The role of recurrent trauma on post-traumatic stress disorder symptoms and substance use among trauma exposed youth.

Comorbidity between post-traumatic stress disorder (PTSD) and substance use disorder may be explained by a prospective trauma risk conferred by both conditions. The current study modeled concurrent and prospective associations of trauma, PTSD symptoms, and substance use (SU) behavior among trauma exposed youth (ages 8-20). Clinical interviews assessed trauma exposure, PTSD symptom severity, and SU behavior at baseline and at six- and 12-month follow up study visits (N = 2,069). Structural equation models assessed the associations of trauma, PTSD symptoms, and SU behavior. Lifetime trauma was associated with more severe PTSD symptoms and SU behaviors, whereas trauma exposure during the study was only associated with PTSD symptoms. PTSD symptom severity was prospectively associated with trauma exposure. PTSD symptom severity and SU behavior at follow-up study visits were prospectively associated. These results highlight the dynamic interplay between trauma, PTSD symptoms, and SU behavior during youth, a developmental period during which complex psychiatric presentations can have longstanding consequences for health.

Childhood maltreatment exposure is differentially associated with transdiagnostic perinatal depression symptoms.

History of childhood maltreatment (CM) is common and robustly associated with prenatal and postpartum (perinatal) depression. Given perinatal depression symptom heterogeneity, a transdiagnostic approach to measurement could enhance understanding of patterns between CM and perinatal depression. METHODS: In two independently collected samples of women receiving care at perinatal psychiatry clinics (n = 523 and n = 134), we categorized longitudinal symptoms of perinatal depression, anxiety, stress, and sleep into transdiagnostic factors derived from the Research Domain Criteria and depression literatures. We split the perinatal period into four time points. We conducted a latent profile analysis of transdiagnostic factors in each period. We then used self-reported history of CM (total exposure and subtypes of abuse and neglect) to predict class membership. RESULTS: A three-class solution best fit our data. In relation to positive adaptive functioning, one class had relatively more positive symptoms (high adaptive), one class had average values (middle adaptive), and one class had fewer adaptive symptoms (low adaptive). More total CM and specific subtypes associated with threat/abuse increased an individual's likelihood of being in the Low Adaptive class in both samples (ORs: 0.90-0.97, p < .05). LIMITATIONS: Generalizability of our results was curtailed by 1) limited racial/ethnic diversity and 2) missing data. CONCLUSIONS: Our results support taking a person-centered approach to characterize the relationship between perinatal depression and childhood maltreatment. Given evidence that increased exposure to childhood maltreatment is associated with worse overall symptoms, providers should consider incorporating preventative, transdiagnostic interventions for perinatal distress in individuals with a history of childhood maltreatment.

Comparing diagnostic criteria for posttraumatic stress disorder in a diverse sample of trauma-exposed youth.

Divergent conceptualization of posttraumatic stress disorder (PTSD) within the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) and International Statistical Classification of Diseases and Related Health Problems (11th ed..; ICD-11) significantly confounds both research and practice. Using a diverse sample of trauma-exposed youth (N = 1,542, age range: 8-20 years), we compared these two diagnostic approaches along with an expanded version of the ICD-11 PTSD criteria that included three additional reexperiencing symptoms (ICD-11+). Within the sample, PTSD was more prevalent using the DSM-5 criteria (25.7%) compared to the ICD-11 criteria (16.0%), with moderate agreement between these diagnostic systems, κ = .57. The inclusion of additional reexperiencing symptoms (i.e., ICD-11+) reduced this discrepancy in prevalence (24.7%) and increased concordance with DSM-5 criteria, κ = .73. All three PTSD classification systems exhibited similar comorbidity rates with major depressive episode (MDE) or generalized anxiety disorder (GAD; 78.0%-83.6%). Most youths who met the DSM-5 PTSD criteria also met the criteria for ICD-11 PTSD, MDE, or GAD (88.4%), and this proportion increased when applying the ICD-11+ criteria (95.5%). Symptom-level analyses identified reexperiencing/intrusions and negative alterations in cognition and mood symptoms as primary sources of discrepancy between the DSM-5 and ICD-11 PTSD diagnostic systems. Overall, these results challenge assertions that nonspecific distress and diagnostically overlapping symptoms within DSM-5 PTSD inflate comorbidity with depressive and anxiety disorders. Further, they support the argument that the DSM-5 PTSD criteria can be refined and simplified without reducing the overall prevalence of psychiatric diagnoses in youth.

