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1.
Adv Exp Med Biol ; 1161: 101-113, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31562625

RESUMO

The treatment of psychiatric disorders remains a significant challenge in part due to imprecise diagnostic criteria and incomplete understanding of the molecular pathology involved. Current diagnostic and pharmacological treatment guidelines use a uniform approach to address each disorder even though psychiatric clinical presentation and prognosis within a disorder are known to be heterogeneous. Limited therapeutic success highlights the need for a precision medicine approach in psychiatry, termed precision psychiatry. To practice precision psychiatry, it is essential to research and develop multiple omics-based biomarkers that consider environmental factors and careful phenotype determination. Metabolomics, which lies at the endpoint of the "omics cascade," allows for detection of alterations in systems-level metabolites within biological pathways, thereby providing insights into the mechanisms that underlie various physiological conditions and pathologies. The eicosanoids, a family of metabolites derived from oxygenated polyunsaturated fatty acids, play a key role in inflammatory mechanisms and have been implicated in psychiatric disorders such as anorexia nervosa and depression. This review (1) provides background on the current clinical challenges of psychiatric disorders, (2) gives an overview of metabolomics application as a tool to develop improved biomarkers for precision psychiatry, and (3) summarizes current knowledge on metabolomics and lipidomic findings in common psychiatric disorders, with a focus on eicosanoids. Metabolomics is a promising tool for precision psychiatry. This research has great potential for both discovering biomarkers and elucidating molecular mechanisms underlying psychiatric disorders.


Assuntos
Biomarcadores , Transtornos Mentais , Medicina de Precisão , Psiquiatria , Humanos , Transtornos Mentais/sangue , Transtornos Mentais/fisiopatologia , Metabolômica
2.
Psychiatr Danub ; 31(Suppl 3): 221-226, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31488730

RESUMO

BACKGROUND: Both Vitamin D deficiency and magnesium deficiency have an increased prevalence and have been associated with an increased risk of and increased severity of symptoms in both depression and schizophrenia (Boerman 2016, Tarleton & Littenberg 2015). This effect appears more pronounced in younger populations and is often apparent from the time of initial diagnosis and is present with adjustment for confounding factors. Thus, the evidence suggests that Vitamin D and magnesium deficiency reflects not only dietary or somatic aspects of health but also may have a role in the pathophysiology of depression and schizophrenia. SUBJECTS AND METHODS: A single site audit of serum Vitamin D and magnesium levels in patients at an Acute Day Treatment Unit was carried out. Blood tests were performed on admission and analysed in house. Data were collected between April - June 2019 and was analysed subsequently, as described below (n=73). RESULTS: Our data show that our psychiatric day treatment unit cohort (n=73) had a higher proportion of vitamin D deficiency (52%) than the general population (40%), although due to the limited sample size this was not significant (p=0.22, Chi-squared test). The percentage of patients who were magnesium deficient was 78.6% (n=22/28). However, the F60 subgroup of patients with personality disorders showed a high prevalence of vit D deficiency (p=0.07), highlighting a trend towards significance despite the limited size of this subgroup. CONCLUSIONS: We carried out a single-site audit of serum vitamin D and magnesium levels in a psychiatric day unit population in order to assess the extent of vitamin deficiency in such patients. These data indicate that that the proportion of patients with vitamin D deficiency is higher than in the general population. Further larger analysis is needed to establish the statistical significance of these data and whether treatment with vitamin D supplementation improves outcomes.


Assuntos
Magnésio/sangue , Transtornos Mentais/sangue , Vitamina D/sangue , Estudos de Coortes , Humanos , Deficiência de Magnésio/sangue , Deficiência de Vitamina D/sangue
3.
Med Hypotheses ; 130: 109279, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31383340

RESUMO

BACKGROUND: The hypotheses of autoimmune, allergic or infectious etiology of severe mental illness have been reported in the scientific literature repeatedly. The main objective of this work is to study the relationship of inflammatory, autoimmunity or recent infection markers with the fact of suffering Severe Mental Disorders (SMD). METHODS: In the present case-control study, adult patients with a diagnosis of SMD were compared with controls who underwent routine health checks that included analytical control. Cases with psychosis substance-induced and controls with diagnosis of any psychiatric illness were excluded. In both groups, patients with chronic inflammatory diseases or intercurrent infectious disease were also excluded. A set of common analytical parameters, markers of infectious diseases and inflammatory markers were retrieved for both groups, as well as demographic and clinical data. RESULTS: A total of 212 subjects (81 cases and 131 controls) were recruited. From cases, 70 (86.4%) have a diagnosis of Schizophrenia Disease (SD) and 11 (13.6%) of Schizoaffective Disorder (SAD). In the multivariate model the female sex (OR 0.24, 95% CI 0.12-0.46) and the neutrophil-lymphocyte ratio (OR 3.00, 95% CI 1.91-4.70) were associated with the fact of being case. CONCLUSIONS: Patients with SMD seem to have higher inflammatory markers compared to the general population, being the neutrophil-lymphocyte ratio, the marker associated with more strength. The role of inflammatory processes in the etiology of this type of disorders, if confirmed, opens interesting and innovative therapeutic possibilities.


