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INTRODUCTION: Hypercholesterolemia is associated with increased inflammation and impaired serotonin neurotransmission, potentially contributing to depressive symptoms. However, the role of statins, particularly pitavastatin, in modulating serotonin transporter (SERT) function within this context remains underexplored. This study aimed to investigate whether pitavastatin counteracts the neurobiological effects of hypercholesterolemia. METHODS: Low-density lipoprotein receptor knockout (LDLR-/-) mice on a C57BL/6 background were assigned to three groups: a control group fed a standard chow diet, a group fed a high-fat diet (HFD), and a third group fed a high-fat diet supplemented with pitavastatin (HFD + Pita). We evaluated the effects of HFD with or without pitavastatin on lipid profiles, inflammatory markers, and SERT availability using small-animal positron emission tomography (PET) scans with the radioligand 4-[18F]-ADAM over a 20-week period. RESULTS: Pitavastatin treatment in HFD-fed mice significantly reduced both total cholesterol and LDL cholesterol levels in HFD-fed mice compared to those on HFD alone. Elevated inflammatory markers such as IL-1α, MCP-1/CCL2, and TNF-α in HFD mice were notably decreased in the HFD + Pita group. PET scans showed reduced SERT availability in the brains of HFD mice; however, pitavastatin improved this in brain regions associated with mood regulation, suggesting enhanced serotonin neurotransmission. Additionally, the sucrose preference test showed a trend towards increased preference in the HFD + Pita group compared to the HFD group, indicating a potential reduction in depressive-like behavior. CONCLUSION: Our findings demonstrate that pitavastatin not only lowers cholesterol and reduces inflammation but also enhances SERT availability, suggesting a potential role in alleviating depressive symptoms associated with hypercholesterolemia. These results highlight the multifaceted benefits of pitavastatin, extending beyond its lipid-lowering effects to potentially improving mood regulation and neurotransmitter function.
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Dieta Alta en Grasa , Hipercolesterolemia , Ratones Endogámicos C57BL , Quinolinas , Proteínas de Transporte de Serotonina en la Membrana Plasmática , Animales , Quinolinas/farmacología , Quinolinas/uso terapéutico , Hipercolesterolemia/tratamiento farmacológico , Hipercolesterolemia/metabolismo , Proteínas de Transporte de Serotonina en la Membrana Plasmática/metabolismo , Proteínas de Transporte de Serotonina en la Membrana Plasmática/genética , Ratones , Dieta Alta en Grasa/efectos adversos , Masculino , Ratones Noqueados , Receptores de LDL/metabolismo , Receptores de LDL/genética , Tomografía de Emisión de Positrones , LDL-Colesterol/sangre , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Encéfalo/diagnóstico por imagen , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéuticoAsunto(s)
Accidentes por Caídas , Enfermedad por Cuerpos de Lewy , Quinolonas , Tiofenos , Humanos , Enfermedad por Cuerpos de Lewy/tratamiento farmacológico , Enfermedad por Cuerpos de Lewy/psicología , Quinolonas/uso terapéutico , Tiofenos/uso terapéutico , Tiofenos/administración & dosificación , Anciano , Masculino , Femenino , Antipsicóticos/uso terapéutico , Anciano de 80 o más Años , Resultado del TratamientoRESUMEN
BACKGROUND: Obstructive sleep apnea (OSA) and alcohol-related diseases (ARDs), including alcohol use disorder, alcohol-related psychiatric disorders, alcoholic liver disease, alcoholic polyneuropathy alcoholic cardiomyopathy, and alcoholic gastritis, are both highly prevalent conditions. Alcohol consumption is associated with a higher risk of sleep apnea. However, whether OSA increases the risk of ARD has not, as yet, been studied comprehensively. Our study aimed to determine whether OSA increases the subsequent risk of ARD. METHODS: This study utilized the data from Taiwan's National Health Insurance Database between 2000 and 2015. We identified 7722 individuals newly diagnosed with OSA and randomly selected sex-, age-, and index date-matched (1:3) 22,166 controls without OSA, with a total of 29,888 subjects. We used the Fine and Gray's survival analysis to estimate the effects of OSA on ARD. RESULTS: The OSA cohort had an adjusted hazard ratio of subsequent ARDs as 1.486 (95% Confidence Interval: 1.301-1.698), when comparing the cohort without OSA. The Kaplan-Meier analysis showed that the cumulative incidence of ARDs was significantly higher in the OSA cohort than in the controls in the first year of follow-up, till the end of the follow-up. A post-hoc analysis showed that OSA was associated with alcohol use disorder, alcohol-related psychiatric disorders, and alcoholic liver disease, but not alcoholic polyneuropathy, alcoholic cardiomyopathy, and alcoholic gastritis. The use of psychoactive medication, including the sedative-hypnotics, antidepressants or antipsychotics were associated with a lower risk of ARDs. CONCLUSIONS: Our study demonstrates that the OSA patients are at a higher risk of developing ARDs.
