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1.
Neurosci Lett ; 746: 135650, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33485991

RESUMO

OBJECTIVE: Serum creatinine (SCR) has been shown to be associated with many neurodegenerative diseases. In this study, we investigated the relationship between SCR levels and the incidence of psychiatric symptoms in patients with anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis. METHODS: The SCR levels were tested in 69 patients with anti-NMDAR encephalitis at admission. Clinical characteristics and blood and CSF parameters were compared between the group of patients with psychiatric symptoms (P + group) and the group of those without psychiatric symptoms (P- group). The association between SCR and the incidence of psychiatric symptoms was determined by multivariate-adjusted linear regression analyses. RESULTS: The SCR levels in the P + group were significantly lower than those in the P- group (P < 0.001). In the female subgroup, the SCR levels in the P + group were significantly lower compared to the P- group (P < 0.001), whereas in the male subgroup, the SCR levels did not differ between the two groups (P = 0.084). Furthermore, the highest SCR tercile overall had a significantly lower incidence of psychiatric symptoms than the lowest tercile (P < 0.001), and a significant negative correlation between the SCR levels and the occurrence of psychiatric symptoms was observed (r = -0.392, P < 0.001). Multivariate logistic regression analysis showed that the association was independent after adjusting for age, cystatin C and the modified Rankin Scale (mRS) score (P = 0.001). A similar result was found in the female subgroup (P = 0.010), but not in the male subgroup (P = 0.225). CONCLUSION: Our study indicated that the SCR level was negatively correlated with incidence of psychiatric symptoms in female patients, and higher SCR level could be a protective factor for psychiatric symptoms in female patients with anti-NMDAR encephalitis.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato/sangue , Encefalite Antirreceptor de N-Metil-D-Aspartato/psicologia , Creatinina/sangue , Transtornos Mentais/sangue , Transtornos Mentais/psicologia , Caracteres Sexuais , Adolescente , Adulto , Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Transtornos Mentais/diagnóstico , Pessoa de Meia-Idade , Adulto Jovem
3.
PLoS One ; 15(9): e0238201, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32877431

RESUMO

BACKGROUND: Therapeutic drug monitoring (TDM) is recommended during valproic acid (VPA) use, and total serum concentration has been widely adopted. However, the free form of VPA is responsible for its pharmacologic and toxic effects, and the total and free concentrations are highly discordant because of VPA's highly protein bound and saturable binding characteristics. Therefore, free VPA monitoring is increasingly advocated. Nevertheless, the correlation between free VPA concentration and associated adverse effects remains unknown. OBJECTIVE: To determine the optimal safety range of free VPA concentration in adult patients. MATERIALS AND METHODS: This prospective cohort study enrolled adult patients undergoing VPA therapy with TDM. Patient characteristics, VPA use, and adverse effects (thrombocytopenia, hyperammonemia, and hepatotoxicity) were recorded. A multivariate logistic regression model was applied to identify the predictors of adverse effects, and the receiver operating characteristic curve was applied to locate the cutoff point of free VPA concentration. RESULTS: A total of 98 free serum concentrations from 51 patients were included for final analysis. In total, 31 (31.6%), 27 (27.6%), and 4 (4.1%) episodes of hyperammonemia, thrombocytopenia, and hepatotoxicity were observed, respectively. Free VPA concentration was a predicting factor for thrombocytopenia but not for hyperammonemia. A free VPA concentration of >14.67 mcg/mL had the greatest discriminating power (area under the curve = 0.77) for the occurrence of thrombocytopenia. CONCLUSIONS: A free VPA serum concentration of 14.67 mcg/mL had the optimal discriminating power for the occurrence of thrombocytopenia. Ammonemia should be monitored even if free VPA concentration is within the safety range.


