Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.

T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).

PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).

PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.

Treatment guidelines recommend evidence-based psychological therapies for adults with intellectual disabilities with co-occurring anxiety or depression. No previous research has explored the effectiveness of these therapies in mainstream psychological therapy settings or outside specialist settings.

To evaluate the effectiveness of psychological therapies delivered in routine primary care settings for people with intellectual disability who are experiencing co-occurring depression or anxiety.

This study used linked electronic healthcare records of 2 048 542 adults who received a course of NHS Talking Therapies for anxiety and depression in England between 2012 and 2019 to build a retrospective, observational cohort of individuals with intellectual disability, matched 1:2 with individuals without intellectual disability. Logistic regressions were used to compare metrics of symptom improvement and deterioration used in the national programme, on the basis of depression and anxiety measures collected before and at the last attended therapy session.

The study included 6870 adults with intellectual disability and 2 041 672 adults without intellectual disability. In unadjusted analyses, symptoms improved on average for people with intellectual disability after a course of therapy, but these individuals experienced poorer outcomes compared with those without intellectual disability (reliable improvement 60.2% for people with intellectual disability v. 69.2% for people without intellectual disability, odds ratio 0.66, 95% CI 0.63–0.70; reliable deterioration 10.3% for people with intellectual disability v. 5.7% for those without intellectual disability, odds ratio 1.89, 95% CI 1.75–2.04). After propensity score matching, some differences were attenuated (reliable improvement, adjusted odds ratio 0.97, 95% CI 1.91–1.04), but some outcomes remained poorer for people with intellectual disability (reliable deterioration, adjusted odds ratio 1.28, 95% CI 1.16–1.42).

Evidence-based psychological therapies may be effective for adults with intellectual disability, but their outcomes may be similar to (for improvement and recovery) or poorer than (for deterioration) those for adults without intellectual disability. Future work should investigate the impact of adaptations of therapies for those with intellectual disability to make such interventions more effective and accessible for this population.

Motor neuron disease (MND) is a progressive, fatal, neurodegenerative condition that affects motor neurons in the brain and spinal cord, resulting in loss of the ability to move, speak, swallow and breathe. Acceptance and commitment therapy (ACT) is an acceptance-based behavioural therapy that may be particularly beneficial for people living with MND (plwMND). This qualitative study aimed to explore plwMND’s experiences of receiving adapted ACT, tailored to their specific needs, and therapists’ experiences of delivering it.

Semi-structured qualitative interviews were conducted with plwMND who had received up to eight 1:1 sessions of adapted ACT and therapists who had delivered it within an uncontrolled feasibility study. Interviews explored experiences of ACT and how it could be optimised for plwMND. Interviews were audio recorded, transcribed and analysed using framework analysis.

Participants were 14 plwMND and 11 therapists. Data were coded into four over-arching themes: (i) an appropriate tool to navigate the disease course; (ii) the value of therapy outweighing the challenges; (iii) relevance to the individual; and (iv) involving others. These themes highlighted that ACT was perceived to be acceptable by plwMND and therapists, and many participants reported or anticipated beneficial outcomes in the future, despite some therapeutic challenges. They also highlighted how individual factors can influence experiences of ACT, and the potential benefit of involving others in therapy.

Qualitative data supported the acceptability of ACT for plwMND. Future research and clinical practice should address expectations and personal relevance of ACT to optimise its delivery to plwMND.

1. (1) To understand the views of people living with motor neuron disease (plwMND) and therapists on acceptance and commitment therapy (ACT) for people living with this condition.

2. (2) To understand the facilitators of and barriers to ACT for plwMND.

3. (3) To learn whether ACT that has been tailored to meet the specific needs of plwMND needs to be further adapted to potentially increase its acceptability to this population.

Depression is an independent risk factor for cardiovascular disease (CVD), but it is unknown if successful depression treatment reduces CVD risk.

Using eIMPACT trial data, we examined the effect of modernized collaborative care for depression on indicators of CVD risk. A total of 216 primary care patients with depression and elevated CVD risk were randomized to 12 months of the eIMPACT intervention (internet cognitive-behavioral therapy [CBT], telephonic CBT, and select antidepressant medications) or usual primary care. CVD-relevant health behaviors (self-reported CVD prevention medication adherence, sedentary behavior, and sleep quality) and traditional CVD risk factors (blood pressure and lipid fractions) were assessed over 12 months. Incident CVD events were tracked over four years using a statewide health information exchange.

The intervention group exhibited greater improvement in depressive symptoms (p < 0.01) and sleep quality (p < 0.01) than the usual care group, but there was no intervention effect on systolic blood pressure (p = 0.36), low-density lipoprotein cholesterol (p = 0.38), high-density lipoprotein cholesterol (p = 0.79), triglycerides (p = 0.76), CVD prevention medication adherence (p = 0.64), or sedentary behavior (p = 0.57). There was an intervention effect on diastolic blood pressure that favored the usual care group (p = 0.02). The likelihood of an incident CVD event did not differ between the intervention (13/107, 12.1%) and usual care (9/109, 8.3%) groups (p = 0.39).

Successful depression treatment alone is not sufficient to lower the heightened CVD risk of people with depression. Alternative approaches are needed.

