Striatal dopamine D2/3 receptors in medication-naïve schizophrenia: an [123I] IBZM SPECT study.

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.

Heart Rate Variability with Deep Breathing in Drug-Naïve Patients with Schizophrenia.

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.

Heart Rate Variability is Associated with Memory in Females.

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.

The Association between Baseline Subjective Anxiety Rating and Changes in Cardiac Autonomic Nervous Activity in Response to Tryptophan Depletion in Healthy Volunteers.

The aim of this study was to investigate the influence of serotonin on anxiety and autonomic nervous system (ANS) function; the correlation between subjective anxiety rating and changes of ANS function following tryptophan depletion (TD) in healthy volunteers was examined. Twenty-eight healthy participants, consisting of 15 females and 13 males, with an average age of 33.3 years, were recruited.Baseline Chinese Symptom Checklist-90-Revised and ANS function measurements were taken. TD was carried out on the testing day, and participants provided blood samples right before and 5 hours after TD. ANS function, somatic symptoms, and Visual Analogue Scales (VASs) were determined after TD. Wilcoxon signed rank test and Spearman ρ correlation were adapted for analyses of the results.The TD procedure reduced total and free plasma tryptophan effectively. After TD, the sympathetic nervous activity increased and parasympathetic nervous activity decreased. Baseline anxiety ratings positively correlated with post-TD changes in sympathetic nervous activity, VAS ratings, and physical symptoms. However, a negative correlation with post-TD changes in parasympathetic nervous activity was found.The change in ANS function after TD was associated with the severity of anxiety in healthy volunteers. This supports the fact that the effect of anxiety on heart rate variability is related to serotonin vulnerability. Furthermore, it also shows that the subjective anxiety rating has a biological basis related to serotonin.

The association between heroin expenditure and dopamine transporter availability--a single-photon emission computed tomography study.

One of the consequences of heroin dependency is a huge expenditure on drugs. This underlying economic expense may be a grave burden for heroin users and may lead to criminal behavior, which is a huge cost to society. The neuropsychological mechanism related to heroin purchase remains unclear. Based on recent findings and the established dopamine hypothesis of addiction, we speculated that expenditure on heroin and central dopamine activity may be associated. A total of 21 heroin users were enrolled in this study. The annual expenditure on heroin was assessed, and the availability of the dopamine transporter (DAT) was assessed by single-photon emission computed tomography (SPECT) using [(99m)TC]TRODAT-1. Parametric and nonparametric correlation analyses indicated that annual expenditure on heroin was significantly and negatively correlated with the availability of striatal DAT. After adjustment for potential confounders, the predictive power of DAT availability was significant. Striatal dopamine function may be associated with opioid purchasing behavior among heroin users, and the cycle of spiraling dysfunction in the dopamine reward system could play a role in this association.

Venlafaxine, paroxetine and milnacipran for major depressive disorder: a pragmatic 24-week study.

Major depressive disorder (MDD), one of the most common psychiatric disorders in the world, is a serious, recurrent and chronic mental disorder, which is associated with significant psychosocial disability and economic burden. Until recently, short-term effectiveness of antidepressants has been measured in terms of patients' response to the medications in significantly reduced depressive symptoms. Remission, a long-term elimination of symptoms and the restoration of normal functioning, has become the primary outcome of therapy. In the current study, the efficacy of three frequently prescribed antidepressants, venlafaxine (75-225 mg/day), paroxetine (20 mg/day) and milnacipran (100 mg/day), used in treating 249 MDD patients with Hamilton Rating Scale of Depression (HRSD17) scores higher than 16 was compared. Each patient was evaluated at week 0, 1, 2, 4, 8, 12, 16, 20 and 24 in a 24-week open-label study. Eighty-two patients took venlafaxine, 97 took paroxetine and 70 patients took milnacipran. No significant differences were found between the three groups in the response condition (HRSD17 scores decreased more than 50%) after 24 weeks of follow-up. For remission, the paroxetine was the least efficacious medication than either the milnacipran (HRSD17 ≤ 7) or the venlafaxine (HRSD17 ≤ 5) by the last observation carried forward (LOCF) analysis. Our results suggest that the absence of depressive symptoms alone may not be an indicator for MDD remission, but the duration of absent depressive symptoms may be a better indicator.

The effects of add-on low-dose memantine on cytokine levels in bipolar II depression: a 12-week double-blind, randomized controlled trial.

