Centre for Youth Mental Health - Research Publications
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ItemAddition of aripiprazole to the clozapine may be useful in reducing anxiety in treatment-resistant schizophrenia.(Hindawi Limited, 2011)There exist many case reports and studies on the antipsychotic augmentation by aripirazole in partial responders to clozapine, the most seem to be finding a slight difference in the PANSS and CGI scores after the aripirazole addition. The results of our report are compatible with those of other studies but, we have found a considerable antianxiety action in both of the cases. The 5HT1A agonism of aripirazole could be hypothesized as mechanism contributing to this effect.
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ItemViolent behaviour in early psychosis patients: Can we identify clinical risk profiles?(WILEY, 2019-06)AIMS: The objective of this study is to explore, within a sample of early psychosis patients (EPP), if subgroups regarding rate of violent behaviour (VB) against others can be identified on the basis of dynamic risk factors (treatment modifiable characteristics). METHODS: In a sample of 265 EPP, treated at the Treatment and Early Intervention in Psychosis Program in Lausanne, we conducted a latent-class analysis on the basis of the main dynamic VB risk factors (substance use disorder [SUD], positive symptoms, insight, and impulsivity). VB were restricted to "serious violence" and were assessed through patients self-report, interview with relatives or forensic services and with a standardized instrument. RESULTS: The analysis confirmed the heterogeneity of the sample regarding rate of VB. Patients could be stratified within 4 subgroups, 3 of which were at increased risk of VB. The two groups with the highest rates of VB displayed specific clinical profiles. The first one was characterized by high levels of impulsivity, hostility, positive symptoms and SUD, and the second, by low level of insight and low social functioning. These patterns suggest that significant difficulties in social interaction may contribute to the emergence of aggressive reactions against others. CONCLUSIONS: Identification of EPP at increased risk of VB seems possible on the basis of dynamic risk factors. If confirmed prospectively, this could pave the way to the development of preventive strategies and specific interventions.
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ItemAssociation Between Plasma Caffeine and Other Methylxanthines and Metabolic Parameters in a Psychiatric Population Treated With Psychotropic Drugs Inducing Metabolic Disturbances(FRONTIERS MEDIA SA, 2018-11-09)Importance: Multiple studies conducted in the general population identified an association between self-reported coffee consumption and plasma lipid levels. To date, no study assessed whether and which plasma methylxanthines (caffeine and/or its metabolites, i.e., paraxanthine, theophylline, and theobromine) are associated with plasma lipids. In psychiatric patients, an important coffee consumption is often reported and many psychotropic drugs can induce a rapid and substantial increase of plasma lipid levels. Objective: To determine whether plasma methylxanthines are associated with metabolic parameters in psychiatric patients receiving treatments known to induce metabolic disturbances. Design, Setting, and Participants: Data were obtained from a prospective study including 630 patients with metabolic parameters [i.e., body mass index (BMI), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and fasting triglycerides (TG)] monitored routinely during psychotropic treatment. Exposures: Plasma methylxanthines levels. Main Outcomes and Measures: Metabolic variables including BMI and plasma lipid levels. Results: Multivariate analyses indicated that BMI, TC, HDL-C, and non-HDL-C increased significantly with increasing total methylxanthines (p corrected ā¤ 0.05). In addition, compared to patients with plasma caffeine concentration in the lowest quartile, those with caffeine concentration in the highest quartile were twice more prone to suffer from non-HDL hypercholesterolemia (p corrected = 0.05), five times more likely to suffer from hypertriglyceridemia (p corrected = 0.01) and four times more susceptible to be overweight (p corrected = 0.01). Conclusions and Relevance: This study showed that plasma caffeine and other methylxanthines are associated with worsening of metabolic parameters in patients receiving psychotropic treatments known to induce metabolic disturbances. It emphasizes that important caffeine consumption could be considered as an additional environmental risk factor for metabolic worsening in patients receiving such treatments.