ClinicalTrials.gov Identifier: NCT02458690

Currently utilized clinician-rated symptom scales for tardive dyskinesia (TD) have not kept up with the expanding spectrum of TD phenomenology. The objective of this study was to develop and test the reliability of a new instrument, the CTI.

A movement disorder neurologist devised the outline of the scale. A steering committee (four neurologists and two psychiatrists) provided revisions until consensus was reached. The resulting instrument assesses frequency of abnormal movements of the eye/eyelid/face, tongue/mouth, jaw, limb/trunk, complex movements (e.g., handwringing, self-caressing), and vocalizations. The CTI rates symptoms from 0–3 with 0 = absent, 1 = infrequent/intermittent or only present with activating maneuvers, 2 = frequent intermittent, brief periods without movements, 3 = constant or nearly constant. Functional impairments including activities of daily living (ADL), social impairment, symptom bother, and harm are rated 0–3 with 0 = patient is unaware or unaffected, 1 = symptoms mildly impact patient, 2 = symptoms moderately impact patient, 3 = symptoms severely impact patient. Following institutional review board approval, the CTI underwent inter-rater and test-retest reliability testing. Videos of patient TD examinations were obtained and reviewed by two movement disorder specialists to confirm the diagnosis of TD by consensus and the adequacy to demonstrate a TD-consistent movement. Vignettes were created to include patients’ symptom descriptions and functional, social, or occupational impairments/limitations. Four clinicians rated each video/vignette. Selected videos/vignettes were also subject to an intra-rater retest. Interrater agreement was analyzed via 2-way random-effects interclass correlation (ICC) and test-retest agreement assessment utilizing Kendall’s tau-b.

45 video/vignettes were assessed for interrater reliability, and 16 for test-retest reliability. ICCs for movement frequency were as follows: abnormal eye movement .89; abnormal tongue/mouth movement .91; abnormal jaw movement .89; abnormal limb movement .76; complex movement .87; abnormal vocalization .77; and functional impairments including harm .82; social embarrassment .88; ADLs .83; and symptom bother .92. Retests were conducted on mean (SD) 15 (3) days later with scores ranging from .66–.87.

The CTI is a new instrument with good reliability in assessing TD symptoms and functional impacts. Future validation study is warranted.

Neurocrine Biosciences

The Residual Lesion Score is a novel tool for assessing the achievement of surgical objectives in congenital heart surgery based on widely available clinical and echocardiographic characteristics. This article describes the methodology used to develop the Residual Lesion Score from the previously developed Technical Performance Score for five common congenital cardiac procedures using the RAND Delphi methodology.

A panel of 11 experts from the field of paediatric and congenital cardiology and cardiac surgery, 2 co-chairs, and a consultant were assembled to review and comment on validity and feasibility of measuring the sub-components of intraoperative and discharge Residual Lesion Score for five congenital cardiac procedures. In the first email round, the panel reviewed and commented on the Residual Lesion Score and provided validity and feasibility scores for sub-components of each of the five procedures. In the second in-person round, email comments and scores were reviewed and the Residual Lesion Score revised. The modified Residual Lesion Score was scored independently by each panellist for validity and feasibility and used to develop the “final” Residual Lesion Score.

The Residual Lesion Score sub-components with a median validity score of ≥7 and median feasibility score of ≥4 that were scored without disagreement and with low absolute deviation from the median were included in the “final” Residual Lesion Score.

Using the RAND Delphi methodology, we were able to develop Residual Lesion Score modules for five important congenital cardiac procedures for the Pediatric Heart Network’s Residual Lesion Score study.

Bloodstream infections (BSIs) are a frequent cause of morbidity in patients with acute myeloid leukemia (AML), due in part to the presence of central venous access devices (CVADs) required to deliver therapy.

To determine the differential risk of bacterial BSI during neutropenia by CVAD type in pediatric patients with AML.

We performed a secondary analysis in a cohort of 560 pediatric patients (1,828 chemotherapy courses) receiving frontline AML chemotherapy at 17 US centers. The exposure was CVAD type at course start: tunneled externalized catheter (TEC), peripherally inserted central catheter (PICC), or totally implanted catheter (TIC). The primary outcome was course-specific incident bacterial BSI; secondary outcomes included mucosal barrier injury (MBI)-BSI and non-MBI BSI. Poisson regression was used to compute adjusted rate ratios comparing BSI occurrence during neutropenia by line type, controlling for demographic, clinical, and hospital-level characteristics.

The rate of BSI did not differ by CVAD type: 11 BSIs per 1,000 neutropenic days for TECs, 13.7 for PICCs, and 10.7 for TICs. After adjustment, there was no statistically significant association between CVAD type and BSI: PICC incident rate ratio [IRR] = 1.00 (95% confidence interval [CI], 0.75–1.32) and TIC IRR = 0.83 (95% CI, 0.49–1.41) compared to TEC. When MBI and non-MBI were examined separately, results were similar.

In this large, multicenter cohort of pediatric AML patients, we found no difference in the rate of BSI during neutropenia by CVAD type. This may be due to a risk-profile for BSI that is unique to AML patients.

Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.

To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.

Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.

Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.

AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.