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  • Characteristics of youth at high risk for bipolar disorder compared to youth with bipolar I or II disorder
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2020-01-25
    Marc J. Weintraub; Christopher D. Schneck; Patricia D. Walshaw; Kiki D. Chang; Manpreet K. Singh; David A. Axelson; Boris Birmaher; David J. Miklowitz

    Significant efforts have been undertaken to characterize the phenomenology of the high-risk period for bipolar disorder (BD) through the examination of youth at familial risk (i.e., having a first- or second-degree relative with BD) or clinical high risk for the disorder (i.e., youth with BD Not Otherwise Specified [NOS] or major depressive disorder [MDD]). However, little is known about the phenomenology of youth at both familial and clinical high risk for BD. In this study, we examined the clinical and psychosocial characteristics of youth at familial and clinical high risk (HR) for BD, and compared these characteristics to those of youth with BD I and II. Both groups were recruited based on current, active mood symptoms from separate randomized trials of family therapy. A total of 127 HR youth were evaluated: 52 (40.9%) were diagnosed with BD-NOS and 75 (59.1%) were diagnosed with MDD. Compared to adolescents with BD I and II (n=145), HR youth had higher rates of anxiety disorders, and comparable rates of attention-deficit/hyperactivity disorder and oppositional defiant disorder/conduct disorder. Mood symptom severity and psychosocial functioning were progressively more impaired consistent with diagnostic severity: BD I>BD II>BD-NOS>MDD. Nonetheless, HR youth exhibited significant depressive symptom severity compared to adolescents with BD I and overall impairment in psychosocial functioning. These results provide further support for the high rates of anxiety disorders and premorbid dysfunction in addition to active mood symptoms for youth at risk for BD, and suggest anxiety is an important phenological characteristics and treatment target of the high-risk period.

    更新日期:2020-01-26
  • Validity of the Mood Disorder Questionnaire (MDQ) as a Screening Tool for Bipolar Spectrum Disorders in Anabaptist Populations
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2020-01-25
    Cassandra M. Dumont; Laura M. Sheridan; Emily K. Besancon; Meghan Blattner; Fabiana Lopes; Layla Kassem; Francis J. McMahon

    The Mood Disorder Questionnaire (MDQ) is an established screening tool for bipolar spectrum disorders (BSD), but has not been validated in diverse populations and the best scoring method remains uncertain. This study assessed diagnostic validity of the MDQ among Anabaptists, an underserved population frequently involved in genetic research. 161 participants completed the MDQ and were diagnosed by a best-estimate final diagnosis (BEFD). Diagnostic agreements between alternate MDQ scoring methods and the BEFD were quantified using Cohen’s Kappa (κ), sensitivity (α), and specificity (β). Scoring criteria evaluated included >7 simultaneous symptoms and at least moderate impairment, >7 simultaneous symptoms, with at least mild impairment, >7 symptoms only, with no further requirement, and three novel scoring methods that require > 5 symptoms or fewer. Diagnostic agreement varied. The original method proved most specific but had the lowest κ and sensitivity. κ increased with more liberal scoring criteria, reaching a maximum under the lower-threshold symptom methods, with little loss of specificity in the 5-symptom method. Decreasing the symptom threshold below 5 conferred little or no benefit. These results support the diagnostic validity of the MDQ among this Anabaptist sample and suggest that a 5-symptom scoring method may increase diagnostic sensitivity.

    更新日期:2020-01-26
  • Global prevalence of burnout symptoms among nurses: A systematic review and meta-analysis
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2020-01-22
    Tiffany Woo; Roger Ho; Arthur Tang; Wilson Tam
    更新日期:2020-01-23
  • Working conditions and depression in the French national working population: Results from the SUMER study
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2020-01-22
    Isabelle Niedhammer; Kylian Coindre; Sarah Memmi; Sandrine Bertrais; Jean-François Chastang

    Objectives The objectives were to explore the associations between various types of occupational exposures and depression in the French national working population, most of the studies in the literature focussing on a limited number of exposures and on symptom scales. Methods The study was based on a nationally representative sample of 25 977 employees, 14 682 men and 11 295 women. Depression was measured using the PHQ-9 instrument and algorithm. Occupational exposures included factors related to both the psychosocial and physical work environment. Weighted logistic regression analyses were performed to study the associations between exposures and outcome with adjustment for covariates among men and women separately. Results The prevalence of depression was higher for women than for men (5.70% versus 3.78%). The final models showed that low decision latitude, low reward, bullying, work-family and ethical conflicts for both genders, and high psychological demands, low social support, and long working hours among women were risk factors for depression. No occupational exposure of physical, biomechanical, chemical and biological nature was associated with depression. Sensitivity analyses confirmed the robustness of the results. Conclusions Significant associations were found between psychosocial work exposures and depression, and there were some differences in these associations between genders. This study is one of the first to provide a comprehensive overview of occupational exposures in association with depression. More prevention towards the psychosocial work environment is needed to improve mental health of working populations.

    更新日期:2020-01-22
  • Comparison of serum microbiome composition in bipolar and major depressive disorders
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2020-01-21
    Sang Jin Rhee; Hyeyoung Kim; Yunna Lee; Hyun Jeong Lee; C. Hyung Keun Park; Jinho Yang; Yoon-Keun Kim; Sungmin Kym; Yong Min Ahn

    Bipolar disorder and major depressive disorder are debilitating psychiatric conditions which can be difficult to differentiate; however, recent studies have suggested that microbiome composition may be a potential tool in distinguishing between these two disorders. This study aimed to compare the serum microbiome composition of patients with bipolar disorder, major depressive disorder, and healthy controls. Serum samples were collected from 42 subjects with bipolar disorder, 30 with major depressive disorder, and 36 healthy controls. Bacterial DNA was isolated from bacteria-derived extracellular vesicles in the serum and then amplified and quantified with primers specific to the V3–V4 hypervariable region of the 16S rDNA gene. Sequence reads were clustered into operational taxonomic units and classified using the SILVA database. Alpha and beta diversity, individual taxa analysis based on phylum and genus, and functional pathways were compared. There was no statistical difference between alpha or beta diversity in patients with bipolar disorder and major depressive disorder; however, the Prevotella 2 and Ruminococcaceae UCG-002 genera were significantly more prevalent in patients with major depressive disorder than in either those with bipolar disorder or in healthy controls. Functional analysis of pathways revealed that the apoptosis function differed between all three groups. In conclusion, the Prevotella 2 and Ruminococcaceae UCG-002 genera were identified as potential candidates for distinguishing bipolar disorder and major depressive disorder. Further studies with larger sample sizes, longitudinal designs, and control for other various confounders are warranted.

    更新日期:2020-01-22
  • Antidepressant and neurocognitive effects of serial ketamine administration versus ECT in depressed patients
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2020-01-16
    Laura Basso; Luisa Bönke; Sabine Aust; Matti Gärtner; Isabella Heuser-Collier; Christian Otte; Katja Wingenfeld; Malek Bajbouj; Simone Grimm

    Background While electroconvulsive therapy (ECT) is considered the gold standard for acute treatment of patients with otherwise treatment-resistant depression, ketamine has recently emerged as a fast-acting treatment alternative for these patients. Efficacy and onset of action are currently among the main factors that influence clinical decision making, however, the effect of these treatments on cognitive functions should also be a crucial point, given that cognitive impairment in depression is strongly related to disease burden and functional recovery. ECT is known to induce transient cognitive impairment, while little is known about ketamine's impact on cognition. This study therefore aims to compare ECT and serial ketamine administration not only with regard to their antidepressant efficacy but also to acute neurocognitive effects. Methods Fifty patients suffering from depression were treated with either serial ketamine infusions or ECT. Depression severity and cognitive functions were assessed before, during, and after treatment. Results ECT and ketamine administration were equally effective, however, the antidepressant effects of ketamine occurred faster. Ketamine improved neurocognitive functioning, especially attention and executive functions, whereas ECT was related to a small overall decrease in cognitive performance. Conclusions Due to its pro-cognitive effects and faster antidepressant effect, serial ketamine administration might be a more favorable short-term treatment option than ECT. Limitations As this research employed a naturalistic study design, patients were not systematically randomized, there was no control group and patients received concurrent and partially changing medications during treatment. Clinical trials registration Functional and Metabolic Changes in the Course of Antidepressive Treatment, https://clinicaltrials.gov/ct2/show/NCT02099630, NCT02099630.

    更新日期:2020-01-16
  • Association between anemia and maternal depression: A systematic review and meta-analysis
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2020-01-08
    Seo Young Kang; Hong-Bae Kim; Sung Sunwoo

    Previous observational epidemiological studies have reported inconsistent findings regarding the association between anemia and the risk of maternal depression. In the present study, we investigated the relationship between anemia and the risk of maternal depression using a meta-analysis. We searched PubMed, EMBASE, and the bibliographies of relevant articles in May 2019. Three evaluators independently reviewed and selected the eligible studies based on the predetermined selection criteria. A random-effects model was employed to calculate meta-estimates of the association between anemia and maternal depression. Of the 1,305 articles, 15 observational epidemiological studies (five case-control studies and 10 cohort studies) were included in the final analysis. A total of 32,792,378 women were included. Anemia was significantly associated with an increased risk of maternal depression in the random-effects meta-analysis of 15 studies (OR/RR: 1.53, 95% CI: 1.32–1.78). The association was consistent in both antepartum (OR/RR: 1.36, 95% CI: 1.07–1.72) and postpartum depression (OR/RR: 1.53, 95% CI: 1.32–1.78). Subgroup meta-analyses based on definition of anemia, definition of depression, and methodological quality reported consistent findings. The current meta-analysis showed that anemia was associated with an increased risk of maternal depression.

    更新日期:2020-01-08
  • White matter fiber density abnormalities in cognitively normal adults at risk for late-onset Alzheimer´s disease.
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2020-01-03
    Stella M. Sánchez; Bárbara Duarte-Abritta; Carolina Abulafia; Gabriela De Pino; Hernan Bocaccio; Mariana N. Castro; Gustavo E. Sevlever; Greg A. Fonzo; Charles B. Nemeroff; Deborah R. Gustafson; Salvador M. Guinjoan; Mirta F. Villarreal

    Tau accumulation affecting white matter tracts is an early neuropathological feature of late-onset Alzheimer’s disease (LOAD). There is a need to ascertain methods for the detection of early LOAD features to help with disease prevention efforts. The microstructure of these tracts and anatomical brain connectivity can be assessed by analyzing diffusion MRI (dMRI) data. Considering that family history increases the risk of developing LOAD, we explored the microstructure of white matter through dMRI in 23 cognitively normal adults who are offspring of patients with Late-Onset Alzheimer’s Disease (O-LOAD) and 22 control subjects (CS) without family history of AD. We also evaluated the relation of white matter microstructure metrics with cortical thickness, volumetry, in vivo amyloid deposition (with the help of PiB positron emission tomography -PiB-PET) and regional brain metabolism (as FDG-PET) measures. Finally we studied the association between cognitive performance and white matter microstructure metrics. O-LOAD exhibited lower fiber density and fractional anisotropy in the posterior portion of the corpus callosum and right fornix when compared to CS. Among O-LOAD, reduced fiber density was associated with lower amyloid deposition in the right hippocampus, and greater cortical thickness in the left precuneus, while higher mean diffusivity was related with greater cortical thickness of the right superior temporal gyrus. Additionally, compromised white matter microstructure was associated with poorer semantic fluency. In conclusion, white matter microstructure metrics may reveal early differences in O-LOAD by virtue of parental history of the disorder, when compared to CS without a family history of LOAD. We demonstrate that these differences are associated with lower fiber density in the posterior portion of the corpus callosum and the right fornix.