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Trastornos Relacionados con Alcohol , Alcoholismo , Gastritis , Hepatopatías Alcohólicas , Síndrome de Dificultad Respiratoria , Apnea Obstructiva del Sueño , Humanos , Consumo de Bebidas Alcohólicas , Trastornos Relacionados con Alcohol/complicaciones , Trastornos Relacionados con Alcohol/epidemiología , Alcoholismo/complicaciones , Alcoholismo/epidemiología , Estudios de Cohortes , Gastritis/complicaciones , Incidencia , Hepatopatías Alcohólicas/complicaciones , Síndrome de Dificultad Respiratoria/complicaciones , Estudios Retrospectivos , Factores de Riesgo , Apnea Obstructiva del Sueño/complicaciones , Taiwán/epidemiología , Masculino , FemeninoRESUMEN
OBJECTIVE: Atypical antipsychotic-induced hyponatremia has been reported in patients with psychiatric disorders. To date, hyponatremia due to lurasidone, an atypical antipsychotic approved for the treatment of schizophrenia and bipolar depression, has never been reported. CASE REPORT: A female patient with bipolar depression and a history of subdural hematoma experienced a rapid onset of hyponatremia after the initiation of low-dose lurasidone. The hyponatremia worsened after the dose of lurasidone was increased and resolved only after lurasidone was ceased. According to the Naranjo Adverse Drug Reaction Probability Scale, this case report scores 6 as a possible drug reaction between lurasidone and hyponatremia. RESULTS: Based on laboratory results, the syndrome of inappropriate antidiuretic hormone secretion and thyroid or adrenal dysfunction as differential diagnoses were excluded. Lurasidone-induced polydipsia complicated by hyponatremia was confirmed. Lurasidone was subsequently discontinued. The sodium level returned to normal within 1 week without any sodium supplementation. CONCLUSIONS: This case report highlighted that low-dose lurasidone may induce polydipsia complicated by hyponatremia. Physicians should be aware of the adverse reactions of hyponatremia associated with lurasidone, particularly in patients with a history of intracranial hemorrhage.
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Antipsicóticos , Trastorno Bipolar , Hiponatremia , Antipsicóticos/efectos adversos , Trastorno Bipolar/complicaciones , Trastorno Bipolar/tratamiento farmacológico , Femenino , Humanos , Hiponatremia/inducido químicamente , Clorhidrato de Lurasidona/efectos adversos , Polidipsia/tratamiento farmacológicoRESUMEN
Pisa syndrome (PS) is a rare lateral truncal dystonia that is related to dopamine-acetylcholine imbalances, and most cases develop during antipsychotic treatment. Here, we report a case of PS that developed during switching to new antipsychotics and titrating lithium, and PS was aggravated when the lithium dose was increased. Truncal deviation was not relieved with switching back to prior antipsychotics or by discontinuation of all antipsychotics. Pisa syndrome resolved only after discontinuing the lithium treatment. This is the first report of dose-dependent effects of lithium treatment on the aggravation of PS, which may be related to dose-related effects on dopaminergic and cholinergic transmission.
