A 7‐year follow‐up study of the Mindfulness‐Based Program for Infertility: Are there long‐term effects?

The Mindfulness‐Based Program for Infertility (MBPI) was developed for people facing infertility and proved effective in cultivating mindfulness skills, improving infertility self‐efficacy, and decreasing depression, shame, entrapment, and defeat feelings. Fifty‐five women attended the MBPI sessions and completed self‐report measures of depression, anxiety, mindfulness, and experiential avoidance at post‐MBPI (T1), 6‐month follow‐up (T2), and 7‐year follow‐up (T3). There were significant direct time effects regarding experiential avoidance (F = 3.81; p < 0.033; η_p² = 0.08), the mindfulness facets describing (F = 3.54; p = 0.037; η_p² = 0.13), acting with awareness (F = 6.87; p = 0.002; η_p² = 0.22), nonjudging of inner experience (F = 10.66; p < 0.001; η_p² = 0.31), and depressive symptoms (F = 4.85; p = 0.020; η_p² = 0.10). There was an increase in the describing facet from T1 to T3 (p = 0.036). The act with awareness facet increased from T1 to T2 (p = 0.010) and from T1 to T3 (p = 0.007), as well as the nonjudging of inner experience facet (T1 to T2 [p = 0.030] and T1 to T3 [p = 0.002]). Experiential avoidance decreased from T1 to T3 (p = 0.022) and depressive symptoms from T1 to T2 (p = 0.019). Post‐MBPI scores were maintained at T2 and T3 concerning anxiety symptoms and the observing and no‐reactivity mindfulness facets. There were long‐term effects of MBPI on mindfulness and experiential avoidance. Moreover, therapeutic gains were maintained regarding depression and anxiety symptoms, independently of the reproductive outcome.     

Marked for life? Effects of early cage‐cleaning frequency,delivery batch,and identification tail‐marking on rat anxiety profiles

Daily handling of preweanling rats reduces their adult anxiety. Even routine cage-cleaning, involving handling, reduces adult anxiety compared with controls. Cage-cleaning regimes differ between animal breeders, potentially affecting rodent anxiety and experimental results. Here, 92 adult male rats given different cage-cleaning rates as pups, were compared on plus-maze, hyponeophagia, corticosterone, and handling tests. They were pair-housed and half were tail-marked for identification. Anxiety/stress profiles were unaffected by cage-cleaning frequency, suggesting that commercial-typical differences in husbandry contribute little variance to adult rat behavior. However, delivery batch affected some elevated plus-maze measures. Also, tail-marked rats spent three times longer on the plus-maze open arms than their unmarked cagemates, suggesting reduced anxiety, yet paradoxically they showed greater chromodacryorrhoea responses to handling, implying increased aversion to human contact. A follow-up study showed that rats avoided the odor released from the marker pen used. Thus, apparently trivial aspects of procedure can greatly affect experimental results.     

Can assessors and therapists predict the outcome of long‐term psychotherapy in borderline personality disorder?

Surprisingly few studies have investigated the accuracy of prognostic assessments of therapy outcome by clinicians. The objective of the present study was to investigate the relationship between clinicians' prognostic assessments and patient characteristics and treatment outcome. Seventy-one patients with a borderline personality disorder randomly allocated to schema-focused therapy (SFT) or transference-focused psychotherapy (TFP) were assessed every 3 months for 3 years. Prognostic assessments proved to be unrelated to patients' biographical (i.e., age, gender, education level, and employment level) and clinical characteristics (i.e., number of Axis I and Axis II diagnoses, and severity of psychiatric symptoms or borderline personality pathology). Clinical assessors as well as therapists rated the probability of success for SFT to be higher than for TFP. Prospective assessments of assessors and therapists accurately predicted different indices of outcome above and independent of patient characteristics. The prediction of outcome in the TFP condition in particular proved to be valid. Identifying prognostic markers of treatment outcome as used by clinicians in their prognostic assessments may improve current prediction models and patient-treatment matching.     

Total cholesterol and oxysterols: early markers for cognitive decline in elderly?

In this prospective study we examined whether total cholesterol and the oxysterols 24S- and 27-hydroxycholesterol were related to cognitive performance and rate of cognitive decline in elderly, and whether these associations were modified by ApoE epsilon 4. Data were collected during 6 years of follow-up as part of the Longitudinal Aging Study Amsterdam (N=1181, age >or=65 years), and analyzed using generalized estimating equations. Cognitive performance was measured with the mini-mental state examination (general cognition), the auditory verbal learning test (memory) and the coding task (information processing speed). Lower cholesterol at baseline was negatively associated with both general cognition (p=.012) and information processing speed (p=.045). ApoE modified the association between cholesterol and cognitive decline, and the association between the ratio of 27-hydroxycholesterol to cholesterol and cognitive functioning. In ApoE epsilon 4 carriers, lower cholesterol was related to a higher rate of decline on information processing speed (p=.006), and a higher ratio of 27-hydroxycholesterol to cholesterol was related to a lower level of general performance (p=.002) and memory functioning (p=.045). The results implicate that lower total cholesterol may be considered as a frailty marker, predictive of lower cognitive functioning in elderly.     