The role of resilience in the development of depression, anxiety, and post-traumatic stress disorder after trauma in children and adolescents.

This investigation, conducted within the Texas Childhood Trauma Research Network, investigated the prospective relationships between resiliency and emergent internalizing symptoms among trauma-exposed youth. The cohort encompassed 1262 youth, aged 8-20, from twelve health-related institutions across Texas, who completed assessments at baseline and one- and six-month follow-ups for resiliency, symptoms of depression, generalized anxiety, posttraumatic stress disorder (PTSD), and other demographic and clinical characteristics. At baseline, greater resilience was positively associated with older age, male (vs female) sex assigned at birth, and history of mental health treatment. Unadjusted for covariates, higher baseline resilience was associated with greater prospective depression and PTSD symptoms but not anxiety symptoms. Upon adjusting for demographic and clinical factors, higher baseline resilience was no longer associated with depression, PTSD, or anxiety symptoms. Our analyses demonstrate that the predictive value of resilience on psychopathology is relatively small compared to more readily observable clinical and demographic factors. These data suggest a relatively minor prospective role of resilience in protecting against internalizing symptoms among trauma-exposed youth and highlight the importance of controlling for relevant youth characteristics when investigating a protective effect of resilience on internalizing symptoms.

Characterizing patterns of substance use in trauma exposed youth.

OBJECTIVE: Previous work investigating the impact of childhood trauma on substance use and co-occurring psychiatric disorders has primarily been conducted in adults or on specific trauma types. This limits understanding of traumas impact in childhood and how different types of traumas play a role. We sought to characterize substance use in a sample of trauma-exposed youth in the context of psychiatric comorbidities. METHOD: 1152 youth from the Texas Childhood Trauma Research Network (TX-CTRN) that were exposed to at least one trauma meeting DSM-5 Criterion A were assessed for current substance use and psychiatric diagnoses. Latent class analysis was used to identify patterns of substance use. To characterize these patterns, we examined if demographics, number of trauma types experienced, or childhood psychiatric disorders predicted class membership. RESULTS: We identified four primary patterns of substance use: Non-use (66.1%), predominantly alcohol use (19.7%), predominantly cannabis use (4.5%), and polysubstance use (9.7%). Compared to the non-users, polysubstance users tended to be older, Non-Hispanic White, have experienced more types of trauma. They were also more likely to have fulfilled diagnostic criteria for suicidality and ADHD. Comparisons among the substance using classes were more nuanced. CONCLUSION: The findings highlight the need for universal assessments of trauma, substance misuse, and mental health symptoms in youth as the presence or absence of their co-occurrence has implications for treatment.

Associations between mothers' and fathers' depression and anxiety prior to birth and infant temperament trajectories over the first year of life: Evidence from diagnoses and symptom severity.

BACKGROUND: Developmental shifts in infant temperament predict distal outcomes including emerging symptoms of psychopathology in childhood. Thus, it is critical to gain insight into factors that shape these developmental shifts. Although parental depression and anxiety represent strong predictors of infant temperament in cross-sectional research, few studies have examined how these factors influence temperament trajectories across infancy. METHODS: We used latent growth curve modeling to examine whether mothers' and fathers' anxiety and depression, measured in two ways - as diagnostic status and symptom severity - serve as unique predictors of developmental shifts in infant temperament from 3 to 12 months. Participants included mothers (N = 234) and a subset of fathers (N = 142). Prior to or during pregnancy, both parents were assessed for lifetime diagnoses of depression and anxiety as well as current severity levels. Mothers rated their infants' temperament at 3, 6, and 12 months of age. RESULTS: Mothers' depression and anxiety primarily predicted initial levels of temperament at 3 months. Controlling for mothers' symptoms, fathers' depression and anxiety largely related to temperament trajectories across infancy. Lifetime diagnoses and symptom severities were associated with distinct patterns. LIMITATIONS: Infant temperament was assessed using a parent-report measure. Including an observational measure would provide a more comprehensive picture of the infants' functioning. CONCLUSIONS: These results indicate that mothers' and fathers' mental health are uniquely associated with infant temperament development when measured using diagnostic status and/or symptom severity. Future studies should examine whether these temperament trajectories mediate intergenerational transmission of risk for depression and anxiety.

