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2.
J Affect Disord ; 264: 221-226, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32056754

RESUMO

BACKGROUND: An atypical immune response to Epstein-Barr virus (EBV) infection has been associated with several complex diseases including schizophrenia. The etiology of MDD is unclear; host immune response to EBV infection could play a role. METHODS: We utilized solid phase immunoassays and western blots to measure antibodies to EBV virions, specific viral proteins, and 5 other herpesviruses in 87 individuals with MDD and 312 control individuals. RESULTS: Individuals with MDD had significantly reduced levels of reactivity to EBV Nuclear Antigen-1. Quantitative levels of antibodies to EBV virions and Viral Capsid Antigen did not differ between groups. Individuals with decreased levels of anti-Nuclear Antigen-1, or elevated levels of anti-virion had increased odds of being in the MDD group. The odds of MDD were elevated in individuals who had the combination of high levels of anti-virion and low levels of anti-Nuclear Antigen-1 (OR =13.6). Western blot analysis corroborated decreased reactivity to Nuclear Antigen-1 in the MDD group and revealed altered levels of antibodies to other EBV proteins. There was a trend towards decreased levels of antibodies to varicella virus in the group of individuals with MDD. LIMITATIONS: The MDD sample size was relatively small. There could be unmeasured factors that account for the association between MDD and the immune response to EBV. CONCLUSIONS: Individuals with MDD have altered levels and patterns of antibodies to EBV antigens. This atypical response could contribute to the immunopathology of MDD. Therapeutic interventions available for treatment of EBV infection could potentially be of benefit in MDD.

3.
Psychiatry Res ; 284: 112700, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31791705

RESUMO

Schizophrenia and bipolar disorder are associated with reduced cognitive functioning which contributes to problems in day-to-day functioning and social outcomes. A paucity of research exists relating dietary factors to cognitive functioning in serious mental illnesses, and results are inconsistent. The study aims to describe the nutritional intake of persons with schizophrenia and those with a recent episode of acute mania and to determine relationships between the intake of protein and other nutrients on cognitive functioning in the psychiatric sample. Persons with schizophrenia and those with acute mania were assessed using a 24-h dietary recall tool to determine their intakes of protein and other nutrients. They were also assessed with a test battery measuring different domains of cognitive functioning. Results indicate that lower amounts of dietary protein intake were associated with reduced cognitive functioning independent of demographic and clinical factors. The association was particularly evident in measures of immediate memory and language. There were not associations between cognitive functioning and other nutritional variables, including total energy, gluten, casein, saturated fat, or sugar intakes. The impact of dietary interventions, including protein intake, on improving cognitive functioning in individuals with psychiatric disorders warrants further investigation.

4.
Mol Psychiatry ; 25(3): 560-571, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30022042

RESUMO

Mania is a serious neuropsychiatric condition associated with significant morbidity and mortality. Previous studies have suggested that environmental exposures can contribute to mania pathogenesis. We measured dietary exposures in a cohort of individuals with mania and other psychiatric disorders as well as in control individuals without a psychiatric disorder. We found that a history of eating nitrated dry cured meat but not other meat or fish products was strongly and independently associated with current mania (adjusted odds ratio 3.49, 95% confidence interval (CI) 2.24-5.45, p < 8.97 × 10-8). Lower odds of association were found between eating nitrated dry cured meat and other psychiatric disorders. We further found that the feeding of meat preparations with added nitrate to rats resulted in hyperactivity reminiscent of human mania, alterations in brain pathways that have been implicated in human bipolar disorder, and changes in intestinal microbiota. These findings may lead to new methods for preventing mania and for developing novel therapeutic interventions.

