Association of prescription data with clinical manifestations and polygenic risk scores in patients with bipolar I disorder: An exploratory study.

BACKGROUND: We assessed the association of prescription data with clinical manifestations and polygenic risk scores (PRS) in patients with bipolar I disorder. METHODS: We enrolled 1471 individuals with BID and divided them into several groups according to treatment options and clinical manifestations. BD-PRS of each patient was calculated using the Psychiatric Genomics Consortium data. Data on single nucleotide polymorphisms, clinical manifestations, and prescriptions were extracted from BiGS. RESULTS: Chronicity, suicidality, substance misuse, mixed symptoms, and deterioration of life functioning were significantly more severe in the group that was not prescribed any mood stabilizers (MS). Chronicity, psychotic symptoms, suicidality, and deterioration of life functioning were significantly severe in the group that received two or more antipsychotics (APs). BD-PRS between the group with AP(s) only and that with other treatment options significantly differed. BD-PRS of the group with AP(s) only was significantly lower than that with other treatment options. Our linear regression results showed that high severity of particular clinical aspects, lower BD-PRS, and prescriptions with fewer MSs or more APs were independently associated with poor life functioning. LIMITATIONS: This study had a cross-sectional design, without differentiating the bipolar phase, which could influence our results. CONCLUSIONS: Poor life functioning in patients with BID was associated with a high severity of particular clinical aspects, BD-PRS, and prescriptions including fewer MSs or more APs. BD-PRS was significantly higher in the group receiving only AP(s) than that in the groups receiving other drugs.

Variable alterations in plasma erythropoietin and brain-derived neurotrophic factor levels in patients with major depressive disorder with and without a history of suicide attempt.

It is hypothesized that major depression disorder (MDD) is associated with impaired neuronal plasticity, and that antidepressant treatments restore neuroplasticity. Brain-derived neurotrophic factor (BDNF) and erythropoietin (Epo) show neurotrophic and neuroprotective effects. We evaluated plasma Epo and BDNF levels in 50 MDD inpatients before treatment and in 50 healthy controls. The MDD inpatients consisted of 20 MDD patients without and 30 MDD patients with a recent suicide attempt. The plasma Epo level was significantly higher in nonsuicidal and suicidal MDD patients than in healthy controls (p ≤ 0.001), while the plasma BDNF level was significantly lower in suicidal MDD than in nonsuicidal MDD patients and healthy controls (p ≤ 0.001). When classifying study participants into low-Epo and high-Epo and low-BDNF and high-BDNF subgroups based on the cutoff of Epo or BDNF calculated using receiver operating characteristics (ROC) curve analysis, logistic regression analysis revealed that high-Epo and low-BDNF status correlated with a respective significant odds ratio of 7.367 (p = 0.015) and 33.123 (p ≤ 0.001) for suicidal MDD. In conclusion, plasma BDNF level was decreased in untreated MDD patients, which was presumed to be a dysfunctional effect of the onset of MDD. However, an increase in plasma Epo was observed in MDD in connection with a recent suicide attempt, indicating that this triggers hypoxic stress to induce a compensatory increase in Epo.

Plasma level of brain-derived neurotrophic factor (BDNF) in patients with postpartum depression.

Postpartum depression occurs in 10-15% of mothers. Brain-derived neurotrophic factor (BDNF) is a nerve growth factor that plays a role in neuroplasticity. We hypothesized that the concentration of BDNF is related to reproduction and childbirth, and that women with postpartum depression show alteration in BDNF level. A total of 104 pregnant women was selected as subjects, and 60 non-pregnant women were selected as normal controls. Symptoms of depression were evaluated in the pregnant study subjects using the diagnostic criteria outlined in the Edinburgh Postnatal Depression Scale (EPDS). The pregnant subjects were divided into three groups of perinatal non-depressed controls (n = 61), postpartum depression-recovery (n = 18), and postpartum depression (n = 25). The plasma concentration of BDNF was higher in the pregnant group than in non-pregnant controls and lower in the postpartum depression group at 6 weeks after delivery than in the perinatal non-depressed group. In the postpartum depression-recovery group, the BDNF concentration increased at 6 weeks after delivery compared to that at 24 weeks of gestation. This study found significant changes in plasma BDNF concentration in depressed pregnant women.

