Jo Yung-Wei Wu

Genome-wide association study of bipolar I disorder in the Han Chinese population

We report the first genome-wide association study in 1000 bipolar I patients and 1000 controls, with a replication of the top hits in another 409 cases and 1000 controls in the Han Chinese population. Four regions with most strongly associated single-nucleotide polymorphisms (SNPs) were detected, of which three were not found in previous GWA studies in the Caucasian populations. Among them, SNPs close to specificity protein 8 (SP8) and ST8 α-N-acetyl- neuraminide α-2,8-sialyltransferase (ST8SIA2) are associated with Bipolar I, with P-values of 4.87 × 10−7 (rs2709736) and 6.05 × 10−6 (rs8040009), respectively. We have also identified SNPs in potassium channel tetramerization domain containing 12 gene (KCTD12) (rs2073831, P=9.74 × 10−6) and in CACNB2 (Calcium channel, voltage-dependent, β-2 subunit) gene (rs11013860, P=5.15 × 10−5), One SNP nearby the rs1938526 SNP of ANK3 gene and another SNP nearby the SNP rs11720452 in chromosome 3 reported in previous GWA studies also showed suggestive association in this study (P=6.55 × 10−5 and P=1.48 × 10−5, respectively). This may suggest that there are common and population-specific susceptibility genes for bipolar I disorder.

Neuropsychological functions in patients with bipolar I and bipolar II disorder

UNLABELLED The literature reports persistent cognitive impairments in patients with bipolar disorder even after prolonged remission. However, a majority of studies have focused only on bipolar I disorder (BP-I), primarily because bipolar II disorder (BP-II) is often underdiagnosed or misdiagnosed. More attention should be paid to the differences between BP-I and BP-II, especially the aspects of neuropsychological functioning. We examined the different neuropsychological functions in BP-I and BP-II patients and compared them with those of healthy controls. METHODS The study included 67 patients with interepisode bipolar disorder (BP-I: n = 30; BP-II: n = 37) and 22 healthy controls compared using a battery of neuropsychological tests that assessed memory, psychomotor speed, and certain aspects of frontal executive function. RESULTS The BP-I group performed poorly on verbal memory, psychomotor speed, and executive function compared to the BP-II and control groups. Both bipolar groups performed significantly less well than the control group on measures of working memory and psychomotor speed, while the BP-II group showed an intermediate level of performance in psychomotor speed compared to the BP-I and control groups. There was no difference between the groups on visual memory. CONCLUSIONS BP-I was characterized by reduced performance in verbal memory, working memory, psychomotor speed, and executive function, while BP-II patients showed a reduction only in working memory and psychomotor speed. Cognitive impairment existed in both subtypes of bipolar disorder, and was greater in BP-I patients. Rehabilitation interventions should take into account potential cognitive differences between these bipolar subtypes.

Specific personality traits and dopamine, serotonin genes in anxiety-depressive alcoholism among Han Chinese in Taiwan.

