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The schizo-obsessive spectrum has been a central focus of interest and research within the scientific community in mental health. The increased comorbidity of schizophrenia and obsessive-compulsive symptoms (OCS) or obsessive-compulsive disorder (OCD) appears to be considerably higher than previously expected, with more recent studies suggesting growing prevalence rates. Despite this phenomenon, OCS are not considered primary manifestations of schizophrenia and are therefore not usually explored in these patients. The concept of schizo-obsessiveness mostly emerged in the 1990s, progressing into OCD-schizophrenia spectrum disorders as a dual diagnosis of OCD and schizophrenia. The manifestations of the schizo-obsessive spectrum are diverse, and its diagnoses may be divided overall into four main categories: schizophrenia with OCS; schizotypal personality disorder (SPD) with OCD; OCD with poor insight; schizo-obsessive disorder (SOD). In some cases, distinguishing an intrusive thought from delirium in OCD with poor insight might be challenging. Poor or absent insight can be present in many diagnoses of OCD. Those patients within the schizo-obsessive spectrum present a worse insight than those with OCD without schizophrenia. The comorbidity has important clinical implications, considering its association with an earlier onset of the disorder, more severe positive and negative psychotic symptoms, a greater cognitive deficit, more severe depressive symptoms, more suicide attempts, a reduced social network, increased psychosocial dysfunction, and consequently a worse quality of life and greater psychological suffering. The presence of OCS or OCD in schizophrenia may lead to more severe psychopathology and a worse prognosis. More precise diagnoses allow for a more targeted intervention by offering an optimized psychotherapeutic and psychopharmacological approach. We hereby present four clinical cases that represent each of the four designated categories of the schizo-obsessive spectrum. This case-series report aims to enhance clinical insight regarding the diversity of the schizo-obsessive spectrum and to illustrate the difficult and sometimes misleading process of differentiating OCD from schizophrenia and establishing a diagnosis due to the potential overlap of phenomenology, as well as the course and assessment of symptoms manifested within the spectrum.

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INTRODUCTION: Anorexia nervosa is a psychiatric disorder with various non-psychiatric manifestations that arise from the self-imposed malnourishment and possible purging behaviors. These medical manifestations or complications may mimic non psychiatric disorders and difficult the diagnosis of an eating disorder. CASE REPORT: We report the case of a patient with a binge-eating/purging subtype of anorexia nervosa, whose purges consisted in diuretic abuse. She kept her purges secret and during more than 1 year she was admitted several times in the emergency room for, sometimes life-threatening, hypokalemia. Furthermore, she consulted practitioners from different specialties and was hospitalized in a nephrology service to investigate chronic hypokalemia and other metabolic and hydroelectrolytic disturbances. A Bartter Syndrome was suspected, and she underwent genetic testing. Eventually she started psychiatric follow up and was admitted as an inpatient under the care of a specialized eating disorders unit. CONCLUSION: This patient presented a series of metabolic disturbances secondary to the diuretic abuse, that mimicked the manifestations of hereditary tubulopathies like Bartter Syndrome. Coincidentally it was found that the patient had a mutation in a gene linked to Bartter Syndrome, that wasn't enough to justify this diagnosis. So, a Pseudo Bartter Syndrome secondary to the diuretic abuse was evident. The focus on medical manifestations delayed the recognition of the anorexia nervosa and the associated diuretic abuse as the main cause of the electrolyte and metabolic disturbances. This case emphasizes the importance of being familiarized with the non-psychiatric manifestations of eating disorders, so they may be rapidly recognized and managed. LEVEL OF EVIDENCE: Level V, Case Report.

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In this study, we report the identification of a novel role of SIRT6 in both epirubicin and paclitaxel resistance in breast cancer. We found that SIRT6 protein levels are elevated in paclitaxel- and epirubicin-resistant MCF-7 cells compared with the parental sensitive cells. SIRT6 knockout and depletion sensitized cells to both paclitaxel and epirubicin treatment, whereas SIRT6 ectopic overexpression led to increased resistance to paclitaxel and epirubicin. Moreover, our data suggest that SIRT6 could be mediating epirubicin resistance through enhancing the DNA repair response to epirubicin-induced DNA damage. Clonogenic assays also revealed that mouse embryonic fibroblasts (MEFs) lacking SIRT6 have decreased long-term viability in response to epirubicin. The tumour suppressor FOXO3a increases its levels of acetylation in MEFs depleted of SIRT6, whereas its induction by epirubicin is attenuated in breast cancer cells overexpressing SIRT6. Further cell viability studies demonstrate that deletion of FOXO1/3/4 in MEFs can confer sensitivity to both paclitaxel and epirubicin, suggesting that SIRT6 reduces paclitaxel and epirubicin sensitivity, at least in part, through modulating FOXO acetylation and expression. Consistently, immunohistochemical analysis of 118 breast cancer patient samples revealed that high SIRT6 nuclear staining is significantly associated with poorer overall survival (P = 0.018; Kaplan-Meier analysis). Multivariate Cox analysis demonstrated that nuclear SIRT6 staining remained associated with death after correcting for tumour stage and lymph-node involvement (P = 0.033). Collectively, our data suggest that SIRT6 has a role in paclitaxel and epirubicin sensitivity via targeting FOXO proteins and that SIRT6 could be a useful biomarker and therapeutic target for paclitaxel- and epirubicin-resistant cancer.

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