Assuntos
Monitoramento de Medicamentos/métodos , Epilepsia/tratamento farmacológico , Transtornos Mentais/tratamento farmacológico , Ácido Valproico/administração & dosagem , Ácido Valproico/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/sangue , Formas de Dosagem , Relação Dose-Resposta a Droga , Epilepsia/sangue , Feminino , Humanos , Masculino , Transtornos Mentais/sangue , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC
4.
Ann Pharmacother ; 54(9): 858-865, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32100551

RESUMO

Background: Previous studies show patients with type 2 diabetes (T2D) and a mental health (MH) disorder exhibit poorer glycemic control compared with those without. Objective: Compare mean change in glycosylated hemoglobin (A1C) after 6 months in the Diabetes Intense Medical Management (DIMM) "Tune Up" Clinic in patients with and without MH disorders. Methods: Retrospective cohort study in T2D patients, with A1C at baseline and 6 months, divided into subgroups of those with ≥1 MH diagnoses and without MH. Primary outcome was mean change in A1C from baseline to 6 months. Secondary outcomes were mean change in other metabolic parameters and proportion achieving A1C and related goals. Results: Of 155 patients meeting inclusion criteria, 66 (42.6%) had at least 1 MH disorder (MH group) and 89 (57.4%) did not (non-MH group). Mean A1C, fasting blood glucose (FBG), and triglycerides (TG) change (improvement) did not differ significantly between MH and non-MH groups at 6 months (eg, A1C reduction: -2.1% [SD = 2.0] vs -2.3% [SD = 2.1]; P = 0.61, respectively). Percentage at A1C goal did not differ significantly between groups, though a higher percentage of the non-MH group achieved FBG and TG goals than the MH group. Conclusion and Relevance: In 6 months, both groups in the DIMM clinic achieved a statistically significant mean A1C reduction (over 2%) with no statistical or clinical difference in the magnitude of change between groups. Patients with T2D benefitted from the DIMM model and personalized visits with a pharmacist regardless of having a MH disorder.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Gerenciamento Clínico , Endocrinologistas/organização & administração , Hemoglobina A Glicada/análise , Transtornos Mentais/sangue , Farmacêuticos/organização & administração , Adulto , Idoso , Instituições de Assistência Ambulatorial/organização & administração , Instituições de Assistência Ambulatorial/tendências , Glicemia/análise , California , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Endocrinologistas/tendências , Feminino , Humanos , Hiperglicemia/prevenção & controle , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Masculino , Transtornos Mentais/complicações , Transtornos Mentais/tratamento farmacológico , Pessoa de Meia-Idade , Modelos Organizacionais , Farmacêuticos/tendências , Estudos Retrospectivos , Veteranos
5.
Psychiatry Res ; 284: 112778, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32004894

RESUMO

Adverse childhood experiences (ACEs) lead to devastating long-term health consequences that are associated with a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. Children and adolescents living in institutional care have an increased risk to experience ACEs, particularly linked to missing continuity of care, and a higher risk for consequences of ACEs such as mental disorders. In order to improve the overall quality of care, it is important to better understand the stress-physiology of this high-risk sample and to identify specific stressors linked to adverse outcomes. Therefore, we assessed ACEs due to missing continuity of care and their association with hair cortisol and DHEA levels in children, adolescents and young adults in institutional care. Results show that ACEs resulting from the family of origin, in detail maternal mental illness, and ACEs due to out-of-home placement, namely frequent change of caregivers, are associated with HPA axis over-activation. HPA axis activation is associated with enhanced mental health problems. These results point towards an association between continuity of care and the stress system of children and adolescents in this high-risk sample. Care concepts that focus on continuity of care might help to reduce these physiological alterations and devastating long-term consequences following ACEs.


Assuntos
Experiências Adversas da Infância/tendências , Relações Familiares/psicologia , Sistema Hipotálamo-Hipofisário/metabolismo , Transtornos Mentais/psicologia , Sistema Hipófise-Suprarrenal/metabolismo , Tratamento Domiciliar/tendências , Adolescente , Adulto , Criança , Feminino , Humanos , Hidrocortisona/sangue , Masculino , Transtornos Mentais/sangue , Transtornos Mentais/diagnóstico , Saúde Mental/tendências , Projetos Piloto , Fatores de Risco , Adulto Jovem
6.
Eur J Pharmacol ; 872: 172978, 2020 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-32014487

