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.

Psychotic disorders are severe mental health conditions frequently associated with long-term disability, reduced quality of life and premature mortality. Early Intervention in Psychosis (EIP) services aim to provide timely, comprehensive packages of care for people with psychotic disorders. However, it is not clear which components of EIP services contribute most to the improved outcomes they achieve.

We aimed to identify associations between specific components of EIP care and clinically significant outcomes for individuals treated for early psychosis in England.

This national retrospective cohort study of 14 874 EIP individuals examined associations between 12 components of EIP care and outcomes over a 3-year follow-up period, by linking data from the National Clinical Audit of Psychosis (NCAP) to routine health outcome data held by NHS England. The primary outcome was time to relapse, defined as psychiatric inpatient admission or referral to a crisis resolution (home treatment) team. Secondary outcomes included duration of admissions, detention under the Mental Health Act, emergency department and general hospital attendances and mortality. We conducted multilevel regression analyses incorporating demographic and service-level covariates.

Smaller care coordinator case-loads and the use of clozapine for eligible people were associated with reduced relapse risk. Physical health interventions were associated with reductions in mortality risk. Other components, such as cognitive–behavioural therapy for psychosis (CBTp), showed associations with improvements in secondary outcomes.

Smaller case-loads should be prioritised and protected in EIP service design and delivery. Initiatives to improve the uptake of clozapine should be integrated into EIP care. Other components, such as CBTp and physical health interventions, may have specific benefits for those eligible. These findings highlight impactful components of care and should guide resource allocation to optimise EIP service delivery.

The recent wave of clinical trials of psychedelic substances among patients with life-limiting illness has largely focused on individual healing. This most often translates to a single patient receiving an intervention with researchers guiding them. As social isolation and lack of connection are major drivers of current mental health crises and group work is expected to be an important aspect of psychedelic assisted psychotherapy, it is essential that we understand the role of community in psychedelic healing.

To explore how psychedelic guides in the United States discuss the role of “community” in naturalistic psychedelic groups.

This is a secondary qualitative data study of data from a larger modified ethnographic study of psychedelic plant medicine use in the US. Fifteen facilitators of naturalistic psychedelic groups were recruited via snowball sampling. Content analysis was used to identify themes.

Participants viewed the concept of community as essential to every aspect of psychedelic work, from the motivation to use psychedelics, to the psychedelic dosing experience and the integration of lessons learned during psychedelic experiences into everyday life. Themes and subthemes were identified. Theme 1: The arc of healing through community (Subthemes: Community as intention, the group psychedelic journey experience, community and integration); Theme 2: Naturally occurring psychedelic communities as group therapy (Subthemes [as described in Table 2]: Belonging, authenticity, corrective experience, trust, touch).

Results suggest that existing knowledge about therapeutic group processes may be helpful in structuring and optimizing group psychedelic work. More research is needed on how to leverage the benefit of community connection in the therapeutic psychedelic context, including size and composition of groups, selection and dosing of psychedelic substances in group settings, facilitator training, and role of community integration. Psychedelic groups may provide benefits that individual work does not support.

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

Individuals who are unable to meet their basic needs are more likely to respond reactively to their immediate social and financial hardships with behaviors that lead to “diseases of despair,” which include suicide, drug overdose, and alcohol-induced liver diseases. We sought to assess the feasibility of a community-to-clinic referral approach for diseases of despair-related behaviors.

Guided by the Model for Adaptation Design and Impact, we adapted existing clinical risk assessments into a six-item screener and integrated it into the PA 211 Southwest helpline’s workflow. The screener was created to identify helpline callers at risk for suicidal ideation/behavior, alcohol abuse, drug use, and those in need of seasonal flu vaccination. The screener was implemented from December 2020 to March 2021. We invited at-risk individuals who accepted a service referral to complete baseline and follow-up surveys to learn about their satisfaction with screening and use of referrals.

2,868 callers were invited to take the screener, with 37% (n = 1047) participation. Among screened callers, 19% (n = 196) were at risk of alcohol abuse, 11% (n = 118) for drug use, 9% (n = 98) for suicidal ideation/behavior, and 54% (n = 568) needed flu vaccination. Of those, 265 callers accepted at least one of the offered referrals. Forty-seven individuals took our surveys, with almost half of them (n = 22) reported engaging with a referral and 90% recommended the helpline for health referrals.

