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1.
Artigo em Inglês | MEDLINE | ID: mdl-33753882

RESUMO

The goals of the current study were to determine whether topological organization of brain structural networks is altered in youth with bipolar disorder, whether such alterations predict treatment outcomes, and whether they are normalized by treatment. Youth with bipolar disorder were randomized to double-blind treatment with quetiapine or lithium and assessed weekly. High-resolution MRI images were collected from children and adolescents with bipolar disorder who were experiencing a mixed or manic episode (n = 100) and healthy youth (n = 63). Brain networks were constructed based on the similarity of morphological features across regions and analyzed using graph theory approaches. We tested for pretreatment anatomical differences between bipolar and healthy youth and for changes in neuroanatomic network metrics following treatment in the youth with bipolar disorder. Youth with bipolar disorder showed significantly increased clustering coefficient (Cp) (p = 0.009) and characteristic path length (Lp) (p = 0.04) at baseline, and altered nodal centralities in insula, inferior frontal gyrus, and supplementary motor area. Cp, Lp, and nodal centrality of the insula exhibited normalization in patients following treatment. Changes in these neuroanatomic parameters were correlated with improvement in manic symptoms but did not differ between the two drug therapies. Baseline structural network matrices significantly differentiated medication responders and non-responders with 80% accuracy. These findings demonstrate that both global and nodal structural network features are altered in early course bipolar disorder, and that pretreatment alterations in neuroanatomic features predicted treatment outcome and were reduced by treatment. Similar connectome normalization with lithium and quetiapine suggests that the connectome changes are a downstream effect of both therapies that is related to their clinical efficacy.

2.
Schizophr Res ; 228: 180-187, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33444934

RESUMO

Alterations in polyunsaturated fatty acids (PUFAs), including omega-3 and omega-6, have been implicated in the pathophysiology of psychotic disorders, but little is known about their associations with neuropsychological functioning. The present study includes 46 recent-onset psychosis patients who participated in a larger (n = 50) double blind, placebo-controlled randomized clinical trial comparing 16 weeks of treatment with either risperidone + fish oil (FO) (EPA 740 mg and DHA 400 mg daily) or risperidone + placebo and completed neuropsychological assessments at the baseline timepoint. We investigated the relationship between baseline omega-3 (i.e., eicosapentaenoic acid, EPA; docosapentaenoic acid, DPA and docosahexaenoic acid, DHA) and omega-6 (i.e., arachidonic acid, AA) PUFA with baseline MATRICS Consensus Cognitive Battery (MCCB) and Brief Psychiatric Rating Scale (BPRS) scores. Twenty-five patients had neuropsychological data available at 16 weeks following participation in the clinical trial, which included 12 patients assigned to risperidone + FO and 13 patients assigned to risperidone + placebo. At baseline both higher DHA and EPA correlated significantly with better social cognition after controlling for functioning on other neuropsychological domains, total BPRS score, AA level and substance use. Also, at baseline higher AA correlated significantly with hostility/uncooperativeness after controlling for DHA + EPA + DPA, overall neuropsychological functioning and substance use. Patients treated with risperidone + FO demonstrated a significant longitudinal increase in social cognition that was significantly higher at 16 weeks compared to patients treated with risperidone + placebo. DHA also correlated significantly with social cognition at the 16-week timepoint. This study provides novel evidence for a differential role of omega-3 vs. omega-6 PUFA in neuropsychological deficits and symptoms in recent-onset psychosis and its treatment.

3.
Psychiatry Res Neuroimaging ; 307: 111219, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33221631

RESUMO

We examined the impact of treatment with fish oil (FO), a rich source of omega-3 polyunsaturated fatty acids (n-3 PUFA), on white matter in 37 recent-onset psychosis patients receiving risperidone in a double-blind placebo-controlled randomized clinical trial. Patients were scanned at baseline and randomly assigned to receive 16-weeks of treatment with risperidone + FO or risperidone + placebo. Eighteen patients received follow-up MRIs (FO, n = 10/Placebo, n = 8). Erythrocyte levels of n-3 PUFAs eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and docosapentaenoic acid (DPA) were obtained at both time points. We employed Free Water Imaging metrics representing the extracellular free water fraction (FW) and fractional anisotropy of the tissue (FA-t). Analyses were conducted using Tract-Based-Spatial-Statistics and nonparametric permutation-based tests with family-wise error correction. There were significant positive correlations of FA-t with DHA and DPA among all patients at baseline. Patients treated with risperidone + placebo demonstrated reductions in FA-t and increases in FW, whereas patients treated with risperidone + FO exhibited no significant changes in FW and FA-t reductions were largely attenuated. The correlations of DPA and DHA with baseline FA-t support the hypothesis that n-3 PUFA intake or biosynthesis are associated with white matter abnormalities in psychosis. Adjuvant FO treatment may partially mitigate against white matter alterations observed in recent-onset psychosis patients following risperidone treatment.