Memantine, a noncompetitive N-methyl-d-aspartate receptor antagonist with a mood-stabilizing effect, and an association between bipolar disorder and proinflammatory cytokine levels have been reported. Whether adding-on memantine would reduce cytokine levels and is more effective than valproic acid (VPA) alone in bipolar II disorder was investigated. A randomized, double-blind, controlled, 12-week study was conducted. Patients undergoing regular VPA treatments were randomly assigned to a group: VPA + memantine (5 mg/d) (n = 106) or VPA + placebo (n = 108). The Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS) were used to evaluate clinical response. Symptom severity, plasma tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), IL-8, and IL-1 levels were examined during weeks 0, 1, 2, 4, 8, and 12. To adjust within-subject dependence over repeated assessments, multiple linear regressions with generalized estimating equation methods were used to examine the therapeutic effect. Tumor necrosis factor α levels were significantly lower in the VPA + memantine group than in the VPA + placebo group (P = 0.013). Posttreatment HDRS and YMRS scores decreased significantly in both groups, but not significant, nor was the other between-group cytokine level difference pretreatment and posttreatment. The HDRS score changes were significantly associated with IL-6 (P = 0.012) and IL-1 (P = 0.005) level changes and changes in YMRS score changes with TNF-α (P = 0.005) level changes. Treating bipolar II depression with VPA + memantine may improve the plasma TNF-α level. However, adding-on memantine may not improve clinical symptoms or cytokine levels other than TNF-α. Clinical symptoms may be correlated with certain cytokines.

Association between auditory P300, psychopathology, and memory function in drug-naïve schizophrenia.

The aim of this study was to explore memory deficits and psychopathology and their relationships with P300 in drug-naïve patients with schizophrenia. The Positive and Negative Syndrome Scale (PANSS) and the Wechsler Memory Scale-Revised were administered. Auditory event-related potentials elicited by an oddball paradigm were obtained. After controlling for age, sex, the results showed a statistically significant negative correlation between the total PANSS score and P300 amplitude at the parietal position (r = -0.66, p < 0.05). Moreover, visual memory was significantly positively correlated with P300 amplitude at the parietal position (r = 0.67, p < 0.05). After controlling for the duration of illness, the above correlations remained statistically significant. The correlation between P300 and the severity of psychopathology was reconfirmed in drug-naïve patients with schizophrenia. A possible contribution of memory decompensation in P300 among drug-naïve patients with schizophrenia may be considered, and the compensatory or Default Model Network might be a possible explanation of this association.

Genotype variant associated with add-on memantine in bipolar II disorder.

Memantine is a non-competitive N-methyl-d-asparate (NMDA) receptor antagonist with a mood-stabilizing effect. We investigated whether using valproic acid (VPA) plus add-on memantine to treat bipolar II disorder (BP-II) is more effective than using VPA alone (VPA + Pbo). We also evaluated, in BP-II patients, the association between the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism with treatment response to VPA + add-on memantine and to VPA + Pbo. In this randomized, double-blind, controlled 12 wk study, BP-II patients undergoing regular VPA treatments were randomly assigned to a group: VPA + Memantine (5 mg/day) (n = 115) or VPA + Pbo (n = 117). The Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS) were used to evaluate clinical response during week 0, 1, 2, 4, 8 and 12. The genotypes of the BDNF Val66Met polymorphisms were determined using polymerase chain reactions plus restriction fragment length polymorphism analysis. To adjust within-subject dependence over repeated assessments, multiple linear regression with generalized estimating equation methods was used to analyze the effects of the BDNF Val66Met polymorphism on the clinical performance of memantine. Both groups showed significantly decreased YMRS and HDRS scores after 12 wk of treatment; the differences between groups were non-significant. When stratified by the BDNF Val66Met genotypes, significantly greater decreases in HDRS scores were found in the VPA + memantine group in patients with the Val Met genotype (p = 0.004). We conclude that the BDNF Val66Met polymorphism influenced responses to add-on memantine by decreasing depressive symptoms in patients with BP-II.

Gender-specific association of the SLC6A4 and DRD2 gene variants in bipolar disorder.

