive subjects showed higher levels of distress symptoms on all measures, except for intrusive and avoidant thoughts and images. These findings indicate that the experience of multiple close losses, which is rather common among HIV-infected gay men, chronically exacerbates their emotional distress.

Self-disclosure of HIV infection to sexual partners after repeated counseling.

This study, with the objective of examining voluntary self-disclosure of HIV infection after repeated counseling, was conducted in a private setting, and designed to operate in conjunction with HIV testing. Counseling was provided at entry, and then at 3 months, 6 months, and every six months thereafter. The study was conducted among 129 HIV-positive adults; the primary risk factor was history of: males having sex with males (n = 104); injection drug use (n = 19); or heterosexual contact (n = 6). Results showed that after a mean of 2.3 years since initial HIV-positive notification, 29 percent of subjects had not disclosed the HIV infection to any present partner, and 30 percent to any past sex partner. Casual sex and lower perceived social support were significantly associated with nondisclosure. The authors conclude that even after repeated individual counseling and at least several months to inform others, about one-third of the sexually active subjects did not disclose their HIV infection to any present sex partner. Clinical and public health implications are covered.