4.
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; 42(5): 481-488, Sept.-Oct. 2020. tab
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1132115

RESUMO

Objectives: To prospectively investigate whether baseline clinical characteristics and medication exposure predict development of major depressive disorder or bipolar disorder in offspring of parents with bipolar disorder. Methods: Youth aged 9-20 years with at least one biological parent with bipolar disorder and no prior history of mood or psychotic episodes (n=93) were prospectively evaluated and treated naturalistically during the study. Participants were divided into two groups: converters, defined as those who met DSM-IV criteria for a mood episode during follow-up (n=19); or non-converters (n=74). Logistic regression models were used to investigate associations between baseline clinical variables and medication exposure during follow-up and risk of developing a first mood episode (conversion). Results: Multivariate regression analyses showed that baseline anxiety disorders and subsyndromal mood disorders were associated with increased risk of conversion during follow-up. Adding medication exposure to the multivariate model showed that exposure to antidepressants during follow-up was associated with increased risk of conversion. Conclusions: Caution should be used when treating bipolar offspring with anxiety and/or emerging depressive symptoms using antidepressant agents, given the increased risk of developing a major mood disorder.

5.
Eur J Clin Invest ; : e13398, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32894576

RESUMO

BACKGROUND: A major problem in quantifying symptoms of schizophrenia is establishing a reliable distinction between enduring and dynamic aspects of psychopathology. This is critical for accurate diagnosis, monitoring and evaluating treatment effects in both clinical practice and trials. MATERIALS AND METHODS: We applied Generalizability Theory, a robust novel method to distinguish between dynamic and stable aspects of schizophrenia symptoms in the widely used Positive and Negative Symptom Scale (PANSS) using a longitudinal measurement design. The sample included 107 patients with chronic schizophrenia assessed using the PANSS at five time points over a 24-week period during a multi-site clinical trial of N-Acetylcysteine as an add-on to maintenance medication for the treatment of chronic schizophrenia. RESULTS: The original PANSS and its three subscales demonstrated good reliability and generalizability of scores (G = 0.77-0.93) across sample population and occasions making them suitable for assessment of psychosis risks and long-lasting change following a treatment, while subscales of the five-factor models appeared less reliable. The most enduring symptoms represented by the PANSS were poor attention, delusions, blunted affect and poor rapport. More dynamic symptoms with 40%-50% of variance explained by patient transient state including grandiosity, preoccupation, somatic concerns, guilt feeling and hallucinatory behaviour. CONCLUSIONS: Identified dynamic symptoms are more amendable to change and should be the primary target of interventions aiming at effectively treating schizophrenia. Separating out the dynamic symptoms would increase assay sensitivity in trials, reduce the signal to noise ratio and increase the potential to detect the effects of novel therapies in clinical trials.

7.
Braz J Psychiatry ; 42(5): 481-488, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32401870

RESUMO

OBJECTIVES: To prospectively investigate whether baseline clinical characteristics and medication exposure predict development of major depressive disorder or bipolar disorder in offspring of parents with bipolar disorder. METHODS: Youth aged 9-20 years with at least one biological parent with bipolar disorder and no prior history of mood or psychotic episodes (n=93) were prospectively evaluated and treated naturalistically during the study. Participants were divided into two groups: converters, defined as those who met DSM-IV criteria for a mood episode during follow-up (n=19); or non-converters (n=74). Logistic regression models were used to investigate associations between baseline clinical variables and medication exposure during follow-up and risk of developing a first mood episode (conversion). RESULTS: Multivariate regression analyses showed that baseline anxiety disorders and subsyndromal mood disorders were associated with increased risk of conversion during follow-up. Adding medication exposure to the multivariate model showed that exposure to antidepressants during follow-up was associated with increased risk of conversion. CONCLUSIONS: Caution should be used when treating bipolar offspring with anxiety and/or emerging depressive symptoms using antidepressant agents, given the increased risk of developing a major mood disorder.