Findings on the association between the risk for developing bipolar disorder and the functions of the serotonin transporter-linked polymorphic region gene (5-HTTLPR) and dopamine D2 receptor gene (DRD2) variants are contradictory. One explanation for this is that a gender difference may exist for genetic contributions. We compared the gender-related main effects and the gene-to-gene interaction between serotonin transporter gene (SLC6A4) and DRD2 in adult male and female patients with bipolar I (BP-I) and bipolar II (BP-II) disorder. Patients with BP-I (n = 400) and BP-II (n = 493), and healthy controls (n = 442) were recruited from Taiwan's Han Chinese population. The genotypes of the 5-HTTLPR and DRD2 Taq-IA polymorphisms were determined using polymerase chain reaction-restriction fragment length polymorphism analysis. Logistic regression analysis showed a significant gender-specific association of the DRD2 A1/A1 and the 5-HTTLPR S/S, S/LG , and LG/LG (S+) (p = 0.01) genotypes in men with BP-I (p = 0.002 and 0.01, respectively) and BP-II (p = 0.001 and 0.007, respectively), but not in women. A significant interaction for the DRD2 A1/A1 and 5-HTTLPR S+ polymorphisms was also found only in men with BP-I and BP-II (p = 0.003 and 0.001, respectively). We provide preliminary evidence for a gender-specific effect of the SLC6A4 and DRD2 gene variants for the risk of BP-I and of BP-II. We also found gender-specific interaction between 5-HTTLPR and DRD2 Taq-IA polymorphisms in patients with bipolar disorder.

Serotonin transporter availability in the midbrain and perceived social support in healthy volunteers.

OBJECTIVE: Serotonin modulates human behavior and emotion. Recent evidence implies that a higher level of serotonergic activity could be associated with a higher level of perceived social support. This study aimed to examine the correlation between serotonin transporter (SERT) availability and perceived social support scores in healthy volunteers. METHODS: 111 healthy participants, 50 males and 61 females, were enrolled from the community and completed the Measurement of Support Function questionnaire. Single photon emission computed tomography (SPECT) with [(123)I] ADAM was performed to examine SERT availability. RESULTS: Perceived social support was positively correlated with SERT availability (Spearman's ρ=0.29, p<0.01; χ(2)=7.57, p<0.01), particularly in males (Spearman's ρ=0.37, p<0 .01; χ(2)=11.77, p<0.01). Censored regressions indicated that these associations are not influenced by a ceiling effect and remained significant after controlling the effect of age. CONCLUSIONS: This result confirmed the correlation between perceived social support and central serotonergic activity. However, this correlation was present only in males.

Inflammation's Association with Metabolic Profiles before and after a Twelve-Week Clinical Trial in Drug-Naïve Patients with Bipolar II Disorder.

UNLABELLED: Inflammation is thought to be involved in the pathophysiology of bipolar disorder (BP) and metabolic syndrome. Prior studies evaluated the association between metabolic profiles and cytokines only during certain mood states instead of their changes during treatment. We enrolled drug-naïve patients with BP-II and investigated the correlation between changes in mood symptoms and metabolic indices with changes in plasma cytokine levels after 12 weeks of pharmacological treatment. Drug-naïve patients (n = 117) diagnosed with BP-II according to DSM-IV criteria were recruited. Metabolic profiles (cholesterol, triglyceride, HbA1C, fasting serum glucose, body mass index (BMI) and plasma cytokines (TNF-α, CRP, IL-6, and TGF-ß) were measured at baseline and 2, 8, and 12 weeks post-treatment. To adjust within-subject dependence over repeated assessments, multiple linear regressions with generalized estimating equation methods were used. Seventy-six (65.0%) patients completed the intervention. Changes in plasma CRP were significantly associated with changes in BMI (P = 1.7E-7) and triglyceride (P = 0.005) levels. Changes in plasma TGF-ß1 were significantly associated with changes in BMI (P = 8.2E-6), cholesterol (P = 0.004), and triglyceride (P = 0.006) levels. However, changes in plasma TNF-α and IL-6 were not associated with changes in any of the metabolic indices. Changes in Hamilton Depression Rating Scale scores were significantly associated with changes in IL-6 (P = 0.003) levels; changes in Young Mania Rating Scale scores were significantly associated with changes in CRP (P = 0.006) and TNF-α (P = 0.039) levels. Plasma CRP and TGF-ß1 levels were positively correlated with several metabolic indices in BP-II after 12 weeks of pharmacological intervention. We also hypothesize that clinical symptoms are correlated with certain cytokines. These new findings might be important evidence that inflammation is the pathophysiology of clinical symptoms and metabolic disturbance in BP-II. TRIAL REGISTRATION: ClinicalTrials.gov NCT01188148.

Probing the association between dexamethasone-induced cortisol suppression and serotonin transporter availability among drug-free patients with major depressive disorder--a small-sample SPECT study with [¹²³I]ADAM.

