RESUMO
BACKGROUND: Older companion dogs naturally develop a dementia-like syndrome with biological, clinical and therapeutic similarities to Alzheimer disease (AD). Given there has been no new safe, clinically effective and widely accessible treatment for AD for almost 20 years, an all-new cell therapeutic approach was trialled in canine veterinary patients, and further modelled in aged rats for more detailed neurobiological analysis. METHODS: A Phase 1/2A veterinary trial was conducted in N = 6 older companion dogs with definitive diagnosis of Canine Cognitive Dysfunction (CCD). Treatment comprised direct microinjection of 250,000 autologous skin-derived neuroprecursors (SKNs) into the bilateral hippocampus using MRI-guided stereotaxis. Safety was assessed clinically and efficacy using the validated Canine Cognitive Dysfunction Rating Scale (CCDR) at baseline and 3-month post treatment. Intention to treat analysis imputed a single patient that had a surgical adverse event requiring euthanasia. Three dog brains were donated following natural death and histology carried out to quantify Alzheimer pathology as well as immature neurons and synapses; these were compared to a brain bank (N = 12) of untreated aged dogs with and without CCD. Further, an age-related memory dysfunction rat model (N = 16) was used to more closely evaluate intrahippocampal engraftment of canine SKN cells, focusing on mnemonic and synaptic effects as well as donor cell survival, neurodifferentation and electrophysiologic circuit integration in a live hippocampal slice preparation. RESULTS: Four out-of-five dogs improved on the primary clinical CCDR endpoint, three fell below diagnostic threshold, and remarkably, two underwent full syndromal reversal lasting up to 2 years. At post mortem, synaptic density in the hippocampus specifically was nine standard deviations above non-treated dogs, and intensity of new neurons also several fold higher. There was no impact on AD pathology or long-term safety signals. Modelling in aged rats replicated the main canine trial findings: hippocampally-dependent place memory deficits were reversed and synaptic depletion rescued. In addition, this model confirmed donor cell survival and migration throughout the hippocampus, neuronal differentiation in situ, and physiologically-correct integration into pyramidal layer circuits. CONCLUSIONS: With further development, SKN cell therapy may have potential for treating carefully chosen AD patients based on neurosynaptic restoration in the hippocampus.
Assuntos
Doença de Alzheimer , Terapia Baseada em Transplante de Células e Tecidos , Doenças do Cão , Animais , Cães , Doença de Alzheimer/terapia , Doença de Alzheimer/veterinária , Doenças do Cão/terapia , Hipocampo/patologia , Células-Tronco Neurais/transplanteRESUMO
BACKGROUND: European member states are increasingly vying with one another to recruit patients for clinical trials (CTs). The French national agency for medicines (ANSM) now receives an ever-growing number of CTs, extending response times. The aim of the new methodology presented herein is to reduce assessment times below the national mandatory timeframe of 60 days and to improve patient safety. MATERIALS AND METHODS: Based on an analysis of the criteria defining CTs, 4 key points were identified (safety, fragile population, loss of opportunity, design complexity) to build a criticality score which would determine evaluation type. This score also determines the resources needed (complete evaluation, multidisciplinary advice, ad hoc evaluation) and the timeframe required for appropriate analysis. All post-phase I CTs were analysed from the implementation of the new assessment method, on 01/02/2018 through to 31/12/2019. RESULTS: 447 CTs were analysed (63% industry and 37% academic sponsors). Based on a criticality scale, 27% of the CTs received a type A evaluation (complete), 37% a type B (multidisciplinary evaluation), 23% a type C evaluation (ad hoc evaluation) and 13% a type D evaluation (fast evaluation). From 2014 to 2017, 37% of the CTs were analysed within the mandatory timeframe, with a mean of 68 days, reaching a maximum of 102 days in 2017. Using this new assessment method, 92% of CTs respected the mandatory timeframe in 2019; the mean time in 2018-2019 was 34 days; Grounds for Non-Acceptance (GNA) were raised for 66% of the CTs (69% from academic sponsors and 65% from industrial firms). 3 CTs were refused. CONCLUSION: Here, we demonstrate the feasibility of risk analysis and multidisciplinarity method, which resulted in a dramatic improvement of assessment times.
Assuntos
Hematologia , Projetos de Pesquisa , Humanos , Medição de RiscoRESUMO
Psychosocial Interventions (PIs) have shown positive effects on clinical and functional outcomes of schizophrenia (SZ) in randomized controlled trials. However their effectiveness and accessibility remain unclear to date in "real world" schizophrenia. The objectives of the present study were (i) to assess the proportion of SZ outpatients who benefited from PIs between 2010 and 2015 in France after an Expert Center Intervention in a national multicentric non-selected community-dwelling sample; (ii) to assess PIs' effectiveness at 1-year follow-up. 183 SZ outpatients were recruited from FondaMental Advanced Centers of Expertise for Schizophrenia cohort. Baseline and 1-year evaluations included sociodemographic data, current treatments, illness characteristics and standardized scales for clinical severity, adherence to treatment, quality of life, a large cognitive battery, and daily functioning assessment. Only 7 (3.8%) received a PI before the evaluation, and 64 (35%) have received at least one PI during the 1-year follow-up. Having had at least one PI during the follow-up has been associated in multivariate analyses with significantly higher improvement in positive and negative symptoms (respectively p =0.031; p = 0.011), mental flexibility (TMT B, p = 0.029; C-VF, p = 0.02) and global functioning (p =0.042). CBT and SST were associated with higher cognitive improvements, while CRT was associated with clinical improvement. These results have not been demonstrated before and suggest that the effect of each PI is larger than its initial target. The present study has confirmed the PIs' effectiveness in a large sample of community-dwelling SZ outpatients at 1 year follow-up. Efforts to improve access to PI should be reinforced in public health policies.