Serum Levels of Tumor Necrosis Factor-α and Loudness Dependence of Auditory Evoked Potentials at Pretreatment and Posttreatment in Patients with Major Depressive Disorder.

BACKGROUND: Proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), are associated with the pathophysiology of major depressive disorder (MDD). Several studies have reported that increased TNF-α might be associated with tryptophan depletion, which eventually could result in MDD. However, other studies revealed that TNF-α increased serotonin firing in raphe. Therefore, whether TNF-α increases or decreases serotonin activity remains unclear. Here, we aimed to determine the relationship between serum TNF-α level and central serotonergic activity using the loudness dependence of auditory evoked potentials (LDAEP) and standardized low-resolution brain electromagnetic tomography (sLORETA), as well as to evaluate the effects of antidepressants on TNF-α levels. METHODS: LDAEP, serum TNF-α level, and depression severity were measured in 64 MDD outpatients pre and post 3 months of treatment. RESULTS: Pretreatment TNF-α levels were negatively correlated with the pretreatment N1 sLORETA-LDAEP, P2 sLORETA-LDAEP, and N1/P2 sLORETA-LDAEP (p < 0.05). In multiple regression analysis for N1/P2 sLORETA-LDAEP, lower N1/P2 sLORETA-LDAEP was significantly related to higher TNF-α (CE = -0.047, p = 0.017) when all subjects were dichotomized based on the median TNF-α level (7.16 pg/mL) into pretreatment low- and high-TNF-α groups. In addition, the pretreatment Beck Depression Inventory, P2 LDAEP, and N1/P2 sLORETA-LDAEP were greater in the high-TNF-α groups than in the low-TNF-α groups (p < 0.05). Moreover, the posttreatment TNF-α level was significantly decreased compared to the pretreatment TNF-α level (z = -2.581, p = 0.01). However, the posttreatment TNF-α levels were not associated with posttreatment LDAEP. CONCLUSIONS: Higher TNF-α level is associated with decreased LDAEP, which could indicate compensatory elevation of central serotonin activity in outpatients with MDD, although this effect disappeared and TNF-α level was reduced after three months of antidepressant treatment.

Transgenerational Transmission of Trauma: Psychiatric Evaluation of Offspring of Former "Comfort Women," Survivors of the Japanese Military Sexual Slavery during World War II.

"Comfort women" are survivors of sexual slavery by the Imperial Japanese Army during World War II, who endured extensive trauma including massive rape and physical torture. While previous studies have been focused on the trauma of the survivors themselves, the effects of the trauma on the offspring has never been evaluated before. In this article, we reviewed the first study on the offspring of former "comfort women" and aimed to detect the evidence of transgenerational transmission of trauma. In-depth psychiatric interviews and the Structured Clinical Interview for DSM-5 Axis I Disorders were conducted with six offspring of former "comfort women." Among the six participants, five suffered from at least one psychiatric disorder including major depressive disorder, panic disorder, posttraumatic stress disorder, adjustment disorder, insomnia disorder, somatic symptom disorder, and alcohol use disorder. Participants showed similar shame and hyperarousal symptoms as their mothers regarding stimuli related to the "comfort woman" issue. Increased irritability, problems with aggression control, negative worldview, and low self-esteem were evident in the children of mothers with posttraumatic stress disorder. Finding evidence of transgenerational transmission of trauma in offspring of "comfort women" is important. Future studies should include more samples and adopt a more objective method.

Alterations in Serum BDNF and GDNF Levels after 12 Weeks of Antidepressant Treatment in Female Outpatients with Major Depressive Disorder.