Assuntos
Transtorno Bipolar , Transtorno Depressivo Maior , Adolescente , Adulto , Transtorno Bipolar/induzido quimicamente , Transtorno Bipolar/tratamento farmacológico , Criança , Manual Diagnóstico e Estatístico de Transtornos Mentais , Humanos , Pais , Estudos Prospectivos , Adulto Jovem
8.
J Child Adolesc Psychopharmacol ; 30(5): 293-305, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32167792

RESUMO

Objectives: To evaluate the clinical and neurochemical effects of 12-week fish oil, a source of omega-3 polyunsaturated fatty acids (n-3 PUFAs), in depressed adolescents with a family history of bipolar I disorder. Methods: Adolescents with a current Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision diagnosis of Major Depressive Disorder or Depressive Disorder not otherwise specified, a Childhood Depression Rating Scale-Revised (CDRS-R) Version raw score of ≥40, and at least one biological parent with bipolar I disorder were randomized to double-blind treatment with fish oil (2100 mg/day) or placebo for 12 weeks. The primary outcome measure was change in CDRS-R total score, and secondary outcomes measures were change in manic symptoms (Young Mania Rating Scale), global symptom and functioning measures (Clinical Global Impression-Severity [CGI-S] /CGI Improvement [CGI-I], Children's Global Assessment Scale, and Child Behavior Checklist), safety and laboratory measures, and anterior cingulate cortex (ACC) and bilateral ventrolateral prefrontal cortex neurometabolite concentrations using proton magnetic resonance spectroscopy at 4 T. Results: Fifty-six patients were randomized, and 42 completed the 12-week trial (placebo: n = 21; fish oil, n = 21). Subjects randomized to fish oil, but not placebo, exhibited a significant baseline to endpoint increase in erythrocyte n-3 PUFAs. Reductions in CDRS-R scores did not differ between treatment groups (p = 0.15), and similar remission (p = 0.58) and response (p = 0.77) rates were observed. Fish oil produced a significantly greater decrease in CGI-S (p = 0.0042) and CGI-I (p = 0.036) scores compared with placebo. Baseline to endpoint change in ACC creatine (p = 0.004) and ACC choline (Cho) (p = 0.024) differed significantly between groups. Baseline ACC Cho levels were inversely correlated with baseline and baseline to endpoint change in CDRS-R scores, and baseline to endpoint change in ACC Cho correlated with baseline-endpoint change in CDRS-R scores and n-3 PUFA. There were no group differences in safety and tolerability ratings or laboratory measures. Conclusions: Fish oil monotherapy was not superior to placebo for reducing depressive symptoms in high-risk youth as assessed by the CDRS-R, but was safe and well tolerated and superior to placebo on clinician ratings of global symptom improvement. Associations among ACC Cho levels, depression symptom severity, and n-3 PUFA warrant additional investigation.

9.
J Affect Disord ; 265: 233-238, 2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-32090746

RESUMO

INTRODUCTION: Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are recommended as an integrative treatment for major depressive disorder (MDD). In 2019, the International Society for Nutritional Psychiatry Research (ISNPR) developed the first practice guidelines for n-3 PUFA treatment of MDD. To strengthen these guidelines and enhance their clinical applicability, we synthesized the evidence and clinical experiences previously obtained through the Delphi methodology. METHODS: Nineteen statements covering five major domains in MDD treatment were formulated through internal meetings. Fourteen international experts were invited to participate in the web-based Delphi process that validated the statements. Likert scales were used, and consensus level was set at 7.0/10.0, with the equivocal level set at 5.1-6.9. The items with scores < 5.0 were allocated into a second round Delphi survey with inverse questions. RESULTS: All panelists completed the survey. Sixteen statements reached consensus, and the statement "n-3 PUFAs are one of the potential adjunctive treatments for adult MDD" reached the highest agreement. "N-3 PUFAs are one of the potential monotherapies for adult MDD" instead scored lowest. Regarding "special populations," many items, reached high consensus despite sub-optimal supportive evidence. LIMITATION: The panelists had a specialized interest in n-3 PUFAs; focus was placed on clinical issues rather than on biological mechanisms. CONCLUSIONS: The Delphi process helps bridge the gap between scientific evidence and clinical practice, supports certain uses of PUFA and identifies insufficiency in current evidence that merit future research.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31669935