    更新日期:2020-01-04
  • Genetic association of FKBP5 with PTSD in US service members deployed to Iraq and Afghanistan
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2020-01-03
    Lei Zhang; Xian-Zhang Hu; Tianzheng Yu; Ze Chen; Jacob Dohl; Xiaoxia Li; David M. Benedek; Carol S. Fullerton; Gary Wynn; James E. Barrett; Mian Li; Dale W. Russell; Robert J. Ursano

    Post-traumatic stress disorder (PTSD) is a debilitating mental disorder with a prevalence of more than 7% in the US population and 12% in the military. An interaction of childhood trauma with FKBP5 (a glucocorticoid-regulated immunophilin) has been reported to be associated with PTSD in the general population. However, there are few reports on the association of FKBP5 with PTSD, particularly in important high-risk population such as the military. Here, we examined the association between four single-nucleotide polymorphisms (SNPs; rs3800373, rs9296158, rs1360780, rs9470080) covering the FKBP5 gene and probable PTSD in US service members deployed to Iraq and Afghanistan, a high-risk military population (n = 3890) (Hines et al., 2014). We found that probable PTSD subjects were significantly more likely to carry the A-allele of rs3800373, G-allele of rs9296158, C-allele of rs1360780, and C-allele of rs9470080. Furthermore, the four SNPs were in one block of strong pairwise linkage disequilibrium (r = 0.91–0.96). Within the block there were two major haplotypes of CATT and AGCC (rs3800373-rs9296158-rs1360780-rs9470080) that account for 99% of haplotype diversity. The distribution of the AGCC haplotype was significantly higher in probable PTSD subjects compared to non-PTSD (p<.05). The diplotype-based analysis indicated that the AGCC carriers tended to be probable PTSD. In this study, we demonstrated the association between FKBP5 and probable PTSD in US service members deployed to Iraq and Afghanistan, indicating that FKBP5 might be a risk factor for PTSD.

    更新日期:2020-01-04
  • Seasonal affective disorder and seasonal changes in weight and sleep duration are inversely associated with plasma adiponectin levels
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2020-01-02
    Faisal Akram; Claudia Gragnoli; Uttam K. Raheja; Soren Snitker; Christopher A. Lowry; Kelly A. Sterns-Yoder; Andrew J. Hoisington; Lisa A. Brenner; Erika Saunders; John W. Stiller; Kathleen A. Ryan; Kelly J. Rohan; Braxton D. Mitchell; Teodor T. Postolache

    Overlapping pathways between mood and metabolic regulation have been increasingly reported. Although impaired regulation of adiponectin, a major metabolism-regulating hormone, has been implicated in major depressive disorder, its role in seasonal changes in mood and seasonal affective disorder-winter type (SAD), a disorder characterized by onset of mood impairment and metabolic dysregulation (e.g., carbohydrate craving and weight gain) in fall/winter and spontaneous alleviation in spring/summer, has not been studied previously. We studied a convenience sample of 636 Old Order Amish (53.8 (±15.5) years; 50.1% males), a population isolate with self-imposed restriction on network electric light at home, and low prevalence of total SAD (t-SAD = syndromal + subsyndromal). We calculated the global seasonality score (GSS) and estimated SAD and subsyndromal-SAD after obtaining Seasonal Pattern Assessment Questionnaires (SPAQs) and measured overnight fasting plasma adiponectin levels. We then tested associations between plasma adiponectin levels and GSS, t-SAD, winter-summer difference in self-reported sleep duration and self-reported seasonal weight change, by using analysis of co-variance (ANCOVA) and linear regression analysis after adjusting for age, gender, and BMI. Participants with t-SAD (N = 14; 2.2%) had significantly lower plasma adiponectin levels (8.76 ± 1.56 μg/mL) than those without t-SAD (11.93 ± 0.22 μg/mL) (p = 0.035). In addition, there was significant negative association between adiponectin levels and winter-summer difference in self-reported sleep duration (p = 0.025) and between adiponectin levels and self-reported seasonal change in weight (p = 0.006). There was no significant association between GSS and adiponectin levels (p = 0.88). To our knowledge, this is the first study testing the association of SAD with adiponectin levels. Replication and extension of our findings longitudinally and, then, interventionally, may implicate low adiponectin as a novel target for therapeutic intervention in SAD.

    更新日期:2020-01-02
  • Preliminary study of structural magnetic resonance imaging phenotypes related to genetic variation in Interleukin-1β rs16944 in adolescents with Bipolar Disorder
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2019-12-31
    Daniel O. Shonibare; Ronak Patel; Alvi H. Islam; Arron W.S. Metcalfe; Lisa Fiksenbaum; James L. Kennedy; Natalie Freeman; Bradley J. MacIntosh; Benjamin I. Goldstein

    Background Bipolar disorder (BD), among the most heritable psychiatric conditions, is associated with increased pro-inflammatory blood markers and pro-inflammatory gene expression in post-mortem brain. We therefore examined the effects of pro-inflammatory single nucleotide polymorphism interleukin-1β (IL-1β) rs16944 on brain structure in adolescents with BD and healthy control (HC) adolescents. Methods T1-weighted 3-T magnetic resonance imaging data were acquired for 38 adolescents with BD and 32 HC adolescents (14–20 years). Using FreeSurfer, a priori regions of interest analyses, examining hippocampus, amygdala, dorsolateral prefrontal cortex (DLPFC), and caudal anterior cingulate cortex, were complemented by exploratory whole-brain vertex-wise analyses. General linear models assessed the association between IL-1β rs16944 and the ROIs, controlling for sex, age, and intracranial volume. Results There was an IL-1β rs16944 polymorphism-by-diagnosis interaction effect on the DLPFC; T-carriers with BD had greater surface area compared to non-carriers with BD. Whereas, HC T-carriers had smaller DLPFC volume compared to HC non-carriers. In vertex-wise analyses, similar interactions were evident in a pars triangularis surface area cluster and a lateral occipital cortex volume cluster. Whole-brain analyses also yielded a main effect of IL-1β rs16944 polymorphism, whereby T-carriers had greater lateral occipital cortex surface area and volume. Conclusions The IL-1β rs16944 polymorphism is associated with neurostructural phenotypes in cognitive and visual regions that subserve functions, including facial recognition and response inhibition, which are known to be aberrant in BD. Future studies are warranted to evaluate whether the observed rs16944-related structural differences are relevant to neurocognitive function, functional neuroimaging phenotypes and IL-1β protein levels.

    更新日期:2019-12-31
  • Threat bias and resting state functional connectivity of the amygdala and bed nucleus stria terminalis
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2019-12-31
    Samantha K. Jenks; Sheng Zhang; Chiang-shan R. Li; Sien Hu

    Background Previous research has distinguished the activations of the amygdala and bed nucleus of stria terminalis (BNST) during threat-related contingencies. However, how intrinsic connectivities of the amygdala and BNST relate to threat bias remains unclear. Here, we investigated how resting state functional connectivity (rsFC) of the amygdala and BNST in healthy controls (HC) and patients with anxiety-related disorders (PAD) associate with threat bias in a dot-probe task. Methods Imaging and behavioral data of 30 PAD and 83 HC were obtained from the Nathan Kline Institute - Rockland sample and processed according to published routines. All imaging results were evaluated at voxel p < 0.001 and cluster p < 0.05, FWE corrected in SPM. Results PAD and HC did not show differences in whole brain rsFC with either the amygdala or BNST. In linear regressions threat bias was positively correlated with amygdala-thalamus rsFC in HC but not PAD, and with BNST-caudate rsFC in PAD but not HC. Slope tests confirmed group differences in the correlations between threat bias and amygdala-thalamus as well as BNST-caudate rsFC. Limitations As half of the patients included were diagnosed with comorbid anxiety, the current findings need to be considered with the clinical heterogeneity and require replication in populations specifically with anxiety disorders. Conclusions Together, these results suggest amygdala and BNST connectivities as new neural markers of anxiety disorders. Whereas amygdala-thalamus rsFC support adaptive regulation of threat response in the HC, BNST-caudate rsFC may reflect maladaptive neural processes that are dominated by anticipatory anxiety.

    更新日期:2019-12-31
  • Oral treatment with Lactobacillus reuteri attenuates depressive-like behaviors and serotonin metabolism alterations induced by chronic social defeat stress
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2019-12-24
    Ruining Xie; Pei Jiang; Li Lin; Jian Jiang; Bin Yu; Jingjing Rao; Hui Liu; Wei Wei; Yi Qiao
    更新日期:2019-12-25
  • Comparing the Effectiveness of VA Residential PTSD Treatment for Veterans who Do and Do Not Report a History of MST: A National Investigation
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2019-12-20
    Ryan Holliday; Noelle B. Smith; Nicholas Holder; Georgina M. Gross; Lindsey L. Monteith; Shira Maguen; Rani A. Hoff; Ilan Harpaz-Rotem

    The Department of Veterans Affairs (VA) has implemented initiatives to promote veterans’ recovery from the health sequelae of military sexual trauma (MST), including posttraumatic stress disorder (PTSD). MST can impact emotion regulation, interpersonal functioning, and perceptions of trust and safety, as well as psychiatric comorbidity, which may impede PTSD treatment. VA PTSD Residential Rehabilitation Treatment Programs (RRTPs) may facilitate the therapeutic process by offering increased structure, support, and adjunctive services. Limited research has examined the effect of MST on PTSD RRTP outcomes. Utilizing data from 7,918 men and women veterans participating in a VA PTSD RRTP, the impact of the experience of MST on rates of program completion and changes in PTSD symptoms during and after treatment were examined. Rates of program completion were similar between those who did and did not report experiencing MST. Multilevel modeling was utilized to examine the impact of MST on PTSD symptoms after accounting for gender, age, race/ethnicity, and program completion. MST survivors endorsed more severe PTSD symptoms at admission; however, PTSD symptom severity scores were similar to those who did not report experiencing MST by discharge. Additionally, MST survivors had larger initial reductions in PTSD symptoms, followed by a greater recurrence of PTSD symptoms over time, compared to those who did not report experiencing MST. MST survivors appear able to participate in and benefit from PTSD RRTPs. Nonetheless, the increased recurrence of PTSD symptoms following discharge from residential treatment indicates the need for strategies to maintain post-treatment gains among MST survivors.

    更新日期:2019-12-21
  • Associations between anger and suicidal ideation and attempts: A prospective study using the National Epidemiologic Survey on Alcohol and Related Conditions
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2019-12-20
    Kirsten H. Dillon; Elizabeth E. Van Voorhees; Eric B. Elbogen

    Suicide is among the leading causes of death in the United States, with rates having risen substantially over the past two decades. Anger is a common symptom of several disorders associated with suicide, and the little research that has been done in the area suggests that it may be an often overlooked transdiagnostic risk factor for both suicidal ideation and behavior. The current study used the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) dataset to evaluate anger at Wave 1 as a risk factor for suicidal ideation and suicide attempt at Wave 2 (three years later) in a nationally representative sample of 34,653 participants. Chi-square analyses indicated that participants reporting problematic anger at Wave 1 were significantly more likely to endorse suicidal ideation (χ2 = 65.35, p < .001) and suicide attempt (χ2 = 24.86, p < .001) at Wave 2. Multivariate regression analyses confirmed that problematic anger significantly predicted suicidal ideation (OR = 1.48, 95% CI [1.21,1.82], p < .001) and attempt (OR = 1.53, 95% CI [1.07,2.19], p = .020) over the three year period, even after adjusting for psychiatric risk factors, and demographic and historical covariates. Findings suggests the potential benefit of integrating anger assessment and treatment into research and clinical programs focused on reducing suicide.