Neighborhood‐specific and general social support: which buffers the effect of neighborhood disorder on depression?

Is neighborhood‐specific social support the most effective type of social support for buffering the effect of neighborhood disorder on depression? Matching theory suggests that it is. The authors extend the research on neighborhood disorder and adult depression by showing that individuals who have higher levels of both general and neighborhood‐specific social relationships, measured by social support and neighborhood social ties, are less vulnerable to negative effects of neighborhood disorder. Using the Community, Crime, and Health Survey, the authors found that neighborhood disorder's association with depression is lower for people with supportive social ties with neighbors and for people with more general social support. The latter conditional effect is stronger than the former, indicating that support in which the source of support matches the source of strain is not more effective than general support at buffering the effects of neighborhood strain. © 2009 Wiley Periodicals, Inc.     

Developmental trajectories of abuse – An hypothesis for the effects of early childhood maltreatment on dorsolateral prefrontal cortical development

The United States has a high rate of child maltreatment, with nearly 12 in 1000 children being victims of abuse or neglect. Child abuse strongly predicts negative life outcomes, especially in areas of emotional and mental health. Abused children are also more likely than their peers to engage in violence and enter the juvenile justice system, as well as to become abusive parents themselves. Research has shown that child abuse and trauma can lead to decreased hippocampal volume, which could be indicative of abnormal hippocampal development. Hippocampal development appears to directly affect the development of the dorsolateral prefrontal cortex, a brain area responsible for emotion regulation, cognitive reappraisal, and general executive function. Therefore, I hypothesize that if child abuse results in abnormal hippocampal development, which leads to abnormal dorsolateral prefrontal cortex development, many of the correlated risk factors of child abuse, such as emotionally-laden parenting and unfavorable cognitive distortions regarding children’s behaviors, may be in part caused by underdevelopment or abnormal functioning of the dorsolateral prefrontal cortex, as a function of the individual’s own experiences with abuse during childhood. If this hypothesis is supported with future research, more targeted, successful, and cost-effective prevention and treatment protocols could ensue. For instance, programs that have been empirically shown to increase the activity of the dorsolateral prefrontal cortex, such as cognitive behavioral therapy, could be effective in decreasing the incidence of intergenerational transfer of abuse.     

The genetics of pre‐eclampsia: a feto‐placental or maternal problem?

Pre-eclampsia is a potentially life-threatening disease of women during pregnancy leading to hypertension and proteinuria. It affects 1 in 15 pregnancies but, despite intense research efforts, the cause of the disease remains mysterious. Because pre-eclampsia only occurs during pregnancy and its symptoms resolve after delivery, factors from the placenta are thought to be involved. The role of the placenta could be production of 'abnormal' factors that initiate widespread inflammation and vaso-constriction. Alternatively, because the placenta normally contributes to maternal cardiovascular adaptations of pregnancy, it may be that normal placental functions fail in pre-eclampsia or that susceptibilities in the mother to hypertensive, vascular and/or renal disease prevent the appropriate normal responses to them. The potential contributions of both maternal and fetal genes to the onset of the disease have complicated the genetic analysis of the disease in humans. Recent studies have identified strains of transgenic and mutant mice that develop the hallmark features of pre-eclampsia-like disease - gestational hypertension, proteinuria and kidney lesions (glomerulosclerosis). Comparison of three different mouse models suggests that pre-eclampsia can be initiated by at least three independent mechanisms: pre-existing borderline maternal hypertension that is exacerbated by pregnancy (BPH/5 strain of mice), elevated levels of the vasoconstrictor angiotensin II in the maternal circulation by placental over-production of renin (renin/angiotensinogen transgenic mice), and placental pathology (p57Kip2 mutant mice). These findings imply that the pathogenesis of pre-eclampsia cannot be explained by a single mechanism. Therefore, segregation of the human disease into different subtypes may be a key first step in identifying genetic risk factors.     

