Personality and Alexithymic Disparity in Obsessive-Compulsive Disorder Based on Washing and Checking.

The aim of this study was to investigate pathway relationship of personality characteristics and alexithymic traits in OCD symptoms of obsession, and compulsive behavior of washing and checking. Two-hundred and seventy patients diagnosed with OCD were consecutively recruited from the psychiatric outpatient department of a teaching hospital. Structural equation modeling showed those more neurotic, less extraverted and with higher levels of alexithymia difficulty identifying feelings (DIF), difficulty describing feelings (DDF) and externally oriented thinking (EOT) were more likely to develop obsessive thoughts. Those less extraverted was more prone to develop washing compulsions, and those more neurotic were more likely to develop checking compulsions. EOT was the only alexithymic trait to have no gender difference within this group of patients with OCDs. The different personality and alexithymic trait pathways found between OCD obsession, washing and checking symptoms provide support that they may be different subtypes within the OCD diagnosis. Obsession was associated with washing, but not checking. Furthermore, no gender difference was found between the obsession and compulsive symptoms. Extraversion and neuroticism can be used to differentiate washing and checking, and alexithymia to differentiate washing and obsessions. This should be taken into consideration for intervention targeting patients with different OCD symptoms.

ABCB1 gene polymorphisms are associated with the severity of major depressive disorder and its response to escitalopram treatment.

OBJECTIVE: ATP-binding cassette, sub-family B (MDR/TAP), member 1 (ABCB1) is a drug transporter protein expressed on the epithelial cells of the intestine and the endothelial cells of the blood-brain barrier. Intestinal ABCB1 actively transports drugs from the cell membrane and prevents them from entering the blood stream whereas the blood-brain barrier ABCB1 prevents drugs from entering the central nervous system. In this study, we tested whether genetic polymorphisms within the ABCB1 gene are associated with the severity of depression and the effectiveness of the antidepressant, escitalopram (S-CIT), in treating major depressive disorder (MDD). METHODS: Twenty single nucleotide polymorphisms in the ABCB1 gene were selected and genotyped in 100 MDD patients who had undergone S-CIT treatment continuously for 8 weeks. The serum concentrations of S-CIT and its metabolites (S-desmethylcitalopram and S-didesmethylcitalopram) were then measured at weeks 2, 4, and 8. RESULTS: The ABCB1 genotypes of rs1922242 (P=0.0028) and rs1202184 (P=0.0021) showed significant association with the severity of depressive symptoms as assessed by the Hamilton Rating Scale for Depression adjusted with Hamilton Rating Scale for Anxiety. The haplotype block, rs1882478-rs2235048-rs2235047-rs1045642-rs6949448 (from intron 27 to intron 26), of ABCB1 was found strongly associated with the remission rate (global P=0.003, d.f.=69) in which haplotype T-T-T-C-C was associated with a slower remission rate on S-CIT treatment (P=0.001). The haplotypes may not be indicators of the severity of depression or anxiety. CONCLUSION: Our findings suggest that single nucleotide polymorphisms in the ABCB1 gene may be indicators of the severity of depression and of the likely S-CIT treatment remission response in MDD.

Sarcosine therapy for obsessive compulsive disorder: a prospective, open-label study.

