The psychosocial context of bipolar disorder: environmental, cognitive, and developmental risk factors

In this article, we review empirical research on the role of individuals' current environmental contexts, cognitive styles, and developmental histories as risk factors for the onset, course, and expression of bipolar spectrum disorders. Our review is focused on the following over arching question: Do psychosocial factors truly contribute risk to the onset, course, or expression of bipolar disorders? As a secondary issue, we also address whether the psychosocial risks for bipolar disorders are similar to those for unipolar depression. We begin by discussing the methodological requirements for demonstrating a psychosocial risk factor and the challenges posed by bipolar spectrum disorders for psychosocial risk research. Next, we review the extant studies on the role of recent life events and supportive and non-supportive social interactions (current environment) in bipolar disorders, as well as psychosocial treatments designed to remediate these current environmental factors. We then review the role of cognitive styles featured as vulnerabilities in theories of unipolar depression as risk factors for bipolar disorder alone and in combination with life events, including studies of cognitive-behavioral therapies for bipolar disorder. Finally, we review studies of parenting and maltreatment histories in bipolar disorders. We conclude with an assessment of the state of the psychosocial risk factors literature in bipolar disorder with regard to our guiding questions.     

Predictors of dropout from inpatient treatment for anorexia nervosa: Data from a large French sample

Dropout from anorexia nervosa inpatient treatment programs is frequent and is linked to a poorer outcome. This study aimed to identify predictive factors for dropout among anorexia nervosa inpatients. Between 1988 and 2004, 601 consecutive female inpatients with anorexia, restrictive (AN-R) or binge/purging (AN-B/P) subtype (Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV)), were assessed at admission (clinical, socio-demographic, and psychological data). A stepwise logistic model was developed. Dropout rates were respectively 50.0% and 56.2% for AN-R and AN-B/P. Seven predictive factors were identified in multivariate analysis: having one or more children, low desired body mass index (BMI), a low minimum BMI, high scores on the SCL-90 paranoid ideation and the Morgan and Russell eating behavior subscales, and low educational status. Early dropouts had a particular profile: lower desired BMI, higher score on SCL90 paranoid subscale, and more impulsive behaviors (alcohol use, suicide attempts). Dropout appeared as a multifactorial event. In clinical practice, certain factors could serve as warning messages reflecting the severity of the illness (high EDI score and low minimum BMI); while others could be targeted before hospitalization (having at least one child and low desired BMI).     

Metastasis of lobular breast carcinoma to the cervix

Breast cancers without previous dissemination occasionally result in hematogenous metastases in gynecologic organs, particularly in the cervix. This case report examines a multimodally treated lobular breast cancer patient who was 52 months later diagnosed with malignancy in the uterus. After a tumor was detected at the endocervical and isthmic part of the uterus, a complete hysterectomy with bilateral salpingo-oophorectomy was carried out. The malignant cells were highly positive for carcino-embrional antigen and gross cystic disease fluid protein-15, sensitive breast cancer markers. In conclusion, as breast carcinoma can metastasize to atypical places (cervix, endometrium, etc.), regular surveillance of patients should include gynecologic control.     

Hyperactivity and hyperconnectivity of the default network in schizophrenia and in first-degree relatives of persons with schizophrenia

We examined the status of the neural network mediating the default mode of brain function, which typically exhibits greater activation during rest than during task, in patients in the early phase of schizophrenia and in young first-degree relatives of persons with schizophrenia. During functional MRI, patients, relatives, and controls alternated between rest and performance of working memory (WM) tasks. As expected, controls exhibited task-related suppression of activation in the default network, including medial prefrontal cortex (MPFC) and posterior cingulate cortex/precuneus. Patients and relatives exhibited significantly reduced task-related suppression in MPFC, and these reductions remained after controlling for performance. Increased task-related MPFC suppression correlated with better WM performance in patients and relatives and with less psychopathology in all 3 groups. For WM task performance, patients and relatives had greater activation in right dorsolateral prefrontal cortex (DLPFC) than controls. During rest and task, patients and relatives exhibited abnormally high functional connectivity within the default network. The magnitudes of default network connectivity during rest and task correlated with psychopathology in the patients. Further, during both rest and task, patients exhibited reduced anticorrelations between MPFC and DLPFC, a region that was hyperactivated by patients and relatives during WM performance. Among patients, the magnitude of MPFC task suppression negatively correlated with default connectivity, suggesting an association between the hyperactivation and hyperconnectivity in schizophrenia. Hyperactivation (reduced task-related suppression) of default regions and hyperconnectivity of the default network may contribute to disturbances of thought in schizophrenia and risk for the illness.     

Classification of soil samples according to geographic origin using gamma-ray spectrometry and pattern recognition methods.

