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BACKGROUND: The leopard coral grouper (Plectropomus leopardus) is an important economic species in East Asia-Pacific countries. To meet the market demand, leopard coral grouper is facing overfishing and their population is rapidly declining. With the improvement of the artificial propagation technique, the leopard coral grouper has been successfully cultured by Fisheries Research Institute in Taiwan. However, the skin color of farmed individuals is often lacking bright redness. As such, the market price of farmed individuals is lower than wild-type. RESULTS: To understand the genetic mechanisms of skin coloration in leopard coral grouper, we compared leopard coral grouper with different skin colors through transcriptome analysis. Six cDNA libraries generated from wild-caught leopard coral grouper with different skin colors were characterized by using the Illumina platform. Reference-guided de novo transcriptome data of leopard coral grouper obtained 24,700 transcripts, and 1,089 differentially expressed genes (DEGs) were found between red and brown skin color individuals. The results showed that nine candidate DEGs (epha2, sema6d, acsl4, slc7a5, hipk1, nol6, timp2, slc25a42, and kdf1) significantly associated with skin color were detected by using comparative transcriptome analysis and quantitative real-time polymerase chain reaction (qRT-PCR). CONCLUSIONS: The findings may provide genetic information for further skin color research, and to boost the market price of farmed leopard coral grouper by selective breeding.
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Antozoos , Lubina , Animales , Lubina/genética , Transcriptoma , Antozoos/genética , Pigmentación de la Piel/genética , Conservación de los Recursos Naturales , Explotaciones Pesqueras , Perfilación de la Expresión GénicaRESUMEN
BACKGROUND: Long-term opioid and amphetamine-type stimulants (ATS) abuse may affect immunological function and impair executive function. We aimed to determine whether biomarkers of inflammation and executive function were associated with substance use in individuals with opioid use disorder (OUD) and ATS use disorder (ATSUD). The interactions between these biomarkers were also explored. METHODS: We assessed plasma cytokines [tumor necrosis factor (TNF)-α, C-reactive protein (CRP), interleukin (IL)-8, IL-6, transforming growth factor (TGF)-ß1, brain-derived neurotrophic factor (BDNF), and executive function in terms of the Wisconsin Card Sorting Test (WCST) and Continuous Performance Test (CPT) in OUD and ATSUD patients and healthy controls (HC). OUD and ATSUD patients were followed for 12 weeks, and their urine morphine and amphetamine tests, cytokine levels, and executive function were repeatedly measured. RESULTS: We enrolled 483 patients and 145 HC. Plasma TNF-α, CRP, IL-8, IL-6, and BDNF levels and most subscale scores on the WCST and CPT significantly differed between OUD and ATSUD patients and HC. Increased TNF-α levels and more perseveration error on the WCST were significantly associated with more urine drug-positive results and less abstinence. Plasma IL-6 and CRP levels were significantly negatively correlated with WCST and CPT performance. CONCLUSION: OUD and ATSUD patients had more inflammation and worse executive function than HC. Inflammatory markers and WCST performance were associated with their urinary drug results, and higher inflammation was associated with poor executive function. Studies on regulating the inflammatory process and enhancing executive function in OUD and ATSUD are warranted.
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Estimulantes del Sistema Nervioso Central , Trastornos Relacionados con Opioides , Humanos , Citocinas , Función Ejecutiva , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Factor de Necrosis Tumoral alfa , Interleucina-6/uso terapéutico , Anfetamina/efectos adversos , Trastornos Relacionados con Opioides/tratamiento farmacológico , Proteína C-Reactiva , Biomarcadores , Inflamación , Estimulantes del Sistema Nervioso Central/efectos adversosRESUMEN
BACKGROUND: Treatment-resistant schizophrenia (TRS) and non-TRS may be associated with different dopaminergic and glutamatergic regulations. The concept of dysregulated glutamatergic concentrations in specific brain regions remains controversial. Herein, we aimed to assess (i) the distribution of the glutamatergic concentration in the brain, (ii) the association between working memory (WM) differences in TRS and non-TRS patients, and (iii) whether an alteration in the glutamate (Glu) level is associated with WM. METHODS: The participants included 38 TRS patients, 35 non-TRS patients, and 19 healthy controls (HCs), all of whom underwent 1.5-Tesla proton magnetic resonance spectroscopy of anterior cingulate cortex (ACC) and medial prefrontal cortex (MPFC). The ratios of glutamatergic neurometabolites to N-acetylaspartate + N-acetyl aspartylglutamate (NAAx) were calculated. Cognitive function was assessed using the Wechsler Adult Intelligence Scales, 4th Edition, which included the working memory index (WMI). RESULT: The TRS patients had a higher glutamate + glutamine (Glx)/NAAx ratio compared to the non-TRS patients and HCs in the ACC, but this was not significantly different in the MPFC. WM was negatively correlated with Glx/NAAx in the ACC among the non-TRS patients, but not in the TRS patients or HCs. CONCLUSIONS: Our findings were consistent with most studies indicating that the glutamatergic concentration in the ACC plays important roles in the classification of TRS and cognition. Our results may provide potential evidence for predictors and treatment response biomarkers in TRS patients. Further research is needed to probe the value using the relationship between Glu and WM as a potential prognostic predictor of schizophrenia.