BACKGROUND: Several lines of evidence implicate glutamatergic neurotransmission in the pathophysiology of obsessive compulsive disorder (OCD). Sarcosine is an endogenous antagonist of glycine transporter-1. By blocking glycine uptake, sarcosine may increase the availability of synaptic glycine and enhance N-methyl-d-aspartate (NMDA) subtype glutamatergic neurotransmission. In this 10-week open-label trial, we examined the potential benefit of sarcosine treatment in OCD patients. METHOD: Twenty-six outpatients with OCD and baseline Yale-Brown Obsessive Compulsive Scale (YBOCS) scores higher than 16 were enrolled. Drug-naive subjects (group 1, n = 8) and those who had discontinued serotonin reuptake inhibitors for at least 8 weeks at study entry (group 2, n = 6) received sarcosine monotherapy. The other subjects (group 3, n = 12) received sarcosine as adjunctive treatment. A flexible dosage schedule of sarcosine 500 to 2000 mg/d was applied. The primary outcome measures were Y-BOCS and Hamilton Anxiety Inventory, rated at weeks 0, 2, 4, 6, 8, and 10. Results were analyzed by repeated-measures analysis of variance. RESULTS: Data of 25 subjects were eligible for analysis. The mean ± SD Y-BOCS scores decreased from 27.6 ± 5.8 to 22.7 ± 8.7, indicating a mean decrease of 19.8% ± 21.7% (P = 0.0035). Eight (32%) subjects were regarded as responders with greater than 35% reduction of Y-BOCS scores. Five of the responders achieved the good response early by week 4. Although not statistically significant, drug-naive (group 1) subjects had more profound and sustained improvement and more responders than the subjects who had received treatment before (groups 2 and 3). Sarcosine was tolerated well; only one subject withdrew owing to transient headache. CONCLUSION: Sarcosine treatment can achieve a fast therapeutic effect in some OCD patients, particularly those who are treatment naive. The study supports the glycine transporter-1 as a novel target for developing new OCD treatment. Large-series placebo-controlled, double-blind studies are recommended.

White matter abnormalities of fronto-striato-thalamic circuitry in obsessive-compulsive disorder: A study using diffusion spectrum imaging tractography.

Previous studies have reported white matter abnormalities in patients with obsessive-compulsive disorder (OCD). This study aimed to further explore white matter abnormalities in OCD patients through diffusion spectrum imaging (DSI) and tractography of the two white matter tracts which most probably play an important role in OCD neuropathology: the anterior segment of cingulum bundles (ACB) and the anterior thalamic radiations (ATR). Twelve right-handed, medicated adult patients with OCD and 12 matched controls underwent DSI on a 3 tesla magnetic resonance imaging (MRI) system. Tractography based on DSI data was reconstructed to define the ACB and ATR. Mean generalized fractional anisotropy (GFA) was calculated for each targeted tract and was used to analyze local changes in microstructural integrity along individual tracts. There was a significantly lower mean GFA in both the right ATR and left ACB in OCD subjects compared to controls. OCD subjects also demonstrated decreased left-lateralized asymmetry of the ACB when compared to controls. Furthermore, the mean GFA of the left ACB positively correlated with OCD subjects' obsessive subscores on the Yale-Brown Obsessive-Compulsive scale. This study supports the white matter abnormalities in the ACB and ATR of OCD subjects, which corroborates neurobiological models that posit a defect in fronto-striato-thalamic circuitry in OCD.

Anxiety, depressive symptom and suicidal ideation of outpatients with obsessive compulsive disorders in Taiwan.

AIMS AND OBJECTIVES: The major aims of this study were to explore the differences in anxiety, depressive symptoms and suicidal ideation between high and low obsessive compulsive symptom groups, as well as predictors for suicidal ideation among outpatients with obsessive compulsive disorder. BACKGROUND: Obsessive compulsive disorder is often accompanied by anxiety, depression and even suicidal ideation. However, there have been very few studies exploring the inter-relationships among anxiety, depressive symptoms and suicidal ideation for patients with obsessive compulsive disorder. DESIGN: This study employed a cross-sectional comparative research design. METHODS: A sample of 128 outpatients with obsessive compulsive disorder was recruited from a medical teaching hospital in Northern Taiwan. The major study instruments included the Beck Anxiety Inventory, Beck Depression Inventory II, Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Beck Scale for Suicide Ideation. We divided outpatients into two groups: outpatients with Y-BOCS scores higher than 15 were placed in the high obsessive compulsive symptom group, while outpatients with Y-BOCS score lower than or equal to 15 were placed in the low obsessive compulsive symptom group. Statistical methods included Pearson's product-moment correlation, independent samples t-test, chi-square test and multiple regressions. RESULTS: Results revealed that obsessive compulsive disorder outpatients with high Y-BOCS scores also had higher rates of being single and having an earlier onset age, poorer disease control, higher levels of anxiety, depressive symptoms and suicidal ideation. The predictors for suicidal ideation were anxiety and depressive symptoms. CONCLUSIONS: Obsessive compulsive disorder patients with higher obsessive compulsive symptoms are at greater risk of higher levels of anxiety, depressive symptoms and suicidal ideation. In addition to depression, anxiety symptoms contribute significantly to suicidal ideation among patients with obsessive compulsive disorder. RELEVANCE TO CLINICAL PRACTICE: Standard nursing care of patients with obsessive compulsive disorder should incorporate assessing levels of obsessive compulsive symptoms to identify the severity of anxiety, depressive symptoms and suicidal ideation more accurately.