Assuntos
Terapia Cognitivo-Comportamental , Remediação Cognitiva , Acessibilidade aos Serviços de Saúde , Educação de Pacientes como Assunto , Qualidade de Vida/psicologia , Esquizofrenia/reabilitação , Habilidades Sociais , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Psicologia do Esquizofrênico , Adulto JovemRESUMO
Tobacco smoking is common in schizophrenia and is one of the main causes of premature mortality in this disorder. Little is known about clinical correlates and treatments associated with tobacco smoking in patients with schizophrenia. Still, a better characterization of these patients is necessary, in a personalized care approach. Aggressiveness and childhood trauma have been associated with tobacco smoking in general population, but this association has never been explored in schizophrenia. Our study examines the clinical and therapeutic characteristics of tobacco smoking in schizophrenia. 474 stabilized patients (mean age = 32.2; 75.7% male gender; smokers n = 207, 54.6%) were consecutively included in the network of the FondaMental Expert centers for Schizophrenia and assessed with valid scales. Current tobacco status was self-declared. Aggressiveness was self-reported with Buss-Perry Aggressiveness Questionnaire and Childhood Trauma with Childhood Trauma Questionnaire. Ongoing treatment was reported. In univariate analysis, tobacco smoking was associated with lower education level (p < 0.01), positive syndrome (p < 0.01), higher physical aggressiveness (p < 0.001), alcohol dependence (p < 0.001), and First Generation Antipsychotics (FGAs) use (p = 0.018). In a multivariate model, tobacco smoking remained associated with physical aggressiveness (p < 0.05), current alcohol dependence (p < 0.01) and FGA use (p < 0.05). No association was observed with childhood trauma history, mood disorder, suicidal behavior, psychotic symptom, global functioning or medication adherence. Patients with tobacco use present clinical and therapeutic specificities, questioning the neurobiological links between tobacco and schizophrenia. They could represent a specific phenotype, with specific clinical and therapeutic specificities that may involve interactions between cholinergic-nicotinic system and dopaminergic system. Further longitudinal studies are needed to confirm the potential efficacy of second generation antipsychotics (SGAs) on tobacco use in schizophrenia and to develop effective strategies for tobacco cessation in this population.
Assuntos
Experiências Adversas da Infância , Agressão/fisiologia , Alcoolismo/fisiopatologia , Transtornos Psicóticos/fisiopatologia , Esquizofrenia/fisiopatologia , Fumar Tabaco/fisiopatologia , Adulto , Adultos Sobreviventes de Eventos Adversos na Infância , Alcoolismo/epidemiologia , Antipsicóticos/uso terapêutico , Comorbidade , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/epidemiologia , Esquizofrenia/tratamento farmacológico , Esquizofrenia/epidemiologia , Fumar Tabaco/epidemiologia , Adulto JovemRESUMO
A high rate of patients with schizophrenia (SZ) does not sufficiently respond to antipsychotic medication, which is associated with relapses and poor outcomes. Chronic peripheral inflammation has been repeatedly associated with schizophrenia risk and particularly to poor responders to treatment as usual with cognitive impairment in SZ subjects. The objective of present study was to confirm if ultra resistance to treatment in schizophrenia (UTRS) was associated to chronic peripheral inflammation in a non-selected sample of community-dwelling outpatients with schizophrenia. Participants were consecutively included in the network of the FondaMental Expert Centers for Schizophrenia and received a thorough clinical assessment, including recording of current treatment. Current psychotic symptomatology was evaluated by the Positive and Negative Syndrome scale for Schizophrenia (PANSS). UTRS was defined by current clozapine treatment + PANSS total score ≥ 70. Functioning was evaluated by the Global Assessment of Functioning scale. High sensitivity CRP (hs-CRP) was measured for each participant as a proxy to define peripheral low-grade inflammation. 609 stabilized community-dwelling SZ subjects (mean age = 32.5 years, 73.6% male gender) have been included. 60 (9.9%) patients were classified in the UTRS group. In multivariate analyses, UTRS has been associated independently with chronic peripheral inflammation (OR = 2.6 [1.2-5.7], p = 0.01), illness duration (0R = 1.1 [1.0-1.2], p = 0.02) and impaired functioning (OR = 0.9 [0.9-0.9], p = 0.0002) after adjustment for age, sex, current daily tobacco smoking, metabolic syndrome and antidepressant consumption. Peripheral low-grade inflammation is associated with UTRS. Future studies should explore if anti-inflammatory strategies are effective in UTRS with chronic low-grade peripheral inflammation.