The association between hypothalamo-pituitary-adrenal (HPA) axis function and the serotonergic system could be involved in the mechanism of depression. However, neuroimaging evidence is scarce. The aim of the present study was to probe the association between dexamethasone suppression test response and serotonin transporter (SERT) availability in drug-free patients with major depressive disorder (MDD). Seventeen MDD patients (five males and twelve females) were recruited. SPECT with [(123)I] ADAM was used to measure the midbrain SERT availability, and HPA axis function was measured by the dexamethasone suppression test (DST). The association was significant when considering all participants (ρ=0.69, p=0.002). This association may have clinical implications for the treatment of MDD.

Associations among hypothalamus-pituitary-adrenal axis function, novelty seeking, and retention in methadone maintenance therapy for heroin dependency.

OBJECTIVE: The efficacy of methadone maintenance therapy for heroin dependence is compromised by the low retention rate. Hypothalamus-pituitary-adrenal (HPA) axis function, which is associated with stress response, and novelty seeking (NS), a personality trait associated with low dopaminergic activity, may play roles in retention. METHOD: We conducted a prospective study in which HPA axis function and NS were assessed by the dexamethasone suppression test and the Tridimensional Personality Questionnaire at baseline, respectively. The retention rate was assessed at the half- and 1-year points of methadone maintenance therapy. RESULTS: A low suppression rate of dexamethasone suppression test (D%) was associated with a high level of NS. A low D% was associated with half-year dropout, whereas a high level of NS was associated with 1-year dropout. Survival analysis confirmed that D% and NS were significant time-dependent covariates for retention. CONCLUSION: The findings showed that HPA axis function and NA were associated with retention at different time points.

Add-on memantine to valproate treatment increased HDL-C in bipolar II disorder.

UNLABELLED: Memantine is a noncompetitive NMDA receptor antagonist. As an augmenting agent, it has an antidepressant-like and mood-stabilizing effect. Memantine also reduces binge eating episodes and weight. We investigated whether memantine added on to valproate (VPA) is more effective than VPA alone for treating BP-II depression and improving the patient's metabolic profile. This was a randomized, double-blind, controlled study. BP-II patients undergoing regular VPA treatments were randomly assigned to one of two groups: VPA plus either add-on [1] memantine (5 mg/day) (n = 62) or [2] placebo (n = 73) for 12 weeks. The Young Mania Rating Scale (YMRS) and Hamilton Depression Rating Scale (HDRS) were used to evaluate clinical response. Height, weight, fasting serum glucose, fasting total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides were followed regularly. Multiple linear regressions with generalized estimating equation methods were used to analyze the effects of memantine on clinical performance. There were no significant differences in pre- and post-treatment YMRS and HDRS scores between the VPA + memantine and VPA + placebo groups. Although there were no significant differences in the pre- and post-treatment values of most metabolic indices between the two groups, there was a significant increase of HDL-C (p = 0.009) in the VPA + memantine group compared with the VPA + placebo group. This increase remained significant even after controlling for body mass index (BMI) (p = 0.020). We conclude that add-on memantine plus VPA treatment of BP-II depression increases the blood level of HDL-C even in the absence of change in affective symptoms. TRIAL REGISTRATION: NCT01188148 (https://register.clinicaltrials.gov/), Trial date was from 1st August, 2008 to 31st July, 2012 in National Cheng Kung University and Tri-Service General Hospital.

Gender difference in antidepressant-related sexual dysfunction in Taiwan.

OBJECTIVE: Sexual dysfunction accompanied by depression may be altered by antidepressants. The effects of antidepressants on sexual dysfunction among males and females remain to be investigated. METHODS: Three groups of subjects, drug-free patients with depression (N=125), medicated patients with depression (N=145) and healthy volunteers (N=255), were recruited. A Chinese version of the Changes in Sexual Functioning Questionnaire was employed to assess sexual function as the primary outcome. RESULTS: Drug-free depressed females and medicated depressed males had more sexual dysfunction than healthy controls. The desire for sexual behaviors among healthy females and medicated depressed females was higher than that of drug-free depressed females. CONCLUSION: Depression and antidepressants may have different impacts on the sexual function of males and females.

Management of chronic depressive patients with residual symptoms.