Assuntos
Inflamação/metabolismo , Linfócitos/citologia , Transtornos Mentais/sangue , Neutrófilos/citologia , Transtornos Psicóticos/sangue , Esquizofrenia/sangue , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Transtornos Mentais/imunologia , Pessoa de Meia-Idade , Análise Multivariada , Transtornos Psicóticos/imunologia , Esquizofrenia/imunologia
4.
PLoS One ; 14(7): e0219454, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31291336

RESUMO

The association of latent toxoplasmosis with mental disorders in general and with schizophrenia in particular was noticed in the mid-1950s. In subsequent years, the role of Toxoplasma gondii was established based on its ability to survive for long periods of time in the nerve cells of the brain. The acute manifestations of the infection include psychopathic symptoms resembling those of schizophrenia. In the former USSR, and in other parts of the world, a number of studies were performed with respect to the association of latent toxoplasmosis and schizophrenia. However, with the dissolution of the USSR at the beginning of the 1990s, studies on the subject were halted due to financial problems and have resumed only recently. The reasons for the resumption of such studies in contemporary Russia are related to the progressively increasing incidence of schizophrenia over the last 25-30 years in the country. According to official data, approximately 550 000 persons reported suffering from the disease in 2014. There are reasons to believe that this is only a fraction of the real burden of the disease. Economically, it cost the state no less than approximately US $10 billion. The purpose of the study was to identify the level of toxoplasmosis seroprevalence in patients with verified diagnoses of schizophrenia in comparison to healthy people in Moscow City and in the Moscow region. A total of 155 persons constituted the patients group and 152 healthy people were in the control group. An integrated approach to the diagnosis and comparison of data from the entire spectrum of serological markers of infection was used, including the detection of specific IgM and the determination of IgG concentrations. It was found that among persons with neuropsychiatric disorders, the incidence of cases with latent toxoplasmosis was higher than in the control group. The effect of toxoplasmosis was significant and similar for men and women. Further statistical analyses revealed that among patients with a diagnosis of schizophrenia, the incidence of latent toxoplasmosis was significantly higher than in the control group. These data are in agreement with the results of similar studies in other countries.


Assuntos
Transtornos Mentais/epidemiologia , Esquizofrenia/epidemiologia , Toxoplasmose/epidemiologia , Adolescente , Adulto , Encéfalo/imunologia , Encéfalo/patologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Transtornos Mentais/sangue , Transtornos Mentais/complicações , Transtornos Mentais/imunologia , Pessoa de Meia-Idade , Moscou/epidemiologia , Neurônios/imunologia , Neurônios/patologia , Federação Russa/epidemiologia , Esquizofrenia/sangue , Esquizofrenia/complicações , Esquizofrenia/imunologia , Estudos Soroepidemiológicos , Toxoplasma/imunologia , Toxoplasma/patogenicidade , Toxoplasmose/sangue , Toxoplasmose/complicações , Toxoplasmose/imunologia , Adulto Jovem
5.
Pharmacopsychiatry ; 52(5): 237-244, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31158907

RESUMO

INTRODUCTION: To investigate the metabolism of mirtazapine (MIR) in Japanese psychiatric patients, we determined the plasma levels of MIR, N-desmethylmirtazapine (DMIR), 8-hydroxy-mirtazapine (8-OH-MIR), mirtazapine glucuronide (MIR-G), and 8-hydroxy-mirtazapine glucuronide (8-OH-MIR-G). METHODS: Seventy-nine Japanese psychiatric patients were treated with MIR for 1-8 weeks to achieve a steady-state concentration. Plasma levels of MIR, DMIR, and 8-OH-MIR were determined using high-performance liquid chromatography. Plasma concentrations of MIR-G and 8-OH-MIR-G were determined by total MIR and total 8-OH-MIR (i. e., concentrations after hydrolysis) minus unconjugated MIR and unconjugated 8-OH-MIR, respectively. Polymerase chain reaction was used to determine CYP2D6 genotypes. RESULTS: Plasma levels of 8-OH-MIR were lower than those of MIR and DMIR (median 1.42 nmol/L vs. 92.71 nmol/L and 44.96 nmol/L, respectively). The plasma levels (median) of MIR-G and 8-OH-MIR-G were 75.00 nmol/L and 111.60 nmol/L, giving MIR-G/MIR and 8-OH-MIR-G/8-OH-MIR ratios of 0.92 and 59.50, respectively. Multiple regression analysis revealed that smoking was correlated with the plasma MIR concentration (dose- and body weight-corrected, p=0.040) and that age (years) was significantly correlated with the plasma DMIR concentration (dose- and body weight-corrected, p=0.018). The steady-state plasma concentrations of MIR and its metabolites were unaffected by the number of CYP2D6*5 and CYP2D6*10 alleles. DISCUSSION: The plasma concentration of 8-OH-MIR was as low as 1.42 nmol/L, whereas 8-OH-MIR-G had an approximate 59.50 times higher concentration than 8-OH-MIR, suggesting a significant role for hydroxylation of MIR and its glucuronidation in the Japanese population.