5.
Mol Psychiatry ; 25(1): 194-205, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30127472

RESUMO

Clinical studies frequently report that patients with major mental illness such as schizophrenia and bipolar disorder have co-morbid physical conditions, suggesting that systemic alterations affecting both brain and peripheral tissues might underlie the disorders. Numerous studies have reported elevated levels of anti-Toxoplasma gondii (T. gondii) antibodies in patients with major mental illnesses, but the underlying mechanism was unclear. Using multidisciplinary epidemiological, cell biological, and gene expression profiling approaches, we report here multiple lines of evidence suggesting that a major mental illness-related susceptibility factor, Disrupted in schizophrenia (DISC1), is involved in host immune responses against T. gondii infection. Specifically, our cell biology and gene expression studies have revealed that DISC1 Leu607Phe variation, which changes DISC1 interaction with activating transcription factor 4 (ATF4), modifies gene expression patterns upon T. gondii infection. Our epidemiological data have also shown that DISC1 607 Phe/Phe genotype was associated with higher T. gondii antibody levels in sera. Although further studies are required, our study provides mechanistic insight into one of the few well-replicated serological observations in major mental illness.

6.
PLoS One ; 14(12): e0225320, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31790431

RESUMO

BACKGROUND: Serious psychiatric disorders such as schizophrenia and bipolar disorder have been associated with environmental exposures in early life. Contact with household pets such as cats and dogs can serve as a source of environmental exposure during these time periods. METHODS: We investigated the relationship between exposure to a household pet cat or dog during the first 12 years of life and having a subsequent diagnosis of schizophrenia or bipolar disorder. These studies were performed in a cohort of 396 individuals with schizophrenia, 381 with bipolar disorder, and 594 controls. The hazards of developing schizophrenia or bipolar disorder associated with first exposure to a household pet cat or dog were calculated using Cox Proportional Hazard and multivariate logistic regression models including socio-demographic covariates. RESULTS: We found that exposure to a household pet dog was associated with a significantly decreased hazard of having a subsequent diagnosis of schizophrenia (Hazard Ratio .75, p < .002) Furthermore, a significant decreased relative risk of schizophrenia was detected following exposure at birth and during the first years of life. There was no significant relationship between household exposure to a pet dog and bipolar disorder. There were no significant associations between exposure to a household pet cat and subsequent risk of either a schizophrenia or bipolar disorder diagnosis. However, there were trends towards an increased risk of both disorders at defined periods of exposure. CONCLUSIONS: Exposure to household pets during infancy and childhood may be associated with altered rates of development of psychiatric disorders in later life.

7.
J Psychiatr Res ; 118: 66-72, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31494376

RESUMO

BACKGROUND: Schizophrenia (SZ) is associated with cognitive impairment that contributes to disability, but the cognitive dysfunction is relatively refractory to pharmacologic intervention. Though Valproate augmentation is reported to improve psychopathology among patients with SZ, its effects on cognitive functions have not been investigated systematically. METHODS: Using a randomized double blind placebo controlled design, the effects of Valproate or placebo as adjuncts to risperidone (RISP) treatment were evaluated among patients with early course SZ (N = 109). Domains of cognitive function, estimated using the Arabic version of the Penn Computerized Neurocognitive Battery, were the prime outcomes. Clinical severity and social function were secondary outcomes. We also explored the effects of valproate treatment on serological responses to Toxoplama Gondii (TOXO), a putative risk factor for cognitive dysfunction in SZ. RESULTS: There were no significant differences between Valproate and placebo (PLA) treated groups with respect to changes in cognitive functions, positive or negative symptom scores or daily function scores at the beginning and end of the study. No significant Valproate/PLA differences were noted on TOXO serostatus or TOXO-related cognitive dysfunction. CONCLUSION: Valproate treatment may not be beneficial for cognitive dysfunction in SZ or for TOXO infection.

8.
Psychiatry Res ; 275: 283-286, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30952072

RESUMO

There has been little previous study of the association between dietary factors and suicide. The association between food exposures and suicide attempt history was investigated in a sample of 270 individuals with schizophrenia, bipolar disorder, or major depressive disorder. Individuals who had a suicide attempt history were almost 3 times as likely to report eating cured meat, typically prepared with added nitrates, compared to patients without a suicide attempt history, adjusting for demographic and clinical variables. A suicide attempt history was 6 times greater in those who in addition were cigarette smokers and had a history of substance abuse compared to those who did not have any of these risk factors. If dietary factors were shown to affect suicide risk, an additional method of risk reduction would be available which could be widely disseminated to address this major public health problem.