OBJECTIVE: Some clinical studies have found alterations in the levels of serum brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) after applying antidepressant treatment in patients with major depressive disorder (MDD). We evaluated the serum BDNF and GDNF levels before and after 12 weeks of antidepressant treatment in MDD outpatients. METHODS: Serum BDNF and GDNF levels were measured in 23 female MDD outpatients at baseline and after 12 weeks of treatment. The severity of depression was measured with the Hamilton Depression Rating Scale-17 (HAMD-17). Remission of MDD to the treatment was defined as a posttreatment HAMD-17 score of <7. RESULTS: Among MDD patients, 19 (82.6%) subjects were in mild to moderate depression. The whole MDD patients had significantly higher serum BDNF and GDNF levels at baseline than those after 12 weeks of antidepressant treatment. The baseline serum BDNF and GDNF levels did not significantly between the remission and nonremission groups. The significant alteration in both BDNF and GDNF levels after antidepressant treatment were observed in patients with remission. CONCLUSION: The present study suggests that the baseline serum BDNF and GDNF levels are higher than the posttreatment levels in some mild-to-moderate MDD outpatients and the significant alteration in BDNF and GDNF level after treatment were observed in patients with remission.

Psychiatric Sequelae of Former "Comfort Women," Survivors of the Japanese Military Sexual Slavery during World War II.

"Comfort women" refers to young women and girls who were forced into sexual slavery by the Imperial Japanese military during World War II. They were abducted from their homes in countries under Imperial Japanese rule, mostly from Korea, and the rest from China, Philippines, Malaysia, Taiwan, Indonesia, the Netherlands, etc. "Comfort women" endured extreme trauma involving rape, sexual torture, physical abuse, starvation, threats of death, and witnessed many others being tortured and killed. This article reviews all the studies that have investigated the psychiatric or psychosocial sequelae of the survivors of the Japanese military sexual slavery. Most importantly, a recent study which conducted a psychiatric evaluation on the former "comfort women" currently alive in South Korea is introduced. The participants' unmarried rate was relatively high and their total fertility rate was relatively low. Majority of the participants reported having no education and being the low economic status. They showed high current and lifetime prevalence of posttraumatic disorder, major depressive disorder, somatic symptom disorder, social anxiety disorder, panic disorder, and alcohol use disorder. Participants showed high suicidality and majority of the participants still reported being ashamed of being former "comfort women" after all these years. This article high-lights the fact that the trauma has affected the mental health and social functioning of former "comfort women" throughout their lives, and even to the present day.

Psychiatric Findings in Suspected and Confirmed Middle East Respiratory Syndrome Patients Quarantined in Hospital: A Retrospective Chart Analysis.

OBJECTIVE: Little is known about the psychiatric complications or risk factors for depression in suspected or confirmed Middle East Respiratory Syndrome (MERS) patients quarantined in hospital. METHODS: A retrospective chart review was performed of all the patients admitted to the acute MERS inpatient unit at the NMC during the 2015 outbreak. RESULTS: 30 (75%) were confirmed to be MERS-CoV positive among 40 admitted cases. Among the 24 MERS survivors, 17 (70.8%) exhibited psychiatric symptoms and 10 (41.7%) received a psychiatric diagnosis and medication during their hospital stay. Suspected MERS patients did not exhibit psychiatric symptoms or receive a psychiatric diagnosis. 27 suspected or confirmed MERS patients (age 41.15±18.64, male 37.0%) completed psychological assessments. A multiple linear regression analysis revealed that the Korean National Health and Nutrition Examination Survey-Short form and the Impact of Event Scale-Revised scores were significantly positively correlated with Patient Health Questionnaire-9 scores. CONCLUSION: Our findings indicate that the acute treatment of MERS-CoV infections in quarantine had a significant impact on the patients' mental health. Furthermore, assessment of the risk factors for depression may identify vulnerable patients who require psychiatric care and attention during hospital quarantine.

Korean Guidelines for the Pharmacological Treatment of Social Anxiety Disorder: Initial Treatment Strategies.