Assuntos
Grupo com Ancestrais do Continente Asiático , Glucuronídeos/sangue , Hidroxilação , Mianserina/análogos & derivados , Mirtazapina/farmacocinética , Fatores Etários , Alelos , Ansiolíticos/sangue , Ansiolíticos/farmacocinética , Citocromo P-450 CYP2D6/genética , Genótipo , Humanos , Japão , Transtornos Mentais/sangue , Mianserina/sangue , Mirtazapina/análogos & derivados , Mirtazapina/sangue , Fumar/sangue
6.
Psychiatry Res ; 273: 22-29, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30639560

RESUMO

There is a scarcity of studies assessing the influence of biomarkers in metabolic syndrome in psychiatric patients. Our aim was to correlate serum or plasma levels of 25-hydroxyvitamin D (25-OH-VD), retinol, vitamin B12 (VB12), folate and homocysteine (Hcy), with the metabolic status, in a sample of 289 outpatients with Schizophrenia or Bipolar Disorder. Logistic regression and multiple linear regressions were performed to assess the ability of biomarkers to predict the presence of MetS, the number of risk factors for MetS, and insulin resistance indexes (HOMA and QUICKI). Regarding the association between biomarkers and the QUICKI index, the model explained 6.8% of the variance, with folate and 25-OH-VD levels contributing significantly to the model. The model predicting the number of MetS risk factors was significant and explained 21.7% of the variance, being 25-OH-VD and retinol the statistically significant factors. As for the impact of biomarkers on MetS, the model was statistically significant, being 25-OH-VD and retinol levels the significant factors.  We report for the first time an association between MetS and both low 25-OH-VD and high retinol concentrations. Inflammation-related biomarkers may help identify patients with a high risk of MetS who might benefit from healthy lifestyle counselling and early intervention.


Assuntos
Carbono/metabolismo , Transtornos Mentais/sangue , Síndrome Metabólica/sangue , Vitamina A/sangue , Vitamina D/análogos & derivados , Adulto , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Resistência à Insulina/fisiologia , Masculino , Transtornos Mentais/diagnóstico , Transtornos Mentais/psicologia , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/psicologia , Pessoa de Meia-Idade , Fatores de Risco , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/diagnóstico , Deficiência de Vitamina D/psicologia
7.
Diabetes Metab Syndr ; 13(1): 510-516, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30641756

RESUMO

BACKGROUND: Exponential growth of metabolic syndrome in psychiatric disorders is becoming alarming situation to handle with. It is associated with reduced life span of 10-30 years in psychiatric patients attributed to metabolic syndrome, thus needs to be screened and addressed in all psychiatric patients. OBJECTIVE: the objective of this study was to know the prevalence and its risk factors in various psychiatric disorder and comparing them in older vs younger patients. METHODOLOGY: A cross sectional indoor based study was conducted after taking ethical committee approval in 140 patients (substance use disorder, schizophrenia, bipolar and depressive disorders). All the metabolic parameters as per International diabetes federation criteria for metabolic syndrome were assessed involving waist circumference, weight, height, Systolic/diastolic blood pressure, fasting blood sugar, high density lipoprotein and triglycerides. STATISTICS: Chi square and t-test were used. RESULTS: It was seen that prevalence of metabolic syndrome (MS); 21.4% in psychiatric illness, up to 40% in major depressive disorders, followed by 33% in substance use disorder and 26.7% in psychotic disorders. Prevalence of MS was higher in older patients >30 years group (26% Vs. 16.4% in <30 years group). It was observed that substance use and depressive disorder and high BP in older male patients are all the significant risk factors for metabolic syndrome. CONCLUSION: More than 1/5th psychiatric patients are affected by metabolic syndrome. Thus, all male psychiatric patients with high BP must be evaluated for metabolic syndrome.