Positive affect improves a transdiagnostic model of perinatal depression symptoms.

INTRODUCTION: Accurate measurement of perinatal depression is vital. We aimed to 1) test whether a factor that measured positive affect (PA) bettered a transdiagnostic model of depression symptoms and 2) replicate the model in a second sample. METHODS: We conducted secondary analyses from two samples (n's = 657 and 142) of women in treatment at perinatal psychiatric clinics. Data were derived from items from seven commonly used measures. We compared fit indices from our original factor model-one general and six specific factors derived from the Research Domain Criteria (Loss, Potential Threat, Frustrative Nonreward, and Sleep-Wakefulness) and depression literatures (Somatic and Coping)-to our novel factor model with a PA factor. The PA factor was created by recategorizing items that measured affective states with a positive valence into a new factor. Sample 1 data were split into six perinatal periods. RESULTS: In both samples, the addition of a PA factor improved model fit. At least partial metric invariance was found between perinatal periods, with the exception of trimester 3 - postpartum period 1. LIMITATIONS: Our measures did not operationalize PA in the same way as in the positive valence system in RDoC and we were unable to perform longitudinal analyses on our cross-validation sample. CONCLUSIONS: Clinicians and researchers are encouraged to consider these findings as a template for understanding symptoms of depression in perinatal patients, which can be used to guide treatment planning and the development of more effective screening, prevention, and intervention tools to prevent deleterious outcomes.

Establishing a training plan and estimating inter-rater reliability across the multi-site Texas childhood trauma research network.

OBJECTIVE: Minimal guidance is available in the literature to develop protocols for training non-clinician raters to administer semi-structured psychiatric interviews in large, multi-site studies. Previous work has not produced standardized methods for maintaining rater quality control or estimating interrater reliability (IRR) in such studies. Our objective is to describe the multi-site Texas Childhood Trauma Research Network (TX-CTRN) rater training protocol and activities used to maintain rater calibration and evaluate protocol effectiveness. METHODS: Rater training utilized synchronous and asynchronous didactic learning modules, and certification involved critique of videotaped mock scale administration. Certified raters attended monthly review meetings and completed ongoing scoring exercises for quality assurance purposes. Training protocol effectiveness was evaluated using individual measure and pooled estimated IRRs for three key study measures (TESI-C, CAPS-CA-5, MINI-KID [Major Depressive Episodes - MDE & Posttraumatic Stress Disorder - PTSD modules]). A random selection of video-recorded administrations of these measures was evaluated by three certified raters to estimate agreement statistics, with jackknife (on the videos) used for confidence interval estimation. Kappa, weighted kappa and intraclass correlations were calculated for study measure ratings. RESULTS: IRR agreement across all measures was strong (TESI-C median kappa 0.79, lower 95% CB 0.66; CAPS-CA-5 median weighted kappa 0.71 (0.62), MINI-MDE median kappa 0.71 (0.62), MINI-PTSD median kappa 0.91 (0.9). The combined estimated ICC was ≥0.86 (lower CBs ≥0.69). CONCLUSIONS: The protocol developed by TX-CTRN may serve as a model for other multi-site studies that require comprehensive non-clinician rater training, quality assurance guidelines, and a system for assessing and estimating IRR.

Detection of differential depressive symptom patterns in a cohort of perinatal women: an exploratory factor analysis using a robust statistics approach.