OBJECTIVE: The aim of the present study was to provide clinical consensus and evidence regarding initial treatment strategies for the pharmacological treatment of social anxiety disorder (SAD) in Korea. METHODS: We prepared a questionnaire to derive a consensus from clinicians regarding their preference for the pharmacological treatment of SAD in Korea. Data regarding medication regimens and psychotropic drugs used during initial treatment, the doses used, and the pharmacological treatment duration were obtained. Responses were obtained from 66 SAD experts, and their opinions were classified into three categories (first-line, second-line, third-line) using a chi-square analysis. RESULTS: Clinicians agreed upon first-line regimens for SAD involving monotherapy with selective serotonin reuptake inhibitors (SSRIs) or the serotonin-norepinephrine reuptake inhibitor (SNRI) venlafaxine, or combined therapy using antidepressants with betablockers or benzodiazepines on a standing or as-needed basis. First-line psychotropic drug choices for initial treatment included the following: escitalopram, paroxetine, sertraline, venlafaxine, and propranolol. The medication dosage used by domestic clinicians was found to be comparable with foreign guidelines. Domestic clinicians tended to make treatment decisions in a shorter amount of time and preferred a similar duration of maintenance treatment for SAD when compared with foreign clinicians. CONCLUSION: This study may provide significant information for developing SAD pharmacotherapy guidelines in Korea, especially in the early stage of treatment.

Treatment response in relation to subthreshold bipolarity in patients with major depressive disorder receiving antidepressant monotherapy: a post hoc data analysis (KOMDD study).

BACKGROUND: The aim of this observational study was to determine whether subthreshold bipolarity affects treatment response and remission in patients with major depressive disorder receiving antidepressant (AD) monotherapy over a 6-month follow-up period. METHODS: Seventy-eight patients with major depressive disorder were stratified into two subgroups according to the presence of subthreshold bipolarity, identified using the Korean version of the Mood Disorder Questionnaire (K-MDQ), which classifies patients as positive for a screening of bipolarity based on the cutoff for the total K-MDQ score (ie, 7 points). They received AD monotherapy such as escitalopram, sertraline, paroxetine, or tianeptine for 6 months. The Beck Depression Inventory (BDI), Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Scale, and Beck Scale for Suicide Ideation were applied at baseline, 1 week, 3 weeks, 2 months, 3 months, and 6 months. RESULTS: The mean HAMD, BDI, and Beck Scale for Suicide Ideation scores were higher in the bipolarity group than in the nonbipolarity group at 3 weeks. The mean BDI score was also higher in the bipolarity group than in the nonbipolarity group at 6 months. Evaluation of the ratio of improvement for each scale revealed different patterns of percentage changes between the two groups over the 6-month follow-up period. Furthermore, the response and remission rates (as assessed using BDI and HAMD scores) were higher in the nonbipolarity group than in the bipolarity group, with the exception of HAMD scores at the 3-week follow-up time point. CONCLUSION: The findings of this study showed that depressed patients with bipolarity had a worse response to AD monotherapy than did those without bipolarity.

How Childhood Maltreatment Is Related to Suicidality, Bipolarity and Central Serotonergic Activity in Patients with Major Depressive Disorder: A Cross-Sectional Pilot Study.

OBJECTIVE: The aims of this study were to determine whether childhood maltreatment contributes to the occurrence of major depressive disorder (MDD) with bipolarity, and whether there is a relationship between central serotonergic activity, as assessed using loudness dependence of auditory evoked potentials (LDAEP), and childhood maltreatment. METHODS: Thirty-five MDD patients were stratified according to the presence or absence of childhood trauma into two subgroups, childhood trauma (CT) and no childhood trauma (NCT), using the Korean version of the Childhood Trauma Questionnaire (K-CTQ). The CT group was subjected to further analysis. Several psychometric ratings were also applied. In addition, auditory processing for the loudness dependence of auditory evoked potentials (LDAEP), which was used as a marker of serotonergic activity, was measured before beginning medication. RESULTS: There was a significant difference in total Korean Bipolar Spectrum Disorder Scale score between the CT and NCT groups (t=-2.14, p=0.04). The total K-CTQ score was positively correlated with the total Beck Scale for Suicidal Ideation (BSS) score (r=0.36, p=0.036). In particular, emotional abuse was positively correlated with the total Barratt Impulsiveness Scale (r=0.38, p=0.026), BSS (r=0.38, p=0.025), and Hamilton Depression Rating Scale (HAMD) (r=0.36, p=0.035) scores. There was also a positive correlation between LDAEP and total Hypomania Personality Scale (r=0.49, p=0.02) and HAMD (r=0.58, p=0.004) scores within CT group. CONCLUSION: The findings of this study support that there is a relationship between childhood maltreatment and bipolarity in patients with MDD.

