Yinyin Zang

Influence of GNB3 C825T polymorphism on the efficacy of antidepressants in the treatment of major depressive disorder: A meta-analysis

OBJECTIVE We performed the present meta-analysis in order to evaluate the influence of a common polymorphism (C825T, rs5443 C>T) in the GNB3 gene on the efficacy of antidepressants in the treatment of major depressive disorder (MDD). METHOD A relevant literature was searched using the PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, CBM and CNKI databases without any language restrictions. STATA Version 12.0 software (Stata Corporation, College Station, Texas USA) was used for this meta-analysis. Odds ratio (OR) and its corresponding 95% confidence interval (95% CI) were calculated. RESULTS Our findings suggested that the GNB3 C825T polymorphism was significantly correlated with a higher response rate to antidepressants in MDD patients under the allele and dominant models. Furthermore, we found significant associations between GNB3 C825T polymorphisms and antidepressant-induced remission in MDD patients. Ethnicity-stratified analysis indicated that GNB3 C825T polymorphisms may be strongly related to the efficacy of antidepressants in the treatment of MDD among Asians, but not in Caucasians (all P>0.05). CONCLUSION Our findings provide empirical evidence that GNB3 C825T polymorphisms may be correlated with the efficacy of antidepressants in the treatment of MDD, especially among Asians patients.

Predictors of suicidal ideation among active duty military personnel with posttraumatic stress disorder

BACKGROUND Given the alarming rate of military suicides, it is critical to identify the factors that increase risk of suicidal thoughts and behaviors among active duty military personnel. METHODS This study examined a predictive model of suicidal ideation among 366 treatment-seeking active duty military personnel with posttraumatic stress disorder (PTSD) following deployments to or near Iraq or Afghanistan. Structural equation modeling was employed to examine the relative contribution of combat exposure, social support, PTSD severity, depressive symptoms, guilt, and trauma-related cognitions on suicidal ideation. RESULTS The final structural equation model had a highly satisfactory fit [χ2 (2) =2.023, p=.364; RMSEA =.006; CFI =1; GFI =.998]. PTSD severity had an indirect effect on suicidal ideation via trauma-related cognitions. Depression had a direct positive effect on suicidal ideation; it also had an indirect effect via trauma-related cognitions and interpersonal support. Among participants who had made a previous suicide attempt, only depression symptom severity was significantly linked to suicidal ideation. LIMITATIONS Data are cross-sectional, precluding causal interpretations. Findings may only generalize to treatment seeking active duty military personnel with PTSD reporting no more than moderate suicidal ideation. CONCLUSIONS These findings suggest that depression and trauma-related cognitions, particularly negative thoughts about the self, play an important role in suicidal ideation among active duty military personnel with PTSD. Negative cognitions about the self and interpersonal support may be important targets for intervention to decrease suicidal ideation.

Clinical significance of decreased protein expression of dehydroepiandrosterone sulfate in the development of depression: A meta-analysis

BACKGROUND Previous evidence has shown that adrenal androgens, dehydroepiandrosterone (DHEA) and its sulfate derivative (DHEAS) have significant functions related to the control of mood, affect, and anxiety. Changes in their expression levels are reportedly related to several psychiatric disorders. The objective of this meta-analysis was to explore the role of DHEAS protein expression in patients with depression. METHOD Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, China BioMedicine (CBM) and China National Knowledge Infrastructure (CNKI) were electronically searched. Only those studies that analyzing DHEAS expression in depression patients were considered eligible for inclusion. Standardized mean differences (SMDs) were pooled with a 95% confidence interval (CI) in accordance with the random-effects model. RESULTS Ten clinical case-control studies, consisting of 4496 subjects (493 patients with depression and 4003 healthy controls) were incorporated for analysis. Results revealed a lower DHEAS protein expression level in patients with depression than in normal controls (SMD=0.17, 95% CI: 0.06-0.27, P=0.002). Ethnicity-stratified analysis indicated that lower levels of DHEAS expression in depression patients were not observed in Caucasians or Asians (both P>0.05). CONCLUSION Elevated DHEAS protein expression may be correlated with the biological pathophysiology of depression, indicating that checking DHEAS levels and administration of DHEAS could contribute to the effective treatment of depression.

Change in obsessive-compulsive symptoms mediates subsequent change in depressive symptoms during exposure and response prevention.

OBJECTIVE The current study examines the temporal relationship between changes in obsessive-compulsive symptoms and changes in depressive symptoms during exposure and response prevention (EX/RP) therapy for obsessive-compulsive disorder (OCD). METHOD Participants were 40 adults (53% female) who received EX/RP in a randomized controlled trial comparing serotonin reuptake inhibitor (SRI) augmentation strategies. Participants completed clinician-administered assessments of OCD (Yale-Brown Obsessive Compulsive Scale) and depressive symptoms (Hamilton Depression Rating Scale) every four weeks from baseline to 32-week follow-up. RESULTS Lagged multilevel mediational analyses indicated that change in OCD symptoms accounted for 65% of subsequent change in depressive symptoms. In contrast, change in depressive symptoms only partially mediated subsequent change in OCD symptoms, accounting for 20% of the variance in outcome. CONCLUSIONS These data indicate that reductions in co-morbid depressive symptoms during EX/RP for OCD are largely driven by reductions in obsessive-compulsive symptoms.