Background: Postpartum depression can take many forms. Different symptom patterns could have divergent implications for how we screen, diagnose, and treat postpartum depression. We sought to utilise a recently developed robust estimation algorithm to automatically identify differential patterns in depressive symptoms and subsequently characterise the individuals who exhibit different patterns. Methods: Depressive symptom data (N = 548) were collected from women with neuropsychiatric illnesses at two U.S. urban sites participating in a longitudinal observational study of stress across the perinatal period. Data were collected from Emory University between 1994 and 2012 and from the University of Arkansas for Medical Sciences between 2012 and 2017. We conducted an exploratory factor analysis of Beck Depression Inventory (BDI) items using a robust expectation-maximization algorithm, rather than a conventional expectation-maximization algorithm. This recently developed method enabled automatic detection of differential symptom patterns. We described differences in symptom patterns and conducted unadjusted and adjusted analyses of associations of symptom patterns with demographics and psychiatric histories. Findings: 53 (9.7%) participants were identified by the algorithm as having a different pattern of reported symptoms compared to other participants. This group had more severe symptoms across all items-especially items related to thoughts of self-harm and self-judgement-and differed in how their symptoms related to underlying psychological constructs. History of social anxiety disorder (OR: 4.0; 95% CI [1.9, 8.1]) and history of childhood trauma (for each 5-point increase, OR: 1.2; 95% CI [1.1, 1.3]) were significantly associated with this differential pattern after adjustment for other covariates. Interpretation: Social anxiety disorder and childhood trauma are associated with differential patterns of severe postpartum depressive symptoms, which might warrant tailored strategies for screening, diagnosis, and treatment to address these comorbid conditions. Funding: There are no funding sources to declare.

Experimental evaluation of a patient specific Brachio-Cephalic Arterio Venous Fistula (AVF): Velocity flow conditions under steady and pulsatile waveforms.

Arterio-Venous Fistulas (avf) are the most popular form of vascular access used for hemodialysis. However they continue to present complications leading to early and late failure. To understand the reasons for failure, it is necessary to analyze the hemodynamics involved. Wall shear stress (wss) is commonly studied in avfs as it often relates to cardiovascular disease, although there is dispute over whether high or low wss is detrimental to avf patency. The goal of this paper is to investigate velocity flow conditions in a rigid, patient-specific brachio-cephalic avf model in both steady flow (Re = 1817) and patient-specific pulsatile flow (Reav=1817, Remax=2233). Particle Image Velocimetry (piv) measurements were performed at the anastomosis to capture the complex 3D-3C flow present. The results from this study found regions of recirculation and high velocity fluctuations in the distal artery and proximal vein, and flow impingement at the anastomosis toe. Steady and pulsatile flow demonstrated similar flow features, possibly owed to the low pulsatility index. In addition, the recirculation zone did not vary along the waveform. The directional variability was seen to be the highest at the regions of recirculation and flow impingement suggesting regions of high transWSS while the coefficient of variation was greatest at the walls and in areas of flow separation indicating high temporal wall shear stress.

Occupational Risk Factors and Mental Health Among Frontline Health Care Workers in a Large US Metropolitan Area During the COVID-19 Pandemic.

Objective: To assess depression, anxiety, and burnout among health care workers using well-established validated scales and to examine associations of these mental health outcomes with personal protective equipment (PPE) and high-risk patient contact.Methods: This prospective survey was conducted between August and October 2020 among 970 essential health care workers from 2 health systems in central Texas. The survey captured basic demographic, occupational, and baseline health information including history of mental health disorders. Depression, anxiety, and burnout were assessed with the 8-item Patient Health Questionnaire, 7-item Generalized Anxiety Disorder Scale, and 23-item Burnout Assessment Tool. Questions about clinical contact with patients with suspected or known COVID-19 were also incorporated.Results: Approximately 24% of respondents had moderate or severe anxiety, 14% had moderate or severe depression, and 7% were at high risk for burnout. Statistically significant associations were found between perceived PPE adequacy and the 3 mental health outcomes, while accounting for age, gender, and education. Hours of contact with COVID-19 patients during aerosolizing procedures was positively correlated with measures of anxiety, burnout, and depression after adjustment for age, gender, and occupational role. Perception of PPE adequacy was inversely correlated with measures of depression, anxiety, and burnout among essential members of 2 health care systems, whose roles precluded working remotely during the pandemic.Conclusion: This study highlights the correlations of perceptions of PPE adequacy and contact hours with COVID-19 patients undergoing aerosolizing procedures and employee mental well-being. Future work confirming the findings can help identify ways that systems can support their employees through similarly stressful and demanding events.