Prolactin and macroprolactin levels in psychiatric patients receiving atypical antipsychotics: A preliminary study.

The aims of this study were to clarify whether atypical antipsychotics can elevate serum levels of both macroprolactin and prolactin, and whether the macroprolactin levels differ according to the type of atypical antipsychotic being taken. In total, 245 subjects were enrolled consecutively in 6 hospitals. Serum prolactin and macroprolactin levels were measured at a single time point during maintenance antipsychotic monotherapy. The mean total serum prolactin levels including macroprolactin were 11.91, 20.73, 16.41, 50.83, 12.84, and 59.1ng/mL for patients taking aripiprazole, blonanserin, olanzapine, paliperidone, quetiapine, and risperidone, respectively, while those for macroprolactin were 1.71, 3.86, 3.73, 7.28, 2.77, and 8.0ng/mL. The total prolactin and macroprolactin levels were significantly higher among those taking paliperidone and risperidone than among those taking any of the other antipsychotics (p<0.01). Moreover, there was a strong positive correlation between serum levels of prolactin and macroprolactin. Sexual dysfunction was reported in 35.5% (87/245) of the total subjects. However, the total prolactin level did not differ significantly between subjects with and without sexual dysfunction except gynecomastia. These findings suggest that treatment with risperidone and paliperidone can induce hyperprolactinemia and macroprolactinemia in psychiatric patients.

Plasma glial cell line-derived neurotrophic factor in patients with major depressive disorder: a preliminary study.

BACKGROUND: Some clinical studies have reported reduced peripheral glial cell line-derived neurotrophic factor (GDNF) level in elderly patients with major depressive disorder (MDD). We verified whether a reduction in plasma GDNF level was associated with MDD. METHOD: Plasma GDNF level was measured in 23 healthy control subjects and 23 MDD patients before and after 6 weeks of treatment. RESULTS: Plasma GDNF level in MDD patients at baseline did not differ from that in healthy controls. Plasma GDNF in MDD patients did not differ significantly from baseline to the end of treatment. GDNF level was significantly lower in recurrent-episode MDD patients than in first-episode patients before and after treatment. CONCLUSIONS: Our findings revealed significantly lower plasma GDNF level in recurrent-episode MDD patients, although plasma GDNF levels in MDD patients and healthy controls did not differ significantly. The discrepancy between our study and previous studies might arise from differences in the recurrence of depression or the ages of the MDD patients.

Alterations in plasma vascular endothelial growth factor levels in patients with schizophrenia before and after treatment.

Vascular endothelial growth factor (VEGF), a potent angiogenetic factor, is a known neurotrophic factor. In this study, we examined plasma levels of VEGF in 50 patients with schizophrenia (SPR) and 50 healthy control subjects. We also explored any changes in plasma VEGF levels after 6-week treatment with antipsychotic agents in patients with schizophrenia. All subjects with schizophrenia were either medication-naïve or medication-free for at least 4 weeks before assessment. Plasma VEGF levels in all subjects were significantly correlated with smoking duration, which was considered to be a significant covariate. Pre-treatment plasma VEGF levels in patients with schizophrenia were significantly lower than those in healthy controls. Post-treatment VEGF levels were significantly increased in patients with schizophrenia. Plasma VEGF levels in patients with schizophrenia did not exhibit significant correlation with the total or subscale scores of the Positive and Negative Syndrome Scale (PANSS) either at baseline or at the end of the 6-week treatment. In conclusion, our findings reveal that plasma VEGF levels before treatment were lower in patients with schizophrenia and that their VEGF levels increased after treatment. Thus, VEGF may have a neuroprotective role in the improvement of schizophrenia or in the treatment effects of antipsychotics.

Prediction of long-term treatment response to selective serotonin reuptake inhibitors (SSRIs) using scalp and source loudness dependence of auditory evoked potentials (LDAEP) analysis in patients with major depressive disorder.