Assuntos
Dieta/psicologia , Produtos da Carne/análise , Transtornos Mentais/psicologia , Nitratos/análise , Tentativa de Suicídio/psicologia , Adulto , Transtorno Bipolar/psicologia , Transtorno Depressivo Maior/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Psicologia do Esquizofrênico , Transtornos Relacionados ao Uso de Substâncias/psicologia , Ideação Suicida
9.
Obes Res Clin Pract ; 13(2): 205-210, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30852244

RESUMO

BACKGROUND: Persons with serious mental illnesses (SMI) such as schizophrenia and bipolar disorder have an increased risk of obesity and related chronic diseases and die 10-20years earlier than the overall population, primarily due to cardiovascular disease. In the ACHIEVE trial, a behavioural weight loss intervention led to clinically significant weight loss in persons with SMI. As the field turns its attention to intervention scale-up, it is important to understand whether the effectiveness of behavioural weight loss interventions for people with SMI, like ACHIEVE, differ for specific subgroups. METHODS: This study examined whether the effectiveness of the ACHIEVE intervention differed by participant characteristics (e.g. age, sex, race, psychiatric diagnosis, body mass index) and/or their weight-related attitudes and behaviours (e.g. eating, food preparation, and shopping habits). We used likelihood-based mixed effects models to examine whether the baseline to 18 month effects of the ACHIEVE intervention differed across subgroups. RESULTS: No statistically significant differences were found in the effectiveness of the ACHIEVE intervention across any of the subgroups examined. CONCLUSIONS: These findings suggest that the ACHIEVE behavioural weight loss intervention is broadly applicable to the diverse population of individuals with SMI.

10.
Psychol Med ; 49(2): 243-249, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29552990

RESUMO

BACKGROUND: Depression can impair the immunogenicity of vaccine administration in adults. Whereas many vaccinations are administered in childhood, it is not known whether adolescent or adult onset depression is associated with impairments in the maintenance of protection of childhood vaccines. This study tested the hypothesis that individuals with adolescent or adult onset mood disorders would display compromised immunity to measles, a target of childhood vaccination. METHODS: IgG antibodies to measles were quantified using a solid phase immunoassay in volunteers with bipolar disorder (BD, n = 64, mean age of onset = 16.6 ± 5.6), currently depressed individuals with major depressive disorder (cMDD, n = 85, mean age of onset = 17.9 ± 7.0), remitted individuals with a history of MDD (rMDD, n = 82, mean age of onset = 19.2 ± 8.6), and non-depressed comparison controls (HC, n = 202), all born after the introduction of the measles vaccine in the USA in 1963. RESULTS: Relative to HC, both the cMDD group (p = 0.021, adjusted odds ratios (OR) = 0.47, confidence interval (CI) = 0.24-0.90), and the rMDD group (p = 0.038, adjusted OR = 0.50, CI = 0.26-0.97) were less likely to test seropositive for measles. Compared with unmedicated MDD participants, currently medicated MDD participants had a longer lifetime duration of illness and were less likely to test seropositive for measles. CONCLUSIONS: Individuals with adolescent or adult onset MDD are less likely to test seropositive for measles. Because lower IgG titers are associated with increased risk of measles infection, MDD may increase the risk and severity of infection possibly because of impaired maintenance of vaccine-related protection from measles.