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Ácido Glutámico , Esquizofrenia , Adulto , Humanos , Espectroscopía de Protones por Resonancia Magnética/métodos , Memoria a Corto Plazo/fisiología , Esquizofrenia/diagnóstico por imagen , Esquizofrenia/tratamiento farmacológico , Esquizofrenia Resistente al Tratamiento , Giro del Cíngulo/diagnóstico por imagen , GlutaminaRESUMEN
BACKGROUND: The hyper-function of the striatal dopamine system has been suggested to underlie key pathophysiological mechanisms in schizophrenia. Moreover, patients have been observed to present a significant elevation of dopamine receptor availability compared to healthy controls. Although it is difficult to measure dopamine levels directly in humans, neurochemical imaging techniques such as single-photon emission computed tomography (SPECT) provide indirect indices of in vivo dopamine synthesis and release, and putative synaptic levels. METHODS: We focused on the role of dopamine postsynaptic regulation using [123I] iodobenzamide (IBZM) SPECT. We compared D2/3 receptor availability between 53 healthy controls and 21 medication-naive patients with recent-onset schizophrenia. RESULT: The mean specific striatal binding showed no significant difference between patients and controls (estimated difference = 0.001; 95% CI -0.11 to 0.11; F = 0.00, df = 1, 69; p = 0.99). There was a highly significant effect of age whereby IBZM binding declined with advancing age [estimated change per decade of age = -0.01(binding ratio); 95% CI -0.01 to -0.004; F = 11.5, df = 1, 69; p = 0.001]. No significant correlations were found between the mean specific striatal binding and psychopathological or cognitive rating scores. CONCLUSIONS: Medication-naïve patients with recent-onset schizophrenia have similar D2/3 receptor availability to healthy controls. We suggest that, rather than focusing exclusively on postsynaptic receptors, future treatments should target the presynaptic control of dopamine synthesis and release.
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Esquizofrenia , Humanos , Recién Nacido , Antagonistas de Dopamina/farmacología , Dopamina/metabolismo , Receptores de Dopamina D2/metabolismo , Cuerpo Estriado , Tomografía Computarizada de Emisión de Fotón Único/métodosRESUMEN
PURPOSE: Loneliness is a subjective feeling by which an individual perceives a lack of closeness in interpersonal relationships. An isolated living status is linked with higher odds of risky health behavior. The conflicting impacts of loneliness and isolated living status on stress-related biomarkers, depressive symptoms, and disability remain unexplained. METHODS: Six hundred twenty-nine participants aged 66.0 (SD=7.3) separated into four groups: "Lonely and Isolated," "Not Lonely, but Isolated," "Lonely, but Not Isolated," and "Neither Lonely, nor Isolated," were retrieved from the Social Environment and Biomarkers of Aging Study conducted in 2000. Follow-up health indicators in 2006 included three stress-related biomarkers, depressive symptoms, and two physical disability indicators. A hierarchical regression was performed for the analysis. RESULTS: Firstly, compared to the "Neither Lonely nor Isolated" group, only the "Lonely, but Not Isolated" participants at baseline retained positive associations with the stress-related biomarkers levels 6 years later (urine cortisol level (B=9.25, 95% CI=3.24-15.27), serum Interleukin-6 level (B=2.76, 95% CI=0.72-4.79) and the serum high sensitivity C-reactive protein (hsCRP) level (B=0.40, 95% CI=0.17-0.62)). However, such associations were not observed in the "Lonely and Isolated" participants. Secondly, only "Lonely and Isolated" participants at baseline were positively associated with depressive symptoms 6 years later (B=1.70, 95% CI=0.11-3.30). Finally, the associations between combinations of loneliness and isolated living status and physical disability were eliminated after adjusting the covariables. CONCLUSION: Four combinations of loneliness and isolated living status were associated with different impacts on stress-related biomarkers, depressive symptoms, and physical disability. Further dynamic investigations are warranted.
