McLean Hospital

Childhood maltreatment and FKBP5 CATT haplotypes increase identity dissociation risk. While maltreatment often fosters disorganized attachment, the specific role of the FKBP5 CATT haplotype within this developmental pathway remains unknown. In 310 trauma-exposed adults, we assessed childhood maltreatment, disorganized attachment, and identity dissociation. FKBP5 CATT haplotype status was dichotomized (present/absent). Regression models were estimated to examine the pathway Childhood Maltreatment → Disorganized Attachment → Identity Dissociation, comparing two competing hypotheses: 1) The Formation Hypothesis (Maltreatment × CATT → Disorganization), and 2) The Translation Hypothesis (Disorganization × CATT → Identity Dissociation). Model fit was compared using BIC, and simple slopes were examined. Disorganized attachment predicted identity dissociation (β = 0.143, z = 3.83, p < .001), and childhood maltreatment predicted disorganization (β = 0.007, z = 4.46, p < .001). The Formation hypothesis was not supported, as the Maltreatment × CATT interaction did not predict disorganization (β = -0.004, z = -1.18, p = .24). However, the Translation hypothesis was supported by three pieces of evidence: a significant Disorganization × CATT interaction predicting identity dissociation (β = 0.133, z = 2.22, p = .027), model fit (∆BIC = 265.3), and simple slopes showing a strong effect of disorganization on identity dissociation for CATT carriers (β = 0.15, p < .001; +16.5 % per unit) but not for non-carriers (β = 0.02, p = .65). The FKBP5 CATT haplotype does not promote disorganized attachment but amplifies the translation of disorganized attachment into identity dissociation. This result highlights a genetically influenced failure of identity development following disorganized attachment.

Posttraumatic stress disorder (PTSD) is associated with accelerated biological aging. In general, psychological resilience is related to more normative aging patterns; however, among individuals with PTSD, resilience may be associated with older biological aging. For example, prior work suggests that individuals with PTSD who have higher psychological resilience show more advanced epigenetic aging than individuals with lower psychological resilience. We investigated whether psychological resilience moderated the relationship between PTSD and brain aging in a community sample of South African women. Individuals (N = 189) were recruited as part of the Drakenstein Child Health Study. Participants underwent a structural MRI and completed questionnaires of PTSD (modified-PTSD Symptom Scale, mPSS) and psychological resilience (Connor-Davidson Resilience Scale; CD-RISC). Using a pre-trained model, a predicted brain age gap was derived. Linear models tested a CD-RISCxGroup (no trauma exposure (NTE), trauma-exposed [TE], and PTSD) interaction on brain age gap. Follow-up models probed regional brain age gap (e.g., subcortical, frontal, parietal). There was no main effect of Group on brain age gap. There was a significant CD-RISCxGroup interaction, such that higher CD-RISC scores were associated with a positive brain age gap (reflecting an older appearing brain) only in women with suspected PTSD but not in NTE or TE individuals. Follow-up tests showed the CD-RISCxGroup interaction was only significant in the subcortical region, suggesting the effect was driven by alterations in subcortical structures frequently implicated in PTSD. Future longitudinal work should examine whether psychological resilience moderates PTSD-related brain aging across time.

