BackgroundFrontotemporal dementia (FTD) may present with psychiatric symptoms, usually together with neurological ones and in cases with a family history of dementia. We describe the case of an FTD behavioural variant with a psychiatric presentation and a normal neurological examination, due to a C9Orf72 gene mutation.Case presentationThe patient was a 57 years-old Caucasian woman with a recent onset of bizarre behaviours and mystic delusions. She had a negative clinical history for previous psychiatric disorders and treatments and this was her first admission to a Psychiatry Ward. A careful assessment was performed including, beyond psychiatric evaluation, the following: blood sampling, neurological examination (including electroencephalogram, electroencephalogram with zygomatic electrodes, Positron Emission Tomography, Cerebrospinal Fluid Analysis), carotid artery Doppler ultrasound, brain Magnetic Resonance Imaging – angio Magnetic Resonance Imaging. Blood sampling for the genetic assessment of mutations associated to primary dementias was performed as well: the genes investigated were FUS, C9Orf72, PSEN-1, PSEN-2.ConclusionsSerological tests were negative, neurological examination was normal, instrumental examinations showed theta waves in the posterior temporal areas bilaterally and frontotemporal cortical atrophy bilaterally. The genetic assessment of mutations associated revealed she carried a GGGGCC hexanucleotide repeat expansion (at least 80 repeats) in C9Orf72 intron 1. Patients carrying the C9Orf72 mutation are likely to receive a psychiatric diagnosis (mainly mood disorder or schizophrenia) prior to correct diagnosis; this may be particularly problematic for those patients with no neurological signs to orientate diagnosis. Understanding the manner in which such FTD variant may present as a psychiatric syndrome, with a negative neurological examination, is essential to provide the best treatment for patients, as soon as possible, especially when the behavioural anomalies interfere with their care.
IntroductionMitochondrial disorders of energetic metabolism (MD) represent a heterogeneous group of diseases manifesting at any age and its one of a number of mitochondria syndromes that share the common characteristics of encephalopathy and myopathy. The clinical expression of MELAS (Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis and Stroke-like episodes) is highly variable and ppsychiatric symptoms are rarely reported in literature even if are more common in MELAS syndrome than in the general population.ObjectiveThe first aim of the study is describing the clinically observed primary psychiatric symptoms in a patient affected by MELAS syndrome admitted to the Psychiatric ward. The second aim is to go back over the diagnostic process, which led, from the uncommon psychiatric symptoms and signs to the final genetic diagnosis of MD.Methods and resultsWe report the case of a 44-year-old male with MELAS in whom psychiatric symptoms preceded the establishment of the clinical diagnosis for several months. Diagnosis was initially based on the neuroimaging and metabolic findings and subsequently confirmed with genetic analysis.ConclusionsIn case of aggressive and paranoid behaviour with delusions of persecution and disorganised behaviour mmitochondrial disorders deserve consideration as part of the differential diagnosis, especially if there is suspected involvement of other organ groups or positive family history of MD. There is no specific consensus approach for treating MELAS syndrome. Management is largely symptomatic and should involve a multidisciplinary team.Disclosure of interestThe authors have not supplied their declaration of competing interest.
Purpose:Bipolar patients have an increased risk of cardiovascular diseases for lifestyle habits and the use of antipsychotics that correlates with endothelial dysfunctions, in particular the decrease of eNOS activity and plasma NO levels. We aimed to examine the effects of the new atypical antipsychotic Asenapine on NO release and oxidative stress in porcine coronary endothelial cells (CEC).Methods:NO production was measured in CEC isolated from coronary arteries of pigs and plated in 0.1% gelatin-coated dishes with starvation medium overnight at 37 °C with 5% CO2. Cells were treated with asenapine 10 pM-100 μM and asenapine+inhibitors. Oxidative stress was generated with 200 μM hydrogen peroxide in the presence of asenapine for 15 min. The cells undergoing apoptosis were measured and proteins extracted from cell lysates were quantified and used for electrophoresis and immunoblotting studies.Results:Asenapine increased NO release in CEC in a time-dependent way (p<0.05) by the phosphorylation of eNOS and plateau was reached at 120s stimulation; no effect was observed on iNOS activation. The association of asenapine and inhibitors suggested the involvement of cAMP/PKA, PLC, p38MAPK, PI3K and ERK1/2 in the intracellular signaling and the β2 adrenergic receptors-related pathway. Data were confirmed by Western blot analysis. Pre-treatment of CEC with asenapine prevented cell death and mitochondrial membrane potential collapse caused by hydrogen peroxide (p<0.05) and counteracted the activation of apoptotic markers.Conclusions:Asenapine could play a protective role on endothelial function and cardiac cell survival, reducing the risk of cardiovascular disease in maniac patients.
