RESUMO
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.
Assuntos
Transtornos Relacionados ao Uso de Anfetaminas/genética , Transtornos Relacionados ao Uso de Anfetaminas/psicologia , Comportamento de Procura de Droga , Polimorfismo de Nucleotídeo Único/genética , Receptores de Dopamina D3/genética , Adulto , Idade de Início , Povo Asiático/etnologia , Povo Asiático/genética , Feminino , Genótipo , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Personalidade , Inventário de Personalidade , Estudos Retrospectivos , Taiwan , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVES: Heroin dependence (HD) is a chronic relapsing brain illness with substantial heritability. Nerve growth factor (NGF) is a crucial modulator in the neurodevelopment, and may be a key mediator of reward processes in HD. The purpose of this genetic study was to investigate whether NGF gene polymorphisms associate with the occurrence of HD and the specific personality traits of patients with HD. METHODS: We selected a homogeneous Han Chinese male population to overcome possible confounding effects of population and gender. For the study, 272 HD patients and 141 controls completed the Tridimensional Personality Questionnaire to evaluate their personality traits. In addition, a further sample 303 HD patients and 204 controls was added (with totally 920 participants) for the gene association and genotype-phenotype interaction studies. RESULTS: Patients with HD had higher novelty seeking (NS) and harm avoidance (HA) scores than healthy subjects. Nonetheless, NGF gene polymorphisms did not associate with specific personality traits in HD patients and controls. There is no significant difference in NGF gene polymorphisms between patients with HD and controls. DISCUSSION AND CONCLUSIONS: The NGF gene may neither contribute to the risk of development of HD, nor mediate the relationship between specific personality traits and HD in Han Chinese male population. SCIENTIFIC SIGNIFICANCE: Patients with HD had higher novelty seeking (NS) and harm avoidance (HA) scores than healthy subjects. However, none of the polymorphisms in the NGF gene affected the NS and HA scores in both patients and healthy subjects. (Am J Addict 2018;27:516-523).
Assuntos
Dependência de Heroína , Fator de Crescimento Neural/genética , Adulto , Comportamento Exploratório , Redução do Dano , Dependência de Heroína/epidemiologia , Dependência de Heroína/genética , Dependência de Heroína/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Personalidade , Inventário de Personalidade , Polimorfismo Genético , Psicometria/métodos , Inquéritos e Questionários , Taiwan/epidemiologiaRESUMO
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.
Assuntos
Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Memória de Curto Prazo , Neostriado/metabolismo , Transtornos Relacionados ao Uso de Opioides/metabolismo , Adulto , Núcleo Caudado/diagnóstico por imagem , Núcleo Caudado/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Neostriado/diagnóstico por imagem , Testes Neuropsicológicos , Transtornos Relacionados ao Uso de Opioides/diagnóstico por imagem , Transtornos Relacionados ao Uso de Opioides/psicologia , Compostos de Organotecnécio , Putamen/diagnóstico por imagem , Putamen/metabolismo , Compostos Radiofarmacêuticos , Tomografia Computadorizada de Emissão de Fóton Único , TropanosRESUMO
BACKGROUND: Many lines of evidence suggest the role of serotonin transporter (SERT)-mediated reuptake of serotonin in the pathophysiology and treatment of major depressive disorder (MDD). This study aimed to examine whether the pretreatment of SERT binding potential or SERT binding ratio between terminal projection regions relative to the midbrain raphe nuclei was associated with treatment outcomes to SERT-targeted antidepressants. METHODS: We recruited 39 antidepressant-naïve patients with MDD and 39 heathy controls. Positron emission tomography with N,N-dimethyl-2-(2-amino-4-[(18)F]fluorophenylthio)benzylamine (4-[(18)F]-ADAM) was used to measure in vivo SERT availability prior to antidepressant treatment. The 21-item Hamilton Depression Rating Scale (HDRS) was use to assess the severity of depression from baseline to week 6. All the patients with MDD had HDRS scores of 18 or more. RESULTS: Pretreatment SERT binding in the thalamus and striatum positively correlated with an early reduction in HDRS scores at week 3. Nonresponders and dropout patients showed a proportionate reduction in SERT binding in the terminal projection regions and midbrain compared to healthy controls. In contrast, a disproportionate reduction in SERT binding in the terminal projection regions relative to midbrain was observed in responders. CONCLUSIONS: The results of this study suggested that a disproportionate reduction in SERT binding between terminal projection regions and midbrain may predict better treatment outcomes in patients with MDD.
