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1.
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.

2.
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.

3.
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.

4.
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.

5.
Schizophr Res ; 2018 Sep 18.
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.

6.
Cell Rep ; 23(12): 3607-3620, 2018 Jun 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.

7.
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
8.
Bipolar Disord ; 20(7): 658-665, 2018 Nov.
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.

9.
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.

10.
Dev Neurosci ; 40(1): 84-92, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29216635

RESUMO

Neuropsychiatric disorders that frequently initially emerge during adolescence are associated with deficits in the omega-3 (n-3) fatty acid docosahexaenoic acid (DHA), elevated proinflammatory signaling, and regional reductions in white matter integrity (WMI). This study determined the effects of altering brain DHA accrual during adolescence on WMI in the rat brain by diffusion tensor imaging (DTI), and investigated the potential mediating role of proinflammatory signaling. During periadolescent development, male rats were fed a diet deficient in n-3 fatty acids (DEF, n = 20), a fish oil-fortified diet containing preformed DHA (FO, n = 20), or a control diet (CON, n = 20). In adulthood, DTI scans were performed and brain WMI was determined using voxelwise tract-based spatial statistics (TBSS). Postmortem fatty acid composition, peripheral (plasma IL-1ß, IL-6, and C-reactive protein [CRP]) and central (IL-1ß and CD11b mRNA) proinflammatory markers, and myelin basic protein (MBP) mRNA expression were determined. Compared with CON rats, forebrain DHA levels were lower in DEF rats and higher in FO rats. Compared with CON rats, DEF rats exhibited greater radial diffusivity (RD) and mean diffusivity in the right external capsule, and greater axial diffusivity in the corpus callosum genu and left external capsule. DEF rats also exhibited greater RD than FO rats in the right external capsule. Forebrain MBP expression did not differ between groups. Compared with CON rats, central (IL-1ß and CD11b) and peripheral (IL-1ß and IL-6) proinflammatory markers were not different in DEF rats, and DEF rats exhibited lower CRP levels. These findings demonstrate that deficits in adolescent DHA accrual negatively impact forebrain WMI, independently of elevated proinflammatory signaling.


Assuntos
Ácidos Docosa-Hexaenoicos/deficiência , Neurogênese/fisiologia , Prosencéfalo/patologia , Substância Branca/patologia , Animais , Imagem de Tensor de Difusão , Masculino , Ratos , Ratos Long-Evans
11.
J Affect Disord ; 227: 698-704, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29174744

RESUMO

BACKGROUND: The distinction between temporary versus enduring or state/trait aspects of depression is important. More precise distinction would improve understanding of the aetiology of depression and those aspects most amenable to intervention thus identifying more homogeneous, dynamic targets for clinical trials. Generalizability Theory has been proposed as useful for disentangling state and trait components of psychopathology. METHODS: We applied Generalizability Theory to determine the relative contributions of temporary and enduring aspects of depression in a widely used screening measure of depression the - 10-item Children's Depression Inventory (CDI-10; Kovacs, 1985). Participants were children of Pacific Island descent living in New Zealand (n = 668). Data were collected at ages - 9, 11, and 14 years. RESULTS: The CDI-10 demonstrated acceptable generalizability across occasions (G = 0.79) with about one third of variance in total scores attributed to temporary and two thirds to more enduring aspects of depression. There were no other significant sources of error variance. Two items were identified as more sensitive than the remaining eight to more dynamic symptoms. LIMITATIONS: Studies with briefer test-retest intervals are warranted. Use of this Pacific Island cohort limits generalizability of findings to other cultures and ethnicities. No data were collected on whether participants had received intervention for depression. CONCLUSIONS: While the CDI-10 reliably measures both stable and transient aspects of depression in children, the scale does not permit clear distinction between them. We advocate application of Generalizability Theory for developing state/trait depression measures and determining which existing measures are most suitable for capturing modifiable features of depression.


Assuntos
Depressão/diagnóstico , Transtorno Depressivo/diagnóstico , Adolescente , Criança , Estudos de Coortes , Depressão/psicologia , Transtorno Depressivo/psicologia , Feminino , Humanos , Masculino , Nova Zelândia , Ilhas do Pacífico , Inventário de Personalidade
12.
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.

