The Effects of Altered Prenatal Melatonin Signaling on Adult Behavior and Hippocampal Gene Expression of the Male Rat: A Circadioneuroendocrine-Axis Hypothesis of Psychopathology

Disturbances in melatonin - the neurohormone that signals environmental darkness as part of the circadian circuit of mammals - have been implicated in various psychopathologies in humans. At present, experimental evidence linking prenatal melatonin signaling to adult physiology, behavior, and gene expression is lacking. We hypothesized that administration of melatonin (5 mg/kg) or the melatonin receptor antagonist luzindole (5 mg/kg) to rats in utero would permanently alter the circadian circuit to produce differential growth, adult behavior, and hippocampal gene expressionin the male rat. Prenatal treatment was found to increase growth in melatonin-treated animals. In addition, subjects exposed to melatonin prenatally displayed increased rearing in the open field test and an increased right turn preference in the elevated plusmaze. Rats administered luzindole prenatally, however, displayed greater freezing and grooming behavior in the open field test and improved learning in the Morris water maze. Analysis of relative adult hippocampal gene expression with RT-PCR revealed increasedexpression of brain-derived neurotrophic factor (BDNF) with a trend toward increased expression of melatonin 1A (MEL1A) receptors in melatonin-exposed animals whereas overall prenatal treatment had a significant effect on microtubule-associated protein 2(MAP2) expression. Our data support the conclusion that the manipulation of maternal melatonin levels alters brain development and leads to physiological and behavioral abnormalities in adult offspring. We designate the term circadioneuroendocrine (CNE)axis and propose the CNE-axis hypothesis of psychopathology.

Alcohol consumption and binge drinking in young adult childhood cancer survivors

Background This study compared frequency of alcohol consumption and binge drinking between young adult childhood cancer survivors and the general population in Switzerland, and assessed its socio-demographic and clinical determinants. Procedure Childhood cancer survivors aged <16 years when diagnosed 1976–2003, who had survived >5 years and were currently aged 20–40 years received a postal questionnaire. Reported frequency of alcohol use and of binge drinking were compared to the Swiss Health Survey, a representative general population survey. Determinants of frequent alcohol consumption and binge drinking were assessed in a multivariable logistic regression. Results Of 1,697 eligible survivors, 1,447 could be contacted and 1,049 (73%) responded. Survivors reported more often than controls to consume alcohol frequently (OR = 1.7; 95%CI = 1.3–2.1) and to engage in binge drinking (OR = 2.9; 95%CI = 2.3–3.8). Peak frequency of binge drinking in males occurred at age 24–26 years in survivors, compared to age 18–20 in the general population. Socio-demographic factors (male gender, high educational attainment, French and Italian speaking, and migration background from Northern European countries) were most strongly associated with alcohol consumption patterns among both survivors and controls. Conclusions The high frequency of alcohol consumption found in this study is a matter of concern. Our data suggest that survivors should be better informed on the health effects of alcohol consumption during routine follow-up, and that such counseling should be included in clinical guidelines. Future research should study motives of alcohol consumption among survivors to allow development of targeted health interventions for this vulnerable group.

[Joint preserving surgery of the adult hip: pelvic osteotomies]

Deformity and malposition of the acetabulum can occur during the development of the hip. Developmental hip dysplasia and acetabular retroversion are possible causes of osteoarthritis in the young adult. Surgical management with reorientation of the acetabulum allows causal therapy of the deformity and preservation of the native hip joint. Established techniques are the Bernese periacetabular osteotomy (PAO) and the Tönnis and Kalchschmidt triple osteotomy of the pelvis. Both techniques permit three-dimensional correction of the position of the acetabulum. Advantages and disadvantages of each technique must be considered and are summarized in the present paper. If performed early (osteoarthritis grade Tönnis 0 and 1) with correct indication and proper technique, good results can be expected.

Comparison of cartilage histopathology assessment systems on human knee joints at all stages of osteoarthritis development

To compare the MANKIN and OARSI cartilage histopathology assessment systems using human articular cartilage from a large number of donors across the adult age spectrum representing all levels of cartilage degradation.