11.
Schizophr Bull ; 45(5): 1112-1119, 2019 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-30462333

RESUMO

BACKGROUND: Epstein-Barr virus (EBV) is a highly prevalent human herpesvirus capable of infecting the central nervous system and establishing persistent infection. METHODS: We employed solid phase immunoassay techniques to measure immunoglobulin G (IgG) class antibodies to EBV virions and defined proteins in 432 individuals with schizophrenia and 311 individuals without a history of a psychiatric disorder. Western blot testing was performed to document reactivity to specific EBV proteins. Polygenic risk for schizophrenia was calculated from genome sequencing arrays. Levels of antibodies between the groups were compared by multivariate analyses incorporating clinical, genetic, and demographic measures. RESULTS: Individuals with schizophrenia had marked elevations in the levels of antibodies to EBV virions as compared to the control population. Further analyses indicated increased levels of reactivity to EBV-viral capsid antibody (VCA) but not to EBV nuclear antigen-1 (EBNA-1) or to other human herpesviruses. Western blot analysis confirmed increased reactivity to VCA proteins in the group of individuals with schizophrenia and documented a lack of increased levels of antibodies to EBNA-1. Genetic analyses indicated an additive effect of increased levels of antibodies to EBV virions and genetic susceptibility to schizophrenia, with individuals with elevated levels of both type of markers having a greater than 8.5-fold odds of a schizophrenia diagnosis. CONCLUSIONS: Individuals with schizophrenia have increased levels of antibodies to some but not all EBV proteins indicating an aberrant response to EBV infection. This aberrant response may contribute to the immunopathology of schizophrenia and related disorders.

12.
Schizophr Res ; 206: 291-299, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30478008

RESUMO

BACKGROUND: Several studies have implicated herpes simplex virus-type 1 (HSV-1) in the pathophysiology of schizophrenia. A recent trial demonstrated that the anti-viral medication valacylovir, which prevents replication of activated HSV-1, improved selected cognitive deficits in people with schizophrenia. In this study, we examined demographic and illness related differences between HSV-1 positive versus HSV-1 negative subjects with early phase schizophrenia and attempted to replicate the previous valacyclovir treatment results in this population. METHODS: 170 subjects with schizophrenia (HSV-1 positive N = 70; HSV-1 negative N = 96) from 12 US sites participated in the HSV-1 positive versus negative comparisons, and were randomized 1:1 to valacyclovir (1.5 g BID) or placebo for a 16-week, double-blind efficacy trial. The primary endpoints were working and verbal memory. RESULTS: The HSV-1 positive group, as compared to the HSV-1 negative group, were older (p < 0.001) with fewer males (p = 0.003), and had a longer duration of illness (p = 0.008), more positive symptoms (p = 0.013), poorer quality of life (p = 0.034) and more impairment on the letter-number sequencing test, which is a measure of working memory (p = 0.045). Valacyclovir failed to significantly improve any of the cognitive indices, symptom or functioning measures. CONCLUSIONS: HSV-1 sero-positivity appears to be a marker of a subgroup with a more severe form of schizophrenia. Valacyclovir was not efficacious in the study, perhaps because the herpes virus was in the dormant, non-activated state and therefore non-responsive to valacyclovir effects. ClinicalTrials.gov Identifier: NCT02008773.

13.
Front Psychiatry ; 9: 604, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30515109

RESUMO

People with serious mental illnesses (SMIs) die 10-20 years earlier than the general population, mainly due to cardiovascular disease. Obesity is a key driver of cardiovascular risk in this group. Because behavioral weight loss interventions tailored to the needs of people with SMI have been shown to lead to clinically significant weight loss, achieving widespread implementation of these interventions is a public health priority. In this Perspective, we consider strategies for scaling the ACHIEVE behavioral weight loss intervention for people with SMI, shown to be effective in a randomized clinical trial (RCT), to mental health programs in the U.S. and internationally. Given the barriers to high-fidelity implementation of the complex, multi-component ACHIEVE intervention in often under-resourced mental health programs, we posit that substantial additional work is needed to realize the full public health potential of this intervention for people with SMI. We discuss considerations for successful "scale-up," or efforts to expand ACHIEVE to similar settings and populations as those included in the RCT, and "scale-out," or efforts to expand the intervention to different mental health program settings/sub-populations with SMI. For both, we focus on considerations related (1) intervention adaptation and (2) implementation strategy development, highlighting four key domains of implementation strategies that we believe need to be developed and tested: staff capacity building, leadership engagement, organizational change, and policy strategies. We conclude with discussion of the types of future research needed to support ACHIEVE scale-up/out, including hybrid trial designs testing the effectiveness of intervention adaptations and/or implementations strategies.