Assuntos
Transtornos Mentais/diagnóstico , Transtornos Mentais/epidemiologia , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/epidemiologia , Adulto , Fatores Etários , Glicemia/metabolismo , Estudos Transversais , Feminino , Humanos , Índia/epidemiologia , Masculino , Transtornos Mentais/sangue , Síndrome Metabólica/sangue , Valor Preditivo dos Testes , Prevalência
8.
Am J Emerg Med ; 37(6): 1114-1117, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30194020

RESUMO

BACKGROUND: Previous studies of thyroid stimulating hormone (TSH) levels in Emergency Department (ED) patients largely have centered on patients with atrial fibrillation (AF). In our ED patients with AF as well as patients with Psychiatric diagnoses (psych) are screened. The purpose of the present study was to compare TSH levels in the 2 groups. Our hypotheses were that an abnormal TSH and/or AF predicted the need for hospital admission and that TSH is more likely decreased in AF and increased in psych patients. METHODS: Our goal in the study was to compare the use of TSH testing in two ED populations, AF vs. psych patients. The study was a cross sectional cohort of AF vs. psych patients who had TSH levels drawn in the ED over a two year period. Our laboratory ranges were used to determine high vs. low TSH. Two chart examiners collected data after a training process. Charts were reviewed extracting demographic data, TSH levels, outcome (admit vs. discharge), history of AF, thyroid disease, psych diagnoses, presence of CHF, diabetes, hypertension. We compared AF vs. Psych groups using chi square and t-tests for parametric data. Odds ratios were calculated for comparisons between the 2 groups. For non-parametric data Mann Whitney U was used. A logistic regression was performed with the outcome of admission vs. discharge to find predictors of hospital admission. Kappa was calculated for inter-rater agreement. An a priori power analysis showed 80% power with 2 groups of 100 with an absolute difference of 20% between the 2 groups. RESULTS: 252 patients were included, 101 with AF and 152 Psych. Demographics differed in age only with AF patients being older. Mean TSH for AF vs. 2.4 for AF, 2.9 for psych (NS) with no differences in percentages with high or low TSH in the 2 groups. Fifty-three patients had abnormal TSH levels (21%), 27% of AF and 17% of Psych patients (NS). There were significant differences in incidence of CHF, DM, HTN, and tachycardia with more in the AF group (P < 0.001). Significantly more of the psych patients had a history of hypothyroidism (OR 2.28). Our logistic regression showed that taking into account demographics including age, the only predictors of admission were the presence of CHF (aOR 18.6) and having a diagnosis of AF (aOR 4.0). CONCLUSION: There were no differences in TSH levels between the 2 groups. Twenty-one percent had an abnormal level. CHF and AF predicted hospital admission on regression analysis. Many with these AF or Psych diagnoses had abnormal ED TSH levels that could be useful in diagnosis, maintenance, or continuous treatment for their conditions diagnoses.


Assuntos
Fibrilação Atrial/sangue , Transtornos Mentais/sangue , Tireotropina/análise , Adulto , Idoso , Fibrilação Atrial/epidemiologia , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Programas de Rastreamento/métodos , Programas de Rastreamento/estatística & dados numéricos , Transtornos Mentais/epidemiologia , Pessoa de Meia-Idade , Tireotropina/sangue
9.
Basic Clin Pharmacol Toxicol ; 124(3): 285-297, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30220109

RESUMO

Therapeutic drug monitoring (TDM) is used to determine the concentration of drug in plasma/serum to adjust the dose of the therapeutic drug. Selective and sensitive analytical methods are used to determine drug and metabolite levels for the successful application of TDM. The aim of the study was to develop and validate using LC-MS/MS to analyse quantitative assay of escitalopram (S-CT) and metabolites in human plasma samples. In order to provide a convenient and safe treatment dose, it was aimed to determine the levels of S-CT and its metabolites in the patients' plasma. A new method with short sample preparation and analysis time was developed and validated using LC-MS/MS to analyse quantitative assay of S-CT and its metabolites in plasma. Also, plasma samples of 30 patients using 20 mg S-CT between the ages of 18 and 65 years were analysed by the validated method. The mean values of S-CT, demethyl escitalopram and didemethyl escitalopram in plasma of patients were 27.59, 85.52 and 44.30 ng/mL, respectively. At the end of the analysis, the metabolic ratio of S-CT and metabolites was calculated. It is considered that the method for the quantitative analysis of S-CT and its metabolites in human plasma samples may contribute to the literature on account of its sensitive and easy application. Additionally, the use of our data by physicians will contribute to the effective drug treatment for their patients who take S-CT.