BACKGROUND Cloninger [Cloninger CR. 1987. Neurogenetic adaptive mechanisms in alcoholism. Science 236: 410-416.] had proposed a psychobiological model suggesting that three main personality dimensions distinguish the alcoholism into two subtypes (type I and type II). However, the classification was equivocal for clinical diagnosis. Recently, anxiety-depressive alcohol dependence (ANX/DEP ALC) has been posited as a genetically specific subtype of alcoholism. Its clinical characteristics were similar to individuals with type I alcoholism [Cloninger, C.R. 1987. Neurogenetic adaptive mechanisms in alcoholism. Science 236: 410-6.] such as having a high comorbidity with mood disorder, late-onset and more anxious/depressed traits. We attempted to investigate whether the dopamine D2 receptor (DRD2) and the serotonin transporter promoter region (5-HTTLPR) genes were involved in Novelty Seeking (NS) and Harm Avoidance (HA) of ANX/DEP ALC. METHODS We recruited 46 pure alcohol dependents (Pure ALC) and 87 anxiety-depression alcohol dependents (ANX/DEP ALC). All participants were diagnosed by DSM-IV criteria, genotyped by the PCR method and assessed with Tridimensional Personality Questionnaire (TPQ). RESULTS Both NS and HA were high in ANX/DEP ALC (p = 0.021; p = 0.001, respectively). The association between NS and ANX/DEP ALC only existed in subjects with DRD2 TaqI A1(+) allele (A1/A1 or A1/A2 genotypes) (p = 0.004) and in those with S/S genotype of 5-HTTLPR (p = 0.005). With the stratification of DRD2 TaqI A1(+) allele, high NS of ANX/DEP ALC existed only in carriers of 5-HTTLPR S/S genotype (p=0.001). Moreover, ANX/DEP ALC was related to high HA only in samples carrying 5-HTTLPR S/L or L/L genotype (p = 0.02). CONCLUSIONS These findings provided the empirical genetic characterization of the specific personality traits in ANX/DEP ALC among Han Chinese population in Taiwan.

Neuropsychological functions in Han Chinese patients in Taiwan with bipolar II disorder comorbid and not comorbid with alcohol abuse/alcohol dependence disorder

OBJECTIVE Studies exploring neuropsychological functions of bipolar disorder (BP) specifically include patients comorbid with alcohol abuse (AB), alcohol dependence (AD), or both (AB/AD). Contradictory assessments of neuropsychological impairment may be caused by not excluding the confounding effects of comorbid AB/AD. Most of the literature discusses BP without subtyping, which overlooks that BP-II may be a valid diagnosis different from BP-I. Because neuropsychological functions are involved in overall BP-II outcomes, we hypothesized that the neuropsychological functions of patients with BP-II comorbid with AD (BP(+AD)) are significantly different from and more impaired than those of patients with BP-II not comorbid with AD (BP(-AD)). METHODS Using DSM-IV criteria, the study included 69 patients with BP-II (19 with BP(+AD); 28 with BP(-AD)) and 22 healthy controls compared using a battery of neuropsychological tests that assessed memory, psychomotor speed, and certain aspects of frontal executive function. All BP-II patients were in an inter-episode period (a period of remission between states of mania, hypomania, and depression). RESULTS BP(+AD) patients had lower scores than did BP(-AD) patients and controls in verbal memory, visual memory, attention, psychomotor speed, and executive function. Working memory was poorer for BP(+AD) than BP(-AD) patients and for both BP groups than for controls. CONCLUSIONS BP(+AD) patients manifested wide neuropsychological dysfunctions, and BP(-AD) patients showed a reduction in working memory, which suggested that working memory might be related to a history of BP-II. Neuropsychological dysfunctions seemed more strongly associated with AB/AD than with BP-II in inter-episode periods.

The Relationship Between Serotonin Receptor 1B Polymorphisms A‐161T and Alcohol Dependence

BACKGROUND Several studies have suggested that the serotonin receptor 1B gene (5HT1B) may be important in the pathogenesis of alcohol dependence (alcoholism; ALC; AD). We examined whether 5HT1B gene A-161T polymorphisms (rs130058) are a susceptibility factor for total AD and subgroups of AD. We further explored correlation of this 5HT1B gene variant between anxiety-depression alcoholism (ANX/DEP ALC) and antisocial alcoholism (antisocial ALC) subgroups because of the high comorbidity of anxiety-depression, antisocial personality disorder, and AD. METHODS We recruited 522 Han Chinese in Taiwan for this study: 322 AD patients and 200 controls. The patient group was recruited primarily from medical teaching hospitals; patients with antisocial alcoholism were recruited from Taiwanese prisons. Individuals with AD were classified into 3 homogeneous clinical subgroups -- pure alcoholism (pure ALC), ANX/DEP ALC, and antisocial ALC -- using DSM-IV diagnosis. The 5HT1B gene A-161T polymorphism was determined using PCR-RFLP. RESULTS No significant differences in genotypic and allelic frequencies were found between controls and the total AD group or between controls and the 3 AD subgroups. However, there were significant differences in the 5HT1B gene A-161T polymorphism at both the genotype and allelic levels between the ANX/DEP ALC and antisocial ALC subgroups. CONCLUSIONS This study suggests that the 5HT1B gene A-161T polymorphism alone is not a risk factor for increasing susceptibility to either AD or its subtypes. However, 5HT1B gene A-161T polymorphisms might be one of the common genetic factors between the ANX/DEP ALC and antisocial ALC subgroups.