BackgroundIron chelation therapy (ICT) is essential for people with hematological disorders requiring chronic transfusions to minimize the risk of iron overload, yet suboptimal adherence is prevalent. Widespread use of personal technology makes mobile health (mHealth) an attractive platform to promote adherence.ObjectiveThis study aimed to examine access to mobile technology and preferences for an mHealth intervention to improve adherence to ICT.MethodsA cross-sectional survey that included 63 items assessing technology access, mHealth preferences, and demographics was administered through REDCap (Research Electronic Data Capture), a digital research data tool, during packed red blood cell transfusion visits. Parents of children receiving chronic transfusions, as well as adolescents and young adults receiving chronic transfusions, were enrolled between August 2018 and June 2019. Patients had to have a hematologic diagnosis requiring chronic transfusions, be receiving ICT, and be aged 12 years or older to complete the survey. Parents were required to have a child aged 24 months who met these criteria.ResultsA total of 60 participants were included (median age 31.5, IQR 20-39 years; n=40, 67% female), with 29 (48%) being parents and 31 (52%) being patients. All parents and patients owned an electronic tablet, a smartphone, or both. The most endorsed mHealth app features among all participants included laboratory test monitoring (55/60, 92%), reminders to take iron chelation medication (50/60, 83%), and education about ICT (49/60, 82%). Parents’ most endorsed features included laboratory test monitoring (27/29, 93%) and education about ICT (25/29, 86%). Patients’ most endorsed features included laboratory test monitoring (28/31, 90%) and reminders to take iron chelation medication (28/31, 90%). There were no substantial differences between parents and patients in their preferences.ConclusionsBoth parents and adolescents and young adults reported a strong interest in multiple mHealth app features. Participants provided valuable insights into optimal strategies and preferred app features for developing a multifunctional technology-based behavioral intervention to promote ICT adherence.

Chronic insomnia causes malaise and is associated with depression, irritability, cognitive impairment, impaired alertness, and substance abuse. Individuals with posttraumatic stress disorder (PTSD) often have both inadequate and fragmented sleep, putting them at elevated risk for these consequences. Sleep abnormalities in patients with PTSD include frequent trauma-related nightmares, prolonged sleep latency, frequent interruptions, early awakening, nighttime behavioral disorders, and disruptions of sleep cycles. Here, we review the pharmacological treatment for nightmares with an emphasis on noradrenergic (NA) signaling, following the clinical observation that medication treatment with alpha-1 adrenergic blocking agents, such as prazosin, improves nightmares. We discuss the randomized controlled trials (RCTs) examining prazosin's impact on nightmares, including its efficacy and safety, and the limitations of the studies. In addition, we review the accumulating evidence from case reports, chart review, and small studies for several other anti-alpha-1 agents (specifically doxazosin, terazosin, and tamsulosin) and their efficacy in treating nightmares in PTSD. RCT studies for prazosin suggest clinical efficacy for PTSD-related nightmare disorder in subpopulations of individuals with this condition. Case studies, pilot, and open label trails suggest possible clinical use of terazosin, tamsulosin, and doxazosin in PTSD-related nightmares, however, further RCTs are needed. When available and clinically tolerated, prazosin continues to have the best evidence base for use in PTSD-related nightmares. When prazosin use is not feasible, alternative alpha-1 blockers may be effective in a subset of patients.

Treatment-resistant depression (TRD) accounts for approximately 30% of major depressive disorder cases and has been characterized by altered functional connectivity within and between the Default Mode (DMN) and Frontoparietal networks (FPN). Ketamine can be an effective treatment for TRD, and its antidepressant response has been associated with alterations in resting state functional connectivity (rsFC). Here, we evaluated the effect of a single subanesthetic dose of racemic ketamine (0.5 mg/kg) on electroencephalogram (EEG) derived source-based measures of rsFC from 24 participants with TRD (16 women; aged 44.35 ± 15.86 years). Ninety-six channel resting state EEG data were collected 24 h before and after ketamine infusion. Exact low-resolution electromagnetic tomography (eLORETA) was used to estimate theta and beta-band rsFC within and between the DMN and FPN. Ruminative symptoms were assessed using the Ruminative Response Scale. Analogous data were collected from 34 healthy control participants (25 women, aged 32.49 ± 14.07 years) who did not receive any intervention. Twenty-four hours post-infusion, depressive, anhedonic, and ruminative symptoms for the TRD sample were significantly reduced. Interestingly, symptom reduction was not correlated with any changes in rsFC but was associated with initial pre-ketamine rsFC. Moreover, individuals with TRD displayed broad increases in rsFC within the DMN and FPN as well as between these two networks. Based on preclinical findings, we posit that ketamine's synaptogenic effects may be driving this general increase in connectivity. However, these synaptogenic effects can be short lived, and future work probing the full time-course of rsFC via EEG pre- and post-ketamine administration is warranted.