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Antipsicóticos/administración & dosificación , Distonía/inducido químicamente , Distonía/tratamiento farmacológico , Litio/administración & dosificación , Antipsicóticos/efectos adversos , Relación Dosis-Respuesta a Droga , Discinesia Inducida por Medicamentos/tratamiento farmacológico , Humanos , Litio/efectos adversos , Masculino , Persona de Mediana Edad , Olanzapina/administración & dosificación , SíndromeRESUMEN
Exposure to stress not only increases the vulnerability to heroin dependence (HD) but also provokes relapse. The etiology of HD and the role of life stress remain unclear, but prior studies suggested that both genetic and environmental factors are important. Opioid related genes, including OPRM1, OPRD1, OPRK1, and POMC, are obvious candidates for HD. Therefore, this study was conducted to explore whether the genetic polymorphisms of the candidates could affect vulnerability to HD and response to life stress in patients with HD. Ten polymorphisms of the opioid related genes were analyzed in 801 patients and 530 controls. The Life Event Questionnaire was used to assess the perspective and response to life stress in the past year. The genotype distribution and allelic frequency analyses showed that the minor C allele of rs2234918 in OPRD1 is over-represented in the HD group (Pâ¯=â¯.006 and Pâ¯=â¯.002, respectively). This finding was further confirmed by logistic regression analysis, showing that C allele carriers have a 1.42 times greater risk for HD compared to T/T homozygotes. A subgroup of 421 patients and 135 controls were eligible for life stress assessment. Patients with HD have a higher occurrence of negative events (No), negative events score (Ns), and average negative event score (Na) than those of controls (all Pâ¯<â¯.001), but there was no difference regarding positive recent events between the two groups. Gene-stress assessment in the HD group showed that T/T homozygotes of OPRD1 rs2236857 have more severe stress than C allele carriers (Ns, Pâ¯=â¯.004 and Na, Pâ¯=â¯.047). Our results indicate that the OPRD1 gene may not only play a role in the pathogenesis of HD but also affect the response to life stress among patients with HD in our Han Chinese population. Patients with the risk genotype may need additional psychosocial intervention for relapse prevention.
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Predisposición Genética a la Enfermedad , Dependencia de Heroína/genética , Dependencia de Heroína/psicología , Polimorfismo de Nucleótido Simple , Receptores Opioides delta/genética , Estrés Psicológico/genética , Adulto , Pueblo Asiatico/genética , Estudios de Casos y Controles , China , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Haplotipos , Dependencia de Heroína/complicaciones , Heterocigoto , Homocigoto , Humanos , Masculino , Estrés Psicológico/complicacionesRESUMEN
Amphetamine exposure impacts on innate and adaptive immunity and DRD3 may modulate the effect of amphetamine on the immune response. We assessed the immune-cytokine markers in 72 female patients with amphetamine dependence (AD) at baseline and after 4-week drug abstinence and in 51 healthy women. Multiplex magnetic bead assay was used to measure the plasma cytokine expression level simultaneously in all participants and DRD3 rs6280 polymorphism was genotyped in patients. We demonstrated an increase of the T helper 1 (Th1) cytokines (IL-2), Th2 cytokines (IL-4, IL-5, IL-6 and IL-10) and other cytokines (IL-1ß) in the entire AD cohort. A similar cytokine pattern, along with a significantly decreased IL-8 and IL-10 levels was observed after 4-week abstinence. Among AD patients with DRD3 rs6280 TT genotype, the cytokine expression profile was consistent with total AD cohort at baseline and revealed a significant down-regulated plasma level of the Th1, Th2, and other cytokines except for IL-6 after 4-week abstinence. In AD group with DRD3 rs6280 C allele carrier, we found IL-2 level was significantly higher than healthy controls at baseline and remained higher, accompanied with a borderline increase in IL-4, IL-6 and IL-1ß levels after 4-week abstinence. Our results suggest that chronic use of amphetamine increased both pro- and anti-inflammatory cytokines in AD patients, indicating the immune imbalance that may persist for 4 weeks or more. Besides, DRD3 rs6280 TT genotype may be associated with favorable recovery in general inflammatory cytokines during period of abstinence.