Alteration in 5HT1A Receptor Activity from a Prenatal Exposure to Dexamethasone in a Stressed and Non-Stressed Adult Male Rat

Synthetic glucocorticoids (GC) are used as a clinical therapeutic to stimulate lung development in fetuses that present the risk of preterm delivery. Previous studies have shown that a prenatal exposure to Dexamethasone (DEX) causes a disturbance in normal GC mediation of neuritic outgrowth, cell signaling, and serotonergic systems. Our hypothesis is that a prenatal exposure to DEX during the third trimester of pregnancy alters 5HT1A receptor function. Pregnant dams were injected daily with 150μg/ml/kg of DEX from gestation day 14 through 19. Control dams were treated with and equal volume of saline. Swim stress followed by elevated plus maze testing was conducted on male rats an hour and a half prior to being sacrificed to induce postnatal acute stress. The non-stressed group was also tested and allowed to return to baseline before sacrifice. Hippocampi were analyzed using a radioligand-receptor binding assay and GTPγS35 incorporation (3H-MPPF antagonist and 8-OH-DPAT agonist, respectively). A significant increase in Kd was found in non-stressed DEX-exposed animals compared to non-stressed controls (p

EFFECTS OF PRENATAL DEXAMETHASONE ON HIPOPCAMPAL SEROTONIN 1A RECEPTORS IN ADULT MALE RATS

The main activation route for the stress response is the hypothalamo-pituitaryadrenal axis (HPA) and the sympatho-adrenomedullary system. The HPA axis is a neuroendocrine feedback loop mediated by an array of tissue specific hormones, receptors and neurotransmitters that regulate glucocorticoid (GC) release. GCs are steroidal hormones produced by the adrenal glands and are key players in a negativefeedback loop controlling HPA activity. They influence the HPA axis through glucocorticoid receptors in the hypothalamus and pituitary and through both glucocorticoid (GR) and mineralcorticoid receptors (MR) that are co-localized in the hippocampus. Repeated or chronic stress exerts a negative influence on these HPA axis regulatory sites and contributes to potentially pathological conditions, especially during early development. For example, chronic stress promotes increased maternal adrenal gland secretion of glucocortiocoid, leading to abnormally high concentrations of GC inthe fetal environment. The timing and maturation of the HPA axis relative to birth is highly species specific and is closely linked to landmarks in fetal development. In rats this development of the HPA axis takes place in utero and continues even shortly after birth. It is likely that the maternal endocrine environment will affect fetal development during this critical time point and may alter the overall set point for the expression ofgenes and their protein products that mediate fetal HPA axis function. Dexamethasone (DEX) is a synthetic glucocorticoid (sGC) and is a consensus treatment in preterm pregnancies used to expedite fetal lung development. However it has been shown that DEX causes long term physiological and behavioral disorders in prenatally-exposed laboratory animals. Previous studies have also shown that it alters the MR: GR receptor ratio in the hippocampus. Taking into consideration corticosteroid regulation of serotonin receptors, especially 5HT1A receptors and their putative interaction with glucocorticoid receptors in the hippocampus, we hypothesized that prenatal DEX exposure would lead to changes in the expression and function of 5HT1A receptors in the hippocampus. We administered DEX to rat dams during the last trimester of gestation and investigated the changes in these receptors in the adult rat offspring. Radioligand receptor binding assays were used to study hippocampal 5HT1A receptor binding affinity and number. Our results demonstrate that hippocampal 5HT1A receptors are increased in the DEX animalscompared with controls by 36%, with no change in binding affinity. The efficiency of ligand-induced receptor signal transduction via G-protein activation was also studied using [35S]GTPγS incorporation assay. Using this technique, we showed that there was no significant difference in the maximum ligand mediated stimulation (Emax) of 5HT1Areceptors between control and dex exposed animals. However, the intracellular signalling efficiency of hippocampal 5HT1A receptors was diminished, since a significant increase in EC50 values was obtained with the dex exposed group showing a value 51% higherEC50 than controls. Taken together these data illustrate a considerable change in the 5HT1A component of the serotonergic system following prenatal DEX exposure.

