Impaired metabolic reactivity to oxidative stress in early psychosis patients.

Because increasing evidence point to the convergence of environmental and genetic risk factors to drive redox dysregulation in schizophrenia, we aim to clarify whether the metabolic anomalies associated with early psychosis reflect an adaptation to oxidative stress. Metabolomic profiling was performed to characterize the response to oxidative stress in fibroblasts from control individuals (n = 20) and early psychosis patients (n = 30), and in all, 282 metabolites were identified. In addition to the expected redox/antioxidant response, oxidative stress induced a decrease of lysolipid levels in fibroblasts from healthy controls that were largely muted in fibroblasts from patients. Most notably, fibroblasts from patients showed disrupted extracellular matrix- and arginine-related metabolism after oxidative stress, indicating impairments beyond the redox system. Plasma membrane and extracellular matrix, 2 regulators of neuronal activity and plasticity, appeared as particularly susceptible to oxidative stress and thus provide novel mechanistic insights for pathophysiological understanding of early stages of psychosis. Statistically, antipsychotic medication at the time of biopsy was not accounting for these anomalies in the metabolism of patients' fibroblasts, indicating that they might be intrinsic to the disease. Although these results are preliminary and should be confirmed in a larger group of patients, they nevertheless indicate that the metabolic signature of reactivity to oxidative stress may provide reliable early markers of psychosis. Developing protective measures aimed at normalizing the disrupted pathways should prevent the pathological consequences of environmental stressors.

Vulnerabilität und psychische Erkrankung

Vulnerability and psychic illness Based on a sample of 1701 college and university students from four different sites in Switzerland, the U.S., and Argentina, this study investigated the interrelationships between insufficient coping skills under chronic stress and impaired general health. We sought to develop standardised means for "early" identification of students at risk of mental health problems, as these students may benefit from "early" interventions before psychiatric symptoms develop and reach clinically relevant thresholds. All students completed two self-report questionnaires: the Coping Strategies Inventory "COPE" and the Zurich Health Questionnaire "ZHQ", with the latter assessing "regular exercises", "consumption behavior", "impaired physical health", "psychosomatic disturbances", and "impaired mental health". This data was subjected to structure analyses based on neural network approaches, using the different study sites' data subsets as independent "learning" and "test" samples. We found two highly stable COPE scales that quantified basic coping behaviour in terms of "activity-passivity" and "defeatism-resilience". The excellent reproducibility across study sites suggested that the new scales characterise socioculturally independent personality traits. Correlation analyses for external validation revealed a close relationship between high scores on the defeatism scale and impaired physical and mental health, hence underlining the scales' clinical relevance. Our results suggested in particular: (1.) the proposed method to be a powerful screening tool for early detection and prevention of psychiatric disorders; (2.) physical activity like regular exercises to play a critical role not only in preventing health problems but also in contributing to early intervention programs.

Effect of orlistat in obese patients with binge eating disorder.

OBJECTIVE: Binge eating disorder represents a significant public health problem, with up to 50% of weight loss program participants displaying this disorder. In previous studies with orlistat, patients with binge eating disorder were excluded. The goal of this study was to assess the efficacy of orlistat in obese patients with binge eating disorder. RESEARCH METHODS AND PROCEDURES: Eighty-nine patients with clinically diagnosed binge eating disorder and a BMI > or = 30 kg/m2 were randomized in double-blind fashion to 24 weeks of treatment with 120 mg of orlistat or placebo three times daily, in combination with a mildly reduced-calorie diet. RESULTS: After 24 weeks, the mean weight loss from baseline for orlistat-treated patients was significantly greater than for patients receiving placebo (-7.4% vs. -2.3%; p = 0.0001) (intent-to-treat analysis). The overall Eating Disorder Inventory 2 score at week 24 was significantly lower in patients treated with orlistat than in those in the placebo group (p = 0.011). DISCUSSION: Orlistat may be considered as part of the management for patients with obesity and binge eating disorder.

Developing psychosis and its risk States through the lens of schizotypy.

Starting from the early descriptions of Kraepelin and Bleuler, the construct of schizotypy was developed from observations of aberrations in nonpsychotic family members of schizophrenia patients. In contemporary diagnostic manuals, the positive symptoms of schizotypal personality disorder were included in the ultra high-risk (UHR) criteria 20 years ago, and nowadays are broadly employed in clinical early detection of psychosis. The schizotypy construct, now dissociated from strict familial risk, also informed research on the liability to develop any psychotic disorder, and in particular schizophrenia-spectrum disorders, even outside clinical settings. Against the historical background of schizotypy it is surprising that evidence from longitudinal studies linking schizotypy, UHR, and conversion to psychosis has only recently emerged; and it still remains unclear how schizotypy may be positioned in high-risk research. Following a comprehensive literature search, we review 18 prospective studies on 15 samples examining the evidence for a link between trait schizotypy and conversion to psychosis in 4 different types of samples: general population, clinical risk samples according to UHR and/or basic symptom criteria, genetic (familial) risk, and clinical samples at-risk for a nonpsychotic schizophrenia-spectrum diagnosis. These prospective studies underline the value of schizotypy in high-risk research, but also point to the lack of evidence needed to better define the position of the construct of schizotypy within a developmental psychopathology perspective of emerging psychosis and schizophrenia-spectrum disorders.