Assuntos
Citalopram/sangue , Transtornos Mentais/sangue , Adolescente , Adulto , Idoso , Cromatografia Líquida/métodos , Citalopram/administração & dosagem , Citalopram/farmacocinética , Monitoramento de Medicamentos/métodos , Humanos , Transtornos Mentais/tratamento farmacológico , Pessoa de Meia-Idade , Inibidores de Captação de Serotonina/administração & dosagem , Inibidores de Captação de Serotonina/sangue , Inibidores de Captação de Serotonina/metabolismo , Inibidores de Captação de Serotonina/farmacocinética , Espectrometria de Massas em Tandem/métodos , Adulto Jovem
10.
Osteoporos Int ; 30(2): 469-480, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30215116

RESUMO

Hypophosphatasia (HPP) typically manifests with fractures, tooth loss, and muscle pain. Although mental health diagnoses and neurological symptoms have not been previously well documented in HPP, they occur commonly. The recognition of non-traditional symptoms may improve patient satisfaction, preempt costly evaluation and misdiagnosis, and lead to further treatment options. INTRODUCTION: Hypophosphatasia (HPP) is an inborn error of metabolism due to deficiency of tissue non-specific alkaline phosphatase (TNSALP). It is traditionally characterized by rickets in children and osteomalacia in adults, along with fractures, tooth loss, and muscle pain. Neurological symptoms and mental health diagnoses have not been widely reported, and we therefore report their prevalence in a cohort of patients with HPP. METHODS: A retrospective chart review was performed on a series of 82 HPP patients. Patient charts were reviewed to identify the possible presence and onset of 13 common neurological symptoms. RESULTS: Median age was 36 years (2 to 79). Seventeen had adult onset HPP (> 18 years) and 65 had pediatric onset HPP (< 18 years). Median time from symptom onset to HPP diagnosis was 8 years (0 to 67). Seventy-four percent had a family history of bone disease, while 17% had a family history of neurologic disease. Bone problems occurred in 89%, dental problems in 77%, and muscle problems in 66%. Fatigue occurred in 66%, headache in 61%, sleep disturbance in 51%, gait change in 44%, vertigo in 43%, depression in 39%, anxiety in 35%, neuropathy in 35%, and hearing loss in 33%. CONCLUSIONS: The extra-skeletal manifestations of HPP, specifically neurological symptoms, have not been previously well documented. However, mental health diagnoses and neurological symptoms such as headache and sleep disturbance occur commonly in patients with HPP. The recognition of non-traditional symptoms in HPP may improve patient satisfaction, preempt costly evaluation and misdiagnosis, and may lead to further treatment options.


Assuntos
Hipofosfatasia/complicações , Transtornos Mentais/etiologia , Doenças do Sistema Nervoso/etiologia , Adolescente , Adulto , Idoso , Fosfatase Alcalina/sangue , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Hipofosfatasia/sangue , Hipofosfatasia/epidemiologia , Hipofosfatasia/psicologia , Masculino , Transtornos Mentais/sangue , Transtornos Mentais/epidemiologia , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/sangue , Doenças do Sistema Nervoso/epidemiologia , Prevalência , Estudos Retrospectivos , Estados Unidos/epidemiologia , Vitamina B 6/sangue , Adulto Jovem
11.
J Trace Elem Med Biol ; 51: 123-129, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30466921

RESUMO

OBJECTIVES: Mental, personality and substance use disorders are over represented among prisoners and aggressive individuals. The psychopathological and biological markers linked to mental functioning remain still unclear. In particular, the role of trace elements in mental illness is still matter of debate. Here, we investigated whether trace elements are correlated to specific psychopathological phenotype groups. METHODS: Axis I and II disorders, aggression, impulsivity, adult attention deficit/hyperactivity disorders (ADHD) indices and serum levels of zinc, copper and cadmium were evaluated in 160 male prisoners. RESULTS: Using latent class analysis we could subdivide prisoners into three distinct psychopathological classes: Class 1 characterized by low prevalence of aggression, personality disorders and substance abuse/dependence (alcohol, cannabis, cocaine); Class 2 represented by low prevalence of aggression and high prevalence of personality disorders and substance abuse/dependence; Class 3 defined by high prevalence of aggression, personality disorders and substance abuse/dependence. Serum levels of zinc were higher in Class 2 and 3 compared to Class 1. Moreover, Class 3 was associated with higher scores of impulsivity and ADHD indices. CONCLUSION: Our results suggest that impulsivity but also adult ADHD indices are related to aggressive behaviour, and higher zinc levels are linked to personality disorders and addictions, but not to aggression.


Assuntos
Agressão , Transtorno do Deficit de Atenção com Hiperatividade/sangue , Comportamento Impulsivo , Transtornos Mentais/sangue , Transtornos da Personalidade/sangue , Prisioneiros/psicologia , Oligoelementos/sangue , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Humanos , Masculino , Transtornos Mentais/epidemiologia , Transtornos da Personalidade/epidemiologia
12.
Behav Pharmacol ; 30(1): 89-94, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29847340