Assuntos
Antidepressivos/uso terapêutico , Encéfalo/metabolismo , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/metabolismo , Tomografia por Emissão de Pósitrons , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Adulto , Benzilaminas/administração & dosagem , Encéfalo/diagnóstico por imagem , Corpo Estriado/metabolismo , Transtorno Depressivo Maior/diagnóstico por imagem , Feminino , Humanos , Masculino , Mesencéfalo/metabolismo , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos/administração & dosagem , Tálamo/metabolismo , Resultado do Tratamento , Adulto JovemRESUMO
Dopamine transporter and its genetic factors have been suggested to play a critical role in the development of bipolar disorder (BPD). However, the importance of the dopamine transporter gene (DAT1) in the pathogenesis of BPD remains unclear. The aims of this study were to assess 18 polymorphisms of the DAT1 gene to determine whether this gene is associated with BPD and whether it influences personality traits of patients with BPD. DAT1 polymorphisms were analyzed in 492 BPD (374 BPDI and 118 BPDII) patients and 436 controls. All participants were screened using the same assessment tool, and all met the criteria for BPD. The Tridimensional Personality Questionnaire was used to assess personality traits in both patients and controls. Several polymorphisms had a weak association with BPD, including rs2550948, rs2652511, and rs2975226 in allele distribution analysis (P < 0.05). Furthermore, the promoter G-A-C-G haplotype (rs6350-rs2975226-rs2652511-rs6413429) was over-represented in the BPD patients compared to the controls (P = 0.007). In personality assessment, the BPDII patients had the highest harm avoidance score, followed by the BPDI patients and controls (P = 3.7 × 10(-32)). In addition, a significant association between rs40184 and harm avoidance was found in the patients with BPD. The DAT1 promoter may be associated with vulnerabilities in BPD. The BPD patients had a higher rate of harm avoidance personality traits than the controls, and DAT1 variants may influence personality traits in patients with BPD.
Assuntos
Transtorno Bipolar/complicações , Transtorno Bipolar/genética , Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Transtornos da Personalidade/complicações , Transtornos da Personalidade/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Distribuição de Qui-Quadrado , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Inventário de Personalidade , Escalas de Graduação Psiquiátrica , Taiwan , Adulto JovemRESUMO
BACKGROUND: Much evidence supports the role of the serotonin transporter (SERT) in the pathophysiology and pharmacotherapy of major depressive disorder (MDD) and suicidal behaviors. METHODS: In this study, we recruited 17 antidepressant-naïve patients with MDD and 17 age- and gender-matched healthy controls. SERT availability was measured in vivo with N,N-dimethyl-2-(2-amino-4-[(18)F]fluorophenylthio)benzylamine (4-[(18)F]-ADAM) positron emission tomography (PET) imaging. The 21-item Hamilton Depression Rating Scale (HDRS) and Beck Scale for Suicide Ideation were used to assess the severity of depression and the intent of suicide ideation prior to PET imaging. All subjects with MDD were in a current state of depression with HDRS scores â§18. Subjects who attempted suicide within two weeks of the study onset were recruited in the depressed suicidal group (n = 8). Subjects with MDD who denied any prior suicide attempt were recruited into the depressed non-suicidal group (n = 9). RESULTS: A significant reduction of SERT availability in the midbrain, thalamus, and striatum was noted in the MDD group relative to the control group (Bonferroni-adjusted p-value < 0.05). Moreover, this effect was more pronounced in the depressed suicidal group compared to the control group (Bonferroni-adjusted p-value < 0.01). Relative to both the depressed non-suicidal and control groups, the depressed suicidal group showed an increased prefrontal cortex (PFC)/midbrain SERT binding ratio (Bonferroni-adjusted p-value < 0.01). CONCLUSIONS: This study suggests an incongruent reduction of PFC SERT binding relative to the midbrain might discriminate between depressed suicide attempters and non-attempters in patients with MDD and may be involved in the pathophysiology of suicide behaviors.
Assuntos
Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/psicologia , Tomografia por Emissão de Pósitrons , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Tentativa de Suicídio/psicologia , Adulto , Idoso , Benzilaminas , Distribuição de Qui-Quadrado , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Compostos Radiofarmacêuticos , Adulto JovemRESUMO
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.