Assuntos
Antipsicóticos/uso terapêutico , Inflamação/complicações , Esquizofrenia/tratamento farmacológico , Adulto , Proteína C-Reativa/análise , Estudos de Coortes , Feminino , Humanos , Masculino , Síndrome Metabólica/complicações , Escalas de Graduação Psiquiátrica , Esquizofrenia/complicações , Falha de TratamentoRESUMO
OBJECTIVES: The present article is a synthesis of the first 10 years of follow-up of the FondaMental Academic Center of Expertise for Schizophrenia (FACE-SZ) cohort. METHODS: More than 700 community-dwelling stabilized subjects have been recruited and evaluated to date. The mean age was 32 years with 75 % males, the mean illness duration was 11 years, the mean age at illness onset was 21 years, the mean duration of untreated psychosis was 1.5 years and 55 % were current daily tobacco smokers. RESULTS: The major findings of the FACE-SZ cohort may be summarized as follows: the metabolic syndrome is twice more frequent in schizophrenia as compared to the general population and is not correctly assessed and treated; cognitive disturbances have been found in benzodiazepine consumers and in patients with chronic low-grade peripheral inflammation; major depressive disorder (MDD) is a common current comorbid condition in about 20% of the subjects at the evaluation. MDD is associated with impaired quality of life and with increased nicotine dependency in SZ daily tobacco smokers. Improving depression and negative symptoms may be the most effective strategies to improve quality of life in schizophrenia; the duration of untreated psychosis is much longer in cannabis smokers and in subjects with an age at illness onset<19 years. Adherence to treatment is diminished in subjects who report a subjective negative feeling after treatment intake independent of objective side effects (extrapyramidal syndrome and weight gain). Akathisia has been found in 18% of the subjects and has been associated with antipsychotic polytherapy. CONCLUSIONS: In the light of these results, some recommendations for clinical care may be suggested. The early detection of schizophrenia should be specifically increased in adolescents and/or cannabis smokers. All patients should be administered a comprehensive neuropsychological evaluation at the beginning of the illness and after stabilization under treatment. Improving metabolic parameters and lifestyle (diet and physical activity) should be reinforced. The benefit/risk ratio of benzodiazepine and antipsychotic polytherapy should be regularly reevaluated and withdrawn as soon as possible. If MDD remains underdiagnosed and undertreated, improving depression may strongly improve the quality of life of SZ subjects. In the end, Cognitive Remediation Therapy and anti-inflammatory strategies should be more frequently included in therapeutic strategies.
Assuntos
Psiquiatria/normas , Esquizofrenia/terapia , Adulto , Idade de Início , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Transtornos Cognitivos/complicações , Transtornos Cognitivos/epidemiologia , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/epidemiologia , Feminino , França , Humanos , Masculino , Síndrome Metabólica/complicações , Síndrome Metabólica/epidemiologia , Cooperação do Paciente , Qualidade de Vida , Esquizofrenia/complicações , Esquizofrenia/epidemiologia , Psicologia do Esquizofrênico , Fumar/epidemiologiaRESUMO
BACKGROUND: Aggressiveness is a stigma frequently associated with schizophrenia. The role of insight as a risk factor of aggressiveness remains contradictory; mainly because single measures of these states mask their complexity and heterogeneity. METHODS: This study was conducted on 666 patients aged 15 and above with a DSM-IV-TR diagnosis of schizophrenia spectrum disorder, drawn from the French national network of schizophrenia expert center database. Collected data comprised socio-demographics and standardized psychiatric assessments. Aggressiveness was evaluated using the Buss-Perry Aggression Questionnaire and insight using the Scale to assess Unawareness of Mental Disorder (SUMD) and Birchwood Insight Scale (BIS). RESULTS: Hostility was the aggressiveness dimension the most strongly associated with SUMD insight dimensions. Patients aware of their illness were nearly twice as likely to show hostility than those seriously unaware (ORâ¯=â¯1.95, 95% CI.: 1.08-3.5), but not when further adjusting for depression. Similarly, those aware of the consequences of their illness and of their symptoms were more hostile. Patients moderately aware of illness consequences had a higher risk of both anger and physical aggressiveness than those unaware (ORâ¯=â¯2.63, 95% CI.: 1.42-4.86, ORâ¯=â¯2.47, 95% CI.: 1.33-4.60, respectively), even when adjusting for depression for anger. CONCLUSION: Our study confirms that a multi-dimensional approach to insight and aggressiveness is essential to understand the types of links between these clinical states. Insight may trigger the expression of an underlying hostile tendency, maybe via depression and self-stigmatisation. This should be taken into account in therapeutic approaches to improve insight.