RESUMO

Evidences from human and animal studies indicate that exposure to infection during early life act as a stressor to impair the hypothalamic-pituitary-adrenal (HPA) axis and may be one of the contributing factors of mental illness of later life. Several atypical antipsychotic drugs (AAPDs) proved to be effective in alleviating psychiatric illness through normalization of HPA axis. However, AAPD are least tried to evaluate their efficacy in modulation of HPA axis impaired under infection. The present study elucidated that the treatment with AAPD paliperidone (PAL: 0.025 mg/kg/bw and 0.05 mg/kg/bw) during periadolescence period (postnatal day 35- postnatal day 56) dose-dependently normalized the HPA axis of the female mice who were gestationally (gestational day 15 and 17) exposed to bacterial endotoxin lipopolysaccharide (LPS: 800 µg/kg/bw; intraperitoneally). The effectiveness of PAL treatment in counteracting the LPS induced hyperactivity of HPA axis was age-related, better observed at postnatal day 120 than at postnatal day 200. The PAL modulation of HPA axis reflected at different levels: inhibition of hypothalamic CRF expression and reduction in plasma levels of adrenocorticotropin and corticosterone. Histopathological alterations such as hypertrophy and/or hyperplasia in cortical zona fasciculata as well as medullary chromaffin cells of adrenal also normalized on PAL treatment. The comparatively long wash out period after drug treatment (postnatal day 57- postnatal day 200) along with age related hormonal imbalance could be correlated to less effectiveness of PAL on HPA axis at postnatal day 200. PAL modulation of HPA axis might be through maintenance of cytokines and reproductive axis homeostasis.


Assuntos
Antipsicóticos/administração & dosagem , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Transtornos Mentais/tratamento farmacológico , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Complicações Infecciosas na Gravidez/imunologia , Efeitos Tardios da Exposição Pré-Natal/tratamento farmacológico , Adolescente , Hormônio Adrenocorticotrópico/sangue , Hormônio Adrenocorticotrópico/metabolismo , Adulto , Fatores Etários , Animais , Células Cromafins/efeitos dos fármacos , Células Cromafins/metabolismo , Corticosterona/sangue , Corticosterona/metabolismo , Hormônio Liberador da Corticotropina/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Lipopolissacarídeos/imunologia , Masculino , Transtornos Mentais/sangue , Transtornos Mentais/imunologia , Transtornos Mentais/fisiopatologia , Camundongos , Palmitato de Paliperidona/administração & dosagem , Sistema Hipófise-Suprarrenal/fisiopatologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/imunologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Adulto Jovem , Zona Fasciculada/efeitos dos fármacos , Zona Fasciculada/metabolismo , Zona Fasciculada/patologia
7.
Soc Psychiatry Psychiatr Epidemiol ; 55(6): 723-733, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31897578

RESUMO

BACKGROUND: Early life adversity (ELA) is a significant risk factor for mental health disorders. One hypothesised mechanism by which this occurs is via an effect on immune response. In this analysis of epidemiological data, we tested whether ELA was associated with cognitive performance, and if so, whether these effects were influenced by immune function. METHODS: We investigated the longitudinal relationship between ELA, inflammatory markers, and cognition in data from Avon Longitudinal Study of Parents And Children (ALSPAC; n ~ 5000). ELA was defined in terms of physical/emotional abuse, harsh parenting, or domestic violence before 5 years. Social cognition was measured in terms of theory of mind, and general cognitive ability was measured using IQ. Inflammatory markers included serum C-reactive protein and interleukin-6 levels. RESULTS: A significant association was observed between IQ and harsh parenting, whereby children who were physically disciplined had lower IQ scores (accounting for relevant social factors). Both immune markers were associated with variation in cognition, however, neither accounted for the effects of ELA on cognition. DISCUSSION: This study highlights the impact of ELA on cognition. In the absence of evidence that these effects are explained by inflammation, other mechanisms by which the effects of ELA are mediated are discussed.