14.
J Psychiatr Res ; 106: 38-42, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30261413

RESUMO

BACKGROUND: Increased inflammatory markers have been linked to suicidal behavior in numerous studies. Measures of aggression and of impulsivity also comprise risks factors for suicidal behavior and there is evidence that inflammatory markers correlate with these traits. The following analyses compare suicide attempters and non-attempters to determine whether inflammatory markers mediate relationships between aggression or impulsivity and proclivities to suicidal behavior. METHODS: Investigators at three academic centers recruited patients in major depressive episodes who had a history of two or more suicide attempts (n = 79), or who had no history of suicide attempts (n = 123). Analyses compared these groups by five inflammatory marker levels and by measures of aggression and of impulsivity. RESULTS: These results did not confirm the hypotheses that cytokine levels would explain relationships between aggressive behavior and suicide attempt history. However, scores for aggressive behavior and for impulsivity were significantly higher among suicide attempters. One of five of the inflammatory markers, (IL-1ß), distinguished the two groups with lower values in the suicide attempt group. IL-1ß levels correlated inversely with measures of aggression but neither impulsivity or aggressive behavior appear to explain the association between IL-1ß levels and suicide attempt status. CONCLUSION: These results identify recent aggressive behavior, higher levels of impulsivity, and lower levels of IL-1ß as risk factors for a history of multiple suicide attempts in a group suffering from major depressive episodes. These measures appear to be additive in their effects.


Assuntos
Agressão/fisiologia , Transtorno Bipolar/sangue , Transtorno Bipolar/fisiopatologia , Citocinas/sangue , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/fisiopatologia , Comportamento Impulsivo/fisiologia , Inflamação/sangue , Tentativa de Suicídio , Adulto , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
16.
Schizophr Bull ; 44(5): 983-992, 2018 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-29889280

RESUMO

It is increasingly evident that the brain is not truly an immune privileged site and that cells of the central nervous system are sensitive to the inflammation generated when the brain is fighting off infection. Among the many microorganisms that have access to the brain, the apicomplexan protozoan Toxoplasma gondii has been one of the most studied. This parasite has been associated with many neuropsychiatric disorders including schizophrenia. This article provides a comprehensive review of the status of Toxoplasma research in schizophrenia. Areas of interest include (1) the limitations and improvements of immune-based assays to detect these infections in humans, (2) recent discoveries concerning the schizophrenia-Toxoplasma association, (3) findings of Toxoplasma neuropathology in animal models related to schizophrenia pathogenesis, (4) interactions of Toxoplasma with the host genome, (5) gastrointestinal effects of Toxoplasma infections, and (6) therapeutic intervention of Toxoplasma infections.


Assuntos
Encéfalo , Microbioma Gastrointestinal , Esquizofrenia , Toxoplasma , Toxoplasmose , Animais , Encéfalo/imunologia , Microbioma Gastrointestinal/imunologia , Humanos , Esquizofrenia/epidemiologia , Esquizofrenia/etiologia , Esquizofrenia/imunologia , Toxoplasma/isolamento & purificação , Toxoplasma/patogenicidade , Toxoplasmose/complicações , Toxoplasmose/epidemiologia , Toxoplasmose/imunologia
17.
J Clin Psychopharmacol ; 38(4): 317-326, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29912799