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Depresión , Soledad , Anciano , Envejecimiento , Biomarcadores , Depresión/diagnóstico , Humanos , Persona de Mediana Edad , TaiwánRESUMEN
BACKGROUND: It is well-known that attention deficit hyperactivity disorder (ADHD) is associated with changes in the dopaminergic system. However, the relationship between central dopaminergic tone and the blood oxygen level-dependent (BOLD) signal during receipt of rewards and penalties in the corticostriatal pathway in adults with ADHD is unclear. METHODS: Single-photon emission computed tomography with [99mTC]TRODAT-1 was used to assess striatal dopamine transporter (DAT) availability. Event-related functional magnetic resonance imaging was conducted on subjects performing the Iowa Gambling Test. RESULT: DAT availability was found to be associated with the BOLD response, which was a covariate of monetary loss, in the medial prefrontal cortex (r = 0.55, P = .03), right ventral striatum (r = 0.69, P = .003), and right orbital frontal cortex (r = 0.53, P = .03) in adults with ADHD. However, a similar correlation was not found in the controls. CONCLUSIONS: The results confirmed that dopaminergic tone may play a different role in the penalty-elicited response of adults with ADHD. It is plausible that a lower neuro-threshold accompanied by insensitivity to punishment could be exacerbated by the hypodopaminergic tone in ADHD.
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Trastorno por Déficit de Atención con Hiperactividad/diagnóstico por imagen , Conectoma , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Imagen por Resonancia Magnética , Recompensa , Tomografía Computarizada de Emisión de Fotón Único , Adulto , Trastorno por Déficit de Atención con Hiperactividad/metabolismo , Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Femenino , Humanos , Masculino , Compuestos de Organotecnecio , Radiofármacos , TropanosRESUMEN
Background: Repetitive transcranial magnetic stimulation (rTMS) shows potential therapeutic effects for individuals with addiction, but few studies have examined individuals with opioid use disorder (OUD).Objectives: We conducted an add-on double-blinded, sham-controlled rTMS feasibility pilot trial to examine OUD participants undergoing methadone maintenance therapy (MMT). The current report focused on the effects of rTMS on (1) craving and heroin use behavior and (2) depression, impulsivity, and attention.Methods: Active or sham rTMS treatment was applied to the left dorsolateral prefrontal cortex (DLPFC) over a total of 11 sessions in 4 weeks (15-Hz frequency, 4 seconds per train, intertrain interval of 26 seconds, 40 trains per session) in OUD participants (ClinicalTrials.gov registration number: NCT03229642). Craving, heroin use severity, urine morphine tests, the Hamilton Depression Rating Scale (HDRS), the Barratt Impulsiveness Scale-11 (BIS-11), and the Continuous Performance Tests (CPTs) were measured.Results: Twenty-two OUD participants were enrolled, of which eleven (8 males) were undergoing active rTMS and nine (8 males) were in the sham rTMS group. After 12 weeks of follow-up, the active rTMS group did not show significantly greater improvements than the sham group with respect to craving, heroin use, or urine morphine test results. However, HDRS scores, BIS-11 attentional subscales, and CPTs commission T-scores (C-TS) were significantly lower in the active rTMS group (P = .003, 0.04, and 0.02, respectively) than in the sham group.Conclusion: Add-on rTMS did not appear to improve heroin use behavior but may have benefitted depressive symptoms, impulse control and attention in OUD participants undergoing MMT.