Assuntos
Experiências Adversas da Infância , Proteína C-Reativa/análise , Cognição , Interleucina-6/sangue , Transtornos Mentais/sangue , Adolescente , Adulto , Biomarcadores/sangue , Criança , Pré-Escolar , Feminino , Humanos , Inflamação , Estudos Longitudinais , Masculino , Transtornos Mentais/epidemiologia , Transtornos Mentais/psicologia , Fatores de Risco , Teoria da Mente , Reino Unido/epidemiologia , Adulto Jovem
8.
J Neuroimmunol ; 339: 577119, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31786499

RESUMO

The aim of this study was to investigate inflammatory perturbations in 40 patients with severe and complex psychiatric disorders by studying the activity of the NLRP3 inflammasome, with a trans-diagnostic approach. Gene expression of CASP1, NLRP3, PYCARD, IL1B, IL1RN, TNF showed a significant increase in the patient group compared to a matched control group. Plasma levels of IL1Ra, IL-18, TNF, IL-6 and CRP were increased in the patient group. Within the patient group, increased gene expression of inflammatory markers correlated with increased disease severity. The findings support the inflammation hypothesis for markedly ill psychiatric patients across diagnostic groups.


Assuntos
Inflamassomos/sangue , Transtornos Mentais/sangue , Transtornos Mentais/diagnóstico , Índice de Gravidade de Doença , Adolescente , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Caspase 1/sangue , Criança , Feminino , Humanos , Proteína Antagonista do Receptor de Interleucina 1/sangue , Masculino , Transtornos Mentais/psicologia , Pessoa de Meia-Idade , Proteína 3 que Contém Domínio de Pirina da Família NLR/sangue , Adulto Jovem
9.
J Neuropsychiatry Clin Neurosci ; 32(2): 154-160, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31530118

RESUMO

OBJECTIVE: The authors examined and compared the clinical presentation of CSF positive and negative N-methyl-d-aspartate receptor (NMDAR) antibody. METHODS: The investigators performed a retrospective chart review of NMDAR-antibody-positive cases (serum or CSF) involving patients presenting to psychiatric services from 2010 to 2018 in Queensland, Australia. Presentation, progress, investigations, and efficacy of treatment are detailed. RESULTS: There were 24 serum or CSF NMDAR-antibody-positive cases and three equivocal serum results. High rates of prodromal cognitive deficits, catatonia, speech disturbance, and antipsychotic sensitivity were observed in the 16 CSF NMDAR-antibody-positive case patients and two CSF NMDAR-antibody-negative case patients, all evident before neurological deterioration with seizures, movement disorder, and autonomic disturbance occurring in the weeks following admission. The majority of these patients (N=17) were treated successfully with immunomodulatory therapy. The nine remaining patients, who were CSF NMDAR antibody negative or equivocal, did not demonstrate any of these features and improved with psychiatric care alone. CONCLUSIONS: These findings suggest that traditional psychiatric care may be appropriate for patients with isolated psychiatric symptoms who have positive serum NMDAR testing when CSF is negative and there are no key clinical features such as cognitive deficits, catatonia, speech disturbance, and antipsychotic sensitivity. However, if these key features are present, a trial of immunomodulatory treatment should be considered with repeated examination of CSF for neuronal antibodies.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato , Autoanticorpos/sangue , Autoanticorpos/líquido cefalorraquidiano , Catatonia , Disfunção Cognitiva , Fatores Imunológicos/uso terapêutico , Transtornos Mentais , Receptores de N-Metil-D-Aspartato/imunologia , Distúrbios da Fala , Adulto , Encefalite Antirreceptor de N-Metil-D-Aspartato/sangue , Encefalite Antirreceptor de N-Metil-D-Aspartato/líquido cefalorraquidiano , Encefalite Antirreceptor de N-Metil-D-Aspartato/tratamento farmacológico , Encefalite Antirreceptor de N-Metil-D-Aspartato/imunologia , Catatonia/sangue , Catatonia/líquido cefalorraquidiano , Catatonia/tratamento farmacológico , Catatonia/imunologia , Disfunção Cognitiva/sangue , Disfunção Cognitiva/líquido cefalorraquidiano , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/imunologia , Feminino , Células HEK293 , Humanos , Masculino , Transtornos Mentais/sangue , Transtornos Mentais/líquido cefalorraquidiano , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/imunologia , Pessoa de Meia-Idade , Queensland , Estudos Retrospectivos , Distúrbios da Fala/sangue , Distúrbios da Fala/líquido cefalorraquidiano , Distúrbios da Fala/tratamento farmacológico , Distúrbios da Fala/imunologia , Adulto Jovem
10.
Acta Neuropsychiatr ; 32(1): 23-31, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31576798