Aging and Mental Health: Business as Usual?

Cautions that in developing training models in mental health and aging, psychologists must not overlook what experience has taught them about mental health intervention or what they know already about older adults. It is suggested that a life-span developmental view complements a community and preventive approach to the mental health needs of the elderly. Creation of a separate subspecialty of clinical geropsychology will not effectively serve older adults. What is needed is a synthesis ofalready existing expertise in areas such as life-span development, clinical psychology, and community psychology. This synthesis provides a conceptual foundation and set of intervention approaches on which to base training programs in mental health and aging.

The Development, Reliability, and Validity of the OARS Multidimensional Functional Assessment Questionnaire

This report outlines the development, validity, and reliability of Part A of the OARS Multidimensional Functional Assessment Questionnaire. Part A permits assessment of individuals' functioning on each of five dimensions (social, economic, mental health, physical health and self-care capacity), the detailed information in each area being summarized on a 6-point rating scale by a rater. Content and consensual validity were ensured by the manner of construction. Information on criterion validity was obtained for all dimensions except social. The criterion used and their associated Kendall's Tau values were: an objective economic scale (.62); ratings based on personal interviews by geropsychiatrists (.60); physician's associates (.82); and physical therapists (.89). For 11 geographically dispersed raters from research and clinic settings, intraclass correlational coefficients, based on 30 subjects, ranged from .66 on physical health to .87 in self-care capacity; 74% of the ratings were in complete agreement, 24% differed by one point.

Assessing Nursing Assistants' Knowledge of Behavioral Approaches to Mental Health Problems

Nurse's aides are the primary caregivers in nursing homes, a major receiving site for elders with behavioral and psychiatric problems. We describe the development, psychometric properties, and utility of a brief instrument designed to assess aides' knowledge of three specific mental health problems (depression, agitation, and disorientation) and behavioral approaches to them. The instrument was administered to 191 nurse's aides and 21 clinicians with training in behavioral management and experience with older residents. The nurse's aides averaged 11 of 17 correct answers, and the clinicians averaged 15 of 17 correct answers. Implications for staff training and consultation activities in nursing homes are discussed.

[Integrating psychotherapeutic treatment of severe mental illness: between desirability and clinical practice]

Psychiatric care for severe and persistent mentally ill individuals has considerably changed over the last three decades. Striving for improvement in services provision for these patients has led to the emergence of various specialized community services, suited housing and supported work offers. Moreover, community-based treatment is also offered during acute episodes of mental illness. At the same time a range of evidence-based psychotherapeutic approaches targeting treatment needs of people with severe mental illness were developed in a process independent of the rise of community psychiatry. At present, however, a sufficient level of coordination of psychiatric services and integration of evidence-based psychological treatment into psychiatric care has not been achieved. Thus, these issues represent important steps in the further development.This paper discusses recent developments in psychiatric care of people with severe mental illness and reviews the evidence-based psychotherapy approaches suited to fit the needs of patient-centered integrated care.

Mental Health and Aging: Progress and Prospects

This volume originally appeared as an issue of the ASA journal, Generations. It contains contributions by prestigious writers in the field of gerontology, who present current concepts in research and clinical practice on mental health and aging. This book provides the latest perspectives on assessment and prevention techniques, depressive and anxiety disorders, the aging brain and neuroimaging, family therapy, and adult day care.

Maternal mental health in the first 3-week postpartum: the impact of caregiver support and the subjective experience of childbirth - a longitudinal path model

Acute stress reactions (ASR) and postpartum depressive symptoms (PDS) are frequent after childbirth. The present study addresses the change and overlap of ASR and PDS from the 1- to 3-week postpartum and examines the interplay of caregiver support and subjective birth experience with regard to the development of ASR/PDS within a longitudinal path model.