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Metadona/uso terapéutico , Tratamiento de Sustitución de Opiáceos , Trastornos Relacionados con Opioides/terapia , Estimulación Magnética Transcraneal/métodos , Adulto , China , Ansia , Trastorno Depresivo Mayor/terapia , Femenino , Dependencia de Heroína/terapia , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Abnormal autonomic nervous system (ANS) function may result in poor outcomes in patients with schizophrenia. Altered cardio-respiratory coupling, which indicates suppression of vagal activity, was identified as an important trait in patients with schizophrenia and their unaffected relatives. Heart rate variability (HRV) in standardized bedside reflex tests has been studied, mostly in medicated patients with schizophrenia whose ANS function could be influenced by medication. Our study aimed to explore the autonomic function differences between drug-naïve patients with schizophrenia and healthy individuals during challenge tests combining respiration and HRV analysis. Forty-two drug-naïve patients with schizophrenia were matched with 42 healthy controls in terms of age and gender. Their beat-to-beat blood pressure and heart rate were monitored in the supine position as a survey of ANS function, and the mean heart rate range (MHRR) was measured under deep-breathing challenge. A decreased MHRR, a sensitive sign indicating an impaired parasympathetic response, during the deep-breathing challenge among the drug-naïve patients with schizophrenia was found. Drug-naïve patients with schizophrenia may have a parasympathetic dysfunction in the early stages of schizophrenia before medication is introduced, which could be considered a neurobiological marker in the pathophysiology of schizophrenia.
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Sistema Nervioso Autónomo/fisiopatología , Frecuencia Cardíaca/fisiología , Respiración , Esquizofrenia/fisiopatología , Adulto , Presión Sanguínea/fisiología , Femenino , Humanos , Masculino , Sistema Nervioso Parasimpático/fisiologíaRESUMEN
Research into the association between heart rate variability (HRV) and cognitive function is scarce, particularly with regard to gender differences. HRV in 182 healthy volunteers was assessed by the root mean square of the successive difference (RMSSD) and spectrum analysis, while the Wechsler Memory Scale-Revised (WMS-R) was used to determine memory function. Robust and significant associations were found to exist between HRV (RMSSD and high-frequency HRV) and domains of the WMS-R in females. Caution should therefore be taken to control for gender when conducting studies on the relationships between HRV and cognitive variables.
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Sistema Nervioso Autónomo/fisiología , Frecuencia Cardíaca/fisiología , Memoria/fisiología , Femenino , Voluntarios Sanos , Humanos , Masculino , Pruebas Neuropsicológicas/estadística & datos numéricos , Factores SexualesRESUMEN
BACKGROUND: Bipolar disorder (BD), especially BD-II, is frequently comorbid with alcohol dependence. Because BD-II and alcohol dependence are neurodegenerative disorders, agents with anti-inflammatory and neurotrophic effects might provide effective therapy. We investigated whether add-on memantine to regular valproic acid treatment ameliorated clinical symptoms, reduced alcohol use, and cytokine levels, and increased plasma brain-derived neurotrophic factor (BDNF) in BD-II patients with comorbid alcohol dependence. METHODS: In a single-arm 12-week clinical trial, BD-II patients with comorbid alcohol dependence (n = 45) undergoing regular valproic acid treatments were given add-on memantine (5 mg/d). Symptom severity, alcohol use, cytokine (plasma tumor necrosis factor-α and C-reactive protein [CRP], transforming growth factor-ß1 [TGF-ß1], interleukin-8 [IL-8], IL-10), and plasma BDNF levels were regularly assessed. RESULTS: Mean within-group decreases in Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS) scores, alcohol use, CRP, BDNF, and IL-8 levels were significantly different from baseline after 12 weeks of treatment. We found no significant correlation between alcohol use levels and changes in HDRS or YMRS scores. The correlation between reduced alcohol use and reduced TGF-ß1 level was significant (B = 0.003, p = 0.019). CONCLUSIONS: BD-II comorbid with alcohol dependence might benefit from add-on memantine treatment, which significantly reduced clinical severity, alcohol use, and plasma cytokine levels, and increased BDNF levels.