13.
Nutr Neurosci ; : 1-9, 2017 Dec 29.
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.

14.
Psychiatry Res Neuroimaging ; 270: 39-45, 2017 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-29049903

RESUMO

Major psychiatric disorders are associated with dysregulated glutamate homeostasis and deficits in the omega-3 fatty acid docosahexaenoic acid (DHA). This study determined the effects of dietary-induced alterations in brain DHA accrual on cortical glutamate homeostasis in the adult rat brain. Adolescent rats were fed a control diet (n = 20), a n-3 fatty acid-deficient diet (DEF, n = 20), or a fish oil-fortified diet containing preformed DHA (FO, n = 20). In adulthood 1H MRS scans were performed with voxels in the prefrontal cortex (PFC) and thalamus. Compared with controls, erythrocyte, PFC, and thalamus DHA levels were significantly lower in DEF rats and significantly higher in FO rats. In the PFC, but not the thalamus, glutamate was significantly elevated in DEF rats compared with controls and FO rats. Glutamine did not differ between groups and the glutamine/glutamate ratio was lower in DEF rats. No differences were observed for markers of excitotoxicity (NAA, GFAP), or astrocyte glutamate transporter (GLAST, GLT-1) or glutamine synthetase expression. Across diet groups, PFC DHA levels were inversely correlated with PFC glutamate levels and positively correlated with GLAST expression. Together these findings demonstrate that rat cortical DHA accrual during adolescence impacts glutamate homeostasis in the adult PFC.


Assuntos
Envelhecimento/metabolismo , Ácidos Docosa-Hexaenoicos/metabolismo , Ácido Glutâmico/metabolismo , Homeostase , Córtex Pré-Frontal/metabolismo , Sistema X-AG de Transporte de Aminoácidos/metabolismo , Animais , Astrócitos/metabolismo , Dieta , Ácidos Docosa-Hexaenoicos/deficiência , Glutamato-Amônia Ligase/metabolismo , Glutamina/metabolismo , Masculino , Espectroscopia de Prótons por Ressonância Magnética , Ratos , Ratos Long-Evans
15.
J Psychiatr Res ; 95: 143-146, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28846858

RESUMO

Evidence from 31P magnetic resonance spectroscopy (31P MRS) studies suggest that different psychiatric disorders, which typically emerge during adolescence and young adulthood, are associated with abnormalities in mitochondrial bioenergetics and membrane phospholipid metabolism. These disorders are also associated with deficits in omega-3 polyunsaturated fatty acids (n-3 PUFA), including docosahexaenoic acid (DHA) which accumulates in mitochondrial and synaptic membranes. The present study investigated the effects of dietary-induced alterations in brain DHA accrual during adolescence on phospholipid metabolism and bioenergetics in the adult rat brain using 31P MRS. During the peri-adolescent period (P21-P90), 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 (18:3n-3, n = 20). On P90, 31P MRS was performed under isoflurane anesthetic using a 7 T Bruker Biospec system. Compared with controls, brain DHA levels were significantly lower in adult rats fed the DEF diet (-17%, p ≤ 0.0001) and significantly higher in rats fed the FO diet (+14%, p ≤ 0.0001). There were no significant group differences for indices of bioenergetics, including adenosine triphosphate and phosphocreatine levels, or indices of membrane phospholipid metabolism including phosphomonoesters and phosphodiesters. Therefore, the present 31P MRS data suggest that rat brain DHA levels are not a significant predictor of mitochondrial bioenergetics or membrane phospholipid metabolism.


Assuntos
Trifosfato de Adenosina/metabolismo , Encéfalo/metabolismo , Dieta , Ácidos Docosa-Hexaenoicos/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Mitocôndrias/metabolismo , Fosfolipídeos/metabolismo , Animais , Encéfalo/diagnóstico por imagem , Ácidos Docosa-Hexaenoicos/administração & dosagem , Metabolismo Energético/fisiologia , Masculino , Fósforo , Ratos , Ratos Long-Evans
16.
Prog Lipid Res ; 66: 1-13, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28069365

RESUMO

A body of evidence has implicated dietary deficiency in omega-3 polyunsaturated fatty acids (n-3 PUFA), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in the pathophysiology and etiology of recurrent mood disorders including major depressive disorder (MDD) and bipolar disorder. Cross-national and cross-sectional evidence suggests that greater habitual intake of n-3 PUFA is associated with reduced risk for developing mood symptoms. Meta-analyses provide strong evidence that patients with mood disorders exhibit low blood n-3 PUFA levels which are associated with increased risk for the initial development of mood symptoms in response to inflammation. While the etiology of this n-3 PUFA deficit may be multifactorial, n-3 PUFA supplementation is sufficient to correct this deficit and may also have antidepressant effects. Rodent studies suggest that n-3 PUFA deficiency during perinatal development can recapitulate key neuropathological, neurochemical, and behavioral features associated with mood disorders. Clinical neuroimaging studies suggest that low n-3 PUFA biostatus is associated with abnormalities in cortical structure and function also observed in mood disorders. Collectively, these findings implicate dietary n-3 PUFA insufficiency, particularly during development, in the pathophysiology of mood dysregulation, and support implementation of routine screening for and treatment of n-3 PUFA deficiency in patients with mood disorders.