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Inmunidad Adaptativa/efectos de los fármacos , Inmunidad Innata/efectos de los fármacos , Receptores de Dopamina D3/genética , Adulto , Alelos , Trastornos Relacionados con Anfetaminas/complicaciones , Trastornos Relacionados con Anfetaminas/genética , Citocinas/genética , Femenino , Frecuencia de los Genes/genética , Genotipo , Humanos , Inflamación/genética , Interleucina-10/análisis , Interleucina-10/sangre , Interleucina-2/análisis , Interleucina-2/sangre , Interleucina-4/análisis , Interleucina-4/sangre , Interleucina-5/análisis , Interleucina-5/sangre , Interleucina-6/análisis , Interleucina-6/sangre , Células TH1 , Células Th2RESUMEN
The dopamine receptor D3 (DRD3) gene, one of the candidate genes for amphetamine dependence (AD), is involved in the mesolimbic dopaminergic system, implicated as the underlying mechanism of addiction. Our case-control study aimed to investigate whether the DRD3 gene is associated with the susceptibility to AD and specific personality traits in AD patients. A total of 1060 unrelated Han Chinese subjects (559 AD patients and 501 controls) were screened using the same assessment tool and genotyped for eight DRD3 polymorphisms. All patients met the DSM-IV-TR criteria for AD, and personality traits of 539 were assessed using a Tridimensional Personality Questionnaire. Furthermore, AD individuals were divided into four clinical subgroups based on gender and psychosis status, to reduce the clinical heterogeneity. We found that the ATA haplotype combination for SNPs rs324029, rs6280, and rs9825563, respectively, was significantly associated with total AD patients (p = 0.0003 after 10,000 permutations). Similar results were observed in the both male and non-psychosis subgroup but not in other subgroups. In addition, DRD3 rs9825563 may influence onset age of drug use, partially mediated by novelty seeking in the non-psychosis AD group. In conclusion, DRD3 is a potential genetic factor in the susceptibility to AD and is associated with onset age of drug use through interaction with novelty seeking in a specific patient group in the Han Chinese population.
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Trastornos Relacionados con Anfetaminas/genética , Trastornos Relacionados con Anfetaminas/psicología , Comportamiento de Búsqueda de Drogas , Polimorfismo de Nucleótido Simple/genética , Receptores de Dopamina D3/genética , Adulto , Edad de Inicio , Pueblo Asiatico/etnología , Pueblo Asiatico/genética , Femenino , Genotipo , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Personalidad , Inventario de Personalidad , Estudios Retrospectivos , Taiwán , Adulto JovenRESUMEN
Inflammatory processes play a crucial role in the pathophysiology of depression, and identifying the specific cytokines targeted by different antidepressants is important for personalized treatment. The aims of this study were to examine whether venlafaxine and paroxetine cause different immunomodulatory effects when used to treat patients with major depression and to clarify the relationships between plasma cytokine levels and the therapeutic effectiveness of these drugs. A total of 91 Han Chinese patients with major depression completed the 8-week paroxetine or venlafaxine treatment and 90 healthy controls were recruited. A multiplex assay was used to measure cytokines levels in patients with major depression before and after an 8-week venlafaxine and paroxetine treatment. Cytokine levels were measured in healthy controls at the baseline. The 21-item Hamilton Depression Rating Scale was used to assess the changes in psychopathological symptoms from the baseline to the end point in each patient. Venlafaxine treatment caused greater decreases in the levels of interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin 4 (IL-4), IL-5, IL-1ß, and IL-8 than did paroxetine. Paroxetine treatment increased the levels of proinflammatory cytokines IFN-γ, TNF-α, and IL-6 and decreased Th2 cytokine levels. After paroxetine treatment, IL-6 levels increased more in the non-remitter group than in the remitter group. In the remitter group, IL-4 and IL-5 levels decreased to values seen in the healthy controls. After venlafaxine treatment in both the remitter and non-remitter groups, IL-1ß levels decreased to values seen in the healthy controls. Our results suggest that venlafaxine and paroxetine have different immunomodulatory properties and that venlafaxine has greater anti-inflammatory effects than paroxetine.