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Alcoholismo/tratamiento farmacológico , Alcoholismo/epidemiología , Trastorno Bipolar/tratamiento farmacológico , Trastorno Bipolar/epidemiología , Memantina/uso terapéutico , Consumo de Bebidas Alcohólicas/tratamiento farmacológico , Alcoholismo/sangre , Antimaníacos/uso terapéutico , Trastorno Bipolar/sangre , Factor Neurotrófico Derivado del Encéfalo/sangre , Comorbilidad , Citocinas/sangre , Diagnóstico Dual (Psiquiatría) , Dopaminérgicos/uso terapéutico , Quimioterapia Combinada , Estudios de Seguimiento , Humanos , Taiwán/epidemiología , Resultado del Tratamiento , Ácido Valproico/uso terapéuticoRESUMEN
OBJECTIVE: Previous studies have indicated that there is dopamine transporter (DAT) dysregulation and P300 abnormality in adults with attention-deficit hyperactivity disorder (ADHD); however, the correlations among the three have not been fully explored. METHODS: A total of 11 adults (9 males and 2 females) with ADHD and 11 age-, sex-, and education-level-matched controls were recruited. We explored differences in DAT availability using single-photon emission computed tomography and P300 wave of event-related potentials between the two groups. The correlation between DAT availability and P300 performance was also examined. RESULTS: DAT availability in the basal ganglia, caudate nucleus, and putamen was significantly lower in the ADHD group. Adults with ADHD had lower auditory P300 amplitudes at the Pz and Cz sites, as well as longer Fz latency than controls. DAT availability was negatively correlated to P300 latency at Pz and Fz. CONCLUSIONS: Adults with ADHD had both abnormal DAT availability and P300 amplitude, suggesting that ADHD is linked to dysfunction of the central dopaminergic system and poor cognitive processes related to response selection and execution.
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Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Potenciales Relacionados con Evento P300 , Potenciales Evocados Auditivos , Adulto , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Encéfalo/fisiopatología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Compuestos de Organotecnecio , Radiofármacos , Tomografía Computarizada de Emisión de Fotón Único , TropanosRESUMEN
OBJECTIVES: We investigated the association of the aldehyde dehydrogenase 2 ( ALDH2) polymorphism (rs671), which is involved with the dopaminergic function, and with changes in cytokine levels and cognitive function, in a 12-week follow-up study in patients with bipolar disorder. METHODS: Patients with a first diagnosis of bipolar disorder were recruited. Symptom severity and levels of plasma cytokines (tumor necrosis factor α, C-reactive protein, interleukin 6 and transforming growth factor ß1) were examined during weeks 0, 1, 2, 4, 8 and 12. Neurocognitive function was evaluated at baseline and endpoint. The ALDH2 polymorphism genotype was determined. RESULTS: A total of 541 patients with bipolar disorder were recruited, and 355 (65.6%) completed the 12-week follow-up. A multiple linear regression analysis showed a significant ( p = 0.000226) association between the ALDH2 polymorphism and changes in C-reactive protein levels. Different aspects of cognitive function improved in patients with different ALDH2 genotypes. Only patients with the ALDH2*1*1 genotype showed significant correlations between improvement of cognitive function and increased transforming growth factor -ß1. CONCLUSION: The ALDH2 gene might influence changes in cytokine levels and cognitive performance in patients with bipolar disorder. Additionally, changes in cytokine levels and cognitive function were correlated only in patients with specific ALDH2 genotypes.
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Aldehído Deshidrogenasa Mitocondrial/genética , Trastorno Bipolar , Disfunción Cognitiva , Citocinas/sangre , Adulto , Antimaníacos/farmacología , Trastorno Bipolar/sangre , Trastorno Bipolar/complicaciones , Trastorno Bipolar/tratamiento farmacológico , Trastorno Bipolar/genética , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/etiología , Disfunción Cognitiva/genética , Disfunción Cognitiva/fisiopatología , Quimioterapia Combinada , Antagonistas de Aminoácidos Excitadores/farmacología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Polimorfismo Genético , Ensayos Clínicos Controlados Aleatorios como Asunto , Adulto JovenRESUMEN
BACKGROUND: Animal studies have demonstrated that oxytocin can influence addiction behaviors and might interact with the dopaminergic system, which is a key component of addiction behaviors. However, related evidence from clinical studies is scarce. The aim of our study was to explore the relationship between plasma oxytocin level and heroin craving among patients receiving methadone maintenance treatment, and to ascertain whether this relationship is moderated by novelty-seeking. METHODS: The study was conducted in a methadone maintenance therapy clinic of a medical center in Taiwan. Seventy-seven patients with heroin addiction were enrolled. Plasma oxytocin was measured using an ELISA kit. Craving was assessed using an established instrument, the Chinese Craving Scale. RESULTS: A significant negative association was found between the plasma oxytocin level and craving score, which remained robust after controlling the effects of social support and low-density lipoprotein cholesterol. An interaction between oxytocin and novelty-seeking indicated that this relationship was stronger among patients with a lower level of novelty-seeking. CONCLUSION: This finding may be taken into account in future studies and may provide a basis for the development of potential treatment for addiction. The effect of oxytocin for the treatment of opioid dependence might be modulated by some psychological factors.