RESUMO

The relationship between seafood eaten during pregnancy and neurocognition in offspring has been the subject of considerable scientific study for over 25 years. Evaluation of this question led two scientific advisory committees to the Dietary Guidelines for Americans (DGAC), the Food and Agriculture Organization of the United Nations with the World Health Organization (FAO/WHO), Health Canada, the European Food Safety Authority (EFSA), and the U.S. Food and Drug Administration (FDA) to conclude through 2014 that seafood consumed by pregnant women is likely to benefit the neurocognitive development of their children. The evidence they reviewed included between four and ten studies of seafood consumption during pregnancy that reported beneficial associations. In contrast there are now 29 seafood consumption studies available describing over 100,000 mothers-child pairs and 15 studies describing over 25,000 children who ate seafood. A systematic review of these studies using Nutrition Evaluation Systematic Review methodology is warranted to determine whether recent research corroborates, builds on, or significantly alters the previous conclusions. Studies that evaluate the integrated effects of seafood as a complete food more directly and completely evaluate impacts on neurocognition as compared to studies that evaluate individual nutritients or toxicological constituents in isolation. Here we address how the findings could add to our understanding of whether seafood consumed during pregnancy and early childhood affects neurocognition, including whether such effects are clinically meaningful, lasting, related to amounts consumed, and affected by any neurotoxicants that may be present, particularly mercury, which is present at varying levels in essentially all seafood. We provide the history, context and rationale for reexamining these questions in light of currently available data.


Assuntos
Ácidos Graxos Ômega-3/farmacologia , Processos Mentais/efeitos dos fármacos , Fenômenos Fisiológicos da Nutrição Pré-Natal/efeitos dos fármacos , Criança , Desenvolvimento Infantil/efeitos dos fármacos , Saúde da Criança , Feminino , Humanos , Política Nutricional , Gravidez , Alimentos Marinhos
11.
Nutr Neurosci ; : 1-12, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31599208

RESUMO

Objectives: Maternal-pup nurturing behavior has previously been shown to impact offspring neurodevelopment independent of diet. Here we investigated the effects of perinatal maternal n-3 fatty acid deficiency on maternal-pup nurturing behavior and potential associations with pro-inflammatory signaling. Methods: Eight-week-old virgin female Long-Evans hooded rats were randomized to a control diet containing alpha-linolenic acid (ALA, 18:3n-3) (CON, n = 10) or an ALA-free diet (Deficient, DEF, n = 11) 30 d prior to mating. On postnatal day 2 (P2) litters were culled to eight per dam. On P3, P6, and P9 dams and their litters were video recorded and maternal nurturing behaviors, including licking/grooming of pups and arched-back nursing, were scored by a blinded rater. Following weaning on P21, dam postmortem central (prefrontal cortex, PFC) and peripheral (red blood cell, RBC) fatty acid composition and central (PFC IL-1ß, IL-2, IL-6, TNFα, cPLA2, COX-2 mRNA) and peripheral (plasma IL-1ß, IL-2, IL-6, TNFα, CRP) pro-inflammatory biostatus assessed. Results: DEF dams exhibited significantly lower RBC (p ≤ 0.0001) and PFC (p ≤ 0.0001) docosahexaenoic acid (DHA) levels compared with CON dams. Irrespective of diet dams exhibited significantly lower RBC, but not PFC, DHA levels compared with non-parous rats. DEF dams exhibited less licking/grooming (p = 0.008), arched-back nursing (p ≤ 0.0001) and blanket nursing (p = 0.003), and exhibited more passive nursing (p = 0.003) but not time off pups (p = 0.1), compared with CON dams. PFC and plasma inflammatory measures did not differ significantly between groups. Discussion: Perinatal dietary n-3 fatty acid deficiency reduces maternal nurturing behavior and this effect is not associated with enduring elevations in pro-inflammatory signaling.