    更新日期:2019-12-20
  • Negative association of perceived risk and willingness to participate in innovative psychiatric research protocols
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2019-12-18
    Tenzin Tsungmey; Jane Paik Kim; Laura B. Dunn; Katie Ryan; Kyle Lane-McKinley; Laura Weiss Roberts

    Psychiatric researchers grapple with concerns that individuals with mental illness may be less likely to appreciate risks of research participation, particularly compared to people not suffering from mental illness. Therefore, empirical studies that directly compare the perspectives of such individuals are needed. In addition, it is important to evaluate perspectives regarding varied types of research protocols, particularly as innovative psychiatric research protocols emerge. In this pilot study, respondents with a mood disorder (n = 25) as well as respondents without a mood disorder (n = 55) were recruited using Amazon's Mechanical Turk (MTurk) platform. These respondents were surveyed regarding four psychiatric research projects (i.e., experimental medication [pill form]; non-invasive magnetic brain stimulation; experimental medication [intravenous infusion]; and implantation of a device in the brain). Regardless of health status, respondents rated the four research protocols as somewhat to highly risky. The brain-device implant protocol was seen as the most risky, while the magnetic brain stimulation project was viewed as “somewhat risky”. Respondents, on average and regardless of health status, rated their willingness at or below “somewhat willing.” Respondents were least willing to participate in the brain-device implant protocol, whereas they were “somewhat willing” to participate in the magnetic brain stimulation protocol. Trust in medical research was negatively associated with perceived risk of research protocols. Perceived risk was negatively associated with willingness to participate, even when adjusting for potential confounders, suggesting that attunement to risk crosses diagnostic, gender, and ethnic categories, and is more salient to research decision-making than trust in medical research and dispositional optimism. The findings of this study may offer reassurance about the underlying decision-making processes of individuals considering participation in innovative neuroscience studies.

    更新日期:2019-12-19
  • The patterns of adverse childhood experiences among Chinese children: Four-year longitudinal associations with psychopathological symptoms
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2019-12-17
    Lei Zhang; Jiao Fang; Yuhui Wan; Chun Gong; Puyu Su; Fangbiao Tao; Ying Sun

    The objective of this longitudinal study was to identify the contribution of individual, cumulative and patterns of adverse childhood experiences (ACEs) exposure in the prediction of psychopathological outcomes during adolescence in the context of Chinese culture. Children from 3 large elementary schools of Bengbu, Anhui Province, China were enrolled in the 3 waves survey from 2013 (mean age = 8.15 years, SD = 0.88) to 2017 (mean age = 11.92 years, SD = 0.88). Latent class analysis (LCA) was used to identify homogeneous, mutually exclusive “classes” of 10 most common ACEs. Logistic regression was used to examine the association between individual, cumulative and patterns of ACEs and depressive and externalizing symptoms at Wave 3. Of the 1766 respondents included in the sample, 75% had at least 1 and 21.5% reported 4 or more ACEs. We found the dose-response relationship between cumulative ACEs and psychopathological outcomes. Results from LCA revealed three high-risk profiles and one low-risk profile, which were labeled: high ACEs (5.7%), highly abusive and adverse events (20.1%), highly abusive and neglected (21.3%), and low ACEs (52.9%). Compared to low ACEs class, each high-risk profile was differentially associated with psychopathological outcomes over 4-year period. Children exposed to high ACEs were at higher risk for future depressive and externalizing symptoms than other classes. This study provides evidence for the predictive impact of ACEs on adolescent psychopathological symptoms in Chinese culture. Clinicians should routinely assess for ACEs to identify children exposed to the most problematic ACE patterns and provide preventive intervention immediately, rather than provide treatment later in life.

    更新日期:2019-12-18
  • Emotion dysregulation is associated with increased prospective risk for chronic PTSD development
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2019-12-14
    Ioana Pencea; Adam P. Munoz; Jessica L. Maples-Keller; Devika Fiorillo; Katharina Schultebraucks; Isaac Galatzer-Levy; Barbara O. Rothbaum; Kerry J. Ressler; Jennifer S. Stevens; Vasiliki Michopoulos; Abigail Powers

    While emotion dysregulation is associated with many psychological disorders, including posttraumatic stress disorder (PTSD), it remains uncertain whether pre-existing emotion dysregulation increases individual risk for prospectively developing PTSD in the aftermath of trauma exposure. Thus, the objective of the current study was to determine whether emotion dysregulation could prospectively predict the development of chronic PTSD symptoms following a traumatic event above and beyond other known associated factors, including depressive symptoms, baseline PTSD symptoms, total traumas experienced, and exposure to interpersonal trauma. Participants (N = 135) were recruited from the emergency department (ED) at Grady Memorial Hospital in Atlanta and follow-up assessments were conducted at 1-, 3-, 6-, and 12-months following trauma exposure. Latent Growth Mixture Modeling was used to identify PTSD symptom trajectories based on symptoms assessed at 1, 3, 6, and 12 months; three trajectories emerged: “chronic”, “recovery”, and “resilient”. For the present study, probability of chronic PTSD symptoms was used as the outcome variable of interest. Linear regression modeling showed that emotion dysregulation was significantly associated with probability of developing chronic PTSD symptoms (p = 0.001) and accounted for an additional 7% of unique predictive variance when controlling for trauma exposure, baseline PTSD, and depressive symptoms. Our findings suggest that emotion dysregulation can be used as both a predictor of chronic PTSD and as a treatment target. Thus, identifying individuals with high levels of emotion dysregulation at the time of trauma and implementing treatments designed to improve emotion regulation could aid in decreasing the development of chronic PTSD among these at-risk individuals.

    更新日期:2019-12-17
  • Predicting suicidal behavior among lesbian, gay, bisexual, and transgender youth receiving psychiatric emergency services
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2019-12-13
    Johnny Berona; Adam G. Horwitz; Ewa K. Czyz; Cheryl A. King

    Lesbian, gay, bisexual, and transgender (LGBT) youth are at elevated risk for self-injurious thoughts and behaviors (SITBs). However, few studies have comprehensively examined SITBs and their longitudinal course in LGBT youth at high risk for suicide. The aims of the present study were to characterize histories of SITBs among high-risk LGBT youth and to examine prospective associations with suicidal behavior. Participants were 285 youth (41.8% LGBT) ages 13 to 25 years receiving psychiatric emergency department (ED) services. Post-discharge suicidal behavior was assessed via 4-month phone interviews and 12 month chart reviews. The sample was 42.1% male, 57.9% female, 2.5% gender minority, 41.8% sexual minority. LGBT participants were more likely to have prior psychiatric ED visits and hospitalizations, more frequent past week suicide ideation, and more severe nonsuicidal self-injury (NSSI). We conducted stratified survival analyses to identify predictors of time to suicidal behavior post discharge. The final model for LGBT youth included past week suicide ideation and past month NSSI episodes. Among non-LGBT youth, the final model included number of lifetime NSSI methods and use of a highly lethal suicide attempt method. Within this sample of youth receiving psychiatric emergency services, LGBT youth were overrepresented and had more severe histories of SITBs. Results suggest the importance of assessing both lifetime and recent factors (i.e., past week and month), particularly for LGBT youth. Future research should replicate these findings in larger samples to explore whether there are unique risk factors that can aid in predicting and preventing suicide among LGBT youth.

    更新日期:2019-12-13
  • Comprehensive phenotyping of depression disease trajectory and risk: Rationale and design of Texas Resilience Against Depression study (T-RAD)
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2019-12-10
    Madhukar H. Trivedi, Cherise Chin Fatt, Manish K. Jha, Crystal M. Cooper, Joseph M. Trombello, Brittany L. Mason, Jennifer Hughes, Bharathi S. Gadad, Andrew H. Czysz, Russell T. Toll, Anne K. Fuller, Sangita Sethuram, Taryn L. Mayes, Abu Minhajuddin, Thomas Carmody, Tracy L. Greer

    Depression has a chronic and recurrent course often with early onset and is the leading cause of disability worldwide. In contrast to diagnoses for other conditions which rely on precise medical tests, the diagnosis of depression still focuses exclusively on symptom reports. As a result, heterogeneous patient groups are included under broad categories. Furthermore, in the absence of companion diagnostic tests, choosing specific treatments for patients remains imprecise with only one-third of patients enter remission with initial treatment, with others requiring multiple intervention steps to achieve remission. In addition to improving treatment outcomes, disease prevention is essential to reduce overall disease burden. Adolescence is a critical window where complex emotional, social, familial, and biological shifts may predispose to lifelong depression. Thus, personalized medicine, integrating individual variability in genes, brain function and clinical phenotypes, can offer a comprehensive approach to provide precise diagnosis, novel drug development, optimal treatment assignment, and prevention of illness and its associated burden. Texas Resilience Against Depression study (T-RAD) encompasses two natural history, longitudinal (10+ years), prospective studies D2K and RAD, each enrolling 2,500 participants. D2K follows participants (ages 10 years and older) who have a current or past diagnosis of a depression or bipolar disorder. RAD follows participants aged 10-24 years who are at risk for depression but not yet suffering from the disease. The study will help to uncover the socio-demographic, lifestyle, clinical, psychological, and neurobiological factors that contribute to mood disorder onset, recurrence, progression, and differential treatment response.

    更新日期:2019-12-11
  • Decoding rumination: A machine learning approach to a transdiagnostic sample of outpatients with anxiety, mood and psychotic disorders
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2019-12-07
    Érico de Moura Silveira, Ives Cavalcanti Passos, Jan Scott, Giovana Bristot, Ellen Scotton, Lorenna Sena Teixeira Mendes, Ana Claudia Umpierre Knackfuss, Luciana Gerchmann, Adam Fijtman, Andrea Ruschel Trasel, Giovanni Abrahão Salum, Márcia Kauer-Sant’Anna

    Objective To employ machine learning algorithms to examine patterns of rumination from RDoC perspective and to determine which variables predict high levels of maladaptive rumination across a transdiagnostic sample. Method Sample of 200 consecutive, consenting outpatient referrals with clinical diagnoses of schizophrenia, schizoaffective, bipolar, depression, anxiety disorders, obsessive compulsive and post-traumatic stress. Machine learning algorithms used a range of variables including sociodemographics, serum levels of immune markers (IL-6, IL-1β, IL-10, TNF-α and CCL11) and BDNF, psychiatric symptoms and disorders, history of suicide and hospitalizations, functionality, medication use and comorbidities. Results The best model (with recursive feature elimination) included the following variables: socioeconomic status, illness severity, worry, generalized anxiety and depressive symptoms, and current diagnosis of panic disorder. Linear support vector machine learning differentiated individuals with high levels of rumination from those ones with low (AUC = 0.83, sensitivity = 75, specificity = 71). Conclusions Rumination is known to be associated with poor prognosis in mental health. This study suggests that rumination is a maladaptive coping style associated not only with worry, distress and illness severity, but also with socioeconomic status. Also, rumination demonstrated a specific association with panic disorder.

    更新日期:2019-12-07
  • Pre-deployment predictors of suicide attempt during and after combat deployment: Results from the Army Study to Assess Risk and resilience in servicemembers
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2019-12-07
    Kelly L. Zuromski, Samantha L. Bernecker, Carol Chu, Chelsey R. Wilks, Peter M. Gutierrez, Thomas E. Joiner, Howard Liu, James A. Naifeh, Matthew K. Nock, Nancy A. Sampson, Alan M. Zaslavsky, Murray B. Stein, Robert J. Ursano, Ronald C. Kessler

    Background Deployment-related experiences might be risk factors for soldier suicides, in which case identification of vulnerable soldiers before deployment could inform preventive efforts. We investigated this possibility by using pre-deployment survey and administrative data in a sample of US Army soldiers to develop a risk model for suicide attempt (SA) during and shortly after deployment. Methods Data came from the Army Study to Assess Risk and Resilience in Servicemembers Pre-Post Deployment Survey (PPDS). Soldiers completed a baseline survey shortly before deploying to Afghanistan in 2011–2012. Survey measures were used to predict SAs, defined using administrative and subsequent survey data, through 30 months after deployment. Models were built using penalized regression and ensemble machine learning methods. Results Significant pre-deployment risk factors were history of traumatic brain injury, 9 + mental health treatment visits in the 12 months before deployment, young age, female, previously married, and low relationship quality. Cross-validated AUC of the best penalized and ensemble models were .75–.77. 21.3–40.4% of SAs occurred among the 5–10% of soldiers with highest predicted risk and positive predictive value (PPV) among these high-risk soldiers was 4.4–5.7%. Conclusions SA can be predicted significantly from pre-deployment data, but intervention planning needs to take PPV into consideration.