Romany Families in Romania: Intelligence and Personality of Children Cross-cultural and Specific Problems of Development

Psychogenetic research has emphasised the influence of social factors on a child's intellectual development. In her work, Ms. Dumitrascu examines two such factors; family size and order of birth. However, since these formal parameters tend to be unstable, other more informal factors should be taken into consideration. Of these, perhaps the most interesting is the "style" of parental education, which Ms. Dumitrascu regards as an expression of national traditions at the family level. This educational style is culture dependent. Only a comparative, cross-cultural study can reveal the real mechanism through which educational style influences the development of a child's intellect and personality. Ms. Dumitrascu conducted an experimental cross-cultural study aimed at examining the effects of the family environment on a child's intellectual development. Three distinct populations were involved in her investigation, each having quite a distinct status in their geographical area; Romanians, Romanies (Gypsies) from Romania, and Russians from the Republic of Moldova. She presented her research in the form of a series of articles written in English totalling 85 pages, and also on disc. A significant difference was revealed between the intelligence of a child living in a large family, and that of a child with no brothers or sisters. In the case of Romany children, the gap is remarkably large. Ms. Dumitrascu concludes that the simultaneous action of several negative factors (low socio-economic status, large family size, socio-cultural isolation of a population) may delay child development. Subjected to such a precarious environment, Romany children do not seek self-realisation, but rather struggle to survive the hardship. Most of them remain out of civilisation. Unfortunately, adult Romanies seldom express any concern regarding their children's successful social integration. The school as main socialisation tool has no value for most parents. Ms. Dumitrascu argues the need for a major effort aimed at helping Romany's social integration. She hopes this project will be of some help for psychologists, social workers, teachers, and all those who are interested in the integration into society of minority groups.

Differential expression of IGF-I mRNA and peptide in the male and female gonad during early development of a bony fish, the tilapia Oreochromis niloticus

Insulin-like growth factor I (IGF-I) plays a key role in the complex system that regulates bony fish growth, differentiation, and reproduction. The major source of circulating IGF-I is liver, but IGF-I-producing cells also occur in other organs, including the gonads. Because no data are available on the potential production sites of IGF-I in gonad development, developmental stages of monosex breedings of male and female tilapia from 0 day postfertilization (DPF) to 90 DPF were investigated for the production sites of IGF-I at the peptide (immunohistochemistry) and mRNA (in situ hybridization) level. IGF-I mRNA first appeared in somatic cells of the male and female gonad anlage at 7 DPF followed by IGF-I peptide around 9-10 DPF. Gonad anlagen were detected from 7 DPF. Starting at 7 DPF, IGF-I peptide but no IGF-I mRNA was observed in male and female primordial germ cells (PGCs) provided that IGF-I mRNA was not under the detection level, this observation may suggest that IGF-I originates from the somatic cells and is transferred to the PGCs or is of maternal origin. While in female germ cells IGF-I mRNA and peptide appeared at 29 DPF, in male germ cells both were detected as late as at 51-53 DPF. It is assumed that the production of IGF-I in the germ cells is linked to the onset of meiosis that in tilapia ovary starts at around 28 DPF and in testes at around 52-53 DPF. In adult testis, IGF-I mRNA and peptide occurred in the majority of spermatogonia and spermatocytes as well as in Leydig cells, the latter indicating a role of IGF-I in the synthesis of male sex steroids. In adult ovary, IGF-I mRNA and IGF-I peptide were always present in small and previtellogenic oocytes but only IGF-I peptide infrequently occurred in oocytes at the later stages. IGF-I expression appeared in numerous granulosa and some theca cells of follicles at the lipid stage and persisted in follicles with mature oocytes. The results suggest a crucial role of local IGF-I in the formation, differentiation and function of tilapia gonads.

Mental Health and Gun Control Briefing Report

The issue of gun control has once again become a highly contested issue in the United States after the most recent mass shootings at a movie theatre in Aurora, CO, a Sikh temple in Wisconsin, a mall in Portland, OR, and involving Representative Gabby Giffords in Arizona. However, it was not until the horrific tragedy in Newtown, CT, where 20 children and 6 adult staff members were fatally shot at Sandy Hook Elementary School, that the gun control debate reached its peak.