12.
Psychother Psychosom ; 88(5): 263-273, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31480057

RESUMO

Major depressive disorder (MDD) is a complex mental illness with unmet therapeutic needs. The antidepressant effects of ω-3 polyunsaturated fatty acids (n-3 PUFAs) have been widely reported. The subcommittee of the International Society for Nutritional Psychiatry Research organized an expert panel and conducted a literature review and a Delphi process to develop a consensus-based practice guideline for clinical use of n-3 PUFAs in MDD. The guideline focuses on 5 thematic areas: general concepts, acute treatment strategy, depression recurrence monitoring and prevention, use in special populations, and potential safety issues. The key practice guidelines contend that: (1) clinicians and other practitioners are advised to conduct a clinical interview to validate clinical diagnoses, physical conditions, and measurement-based psychopathological assessments in the therapeutic settings when recommending n-3 PUFAs in depression treatment; (2) with respect to formulation and dosage, both pure eicosapentaenoic acid (EPA) or an EPA/docosahexaenoic acid (DHA) combination of a ratio higher than 2 (EPA/DHA >2) are considered effective, and the recommended dosages should be 1-2 g of net EPA daily, from either pure EPA or an EPA/DHA (>2:1) formula; (3) the quality of n-3 PUFAs may affect therapeutic activity; and (4) potential adverse effects, such as gastrointestinal and dermatological conditions, should be monitored, as well as obtaining comprehensive metabolic panels. The expert consensus panel has agreed on using n-3 PUFAs in MDD treatment for pregnant women, children, and the elderly, and prevention in high-risk populations. Personalizing the clinical application of n-3 PUFAs in subgroups of MDD with a low Omega-3 Index or high levels of inflammatory markers might be regarded as areas that deserve future research.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Ácidos Docosa-Hexaenoicos/uso terapêutico , Ácido Eicosapentaenoico/uso terapêutico , Ácidos Graxos Ômega-3/sangue , Idoso , Biomarcadores , Criança , Transtorno Depressivo Maior/prevenção & controle , Feminino , Humanos , Gravidez , Sociedades Médicas
13.
Harv Rev Psychiatry ; 27(2): 94-107, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30633010

RESUMO

Meta-analytic evidence indicates that mood and psychotic disorders are associated with both omega-3 polyunsaturated fatty acid (omega-3 PUFA) deficits and progressive regional gray and white matter pathology. Although the association between omega-3 PUFA insufficiency and progressive neuropathological processes remains speculative, evidence from translational research suggests that omega-3 PUFA insufficiency may represent a plausible and modifiable risk factor not only for enduring neurodevelopmental abnormalities in brain structure and function, but also for increased vulnerability to neurodegenerative processes. Recent evidence from human neuroimaging studies suggests that lower omega-3 PUFA intake/status is associated with accelerated gray matter atrophy in healthy middle-aged and elderly adults, particularly in brain regions consistently implicated in mood and psychotic disorders, including the amygdala, anterior cingulate, hippocampus, prefrontal cortex, and temporal cortex. Human neuroimaging evidence also suggests that both low omega-3 PUFA intake/status and psychiatric disorders are associated with reductions in white matter microstructural integrity and increased rates of white matter hyperintensities. Preliminary evidence suggests that increasing omega-3 PUFA status is protective against gray matter atrophy and deficits in white matter microstructural integrity in patients with mood and psychotic disorders. Plausible mechanisms mediating this relationship include elevated pro-inflammatory signaling, increased synaptic regression, and reductions in cerebral perfusion. Together these associations encourage additional neuroimaging research to directly investigate whether increasing omega-3 PUFA status can mitigate neuropathological processes in patients with, or at high risk for, psychiatric disorders.


Assuntos
Deficiências Nutricionais , Ácidos Graxos Ômega-3 , Substância Cinzenta , Transtornos Mentais , Substância Branca , Animais , Deficiências Nutricionais/dietoterapia , Deficiências Nutricionais/patologia , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-3/deficiência , Substância Cinzenta/efeitos dos fármacos , Substância Cinzenta/metabolismo , Substância Cinzenta/patologia , Humanos , Transtornos Mentais/dietoterapia , Transtornos Mentais/metabolismo , Transtornos Mentais/patologia , Substância Branca/efeitos dos fármacos , Substância Branca/metabolismo , Substância Branca/patologia
14.
Nutr Neurosci ; 22(8): 587-595, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29286866

RESUMO

Although attention deficit hyperactivity disorder is associated with deficits in docosahexaenoic acid (DHA), an omega-3 fatty acid implicated in dopamine and glutamate synaptic plasticity, its role in neuroplastic brain changes that occur following repeated amphetamine (AMPH) treatment are not known. This study used pharmacological magnetic resonance imaging to investigate the impact of repeated AMPH exposure and alterations in brain DHA levels on AMPH-induced brain activation patterns. Male rats were fed a diet with no n-3 fatty acids (Deficient, DEF, n = 20), a diet fortified with preformed DHA (fish oil, FO, n = 20), or a control diet fortified with alpha-linolenic acid (n = 20) from P21 to P90. During adolescence (P40-60), one-half of each diet group received daily AMPH injections escalated weekly (0.5, 1.0, 2.5, 5.0 mg/kg/d) or drug vehicle. Following a 30-d abstinence period blood oxygen level dependent (BOLD) responses were determined in a 7 T Bruker Biospec system following an AMPH challenge (7.5 mg/kg, i.v). Postmortem erythrocyte and forebrain DHA composition were determined by gas chromatography. Compared with control rats, forebrain and erythrocyte DHA levels were significantly lower in DEF rats and significantly higher in FO rats. Across AMPH doses DEF rats exhibited greater locomotor activity compared to control and FO rats. In AMPH-naïve rats, the AMPH challenge increased BOLD activity in the substantia nigra and basal forebrain and no diet group differences were observed. In AMPH-pretreated control and FO rats, the AMPH challenge similarly increased BOLD activation in the bilateral caudate putamen, thalamus, and motor and cingulate cortices. In contrast, BOLD activation in AMPH-pretreated DEF rats was similar to AMPH-naïve DEF animals, and AMPH-pretreated DEF rats exhibited attenuated frontostriatal BOLD activation compared with AMPH-pretreated control and FO rats. These findings demonstrate that chronic escalating AMPH treatment induces enduring frontostriatal recruitment and that peri-adolescent deficits in brain DHA accrual impair this response.