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Ansia/efectos de los fármacos , Dependencia de Heroína/tratamiento farmacológico , Metadona/uso terapéutico , Oxitocina/sangre , Adulto , Conducta Adictiva/tratamiento farmacológico , Femenino , Dependencia de Heroína/rehabilitación , Humanos , Masculino , Tratamiento de Sustitución de Opiáceos , Síndrome de Abstinencia a Sustancias/sangreRESUMEN
BACKGROUND: Dopaminergic dysfunction, namely, dopamine transporter (DAT) availability variations in patients with drug-naive schizophrenia after long-term treatment, is still not well understood. The aims of the study were to explore (i) whether the DAT availability in patients with drug-naive schizophrenia differed after antipsychotic treatment and (ii) whether treatment with different generations of antipsychotics influenced the DAT availability after follow-up for 6 months. METHODS: Twenty-four first-episode, drug-naive patients with schizophrenia were divided into first- and second-generation antipsychotic groups naturalistically. After 6 months of follow-up, 7 patients who received first-generation antipsychotic treatment and 17 patients who received second-generation antipsychotic treatment completed the study. The patients underwent premedication and 6-month follow-up measurements using single-photon emission computed tomography with technetium Tc 99m (Tc) TRODAT-1. Psychopathological evaluations and adverse effects were recorded using appropriate scales. RESULTS: Both of the treatment groups significantly improved according to Positive and Negative Symptoms Scale evaluation. However, no significant difference was noticed between the premedication and 6-month follow-up DAT scans. Nonsignificant differences existed even in the groups of different generations of antipsychotics. CONCLUSIONS: Improvements in psychotic symptoms in patients with schizophrenia may not be influenced by DAT availability, even under treatment with different antipsychotics for a sufficient treatment period.
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Antipsicóticos/farmacología , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Compuestos de Organotecnecio , Evaluación de Resultado en la Atención de Salud , Radiofármacos , Esquizofrenia , Tomografía Computarizada de Emisión de Fotón Único/métodos , Tropanos , Adulto , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/efectos de los fármacos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Esquizofrenia/diagnóstico por imagen , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/metabolismo , Adulto JovenRESUMEN
PURPOSE/BACKGROUND: We previously conducted a randomized, double-blind, controlled, 12-week study evaluating the effect of add-on dextromethorphan (DM), a noncompetitive N-methyl-D-aspartate receptor antagonist, on patients with bipolar disorder (BD) treated using valproate (VPA), which showed negative clinical differences. The genetic variation between each individual may be responsible for interindividual differences. The catechol-O-methyltransferase (COMT) gene has been a candidate gene for BD. In the current study, we investigated whether the COMT Val158Met polymorphism predicts treatment response to VPA + add-on DM and to VPA + placebo. METHODS/PROCEDURES: Patients with BD (n = 309) undergoing regular VPA treatments were randomly assigned to groups given either add-on DM (30 mg/d) (n = 102), DM (60 mg/d) (n = 101), or placebo (n = 106) for 12 weeks. The Hamilton Depression Rating Scale and Young Mania Rating Scale were used to evaluate clinical response during weeks 0, 1, 2, 4, 8, and 12. The genotypes of the COMT Val158Met polymorphism were determined using polymerase chain reaction plus restriction fragment length polymorphism analysis. To adjust for within-subject dependence over repeated assessments, multiple linear regression with generalized estimating equation methods was used. FINDINGS/RESULTS: When stratified by the COMT Val158Met genotypes, significantly greater decreases in Hamilton Depression Rating Scale scores were found in the VPA + DM (30 mg/d) group in patients with the Val/Met genotype (P = 0.008). CONCLUSIONS: We conclude that the COMT Val158Met polymorphism may influence responses to DM (30 mg/d) by decreasing depressive symptoms in BD patients.