Assuntos
Ácidos Graxos Insaturados/metabolismo , Transtornos do Humor/metabolismo , Animais , Suplementos Nutricionais , Ácidos Graxos Insaturados/biossíntese , Ácidos Graxos Insaturados/farmacologia , Ácidos Graxos Insaturados/uso terapêutico , Humanos , Transtornos do Humor/tratamento farmacológico , Recidiva
17.
Nutr Neurosci ; 20(4): 246-254, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-26463682

RESUMO

OBJECTIVE: Although extant preclinical evidence suggests that the long-chain omega-3 fatty acid docosahexaenoic acid (DHA) is important for neurodevelopment, little is known about its role in human cortical structural and functional maturation. In the present cross-sectional study, we investigated the relationship between DHA biostatus and functional connectivity in cortical attention networks of typically developing children. METHODS: Male children (aged 8-10 years, n = 36) were divided into 'low-DHA' (n = 18) and 'high-DHA' (n = 18) biostatus groups by a median split of erythrocyte DHA levels. Event-related functional connectivity during the performance of a sustained attention task (identical pairs continuous performance task (CPT-IP)) was conducted using functional magnetic resonance imaging. A voxelwise approach used the anterior cingulate cortex (ACC) as the seed-region. RESULTS: Erythrocyte DHA composition in the low-DHA group (2.6 ± 0.9%) was significantly lower than the high-DHA group (4.1 ± 1.1%, P ≤ 0.0001). Fish intake frequency was greater in the high-DHA group (P = 0.003) and was positively correlated with DHA levels among all subjects. The low-DHA group exhibited reduced functional connectivity between the ACC and the ventrolateral prefrontal cortex, insula, precuneus, superior parietal lobule, middle occipital gyrus, inferior temporal gyrus, and lingual gyrus compared with the high-DHA group (P < 0.05; corrected). The low-DHA group did not exhibit greater ACC functional connectivity with any region compared with the high-DHA group. On the CPT-IP task, the low-DHA group had slower reaction time (P = 0.03) which was inversely correlated with erythrocyte DHA among all subjects. DISCUSSION: These data suggest that low-DHA biostatus is associated with reduced event-related functional connectivity in cortical attention networks of typically developing children.


Assuntos
Córtex Cerebral/fisiologia , Ácidos Docosa-Hexaenoicos/sangue , Giro do Cíngulo/fisiologia , Lobo Parietal/fisiologia , Atenção/fisiologia , Criança , Desenvolvimento Infantil , Estudos Transversais , Humanos , Processamento de Imagem Assistida por Computador , Imagem por Ressonância Magnética , Masculino , Tempo de Reação/fisiologia
18.
Neuroscience ; 343: 423-433, 2017 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-27998778

RESUMO

Adolescence is a period of major brain white matter (WM) changes, and membrane lipid metabolism likely plays a critical role in brain WM myelination. Long-chain polyunsaturated fatty acids (LC-PUFAs) are essential components of cell membranes including oligodendrocytes, and LC-PUFA release and turnover in membranes is regulated by phospholipase A2 enzymes. To investigate the role of membrane lipid metabolism in healthy WM myelination across adolescence, the present study examined the relationship between membrane LC-PUFA biostatus, phospholipase A2 activity, and brain WM microstructure in healthy subjects aged 9-20years (n=30). Diffusion tensor imaging (DTI) was performed to measure average fractional anisotropy (FA) and diffusivity (indices sensitive to WM myelination) of nine major cerebral WM tracts. Blood samples were collected to measure erythrocyte membrane fatty acid concentrations and plasma intracellular phospholipase A2 activity (inPLA2). Plasma inPLA2 activity showed a significant U-curved association with WM radial diffusivity, and an inverted U-curved association with WM FA, independent of age. A significant positive linear correlation was observed between docosahexaenoic acid concentration and axial diffusivity in the corpus callosum. These findings suggest that there may be optimal physiological inPLA2 activity levels associated with healthy WM myelination in late childhood and adolescence. Myelination may be mediated by cleavage of docosahexaenoic acid from membrane phospholipids by inPLA2. These findings have implications for our understanding of the role of LC-PUFA homeostasis in myelin-related neurodevelopmental disorders.