Validity and severity thresholds for the depression subscale of the affective self rating scale: An equipercentile equating study using classical test theory.

BACKGROUND: The Affective Symptoms Scale (ASRS) is a unique instrument designed to separately measure depressive and manic symptoms in mood disorders. We validated the ASRS against the Patient Health Questionnaire (PHQ-9) and the Quick Inventory of Depressive Symptomatology (QIDS-16). METHODS: A retrospective study of 258 patients who completed the PHQ-9, QIDS-16 and ASRS as part of routine clinical care. To establish meaningful clinical thresholds for the depression subscale of the ASRS, it was equated with the QIDS and the PHQ-9. RESULTS: The depression subscale of the ASRS had significant positive correlations with the QIDS-16 and the PHQ-9 (respectively, r= 0.8, t[253] = 19.8, p < 0.001, and r= 0.8, t[245] = 28.2, p < 0.001). The equipercentile equating method with the PHQ-9 indicated that the thresholds corresponded to ASRS depression subscale scores of 5.4, 10.6, 16.1, and 23. Equating with the QIDS indicated that thresholds corresponded to ASRS depression subscale scores of 5.1, 11, 18.4, and 27.5. LIMITATIONS: Limitations include a small sample size that did not allow more detailed statistical analysis, such as Item Response Theory. The population is a heterogenous population at a university outpatient setting. CONCLUSIONS: The ASRS depression subscale significantly correlated with the PHQ-9 and QIDS-16. Our proposed threshold scores for the ASRS are 5, 11, 16 and 23 to indicated mild, moderate, severe and very severe depression respectively.

The severity and role of somatic depressive symptoms in psychological networks in a longitudinal sample of peripartum women.

The inclusion of somatic symptoms in assessing peripartum depression (PPD), which encompasses depression during pregnancy and the postpartum period, has remained controversial, as there is substantial overlap between somatic depression symptoms and normal features of pregnancy/postpartum. This study examined whether trajectories differed by PPD symptom subscale and whether PPD symptom networks changed as a function of the peripartum phase. 418 women with a history of neuropsychiatric illness participated in a longitudinal observational study, completing symptom questionnaires assessing affective, cognitive, and somatic symptoms throughout pregnancy and the first year postpartum. Assessments were grouped into five peripartum phases: three trimesters of pregnancy and early/late postpartum. Two analyses were performed. First, a series of multilevel spline regression models examined depression subscale trajectories over peripartum phase. Second, symptom networks and related metrics were estimated for each peripartum phase and compared. Somatic symptoms were most severe and had the most variable peripartum trajectory. The role of somatic symptoms within the networks also changed as a function of peripartum phase. Our results suggest that somatic symptoms can be severe and may play a crucial role in the maintenance of PPD. Thus, somatic symptoms should not be disregarded when assessing for PPD in obstetrical, psychiatric, and pediatric clinics, and clinical research.

Efficacy of Vortioxetine Monotherapy for Posttraumatic Stress Disorder: A Randomized, Placebo-Controlled Trial.

PURPOSE/BACKGROUND: There are few efficacious pharmacological treatments for posttraumatic stress disorder (PTSD) and many patients fail to benefit from existing treatments. Vortioxetine, a recently developed antidepressant, acts as a serotonin modulator through inhibition of the serotonin transporter and actions at multiple types of serotonin receptors. Its unique pharmacodynamic profile suggests it may have efficacy for the treatment of PTSD. METHODS/PROCEDURES: We conducted a 12-week placebo-controlled, randomized clinical trial of vortioxetine (flexibly dosed from 10 to 20 mg/d) versus placebo in adults with PTSD. The primary outcome was change from baseline in the past-month version of the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), analyzed using a mixed-model repeated-measures analysis of variance. FINDINGS/RESULTS: Forty-one patients were randomized, and 32 (78%) completed the 12 weeks of treatment. The mean reduction in CAPS-5 scores at week 12 did not significantly differ between the 2 arms; the effect size for the difference in changes between vortioxetine and placebo on CAPS-5 total scores at week 12 was Cohen d = 0.29. However, at week 8, the drug-placebo difference was d = 0.78, which met the multivariate criteria for statistical significance, P = 0.014. IMPLICATIONS/CONCLUSIONS: In this study of 41 patients, vortioxetine did not demonstrate superiority over placebo for adults with PTSD. Future PTSD trials may benefit from stratifying the randomization based on number of years since the index traumatic event and a history of failure to respond to treatment.