    更新日期:2019-12-07
  • The use of machine learning techniques in trauma-related disorders: A systematic review
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2019-12-06
    Luis Francisco Ramos-Lima, Vitoria Waikamp, Thyago Antonelli Salgado, Ives Calvalcante Passos, Lucia Helena Machado Freitas

    Establishing the diagnosis of trauma-related disorders such as Acute Stress Disorder (ASD) and Posttraumatic Stress Disorder (PTSD) have always been a challenge in clinical practice and in academic research, due to clinical and biological heterogeneity. Machine learning (ML) techniques can be applied to improve classification of disorders, to predict outcomes or to determine person-specific treatment selection. We aim to review the existing literature on the use of machine learning techniques in the assessment of subjects with ASD or PTSD. We systematically searched PubMed, Embase and Web of Science for articles published in any language up to May 2019. We found 806 abstracts and included 49 studies in our review. Most of the included studies used multiple levels of biological data to predict risk factors or to identify early symptoms related to PTSD. Other studies used ML classification techniques to distinguish individuals with ASD or PTSD from other psychiatric disorder or from trauma-exposed and healthy controls. We also found studies that attempted to define outcome profiles using clustering techniques and studies that assessed the relationship among symptoms using network analysis. Finally, we proposed a quality assessment in this review, evaluating methodological and technical features on machine learning studies. We concluded that etiologic and clinical heterogeneity of ASD/PTSD patients is suitable to machine learning techniques and a major challenge for the future is to use it in clinical practice for the benefit of patients in an individual level.

    更新日期:2019-12-06
  • Biotypes of functional brain engagement during emotion processing differentiate heterogeneity in internalizing symptoms and interpersonal violence histories among adolescent girls
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2019-12-06
    Kyrie Sellnow, Anneliis Sartin-Tarm, Marisa C. Ross, Shelby Weaver, Josh M. Cisler

    Youth exposed to early life interpersonal violence (IPV) demonstrate heterogeneous clinical symptoms. Studies based on univariate methods suggest that neurocircuitry related to emotion processing explains heterogeneity in internalizing symptoms. Here, we use a multivariate, data-driven method of identifying distinct functional brain activation profiles (i.e., “biotypes”) and test whether these biotypes differentiate internalizing symptoms among IPV-exposed youth. 114 adolescent girls (n = 38 with no IPV exposure or psychopathology; n = 76 with IPV exposure and heterogeneous internalizing symptoms), aged 11–17, completed an emotion processing task during fMRI. To identify distinct biotypes of brain engagement profiles, data-driven clustering analysis was applied to patterns of voxel activation, constrained within a mask of distributed regions implicated in emotion processing. Resulting biotypes (BT1-3) were compared on measures of IPV exposure and internalizing symptoms, as well as symptom reduction during Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) among a subset of participants (n = 21). Cluster analyses identified three biotypes, differentiated by engagement of medial prefrontal, anterior insula, hippocampus, parietal, and ventral visual cortex during emotion processing. BT1 exhibited low levels of IPV exposure and internalizing symptoms. BT2 exhibited elevated levels of IPV, except sexual assault, and demonstrated moderate severity across internalizing symptom domains. BT3 exhibited elevated severity across all IPV and internalizing symptom domains. Greater symptom reduction during TF-CBT was associated with increased pre-to post-treatment changes in similarity with BT1. These results demonstrate distinct profiles of emotion processing neurocircuitry that differentiate heterogeneity in internalizing symptoms in IPV-exposed adolescent girls.

    更新日期:2019-12-06
  • Developing algorithms to predict adult onset internalizing disorders: An ensemble learning approach
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2019-12-06
    Anthony J. Rosellini, Siyu Liu, Grace N. Anderson, Sophia Sbi, Esther Tung, Evdokia Knyazhanskaya

    A growing literature is utilizing machine learning methods to develop psychopathology risk algorithms that can be used to inform preventive intervention. However, efforts to develop algorithms for internalizing disorder onset have been limited. The goal of this study was to utilize prospective survey data and ensemble machine learning to develop algorithms predicting adult onset internalizing disorders. The data were from Waves 1–2 of the National Epidemiological Survey on Alcohol and Related Conditions (n = 34,653). Outcomes were incident occurrence of DSM-IV generalized anxiety, panic, social phobia, depression, and mania between Waves 1–2. In total, 213 risk factors (features) were operationalized based on their presence/occurrence at the time of or before Wave 1. For each of the five internalizing disorder outcomes, super learning was used to generate a composite algorithm from several linear and non-linear classifiers (e.g., random forests, k-nearest neighbors). AUCs achieved by the cross-validated super learner ensembles were in the range of 0.76 (depression) to 0.83 (mania), and were higher than AUCs achieved by the individual algorithms. Individuals in the top 10% of super learner predicted risk accounted for 37.97% (depression) to 53.39% (social anxiety) of all incident cases. Thus, the algorithms achieved acceptable-to-excellent prediction accuracy with a high concentration of incident cases observed among individuals predicted to be highest risk. In parallel with the development of effective preventive interventions, further validation, expansion, and dissemination of algorithms predicting internalizing disorder onset/trajectory could be of great value.

    更新日期:2019-12-06
  • Factors associated with PTSD and partial PTSD among first responders following the Paris terror attacks in November 2015
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2019-11-30
    Yvon Motreff, Thierry Baubet, Philippe Pirard, Gabrielle Rabet, Matthieu Petitclerc, Lise Eilin Stene, Cécile Vuillermoz, Pierre Chauvin, Stéphanie Vandentorren

    During the evening of 13 November 2015, the deadliest terror attacks in France in recent times occurred in the Paris area. Overall, 130 people were killed, 643 were physically injured and several thousands were psychologically impacted. Thousands of first responders, including health professionals, firefighters, affiliated volunteers and police officers were mobilized that night and during the subsequent weeks. The aims of our study were to measure the psychological impact on first responders in terms of post-traumatic stress disorder (PTSD) and partial PTSD as well as associated factors 12 months after the 13 November 2015 terrorist attacks. First responders who had intervened during the night and/or the aftermath of the terror attacks had the possibility of answering a web-based study 8 to 12 months after the attacks. They satisfied criterion A of the DSM 5 definition of PTSD. PTSD and partial PTSD were measured using the PCL-5. Gender, age, educational level, exposure, first responder category, mental health and traumatic event history, training and social support were all analysed as potential factors associated with PTSD and partial PTSD, using multinomial logistic regression. Overall, 663 participants were included in this analysis. Prevalence of PTSD in our sample went from 3.4% among firefighters to 9.5% among police officers and prevalence of partial PTSD from 10.4% among health professionals to 23.2% among police officers. Low educational level and social isolation were associated with PTSD and partial PTSD. Intervention on unsecured crime scenes and lack of training were associated with PTSD. Special attention should be given to first responders living in social isolation, those with low educational levels and those who intervene in unsecured crime scenes. Education and training about the potential mental health consequences of mass trauma intervention should be developed.

    更新日期:2019-11-30
  • Psychiatric symptoms and expression of glucocorticoid receptor gene in cocaine users: A longitudinal study
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2019-11-27
    B. Kluwe-Schiavon, A.B. Schote, M. Vonmoos, L.M. Hulka, K.H. Preller, J. Meyer, M.R. Baumgartner, E. Grünblatt, B.B. Quednow

    Background Chronic cocaine users (CU) display reduced peripheral expression of the glucocorticoid receptor gene (NR3C1), which is potentially involved in stress-related psychiatric symptoms frequently occurring in CU. However, it is unknown whether psychiatric symptoms and lower NR3C1 expression are related to each other and whether reduction of drug consumption reverse them. Method At baseline, NR3C1 mRNA expression was measured in 68 recreational CU, 30 dependent CU, and 68 stimulant-naïve controls. Additionally, the Revised Symptom Checklist (SCL-90R) and the Barratt Impulsiveness Scale (BIS) were assessed. At a one-year follow-up, the association between change in NR3C1 expression and psychiatric symptoms was examined in 48 stimulant-naïve controls, 19 CU who increased and 19 CU who decreased their consumption. At both test sessions, cocaine concentrations in hair samples were determined. Mixed-effects models were used to investigate how changes in drug use intensity affect severity of psychiatric symptoms and NR3C1 expression over time. Results At baseline, recreational and dependent CU displayed elevated impulsivity and considerable symptom burden across most of the SCL-90R subscales. Time-group interaction effects were found for several impulsivity scores, SCL-90R Global Severity Index, Paranoid Thoughts, and Depression subscales as well as for NR3C1 expression. Pairwise comparisons showed that decreasing CU specifically improved in these SCL-90R subscales, while their NR3C1 expression was adapted. Finally, changes in NR3C1 expression were negatively correlated with changes in impulsivity but not SCL-90R scores. Conclusion Our findings suggest that NR3C1 expression changes and some psychiatric symptoms are reversible upon reduction of cocaine intake, thus favouring abstinence-oriented treatment approaches.

    更新日期:2019-11-28
  • Neurocognitive markers of childhood abuse in individuals with PTSD: Findings from the INTRuST Clinical Consortium
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2019-11-23
    Jessica Bomyea, Alan N. Simmons, Martha E. Shenton, Michael J. Coleman, Sylvain Bouix, Yogesh Rathi, Ofer Pasternak, Raul Coimbra, Lori Shutter, Mark S. George, Gerald Grant, Ross D. Zafonte, Thomas W. McAllister, Murray B. Stein

    To date, few studies have evaluated the contribution of early life experiences to neurocognitive abnormalities observed in posttraumatic stress disorder (PTSD). Childhood maltreatment is common among individuals with PTSD and it is thought to catalyze stress-related biobehavioral changes that might impact both brain structure and function into adulthood. The current study examined differences in brain morphology (brain volume, cortical thickness) and neuropsychological performance in individuals with PTSD characterized by low or high self-reported childhood maltreatment, compared with healthy comparison participants. Data were drawn from the INjury and TRaUmatic STress (INTRuST) Clinical Consortium imaging repository, which contains MRI and self-report data for individuals classified as PTSD positive (with and without a history of mild traumatic brain injury [mTBI]), individuals with mild traumatic brain injury only, and healthy comparison participants. The final sample included 36 individuals with PTSD without childhood maltreatment exposure (PTSD, n = 30 with mTBI), 31 individuals with PTSD and childhood maltreatment exposure (PTSD + M, n = 26 with mTBI), and 114 healthy comparison participants without history of childhood maltreatment exposure (HC). The PTSD + M and PTSD groups demonstrated cortical thinning in prefrontal and occipital regions, and poorer verbal memory and processing speed compared to the HC group. PTSD + M participants demonstrated cortical thinning in frontal and cingulate regions, and poorer executive functioning relative to the PTSD and HC groups. Thus, neurocognitive features varied between individuals with PTSD who did versus did not have exposure to childhood maltreatment, highlighting the need to assess developmental history of maltreatment when examining biomarkers in PTSD.