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Trastorno Depresivo Mayor/tratamiento farmacológico , Paroxetina/farmacología , Clorhidrato de Venlafaxina/farmacología , Adulto , Antiinflamatorios/farmacología , Antidepresivos/uso terapéutico , Antidepresivos de Segunda Generación/uso terapéutico , Estudios de Casos y Controles , China , Citocinas/análisis , Citocinas/sangre , Depresión/tratamiento farmacológico , Trastorno Depresivo Mayor/metabolismo , Femenino , Humanos , Interleucina-1beta/análisis , Interleucina-1beta/sangre , Interleucina-1beta/efectos de los fármacos , Interleucina-6/análisis , Interleucina-6/sangre , Masculino , Persona de Mediana Edad , Paroxetina/metabolismo , Paroxetina/uso terapéutico , Escalas de Valoración Psiquiátrica , Resultado del Tratamiento , Clorhidrato de Venlafaxina/metabolismo , Clorhidrato de Venlafaxina/uso terapéuticoRESUMEN
Dopaminergic dysfunction has an important role in the pathoetiology of alcohol dependence (AD). The purpose of this study was to determine whether the solute carrier family 6 member 3 (SLC6A3) gene (also known as the dopamine transporter DAT gene) was associated with AD, and whether variants in the SLC6A3 locus were associated with specific personality traits in patients with AD. Sixteen polymorphisms in SLC6A3 were analyzed using 637 patients with AD and 523 healthy controls. To reduce clinical heterogeneity, patients were classified into two subgroups: early-onset AD (EOAD) and late-onset AD (LOAD). The Tridimensional Personality Questionnaire was used to assess the personality traits novelty seeking (NS) and harm avoidance (HA) in the patients with AD. Using allele frequency and genotype distribution comparisons and logistic regression analysis, we found evidence of association between rs6350 and AD (P < 0.05). Following subgroup analysis, we confirmed evidence of an association in patients with LOAD (P = 0.003), but not in patients with EOAD. Heterozygous carriers of the A allele have a nearly 3 times greater risk to develop LOAD compared to individuals who do not have an A allele. Although we found that patients with AD had higher NS and HA scores compared to controls (P < 0.001), we did not find evidence of association between SLC6A3 polymorphisms and either NS or HA in patients with AD using linear regression analysis. The findings from our study indicate that the SLC6A3 gene may have a role in susceptibility to late-onset AD in the Han Chinese population.
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Alcoholismo/genética , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/genética , Polimorfismo de Nucleótido Simple , Adulto , Edad de Inicio , Estudios de Casos y Controles , China , Conducta Exploratoria , Femenino , Heterocigoto , Humanos , Masculino , Persona de Mediana Edad , Asunción de RiesgosRESUMEN
Alcohol dependence (AD) leads to altered innate and adaptive immune responses, and frequently co-occurs with inflammation. Therefore, inflammatory cytokines potentially play a crucial role in the development of alcohol-related illnesses. This study evaluated changes in plasma cytokine concentrations, liver function, cravings, depression severity, and cognitive function in male patients with AD, during the course of an alcohol-detoxification program. A total of 78 male patients with AD were recruited for a conservative detoxification program; and cytokine levels, depressive score, and cognitive impairment applying the Trail Making Test (TMT) were evaluated during early withdrawal (baseline) and after 4 weeks of abstinence from alcohol. Healthy volunteers (86 males) were also recruited as controls. Inflammatory cytokine expression in all participants was assessed by multiplex magnetic bead assay. AD patients during early withdrawal demonstrated higher cytokine levels than the healthy controls (P≤0.001 for all cytokines). However, the levels of cytokine expression were significantly lower after 4 weeks of abstinence from alcohol (P≤0.001, except for IL-1ß and IL-5). Higher liver function marker levels, depressive severity, and TMT times were observed in patients at the beginning of the detoxification program than in healthy controls. Fortunately, these functions significantly ameliorated after 4 weeks of abstinence. (P≤0.001). Levels of circulating cytokines, liver function, and cognitive function may markers of alcohol use disorder.