Neuropsychological functions impairment in different subtypes of bipolar disorder with or without comorbid anxiety disorders

Bipolar disorder (BP) patients with comorbid anxiety disorders (ADs) showed more severe clinical characteristics and psychosocial function impairment, worse response to treatment, and more substance use than those without AD. However, few studies focus on differences in neuropsychological function between BP-I and BP-II and patients with and without AD. Seventy-nine BP patients in their interepisode state classified into four groups-BP-I without AD (BP-I(-AD)) (n=22), BP-I with AD (BP-I(+AD)) (n=20), BP-II without AD (BP-II(-AD)) (n=18), BP-II with AD (BP-II(+AD)) (n=19), and healthy controls (HC) (n=30)-were given neuropsychological tests. BP-I(+AD) patients did less well than BP-I(-AD) patients, but only in working memory. BP-II(+AD) patients did less well than the BP-II(-AD) patients in visual immediate memory, visual delayed memory, working memory, and psychomotor speed. BP-I(+AD) has limited effects on neuropsychological performance. However, significant effects were found only in BP-II(+AD) patients compared with BPII(-AD) patients. We hypothesized that comorbid AD worsens neuropsychological performance more in BP-II than in BP-I patients.

Temperaments×genes in bipolar I and bipolar II disorder patients

We found the main effects of harm avoidance temperament in predicting bipolar I and II, but the interaction between novelty seeking and Ser9Gly polymorphisms of dopamine D3 receptor gene was demonstrated in bipolar-I patients only. This study provided evidence that differences existed between BP-I and BPII in gene and temperament interactions.

Personality Disorders in Female and Male College Students With Internet Addiction.

Abstract A high rate of personality disorders (PDs) was found in individuals with Internet addiction (IA) in previous studies using clinical and limited sample sizes. The present study further made comparisons between sex and incorporated a control group to compare the frequencies of PD between individuals with IA and those without IA. Five hundred fifty-six college students (341 females) completed self-report surveys and were later given diagnostic interviews to assess for a PD diagnosis. Males with IA showed a higher frequency of narcissistic PD, whereas females with IA showed a higher frequency of borderline, narcissistic, avoidant, or dependent PD when compared with those without IA. The high rate of PD among Internet addicts may be associated with the core features of specific PD psychopathology. Sex differences in the PD frequencies among IA individuals provide indications for understanding the psychopathological characteristics of PDs in Internet addicts.

The effectiveness of dialectical behavior therapy skills training group vs. cognitive therapy group on reducing depression and suicide attempts for borderline personality disorder in Taiwan

In this study the effectiveness of the condensed Dialectical Behavior Therapy Skills Training Group (DBTSTG) was compared to the Cognitive Therapy Group (CTG) in reducing depression and suicide reattempt and modifying emotion regulation strategies among those with borderline personality disorder (BPD). A total of 82 depressed BPD college students with a suicidal history within the past 6-months were randomly allocated to DBTSTG or CTG. Both groups had similar reductions in suicide reattempts and depression after the intervention and 6-month follow-ups. However, the CTG showed improvements in cognitive errors, but the DBTSTG revealed increases in acceptance and decreases in suppression scores. Both groups were effective in decreasing depression and suicide reattempt in BPD college students, probably through increasing adaptive antecedent-focused or response-focused strategies of emotion regulation, respectively.