    更新日期:2019-11-26
  • Effectiveness of electroconvulsive therapy on treatment-resistant depressive disorder: A population-based mirror-image study
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2019-11-23
    Chung-Yi Lin, I-Ming Chen, Hui-Ju Tsai, Chi-Shin Wu, Shih-Cheng Liao

    The clinical effects of electroconvulsive therapy (ECT) in treatment-resistant depressive disorders need to be systemically examined in representative samples. This study aimed to examine whether ECT reduced re-hospitalization within one year after discharge. The authors used the Psychiatric Inpatients Medical Claim Dataset, a subset of a total population health claims database from Taiwan, to include 784 inpatients with treatment-resistant depressive disorders screened for ECT during hospitalization between 2001 and 2011. The same number of comparison subjects was selected by frequency matching on the demographic and clinical characteristics. Using a mirror-image comparison design, we compared group differences in re-hospitalization rate, number of hospital days, number of emergency department visits, and direct medical costs during the 1-year pre- and post-ECT periods. The modifying effects of patients’ characteristics on these outcomes were also explored. The results showed that ECT was associated with a significant decrease in the rate of hospitalizations and emergency department visits over the 1-year follow-up period. However, there were no significant difference in the reduced rate of hospitalizations between ECT and comparison group. Demographic and clinical characteristic had no modifying effect on the odds of psychiatric hospitalization. In conclusions, ECT could reduce the rate of hospitalization and number of emergency department visits in patients with treatment-resistant depressive disorders. However, the study results might be biased by the inherent deficits of mirror-image design.

    更新日期:2019-11-26
  • Unextracted plasma oxytocin levels decrease following in-laboratory social exclusion in young adults with a suicide attempt history
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2019-11-22
    Carol Chu, ElizabethA.D. Hammock, Thomas E. Joiner

    Social exclusion is associated with greater suicide risk and more needs to be known about the biological processes contributing to this association. Oxytocin, a neuropeptide that regulates social interactions, may protect against the negative effects of exclusion by motivating social engagement. Oxytocin levels and desire for social engagement increase when non-psychiatric controls experience acute social exclusion. However, among individuals with serious psychiatric illnesses, oxytocin levels decrease following exclusion. No research has examined changes in oxytocin following social exclusion among individuals at risk for suicide. This quasi-experimental study examined differences in oxytocin levels and perceptions of social connectedness following an in-laboratory, acute social exclusion task among (a) individuals with no depression or suicide attempt histories, (b) individuals with current depression symptoms, and (c) individuals with current depression symptoms and suicide attempt histories. Young adults (N = 100) completed self-report measures and provided blood samples before and after an acute social exclusion task (Cyberball). Oxytocin was quantified via enzyme-linked immunosorbent assay. Mixed-design ANCOVAs were used to evaluate changes in unextracted and extracted oxytocin levels, desire for emotional support, thwarted belongingness, and perceived burdensomeness. Among suicide attempters, unextracted oxytocin levels decreased and desire for emotional support did not significantly change following exclusion. Among depressed and healthy controls, desire for emotional support increased and oxytocin levels did not significantly change. No significant changes in extracted oxytocin, thwarted belongingness and perceived burdensomeness emerged. Further research is needed to determine if dysregulated oxytocin-related processes biologically predispose individuals with suicide attempt histories to greater social disconnection and suicide risk.

    更新日期:2019-11-22
  • Suicide risk among gender and sexual minority college students: The roles of victimization, discrimination, connectedness, and identity affirmation
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2019-11-22
    Danielle R. Busby, Adam G. Horwitz, Kai Zheng, Daniel Eisenberg, Gary W. Harper, Ronald C. Albucher, Laura Weiss Roberts, Todd Favorite, William Coryell, Jacqueline Pistorello, Cheryl A. King

    Background Little is known about how victimization and discrimination relate to suicide risk among sexual and gender minority (SGM) college students, or what is protective for these students. The current study will: 1.) determine the extent to which interpersonal victimization, discrimination, identity affirmation, and social connectedness are associated with suicide risk characteristics, and if race and/or ethnicity moderates this association; 2.) examine whether identity affirmation and social connectedness are protective against associations between victimization or discrimination and suicide risk characteristics. Method Participants were 868 students (63.6% female) from four United States universities who completed an online screening survey and met the following study inclusion criteria: self-identification as gender and/or sexual minority, endorsement of at least one suicide risk characteristic and no current use of mental health services. Participants also completed measures that assessed demographics, non-suicidal self-injury (NSSI), victimization, discrimination, connectedness, and LGBTQ identity affirmation. Results Victimization was positively associated with depression severity, suicidal ideation, alcohol misuse, suicide attempt history, and NSSI. Discrimination was positively associated with depression severity, suicide attempt history, and NSSI. Connectedness was inversely associated with depression severity, suicidal ideation severity, suicide attempt history, and NSSI, and moderated the association between victimization and suicide attempt history. LGBTQ identity affirmation moderated the link between victimization and depression. Conclusions Results suggest efforts to decrease victimization and discrimination and increase connectedness may decrease depressive morbidity and risks for self-harm among SGM college students. Further, increasing LGBTQ identity affirmation may buffer the impact of victimization on depression.

    更新日期:2019-11-22
  • Early score fluctuation and placebo response in a study of major depressive disorder
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2019-11-22
    Steven D. Targum, Beth R. Cameron, Ludvina Ferreira, I. David MacDonald

    Early score fluctuation in double-blind, placebo-controlled studies may affect the reliability of the baseline measurement and adversely affect the eventual study outcome. We examined the effect of early score fluctuation during a 2-week double-blind placebo lead-in period in a phase II, double-blind, placebo-controlled trial of adjunctive s-adenosyl methionine (MSI-195) in MDD subjects who had had an inadequate response to ongoing antidepressant treatment. The overall study failed to meet its specified endpoints. We examined the score trajectories of all placebo-assigned subjects during the double-blind placebo lead-in period and subsequent 6-week treatment period. Placebo-assigned subjects with ≥20% HamD17 or MADRS score fluctuations (improvement or worsening) during the double-blind placebo lead-in period (prior to randomization) had significantly higher rates of placebo response and remission at week 8 compared to subjects with <20% response. A post-hoc analysis of evaluable subjects taken from the ITT population that excluded subjects with ≥20% early score response yielded higher effect sizes for both the HamD17 and MADRS sub-groups and statistical significance for MSI-195 over placebo in the MADRS sub-group (p = 0.012) with an effect size of 0.404. A reliable baseline measure is an asset for signal detection. These post-hoc findings suggest that study designs that anticipate and attempt to manage early response prior to randomization may yield more meaningful outcome data for trials of MDD and possibly other disorders as well.

    更新日期:2019-11-22
  • Schizophrenia polygenic risk score influence on white matter microstructure
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2019-11-19
    Beatriz Simões, Evangelos Vassos, Sukhi Shergill, Colm McDonald, Timothea Toulopoulou, Sridevi Kalidindi, Fergus Kane, Robin Murray, Elvira Bramon, Hugo Ferreira, Diana Prata

    Schizophrenia (SZ) and bipolar disorder (BD) are highly heritable, share symptomatology, and have a polygenic architecture. The impact of recent polygenic risk scores (PRS) for psychosis, which combine multiple genome-wide associated risk variations, should be assessed on heritable brain phenotypes also previously associated with the illnesses, for a better understanding of the pathways to disease. We have recently reported on the current SZ PRS's ability to predict 1st episode of psychosis case-control status and general cognition. Herein, we test its penetrance on white matter microstructure, which is known to be impaired in SZ, in BD and their relatives, using 141 participants (including SZ, BP, relatives of SZ or BP patients, and healthy volunteers), and two white matter integrity indexes: fractional anisotropy (FA) and mean diffusivity (MD). No significant correlation between the SZ PRS and FA or MD was found, thus it remains unclear whether white matter changes are primarily associated with SZ genetic risk profiles.

    更新日期:2019-11-19
  • Male-specific association of the 2p25 region with suicide attempt in bipolar disorder
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2019-11-18
    Sophia C. Gaynor, Eric T. Monson, Marie E. Gaine, Michael S. Chimenti, Rachel D. Reichman, Meredith Parsons, Lalita Oonthonpan, Peter P. Zandi, James B. Potash, Virginia L. Willour

    We previously conducted a genome-wide association study (GWAS) of attempted suicide within bipolar disorder, which implicated common variation in the 2p25 region primarily in males. The top association signal from our GWAS occurred in an intergenic region of 2p25 (p = 5.07 × 10−8) and was supported by two independent studies. In the current study, to better characterize the association of the 2p25 region with attempted suicide, we sequenced the entire 350 kb 2p25 region in 476 bipolar suicide attempters and 473 bipolar non-attempters using targeted next-generation sequencing. This fine-mapping project identified 4681 variants in the 2p25 region. We performed both gene-level and individual-variant tests on our sequencing results and identified 375 variants which were nominally significant (p < 0.05) and three common variants that were significantly associated with attempted suicide in males (corrected p = 0.035, odds ratio (OR) = 2.13). These three variants are in strong linkage disequilibrium with the top variant from our GWAS. Our top five variants are also predicted expression quantitative trait loci (eQTL) for three genes in the 2p25 region based on publicly available brain expression databases. Our sequencing and eQTL data implicate these three genes – SH3YL1, ACP1, and FAM150B – and three additional pathways – androgen receptor, Wnt signaling, and glutamatergic/GABAergic signaling – in the association of the 2p25 region with suicide. The current study provides additional support for an association of the 2p25 region with attempted suicide in males and identifies several candidate genes and pathways that warrant further investigation to understand their role in suicidal behavior.

    更新日期:2019-11-18
  • History of premenstrual syndrome and development of postpartum depression: A systematic review and meta-analysis
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2019-11-17
    Sifan Cao, Mark Jones, Leigh Tooth, Gita D. Mishra

    Background Premenstrual syndrome (PMS) is thought to be a risk factor for postpartum depression (PPD), but results from studies examining the association have been mixed. Objectives To estimate the association between pre-pregnancy history of PMS and development of PPD and evaluate the risk of bias of included evidence. Search strategy PubMed, EMBASE, CINAHL, PsycINFO, Cochrane Library, CNKI, Wanfang Data, and reference lists of relevant papers were searched. Selection criteria Observational studies that collected pre-pregnancy history of PMS and measured PPD status between one week and one year after delivery were included. Data collection and analysis This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Random-effect models were used to calculate pooled odds ratios (ORs) with 95% confidence interval (CI). Small study effect was analysed by funnel plot. Risk of bias was assessed using the Risk of Bias Instrument for Non-Randomized Studies of Exposures (ROBINS-E). Main results Our meta-analysis included 19 studies. Overall, women with a pre-pregnancy history of PMS had more than double the odds of PPD compared to those without PMS (OR: 2.20, 95% CI: 1.81–2.68). However, the quality of evidence was low: five studies had moderate risk, eleven studies had serious risk, and three studies had critical risk of bias. Conclusions Current evidence supports a significant association between history of PMS and development of PPD. Well-designed prospective studies are needed to further investigate this relationship.

    更新日期:2019-11-18
  • Acute zebrafish embryonic exposure to permethrin induces behavioral changes related to anxiety and aggressiveness in adulthood
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2019-11-15
    M.E.M. Nunes, L.E. Schimith, D.G. Costa-Silva, L.P. Leandro, I.K. Martins, R.S. De Mello, F.V.M. Nunes, M. Santer, P.B. Vieira, T. Posser, J.L. Franco

    Permethrin (PM) is one of the most used type I synthetic pyrethroid worldwide. Exposure to this compound during pregnancy and early childhood has been indicated as a risk factor for neurodevelopmental disorders. We evaluated the long-term effects of embryonic PM exposure in different stages of zebrafish development. Briefly, embryos (3 hpf) were exposed to sub-lethal concentrations of PM (25 and 50 μg.L−1) during 24 h and then behavioral parameters were evaluated during embryonic (28 hpf), eleutheroembryonic (3 dpf), larval (7 dpf), and adult stages (90 dpf). PM exposure was decreased spontaneous movement at 28 hpf and decreased thigmotaxis in eleutheroembryos. The long-term effects of PM include changes in non-motor behaviors such as fear and anxiety in larva and adults. Adults embryonically exposed to PM also showed a significant increase in aggressiveness parameters. These results demonstrated that embryonic exposure to PM induces persistent neurotoxic effects in adulthood, which can impair the cognitive and behavioral fitness of non-target species contributing to a rise in neurodevelopmental disorders.