Assuntos
Agressão/fisiologia , Conscientização/fisiologia , Autoavaliação Diagnóstica , Hostilidade , Transtornos Psicóticos/fisiopatologia , Esquizofrenia/fisiopatologia , Adolescente , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVE: Hypovitaminosis D has been associated with respectively major depressive disorder, schizophrenia (SZ) and cognitive disorders in the general population, and with positive and negative symptoms and metabolic syndrome in schizophrenia. The objectives were (i) to determine the prevalence of hypovitaminosis D and associated factors (with a focus on depression and cognition) in a national non-selected multicentric sample of community-dwelling SZ subjects (ii) to determine the rate of SZ patients being administered vitamin D supplementation and associated factors. METHODS: A comprehensive 2 daylong clinical and neuropsychological battery was administered in 140 SZ subjects included between 2015 and 2017 in the national FondaMental Expert Center (FACE-SZ) Cohort. Hypovitaminosis D was defined by blood vitamin D level <25â¯nM. Depressive symptoms were assessed by the Positive and Negative Syndrome Scale depressive subscore and current anxiety disorder by the Structured Clinical Interview for Mental Disorders. RESULTS: Hypovitaminosis D has been found in 21.4% of the subjects and none of them had received vitamin D supplementation in the previous 12 months. In multivariate analysis, hypovitaminosis D has been significantly associated with respectively higher depressive symptoms (aORâ¯=â¯1.18 [1.03-1.35], pâ¯=â¯0.02) and current anxiety disorder (aORâ¯=â¯6.18 [2.15-17.75], pâ¯=â¯0.001), independently of age and gender. No association of hypovitaminosis D with respectively positive and negative symptoms, cognitive scores or other biological variables has been found (all pâ¯>â¯0.05), however, a trend toward significance has been found for metabolic syndrome (pâ¯=â¯0.06). Vitamin D supplementation has been administered during the previous 12 months in only 8.5% of the subjects but was associated with lower depressive symptoms (aORâ¯=â¯0.67 [0.46-0.98], pâ¯=â¯0.04) and lower rate of current anxiety disorder (aORâ¯=â¯0.06 [0.01-0.66], pâ¯=â¯0.02) compared to patients with hypovitaminosis D. CONCLUSION: Hypovitaminosis D is frequent and associated with depressive symptoms and anxiety disorders in schizophrenia. Vitamin D supplementation is associated with lower depressive and anxiety symptoms, however patients with hypovitaminosis D remain insufficiently treated.
Assuntos
Ansiedade/epidemiologia , Depressão/epidemiologia , Síndrome Metabólica/epidemiologia , Esquizofrenia/epidemiologia , Deficiência de Vitamina D/epidemiologia , Adulto , Estudos de Coortes , Feminino , França/epidemiologia , Humanos , Masculino , Adulto JovemRESUMO
OBJECTIVE: Latent Toxoplasma infection has been associated with widespread brain immune activation, increased blood brain barrier permeability, neural disruption, increased dopamine release in dopaminergic neurons, with NMDA activation and with schizophrenia (SZ) onset risk. Toxoplasma has been suggested to be a source of chronic low-grade inflammation and this inflammation has been associated with cognitive impairment in SZ. The objective of the present study were (i) to determine if latent Toxoplasma infection was associated with specific clinical features in stabilized SZ subjects, with cognitive impairment and with increased low-grade peripheral inflammation and (ii) to determine if Treatments with Anti-Toxoplasmic Activity (TATA) were associated with improved outcomes in subjects with latent Toxoplasma infection. METHODS: A comprehensive 2 daylong clinical and neuropsychological battery was administered in 250 SZ subjects included between 2015 and 2017 in the national FondaMental Expert Center (FACE-SZ) Cohort. Solid phase-enzyme microplate immunoassay methods were used to measure IgG class of antibodies to T. gondii in blood sample. Latent Toxoplasma infection was defined by T. gondii IgG ratio ≥0.8, equivalent to ≥10 international units. Chronic peripheral inflammation was defined by highly sensitive C reactive protein blood levelâ¯≥â¯3â¯mg/L. RESULTS: Latent Toxoplasma infection has been found in 184 (73.6%) of this national multicentric sample. In the multivariate analyses, latent Toxoplasma infection has been significantly associated with higher PANSS negative (aORâ¯=â¯1.1 [1.1-1.1], pâ¯=â¯0.04) and excitement subscores (aORâ¯=â¯1.3 [1.1-1.6], pâ¯=â¯0.01), with two specific symptoms (i.e., reference delusion (aORâ¯=â¯3.6 [1.2-10.6] pâ¯=â¯0.01) and alogia (aORâ¯=â¯16.7 [2.0-134.7], pâ¯=â¯0.008)) and with chronic low-grade peripheral inflammation (27.2% vs. 7.6%, aORâ¯=â¯3.8 [1.4-10.3], pâ¯=â¯0.004). Extrapyramidal symptoms remained significantly associated with latent Toxoplasma infection. On the opposite, no significant association of latent Toxoplasma infection with age, gender, age at SZ onset, suicide behavior or cognitive deficits has been found in these models (all pâ¯>â¯0.05). TATA were associated with lower depressive symptoms (aORâ¯=â¯0.8[0.7-0.9], pâ¯=â¯0.01), and with lower rates of chronic peripheral inflammation (20.9% vs. 48.6%, aORâ¯=â¯3.5 [1.5-7.9], pâ¯=â¯0.003) but not with higher cognitive scores (pâ¯>â¯0.05). CONCLUSION: The present findings suggest that Toxoplasma is almost 3 times more frequent in SZ population compared to general population in France. The potential cerebral underpinnings of the association of latent Toxoplasma infection and the above-mentioned outcomes have been discussed. Future studies should confirm that TATA may be effective to reduce Toxoplasma-associated depressive symptoms and low-grade peripheral inflammation.