Assuntos
Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Ácidos Docosa-Hexaenoicos/metabolismo , Fosfolipases A2/sangue , Substância Branca/crescimento & desenvolvimento , Substância Branca/metabolismo , Adolescente , Encéfalo/diagnóstico por imagem , Criança , Imagem de Difusão por Ressonância Magnética , Imagem de Tensor de Difusão , Ácido Eicosapentaenoico/metabolismo , Eritrócitos/metabolismo , Feminino , Humanos , Masculino , Bainha de Mielina/metabolismo , Fatores Sexuais , Substância Branca/diagnóstico por imagem , Adulto Jovem
19.
J Am Acad Child Adolesc Psychiatry ; 55(11): 980-989, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27806866

RESUMO

OBJECTIVE: To examine prefrontal and amygdala activation during emotional processing in youth with or at varying risk for developing mania to identify candidate central prodromal risk biomarkers. METHOD: Four groups of medication-free adolescents (10-20 years old) participated: adolescents with first-episode bipolar I disorder (BP-I; n = 32), adolescents with a parent with bipolar disorder and a depressive disorder (at-risk depressed [ARD]; n = 32), healthy adolescents with a parent with bipolar disorder (at-risk healthy [ARH]; n = 32), and healthy adolescents with no personal or family history of psychiatric illness (healthy comparison [HC]; n = 32). Participants underwent functional magnetic resonance imaging while performing a continuous performance task with emotional and neutral distracters. Region-of-interest analyses were performed for the bilateral amygdala and for subregions of the ventrolateral prefrontal cortex and anterior cingulate cortex. RESULTS: Overall, no group differences in bilateral amygdala and ventrolateral prefrontal cortex (Brodmann area [BA] 45/47) activation during emotional or neutral stimuli were observed. The BP-I group exhibited lower right pregenual anterior cingulate cortex activation compared with the HC group, and activation in the left BA 44 was greater in the ARH and ARD groups compared with the HC group. BP-I and ARD groups exhibited blunted activation in the right BA 10 compared with the ARH group. CONCLUSION: During emotional processing, amygdala and ventrolateral prefrontal cortex (BA 45/47) activation does not differ in youth with or at increasing risk for BP-I. However, blunted pregenual anterior cingulate cortex activation in first-episode mania could represent an illness biomarker, and greater prefrontal BA 10 and BA 44 activations in at-risk youth could represent a biomarker of risk or resilience warranting additional investigation in prospective longitudinal studies.


Assuntos
Tonsila do Cerebelo/fisiopatologia , Transtorno Bipolar/fisiopatologia , Filho de Pais Incapacitados , Córtex Pré-Frontal/fisiopatologia , Adolescente , Adulto , Tonsila do Cerebelo/diagnóstico por imagem , Transtorno Bipolar/diagnóstico por imagem , Criança , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Córtex Pré-Frontal/diagnóstico por imagem , Risco , Adulto Jovem
20.
Psychiatry Res ; 246: 803-807, 2016 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-27825781

RESUMO

Bipolar I disorder is associated with deficits in the long-chain omega-3 fatty acid docosahexaenoic acid (DHA, 22:6n-3). The final biosynthesis of DHA is mediated by peroxisomes, and some heritable peroxisomal disorders are associated with DHA deficits and progressive psychopathology. The present cross-sectional study investigated whether medication-free asymptomatic and symptomatic youth with familial risk for bipolar I disorder exhibit impaired peroxisomal function using a comprehensive diagnostic blood panel. Measures of peroxisomal impairment included plasma concentrations of very long-chain fatty acids (VLCFA), branched-chain fatty acids, bile acid intermediates, and pipecolic acid, and erythrocyte plasmalogen and DHA levels. Compared with healthy subjects, significant erythrocyte DHA deficits were observed in ultra-high risk and first-episode bipolar groups, and there was a trend for lower DHA in the high-risk group. There were no significant group differences for any other measure of peroxisomal function, and erythrocyte DHA levels were not correlated with any measure of peroxisome function. These results indicate that familial risk for bipolar I disorder is not associated with impaired peroxisomal function, and that DHA deficits associated with familial bipolar disorder are not attributed to heritable defects in peroxisomal function.


Assuntos
Transtorno Bipolar/sangue , Ácidos Docosa-Hexaenoicos/sangue , Ácidos Docosa-Hexaenoicos/deficiência , Peroxissomos/metabolismo , Adolescente , Biomarcadores/sangue , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/genética , Criança , Estudos Transversais , Ácidos Docosa-Hexaenoicos/genética , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-3/deficiência , Ácidos Graxos Ômega-3/genética , Feminino , Humanos , Masculino , Peroxissomos/genética , Plasmalogênios/sangue , Plasmalogênios/genética , Fatores de Risco , Adulto Jovem
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