    更新日期:2019-11-15
  • Risk and protective factors associated with comorbid PTSD and depression in U.S. military veterans: Results from the National Health and Resilience in Veterans Study
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2019-11-15
    Brandon Nichter, Moira Haller, Sonya Norman, Robert H. Pietrzak

    Converging evidence suggests that veterans with co-occurring PTSD/MDD represent a high-risk group for poor mental health compared to those with PTSD alone. To date, however, little is known about the specific factors that may increase vulnerability for and help buffer risk for comorbid PTSD/MDD. The purpose of this study was to provide a population-based characterization of sociodemographic, risk, and protective variables associated with comorbid PTSD/MDD among U.S. military veterans. Data were analyzed from the National Health and Resilience in Veterans Study, a nationally representative survey of U.S. military veterans (n = 2,732). Analyses compared veterans with PTSD alone and co-occurring PTSD/MDD on sociodemographic, military, and psychosocial characteristics; and examined variables independently associated with PTSD/MDD status. Multivariable logistic regression analyses revealed that racial/ethnic minority status (odds ratio [OR] = 12.5), number of lifetime traumas (OR = 1.3), and time spent engaged in private religious/spiritual activities (OR = 1.8) were associated with PTSD/MDD status, while higher scores on measures of community integration (OR = 0.6) and dispositional optimism (OR = 0.7) were negatively associated with comorbid PTSD/MDD status. Relative importance analyses revealed that dispositional optimism (34%) and community integration (24%) explained the largest proportions of variance in PTSD/MDD comorbidity. Taken together, results of this study suggest that racial/ethnic minority status, greater lifetime trauma burden, and engagement in private religious/spiritual activities are key distinguishing characteristics of U.S. military veterans with comorbid PTSD/MDD vs. PTSD alone. They further underscore the need to study whether targeting dispositional optimism and community integration in prevention and treatment efforts may enhance clinical outcomes in this population.

    更新日期:2019-11-15
  • On the relationship between mathematics and visuospatial processing in Turner syndrome
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2019-11-14
    Joseph M. Baker, Megan Klabunde, Booil Jo, Tamar Green, Allan L. Reiss

    A common neurocognitive phenotype of Turner syndrome (TS) includes coincident deficits in math and visuospatial reasoning while overall IQ remains intact. However, research has highlighted disparities in the relationship between these properties in women with TS, suggesting that not all visuospatial domains are equally related to mathematics in this group. Here, we present findings from a longitudinal investigation of visuospatial processing and its relationship to math performance in adolescent girls with TS and age-matched healthy controls. Participants completed a standardized battery of math and visuospatial tests once a year for 4 years. Linear mixed effects modeling was used to examine the relationship between mathematics and each visuospatial domain over time. Our results indicate that math performance was related to visual tracking, visual-motor coordination, and figure-ground processing. Such visuospatial domains appear to be uniquely affected by TS and could contribute to their deficits in math performance. Furthermore, differences in math and visuospatial test performance between girls with TS and healthy controls remain stable over time. Our results have important implications for the role of visuospatial processing in early math performance and may inform the development of effective interventions aimed at improving math education in children with TS.

    更新日期:2019-11-14
  • Differences in associations between problematic video-gaming, video-gaming duration, and weapon-related and physically violent behaviors in adolescents
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2019-11-14
    Zu Wei Zhai, Rani A. Hoff, Jordan C. Howell, Jeremy Wampler, Suchitra Krishnan-Sarin, Marc N. Potenza

    Seemingly mixed findings have been reported on possible relationships between video-gaming and violent or aggressive behaviors. Given the prevalence of gaming in adolescents and potential harms associated with violent behaviors, relationships between problematic gaming, gaming engagement, and risk behaviors involving weapons and physical violence require further research. This study examined in a large sample of high-school students relationships between problem-gaming severity, gaming duration, and violence-related measures including weapon-carrying, having been threatened by someone with a weapon, perceived insecurity, physical fights and serious fights leading to injuries. Potential moderation by sensation-seeking and impulsivity was also tested. Participants were 3,896 Connecticut high-school adolescents. Chi-square, logistic regression, and moderation models were conducted. Adolescents with at-risk/problem gaming, compared to low-risk and non-gaming adolescents, reported more weapon-carrying, having been threatened with weapons, feeling unsafe at school, and serious fighting leading to injury. Among those reporting gaming, weekly time spent gaming was associated with problem-gaming severity. Those with longer (versus shorter) gaming durations were more likely to report weapon-carrying and feeling unsafe at school. Sensation-seeking moderated associations between at-risk/problem gaming and weapon-carrying frequency. Associations between gaming quantity and problem-gaming severity and measures of weapon-carrying and physical violence in adolescents suggest that understanding further their mechanistic relationships may be important in promoting safer developmental trajectories for youth. Future longitudinal studies may provide important insight into the etiologies underlying these relationships and such information may help develop more effective prevention and intervention strategies.

    更新日期:2019-11-14
  • A meta-analysis of self-reported anticipatory and consummatory pleasure in the schizophrenia-spectrum
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2019-11-14
    Katherine Frost Visser, Hannah C. Chapman, Ivan Ruiz, Ian M. Raugh, Gregory P. Strauss

    Objective Recent conceptual frameworks propose anhedonia reflects abnormalities in the temporal dynamics of positive emotion in schizophrenia, characterized by intact consummatory and impaired anticipatory pleasure. A comprehensive meta-analysis can directly test this theory using self-report data. Method A meta-analysis was performed on studies reporting Temporal Experience of Pleasure Scale (TEPS) data from healthy controls and schizophrenia or schizotypy groups. The TEPS was examined as it contains subscales to measure both consummatory and anticipatory pleasure separately. Statistical heterogeneity and study bias were examined. Meta-regressions evaluated moderators. Results 53 studies were retrieved (7,797 participants). Results revealed small effect sizes for comparisons of combined schizophrenia/schizotypy and control groups for both consummatory and anticipatory pleasure. Within-group comparisons of pleasure conditions were nonsignificant. The percentage of male schizophrenia/schizotypy participants significantly moderated anticipatory and consummatory pleasure for the combined sample and schizotypy alone; male participants were found to report reduced pleasure. There was only minor evidence of bias; sensitivity analysis confirmed result robustness. Exploratory outlier removal for schizophrenia within-group pleasure comparisons revealed a statistically significant difference between reported anticipatory and consummatory pleasure, with consummatory pleasure reduced relative to anticipatory (i.e., in the opposite direction of the majority of experimental research findings). Conclusions These findings provided only modest support for the temporal dynamics of positive emotion conceptualization because they revealed no evidence for: 1) specific anticipatory pleasure deficits in schizophrenia-spectrum participants compared to controls; 2) significant reductions in anticipatory pleasure relative to consummatory pleasure in schizophrenia-spectrum participants.

    更新日期:2019-11-14
  • Prefrontal cortex alterations in glia gene expression in schizophrenia with and without suicide
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2019-11-09
    L. Zhang, R.W.H. Verwer, P.J. Lucassen, I. Huitinga, D.F. Swaab

    Background Patients with schizophrenia (SCZ) run a lifelong risk of suicide. Alterations in glia activities in the prefrontal cortex (PFC) have been reported in relation to suicide in patients with SCZ. While immune processes in the CNS have been related to the susceptibility and course of SCZ, there are hardly any direct comparisons between individuals with SCZ, both those who died of natural causes and those that committed suicide, and healthy controls. Materials and methods We compared mRNA expression using real time qPCR of 16 glia-related genes in the dorsal lateral prefrontal cortex (DLPFC) and the anterior cingulate cortex (ACC) between 35 patients with SCZ (7 suicide completers and 28 patients who died of natural causes) and 34 well-matched controls without psychiatric or neurological disease. Results We found an increased expression of the astrocytic gene aldehyde dehydrogenase-1 family member L1 (ALDH1L1) mRNA, a marker involved in dopaminergic activity, in SCZ versus controls. Excluding individuals with SCZ that committed suicide resulted in an elevated expression in the DLPFC of both ALDH1L1 and glutamine synthetase (GS) genes in patients with SCZ, compared to suicide completers and non-psychiatric controls. Regarding microglia genes: in the ACC, homeostatic markers such as chemokine (C-X3-C motif) ligand 1 (CX3CR1) mRNA expression was increased in SCZ without suicide as compared to suicide completers, while no change was found when compared to controls. Another, purinergic receptor 12 (P2RY12) mRNA was exclusively elevated in the ACC of suicide completers, compared to either other group. Triggering receptor expressed on myeloid cells 2 (TREM2) expression, which maintains microglial metabolism, was reduced in non-suicide patients with SCZ, compared to suicide victims and control subjects. Conclusions Differential changes are found in astrocyte and microglia genes in PFC subregions in relation to schizophrenia and suicide, indicating possible disturbances of glia homeostasis in these conditions.

    更新日期:2019-11-11
  • Differences in genetic and environmental influences on body weight and shape concerns across pubertal development in females
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2019-11-08
    Shannon M. O'Connor, Kristen M. Culbert, Laura A. Mayhall, S. Alexandra Burt, Kelly L. Klump

    The heritability of disordered eating increases during puberty; however, prior studies have largely examined a composite score of disordered eating, rather than specific symptoms. Body weight and shape concerns cut across all eating disorder diagnoses and are some of the strongest prospective risk factors for the development of eating disorders. Yet, little is known about potential developmental increases or decreases in genetic and environmental influences for these key symptoms. This study examined differences in genetic and environmental effects on a range of body weight and shape concerns during puberty and compared results to findings for overall levels of disordered eating symptoms. Participants were 926 same-sex female twins (ages 8–16) from the Michigan State University Twin Registry. Well-validated questionnaires were used to examine pubertal maturation, overall levels of disordered eating, and a range of cognitive body weight/shape constructs: body dissatisfaction, weight/shape concerns, and weight preoccupation. Findings for overall levels of disordered eating were very similar to those obtained in previous work, with significantly increased genetic effects in girls at more advanced pubertal development. Importantly, these same pubertal increases in genetic influences were observed for body dissatisfaction and weight/shape concerns. However, no pubertal moderation of genetic effects was observed for weight preoccupation; instead, pubertal moderation of nonshared and shared environmental effects was observed. Our findings point to differences in the extent to which genetic and environmental factors contribute to various cognitive body weight and shape symptoms during puberty. (Words: 238/250).

    更新日期:2019-11-08
  • Correlates of nonmedical use of prescription opioids among a cohort of adolescents in Ontario, Canada
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2019-11-01
    Maryam Kebbe, Hugues Sampasa-Kanyinga, Hayley A. Hamilton, Ian Colman, Jean-Philippe Chaput

    Introduction Mortality and morbidity rates related to prescription opioid analgesics have been rising in North America and may be a gateway to the nonmedical use of prescription opioids (NUPO). The purpose of this study was to explore correlates of NUPO in the adolescent population given the scarce literature in this area. Methods Cross-sectional data from 10,163 middle- and high-school students (15.1 ± 1.8 years old; 57.0% female; 55.6% White ethnic background) in Ontario were derived from the 2017 Ontario Student Drug Use and Health Survey. Potential correlates of NUPO in the past year included sociodemographic, behavioral, parental, and school characteristics. Results Overall prevalence of NUPO was 10.7%. In the final multivariable model, NUPO was significantly associated with 8 of the 21 correlates examined. Students who used prescription opioids nonmedically were of black, South Asian, and “other” ethnic backgrounds (OR 2.83, OR 1.77, and OR 1.67, respectively); reported a lower subjective socioeconomic status (OR 0.92), lower parental support (OR 0.90), and lower academic performance (OR 0.86); met physical activity recommendations (OR 1.48); consumed energy drinks (OR 1.42); smoked tobacco cigarettes (OR 2.33); and used cannabis (OR 1.84). Conclusions Findings from this study show a wide variety of correlates of NUPO among Canadian adolescents, and highlight the need for further research and the value in targeted prevention and multi-level intervention programs for NUPO in this population.