Our findings demonstrate the feasibility of using existing community infrastructure and social service systems to actively screen and link at-risk individuals to needed health referrals in their communities.

Chronic insomnia is a highly prevalent disorder affecting approximately one-in-three Americans. Insomnia is associated with increased cognitive and brain arousal. Compared to healthy individuals, those with insomnia tend to show greater activation/connectivity within the default mode network (DMN) of the brain, consistent with the hyperarousal theory. We investigated whether it would be possible to suppress activation of the DMN to improve sleep using a type of repetitive transcranial magnetic stimulation (rTMS) known as continuous theta burst stimulation (cTBS).

Participants (n=9, 6 female; age=25.4, SD=5.9 years) meeting criteria for insomnia/sleep disorder on standardized scales completed a counterbalanced sham-controlled crossover design in which they served as their own controls on two separate nights of laboratory monitored sleep on separate weeks. Each session included two resting state functional magnetic resonance imaging (fMRI) sessions separated by a brief rTMS session. Stimulation involved a 40 second cTBS stimulation train applied over an easily accessible cortical surface node of the DMN located at the left inferior parietal lobe. After scanning/stimulation, the participant was escorted to an isolated sleep laboratory bedroom, fitted with polysomnography (PSG) electrodes, and allowed an 8-hour sleep opportunity from 2300 to 0700. PSG was monitored continuously and scored for standard outcomes, including total sleep time (TST), percentage of time various sleep stages, and number of arousals.

Consistent with our hypothesis, a single session of active cTBS produced a significant reduction of functional connectivity (p < .05, FDR corrected) within the DMN. In contrast, the sham condition produced no changes in functional connectivity from pre- to post-treatment. Furthermore, after controlling for age, we also found that the active treatment was associated with meaningful trends toward greater overnight improvements in sleep compared to the sham condition. First, the active cTBS condition was associated with significantly greater TST compared to sham (F(1,7)=14.19, p=.007, partial eta-squared=.67). Overall, individuals obtained 26.5 minutes more sleep on the nights that they received the active cTBS compared to the sham condition. Moreover, the active cTBS condition was associated with a significant increase in the percentage of time in rapid eye movement (REM%) sleep compared to the sham condition (F(1,7)=7.05, p=.033, partial eta-squared=.50), which was significant after controlling for age. Overall, active treatment was associated with an increase of 6.76% more of total sleep time in REM compared to sham treatment. Finally, active cTBS was associated with fewer arousals from sleep (t(8) = -1.84, p = .051, d = .61), with an average of 15.1 fewer arousals throughout the night than sham.

Overall, these findings suggest that this simple and brief cTBS approach can alter DMN brain functioning in the expected direction and was associated with trends toward improved objectively measured sleep, including increased TST and REM% and fewer arousals during the night following stimulation. These findings emerged after only a single 40-second treatment, and it remains to be seen whether multiple treatments over several days or weeks can sustain or even improve upon these outcomes.

Traumatic brain injury (TBI) and concussion are associated with increased dementia risk. Accurate TBI/concussion exposure estimates are relatively unknown for less common neurodegenerative conditions like frontotemporal dementia (FTD). We evaluated lifetime TBI and concussion frequency in patients diagnosed with a range of FTD spectrum conditions and related prior head trauma to cavum septum pellucidum (CSP) characteristics observable on MRI.

We administered the Ohio State University TBI Identification and Boston University Head Impact Exposure Assessment to 108 patients (age 69.5 ± 8.0, 35% female, 93% white or unknown race) diagnosed at the UCSF Memory and Aging Center with one of the following FTD or related conditions: behavioral variant frontotemporal dementia (N=39), semantic variant primary progressive aphasia (N=16), nonfluent variant PPA (N=23), corticobasal syndrome (N=14), or progressive supranuclear palsy (N=16). Data were also obtained from 217 controls (“HC”; age 76.8 ± 8.0, 53% female, 91% white or unknown race). CSP characteristics were defined based on width or “grade” (0-1 vs. 2+) and length of anterior-posterior separation (millimeters). We first describe frequency of any and multiple (2+) prior TBI based on different but commonly used definitions: TBI with loss of consciousness (LOC), TBI with LOC or posttraumatic amnesia (LOC/PTA), TBI with LOC/PTA or other symptoms like dizziness, nausea, “seeing stars,” etc. (“concussion”). TBI/concussion frequency was then compared between FTD and HC using chi-square. Associations between TBI/concussion and CSP characteristics were analyzed with chi-square (CSP grade) and Mann-Whitney U tests (CSP length). We explored sex differences due to typically higher rates of TBI among males.