RESUMO

The development of Parkinson's disease (PD) involves the degeneration of dopaminergic neurons caused by oxidative stress. Accumulating clinical evidence indicates that high blood levels of uric acid (UA), an intrinsic antioxidative substance, are associated with reduced risk of PD. However, this hypothesis has not been confirmed by in-vivo experiments. The present study investigated the effects of UA on behavioral abnormalities in the development of PD. We used unilateral 6-hydroxydopamine-lesioned mice, which were fed on a diet containing 1% UA and 2.5% potassium oxonate (an uricase inhibitor) to induce hyperuricemia. A significant elevation in UA levels was found in groups that were fed a UA diet. The 6-hydroxydopamine-lesioned mice showed impaired rotarod performance and increased apomorphine-induced contralateral rotations. These behavioral abnormalities were significantly reversed by feeding a UA diet for 1 week before and 5 weeks after surgery (subchronic hyperuricemia). These behavioral improvements occurred in parallel with recovery of tyrosine hydroxylase protein levels in the lesioned striatal side. The present study with a dietary hyperuricemia mice model confirms that UA exerts a neuroprotective effect on dopaminergic neuronal loss, improving motor dysfunction and ameliorating PD development.


Assuntos
Transtornos Mentais/sangue , Transtornos Mentais/etiologia , Doença de Parkinson Secundária/complicações , Ácido Úrico/sangue , Adrenérgicos/toxicidade , Animais , Apomorfina/farmacologia , Modelos Animais de Doenças , Hiperuricemia/sangue , Hiperuricemia/etiologia , Masculino , Transtornos Mentais/dietoterapia , Camundongos , Camundongos Endogâmicos ICR , Atividade Motora/efeitos dos fármacos , Oxidopamina/toxicidade , Ácido Oxônico/administração & dosagem , Doença de Parkinson Secundária/induzido quimicamente , Teste de Desempenho do Rota-Rod , Tirosina 3-Mono-Oxigenase/metabolismo
13.
Psychiatry Clin Neurosci ; 73(4): 175-178, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30552718

RESUMO

AIMS: Non-adherence or partial adherence to psychotropic medication is found in 18-70% of patients. Many previously used methods for the assessment of adherence (e.g. questionnaires, pill counts, and electronic systems), however, might underreport actual rates of non-adherence to medication. The aim of this study was to quantify adherence using plasma level. METHODS: We conducted a 6-week prospective study of all consecutive admitted patients at the Paracelsus Medical University of Salzburg, Clinics of Psychiatry and Psychotherapy, who had been treated with antipsychotics/antidepressants prior to admission (pre-medication dosage in 161 of 233). Plasma drug levels were determined and compared with expected levels based on known preadmission dosing regimens and average pharmacokinetic data. RESULTS: Seventy-three percent of the patients had actual plasma levels clearly below or above the intended level. Significantly more patients with schizophrenia (66%) did not take the medication as prescribed, when compared with patients with affective disorders (47%) or those with other psychiatric diagnoses (41%). Only 27% (44 of 161) of the patients had plasma level in the expected range based on the dosage. CONCLUSION: The risk of partial adherence or non-adherence is expected in two-thirds of patients with schizophrenia, half of patients with affective disorders, and approximately 40% of patients with other psychiatric diagnoses. Given that admitting psychiatrists could not provide an accurate assessment of patient adherence, it is strongly suggested that clinical judgment be supplemented with the actual monitoring of adherence - and further optimization of pharmacotherapy - by means of therapeutic drug monitoring.


Assuntos
Antidepressivos/administração & dosagem , Antipsicóticos/administração & dosagem , Hospitais Psiquiátricos , Adesão à Medicação , Transtornos Mentais/tratamento farmacológico , Transtornos do Humor/tratamento farmacológico , Admissão do Paciente , Esquizofrenia/tratamento farmacológico , Adulto , Antidepressivos/sangue , Antipsicóticos/sangue , Feminino , Hospitais Psiquiátricos/estatística & dados numéricos , Humanos , Masculino , Adesão à Medicação/estatística & dados numéricos , Transtornos Mentais/sangue , Pessoa de Meia-Idade , Transtornos do Humor/sangue , Admissão do Paciente/estatística & dados numéricos , Prevalência , Estudos Prospectivos , Esquizofrenia/sangue
16.
BMC Neurosci ; 19(1): 68, 2018 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-30390633

RESUMO

BACKGROUND: The clinical significance of anti-neuronal antibodies in patients with psychiatric disorders, but without encephalitis, remains unknown. In patients admitted to acute psychiatric inpatient care we aimed to identify clinical features distinguishing anti-neuronal antibody positive patients from matched controls. RESULTS: Patients who were serum-positive to N-methyl D-aspartate receptor (NMDAR) (n = 21), contactin-associated protein 2 (CASPR2) (n = 14) and/or glutamic acid decarboxylase 65 (GAD65) (n = 9) antibodies (cases) were age and sex matched (1:2) with serum-negative patients from the same cohort (controls). The prevalence and severity of psychiatric symptoms frequently encountered in NMDAR, CASPR2 and GAD65 antibody associated disorders were compared in cases and controls. NMDAR, CASPR2 and GAD65 antibody positive patients did not differ in their clinical presentation from matched serum negative controls. CONCLUSION: In this cohort, patients with and without NMDAR, CASPR2 and GAD65 antibodies admitted to acute psychiatric inpatient care had similar psychiatric phenotypes. This does not exclude their clinical relevance in subgroups of patients, and studies further investigating the clinical significance of anti-neuronal antibodies in patients with psychiatric symptomatology are needed.