The effects of advanced maternal age on T-cell subsets at the maternal–fetal interface prior to term labor and in the offspring: a mouse study

Women who conceive at 35 years of age or older, commonly known as advanced maternal age, have a higher risk of facing parturition complications and their children have an increased risk of developing diseases later in life. However, the immunological mechanisms underlying these pathological processes have yet to be established. To fill this gap in knowledge, using a murine model and immunophenotyping, we determined the effect of advanced maternal age on the main cellular branch of adaptive immunity, T cells, at the maternal–fetal interface and in the offspring. We report that advanced maternal age impaired the process of labor at term, inducing dystocia and delaying the timing of delivery. Advanced maternal age diminished the number of specific proinflammatory T-cell subsets [T helper type 1 (Th1): CD4⁺IFN-γ⁺, CD8⁺IFN-γ⁺ and Th9: CD4⁺IL-9⁺], as well as CD4⁺ regulatory T cells (CD4⁺CD25⁺FoxP3⁺ T cells), at the maternal–fetal interface prior to term labor. Advanced maternal age also altered fetal growth and survival of the offspring in early life. In addition, infants born to advanced-age mothers had alterations in the T-cell repertoire but not in CD71⁺ erythroid cells (CD3⁻CD71⁺TER119⁺ cells). This study provides insight into the immune alterations observed at the maternal–fetal interface of advanced-age mothers and their offspring.     

IGFs and IGFBPs: surrogate markers for diagnosis and surveillance of tumour growth?

Insulin-like growth factors (IGFs), IGF receptors, and IGF binding proteins (IGFBPs) constitute the IGF system. Comprehensive data indicate that these factors play a pivotal role in tumorigenesis. Epidemiological data indicate that cancer risk is associated with high serum IGF-I values. Because dysregulation of the IGF system is a frequent pattern in malignancy, IGFs/IGFBPs might represent novel tumour markers that could be useful both for diagnosis and surveillance.     

Cognitive–affective strategies and cortisol stress reactivity in children and adolescents: Normative development and effects of early life stress

This study examined cognitive–affective strategies as predictors of hypothalamic–pituitary–adrenal (HPA) axis responses to a social-evaluative stressor in adolescence as compared to late childhood as a function of early life experiences. Participants included 159 children (9–10 years) and adolescents (15–16 years) divided into two groups based on early care experiences: non-adopted youth raised in their birth families (n = 81) and post-institutionalized youth internationally adopted from orphanage care (n = 78). Youth completed a version of the Trier Social Stress Test modified for use with children and reported on their trait emotion regulation and coping strategies. Children reported more use of suppression and disengagement than adolescents, while adolescents reported more engagement coping strategies. Non-adopted and post-institutionalized youth did not differ in reported strategies. Cognitive reappraisal predicted higher cortisol reactivity in non-adopted children and adolescents, and was not associated with reactivity in the post-institutionalized group. This study has implications for efforts aimed at promoting self-regulation and adaptive stress responses during the transition to adolescence for both typically developing children and children who experienced adverse early care.     

Tissue‐specific p53 responses to ionizing radiation and their genetic modification: the key to tissue‐specific tumour susceptibility?

Although little is understood of the underlying mechanisms, there are tissue-specific responses to tumourigenic and therapeutic agents and these responses are influenced by genetic factors. Ionizing radiation is an important tumourigenic and therapeutic agent for which there is substantial evidence for such tissue-dependent and genotype-dependent responses. Because the p53 tumour suppressor protein is a major determinant of cellular responses to radiation, the present study has investigated whether modification of the p53 pathway contributes to tissue-dependent and genotype-dependent responses using inbred strains of mice. Comparison of responses in haemopoietic and epithelial cells in irradiated C57BL/6 and DBA/2 mice revealed significant differences in p53 and apoptotic responses in different cell types and in different cells of the same type, reflecting the complexity of damage responses operating in the whole organism. The data suggest that p53-mediated up-regulation of Bax is a major determinant of apoptosis in the spleen, but not in the intestine, whereas p53-mediated induction of p21(waf1) plays an anti-apoptotic role in the spleen, but not in the intestine. It is also shown that p53 stabilization and differential transactivational activities towards Bax or p21(waf1) are influenced by genetic factors that act in a tissue-specific manner. Analysis of ATM, a potential mediator of differential p53 activation, indicates that this key regulator of radiation responses is preferentially induced in epithelial cells, but is unlikely to account for genetic modification of p53 or apoptotic responses in the mouse strains studied. Polymorphisms in the p53 or DNA-PKcs genes are also unlikely to account for the genetic modifications that are reported here. There are numerous further potential modifiers of the p53 pathway, but analysis of backcross and inter-cross mice demonstrates that genes responsible for the complex modification of these in vivo responses can be identified by linkage analysis. This approach has the potential to reveal new or unexpected interactions involving the p53 pathway that determine both short-term and long-term effects of radiation exposure and the basis of tissue-specific responses and tumour susceptibility.