RESUMO

OBJECTIVE: Cross-sectional data show elevated levels of circulating cytokines in psychiatric patients. The literature is divided concerning anti-inflammatory drugs' ability to relieve symptoms, questioning a causal link between inflammatory pathways and psychiatric conditions. We hypothesised that the development of circulating cytokine levels is related to mental distress, and that this relationship is affected by the use of anti-inflammatory drugs. METHODS: The study was a longitudinal assessment of 12-week inpatient treatment at Modum Bad Psychiatric Center, Norway. Sera and self-reported Global Severity Index (GSI) scores, which measure psychological distress, were collected at admission (T0), halfway (T1) and before discharge (T2). Other variables known to distort the neuroimmune interplay were included. These were age, gender, diagnosis of PTSD, antidepressants and anti-inflammatory drugs. A total of 128 patients (92 women and 36 men) were included, and 28 were using anti-inflammatory medication. Multilevel modelling was used for data analysis. RESULTS: Patients with higher levels of IL-1RA and MCP-1 had higher GSI scores (p = 0.005 and p = 0.020). PTSD patients scored higher on GSI than non-PTSD patients (p = 0.002). These relationships were mostly present among those not using anti-inflammatory drugs (n = 99), with higher levels of IL-1RA and MCP-1 being related to higher GSI score (p = 0.023 and 0.018, respectively). Again, PTSD patients showed higher GSI levels than non-PTSD patients (p = 0.014). CONCLUSIONS: Cytokine levels were associated with level of mental distress as measured by the GSI scores, but this relationship was not present among those using anti-inflammatory drugs. We found no association between cytokine levels and development of GSI score over time.


Assuntos
Citocinas/sangue , Transtornos Mentais/sangue , Angústia Psicológica , Adulto , Fatores Etários , Anti-Inflamatórios/uso terapêutico , Antidepressivos/uso terapêutico , Feminino , Humanos , Pacientes Internados/psicologia , Estudos Longitudinais , Masculino , Transtornos Mentais/tratamento farmacológico , Pessoa de Meia-Idade , Fatores Sexuais
11.
Sci Rep ; 9(1): 16842, 2019 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-31727978

RESUMO

The lack of effective treatments and a high rate of relapse in cocaine addiction constitute a major health problem. The present study was conducted to examine the expression of tryptophan-derived metabolites in the context of cocaine addiction and psychiatric comorbidity, which is common in addicted subjects. Abstinent patients with cocaine use disorder (CUD) and control subjects were recruited for a cross-sectional study. Participants were assessed with a semi-structured diagnostic interview (PRISM) based on DSM-IV-TR for substance and mental disorders. Plasma concentrations of tryptophan metabolites and their association with relevant CUD-related variables and psychiatric comorbidity were explored. We observed decreased plasma kynurenic acid concentrations in the cocaine group, however no associations between CUD-related variables and tryptophan-derived metabolites were found. In contrast, 5-HT concentrations were increased in CUD-patients and the diagnosis of different psychiatric disorders in the cocaine group was related to higher plasma 5-HT concentrations compared with non-comorbid patients. Therefore, while changes in plasma kynurenic acid concentrations appear to be directly associated with lifetime CUD, changes in 5-HT concentrations are associated with psychiatric comorbidity. These results emphasize the need to find potential biomarkers for a better stratification of cocaine-addicted patients in order to develop therapeutic approaches to prevent cocaine relapse.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/psicologia , Transtornos Mentais/metabolismo , Serotonina/sangue , Triptofano/química , Adulto , Estudos de Casos e Controles , Transtornos Relacionados ao Uso de Cocaína/metabolismo , Comorbidade , Estudos Transversais , Feminino , Humanos , Ácido Cinurênico/sangue , Masculino , Transtornos Mentais/sangue , Triptofano/sangue
12.
J Nerv Ment Dis ; 207(12): 1025-1030, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31688493