Assuntos
Autoanticorpos/sangue , Glutamato Descarboxilase/imunologia , Proteínas de Membrana/imunologia , Transtornos Mentais/imunologia , Proteínas do Tecido Nervoso/imunologia , Receptores de N-Metil-D-Aspartato/imunologia , Doença Aguda , Adulto , Estudos de Casos e Controles , Feminino , Hospitalização , Humanos , Masculino , Transtornos Mentais/sangue , Transtornos Mentais/epidemiologia , Transtornos Mentais/terapia , Pessoa de Meia-Idade , Prevalência , Escalas de Graduação Psiquiátrica , Estudos Retrospectivos , Índice de Gravidade de Doença
17.
Psychiatry Res ; 270: 611-615, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30384279

RESUMO

Peripheral biomarkers for suicide have been studied generating mixed results. We investigated the association between serum lipid levels and suicide attempts in subjects with different mental disorders. We conducted a cross-sectional study, including 593 inpatients with schizophrenia spectrum, bipolar, major depressive, and personality disorders, hypothesizing that subjects with lower total cholesterol levels would have higher rates of recent suicide attempts. Contrary to our hypothesis, individuals with lower total cholesterol levels (<160 mg/dL) showed lower rates also of suicide attempts (OR adjusted for age and gender: 0.56; one-tailed p = 0.03). Further logistic regression models failed to estimate any association of continuous levels between total/low-density lipoprotein (LDL) cholesterol/ triglycerides, and suicide attempts, also considering diagnosis and suicide methods. An association between lipid profile and suicide attempts in subjects with mental disorders is not fully supported. Further research is needed to clarify the role of biomarkers in suicidal behaviors.


Assuntos
Lipídeos/sangue , Transtornos Mentais/sangue , Transtornos Mentais/psicologia , Tentativa de Suicídio/psicologia , Adulto , Transtorno Bipolar/sangue , Transtorno Bipolar/psicologia , Colesterol/sangue , LDL-Colesterol/sangue , Correlação de Dados , Estudos Transversais , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/psicologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Transtornos da Personalidade/sangue , Transtornos da Personalidade/psicologia , Valores de Referência , Fatores de Risco , Esquizofrenia/sangue , Psicologia do Esquizofrênico , Ideação Suicida , Triglicerídeos/sangue
18.
J Clin Psychopharmacol ; 38(6): 622-626, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30300290

RESUMO

BACKGROUND: Second-generation antipsychotics (SGAs) are commonly used to treat children with mental health conditions (MHCs) but are associated with adverse effects including obesity, hypertension, dyslipidemia, and type 2 diabetes. The mechanisms underlying these complications are unknown, but it has been suggested that SGAs increase appetite leading to weight gain. The present objective was to perform a pilot study to investigate appetite and satiety hormones in SGA-treated (risperidone or quetiapine) and SGA-naive children with similar mental health conditions. METHODS: Oral glucose tolerance tests (OGTTs) were conducted in SGA-naive (n = 18), risperidone-treated (n = 20), and quetiapine-treated (n = 16) children recruited from the British Columbia Children's Hospital Psychiatry Department. Over 5 time-points during the OGTT, appetite questionnaires using a visual analogue scale were administered, and blood was collected to measure ghrelin, peptide YY, glucose-dependent insulinotropic polypeptide, glucagon-like protein 1, leptin, and adiponectin. Mixed model analyses were conducted to examine between-group differences. RESULTS: The children were similar in age, psychiatric diagnosis, and global assessment of functioning scores. Body mass index z-scores were also similar between groups. Appetite was increased during the OGTT in the risperidone-treated compared with the SGA-naive group for 2 questions ("How strong is your desire to eat"; P = 0.003 and "How much food do you think you can eat"; P = 0.028). No differences in satiety hormones were observed between the 3 groups. CONCLUSIONS: Risperidone treatment in youth is associated with elevated appetite during an OGTT, with no differences in gut peptides or adipocytokines to explain risperidone's effect on appetite. Further research is needed to explore other mediators of weight gain and metabolic dysfunction in SGA-treated youth.