Various clinical issues are involved in the appropriate diagnosis and proper treatment interventions for patients with major depressive disorder (MDD). Despite a number of diverse antidepressants for treating MDD now, response and remission rates following adequate trials of antidepressant intervention are still not satisfactory. Furthermore, a significant proportion of MDD patients have residual symptoms, which are associated with increased relapse and recurrence of MDD, leading to negative impacts on the clinical course and outcomes of MDD. Timely and appropriate decision-making regarding the proper management of such cases is required in our routine daily practice. These issues are illustrated and also framed by one MDD case with a complicated clinical course. This review paper may give physicians clinical insight into how we can effectively and properly evaluate and manage such patients in clinical practice.

Association between DRD2, 5-HTTLPR, and ALDH2 genes and specific personality traits in alcohol- and opiate-dependent patients.

The vulnerability of developing addictions is associated with genetic factors and personality traits. The predisposing genetic variants and personality traits may be common to all addictions or specific to a particular class of addiction. To investigate the relationship between genetic variances, personality traits, and their interactions in addiction are important. We recruited 175 opiate-dependent patients, 102 alcohol-dependent patients, and 111 healthy controls. All participants were diagnosed using DSM-IV criteria and assessed with Tridimensional Personality Questionnaire (TPQ). The dopamine D2 receptor (DRD2), 5-HTT-linked promoter region (5-HTTLPR), and aldehyde dehydrogenase 2 (ALDH2) genes were genotyped using PCR. The genotype frequency of the 5-HTTLPR and ALDH2 was significantly different between the patients and controls (P=0.013, P<0.001, respectively), and borderline significant (P=0.05) for DRD2 polymorphism. Both Novelty Seeking (NS) and Harm Avoidance (HA) scores were higher for patients (P<0.001). After stratification by candidate genes, addicts with ALDH2 *1/*1 interacting with the low-functional group of DRD2 and 5-HTTLPR genes have higher HA traits, whereas addicts with ALDH2 *1/*2 or *2/*2 and low-functional group of DRD2 and 5-HTTLPR genes have higher NS traits. We concluded that addicts, both alcohol- and opiate-dependent patients, have common genetic variants in DRD2 and 5-HTTLPR but specific for ALDH2. Higher NS and HA traits were found in both patient groups with the interaction with DRD2, 5-HTTLPR, and ALDH2 genes. The ALDH2 gene variants had different effect in the NS and HA dimension while the DRD2 and 5-HTTLPR genes did not.

Challenges in treating patients with major depressive disorder: the impact of biological and social factors.

Major depressive disorder (MDD) is frequently unrecognized and underdiagnosed by clinicians and thus remains untreated or inappropriately treated in routine clinical practice. Although the symptoms of MDD are widely acknowledged and recognized by clinicians, numerous epidemiological studies have reported that this disorder is more prevalent than had previously been thought, and that it is challenging to diagnose and treat, particularly because somatic symptoms and comorbid conditions are common in real clinical situations. MDD is associated with increased morbidity and mortality as well as with higher healthcare costs and more severe functional impairment. Therefore, optimal treatment for MDD should include collaboration focussed on comorbid physical diseases, rehabilitation aimed at restoring social functioning, and pharmacotherapy designed to ensure complete remission including psychological and physical symptoms, as well as functional recovery.

Interaction between novelty seeking and the aldehyde dehydrogenase 2 gene in heroin-dependent patients.

OBJECTIVES: Heroin dependence is a multifactor disorder. We investigated the association of genetic factors and heroin-dependent temperaments to determine whether a temperament-gene interaction is involved in the pathogenesis of heroin dependence. METHODS: Three hundred seventy participants (259 heroin-dependent patients and 111 healthy controls) were recruited and finished the Tridimensional Personality Questionnaire to assess personality traits (temperament). The genotypes of the aldehyde dehydrogenase 2 (ALDH2) gene and the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene using polymerase chain reactions plus restriction fragment length polymorphism analysis. RESULTS: Multiple logistic regression analysis showed significant main effects for novelty seeking (P ≤ 0.001) and harm-avoidance (P = 0.001) scores, and a significant interaction effect between novelty seeking and ALDH2 genotypes (P = 0.016) in heroin-dependent patients compared with controls. When stratified by the ALDH2 genotypes, only heroin-dependent patients with the *1*2 and *2*2 genotypes at ALDH2 had higher novelty-seeking scores than did controls (heroin dependence = 15.94, controls = 12.46; P ≤ 0.001). CONCLUSIONS: Our results provide initial evidence that the ALDH2 gene interacted with novelty seeking in heroin-dependent Han Chinese patients in Taiwan.