Assuntos
Esquizofrenia/epidemiologia , Toxoplasmose/epidemiologia , Adulto , Antígenos de Protozoários/sangue , Proteína C-Reativa/metabolismo , Disfunção Cognitiva/sangue , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/parasitologia , Estudos de Coortes , Estudos Transversais , Depressão/sangue , Depressão/epidemiologia , Depressão/parasitologia , Feminino , Humanos , Imunoglobulina G/sangue , Inflamação/sangue , Inflamação/epidemiologia , Inflamação/parasitologia , Inflamação/psicologia , Masculino , Prevalência , Esquizofrenia/sangue , Esquizofrenia/parasitologia , Psicologia do Esquizofrênico , Toxoplasma/imunologia , Toxoplasmose/sangue , Toxoplasmose/psicologiaRESUMO
OBJECTIVE: The effect of benzodiazepine long-term administration (BLTA) in cognitive functioning of subjects with schizophrenia (SZ) has been partially explored to date. The objective was to assess BLTA-associated cognitive impairment with a comprehensive cognitive battery in a non-selected multicentric/national community-dwelling sample of stabilized SZ subjects. METHOD: 407 community-dwelling stabilized SZ subjects were consecutively included in the FondaMental Academic Centers of Expertise for Schizophrenia Cohort (FACE-SZ). Patients taking daily benzodiazepine were defined as BLTA+ as all patients examined by the Expert Center were clinically stabilized and under stable dose of treatment for at least 3 months. Each patient has been administered a 1-day long comprehensive cognitive battery (including The National Adult Reading Test, the Wechsler Adult Intelligence Scale, the Trail Making Test, the California Verbal Learning Test, the Doors test, and The Continuous Performance Test-Identical Pairs). RESULTS: In the multivariate analyses, results showed that BLTA was associated with impaired attention/working memory (OR 0.60, 95% confidence interval 0.42-0.86; p = 0.005) independently of socio-demographic variables and illness characteristics. Verbal and performance current IQ-[respectively, OR 0.98, 95% CI (0.96;0.99), p = 0.016 and 0.98, 95% CI(0.97;0.99), p = 0.034] but not premorbid IQ-(p > 0.05) have been associated with BLTA in a multivariate model including the same confounding variables. CONCLUSION: BLTA is associated with impaired attention/working memory in schizophrenia. The BLTA benefit/risk ratio should be regularly reevaluated. Alternative pharmacological and non-pharmacological strategies for comorbid anxiety disorders and sleep disorders should be preferred when possible. It seems reasonable to withdraw BLTA before the start of cognitive remediation therapy, as soon as possible, to improve the effectiveness of this therapy. Limits: the delay between the last benzodiazepine intake and testing, as well as the specific class of benzodiazepines (long half-life vs. short half-life), and the number of benzodiazepine daily intakes have not been recorded in the present study. The precise motive for BLTA prescription and sleep disturbances have not been reported, which is a limit for the interpretation of the present results.
Assuntos
Antipsicóticos/efeitos adversos , Transtorno do Deficit de Atenção com Hiperatividade/induzido quimicamente , Benzodiazepinas/efeitos adversos , Transtornos da Memória/induzido quimicamente , Memória de Curto Prazo/efeitos dos fármacos , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Análise de Componente Principal , Escalas de Graduação Psiquiátrica , Esquizofrenia/tratamento farmacológicoRESUMO
OBJECTIVES: Reducing the duration of untreated psychosis (DUP) may improve the prognosis of schizophrenia. This study investigated the prevalence, and associated risk factors, of long DUP in a large, non-selected sample of community-dwelling schizophrenia patients (SZ). METHOD: 478 community-dwelling stable SZ participants (122 women and 356 men; mean age 32.37±9.86years) were recruited between 2010 and 2016. The mean retrospective DUP was evaluated from both patient and family reports, as well as hospital/psychiatrists records. Long DUP was defined as >2years. RESULTS: The mean DUP was 1.5years. 80 participants (16.7%) had a DUP>2years. In multivariate analyses, after adjustment for sex, education level, history of childhood trauma and history of maternal schizophrenia or bipolar disorder, long DUP was associated with a younger age of illness onset (19.3±6.67years vs. 22.0±6.51years, adjusted odd ratio aOR=0.91, 95%CI [0.86; 0.97], p=0.003) and cannabis use disorder (20.0% vs. 10.3%, aOR=2.41, 95%CI [1.14-5.09], p=0.02). CONCLUSION: A high proportion of SZ patients still have a long DUP. The present results suggest that illness onset before age 19years and cannabis use are associated with long DUP in schizophrenia patients. Early psychosis detection programs should prioritize the targeting of these populations.