Maternal prenatal depression and epigenetic age deceleration: testing potentially confounding effects of prenatal stress and SSRI use.

Previous studies suggest epigenetic alterations may contribute to the association between maternal prenatal depression and adverse offspring outcomes. Developmental researchers have recently begun to examine these associations in relation to epigenetic age acceleration/deceleration, a biomarker of developmental risk that reflects the deviation between epigenetic age and chronological age. In the perinatal period, preliminary studies indicate that maternal prenatal depression may lead to epigenetic age deceleration in newborns, which may predict adverse developmental outcomes. The present study examined the relationship between maternal prenatal exposures (i.e., depression, stress, and SSRI use) and offspring epigenetic age deceleration in 303 mother-offspring dyads. Women were recruited in the first trimester of pregnancy and followed longitudinally until delivery. Maternal depression, perceived stress, and SSRI use were assessed at each prenatal visit. Newborn epigenetic age was determined via cord blood samples. Results indicated maternal prenatal stress was not associated with newborn epigenetic age deceleration (ΔR2 = 0.002; p = 0.37). Maternal prenatal depression was associated with decelerated epigenetic age (ΔR2 = 0.01, p = 0.04), but this relationship did not hold when accounting for maternal use of SSRIs (ΔR2 = 0.002, p = 0.43). Conversely, maternal SSRI use significantly predicted newborn epigenetic age deceleration over and above the influence of maternal depression (ΔR2 = 0.03, p = 0.001). These findings suggest maternal prenatal SSRI use may significantly contribute to the previously documented association between maternal prenatal depression and epigenetic age deceleration. Further studies are needed to examine how these epigenetic differences at birth may contribute to adverse outcomes in later development.

Consistency of EEG asymmetry patterns in infants of depressed mothers.

We evaluated frontal electroencephalogram (EEG) asymmetry across multiple contexts as an index of a general affective response predisposition in 12-month-old infants whose mothers were at elevated risk for perinatal depression due to their mother's history of depression. We further examined mothers' prenatal, postnatal, and concurrent depressive symptom levels in relation to infants' frontal EEG asymmetry consistency. Mothers (n = 132) with a history of depression prior to pregnancy completed depressive symptom scales repeatedly during pregnancy and the first year postpartum. Their 12-month-old infants' frontal EEG asymmetry was recorded across five contexts (baseline/bubbles, peek-a-boo, play, feeding, and distract). Frontal EEG asymmetries showed small to moderate correlations across contexts. Mothers' prenatal depression symptom levels (not postnatal or concurrent) were associated with infants having consistent right, rather than left, frontal EEG asymmetry, even after controlling for infants' observed affect. These findings demonstrate the consistency of EEG asymmetry scores across contexts in 12-month-old infants at risk for the development of psychopathology, providing support for relative right frontal EEG asymmetry as a trait marker of vulnerability to depression. Findings also suggest the importance of mothers' prenatal, rather than postnatal or concurrent depression, in predicting infants' consistent patterns of relative right frontal EEG asymmetry across contexts.

A transdiagnostic approach to conceptualizing depression across the perinatal period in a high-risk sample.

