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.Key words: mental disorder, glutathione, arginine, extracellular matrix, phospholipid, metabolism     

Considération critique sur l’extension de la bipolarité, psychopathologie des mouvements d’humeur et de l’euphorie morbide

Objectives

From manic-depressive psychosis to bipolar spectrum, today's psychiatry allows us to observe a widening of bipolar criteria. This article aims at studying this evolution, its consequences with a critical look and the psychopathology of mood changes and morbid euphoria.

Methods

All of our considerations refer to current data on bipolar disorders (review with Medline and Science Direct) compared with studies from classical psychiatrists (Kraepelin, Ey) and various authors inspired by psychoanalysis (Freud, Racamier) and phenomenology (Binswanger, Tellenbach, Tatossian).

Results

Many contemporary authors encourage clinicians to detect bipolar disorders from symptoms, early signs and attenuated or atypical expressions. The concept of a widened spectrum is supposed to be closer to clinical reality and it would be an opportunity to diagnose this disease and its deleterious consequences better and thus to set up an appropriate therapy at an early stage. Other authors, on the other hand, deplore a dilution of bipolar disorders together with harmful diagnostic inflation around a concept that has become too heterogeneous to be effective, that subjugates or interferes with other pathologic entities in an excessive manner and abandoning a psychopathological approach. In this view, we shall analyze the nosographic shifts of bipolar disorders throughout the history of psychiatry, from manic-depressive psychosis to bipolar disorder and spectrum. We shall then scrutinize the autonomy and limitations related to bipolar disorders as opposed to normality, confusing clinical presentations and other major mental diseases: Psychosis, depression, pathological personality, anxiety, impulse-control, attention deficit-hyperactivity, addiction and psycho-organic disorders. This work shall first introduce a discussion on the concept of bipolar disorders for children, and then through the case of some historical figures. Then we will deal with the contemporary social factors that are currently furthering the extension of this diagnosis. Last, this article sheds a light on psychopathological specificities of mania – the cornerstone in bipolar disorders – mood changes and morbid euphoria.

Conclusion

We think that classic psychiatry, phenomenology and psychoanalysis would act as a guiding light through this debate and could help the clinician in this daily practice. Mood variations require a careful clinical observation and a rigorous set of interpretation, before being specified too excessively or hastily as a symptom of a real bipolarity.     

Assertive Community Treatment and Associations with Substance Abuse Problems

This study examined the associations between substance abuse problems in severely mentally ill patients, outcome and Assertive Community Treatment (ACT) model fidelity. In a prospective longitudinal study, ACT model fidelity and patient outcomes were assessed in 20 outpatient treatment teams using the Health of the Nation Outcome Scales, Camberwell Assessment of Needs short appraisal schedule and measures of service use. Five hundred and thirty severely mentally ill patients participated in the study. Substance abuse problems were assessed three times during a 2-year follow-up period. This study found that among patients with severe mental illness, patients with an addiction problem had more serious psychosocial problems at baseline. Substance abuse problems showed improvement over time, but this was not associated with ACT model fidelity. The study indicates that investment by teams to improve a patient’s psychosocial situation can lead to improvements on substance problems.     

The efficiency of glutamate uptake differs between neonatal and adult cortical microvascular endothelial cells

Glutamate transporters (excitatory amino-acid transporters (EAATs)) are essential for brain homeostasis. While previous studies indicate that the vascular endothelium contributes to glutamate efflux in the adult brain, little information is available regarding glutamate uptake in the immature brain. The present study shows a differential expression pattern of EAATs between cortical microvessels in adults and newborns. In addition, adult cortical endothelial cells take up glutamate more efficiently than neonatal cells. Our findings indicate age-specific changes in extracellular glutamate regulation by brain endothelial cells, suggesting differences in the efficiency of glutamate efflux during an excitotoxic process that, in turn, may contribute to age-specific brain vulnerability.     

Impaired brain energy metabolism in the BACHD mouse model of Huntington's disease: critical role of astrocyte–neuron interactions

Huntington''s disease (HD) is caused by cytosine-adenine-guanine (CAG) repeat expansions in the huntingtin (Htt) gene. Although early energy metabolic alterations in HD are likely to contribute to later neurodegenerative processes, the cellular and molecular mechanisms responsible for these metabolic alterations are not well characterized. Using the BACHD mice that express the full-length mutant huntingtin (mHtt) protein with 97 glutamine repeats, we first demonstrated localized in vivo changes in brain glucose use reminiscent of what is observed in premanifest HD carriers. Using biochemical, molecular, and functional analyses on different primary cell culture models from BACHD mice, we observed that mHtt does not directly affect metabolic activity in a cell autonomous manner. However, coculture of neurons with astrocytes from wild-type or BACHD mice identified mutant astrocytes as a source of adverse non-cell autonomous effects on neuron energy metabolism possibly by increasing oxidative stress. These results suggest that astrocyte-to-neuron signaling is involved in early energy metabolic alterations in HD.     

Fetal intracranial hemorrhage related to maternal autoimmune thrombocytopenic purpura

Background

Maternal autoimmune thrombocytopenic purpura (AITP) can cause fetal intracranial hemorrhage.

Case report

A 19-year-old primigravida was referred to our institution for prenatally detected ventriculomegaly at 30th week of gestation. Her personal and family histories were unremarkable. Her platelet count was 54?×?109/L. Fetal neurosonography showed intraparenchymal hemorrhage. AITP was diagnosed in the mother and platelet count decreased at 34?×?109/L. Patient was treated with methylprednisolone and intravenous immunoglobulin. She delivered a 2,340-g infant at 37 weeks with elective cesarean section. The platelet count of the newborn was 181?×?109/L and coagulation tests were normal. No antiplatelet specific antibodies were detected in cord blood. Postnatal MRI evaluation confirmed grade IV intracranial hemorrhage. The newborn baby has suffered from mild spasticity and seizures.

Conclusions

Clinicians must be vigilant about the catastrophic fetal complications of maternal AITP; a close follow-up with a multidisciplinary cooperation between obstetricians, hematologists, and neonatologists must be warranted.