Assuntos
Transtornos Psicóticos , Esquizofrenia/epidemiologia , Psicologia do Esquizofrênico , Adulto , Idade de Início , Estudos de Coortes , Diagnóstico Tardio , Escolaridade , Feminino , França/epidemiologia , Humanos , Vida Independente , Masculino , Escalas de Graduação Psiquiátrica , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/epidemiologia , Transtornos Psicóticos/psicologia , Fatores de Risco , Fatores Sexuais , Adulto JovemRESUMO
Low-grade inflammation has repeatedly been associated with schizophrenia (SZ) and in particular with cognitive impairment. Female gender, overweight and tobacco smoking have been suggested as risk factors to increase inflammation while preclinical inconsistent findings have been found regarding the association with psychotropic drugs. The aim of this study was to explore if psychotropic drugs were associated with inflammation in SZ and to determine which psychotropic drug was associated with inflammation in stable SZ subjects while considering clinical confounding factors. Participants were consecutively included in the network of the FondaMental Expert Centers for Schizophrenia and received a thorough clinical assessment, including recording of current treatment. High-sensitivity CRP (hs-CRP) was measured for each participant as a proxy to define peripheral low-grade inflammation. The zero-inflated Poisson regression model estimated the relationship between low-grade inflammation and psychotropic drug. Four hundred and five stabilized, community-dwelling SZ subjects (mean age = 32.6 years, 74% male gender) have been included. In total, 148 participants (36.5%) were found with undetectable blood hs-CRP level. The probability of having an undetectable CRP was associated with a lower body mass index (p < 0.0001) and no cyamemazine add-on antipsychotic therapy (p = 0.001). The other 257 participants (63.5%) were found to have low-grade inflammation (hs-CRP > 0 mg/L). Low-grade inflammation was significantly associated with female gender (p = 0.004), higher body mass index (p < 0.0001), current tobacco smoking (p < 0.0001), clomipramine (p = 0.04), quetiapine (p < 0.0001) and hypnotic (p = 0.0006) consumption while decreased hs-CRP blood levels was associated with aripiprazole (p = 0.004) and valproate/valpromide (p = 0.03) consumption. The present study suggests that some psychotropic drugs (quetiapine, cyamemazine, clomipramine) may be associated with increased peripheral low-grade inflammation in SZ patients while others (aripiprazole, valproate) may be associated with decreased peripheral low-grade inflammation. These results should be replicated in SZ and non-SZ populations and the biological underpinnings should be further explored.
Assuntos
Antidepressivos/uso terapêutico , Antimaníacos/uso terapêutico , Antipsicóticos/uso terapêutico , Proteína C-Reativa , Hipnóticos e Sedativos/uso terapêutico , Inflamação/sangue , Transtornos Psicóticos , Esquizofrenia , Adulto , Estudos de Coortes , Feminino , França/epidemiologia , Humanos , Inflamação/epidemiologia , Masculino , Pessoa de Meia-Idade , Transtornos Psicóticos/sangue , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/epidemiologia , Esquizofrenia/sangue , Esquizofrenia/tratamento farmacológico , Esquizofrenia/epidemiologia , Fatores Sexuais , Adulto JovemRESUMO
OBJECTIVES: Sex differences can yield important clues regarding illness pathophysiology and its treatment. Schizophrenia (SZ) has a lower incidence rate, and a better prognosis, in women versus men. The present study investigated the cognitive profiles of both sexes in a large multi-centre sample of community-dwelling SZ patients. METHOD: 544 community-dwelling stable SZ subjects (141 women and 403 men; mean age 34.5±12.1 and 31.6±8.7years, respectively) were tested with a comprehensive battery of neuropsychological tests. RESULTS: Although community-dwelling SZ men had more risk factors for impaired cognition (including first-generation antipsychotics administration and comorbid addictive disorders), women had lower scores on a wide range of cognitive functions, including current and premorbid intellectual functioning, working memory, semantic memory, non-verbal abstract thinking and aspects of visual exploration. However, women scored higher in tests of processing speed and verbal learning, as well as having a lower verbal learning bias. No sex difference were evident for visuospatial learning abilities, cued verbal recall, sustained attention and tests of executive functions, including cognitive flexibility, verbal abstract thinking, verbal fluency and planning abilities. CONCLUSION: Sex differences are evident in the cognitive profiles of SZ patients. The impact on daily functioning and prognosis, as well as longitudinal trajectory, should be further investigated in the FACE-SZ follow-up study. Sex differences in cognition have implications for precision-medicine determined therapeutic strategies. LIMITS: Given the restricted age range of the sample, future research will have to determine cognitive profiles across gender in late onset SZ.
Assuntos
Esquizofrenia/complicações , Psicologia do Esquizofrênico , Caracteres Sexuais , Adulto , Análise de Variância , Estudos de Coortes , Feminino , Humanos , Vida Independente , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Adulto JovemRESUMO
BACKGROUND: Tobacco use is common in patients with schizophrenia (SZ) but little is known on the role of tobacco in the physiopathology or on the course of the disease. Only few studies embrace an extensive examination of clinical and therapeutic characteristics in stabilized patients. The objective of the present study was to determine the prevalence of tobacco smoking in stabilized SZ outpatients and the clinical and treatment characteristics associated with daily tobacco use in a large community-dwelling sample of patients. METHODS: Three-hundred-and-sixty-one patients were included in the network of the FondaMental Expert Centers for Schizophrenia. Current tobacco status was self-declared. RESULTS: 53.7% were smokers. Mean age at tobacco onset was 17.2years old. In multivariate analyses, after adjustment for confounding factors, positive symptoms and mean daily antipsychotic dose were associated with a higher frequency of tobacco use (OR=1.06 95%IC[1.02-1.12], for positive symptoms, OR=1.1, 95%IC[1.02-1.18] for daily antipsychotic dose). Education level, negative symptoms, anticholinergic agents, clozapine or aripiprazole administration were independently associated with a lower frequency of tobacco use (respectively OR=0.87, 95%IC [0.79, 0.95], OR=0.95, 95%IC[0.91-0.98], OR=0.41, 95%IC[0.22-0.76], OR=0.56, 95%IC=[0.32, 0.99] and OR=0.49, 95%IC [0.26-0.91]). CONCLUSION: The prevalence of current tobacco smoking in a French community-dwelling SZ patients is higher that observed in the general population. Patients with tobacco use present clinical and therapeutic specificities that may involve interaction between cholinergic-nicotinic and dopaminergic systems. The present study suggests that some therapeutics may improve daily smoking behavior in smokers. These results should be confirmed in longitudinal studies.