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Abstinencia de Alcohol , Alcoholismo , Disfunción Cognitiva , Citocinas/sangre , Inflamación , Síndrome de Abstinencia a Sustancias/fisiopatología , Transferasas/sangre , Adulto , Alcoholismo/sangre , Alcoholismo/enzimología , Alcoholismo/fisiopatología , Disfunción Cognitiva/sangre , Disfunción Cognitiva/enzimología , Disfunción Cognitiva/fisiopatología , Humanos , Inflamación/sangre , Inflamación/enzimología , Inflamación/fisiopatología , Masculino , Persona de Mediana Edad , Síndrome de Abstinencia a Sustancias/sangre , Síndrome de Abstinencia a Sustancias/enzimología , Prueba de Secuencia AlfanuméricaRESUMEN
Novelty seeking (NS) is a core personality trait that primes the susceptibility to drug addiction. Striatal dopamine activity contributes to cognitive flexibility, an important cognitive strategy to inhibit impulsivity and compulsive drug-seeking behavior. Evidence supports the association between dopamine and NS. Opioid-dependent patients show higher levels of NS, and repeated opioid exposure can cause cognitive deficits including poor cognitive flexibility and impaired impulse control. However, in opioid-dependent patients, the link between NS, striatal dopamine activity, and cognitive flexibility is still unclear. We recruited 22 opioid-dependent individuals and 30 age- and sex-matched healthy controls. Single-photon emission computed tomography with [99mTc]TRODAT-1 as a ligand was used to measure the striatal dopamine transporter (DAT) availability. The Trail Making Test (TMT) was performed to assess cognitive flexibility. Cloninger's Tridimensional Personality Questionnaire (TPQ) was used to measure NS. We found that in opioid-dependent patients, the striatal DAT availability was lower and negatively associated with TMT Part B÷Part A. Moreover, an inverted-U shape significantly matched the scores of NS as a function of the striatal DAT availability, with maximum NS potential in the midrange of the DAT availability. An extra sum-of-squares F test was conducted, indicating that a quadratic model fitted the association between the DAT and NS better than a linear model did. In brief, in opioid-dependent patients, the striatal DAT availability is nonlinearly linked to NS and linearly linked to cognitive flexibility. The role of the striatal DAT in the transition from controlled to compulsive opioid use warrants further research.
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Analgésicos Opioides/toxicidad , Trastornos del Conocimiento/etiología , Cuerpo Estriado/metabolismo , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Conducta Exploratoria/fisiología , Trastornos Relacionados con Opioides/complicaciones , Adulto , Cuerpo Estriado/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos Relacionados con Opioides/diagnóstico por imagen , Trastornos Relacionados con Opioides/patología , Trastornos Relacionados con Opioides/psicología , Compuestos de Organotecnecio/metabolismo , Inventario de Personalidad , Estudios Retrospectivos , Estadísticas no Paramétricas , Taiwán , Tomografía Computarizada de Emisión de Fotón Único , Tropanos/metabolismoRESUMEN
Catechol-O-methyltransferase (COMT) enzyme is involved in the pathogenesis of psychotic symptoms and may be associated with a therapeutic response to antipsychotic drugs. The aim of this study was to examine the relationship between COMT variants, plasma prolactin level, and the therapeutic effectiveness of amisulpride treatment in patients with schizophrenia. A 12-week naturalistic study of amisulpride treatment was carried out in 185 Han Chinese patients with schizophrenia. The patients were screened for 14 single-nucleotide polymorphisms of the COMT gene. The Positive and Negative Syndrome Scale (PANSS) was used to assess the improvement of psychopathological symptoms from the baseline to the end point in each subject. For better presentation of time-course changes in response status, a mixed model for repeated-measures (MMRM) analysis of symptom improvement during the 12-week treatment period was conducted. The change in plasma prolactin level after amisulpride treatment was also examined (n=51). No significant differences in the genotype frequencies of the COMT variants investigated were observed between responders and non-responders. Moreover, an MMRM analysis of psychopathological symptom improvement during the 12-week treatment course showed that it depended significantly on COMT variants (rs4680, rs4633, and rs6267), particularly regarding changes in negative symptoms. The increase in plasma prolactin levels observed was influenced by the COMT rs4680 variant and was positively correlated with a reduction in PANSS negative scores. Our results suggest that variation of the COMT gene is associated with treatment response regarding negative symptoms and prolactin changes after amisulpride treatment in patients with schizophrenia.