RESUMO

In this study, we aimed to explore the potential pathophysiological relationship between suicide attempts and Toxoplasma gondii infection. Fifty patients aged between 12 and 18 years who attempted suicide and 50 healthy adolescents were included in this study. All adolescents were evaluated by a child psychiatrist using a semistructured interview and Rosenberg Self-Esteem Scale (RSES), Children's Depression Inventory (CDI), and Inventory of Parent and Peer Attachment. T. gondii IgM and IgG antibodies of patients and control subjects were analyzed from blood samples by enzyme-linked immunosorbent assay. Psychiatric disorders particularly mood disorders were more common in adolescents in the patient group. Adolescents attempting suicide were found to have worse relationships with their parents; their CDI scores were higher, and their RSES scores were lower than their healthy peers. There were no significant differences between the patient and the control groups in terms of Toxoplasma IgG antibody positivity. Although the seropositivity of Toxoplasma IgG antibody was higher in the patient group than that in the control group, the difference between the two groups was not statistically significant.


Assuntos
Transtornos Mentais/sangue , Transtornos Mentais/psicologia , Tentativa de Suicídio/psicologia , Toxoplasma/metabolismo , Toxoplasmose/sangue , Toxoplasmose/psicologia , Adolescente , Criança , Feminino , Humanos , Masculino , Transtornos Mentais/diagnóstico , Estudos Soroepidemiológicos , Toxoplasmose/diagnóstico
13.
Drug Deliv ; 26(1): 1243-1253, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31752566

RESUMO

The aim of this work is to develop self-nano emulsifying drug delivery system (SNEDDS) to enhance the oral bioavailability of zaleplon (Zal) as a poorly water-soluble drug. Moreover, the bioavailability and the effect on the quality of sleep among a sample of psychiatric patients is to be assessed. D-optimal mixture design was used for optimization. Optimized SNEDDS formulation was evaluated for droplet size, transmission electron microscope (TEM) and in-vitro dissolution test. Zal bioavailability was evaluated by determining its serum concentration and pharmacokinetic parameters in 8 patients after oral administration. Effect on sleep quality was assessed among 40 psychiatric patients. Patients' sleep quality was assessed in 40 psychiatric patients before and after medication using the Arabic version of the Pittsburgh Sleep Quality Index (PSQI). Zal- SNEDDS appeared as nano-sized spherical vesicles. Moreover, Zal was completely dissolved from optimized formulation after 45 min indicating improved dissolution rate. Zal-SNEDDS showed significantly higher Cmax, Tmax and AUC0→∞ compared to commercial product after oral administration. Zal-SNEDDS significantly improved the total score of PSQIs (p < .001) with higher subjective sleep quality, reduced sleep latency, improved day time function and sleep disturbance (p < .001). Using sleep medication was reduced significantly (p = .027). However, it did not modify sleep duration or sleep efficiency. SNEDDS have improved Zal solubility and enhanced its bioavailability. Furthermore, Zal-SNEDDS have improved the total score of PSQIs and may be considered a good choice to enhance the quality of sleep among psychiatric patients.


Assuntos
Acetamidas/administração & dosagem , Portadores de Fármacos/química , Hipnóticos e Sedativos/administração & dosagem , Transtornos Mentais/tratamento farmacológico , Nanopartículas/química , Pirimidinas/administração & dosagem , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Acetamidas/farmacocinética , Acetamidas/uso terapêutico , Administração Oral , Adulto , Disponibilidade Biológica , Estudos Transversais , Emulsões , Feminino , Humanos , Hipnóticos e Sedativos/farmacocinética , Hipnóticos e Sedativos/uso terapêutico , Masculino , Transtornos Mentais/sangue , Transtornos Mentais/psicologia , Pessoa de Meia-Idade , Pirimidinas/farmacocinética , Pirimidinas/uso terapêutico , Distúrbios do Início e da Manutenção do Sono/sangue , Distúrbios do Início e da Manutenção do Sono/psicologia , Solubilidade , Adulto Jovem
14.
Artigo em Inglês | MEDLINE | ID: mdl-31617966