BACKGROUND: Animal and clinical studies have demonstrated that the loudness dependence of auditory evoked potentials (LDAEP) is inversely related to central serotonergic activity, with a high LDAEP reflecting weak serotonergic neurotransmission and vice versa, though the findings in humans have been less consistent. In addition, a high pretreatment LDAEP appears to predict a favorable response to antidepressant treatments that augment the actions of serotonin. The aim of this study was to test whether the baseline LDAEP is correlated with response to long-term maintenance treatment in patients with major depressive disorder (MDD). METHODS: Scalp N1, P2 and N1/P2 LDAEP and standardized low resolution brain electromagnetic tomography-localized N1, P2, and N1/P2 LDAEP were evaluated in 41 MDD patients before and after they received antidepressant treatment (escitalopram (n = 32, 10.0 ± 4.0 mg/day), sertraline (n = 7, 78.6 ± 26.7 mg/day), and paroxetine controlled-release formulation (n = 2, 18.8 ± 8.8 mg/day)) for more than 12 weeks. A treatment response was defined as a reduction in the Beck Depression Inventory (BDI) score of >50% between baseline and follow-up. RESULTS: The responders had higher baseline scalp P2 and N1/P2 LDAEP than nonresponders (p = 0.017; p = 0.036). In addition, changes in total BDI score between baseline and follow-up were larger in subjects with a high baseline N1/P2 LDAEP than those with a low baseline N1/P2 LDAEP (p = 0.009). There were significantly more responders in the high-LDAEP group than in the low-LDAEP group (p = 0.041). CONCLUSIONS: The findings of this study reveal that a high baseline LDAEP is associated with a clinical response to long-term antidepressant treatment.

Possible Association between Serotonin Transporter Gene Polymorphism and Suicide Behavior in Major Depressive Disorder.

OBJECTIVE: The serotonin transporter (5-HTT) genes are major candidate genes for modulating the suicidal behavior. We investigated the association between serotonin transporter polymorphisms and suicidal behavior in patients with major depressive disorder (MDD). METHODS: Serotonin transporter intron 2 VNTR polymorphism (5-HTTVNTR) and serotonin transporter linked polymorphic region polymorphism (5-HTTLPR) were analyzed in 132 depressed patients with suicidal attempt as well as in 122 normal controls. Hamilton's 17-item Depression Rating Scale (HDRS), the Risk-Rescue rating system (RRR) and the Lethality Suicide Attempt Rating Scale updated (LSARS-II) were assessed for the depressed patients. RESULTS: Although not statistically significant, a trend was found such that the 10/10 and 10/12 alleles of 5-HTTVNTR were more common in suicidal subjects than in control subjects. Comparing allele frequency, those with a 10 allele or 10 allele carriers were higher in suicidal subjects than in control subjects. No difference was noted in 5-HTTLPR genotypes and haplotype distribution between the suicidal subjects and control subjects. The RRR scores in subjects with the 10/10 5-HTTVNTR genotype or 10 5-HTTVNTR allele were significantly lower than those in subjects with other genotypes. CONCLUSION: These results show the possibility that 10 allele of 5-HTTVNTR is related to suicidal behavior in the suicidal subjects with MDD and suggest that 12 allele of 5-HTTVNTR might be related to more lethality in the suicidal subjects with MDD.

Lower serum brain-derived neurotrophic factor levels are associated with failure to achieve remission in patients with major depression after escitalopram treatment.

BACKGROUND: Remission, the primary goal of treatment for major depressive disorder (MDD), is the absence of significant signs or symptoms and the return to a state of normal functioning. A recent study found that the level of brain-derived neurotrophic factor (BDNF) increased after antidepressant treatment in remitted patients. This study evaluated serum BDNF levels in MDD patients with chronic maintenance treatment, and compared these between remission and nonremission groups. MATERIALS AND METHODS: Serum BDNF levels were measured in 34 MDD patients and 35 healthy controls. The severity of depression was measured using the Hamilton Depression Rating Scale (Ham-D). The MDD patients were divided into remission and nonremission groups according to a cutoff total Ham-D score of either ≤7 or ≤6. RESULTS: Serum BDNF levels differed significantly between the remission, nonremission, and healthy control groups (P<0.05). The Bonferroni post hoc test confirmed that serum BDNF levels were significantly lower in the nonremission group than in the healthy-control group (P<0.05), but did not differ significantly between the remission and healthy-control groups. LIMITATIONS: This study included a small sample, and measured serum BDNF levels in the MDD patients at only one point during the maintenance treatment. CONCLUSION: This study found that serum BDNF levels during maintenance treatment were lower in MDD patients with failure to achieve remission than in controls, while the remitted subjects had normalized serum BDNF levels. A lower level of serum BDNF during maintenance treatment is associated with failure to achieve remission in patients with major depression. Moreover, serum BDNF levels after chronic antidepressant treatment can be used as a biological marker for detecting nonremission.