Previous studies of antidepressant prescribing patterns largely were limited to a single location or time, and very few involved Asia. This Asian Psychotropic Prescription Patterns Consortium study investigated pharmacoepidemiologic trends and factors associated with use and dosing of newer antidepressants across 12 Asian sites in 2003, 2013, and 2023. Data from each site included demographic, treatment setting, clinical features, and type and dosage of antidepressants prescribed. Sociodemographic and clinical variables were examined using univariate methods, followed by multivariable logistic and linear modeling. Of 8357 adult participants (59.8% female), 82.8% received at least one modern antidepressant. Use of these drugs was strongly associated with more recent year, younger age, inpatient status, and affective or anxiety-related disorders. Higher daily antidepressant doses were associated with inpatient status, male gender, more recent year, and younger age. This large, multisite study provides a two-decade overview of evolving antidepressant-prescribing patterns in 12 Asian sites and highlights patient characteristics associated with prescription of newer antidepressants and their dosage. Needed are further studies of psychotropic prescribing practices related to specific illness subtypes and their impact on psychosocial functioning over time among Asian patients.

<title>Abstract</title> 5 February, 2026. Research Square has withdrawn this preprint due to serious research integrity concerns, including concerns regarding statistical methods, data consistency, and ethics. Further details are available on [PubPeer](https://pubpeer.com/publications/77580FB7BCE96B8A8999C39911F9CB).

ABSTRACT Fear extinction processes are central to the pathology and treatment of anxiety disorders. Emerging evidence implicates rapid eye movement (REM) sleep in the consolidation of extinction memory. Separately, converging theory and empirical work suggest that vagally mediated heart rate variability (VmHRV) serves as a peripheral index of cortico–subcortical regulatory capacity relevant to extinction circuitry. On this basis, we tested the hypothesis that VmHRV during REM sleep would be associated with the retention of extinction memory in individuals with generalized anxiety disorder (GAD). Participants underwent a validated two-day fear conditioning and extinction paradigm. Subjective extinction retention (sERI) was quantified during a recall test 24 hours after learning and ambulatory polysomnography was recorded on the intervening night. As hypothesized, higher REM VmHRV was significantly associated with better extinction retention. This association remained robust after controlling psychotropic medication use and REM density. In contrast, VmHRV during SWS or wakefulness, as well as other REM sleep measures, were not associated with extinction retention. These findings identify REM VmHRV as a significant predictor of extinction memory retention in GAD, extending prior findings in trauma-exposed individuals. We propose that reduced vagal tone indexes compromised prefrontal inhibitory control over amygdala and noradrenergic circuits, thereby impairing REM sleep-dependent consolidation. These results position VmHRV during REM sleep as a potential transdiagnostic biomarker of extinction memory processing and suggest that interventions enhancing vagal tone could improve treatment outcomes in anxiety disorders.

The Alternative Model for Personality Disorders (AMPD) in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM) assesses personality pathology as a combination of impairment (Criterion A) and problematic personality traits (Criterion B). The current study explores the ability of the traditional Personality Assessment Inventory (PAI) Borderline scales combined with new PAI-derived AMPD borderline personality disorder (BPD) facets in predicting DSM BPD criteria. The DSM BPD criteria were identified by the Structured Clinical Interview for DSM-IV Axis II Disorders (SCID-II) and by the OMNI Borderline Personality Scale. This study employed two clinical samples (n = 143 and n = 129). Correlations among the AMPD BPD facets, PAI BOR scales and SCID-II items or OMNI Borderline scale were calculated. A series of hierarchical linear regressions with stepwise entry revealed that the combination of PAI BOR subscales and AMPD BPD facets provided the strongest prediction of SCID-II Borderline PD criteria and OMNI Borderline scale, explaining 37% and 67% of the variance, respectively. Lastly, we assessed the BPD facet total and PAI BOR full scale's ability to predict psychological health and illness severity. Clinical and research implications are discussed.