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ItemPrevalence of ECG abnormalities and risk factors for QTc interval prolongation in hospitalized psychiatric patients(SAGE PUBLICATIONS LTD, 2019-12)BACKGROUND: Psychiatric patients are at risk of cardiovascular diseases, and many psychotropic drugs can prolong QTc interval. Requirements for electrocardiogram (ECG) monitoring have been set up in our psychiatric university hospital. The objective of this study was to determine the proportion of adult patients who had an ECG during their hospitalization, the prevalence of ECG abnormalities, the evolution of the QTc after admission, and the risk factors for QTc prolongation. METHODS: Retrospective analysis of ECGs and clinical data of all patients with a complete hospitalization in 2015. Assessment of the influence of covariates on QTc using linear mixed-effects models. RESULTS: At least one ECG (nā=ā600) was performed during 37.6% of the stays (nā=ā1198) and in 45.5% of the patients (nā=ā871). Among the patients with an ECG, 17.9% had significant ECG abnormalities, including 7.6% with a prolonged QTc. QTc measured at admission and during hospitalization did not change significantly (nā=ā46, 419.4āĀ±ā29.7 ms, 417.2āĀ±ā27.6 ms, pā=ā0.71). In the multivariate model (292 patients, 357 ECGs), the covariates significantly associated with the QTc were gender (+15.9 ms if female, pā<ā0.0001), age (+0.4 ms/year, pā=ā0.0001), triglyceride levels (+5.7 ms/mmol/l, pā=ā0.005), and drugs with known risk of torsades de pointes (+6.2 ms if ā©¾1 drug, pā=ā0.028). CONCLUSIONS: The prevalence of hospitalized psychiatric patients with an abnormal ECG indicates that ECGs should be performed systematically in this population. Prescription of psychotropic drugs should be done cautiously, particularly in patients with QTc prolongation risk factors.
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ItemAn International Society of Bipolar Disorders task force report: Precursors and prodromes of bipolar disorder(WILEY, 2019-12)OBJECTIVES: To clarify the clinical features preceding the onset of bipolar disorder (BD) has become a public health priority for the prevention of high morbidity and mortality. BD remains frequently under- or misdiagnosed, and under- or mistreated, often for years. METHODS: We assessed the predictive value of precursors and prodromes of BD. We assessed precursors of first-lifetime manic or hypomanic episodes with/without mixed features in retrospective and prospective studies. The task force evaluated and summarized separately assessments of familial risk, premorbid personality traits, retrospective, and prospective studies. RESULTS: Cyclothymic features, a family history of BD, retrospectively reported attenuated manic symptoms, prospectively identified subthreshold symptoms of hypomania, recurrence of depression, panic anxiety and psychotic features, have been identified as clinical precursors of BD. The prodromal symptoms like [hypo]mania often appears to be long enough to encourage early identification and timely intervention. CONCLUSIONS: The predictive value of any risk factor identified remains largely unknown. Prospective controlled studies are urgently needed for prevention and effective treatment.
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ItemFrontal cortical thickness correlates positively with impulsivity in early psychosis male patients(WILEY, 2019-08)AIM: Impulsive behaviours, which are frequent in young people suffering from psychosis have been linked to risky and violent behaviours and participate to the burden of psychotic illness. Given that morphological brain correlates of impulsivity in schizophrenia have been poorly investigated especially in young adults, the aim of this study was to investigate the relationship between impulsivity and cortical thickness in early psychosis (EP) patients. METHOD: A total of 17 male subjects in the early phase of psychosis were recruited. Impulsivity was assessed with the Lecrubier Impulsivity Rating Scale. Mean cortical thickness was extracted from magnetic resonance imaging brain scans, using surface-based methods. RESULTS: Mean cortical thickness in the frontal lobe correlated positively with mean impulsivity in EP male patients. CONCLUSION: Our results suggest that psychotic subjects exhibiting higher impulsivity have larger frontal cortical thickness, which may pave the way towards the identification of patients with a higher risk to display impulsive behaviours.
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ItemCity Avoidance in the Early Phase of Psychosis: A Neglected Domain of Assessment and a Potential Target for Recovery Strategies(FRONTIERS MEDIA SA, 2019-06-03)Background: A considerable amount of research has explored the link between living in an urban environment during childhood and the increased risk to develop psychosis. However, the urban milieu is more than a risk factor as it is also a place for socialization and enrichment. The aims of the current study were to explore, in a large sample of early psychosis (EP) patients, their pattern of use of the city, their perception when exposed to various critical stressors, and their sensitivity to diverse forms of stimuli. Methods: We sent a questionnaire (based on previous work conducted in a group of patients, including video-recorded walk-along in the city and a literature review) to 305 EP patients and to 220 medical students. Results: Response rate in patients was low (38%). City avoidance and negative perceptions towards the urban environment increased in patients after onset of psychosis. Patients' tendency to avoid city center correlates with both problematic social interactions and stimuli perceived as unpleasant. Patients seemed less likely to enjoy urban spaces considered as relaxing, suggesting a lower capacity to benefit from positive aspects of this environment. Conclusions: The development of psychosis influences the way EP patients perceive the city and their capacity to feel at ease in the urban environment, leading to a high rate of city avoidance. Considering the possible influence of city avoidance on social relations and the recovery process, the development of strategies to help patients in this regard may have a significant effect on their recovery process.