DRD3 gene rs6280 polymorphism may be associated with alcohol dependence overall and with Lesch type I alcohol dependence in Koreans.

BACKGROUND: Several polymorphisms of the dopamine D3 receptor (DRD3) gene are reported to be involved in the susceptibility to alcoholism. Although the DRD3 rs6280 (Ser9Gly) polymorphism plays an important role in various psychiatric disorders, findings regarding the association between this single-nucleotide polymorphism (SNP) and alcohol dependence (AD) have been inconsistent. Therefore, the present study investigated the association between the DRD3 gene rs6280 polymorphism with AD and Lesch type I AD in Korean subjects. METHODS: The DRD3 rs6280 SNP was genotyped in a case-control sample comprising 245 AD patients and 130 healthy controls (HCs). Alcohol Use Disorders Identification Test (AUDIT) scores were also compared relative to genotype in all of the participants. RESULTS: This SNP was significantly associated with both AD overall (χ(2) = 10.09 and p = 0.001, and χ(2) = 10.60 and p = 0.005, for the recessive and additive models, respectively) and with Lesch type I AD (χ(2) = 11.70 and p = 0.001, and χ(2) = 11.70 and p = 0.003, for the recessive and additive models, respectively). The allele frequency differed significantly (χ(2) = 8.45, p = 0.004) between Lesch type I AD and HC subjects. The AUDIT total (F = 6.56, p = 0.011), hazardous alcohol use (F = 7.12, p = 0.008), dependence symptoms (F = 5.10, p = 0.025), and harmful alcohol use (F = 4.83, p = 0.029) scores were significantly higher in those who did not possess the S allele (genotype GG) than in those who did (genotypes SS ± SG). CONCLUSIONS: The findings of this study suggest that the DRD3 rs6280 polymorphism is associated with the development of both AD overall and Lesch type I AD in Koreans.

The association between serum lipid levels, suicide ideation, and central serotonergic activity in patients with major depressive disorder.

BACKGROUND: There is some evidence that low lipid levels cause suicide in depressed patients. The purpose of this study was to identify whether low serum lipid levels are associated with suicide ideation or are correlated with central serotonin function. METHODS: Auditory processing for the loudness dependence of auditory evoked potentials (LDAEP) was measured in 73 outpatients with major depressive disorder. The Hamilton Depression Rating Scale (HAMD) and the Beck Depression Inventory (BDI) were administered on the same day as measurement of the LDAEP. In addition, serum levels of total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride (TG) levels were measured. All subjects had received antidepressant monotherapy. RESULTS: The depressed subjects were divided into those with and without suicide ideation according to the score for HAMD item 3 or BDI item 9. TG levels differed significantly between the two groups, whereas body mass index (BMI), total cholesterol, LDL, HDL, and LDAEP did not. The scores for HAMD item 3 and BDI item 9 were negatively correlated with TG levels (p=0.045 and 0.026, respectively). The LDAEP was negatively correlated with TG levels (p=0.012). Although there was tendency toward a negative correlation between the LDAEP and serum LDL, it did not reach statistical significance (p=0.068). LIMITATIONS: The cross-sectional design of this study means that baseline serum lipid levels were not measured. CONCLUSION: The findings of this study revealed a relationship between TG and suicide ideation that is independent of both BMI and body weight. Furthermore, serum lipid levels were associated with central serotonergic activity, as assessed using the LDAEP.