Continuous performance test in drug-naïve patients with obsessive-compulsive disorder: a case-controlled study.

Twenty drug-naïve patients with obsessive-compulsive disorder (OCD) were compared with matched controls on their performance of the Continuous Performance Test (CPT). There was no difference on any measure of the CPT in the two groups. Higher obsession scores, rather than compulsion scores, were associated with poorer sensitivity of the CPT in drug-naïve OCD patients.

Prevalence of psychiatric disorders among bereaved survivors of a disastrous earthquake in taiwan.

This study investigated the prevalence of psychiatric disorders and risk factors for posttraumatic stress disorder (PTSD) and major depressive disorder among bereaved survivors of a severe earthquake in Taiwan. A total of 120 survivors received a psychiatric interview conducted by board-certified psychiatrists. The two most prevalent disorders were PTSD (37 percent) and major depressive disorder (16 percent). The risk factors for PTSD were psychosocial stressors and initial feelings of guilt. The risk factor for major depressive disorder was female gender. Only 25 percent of the survivors with PTSD and 26 percent of those with major depressive disorder sought help at primary care clinics. These results indicate a need to develop an effective outreach strategy for dealing with psychiatric disorders among disaster victims.

CYP1A2 genetic polymorphisms are associated with early antidepressant escitalopram metabolism and adverse reactions.

AIM: The liver CYP1A2 enzyme may metabolize antidepressant escitalopram (S-CIT) to S-desmethylcitalopram (S-DCIT) and S-didesmethylcitalopram (S-DDCIT). This study tested whether genetic polymorphisms in the CYP1A2 gene are associated with the treatment responses to S-CIT. MATERIALS & METHODS: Ten SNPs in CYP1A2 were selected and genotyped in 158 patients under S-CIT treatment. The serum levels of S-CIT and its metabolites were measured by HPLC. RESULTS: CYP1A2 SNPs rs2069521, rs2069526, rs4646425 and rs4646427 are significantly associated with the metabolic ratios of S-DDCIT/S-DCIT (p = 0.002, 0.018, 0.008 and 0.004, respectively) at week 2 of treatment. Carriers of the allele types associated with higher S-DDCIT/S-DCIT ratios had more severe side effects. CONCLUSION: These results suggest that genetic variants in CYP1A2 may be indicators for S-CIT metabolism and that the fast metabolizers may experience more severe adverse reactions in the early stages of S-CIT treatment. Original submitted 27 December 2012; Revision submitted 15 May 2013.

Comparison of escitalopram and paroxetine in the treatment of major depressive disorder.

This is a single-blind, parallel, flexible-dose study to compare the efficacy and tolerability of escitalopram and paroxetine in the treatment of patients with major depressive disorder. We recruited 399 patients from the outpatient clinics of five hospitals in northern Taiwan. Patients were administered either escitalopram (10-30 mg) or paroxetine (20-40 mg) according to the judgment of clinicians. These patients were assessed using the Hamilton Rating Scale for Depression (HAM-D) and the Hamilton Rating Scale for Anxiety at weeks 0, 1, 2, 4, 6, and 8. A total of 302 patients fulfilled the evaluation criteria and were included in a statistical analysis. We found that escitalopram induced more significant symptom reduction and response rate in terms of the mean HAM-D scores at week 6 (P<0.05) and week 8 (P<0.05) than paroxetine, but that there were no significant differences between the two groups in the remission rate. Escitalopram induced significantly less frequency of adverse effects of weakness (P<0.01), nausea and vomiting (P<0.001), drowsiness (P<0.01) as well as somnolence (P<0.01) than paroxetine, although all these side effects were mild and tolerable. However for a more definitive result, future prospective trials with the inclusion of a placebo group and a double-blind design are needed. In patients who did not have severe depression (HAM-D score at baseline<21), but not in severely depressed patients, escitalopram was statistically superior to paroxetine, as shown by the mean change in the HAM-D score.