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ItemN-acetylcysteine add-on treatment leads to an improvement of fornix white matter integrity in early psychosis: a double-blind randomized placebo-controlled trial(SPRINGERNATURE, 2018-10-12)Mechanism-based treatments for schizophrenia are needed, and increasing evidence suggests that oxidative stress may be a target. Previous research has shown that N-acetylcysteine (NAC), an antioxidant and glutathione (GSH) precursor almost devoid of side effects, improved negative symptoms, decreased the side effects of antipsychotics, and improved mismatch negativity and local neural synchronization in chronic schizophrenia. In a recent double-blind randomized placebo-controlled trial by Conus et al., early psychosis patients received NAC add-on therapy (2700āmg/day) for 6 months. Compared with placebo-treated controls, NAC patients showed significant improvements in neurocognition (processing speed) and a reduction of positive symptoms among patients with high peripheral oxidative status. NAC also led to a 23% increase in GSH levels in the medial prefrontal cortex (GSHmPFC) as measured by 1H magnetic resonance spectroscopy. A subgroup of the patients in this study were also scanned with multimodal MR imaging (spectroscopy, diffusion, and structural) at baseline (prior to NAC/placebo) and after 6 months of add-on treatment. Based on prior translational research, we hypothesized that NAC would protect white matter integrity in the fornix. A groupāĆātime interaction indicated a difference in the 6-month evolution of white matter integrity (as measured by generalized fractional anisotropy, gFA) in favor of the NAC group, which showed an 11% increase. The increase in gFA correlated with an increase in GSHmPFC over the same 6-month period. In this secondary study, we suggest that NAC add-on treatment may be a safe and effective way to protect white matter integrity in early psychosis patients.
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ItemImplication of the glutamate-cystine antiporter xCT in schizophrenia cases linked to impaired GSH synthesis(NATURE PUBLISHING GROUP, 2017-09-18)UNLABELLED: xCT is the specific chain of the cystine/glutamate antiporter, which is widely reported to support anti-oxidant defenses in vivo. xCT is therefore at the crossroads between two processes that are involved in schizophrenia: oxidative stress and glutamatergic neurotransmission. But data from human studies implicating xCT in the illness and clarifying the upstream mechanisms of xCT imbalance are still scarce. Low glutathione (GSH) levels and genetic risk in GCLC (Glutamate-Cysteine Ligase Catalytic subunit), the gene of limiting synthesizing enzyme for GSH, are both associated with schizophrenia. In the present study, we aimed at determining if xCT regulation by the redox system is involved in schizophrenia pathophysiology. We assessed whether modulating GCLC expression impact on xCT expression and activity (i) in fibroblasts from patients and controls with different GCLC genotypes which are known to affect GCLC regulation and GSH levels; (ii) in rat brain glial cells, i.e., astrocytes and oligodendrocytes, with a knock-down of GCLC. Our results highlight that decreased GCLC expression leads to an upregulation of xCT levels in patients' fibroblasts as well as in astrocytes. These results support the implication of xCT dysregulation in illness pathophysiology and further indicate that it can result from redox changes. Additionally, we showed that these anomalies may already take place at early stages of psychosis and be more prominent in a subgroup of patients with GCLC high-risk genotypes. These data add to the existing evidence identifying the inflammatory/redox systems as important targets to treat schizophrenia already at early stages. SCHIZOPHRENIA: ANTIOXIDANT DEFICIT INCREASES A KEY NEUROTRANSMITTER TRANSPORTER: Deficit of antioxidant synthesis in schizophrenia leads to oxidative stress and changes in neurotransmitter transporter. Led by Kim Do, a team of researchers from Lausanne University in Switzerland investigated the role of the cell-surface transport protein xCT in schizophrenia. They found that an enzyme responsible for antioxidant production is disturbed in patients. This leads to decreased antioxidant levels and consequently to oxidative stress-i.e. the accumulation of reactive oxygen molecules, damaging the cells component and impairing cell functioning-which in turn affects the functioning of the antioxidant pathway, including xCT. xCT, which exports the neurotransmitter glutamate, is thus overproduced in schizophrenia. The resulting increase of neurotransmitter activity, alongside the increase in oxidative stress, is thought to play a major role in the pathophysiology of schizophrenia, including at early stages of the disease.