Extreme population differentiation in vulnerable slavemaking ant with fragmented distribution

Understanding levels of population differentiation and inbreeding are important issues in conservation biology, especially for social Hymenoptera with fragmented and small population sizes. Isolated populations are more vulnerable to genetic loss and extinction than those with extended continuous distributions. However, small populations are not always a consequence of a recent reduction of their habitat. Thus, determining the history of population isolation and current patterns of genetic variation of a species is crucial for its conservation. Rossomyrmex minuchae is a slave-making ant with patchy distribution in South Eastern Spain and is classified as vulnerable by the IUCN. In contrast, the other three known species of the genus are presumed to show more uniform distributions. Here we investigate the genetic diversity and population structure of R. minuchae and compare it with that found in two other species of the genus: R. anatolicus and R. quandratinodum. We conclude that although genetic diversity of R. minuchae is low, there is no evidence of a recent bottleneck, suggesting a gradual and natural fragmentation process. We also show extreme population differentiation at nuclear and mitochondrial markers, and isolation by distance at a local scale. Despite some evidence for inbreeding and low genetic variation within populations, we found almost no diploid males, a finding which contrasts with that expected in inbred Hymenoptera with single locus complementary sex determination. This could mean that sex is determined by another mechanism. We argue that continued low population size means that detrimental effects of inbreeding and low genetic variation are likely in the future. We suggest that a policy of artificial gene flow aimed at increasing within population variation is considered as a management option.

Pretreatment and outcome correlates of sexual and physical trauma in an epidemiological cohort of first-episode psychosis patients.

OBJECTIVES: High prevalence of trauma has been reported in psychosis. While role of trauma as a risk factor for developing psychosis is still debated, its negative impact on outcome has been described. Few studies have explored this issue in first-episode psychosis (FEP) patients. We assessed rate of stressful events, as well as premorbid and outcome correlates of past sexual and/or physical abuse (SPA) in an epidemiological FEP patients cohort. METHODS: The Early Psychosis Prevention and Intervention Centre admitted 786 FEP patients between 1998 and 2000. Data were collected from patients' files using a standardized questionnaire. A total of 704 files were available, 43 excluded because of a nonpsychotic diagnosis at end point and 3 due to missing data regarding past stressful events; 658 patients were analyzed. RESULTS: A total of 83% patients had been exposed to at least one stressful event and 34% to SPA. SPA patients were more likely to have presented other psychiatric disorders before psychosis onset (posttraumatic stress disorder, substance use disorder), to have made suicide attempts in the past, and to have had poorer premorbid functional levels. Additionally, SPA patients had higher rate of comorbid diagnosis at program entry and were more likely to attempt suicide during treatment. CONCLUSIONS: SPA prevalence is high in FEP patients and must be explored by clinicians considering its durable impact on psychological balance and link with long-lasting suicidal risk. More research is warranted to better understand mechanisms involved between trauma and its potential consequences, as well as to develop psychological interventions adapted to this very sensitive and complex issue.

Sindrome metabolica e rischio di tumore mammario. [Metabolic syndrome and the risk of breast cancer].

Metabolic syndrome has been associated with an increased risk of various cancers. A multicenter study conducted in Italy and Switzerland on 3,869 cases of breast cancer in post-menopause reported a relative risk of 1.75 in women with the metabolic syndrome, confirming the results of other smaller epidemiological studies.

Impacts of upland open drains upon runoff generation: a numerical assessment of catchment-scale impacts

Shallow upland drains, grips, have been hypothesized as responsible for increased downstream flow magnitudes. Observations provide counterfactual evidence, often relating to the difficulty of inferring conclusions from statistical correlation and paired catchment comparisons, and the complexity of designing field experiments to test grip impacts at the catchment scale. Drainage should provide drier antecedent moisture conditions, providing more storage at the start of an event; however, grips have higher flow velocities than overland flow, thus potentially delivering flow more rapidly to the drainage network. We develop and apply a model for assessing the impacts of grips on flow hydrographs. The model was calibrated on the gripped case, and then the gripped case was compared with the intact case by removing all grips. This comparison showed that even given parameter uncertainty, the intact case had significantly higher flood peaks and lower baseflows, mirroring field observations of the hydrological response of intact peat. The simulations suggest that this is because delivery effects may not translate into catchment-scale impacts for three reasons. First, in our case, the proportions of flow path lengths that were hillslope were not changed significantly by gripping. Second, the structure of the grip network as compared with the structure of the drainage basin mitigated against grip-related increases in the concentration of runoff in the drainage network, although it did marginally reduce the mean timing of that concentration at the catchment outlet. Third, the effect of the latter upon downstream flow magnitudes can only be assessed by reference to the peak timing of other tributary basins, emphasizing that drain effects are both relative and scale dependent. However, given the importance of hillslope flow paths, we show that if upland drainage causes significant changes in surface roughness on hillslopes, then critical and important feedbacks may impact upon the speed of hydrological response. Copyright (c) 2012 John Wiley & Sons, Ltd.

Targeting Oxidative Stress and Aberrant Critical Period Plasticity in the Developmental Trajectory to Schizophrenia.

Schizophrenia is a neurodevelopmental disorder reflecting a convergence of genetic risk and early life stress. The slow progression to first psychotic episode represents both a window of vulnerability as well as opportunity for therapeutic intervention. Here, we consider recent neurobiological insight into the cellular and molecular components of developmental critical periods and their vulnerability to redox dysregulation. In particular, the consistent loss of parvalbumin-positive interneuron (PVI) function and their surrounding perineuronal nets (PNNs) as well as myelination in patient brains is consistent with a delayed or extended period of circuit instability. This linkage to critical period triggers (PVI) and brakes (PNN, myelin) implicates mistimed trajectories of brain development in mental illness. Strategically introduced antioxidant treatment or later reinforcement of molecular brakes may then offer a novel prophylactic psychiatry.