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Antipsicóticos/uso terapéutico , Catecol O-Metiltransferasa/genética , Prolactina/sangre , Esquizofrenia/tratamiento farmacológico , Sulpirida/análogos & derivados , Adulto , Amisulprida , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Prolactina/genética , Escalas de Valoración Psiquiátrica , Esquizofrenia/sangre , Esquizofrenia/enzimología , Esquizofrenia/genética , Sulpirida/uso terapéutico , Resultado del TratamientoRESUMEN
Research on the effects of repeated opioid use on striatal dopamine transporters has yielded inconsistent results, possibly confounded by a history of methamphetamine or methadone exposure in opioid-dependent individuals. Previous studies have shown that striatal dopamine transporter density is positively correlated with the cognitive performance of healthy volunteers. This study aimed to investigate changes in striatal dopamine transporter density and their functional significance in opioid-dependent individuals. Single-photon emission computed tomography with [(99m) Tc]TRODAT-1 as a ligand was used to measure striatal dopamine transporter levels in 20 opioid-dependent individuals and 20 age- and sex-matched healthy controls. Opioid-dependent individuals had no history of methamphetamine or methadone use. The Wisconsin Card Sorting Test (WCST) was performed to assess neurocognitive function. We found that compared with healthy controls, opioid-dependent individuals showed a significant reduction in striatal dopamine transporter density. They also showed poorer performance on the WCST in terms of the trials administered, total errors, perseverative responses, perseverative errors, and non-perseverative errors. Striatal dopamine transporter levels negatively correlated with non-perseverative errors not only in opioid-dependent individuals but also in healthy controls. These findings suggest that in human, repeated opioid exposure reduces striatal dopamine transporter density, which can be associated with non-perseverative errors. Non-perseverative errors may be one of the more sensitive parameters in WCST to identify working memory deficits associated with striatal dopamine transporter reduction. Moreover, we suggest that whether opioid-associated neurotoxicity is reversible depends on the brain region.
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Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Memoria a Corto Plazo , Neostriado/metabolismo , Trastornos Relacionados con Opioides/metabolismo , Adulto , Núcleo Caudado/diagnóstico por imagen , Núcleo Caudado/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Neostriado/diagnóstico por imagen , Pruebas Neuropsicológicas , Trastornos Relacionados con Opioides/diagnóstico por imagen , Trastornos Relacionados con Opioides/psicología , Compuestos de Organotecnecio , Putamen/diagnóstico por imagen , Putamen/metabolismo , Radiofármacos , Tomografía Computarizada de Emisión de Fotón Único , TropanosRESUMEN
OBJECTIVES: Suicide is an important issue in the military service, since it can influence military morale and create dangerous situations for other personnel. The serotonin transporter (SERT) has been suggested to be involved in the pathophysiology of depression and suicidal behaviours. The aims of this study were to examine whether the brain SERT availability differs between military conscripts with depression and control subjects, and whether suicidal ideation is correlated with SERT availability. METHODS: We used N,N-dimethyl-2-(2-amino-4-[(18)F]-fluorophenylthio)benzylamine (4-[(18)F]-ADAM) as a radioligand for positron emission tomography (PET) imaging. All participants completed the Hamilton Depression Rating Scale and Beck Scale for Suicide Ideation (BSS) prior to PET imaging. RESULTS: The effect of major depression and BSS scores had an interaction on SERT availability. After adjusting for the BSS score, subjects with depression had lower SERT availability than control subjects (F1,17 = 23.85, P < 0.001). A positive correlation between SERT availability and BSS scores was observed in the depression group (F1,8 = 30.67, P = 0.001). The status of depression and intensity of suicidal ideation exert opposite effects on SERT availability. CONCLUSIONS: The extent of suicidal ideation may moderate the reduction effect in SERT binding observed in major depression in male military conscripts.