RESUMO

PURPOSE/BACKGROUND: Prolactin-related adverse effects contribute to nonadherence and adverse health consequences, particularly in women with severe mental illness. Treating these adverse effects may improve treatment acceptability, adherence, and long-term outcomes. METHODS/PROCEDURES: Premenopausal women with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder were recruited for a randomized, double-blind, placebo-controlled 16-week trial of adjunct aripiprazole (5-15 mg/d). Participants had elevated prolactin (>24 ng/mL) and were experiencing galactorrhea, amenorrhea, oligomenorrhea, or sexual dysfunction on a prolactin-elevating antipsychotic. Participants were evaluated biweekly for prolactin elevation and galactorrhea and completed a menstrual diary review. Psychiatric symptoms and adverse effects were closely monitored. FINDINGS/RESULTS: Forty-six women were randomized (n = 25 aripiprazole, n = 21 placebo). Thirty-seven completed at least 8 weeks of the study (n = 20 [80%] aripiprazole and n = 17 [81%] placebo). Aripiprazole (mean dose, 11.7 ± 2.4 mg/d) was effective for lowering prolactin relative to placebo (P = 0.04). In addition, 45% (9/20) of the aripiprazole group had a normalized prolactin (<24 mg/mL) compared with 12% (2/17) of the placebo group (P = 0.028). Galactorrhea resolved in 77% (10/13) of the aripiprazole-treated participants compared with 33% (4/12) in the placebo group (P = 0.028). Normalization of sexual function (<16 on the Arizona Sexual Experience Scale) occurred in 50% on aripiprazole (7/14) versus 9% (1/11) on placebo (P = 0.030). No differences between groups in symptoms or adverse effects were noted. Overall, women rated a mean score of 4.6 ± 0.6 on a 5-point Likert scale for sexual function improvement, suggesting their particular satisfaction with improvement in this domain. IMPLICATIONS/CONCLUSIONS: Building upon prior studies, this rigorous evaluation confirms the utility of adjunctive aripiprazole as a strategy for improving prolactin and managing prolactin-related adverse effects in premenopausal women with psychosis.


Assuntos
Antipsicóticos/uso terapêutico , Aripiprazol/uso terapêutico , Quimioterapia Combinada/métodos , Pré-Menopausa/efeitos dos fármacos , Prolactina/sangue , Transtornos Psicóticos/tratamento farmacológico , Adulto , Amenorreia/induzido quimicamente , Amenorreia/prevenção & controle , Antipsicóticos/efeitos adversos , Aripiprazol/administração & dosagem , Método Duplo-Cego , Feminino , Galactorreia/induzido quimicamente , Galactorreia/prevenção & controle , Humanos , Adesão à Medicação , Oligomenorreia/induzido quimicamente , Oligomenorreia/prevenção & controle , Qualidade de Vida
18.
Pharmacol Ther ; 189: 184-198, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29742478

RESUMO

Typical and atypical antipsychotics are the first-line treatments for schizophrenia, but these classes of drugs are not universally effective, and they can have serious side effects that impact compliance. Antipsychotic drugs generally target the dopamine pathways with some variation. As research of schizophrenia pathophysiology has shifted away from a strictly dopamine-centric focus, the development of new pharmacotherapies has waned. A field of inquiry with centuries-old roots is gaining traction in psychiatric research circles and may represent a new frontier for drug discovery in schizophrenia. At the forefront of this investigative effort is the immune system and its many components, pathways and phenotypes, which are now known to actively engage the brain. Studies in schizophrenia reveal an intricate association of environmentally-driven immune activation in concert with a disrupted genetic template. A consistent conduit through this gene-environmental milieu is the gut-brain axis, which when dysregulated can generate pathological autoimmunity. In this review, we present epidemiological and biochemical evidence in support of an autoimmune component in schizophrenia and depict gut processes and a dysbiotic microbiome as a source and perpetuator of autoimmune dysfunction in the brain. Within this framework, we review the role of infectious agents, inflammation, gut dysbioses and autoantibody propagation on CNS pathologies such as neurotransmitter receptor hypofunction and complement pathway-mediated synaptic pruning. We then review the new pharmacotherapeutic horizon and novel agents directed to impact these pathological conditions. At the core of this discourse is the understanding that schizophrenia is etiologically and pathophysiologically heterogeneous and thus its treatment requires individualized attention with disease state variants diagnosed with objective biomarkers.