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Antimaníacos/farmacología , Trastorno Bipolar/tratamiento farmacológico , Trastorno Bipolar/genética , Catecol O-Metiltransferasa/genética , Dextrometorfano/farmacología , Antagonistas de Aminoácidos Excitadores/farmacología , Evaluación de Resultado en la Atención de Salud , Ácido Valproico/farmacología , Antimaníacos/administración & dosificación , Dextrometorfano/administración & dosificación , Quimioterapia Combinada , Antagonistas de Aminoácidos Excitadores/administración & dosificación , Humanos , Ácido Valproico/administración & dosificaciónRESUMEN
OBJECTIVES: In the elderly, the risk of mortality because of physical illnesses related to anxiety disorders varies with potential confounding influences, including comorbidity with depressive disorders. Our study aimed to explore (i) whether anxiety disorders increase the risk of mortality in the elderly, and (ii) whether the risk of mortality mediated by anxiety and depressive disorders differs between physical illnesses. METHODS: Our longitudinal cohort study included subjects aged over 60 years from the National Health Insurance Research Database. One thousand and eighty-six subjects with anxiety disorders and 50 554 control subjects without anxiety disorders were included. Propensity score-matched cohorts were analyzed. Rate ratios (RRs) were calculated for the risk of mortality associated with different physical illnesses with comorbidities of either anxiety disorders only or both anxiety and depressive disorders. RESULTS: The risk of mortality in patients with anxiety disorders was significantly higher than controls, and was even higher when subjects had both anxiety and depressive disorder comorbidities. Furthermore, the co-occurrence of anxiety and depressive disorders increased the risk of mortality in elderly patients with ischemic heart diseases (RR = 1.60; 95% CI: 1.14-2.24). CONCLUSIONS: Coexisting anxiety and depressive disorders could increase the risk of mortality in elderly patients with ischemic heart diseases. Copyright © 2016 John Wiley & Sons, Ltd.
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Trastornos de Ansiedad/complicaciones , Trastorno Depresivo/complicaciones , Isquemia Miocárdica/mortalidad , Anciano , Anciano de 80 o más Años , Trastornos de Ansiedad/epidemiología , Estudios de Casos y Controles , Comorbilidad , Bases de Datos Factuales , Trastorno Depresivo/epidemiología , Femenino , Humanos , Incidencia , Modelos Logísticos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Factores de Riesgo , Taiwán/epidemiologíaRESUMEN
AIM: Clozapine-associated fever is common but the specific cytokine changes and treatment durations that may cause fever remain unknown. We investigated the association between inflammatory cytokine changes and clozapine-induced fever in patients who were treated with clozapine. METHODS: Forty-three patients with schizophrenia or schizoaffective disorder, diagnosed by using the Chinese Version of the Mini International Neuropsychiatric Interview, were treated with clozapine for the first time (first-time use group, n = 22) or for more than 6 months (long-term use group, n = 21). The Positive and Negative Syndrome Scale, tympanic temperature, and levels of tumor necrosis factor-α (TNF-α), interferon-γ (INF-γ), interleukin-2 (IL-2), and interleukin-6 (IL-6) were determined at baseline and weeks 1, 2, 3, 4, and 6. A multiple linear regression with generalized estimating equation methods was used to analyze the association between the changes in the cytokine levels and clozapine-induced fever in the different groups. RESULTS: The IL-6 level changes were significantly different between the two groups (P = 0.04). In the first-time use group, the fever rate was increased (47.1%) compared with the long-term use group (5.6%, P = 0.005). Moreover, in these patients, the TNF-α, INF-γ, IL-2, and IL-6 levels were significantly (P < 0.001) different from patients who did not develop a fever. An interaction effect with the different treatment duration groups and fever development was only significant for IL-6 (P < 0.001). CONCLUSION: Patients who were treated with clozapine for the first time have an increased rate of developing a fever, and IL-6 might have a specific role in the interaction effect between treatment duration and fever development.