    更新日期:2019-11-01
  • Alcohol consumption alters Gdnf promoter methylation and expression in rats
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2019-10-31
    Hannah Benedictine Maier, Meraj Neyazi, Alexandra Neyazi, Thomas Hillemacher, Hansi Pathak, Mathias Rhein, Stefan Bleich, Koral Goltseker, Yossi Sadot-Sogrin, Oren Even-Chen, Helge Frieling, Segev Barak

    Alcohol use disorder is one of the most disabling diseases worldwide. Glial-cell derived neurotrophic factor (Gdnf) shows promising results concerning the inhibition of alcohol consumption in rodent models. We investigated the epigenetic regulation of Gdnf following ethanol consumption and withdrawal in a rat model. 32 Wistar rats underwent 7 weeks of intermittent access to alcohol in a 2-bottle choice (IA2BC). Whole blood, Nucleus Accumbens (NAc) and Ventral Tegmental Area (VTA) were collected immediately after the last 24 h of an alcohol-drinking session (alcohol group, AG) or 24 h after withdrawal (withdrawal group, WG). MRNA levels were measured using real-time quantitative PCR. Bisulfite-conversion of DNA and capillary sequencing was used to determine methylation levels of the core promoter (CP) and the negative regulatory element (NRE). The CP of the AG in the NAc was significantly less methylated compared to controls (p < 0.05). In the NAc, mRNA expression was significantly higher in the WG (p < 0.05). In the WG, mRNA expression levels in the VTA were significantly lower (p < 0.05) and showed significantly less methylation in the NRE in the VTA (p < 0.001) and the NAc (p < 0.01) compared to controls. Changes in the cerebral mRNA expression correspond to alterations in DNA methylation of the Gdnf promoter in a rodent model. Our results hold clinical relevance since differences in Gdnf mRNA expression and DNA methylation could be a target for pharmacological interventions.

    更新日期:2019-11-01
  • 更新日期:2019-11-01
  • The efficacy of melatonin and melatonin agonists in insomnia - An umbrella review.
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2019-11-13
    Tian Ling Low,Faith Nadine Choo,Shian Ming Tan

    We conducted an umbrella review to summarize all available systematic reviews and meta-analyses investigating the efficacy of melatonin and melatonin agonists in primary and comorbid insomnia disorders. Two independent reviewers conducted a search of Pubmed, EMBASE, Cochrane Database of Systematic Reviews, Google Scholar, PROSPERO and grey literature from inception to July 2018. Methodological quality was assessed using the revised Assessment of Multiple Systematic Reviews Instrument. Eighteen studies were found, with methodological quality ranging from Moderate to Critically Low. Of the twelve papers evaluating melatonin, there is statistically significant improvement in sleep latency and total sleep time, with a lack of consensus on whether these are clinically meaningful. Similar results are observed across the three reviews on ramelteon. The evidence for other melatonin agonists is sparse. We conclude that existing evidence is limited by disparate methodological quality of the papers, as well as a lack of consensus regarding the type, definition and interpretation of outcome measures in the evaluation of efficacy for insomnia.

    更新日期:2019-11-01
  • Socioeconomic status moderates associations between CNS serotonin and expression of beta2-integrins CD11b and CD11c.
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2009-10-06
    Beverly H Brummett,Stephen H Boyle,Cynthia M Kuhn,Ilene C Siegler,Redford B Williams

    One of the first steps in the development of atherogenesis is adhesion of circulating monocytes to the vascular endothelium that is stimulated by beta(2)-integrins. Stress has been associated with enhanced expression of beta(2)-integrins on monocyte cell surface (Greeson et al., 2008). Central nervous system (CNS) serotonin regulates aspects of the stress response that can influence inflammatory processes that increase risk for atherosclerosis. This study examines effects of an environmental stressor (indexed by socioeconomic status (SES)) and CNS serotonin (indexed by CSF 5HIAA level), on the expression of beta(2)-integrins (CD11a, CD11b, and CD11c) on circulating monocytes in 131 volunteers. Participants completed a protocol consisting of a lumbar puncture for assessment of CSF 5HIAA levels (day 1) followed by an experimental protocol (day 2). Blood samples for the present analyses were obtained at baseline on day 2. The interaction of SES x 5HIAA was a significant predictor of levels of CD11b and CD11c expression (p=.02, and p=.05, respectively); the mean CD11b difference between Hi and Lo SES subjects was significant (p=.003) only in those with Lo levels of 5HIAA, while SES differences in CD11b among those with Mid and Hi levels of 5HIAA did not vary statistically. The pattern of findings was similar for CD11c. The present results suggest that the combination of high environmental stress and low CNS serotonin function could contribute to atherogenesis through processes that lead to increased expression of the beta(2)-integrins CD11b and CD11c on monocyte cell surfaces.

    更新日期:2019-11-01
  • Using behaviour change theory to inform an innovative digital recruitment strategy in a mental health research setting.
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2019-10-15
    Michael Musker,Camille Short,Julio Licinio,Ma-Li Wong,Niranjan Bidargaddi

    Recruitment in mental health research is challenging, as some disorders such as depression or schizophrenia may involve vulnerable participants that lack motivation as part of their illness. A mental health diagnosis can be stigmatising, so privacy and access to hospital-based patient cohorts is carefully controlled. Our team describe a pragmatic portal recruitment process for facilitating timely recruitment into multiple research studies focusing on mental health. Three factors were analysed; evaluating the success and impact of this novel recruitment process; identification of patterns in recruitment to better target participants; and provision of metrics of the different media formats engaged. A web-based recruitment portal was developed by the research team in collaboration with the South Australian Health and Medical Research Institute (SAHMRI) Consumer & Carer Research Advisory Group. A comprehensive marketing campaign was then undertaken to direct participants towards the portal. Recruitment insights from the dates and times of registration across a two-year period is provided. In total, 933 potential participants registered with the recruitment portal across a two-year period at a cost of approximately $10,000. The advertisement campaign linked to the portal page enabled 506 participants to register in just one week. The area of research was self-selected by the potential participants, then eligibility was followed up with telephone and face to face interviews. Of the total 933 people who registered 706 (76%) expressed an interest in the target clinical depression study, 119 (13%) opted to be clinical controls, and the remainder chose one of the alternative studies. 240 (26%) of those who registered were excluded through telephone interviews because they fell outside of the strict eligibility criterion. We learnt that 77% (n = 723/933) of participants were recruited within seven days of promotional events, providing an interesting pattern of recruitment that may assist future recruitment design.

    更新日期:2019-11-01
  • Change in cytokine levels is not associated with rapid antidepressant response to ketamine in treatment-resistant depression.
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2016-11-05
    Minkyung Park,Laura E Newman,Philip W Gold,David A Luckenbaugh,Peixiong Yuan,Rodrigo Machado-Vieira,Carlos A Zarate

    Several pro-inflammatory cytokines have been implicated in depression and in antidepressant response. This exploratory analysis assessed: 1) the extent to which baseline cytokine levels predicted positive antidepressant response to ketamine; 2) whether ketamine responders experienced acute changes in cytokine levels not observed in non-responders; and 3) whether ketamine lowered levels of pro-inflammatory cytokines, analogous to the impact of other antidepressants. Data from double-blind, placebo-controlled studies of patients with major depressive disorder (MDD) or bipolar disorder (BD) who received a single infusion of sub-anesthetic dose ketamine were used (N = 80). Plasma levels of the eight cytokines were measured at baseline and at 230 min, 1 day, and 3 days post-ketamine. A significant positive correlation was observed between sTNFR1 and severity of depression at baseline. Cytokine changes did not correlate with changes in mood nor predict mood changes associated with ketamine administration. Ketamine significantly increased IL-6 levels and significantly decreased sTNFR1 levels. IL-6 and TNF-α levels were also significantly higher-and sTNFR1 levels were significantly lower-in BD compared to MDD subjects. The functional significance of this difference is unknown. Changes in cytokine levels post-ketamine were not related to antidepressant response, suggesting they are not a primary mechanism involved in ketamine's acute antidepressant effects. Taken together, the results suggest that further study of cytokine levels is warranted to assess their potential role as a surrogate outcome in the rapid antidepressant response paradigm.

    更新日期:2019-11-01
  • Assessing measures of suicidal ideation in clinical trials with a rapid-acting antidepressant.
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2015-08-01
    Elizabeth D Ballard,David A Luckenbaugh,Erica M Richards,Tessa L Walls,Nancy E Brutsché,Rezvan Ameli,Mark J Niciu,Jennifer L Vande Voort,Carlos A Zarate

    Rapid reduction of suicidal thoughts is critical for treating suicidal patients. Clinical trials evaluating these treatments require appropriate measurement. Key methodological issues include: 1) the use of single or multi-item assessments, and 2) evaluating whether suicidal ideation measures can track rapid change over time. The current study presents data from two randomized, placebo-controlled, crossover clinical trials evaluating ketamine in individuals with treatment-resistant depression (n = 60). Participants were assessed for suicidal thoughts using the Hamilton Depression Rating Scale (HAM-D), Montgomery-Asberg Depression Rating Scale (MADRS), Beck Depression Inventory (BDI), and Scale for Suicidal Ideation (SSI) at eight time points over three days. Assessments were compared using correlational analyses and effect sizes at 230 min and three days after ketamine infusion. Linear mixed models evaluated change in ideation across all time points. The HAM-D and MADRS suicide items demonstrated correlations of r > .80 with the first five items of the SSI (SSI5). On linear mixed models, an effect for ketamine was found for the HAM-D, MADRS, BDI items, and SSI5 (p < .001), but not for the full SSI (p = .88), which suggests a limited ability to assess change over time in patients with low levels of suicidal thoughts. Taken together, the results suggest that repeated suicidal assessments over minutes to days appear to detect improvement in suicidal thoughts after ketamine infusion compared to placebo. The MADRS suicide item, BDI suicide item, and SSI5 may be particularly sensitive to rapid changes in suicidal thoughts.

    更新日期:2019-11-01
  • Improvement in suicidal ideation after ketamine infusion: relationship to reductions in depression and anxiety.
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2014-08-30
    Elizabeth D Ballard,Dawn F Ionescu,Jennifer L Vande Voort,Mark J Niciu,Erica M Richards,David A Luckenbaugh,Nancy E Brutsché,Rezvan Ameli,Maura L Furey,Carlos A Zarate

    OBJECTIVE Suicide is a psychiatric emergency. Currently, there are no approved pharmacologic treatments for suicidal ideation. Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist that rapidly reduces suicidal ideation as well as depression and anxiety, but the dynamic between these symptoms is not known. The aim of this analysis was to evaluate whether ketamine has an impact on suicidal thoughts, independent of depressive and anxiety symptoms. METHODS 133 patients with treatment-resistant depression (major depressive disorder or bipolar I/II disorder) received a single subanesthetic infusion of ketamine (0.5 mg/kg over 40 min). Post-hoc correlations and linear mixed models evaluated the relationship between suicidal ideation and depression and anxiety symptoms using the Hamilton Depression Rating Scale (HAMD), Scale for Suicidal Ideation (SSI), Beck Depression Inventory (BDI), and Hamilton Anxiety Rating Scale (HAMA) focusing on 230 min post-infusion. RESULTS At 230 min post-infusion, correlations between changes in suicidal ideation and depression ranged from 0.23 to 0.44 (p < .05), accounting for up to 19% in the variance of ideation change. Correlations with anxiety ranged from 0.23 to 0.40 (p < .05), accounting for similar levels of variance. Ketamine infusion was associated with significant reductions in suicidal ideation compared to placebo, when controlling for the effects of ketamine on depression (F1,587 = 10.31, p = .001) and anxiety (F1,567 = 8.54, p = .004). CONCLUSIONS Improvements in suicidal ideation after ketamine infusion are related to, but not completely driven by, improvements in depression and anxiety. Investigation of the specific effects of ketamine on suicidal thoughts is warranted.