Assuntos
Anfetamina/administração & dosagem , Encéfalo/efeitos dos fármacos , Encéfalo/fisiologia , Ácidos Docosa-Hexaenoicos/administração & dosagem , Animais , Prosencéfalo Basal/efeitos dos fármacos , Prosencéfalo Basal/fisiologia , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/fisiologia , Ácidos Docosa-Hexaenoicos/metabolismo , Eritrócitos/metabolismo , Giro do Cíngulo/efeitos dos fármacos , Giro do Cíngulo/fisiologia , Locomoção/efeitos dos fármacos , Imagem por Ressonância Magnética , Masculino , Córtex Motor/efeitos dos fármacos , Córtex Motor/fisiologia , Prosencéfalo/metabolismo , Ratos Long-Evans , Substância Negra/efeitos dos fármacos , Substância Negra/fisiologia , Tálamo/efeitos dos fármacos , Tálamo/fisiologia
15.
Schizophr Res ; 204: 295-303, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30241990

RESUMO

Omega-3 treatment studies for multi-episode schizophrenia or clinical high risk for conversion to psychosis states have had variable, and often negative, results. To examine adjunctive omega-3 treatment for recent onset psychosis, participants aged 15-40 years with recent onset schizophrenia-spectrum (n = 46) or bipolar (n = 4) disorders and current psychotic symptoms were treated for 16 weeks with risperidone and randomly-assigned omega-3 (EPA 740 mg and DHA 400 mg daily) or matching placebo. The primary outcome measure was the Brief Psychiatric Rating Scale (BPRS) total score. Mean lifetime antipsychotic exposure was 18.1 days. Length of time in treatment, risperidone dose and number of omega-3/placebo capsules taken did not differ between conditions. Longitudinal analysis of the total BPRS score revealed a trend level (p = 0.0826) treatment effect favoring omega-3 treatment. Lorazepam was an allowed concomitant medication. Among the subgroup (N = 23) who did not receive lorazepam, the treatment effect on BPRS total scores favoring omega-3 was significant (p = 0.0406) and factor scores analyses revealed a substantial decrease in depression-anxiety with omega-3 but no change with placebo (treatment-by-time interaction, p = 0.0184). Motor side effects did not differ between conditions. Analysis of Systematic Assessment for Treatment Emergent Events assessments revealed fewer adverse events overall with omega-3 compared with placebo with the largest differences between conditions (all favoring omega-3) on confusion, anxiety, depression, irritability, and tiredness/fatigue. These results suggest that omega-3 adjuvant treatment is a potential option for depression and anxiety symptoms of people with recent onset psychosis. Further research is needed to confirm this potential. Clinical trial registration: NCT01786239.


Assuntos
Antipsicóticos/farmacologia , Ansiedade/tratamento farmacológico , Transtorno Bipolar/tratamento farmacológico , Depressão/tratamento farmacológico , Ácidos Graxos Ômega-3/farmacologia , Transtornos Psicóticos/tratamento farmacológico , Risperidona/farmacologia , Esquizofrenia/tratamento farmacológico , Adolescente , Adulto , Antipsicóticos/administração & dosagem , Ansiedade/etiologia , Transtorno Bipolar/complicações , Escalas de Graduação Psiquiátrica Breve , Depressão/etiologia , Quimioterapia Combinada , Ácidos Graxos Ômega-3/administração & dosagem , Feminino , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Transtornos Psicóticos/complicações , Risperidona/administração & dosagem , Esquizofrenia/complicações , Adulto Jovem
16.
Cell Rep ; 23(12): 3607-3620, 2018 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-29925002