Assuntos
Antipsicóticos/efeitos adversos , Apetite/efeitos dos fármacos , Transtornos Mentais/tratamento farmacológico , Hormônios Peptídicos/efeitos dos fármacos , Fumarato de Quetiapina/efeitos adversos , Risperidona/efeitos adversos , Saciação/efeitos dos fármacos , Adolescente , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Transtornos Mentais/sangue , Hormônios Peptídicos/sangue , Projetos Piloto
19.
Diabetes Care ; 41(11): 2289-2296, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30270201

RESUMO

OBJECTIVE: Type 1 diabetes is associated with an increased risk of psychiatric morbidities. We investigated predictors and diabetes outcomes in a pediatric population with and without psychiatric comorbidities. RESEARCH DESIGN AND METHODS: Data from the Danish Registry of Childhood and Adolescent Diabetes (DanDiabKids) and National Patient Register were collected (1996-2015) for this population-based study. We used Kaplan-Meier plots to investigate whether age at type 1 diabetes onset and average glycated hemoglobin (HbA1c) levels during the first 2 years after onset of type 1 diabetes (excluding HbA1c at debut) were associated with the risk of being diagnosed with a psychiatric disorder. Mixed-effects linear and logistic regression models were used to analyze HbA1c, BMI, severe hypoglycemia (SH), or ketoacidosis as outcomes, with psychiatric comorbidities as explanatory factor. RESULTS: Among 4,725 children and adolescents with type 1 diabetes identified in both registers, 1,035 were diagnosed with at least one psychiatric disorder. High average HbA1c levels during the first 2 years predicted higher risk of psychiatric diagnoses. Patients with psychiatric comorbidity had higher HbA1c levels (0.22% [95% CI 0.15; 0.29]; 2.40 mmol/mol [1.62; 3.18]; P < 0.001) and an increased risk of hospitalization with diabetic ketoacidosis (1.80 [1.18; 2.76]; P = 0.006). We found no associations with BMI or SH. CONCLUSIONS: High average HbA1c levels during the first 2 years after onset of type 1 diabetes might indicate later psychiatric comorbidities. Psychiatric comorbidity in children and adolescents with type 1 diabetes increases the risk of poor metabolic outcomes. Early focus on the disease burden might improve outcomes.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 1/complicações , Transtornos Mentais/complicações , Adolescente , Adulto , Criança , Comorbidade , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/terapia , Cetoacidose Diabética/sangue , Cetoacidose Diabética/complicações , Cetoacidose Diabética/epidemiologia , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Hipoglicemia/sangue , Hipoglicemia/epidemiologia , Hipoglicemia/etiologia , Masculino , Transtornos Mentais/sangue , Transtornos Mentais/epidemiologia , Sistema de Registros , Estudos Retrospectivos , Adulto Jovem
20.
Neuropsychopharmacology ; 43(13): 2556-2563, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30082891

RESUMO

Suicide is major public health concern; one million individuals worldwide die by suicide each year of which there are many more attempts. Thus, it is imperative that robust and reliable indicators, or biomarkers, of suicide risk be identified so that individuals at risk can be identified and provided appropriate interventions as quickly as possible. Previous work has revealed a relationship between low levels of circulating cholesterol and suicide risk, implicating cholesterol level as one such potential biomarker, but the factors underlying this relationship remain unknown. In the present study, we applied a combination of bivariate polygenic and coefficient-of-relatedness analysis, followed by mediation analysis, in a large sample of Mexican-American individuals from extended pedigrees [N = 1897; 96 pedigrees (average size = 19.17 individuals, range = 2-189) 60% female; mean age = 42.58 years, range = 18-97 years, sd = 15.75 years] with no exclusion criteria for any given psychiatric disorder. We observed that total esterified cholesterol measured at the time of psychiatric assessment shared a significant genetic overlap with risk for suicide attempt (ρg = -0.64, p = 1.24 × 10-04). We also found that total unesterified cholesterol measured around 20 years prior to assessment varied as a function of genetic proximity to an affected individual (h2 = 0.21, se = 0.10, p = 8.73 × 10-04; ßsuicide = -0.70, se = 0.25, p = 8.90 × 10-03). Finally, we found that the relationship between total unesterified cholesterol and suicide risk was significantly mediated by ABCA-1-specific cholesterol efflux capacity (ßsuicide-efflux = -0.45, p = 0.039; ßefflux-cholexterol = -0.34, p < 0.0001; ßindirect = -0.15, p = 0.044). These findings suggest that the relatively well-delineated process of cholesterol metabolism and associated molecular pathways will be informative for understanding the neurobiological underpinnings of risk for suicide attempt.


Assuntos
Colesterol/sangue , Colesterol/genética , Predisposição Genética para Doença/genética , Predisposição Genética para Doença/psicologia , Ideação Suicida , Tentativa de Suicídio/psicologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Suscetibilidade a Doenças/sangue , Suscetibilidade a Doenças/psicologia , Feminino , Humanos , Masculino , Transtornos Mentais/sangue , Transtornos Mentais/diagnóstico , Transtornos Mentais/psicologia , Pessoa de Meia-Idade , Linhagem , Fatores de Risco , Adulto Jovem
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