Assuntos
Autoimunidade , Esquizofrenia/tratamento farmacológico , Esquizofrenia/imunologia , Animais , Antipsicóticos/uso terapêutico , Quimioterapia Combinada , Humanos , Fenótipo
19.
Bipolar Disord ; 20(7): 614-621, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29693757

RESUMO

OBJECTIVE: Immunological abnormalities play a role in the pathophysiology of mania and have been associated with relapse. Probiotic organisms such as Lactobacilli and Bifidobacteria modulate inflammation in humans and animal models. The trial examined whether the administration of probiotic organisms prevents psychiatric rehospitalizations in patients recently discharged following hospitalization for mania. METHODS: Patients hospitalized for mania (N = 66) were randomized after discharge to receive 24 weeks of adjunctive probiotics (Lactobacillus rhamnosus strain GG and Bifidobacterium animalis subsp. lactis strain Bb12) or adjunctive placebo in a parallel two-group design format. The effect of treatment group on the risk of rehospitalization was calculated using Cox regression models. The modulating effect of systemic inflammation was measured employing an inflammation score based on immunoglobulin levels directed at previously defined antigens. RESULTS: During the 24-week observation period there were a total of 24 rehospitalizations in the 33 individuals who received placebo and eight rehospitalizations in the 33 individuals who received the probiotics (z = 2.63, P = .009). Hazard functions indicated that the administration of the probiotics was associated with a significant advantage in time to all psychiatric rehospitalizations (hazard ratio [HR] = 0.26, 95% confidence interval [CI] 0.10, .69; P = .007). Probiotic treatment also resulted in fewer days rehospitalized (mean 8.3 vs 2.8 days for placebo and probiotic treatment, respectively; χ2  = 5.17, P = .017). The effect of the probiotic treatment on the prevention of rehospitalization was increased in individuals with elevated levels of systemic inflammation at baseline. CONCLUSION: Probiotic supplementation is associated with a lower rate of rehospitalization in patients who have been recently discharged following hospitalization for mania.


Assuntos
Bifidobacterium animalis/fisiologia , Transtorno Bipolar , Lactobacillus rhamnosus/fisiologia , Readmissão do Paciente/estatística & dados numéricos , Probióticos/administração & dosagem , Adulto , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/imunologia , Transtorno Bipolar/terapia , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Inflamação/imunologia , Inflamação/microbiologia , Masculino , Pessoa de Meia-Idade
20.
J Nerv Ment Dis ; 206(3): 173-178, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29474231

RESUMO

Persons with serious mental illness are at high risk for suicide, but this outcome is difficult to predict. Serological markers may help to identify suicide risk. We prospectively assessed 733 persons with a schizophrenia spectrum disorder, 483 with bipolar disorder, and 76 with major depressive disorder for an average of 8.15 years. The initial evaluation consisted of clinical and demographic data as well as a blood samples from which immunoglobulin G antibodies to herpes viruses and Toxoplasma gondii were measured. Suicide was determined using data from the National Death Index. Cox proportional hazard regression models examined the role of baseline variables on suicide outcomes. Suicide was associated with male sex, divorced/separated status, Caucasian race, and elevated levels of antibodies to Cytomegalovirus (CMV). Increasing levels of CMV antibodies were associated with increasing hazard ratios for suicide. The identification of serological variables associated with suicide might provide more personalized methods for suicide prevention.


Assuntos
Transtorno Bipolar/psicologia , Transtorno Depressivo Maior/psicologia , Esquizofrenia/sangue , Suicídio/psicologia , Adolescente , Adulto , Idoso , Anticorpos Antiprotozoários/sangue , Anticorpos Antivirais/sangue , Citomegalovirus/imunologia , Herpesviridae/imunologia , Humanos , Imunoglobulina G/sangue , Estado Civil , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Psicologia do Esquizofrênico , Fatores Sexuais , Suicídio/estatística & dados numéricos , Toxoplasma/imunologia , Adulto Jovem
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