RESUMO

Objective: To assess the pattern of serum folate and vitamin B12 levels in psychiatric inpatients compared with nonpsychiatric controls. Methods: An observational cross-sectional study was conducted with 100 psychiatric inpatients diagnosed with psychiatric illness for the first time per ICD-10 criteria and their age-matched caregivers at a super-specialty center in northern India (from January 1, 2012, to December 31, 2012). Complete blood counts and serum levels of vitamin B12, folate, and homocysteine were measured in all patients and caregivers, who were sharing the same kitchen as that of the patients. Results: Twenty-five percent of the patients were found to have low levels of serum vitamin B12, which was significant compared with healthy controls (P < .001). Similarly, the difference in homocysteine levels between the patient and control groups was significant (35% vs 13%, P = .012). Conclusions: A significant proportion of psychiatric patients were found to be vitamin B12 deficient. In-depth studies are required to establish the cause-effect relationship between vitamin B12 deficiency and psychiatric illness and the effect of vitamin B12 replacement.


Assuntos
Ácido Fólico/sangue , Transtornos Mentais/sangue , Deficiência de Vitamina B 12/sangue , Vitamina B 12/sangue , Adulto , Comorbidade , Estudos Transversais , Feminino , Homocisteína/sangue , Humanos , Índia , Pacientes Internados/estatística & dados numéricos , Masculino , Transtornos Mentais/epidemiologia , Pessoa de Meia-Idade , Deficiência de Vitamina B 12/epidemiologia
15.
Epilepsy Behav ; 100(Pt A): 106439, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31574428

RESUMO

OBJECTIVE: The study investigated overall adverse event (AE) burden and specifically psychiatric and behavioral side effects (PBAEs) in persons with epilepsy (PWE) on antiepileptic drugs (AEDs) monotherapy. It also assessed their correlation with neuroendocrine and oxidative stress biomarkers. METHODS: This cross-sectional observational study was conducted at a tertiary care hospital between 2016 and 2018. Persons with epilepsy above 18 years on monotherapy of levetiracetam (LEV) and conventional AEDs {carbamazepine (CBZ), phenytoin (PHT), or valproate (VPA)} for at least 6 months were enrolled. Validated questionnaires, 'Mini-International Neuropsychiatric Interview (MINI 7.02)', 'Depression, Anxiety, and Stress Scale 21 (DASS-21)', 'Buss-Perry Aggression Questionnaire (BPAQ)', 'patient-weighted Quality of life Index in Epilepsy (QOLIE-10)', 'Pittsburgh Sleep Quality Index (PSQI)', and 'Liverpool Adverse Events Profile (LAEP)' were used to assess the PBAEs, quality of life, sleep quality, and AE profile. A subgroup of PWE recruited consecutively were considered for estimation of the following neuroendocrine biomarker levels: brain-derived neurotrophic factor (BDNF), homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and total antioxidant capacity (TAC) which were then correlated with scores of above questionnaires. RESULTS: After screening 220 PWE, 163 PWE (58 on LEV and 105 on conventional AEDs) with a mean age of 29 ±â€¯10 years were enrolled. Mini-International Neuropsychiatric Interview revealed that LEV group had higher association with PBAEs and lower quality of sleep compared to conventional AEDs (p = 0.032 and 0.046, respectively). Other scales did not show significant difference between LEV and conventional AEDs. In the subset of PWE (n = 74, 36 on LEV and 38 on conventional AEDs), LEV group had more association with the PBAEs (p = 0.010), higher physical aggression and anger components of BPAQ (p = 0.03 and 0.02, respectively), and more AE (p = 0.049) than conventional AED group. However, there was no significant difference in neuroendocrine biomarker levels. CONCLUSION: Levetiracetam had a higher association with PBAEs and more AE when compared to conventional AEDs. There was no differential correlation of AEDs with the following neuroendocrine markers: BDNF, HVA, 5-HIAA, and TAC. These facts necessitate exploration of other mechanisms for LEV-induced PBAEs.


Assuntos
Anticonvulsivantes/efeitos adversos , Epilepsia/tratamento farmacológico , Transtornos Mentais/induzido quimicamente , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticonvulsivantes/uso terapêutico , Biomarcadores/sangue , Estudos Transversais , Epilepsia/psicologia , Feminino , Humanos , Masculino , Transtornos Mentais/sangue , Transtornos Mentais/diagnóstico , Transtornos Mentais/epidemiologia , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Qualidade de Vida , Adulto Jovem
16.
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
17.
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
18.
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
19.
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
20.
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
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