RESUMO

Exposure to cold temperature is well known to upregulate heat shock protein (Hsp) expression and recruit and/or activate brown adipose tissue and beige adipocytes in humans and animals. However, whether and how Hsps regulate adipocyte function for energy homeostatic responses is poorly understood. Here, we demonstrate a critical role of Hsp20 as a negative regulator of adipocyte function. Deletion of Hsp20 enhances non-shivering thermogenesis and suppresses inflammatory responses, leading to improvement of glucose and lipid metabolism under both chow diet and high-fat diet conditions. Mechanistically, Hsp20 controls adipocyte function by interacting with the subunit of the ubiquitin ligase complex, F-box only protein 4 (FBXO4), and regulating the ubiquitin-dependent degradation of peroxisome proliferation activated receptor gamma (PPARγ). Indeed, Hsp20 deficiency mimics and enhances the pharmacological effects of the PPARγ agonist rosiglitazone. Together, our findings suggest a role of Hsp20 in mediating adipocyte function by linking ß-adrenergic signaling to PPARγ activity.


Assuntos
Adipócitos/metabolismo , Proteínas F-Box/metabolismo , Proteínas de Choque Térmico HSP20/metabolismo , PPAR gama/metabolismo , Ubiquitinação , Adipócitos/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Adiposidade/efeitos dos fármacos , Animais , Temperatura Baixa , Metabolismo Energético/efeitos dos fármacos , Glucose/metabolismo , Proteínas de Choque Térmico HSP20/deficiência , Proteínas de Choque Térmico HSP20/genética , Inflamação/patologia , Resistência à Insulina , Metabolismo dos Lipídeos/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/patologia , Estabilidade Proteica/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Rosiglitazona/farmacologia , Ubiquitinação/efeitos dos fármacos
17.
Bipolar Disord ; 20(7): 658-665, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29479787

RESUMO

OBJECTIVES: The aims of the present study were to characterize cardiometabolic risk factors in a cohort of bipolar disorder patients with limited exposure to psychotropic medications, and to evaluate their associations with mood symptoms and omega-3 polyunsaturated fatty acid (PUFA) blood levels. METHODS: Cardiometabolic risk assessments were compared in individuals with bipolar I disorder experiencing a first manic or mixed episode or an early depressive episode (n=117) and healthy subjects (n=56). Patients were medication free at assessment and had no or limited exposure to mood-stabilizer or antipsychotic medications prior to the current admission. Associations among cardiometabolic parameters and Clinical Global Impression-Severity scale (CGI-S), manic (Young Mania Rating Scale [YMRS]), and depressive (Hamilton Depression Rating Scale [HDRS]) symptom ratings were evaluated within the bipolar group. RESULTS: Following adjustment for demographic variables (i.e., age, gender, and parental education), significantly higher fasting triglyceride levels were observed in the bipolar group compared to the healthy group (121.7 mg/dL vs 87.0 mg/dL; P<.01). There were no clear trends for other metabolic indicators, including blood pressure, body mass index, and fasting glucose. Nineteen percent of the bipolar group and 6% of the healthy group met the criteria for metabolic syndrome (P=.23). The omega-3 index was lower in the bipolar group (3.4% vs 3.9%; P<.01). Within the bipolar group, no associations were found between the cardiometabolic parameters and CGI-S, YMRS, and HDRS symptom ratings. CONCLUSIONS: Recent-onset medication-free bipolar disorder is associated with higher triglyceride levels. These findings are suggestive of early metabolic dysregulation prior to long-term psychotropic medication exposure. Lower omega-3 PUFA levels in individuals with bipolar I disorder represent a potential therapeutic target for additional investigation.


Assuntos
Transtorno Bipolar , Ácidos Graxos Ômega-3 , Síndrome Metabólica , Psicotrópicos/uso terapêutico , Triglicerídeos , Adulto , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/epidemiologia , Transtorno Bipolar/fisiopatologia , Índice de Massa Corporal , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-3/metabolismo , Feminino , Humanos , Metabolismo dos Lipídeos , Masculino , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/metabolismo , Síndrome Metabólica/prevenção & controle , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Fatores de Risco , Tempo para o Tratamento/estatística & dados numéricos , Triglicerídeos/sangue , Triglicerídeos/metabolismo
18.
Neurobiol Aging ; 64: 147-156, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29458842