    更新日期:2019-11-01
  • Riluzole likely lacks antidepressant efficacy in ketamine non-responders.
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2014-08-21
    Mark J Niciu,David A Luckenbaugh,Dawn F Ionescu,Erica M Richards,Jennifer L Vande Voort,Elizabeth D Ballard,Nancy E Brutsche,Maura L Furey,Carlos A Zarate

    更新日期:2019-11-01
  • Lithium increases nitric oxide levels in subjects with bipolar disorder during depressive episodes.
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2014-04-29
    Rafael T de Sousa,Marcus V Zanetti,Geraldo F Busatto,Margaret G Mouro,Carlos A Zarate,Wagner F Gattaz,Elisa M Higa,Rodrigo Machado-Vieira

    BACKGROUND Altered nitric oxide (NO) signaling has been associated with the pathophysiology of Bipolar Disorder (BD), directly affecting neurotransmitter release and synaptic plasticity cascades. Lithium has shown to regulate NO levels in preclinical models. However, no study has addressed peripheral NO levels in unmedicated BD. Also, lithium's effects on NO levels have not been studied in humans. METHODS Plasma NO was evaluated in subjects with BD I and II during a depressive episode (n = 26). Subjects had a score of ≥18 in the 21-item Hamilton Depression Rating Scale and were followed-up during a 6-week trial with lithium. Plasma NO levels were also compared to matched healthy controls (n = 28). NO was determined by chemiluminescence method. RESULTS Lithium treatment significantly increased plasma NO levels after 6 weeks of treatment in comparison to baseline levels in bipolar depression (p = 0.016). Baseline NO levels during depressive episodes showed no difference when matching up to healthy controls (p = 0.66). CONCLUSION The present findings suggest that lithium upregulates NO signaling in unmedicated BD with short illness duration. Further studies with larger samples are needed to confirm the effects of lithium on NO pathway and its association with synaptic plasticity and therapeutics of BD.

    更新日期:2019-11-01
  • Oxidative stress in early stage Bipolar Disorder and the association with response to lithium.
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2013-12-18
    Rafael T de Sousa,Carlos A Zarate,Marcus V Zanetti,Alana C Costa,Leda L Talib,Wagner F Gattaz,Rodrigo Machado-Vieira

    BACKGROUND Several studies have described increased oxidative stress (OxS) parameters and imbalance of antioxidant enzymes in Bipolar Disorder (BD) but few is know about the impact of treatment at these targets. However, no study has evaluated OxS parameters in unmedicated early stage BD and their association with lithium treatment in bipolar depression. METHODS Patients with BD I or II (n = 29) in a depressive episode were treated for 6 weeks with lithium. Plasma samples were collected at baseline and endpoint, and were also compared to age-matched controls (n = 28). The thiobarbituric acid reactive substances (TBARS), and the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities were measured. RESULTS Subjects with BD depression at baseline presented a significant increase in CAT (p = 0.005) and GPx (p < 0.001) levels, with lower SOD/CAT ratio (p = 0.001) and no changes on SOD or TBARS compared to healthy controls. Regarding therapeutics, lithium only induced a decrease in TBARS (p = 0.023) and SOD (p = 0.029) levels, especially in BDII. Finally, TBARS levels were significantly lower at endpoint in lithium responders compared to non-responders (p = 0.018) with no difference in any biomarker regarding remission. CONCLUSION The present findings suggest a reactive increase in antioxidant enzymes levels during depressive episodes in early stage BD with minimal prior treatment. Also, decreased lipid peroxidation (TBARS) levels were observed, associated with lithium's clinical efficacy. Overall, these results reinforce the role for altered oxidative stress in the pathophysiology of BD and the presence of antioxidant effects of lithium in the prevention of illness progression and clinical efficacy.

    更新日期:2019-11-01
  • Neural correlates of cognitive flexibility in children at risk for bipolar disorder.
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2011-10-26
    Pilyoung Kim,Sarah E Jenkins,Megan E Connolly,Christen M Deveney,Stephen J Fromm,Melissa A Brotman,Eric E Nelson,Daniel S Pine,Ellen Leibenluft

    BACKGROUND Youth with bipolar disorder (BD) show behavioral and neural deficits in cognitive flexibility; however, whether such deficits exist among youths at risk for BD has not been explored. METHODS The current fMRI study examined the neural basis of cognitive flexibility in BD youth (n = 28), unaffected youth at risk for BD (AR; n = 13), and healthy volunteer youth (HV; n = 21) by comparing brain activation patterns while participants performed the change task. On change trials, subjects must inhibit a prepotent response and execute an alternate one. RESULTS During successful change trials, both BD and AR youth had increased right ventrolateral prefrontal and inferior parietal activity, compared to HV youth. During failed change trials, both BD and AR youth exhibited increased caudate activation relative to HV youth, but BD youth showed increased activation in the subgenual anterior cingulate cortex (ACC) relative to the other two groups. CONCLUSIONS Abnormal activity in ventrolateral prefrontal cortex, inferior parietal cortex, and striatum during a cognitive flexibility task may represent a potential BD endophenotype, but subgenual ACC dysfunction may represent a marker of BD illness itself.

    更新日期:2019-11-01
  • Dysregulation of neurosteroids in obsessive compulsive disorder.
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2008-06-03
    K L Bigos,M M Folan,M R Jones,G L Haas,F J Kroboth,P D Kroboth

    Alterations in hormone concentrations, including adrenocorticotropin, corticotropin releasing hormone, and cortisol have been reported in patients with obsessive compulsive disorder (OCD). Dehydroepiandrosterone (DHEA) and its sulfated metabolite, DHEA-S, have not been assessed in patients with OCD. We report 24-h serum DHEA, DHEA-S, and cortisol concentrations in a young man with OCD and 15 healthy young men. Circadian patterns of DHEA and cortisol were markedly different in the subject with OCD than in the control subjects. DHEA and DHEA-S concentrations were substantially higher in the OCD subject than in the control subjects. In contrast, cortisol concentrations were similar in the OCD subject and the control subjects. Future clinical studies are needed to evaluate the significance of DHEA and DHEA-S in OCD.

    更新日期:2019-11-01
  • The effects of early and sustained intervention on the long-term morbidity of schizophrenia.
    J. Psychiatr. Res. (IF 3.917) Pub Date : 1998-10-30
    R J Wyatt,I D Henter

    By examining the literature concerning early intervention with antipsychotic medications, and how it affects long-term morbidity, this article will review the concept that early intervention with antipsychotic medications improves the long-term course of schizophrenia. It also looks at the potential long-term effects of discontinuing antipsychotic medications early in the course of schizophrenia. It appears that early intervention with antipsychotic medications decreases some of the long-term morbidity associated with schizophrenia. Some of the implications of this finding are discussed in the context of both clinical practice and clinical research.

    更新日期:2019-11-01
  • Automated measurement of hippocampal subfields in PTSD: Evidence for smaller dentate gyrus volume.
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2017-09-20
    Jasmeet P Hayes,Scott Hayes,Danielle R Miller,Ginette Lafleche,Mark W Logue,Mieke Verfaellie

    Smaller hippocampal volume has been consistently observed as a biomarker of posttraumatic stress disorder (PTSD). However, less is known about individual volumes of the subfields composing the hippocampus such as the dentate gyrus and cornu ammonis (CA) fields 1-4 in PTSD. The aim of the present study was to examine the hypothesis that volume of the dentate gyrus, a region putatively involved in distinctive encoding of similar events, is smaller in individuals with PTSD versus trauma-exposed controls. Ninety-seven recent war veterans underwent structural imaging on a 3T scanner and were assessed for PTSD using the Clinician-Administered PTSD Scale. The hippocampal subfield automated segmentation program available through FreeSurfer was used to segment the CA4/dentate gyrus, CA1, CA2/3, presubiculum, and subiculum of the hippocampus. Results showed that CA4/dentate gyrus subfield volume was significantly smaller in veterans with PTSD and scaled inversely with PTSD symptom severity. These results support the view that dentate gyrus abnormalities are associated with symptoms of PTSD, although additional evidence is necessary to determine whether these abnormalities underlie fear generalization and other memory alterations in PTSD.

    更新日期:2019-11-01
  • The UFD1L rs5992403 polymorphism is associated with age at onset of schizophrenia.
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2010-05-18
    Vanessa Kiyomi Ota,Sintia Iole Belangero,Ary Gadelha,Fernanda Teixeira Bellucco,Denise Maria Christofolini,Tatiane Iris Mancini,Andrea Kelly Ribeiro-dos-Santos,Sidney Emanuel Santos,Jair de Jesus Mari,Rodrigo Affonseca Bressan,Maria Isabel Melaragno,Marilia de Arruda Cardoso Smith

    更新日期:2019-11-01
  • A meta-analysis of two genome-wide association studies identifies 3 new loci for alcohol dependence.
    J. Psychiatr. Res. (IF 3.917) Pub Date : 2011-06-28
    Ke-Sheng Wang,Xuefeng Liu,Qunyuan Zhang,Yue Pan,Nagesh Aragam,Min Zeng

    Family, twin and adoption studies have clearly demonstrated that genetic factors are important in modulating the vulnerability to alcohol dependence. Several genome-wide association (GWA) studies of alcohol dependence have been conducted; however, few loci have been replicated. A meta-analysis was performed on two GWA studies of 1283 cases of alcohol dependence and 1416 controls in Caucasian populations. Through meta-analysis we identified 131 SNPs associated with alcohol dependence with p<10(-4). The best novel signal was rs6701037 (p=1.86 × 10(-7)) at 1q24-q25 within KIAA0040 gene while the second best novel hit was rs1869324 (p=4.71 × 10(-7)) at 2q22.1 within THSD7B. The third novel locus was NRD1 at 1p32.2 (the top SNP was rs2842576 with p=7.90 × 10(-6)). We confirmed the association of PKNOX2 at 11q24.4 with alcohol dependence. The top hit of PKNOX2 (rs750338 with p=1.47 × 10(-6)) in the meta-analysis was replicated with the Australian Twin-Family Study of 778 families (p=1.39 × 10(-2)) Furthermore, several flanking SNPs of the top hits in the meta-analysis demonstrated borderline associations with alcohol dependence in the family sample (top SNPs were rs2269655, rs856613, and rs10496768 with p=4.58 × 10(-3), 2.1 × 10(-4), and 2.86 × 10(-3) for KIAA0040, NRD1 and THSD7B, respectively). In addition, ALK, CASC4, and SEMA5A were strongly associated with alcohol dependence (p<2 × 10(-5)) in the meta-analysis. In conclusion, we identified three new loci (KIAA0040, THSD7B and NRD1) and confirmed the previous association of PKNOX2 with alcohol dependence. These findings offer the potential for new insights into the pathogenesis of alcohol dependence.

    更新日期:2019-11-01
Contents have been reproduced by permission of the publishers.
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