Effect of Prolonged Exposure Therapy Delivered Over 2 Weeks vs 8 Weeks vs Present-Centered Therapy on PTSD Symptom Severity in Military Personnel: A Randomized Clinical Trial

Importance Effective and efficient treatment is needed for posttraumatic stress disorder (PTSD) in active duty military personnel. Objective To examine the effects of massed prolonged exposure therapy (massed therapy), spaced prolonged exposure therapy (spaced therapy), present-centered therapy (PCT), and a minimal-contact control (MCC) on PTSD severity. Design, Setting, and Participants Randomized clinical trial conducted at Fort Hood, Texas, from January 2011 through July 2016 and enrolling 370 military personnel with PTSD who had returned from Iraq, Afghanistan, or both. Final follow-up was July 11, 2016. Interventions Prolonged exposure therapy, cognitive behavioral therapy involving exposure to trauma memories/reminders, administered as massed therapy (n = 110; 10 sessions over 2 weeks) or spaced therapy (n = 109; 10 sessions over 8 weeks); PCT, a non–trauma-focused therapy involving identifying/discussing daily stressors (n = 107; 10 sessions over 8 weeks); or MCC, telephone calls from therapists (n = 40; once weekly for 4 weeks). Main Outcomes and Measures Outcomes were assessed before and after treatment and at 2-week, 12-week, and 6-month follow-up. Primary outcome was interviewer-assessed PTSD symptom severity, measured by the PTSD Symptom Scale–Interview (PSS-I; range, 0-51; higher scores indicate greater PTSD severity; MCID, 3.18), used to assess efficacy of massed therapy at 2 weeks posttreatment vs MCC at week 4; noninferiority of massed therapy vs spaced therapy at 2 weeks and 12 weeks posttreatment (noninferiority margin, 50% [2.3 points on PSS-I, with 1-sided &agr; = .05]); and efficacy of spaced therapy vs PCT at posttreatment. Results Among 370 randomized participants, data were analyzed for 366 (mean age, 32.7 [SD, 7.3] years; 44 women [12.0%]; mean baseline PSS-I score, 25.49 [6.36]), and 216 (59.0%) completed the study. At 2 weeks posttreatment, mean PSS-I score was 17.62 (mean decrease from baseline, 7.13) for massed therapy and 21.41 (mean decrease, 3.43) for MCC (difference in decrease, 3.70 [95% CI,0.72 to 6.68]; P = .02). At 2 weeks posttreatment, mean PSS-I score was 18.03 for spaced therapy (decrease, 7.29; difference in means vs massed therapy, 0.79 [1-sided 95% CI, −∞ to 2.29; P = .049 for noninferiority]) and at 12 weeks posttreatment was 18.88 for massed therapy (decrease, 6.32) and 18.34 for spaced therapy (decrease, 6.97; difference, 0.55 [1-sided 95% CI, −∞ to 2.05; P = .03 for noninferiority]). At posttreatment, PSS-I scores for PCT were 18.65 (decrease, 7.31; difference in decrease vs spaced therapy, 0.10 [95% CI, −2.48 to 2.27]; P = .93). Conclusions and Relevance Among active duty military personnel with PTSD, massed therapy (10 sessions over 2 weeks) reduced PTSD symptom severity more than MCC at 2-week follow-up and was noninferior to spaced therapy (10 sessions over 8 weeks), and there was no significant difference between spaced therapy and PCT. The reductions in PTSD symptom severity with all treatments were relatively modest, suggesting that further research is needed to determine the clinical importance of these findings. Trial Registration clinicaltrials.gov Identifier: NCT01049516

Psychometrics of the Child PTSD Symptom Scale for DSM-5 for Trauma-Exposed Children and Adolescents

This study evaluated psychometric properties of interview, self-report, and screening versions of the Child PTSD Symptom Scale for DSM-5 (CPSS-5), a measure of posttraumatic stress disorder (PTSD) for traumatized youth based on DSM-5 criteria. Participants were 64 children and adolescents (51.6% female, 45.3% African American/Black) between 8 and 18 years of age (M = 14.1, SD = 2.5) who had experienced a DSM-5 Criterion A trauma. Participants completed test–retest procedures for the self-report and interviewer versions of the CPSS-5 in 2 visits that were up to 2 weeks apart. Analyses revealed excellent internal consistencies, good to excellent test–retest reliability, and good convergent validity and discriminant validity for interview and self-report versions of the scale. Receiver operating characteristic analysis yielded a cutoff score of 31 on the CPSS-5 self-report version for identifying probable PTSD diagnosis. Six most frequently endorsed items by those with a possible PTSD diagnosis on the CPSS-5 were identified to constitute a screen version of the CPSS-5, showing good internal consistency and test–retest reliability. The three versions of the CPSS-5 scales are valid and reliable measures of DSM-5 PTSD symptomatology in traumatized youth.