Multivariate data analysis methods were used to recognize and classify soils of unknown geographic origin. A total of 103 soil samples were differentiated into classes, according to regions in Serbia and Montenegro from which they were collected. Their radionuclide (226Ra, 238U, 235U, 40K, 134Cs, 137Cs, 232Th and 7Be) activities detected by gamma-ray spectrometry were then used as the inputs in different pattern recognition methods. For the classification of soil samples using eight selected radionuclides, the prediction ability of linear discriminant analysis (LDA), k-nearest neighbours (kNN), soft independent modelling of class analogy (SIMCA) and artificial neural network (ANN) were 82.8%, 88.6%, 60.0% and 92.1%, respectively.     

A selective metabotropic glutamate receptor 7 agonist: activation of receptor signaling via an allosteric site modulates stress parameters in vivo

Metabotropic glutamate receptor (mGluR) subtypes (mGluR1 to mGluR8) act as important pre- and postsynaptic regulators of neurotransmission in the CNS. These receptors consist of two domains, an extracellular region containing the orthosteric agonist site and a transmembrane heptahelical domain involved in G protein activation and recognition of several recently synthesized pharmacological modulators. The presynaptic receptor mGluR7 shows the highest evolutionary conservation within the family, but no selective pharmacological tool was known. Here we characterize an mGluR7-selective agonist, N,N'-dibenzhydrylethane-1,2-diamine dihydrochloride (AMN082), which directly activates receptor signaling via an allosteric site in the transmembrane domain. At transfected mammalian cells expressing mGluR7, AMN082 potently inhibits cAMP accumulation and stimulates GTPgammaS binding (EC50-values, 64-290 nM) with agonist efficacies comparable with those of L-2-amino-4-phosphonobutyrate (L-AP4) and superior to those of L-glutamate. AMN082 (< or = 10 microM) failed to show appreciable activating or inhibitory effects at other mGluR subtypes and selected ionotropic GluRs. Chimeric receptor studies position the binding site of AMN082 in the transmembrane region of mGluR7, and we demonstrate that this allosteric agonist has little, if any, effect on the potency of orthosteric ligands. Here we provide evidence for full agonist activity mediated by the heptahelical domain of family 3 G protein-coupled receptors (which have mGluR-like structure) that may lead to drug development opportunities. Further, AMN082 is orally active, penetrates the blood-brain barrier, and elevates the plasma stress hormones corticosterone and corticotropin in an mGluR7-dependent fashion. Therefore, AMN082 is a valuable tool for unraveling the role of mGluR7 in stress-related CNS disorders.     

Frequency of chromosomal lesions and damaged lymphocytes of workers occupationally exposed to x rays

This paper analyzes the effects of x rays on workers exposed to radiation. In particular, this paper documents the emergence and frequency of non-specific chromosomal lesions with characteristic chromosomal aberrations and the number of damaged lymphocytes before, during, and after occupational exposure. Chromosomal changes were analyzed taking into consideration duration of exposure, dose, age, and sex. Correlation between aberrations and absorbed doses of x rays measured by thermoluminescence dosimeters is shown, as well as correlation between chromosomal lesions and damaged cells and the frequency of chromosomal aberrations. Chromosomal aberrations of karyotype diminish after exposures cease, but the number of non-specific lesions in karyotype do not decrease during the same period. The duration of exposure and age are not significant predictors of analyzed aberrations and lesions.     

The new anticonvulsant retigabine favors voltage-dependent opening of the Kv7.2 (KCNQ2) channel by binding to its activation gate

Retigabine (RTG) is an anticonvulsant drug with a novel mechanism of action. It activates neuronal KCNQ-type K(+) channels by inducing a large hyperpolarizing shift of steady-state activation. To identify the structural determinants of KCNQ channel activation by RTG, we constructed a set of chimeras using the neuronal K(v)7.2 (KCNQ2) channel, which is activated by RTG, and the cardiac K(v)7.1 (KCNQ1) channel, which is not affected by this drug. Substitution of either the S5 or the S6 segment in K(v)7.2 by the respective parts of K(v)7.1 led to a complete loss of activation by RTG. Trp236 in the cytoplasmic part of S5 and the conserved Gly301 in S6 (K(v)7.2), considered as the gating hinge (Ala336 in K(v)7.1), were found to be crucial for the RTG effect: mutation of these residues could either knockout the effect in K(v)7.2 or restore it partially in K(v)7.1/K(v)7.2 chimeras. We propose that RTG binds to a hydrophobic pocket formed upon channel opening between the cytoplasmic parts of S5 and S6 involving Trp236 and the channel's gate, which could well explain the strong shift in voltage-dependent activation.