Genetic polymorphisms of cytochrome P450 enzymes influence metabolism of the antidepressant escitalopram and treatment response.

AIMS: The antidepressant escitalopram (S-CIT) is metabolized by the cytochrome-P450 (CYP) enzymes CYP 2D6, 2C19 and 3A4. This study evaluated the impact of CYP2D6, 2C19 and 3A4 genetic polymorphisms on plasma concentrations of S-CIT and patient treatment response. MATERIALS & METHODS: A total of 100 patients diagnosed with major depressive disorder were recruited to the study and their depression symptoms were assessed using the Hamilton Depression Rating Scale. The genetic polymorphisms *4, *5 and *10 on CYP2D6, *2, *3 and *17 on CYP2C19, and *18 on CYP3A4 were selected based on their function and respective allele frequencies in Asian populations. Polymorphisms were analyzed using the SNPstream genotyping system, PCR and direct sequencing methods. The steady-state serum concentrations of S-CIT and its metabolites S-desmethylcitalopram and S-didesmethylcitalopram were analyzed by HPLC. According to semiquantitative gene dose (SGD) and gene dose (GD) models for allele combinations of these polymorphisms, CYP2D6 was clustered into intermediate (0.5, 1 and 1.5 SGD) and extensive (2 SGD) metabolizers, while CYP2C19 was clustered into poor (0 GD) and extensive (1 and 2 GDs) metabolizers. RESULTS: The group of patients with intermediate CYP2D6 metabolism (0.5 SGD) had a significantly higher frequency of remitters from major depressive disorder during the 8-week treatment (p = 0.0001). Furthermore, CYP2C19 poor metabolizers had significantly higher S-CIT serum levels than did extensive metabolizers at weeks 2, 4 and 8 (p < 0.05). The allele frequencies in CYP3A4*18 and CYP2C19*17 were too low to permit further subgroup analyses. CONCLUSION: Our results suggest that the genetic polymorphisms in CYP2C19 may be influencing S-CIT serum concentrations, and that specific CYP2D6 polymorphisms may be predicting patient treatment outcomes based on gene dosage analyses.

CYP1A2 genetic polymorphisms are associated with treatment response to the antidepressant paroxetine.

AIM: Paroxetine is a drug of choice in the treatment of major depressive disorder (MDD). Its metabolism has recently been reported to be mediated through the CYP enzymes 1A2 and 2D6. In our current study, we tested whether genetic polymorphisms in CYP1A2 are associated with the treatment efficacy and side effects of paroxetine. MATERIALS & METHODS: A total of 241 MDD patients who had taken paroxetine continually for 8 weeks were recruited, and their steady state paroxetine concentrations were measured at weeks 2, 4 and 8. The genotypes of these patients were then assessed for the presence of nine SNPs, which were selected from either the HapMap Chinese ethnic group, the literature report or through their functional role in the CYP1A2 gene. RESULTS: The allele types for SNPs rs4646425 (permutation p = 0.03), rs2472304 (permutation p = 0.01) and rs2470890 (permutation p = 0.004) demonstrated significant associations with paroxetine treatment remission at week 8. Response rates in the Hamilton Rating Scale for Depression (HAM-D) and for The Hamilton Rating Scale for Anxiety (HAM-A) were significantly associated with the SNPs rs4646425 (p = 0.0126 and 0.0088 for HAM-D and HAM-A, respectively) and rs4646427 (p = 0.0067 and 0.0196 for HAM-D and HAM-A, respectively). The inducible SNP rs762551 had a significant association with paroxetine dose at week 4 (permutation p = 0.012). We did not find an association between these SNPs and the side effects or serum concentrations of paroxetine. CONCLUSION: Genetic variants in the CYP1A2 region may be indicators of treatment response in MDD patients to paroxetine.