Assuntos
Transtornos Relacionados ao Uso de Álcool , Alcoolismo , Gastrite , Hepatopatias Alcoólicas , Síndrome do Desconforto Respiratório , Apneia Obstrutiva do Sono , Humanos , Consumo de Bebidas Alcoólicas , Transtornos Relacionados ao Uso de Álcool/complicações , Transtornos Relacionados ao Uso de Álcool/epidemiologia , Alcoolismo/complicações , Alcoolismo/epidemiologia , Estudos de Coortes , Gastrite/complicações , Incidência , Hepatopatias Alcoólicas/complicações , Síndrome do Desconforto Respiratório/complicações , Estudos Retrospectivos , Fatores de Risco , Apneia Obstrutiva do Sono/complicações , Taiwan/epidemiologia , Masculino , FemininoRESUMO
Objectives: Dopamine plays an important role in reward system of heroin dependence (HD), and dopaminergic D2 receptor (DRD2) gene is a candidate for the aetiology of HD. Ankyrin repeat and kinase domain containing 1 (ANKK1) gene is proximal to DRD2 and may influence its expression. We explored whether DRD2 and ANKK1 associate with occurrence of HD, and whether the genetic variants influence personality traits in male patients with HD.Methods:DRD2/ANKK1 polymorphisms were analysed in 950 unrelated Han Chinese male participants (601 HD patients and 349 healthy controls). All participants were screened using the same assessment tools and all patients met the diagnostic criteria of HD. Personality traits were assessed in 274 patients and 142 controls using the Tridimensional Personality Questionnaire.Results: According to the allele, genotype and haplotype frequency analysis, we observed an association between HD and several DRD2/ANKK1 polymorphisms (rs1800497, rs1800498, rs1079597 and rs4648319); this was most notable in the late-onset HD subgroup. However, these DRD2/ANKK1 polymorphisms did not associate with specific personality traits in HD patients and controls.Conclusions:DRD2/ANKK1 may play an important role in occurrence of late-onset HD, but does not mediate the relationship between personality traits and HD in Han Chinese male population.
Assuntos
Dependência de Heroína/genética , Proteínas Serina-Treonina Quinases/genética , Receptores de Dopamina D2/genética , Adulto , Povo Asiático , Estudos de Casos e Controles , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , Modelos Logísticos , Masculino , Polimorfismo de Nucleotídeo Único , Adulto JovemRESUMO
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.
Assuntos
Predisposição Genética para Doença , Dependência de Heroína/genética , Dependência de Heroína/psicologia , Polimorfismo de Nucleotídeo Único , Receptores Opioides delta/genética , Estresse Psicológico/genética , Adulto , Povo Asiático/genética , Estudos de Casos e Controles , China , Feminino , Frequência do Gene , Estudos de Associação Genética , Haplótipos , Dependência de Heroína/complicações , Heterozigoto , Homozigoto , Humanos , Masculino , Estresse Psicológico/complicaçõesAssuntos
Anomia/etiologia , Neoplasias Encefálicas/complicações , Glioblastoma/complicações , Lobo Temporal/patologia , Idoso de 80 Anos ou mais , Anomia/diagnóstico , Neoplasias Encefálicas/patologia , Feminino , Glioblastoma/patologia , Humanos , Imageamento por Ressonância Magnética , Testes Neuropsicológicos , Lobo Temporal/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
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.
Assuntos
Transtorno Depressivo Maior/tratamento farmacológico , Paroxetina/farmacologia , Cloridrato de Venlafaxina/farmacologia , Adulto , Anti-Inflamatórios/farmacologia , Antidepressivos/uso terapêutico , Antidepressivos de Segunda Geração/uso terapêutico , Estudos de Casos e Controles , China , Citocinas/análise , Citocinas/sangue , Depressão/tratamento farmacológico , Transtorno Depressivo Maior/metabolismo , Feminino , Humanos , Interleucina-1beta/análise , Interleucina-1beta/sangue , Interleucina-1beta/efeitos dos fármacos , Interleucina-6/análise , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Paroxetina/metabolismo , Paroxetina/uso terapêutico , Escalas de Graduação Psiquiátrica , Resultado do Tratamento , Cloridrato de Venlafaxina/metabolismo , Cloridrato de Venlafaxina/uso terapêuticoRESUMO
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.
Assuntos
Imunidade Adaptativa/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Receptores de Dopamina D3/genética , Adulto , Alelos , Transtornos Relacionados ao Uso de Anfetaminas/complicações , Transtornos Relacionados ao Uso de Anfetaminas/genética , Citocinas/genética , Feminino , Frequência do Gene/genética , Genótipo , Humanos , Inflamação/genética , Interleucina-10/análise , Interleucina-10/sangue , Interleucina-2/análise , Interleucina-2/sangue , Interleucina-4/análise , Interleucina-4/sangue , Interleucina-5/análise , Interleucina-5/sangue , Interleucina-6/análise , Interleucina-6/sangue , Células Th1 , Células Th2Assuntos
Antineoplásicos/efeitos adversos , Carboplatina/efeitos adversos , Depressão/induzido quimicamente , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/efeitos adversos , Antineoplásicos/uso terapêutico , Carboplatina/uso terapêutico , Quimioterapia Adjuvante/psicologia , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/psicologia , Neoplasias Ovarianas/cirurgia , Paclitaxel/uso terapêutico , Ideação SuicidaRESUMO
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.
Assuntos
Alcoolismo/genética , Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idade de Início , Estudos de Casos e Controles , China , Comportamento Exploratório , Feminino , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Assunção de RiscosRESUMO
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.