IntroductionAlexithymia is characterized by difficulties identifying and communicating feelings, and problems differentiating between feelings and bodily sensations; its concrete cognitive style focused on the external environment is typical of psychosomatic patients. Patients with eating disorders (EDs) have high levels of alexithymia, particularly difficulties identifying and describing their feelings.ObjectiveThe aims of our study are (1) to assess the alexythimia, emotional empathy, facial emotion identification skills and social inference abilities in a sample of ED patients; (2) to compare these variables between ED patients and healthy controls (HC); and (3) to correlate levels of alexithymia with the severity of the ED as measured by the Eating Disorder Inventory-3 (EDI-3) EDRC score in the ED group.MethodsED (N=42) and HC (N=42) were tested with the Toronto Alexithymia Scale (TAS-20), Eating Disorder Inventory (EDI-3), Facial Emotion Identification Test (FEIT), The Awareness of Social Inference Test (TASIT) and Interpersonal Reactivity Index (IRI).ResultsData collection is being completed and the results’ analysis is ongoing. We expect the ED sample to show greater alexythimia and a poorer performance at FEIT and TASIT than HCs. We expect to find a linear correlation between the TAS-20 and EDRC score.ConclusionA better understanding of the role of alexithymia in ED etiology and maintenance might allow the development of targeted treatment approaches to help patients improve their skills in identifying and expressing emotions.
Introduction: Triple-negative breast cancer (TNBC), defined by a lack of expression of the estrogen, progesterone and HER-2 receptors, remains a major clinical challenge due to higher recurrence rates and poorer prognosis compared to other subtypes of breast cancer. Tumors that initially respond to chemotherapy - the core treatment option for the patients with an advanced disease - eventually develop resistance. New therapeutic options are urgently required for TNBC. Autophagy, a lysosome-mediated degradation and recycling process, has been shown to function as an adaptive survival response during chemotherapy. Previous studies in other cancer subtypes have indicated that autophagy inhibition can restore chemotherapeutic sensitivity and enhance treatment response. Objective: Generate proof-of-principle evidence for autophagy inhibition as an effective treatment strategy for TNBC. Experimental Design: We are employing in vitro models using TNBC lines MDA-MB-231 and SUM159PT, as well as their derivative lines (R8 and R75, respectively) resistant to Epirubicin (EPI) and other anthracyclines. In vivo xenograft mouse models of MDA-MB-231 and R8 are being used to evaluate the effects of combinatorial therapy with EPI and autophagy inhibitor hydroxychloroquine (HCQ). Methods: We assessed levels of autophagy in TNBC cell lines treated with EPI, developed EPI- resistant sub-lines, and compared basal autophagy levels in parental and resistant lines, using autophagy flux (degradative completion of autophagy) assays. We evaluated the effects of chemotherapy alone and in combination with autophagy inhibitors (HCQ or siRNAs targeting autophagy-related (Atg) proteins) on both parent and resistant sub-lines by assessing their viability. For in vivo studies, MDA-MB-231 cells were injected subcutaneously in Rag2M mice. After tumor formation, mice were treated with EPI, HCQ or their combination, and treatment efficacy was evaluated by tumor volume measurements. Autophagy levels in tumors were also assessed. Results: TNBC cells demonstrated increased autophagy in response to EPI treatment in vitro and in vivo. EPI- resistant lines showed at least 1.5 fold increased basal autophagy levels compared to their parental lines suggesting a possible adaptive role for autophagy in development of chemoresistance. Knock-down of Atg proteins by siRNA dramatically reduced the viability of EPI-resistant sub-lines, which indicates dependence of drug-resistant cells on autophagy for survival. Resistance of MDA-MB-231-R8 cells to EPI was reverted by autophagy inhibition in vitro. Combination of EPI with HCQ in vivo showed an enhanced tumor response to treatment compared to monotherapy with EPI. Additional in vivo studies are in progress. Conclusion: Our preliminary results suggest that autophagy inhibition may be an effective strategy for the treatment of chemo-refractory TNBC cells. Citation Format: Svetlana Bortnik, Suganthi Chittaranjan, Wieslawa H. Dragowska, Namal Abeysundara, Amy Chen, Lindsay DeVorkin, Nancy Dos Santos, Nancy Erro Go, Amy Leung, Dana Masin, Maria Rizza, Dita Strutt, Sherry Weppler, Jing Xu, Hong Yan, Karen Gelmon, Donald Yapp, Marcel Bally, Sharon M. Gorski. Autophagy inhibition as an effective strategy for sensitizing triple-negative breast cancer cells to chemotherapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1684. doi:10.1158/1538-7445.AM2013-1684
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