Assuntos
Fumar Cigarros/epidemiologia , Esquizofrenia/epidemiologia , Adulto , Antipsicóticos/uso terapêutico , Fumar Cigarros/terapia , Estudos de Coortes , Comorbidade , Estudos Transversais , Escolaridade , Feminino , França/epidemiologia , Humanos , Vida Independente , Masculino , Análise Multivariada , Prevalência , Escalas de Graduação Psiquiátrica , Esquizofrenia/terapiaRESUMO
Metabolic syndrome (MetS) is highly prevalent in schizophrenia. However very little is known about the time course of MetS and its components. The few longitudinal studies that have been carried out had small sample sizes and a short follow-up. The aim of our study was to evaluate the prevalence of MetS and its components, at baseline and one year later, and to investigate predictors of weight gain (WG) in a cohort of individuals with schizophrenia. We followed 167 schizophrenia patients from the FACE-SZ cohort for one year. The Structured Clinical Interview for DSM-IV (SCID) was used to confirm the diagnosis of schizophrenia. Data on socio-demographic and clinical characteristics, antipsychotic treatment, and comorbidities were collected, and a blood sample was drawn. We found that the prevalence of MetS increased from 21.0% to 26.6% after one year. Patients with baseline depressive symptoms had a 4.5-fold higher risk of WG at the one-year follow-up (p = 0.02) than those without depressive symptoms, after adjusting for confounding variables. WG also correlated with high levels of metabolic parameters and peripheral inflammation. These findings highlight the need to systematically diagnose depression in Schizophrenia. Future studies should determine whether specific pharmacological and non-pharmacological interventions for depression in SZ subjects are effective in preventing rapid high weight gain.
Assuntos
Depressão/fisiopatologia , Síndrome Metabólica/diagnóstico , Esquizofrenia/fisiopatologia , Aumento de Peso/fisiologia , Adulto , Comorbidade , Depressão/epidemiologia , Feminino , França/epidemiologia , Humanos , Estudos Longitudinais , Masculino , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Prevalência , Prognóstico , Fatores de Risco , Esquizofrenia/epidemiologia , Adulto JovemRESUMO
Chronic peripheral inflammation (CPI) has been associated with cognitive impairment in schizophrenia (SZ). However, its sources remain unclear, more specifically it is not known whether tobacco smoking is a source of inflammation or not in SZ subjects. Moreover, nicotine (NIC), the major psychoactive compound of tobacco, shows strong anti-inflammatory properties in vitro, as well as inducing a severe biological dependence when administered repeatedly. The objective of the present study was to determine if CPI was associated with tobacco smoking and/or NIC dependence in schizophrenia. Three hundred and forty five stabilized community-dwelling SZ subjects aged 16 years or older (mean age = 32 years, 73% male) were consecutively included in the network of the FondaMental Expert Centers for Schizophrenia and assessed with validated scales. CPI was defined by a highly sensitive C-reactive protein (hsCRP) ≥3 mg/L. Current tobacco status was self-declared. Severe NIC dependence was defined by a Fagerstrom Test for Nicotine Dependence score ≥7. Overall, 159 (46.1%) were non-smokers, 117 (33.9%) and 69 (20%) were current tobacco smokers with, respectively, low and severe nicotine dependence. In a multivariate model, CPI remained associated with severe NIC dependence (29 vs 15%, OR = 2.8, p = 0.003) and body mass index (OR = 1.1, p < 0.0001), independently of socio-demographic characteristics and antidepressant intake. No association of CPI with low to moderate tobacco smoking dependence, number of daily smoked cigarettes, cannabis use, alcohol use or illness characteristics was found (all p > 0.05). CPI was associated with severe NIC dependence but not with tobacco smoking with low to moderate NIC dependence in SZ, independently of socio-demographic variables, body mass index, alcohol consumption and antidepressant intake. This result highlights the potential CPI consequences of the high prevalence of heavy tobacco smoking in SZ, indicating the importance of new therapeutic strategies for tobacco cessation in SZ.