RESUMO

Given evidence that eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and anthocyanin-rich blueberries provide neurocognitive benefit, we investigated long-term supplementation in older adults with cognitive complaints. In a 24-week randomized, double-blind, placebo-controlled trial, elderly men and women received daily fish oil (FO) or blueberry (BB) or both. Diet records confirmed that participants reduced background consumption of EPA, DHA, and anthocyanins as prescribed. Erythrocyte EPA + DHA composition increased in the FO groups (p = 0.0001). Total urinary anthocyanins did not differ between the groups after supplementation but glycoside and native (food) forms increased only in the BB-supplemented groups. The FO (p = 0.03) and BB (p = 0.05) groups reported fewer cognitive symptoms, and the BB group showed improved memory discrimination (p = 0.04), indicating that supplementation improved cognition. Cognitive benefit in the BB group was associated with the presence of urinary anthocyanins reflecting recent BB intake but not with anthocyanin metabolites. However, combined FO + BB treatment was not associated with cognitive enhancement as expected.


Assuntos
Mirtilos Azuis (Planta) , Cognição , Disfunção Cognitiva/dietoterapia , Disfunção Cognitiva/psicologia , Suplementos Nutricionais , Óleos de Peixe/administração & dosagem , Idoso , Antocianinas/administração & dosagem , Antocianinas/urina , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácidos Docosa-Hexaenoicos/sangue , Método Duplo-Cego , Ácido Eicosapentaenoico/administração & dosagem , Ácido Eicosapentaenoico/sangue , Feminino , Glicosídeos/sangue , Humanos , Masculino , Memória , Pessoa de Meia-Idade , Estudos Prospectivos
19.
Artigo em Inglês | MEDLINE | ID: mdl-29358037

RESUMO

The tolerability of antidepressants is poorly characterized in children and adolescents with depressive and anxiety disorders. Among adverse events that affect the tolerability of antidepressants in youth is activation, a cluster of symptoms that represent a hyperarousal event characterized by impulsivity, restlessness, and/or insomnia. This cluster of symptoms was first identified as a side effect of selective serotonin and selective serotonin norepinephrine inhibitors (SSRIs and SSNRIs) in the early 1990s; however, activation remains poorly characterized in terms of prevalence, risk factors, and pathophysiology. This article describes the pathophysiology of antidepressant-related activation, predictors of activation and its clinical management in youth with depressive and anxiety disorders who are treated with antidepressant medications.


Assuntos
Acatisia Induzida por Medicamentos/fisiopatologia , Antidepressivos/efeitos adversos , Transtornos Disruptivos, de Controle do Impulso e da Conduta/induzido quimicamente , Transtornos Disruptivos, de Controle do Impulso e da Conduta/fisiopatologia , Inibidores de Captação de Serotonina/efeitos adversos , Inibidores da Recaptação de Serotonina e Norepinefrina/efeitos adversos , Adolescente , Antidepressivos/uso terapêutico , Transtornos de Ansiedade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/induzido quimicamente , Criança , Transtorno Depressivo/tratamento farmacológico , Humanos , Agitação Psicomotora , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Ideação Suicida
20.
Artigo em Inglês | MEDLINE | ID: mdl-28529008

RESUMO

There is a substantial body of evidence from animal studies implicating polyunsaturated fatty acids (PUFA) in neuroinflammatory, neurotrophic, and neuroprotective processes in brain. However, direct evidence for a role of PUFA in human brain structure and function has been lacking. Over the last decade there has been a notable increase in neuroimaging studies that have investigated the impact of PUFA intake and/or blood levels (i.e., biostatus) on brain structure, function, and pathology in human subjects. The majority of these studies specifically evaluated associations between omega-3 PUFA intake and/or biostatus and neuroimaging outcomes using a variety of experimental designs and imaging techniques. This review provides an updated overview of these studies in an effort to identify patterns to guide and inform future research. While the weight of evidence provides general support for a beneficial effect of a habitual diet consisting of higher omega-3 PUFA intake on cortical structure and function in healthy human subjects, additional research is needed to replicate and extend these findings as well as identify response mediators and clarify mechanistic pathways. Controlled intervention trials are also needed to determine whether increasing n-3 PUFA biostatus can prevent or attenuate neuropathological brain changes observed in patients with or at risk for psychiatric disorders and dementia.


Assuntos
Encéfalo/anatomia & histologia , Encéfalo/fisiologia , Ácidos Graxos Insaturados/metabolismo , Neuroimagem/métodos , Idoso , Encéfalo/metabolismo , Ensaios Clínicos como Assunto , Estudos Transversais , Ácidos Graxos Ômega-3/metabolismo , Feminino , Humanos , Longevidade , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fármacos Neuroprotetores/metabolismo
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