Clinical guidelines recommend assessing depression during pregnancy and postpartum but often overlook potential changes in symptoms across this developmental period. Such changes contribute to difficulties in conceptualizing maternal depression. This study aimed to situate depressive symptoms and related concerns (anxiety, stress, sleep) across the perinatal period within a transdiagnostic framework and to use this framework to better understand how depressive symptoms change across the perinatal period. First, items from seven symptom scales were a priori categorized into six transdiagnostic factors: four based on Research Domain Criteria (loss, potential threat, frustrative nonreward, and sleep-wakefulness) and two based on the depression literature (somatic and coping symptoms). Second, using prospective data from women with a history of an affective disorder (n = 657) in an observational study of neuropsychiatric illness, factor analyses were performed in seven periods (three trimesters of pregnancy and four quarters of first year postpartum). For each period, a bifactor model with six transdiagnostic factors and a general factor fit data better than models that combined or dropped a factor (p < .003). Except around delivery, item loadings and intercepts could be fixed between consecutive periods and still adequately fit data from both periods. Means of sleep-wakefulness and somatic factors increased significantly from second to third trimester (p < .01), with trends reversing early postpartum. In conclusion, depressive symptoms and related concerns exhibit factor structures that are only partly congruent across the perinatal period. This conclusion suggests that greater attention to specific life phases is warranted in the conceptualization of depression during this time in women's lives. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Implementation of Advanced Methods for Reproductive Pharmacovigilance in Autism: A Meta-Analysis of the Effects of Prenatal Antidepressant Exposure.

OBJECTIVE: Observational studies of prenatal antidepressant safety are hindered by methodological concerns, including susceptibility to surveillance bias. Some studies address potential bias by using alternative strategies to operationalize study comparison groups. In a meta-analysis of the association between prenatal antidepressant exposure and autism risk, the authors examined the utility of comparison group operationalization in reducing surveillance bias. METHODS: A systematic search of multiple databases through August 2017 was conducted, selecting controlled observational studies of the association of prenatal antidepressant exposure with autism. Study quality was assessed using the Newcastle-Ottawa Scale. Random-effects meta-analysis produced summary effect measures with 95% confidence intervals stratified by comparator group composition, antidepressant class, and trimester of exposure. RESULTS: Fourteen studies were included, with 13 reporting results using a population-based comparison group, five using a psychiatric control group, and four using a discordant-sibling control group. Eight of the 14 studies were rated poor because of inadequate control for prenatal depression and maternal ethnicity. Autism risk estimates after prenatal exposure to any antidepressant were decidedly different for population-based designs (hazard ratio=1.42, 95% CI=1.18, 1.70; odds ratio=1.58, 95% CI=1.25, 1.99) compared with psychiatric control (hazard ratio=1.14, 95% CI=0.84, 1.53; odds ratio=1.24, 95% CI=0.93, 1.66) and discordant-sibling (hazard ratio=0.97, 95% CI=0.68, 1.37; odds ratio=0.85, 95% CI=0.54, 1.35) designs. Findings for prenatal exposure to selective serotonin reuptake inhibitors were similar. Meta-regression of population-based studies demonstrated that despite statistical adjustment, ethnicity differences remained a significant source of study heterogeneity. CONCLUSIONS: In this meta-analysis, neither psychiatric control nor discordant-sibling designs supported an association between prenatal antidepressant exposure and autism. Discordant-sibling designs effectively addressed surveillance bias in pharmacovigilance reports derived from national registries and other large databases.

The mechanical responses of advecting cells in confined flow.

Fluid dynamics have long influenced cells in suspension. Red blood cells and white blood cells are advected through biological microchannels in both the cardiovascular and lymphatic systems and, as a result, are subject to a wide variety of complex fluidic forces as they pass through. In vivo, microfluidic forces influence different biological processes such as the spreading of infection, cancer metastasis, and cell viability, highlighting the importance of fluid dynamics in the blood and lymphatic vessels. This suggests that in vitro devices carrying cell suspensions may influence the viability and functionality of cells. Lab-on-a-chip, flow cytometry, and cell therapies involve cell suspensions flowing through microchannels of approximately 100-800 µ m. This review begins by examining the current fundamental theories and techniques behind the fluidic forces and inertial focusing acting on cells in suspension, before exploring studies that have investigated how these fluidic forces affect the reactions of suspended cells. In light of these studies' findings, both in vivo and in vitro fluidic cell microenvironments shall also be discussed before concluding with recommendations for the field.