Assuntos
Proteína C-Reativa/metabolismo , Inflamação/epidemiologia , Inflamação/metabolismo , Esquizofrenia/epidemiologia , Psicologia do Esquizofrênico , Tabagismo/epidemiologia , Adolescente , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Vida Independente , Inflamação/diagnóstico , Masculino , Pessoa de Meia-Idade , Tabagismo/etiologia , Adulto JovemRESUMO
OBJECTIVES: Depression and negative symptoms have been associated with impaired Quality of life (QoL) in schizophrenia (SZ). However, childhood trauma may influence both QoL and depression in SZ patients, with consequences for the management of impaired QoL in SZ patients. The aim of the present study was to determine if childhood trauma was associated with impaired QoL in schizophrenia. METHOD: A sample of 544 community-dwelling stabilized SZ patients enrolled in FACE-SZ cohort were utilized in this study (74.1% males, mean aged 32.3years, mean illness duration 10.6years). QoL was self-reported with the S-QoL18 questionnaire. Childhood trauma was self-reported with the Childhood Trauma Questionnaire. Depression was measured by the Calgary Depression Rating Scale for Schizophrenia. Psychotic severity was measured by the Positive and Negative Syndrome Scale for Schizophrenia (PANSS). Other clinical factors, treatments, comorbidities, functioning and sociodemographical variables were also recorded, with validated scales. RESULTS: Overall, 151 participants (27.8%) had a current major depressive episode and 406 (82.5%) reported at least one episode of historical childhood trauma. In multivariate analyses, lower QoL total score was associated with a history of childhood trauma (ß=-0.21, p<0.0001), psychotic negative symptoms (ß=-0.11, p=0.04), current depression (ß=-0.0.38, p<0.0001) and male gender (ß=-0.16, p<0.0001). CONCLUSION: Impaired QoL is independently associated with negative symptoms, depression and childhood trauma in schizophrenia.
Assuntos
Maus-Tratos Infantis/psicologia , Depressão/etiologia , Depressão/psicologia , Qualidade de Vida , Esquizofrenia/complicações , Psicologia do Esquizofrênico , Adulto , Criança , Estudos de Coortes , Feminino , Humanos , Masculino , Análise Multivariada , Escalas de Graduação Psiquiátrica , Inquéritos e QuestionáriosRESUMO
Children born by cesarean section ("c-birth") are known to have different microbiota and a natural history of different disorders including allergy, asthma and overweight compared to vaginally born ("v-birth") children. C-birth is not known to increase the risk of schizophrenia (SZ), but to be associated with an earlier age at onset. To further explore possible links between c-birth and SZ, we compared clinical and biological characteristics of c-born SZ patients compared to v-born ones. Four hundred and fifty-four stable community-dwelling SZ patients (mean age = 32.4 years, 75.8 % male gender) were systematically included in the multicentre network of FondaMental Expert Center for schizophrenia. Overall, 49 patients (10.8 %) were c-born. These subjects had a mean age at schizophrenia onset of 21.9 ± 6.7 years, a mean duration of illness of 10.5 ± 8.7 years and a mean PANSS total score of 70.9 ± 18.7. None of these variables was significantly associated with c-birth. Multivariate analysis showed that c-birth remained associated with lower CRP levels (aOR = 0.07; 95 % CI 0.009-0.555, p = 0.012) and lower premorbid ability (aOR = 0.945; 95 % CI 0.898-0.994, p = 0.03). No significant association between birth by C-section and, respectively, age, age at illness onset, sex, education level, psychotic and mood symptomatology, antipsychotic treatment, tobacco consumption, birth weight and mothers suffering from schizophrenia or bipolar disorder has been found. Altogether, the present results suggest that c-birth is associated with lower premorbid intellectual functioning and lower blood CRP levels in schizophrenia. Further studies should determine the mechanisms underlying this association.
Assuntos
Proteína C-Reativa , Cesárea , Inteligência/fisiologia , Esquizofrenia/sangue , Esquizofrenia/fisiopatologia , Adulto , Idade de Início , Índice de Massa Corporal , Feminino , Humanos , Masculino , Circunferência da Cintura , Adulto JovemRESUMO
BACKGROUND: Childhood trauma (CT) and cannabis use are both environmental and modifier risk factors for schizophrenia. However, little is known about how they interact in schizophrenia. We examined the main effect of each of these two environmental factors on the clinical expression of the disease using a large set of variables, and we tested whether and how cannabis and CT interact to influence the course and the presentation of the illness. METHODS: A sample of 366 patients who met the DSM-IV-TR criteria for schizophrenia was recruited through the FACE-SCZ (Fondamental Advanced Centre of Expertise - Schizophrenia) network. Patients completed a large standardized clinical evaluation including Structured Clinical Interview for DSM Disorders-I (SCID-I), Positive and Negative Symptoms Scale (PANSS), Columbia-Suicide Severity Rating Scale (C-SSRS), Global Assessment of Functioning (GAF), Short-Quality of Life-18 (S-QoL-18), and Medication Adherence Rating Scale (MARS). We assessed CT with the Childhood Trauma Questionnaire and cannabis status with SCID-I. RESULTS: CT significantly predicted the number of hospitalizations, GAF, and S-QoL-18 scores, as well as the PANSS total, positive, excitement, and emotional distress scores. Cannabis use disorders significantly predicted age of onset, and MARS. There was no significant interaction between CT and cannabis use disorders. However, we found evidence of a correlation between these two risk factors. CONCLUSIONS: CT and cannabis both have differential deleterious effects on clinical and functional outcomes in patients with schizophrenia. Our results highlight the need to systematically assess the presence of these risk factors and adopt suitable therapeutic interventions.