Cognitive Emotion Regulation Strategies Associated With the DSM-5 Posttraumatic Stress Disorder Criteria

Maladaptive cognitive emotion regulation strategies have been proposed to contribute to the maintenance of posttraumatic stress disorder (PTSD). Prior work has focused on the relationship between these strategies and PTSD as a whole, rather than on how they are related to each PTSD symptom cluster. The purpose of the current study was to determine whether cognitive emotion regulation strategies are predictive of certain PTSD symptom clusters under the Diagnostic and Statistical Manual of Mental Disorders 5th ed. (DSM-5; American Psychiatric Association, 2013) criteria (intrusive thoughts, avoidance, negative alterations in cognitions and mood, and hyperarousal). Participants included 365 treatment-seeking, active-duty military personnel with PTSD. The negative alterations in cognitions and mood cluster were associated with dysfunctional cognitions: greater negative cognitions about the self, negative cognitions about the world, and self-blame, as well as catastrophizing (Rc2 = .519). The negative alterations in cognitions and mood cluster did not show a strong relationship with blaming others, possibly due to the complex nature of self- and other-blame in this primarily deployment-related PTSD sample. Finally, the intrusive thoughts cluster was associated with catastrophizing (Rc2 = .211), suggesting an association between frequent intrusive memories and excessively negative interpretation of those memories.

Role of CACNA1C gene polymorphisms and protein expressions in the pathogenesis of schizophrenia: a case-control study in a Chinese population

The study aimed to investigate the correlations of CACNA1C genetic polymorphisms and protein expression with the pathogenesis of schizophrenia in a Chinese population. This research included 139 patients diagnosed with schizophrenia (case group) and 141 healthy volunteers (control group). Case and control samples were genotyped using denaturing high-performance liquid chromatography (DHPLC). Haplotypes of rs10848683, rs2238032, and rs2299661 were analyzed using the Shesis software. A mouse model of schizophrenia was established and assigned to test and blank groups. Western blotting was used to detect CACNA1C protein expression. The genotype and allele distribution of rs2238032 and rs2299661 differed between the case and control groups. TT genotype of rs2238032 and G allele of rs2299661 could potentially reduce the risk of schizophrenia. The distribution of rs2238032 genotype has a close connection with cognitive disturbance and the results of the general psychopathology classification exam. The distribution of rs2299661 genotypes was closely related to sensory and perceptual disorders, negative symptom subscales, and the results of the general psychopathology classification exam. CTC haplotype increased and CTG decreased the risk of schizophrenia in healthy people. In the brain tissues of mice with schizophrenia, the CACNA1C protein expression was higher in the test group than in the blank group. Our study demonstrated that CACNA1C gene polymorphisms and CACNA1C protein expression were associated with schizophrenia and its clinical phenotypes.

Changes in posttraumatic stress disorder (PTSD) and depressive symptoms over the course of prolonged exposure.

Objective: Prior studies of prolonged exposure therapy (PE) suggested that reduction of posttraumatic stress disorder (PTSD) precedes reduction in depression, yet no research has collapsed data across multiple studies to examine whether the directionality of reduction remains consistent in larger and diagnostically diverse samples. Thus, the objective of this study is to conduct an evaluation of bidirectional associations between PTSD and depression in PE. Method: Participants (n = 216) from three randomized controlled trials of PE alone, PE + alcohol use disorder treatment, and PE + nicotine use disorder treatment completed weekly PTSD and depression severity measures. First, we analyzed the directional relationship between PTSD and depression over time in 2 single models to separately examine the effects of PTSD on depression and vice versa. Second, we analyzed a combined model to examine the simultaneous effects of reduction in PTSD on reduction in depression over and above the effects of reduction in depression on reduction in PTSD, and vice versa. Results: Two single models suggested that reductions in PTSD lead to reductions in depression and vice versa. The combined models suggested that both directions of change are important and reciprocal. The strength of predictive power from PTSD to depression, and vice versa, is approximately equal. Most significant prediction of PTSD from depression and vice versa occurred early in treatment. Conclusion: The relationship between reductions in PTSD and depression during PE is transactional. Regardless of whether PTSD or depression decreases first, reduction in the other symptom cluster is likely to follow.

The implementation of prolonged exposure: Design of a multisite study evaluating the usefulness of workshop with and without consultation

This randomized trial examines the dissemination and implementation of prolonged exposure (PE) therapy for posttraumatic stress symptoms in U.S. Army medical treatment facilities. The study compares two PE training models: Standard PE training, comprised of a 4-day workshop only, and Extended PE training, comprised of a 4-day workshop plus expert case consultation. Behavioral health providers (N=180) across three medium-to-large Army installations will be randomly assigned to either Standard PE training or Extended PE training. Changes in provider attitudes will be examined across groups. After completing PE training, the use of PE components with patients reporting posttraumatic stress symptoms and clinical outcomes of these participating patients (N=500) will be examined. This article describes the rationale and methods of the study. In addition, a number of methodological issues in conducting a multisite naturalistic study in the U.S. Army are discussed.