Asunto(s)
Clozapina/efectos adversos , Fiebre/inducido químicamente , Interferón gamma/sangre , Interleucina-2/sangre , Interleucina-6/sangre , Factor de Necrosis Tumoral alfa/sangre , Adulto , Antipsicóticos/efectos adversos , Femenino , Fiebre/sangre , Humanos , Masculino , Estudios Prospectivos , Adulto JovenRESUMEN
OBJECTIVE: Emerging evidence suggests that inflammation and neurodegeneration underlies bipolar disorder. To investigate biological markers of cytokines and brain-derived neurotrophic factor between bipolar I, bipolar II, and other specified bipolar disorder with short duration hypomania may support the association with inflammatory dysregulation and bipolar disorder and, more specifically, provide evidence for other specified bipolar disorder with short duration hypomania patients were similar to bipolar II disorder patients from a biological marker perspective. METHODS: We enrolled patients with bipolar I disorder (n=234), bipolar II disorder (n=260), other specified bipolar disorder with short duration hypomania (n=243), and healthy controls (n=140). Their clinical symptoms were rated using the Hamilton Depression Rating Scale and Young Mania Rating Scale. Inflammatory cytokine (tumor necrosis factor-α, C-reactive protein, transforming growth factor-ß1, and interleukin-8) and brain-derived neurotrophic factor levels were measured in each group. Multivariate analysis of covariance and linear regression controlled for possible confounders were used to compare cytokine and brain-derived neurotrophic factor levels among the groups. RESULTS: Multivariate analysis of covariance adjusted for age and sex and a main effect of diagnosis was significant (P<.001). Three of the 5 measured biomarkers (tumor necrosis factor-α, transforming growth factor-ß1, and interleukin-8) were significantly (P=.006, .01, and <.001) higher in all bipolar disorder patients than in controls. Moreover, covarying for multiple associated confounders showed that bipolar I disorder patients had significantly higher IL-8 levels than did bipolar II disorder and other specified bipolar disorder with short duration hypomania patients in multivariate analysis of covariance (P=.03) and linear regression (P=.02) analyses. Biomarkers differences between bipolar II disorder and other specified bipolar disorder with short duration hypomania patients were nonsignificant. CONCLUSION: The immunological disturbance along the bipolar spectrum was most severe in bipolar I disorder patients. Other specified bipolar disorder with short duration hypomania patients and bipolar II disorder patients did not differ in these biological markers.
Asunto(s)
Trastorno Bipolar/sangre , Factor Neurotrófico Derivado del Encéfalo/sangre , Proteína C-Reactiva/metabolismo , Interleucina-8/sangre , Factores de Crecimiento Transformadores/sangre , Factor de Necrosis Tumoral alfa/sangre , Adulto , Biomarcadores/sangre , Biomarcadores/metabolismo , Trastorno Bipolar/diagnóstico , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Adulto JovenRESUMEN
BACKGROUND: Different drug dependencies may have unique genetic vulnerabilities. Changes in serotonin availability and function have been linked to addiction. We investigated whether 2 serotonergic polymorphisms, TPH1 A218C (rs1800532) and 5-HTT-linked promoter region (5-HTTLPR) (rs25531), are differently associated with alcohol or opiate dependence. METHODS: Alcohol-dependent patients (n = 292), opiate-dependent patients (n = 309), and healthy controls (n = 301) were recruited from the Han Chinese population in Taiwan. Genotypes of TPH1 A218C and 5-HTTLPR polymorphisms were analyzed using a polymerase chain reaction with restriction fragment length polymorphism. RESULTS: The genotype frequencies of the TPH1 A218C polymorphisms were not significantly different in the 3 groups. The genotype frequencies of the 5-HTTLPR S+ (S/S, S/LG, LG/LG) polymorphisms were significantly higher in opiate-dependent patients (x03C7;2 = 8.77, p = 0.01), but not after controlling for the covariates of age, gender, and interaction effect in logistic regression analysis. Moreover, there was a significant interaction between the TPH1 A218C A/C and 5-HTTLPR S+ gene polymorphisms in opiate-dependent (OR 2.72, p = 0.01), but not in alcohol-dependent patients. CONCLUSIONS: Our data suggested that there may be a differential genetic vulnerability in serotonergic genes for alcohol and opiate addiction. However, replications of our findings are still needed.