History of any TBI with LOC (FTD=20.0%, HC=19.2%), TBI with LOC/PTA (FTD:32.2%, HC=31.5%), and concussion (FTD: 50.0%, HC=44.3%) was common but not different between study groups (p’s>.4). In both FTD and HC, prior TBI/concussion was nominally more frequent in males but not significantly greater than females. Frequency of repeat TBI/concussion (2+) also did not differ significantly between FTD and HC (repeat TBI with LOC: 6.7% vs. 3.3%, TBI with LOC/PTA: 12.2% vs. 10.3%, concussion: 30.2% vs. 28.7%; p’s>.2). Prior TBI/concussion was not significantly related to CSP grade or length in the total sample or within the FTD or HC groups.

TBI/concussion rates depend heavily on the symptom definition used for classifying prior injury. Lifetime symptomatic TBI/concussion is common but has an unclear impact on risk for FTD-related diagnoses. Larger samples are needed to appropriately evaluate sex differences, to evaluate whether TBI/concussion rates differ between specific FTD phenotypes, and to understand the rates and effects of more extensive repetitive head trauma (symptomatic and asymptomatic) in patients with FTD.

Precariously housed individuals are exposed to multiple adverse factors negatively impacting neurocognitive functioning. Additionally, this population is subjected to poor life outcomes, such as impaired psychosocial functioning. Neurocognitive functioning plays an important role in psychosocial functioning and may be especially critical for precariously housed individuals who face numerous barriers in their daily lives. However, few studies have explicitly examined the cognitive determinants of functional outcomes in this population. Cognitive intraindividual variability (IIV) involves the study of within-person differences in neurocognitive functioning and has been used as marker of frontal system pathology. Increased IIV has been associated with worse cognitive performance, cognitive decline, and poorer everyday functioning. Hence, IIV may add to the predictive utility of commonly used neuropsychological measures and may serve as an emergent predictor of poor outcomes in at-risk populations. The objective of the current study was to examine IIV as a unique index of the neurocognitive contributions to functional outcomes within a large sample of precariously housed individuals. It was hypothesized that greater IIV would be associated with poorer current (i.e., baseline) and long-term (i.e., up to 12 years) psychosocial functioning.

Four hundred and thirty-seven adults were recruited from single-room occupancy hotels located in the Downtown Eastside of Vancouver, Canada (Mage = 44 years, 78% male) between November 2008 and November 2021. Baseline neurocognitive functioning was assessed at study enrolment. Scores from the Social and Occupational Functioning Assessment Scale (SOFAS), the Role Functioning Scale (RFS), the physical component score (PCS) and the mental component score (MCS) of the 36-Item Short Form Survey Instrument were obtained at participants’ baseline assessments and at their last available follow-up assessment to represent baseline and long-term psychosocial functioning, respectively. Using an established formula, an index of IIV was derived using a battery of standardized tests that broadly assessed verbal learning and memory, sustained attention, mental flexibility, and cognitive control. A series of multiple linear regressions were conducted to predict baseline and long-term social and role functioning (average across SOFAS and RFS scores), and PCS and MCS scores from IIV. In each of the models, we also included common predictors of functioning, including a global cognitive composite score, age, and years of education.

The IIV index and the global composite score did not explain a significant proportion of the variance in baseline and long-term social and role functioning (p > .05). However, IIV was a significant predictor of baseline (B = -3.84, p = .021) and long-term (B = -3.58, p = .037) PCS scores, but not MCS scores (p > .05). The global composite score did not predict baseline or long-term PCS scores.

IIV significantly predicted baseline and long-term physical functioning, but not mental functioning or social and role functioning, suggesting that IIV may be a sensitive marker for limitations in everyday functioning due to physical health problems in precariously housed individuals. Critically, the present study is the first to show that IIV may be a useful index for predicting poor long-term health-related outcomes in this population compared to traditional neuropsychological measures.

Repetitive transcranial magnetic stimulation (TMS) is an evidenced based treatment for adults with treatment resistant depression (TRD). The standard clinical protocol for TMS is to stimulate the left dorsolateral prefrontal cortex (DLPFC). Although the DLPFC is a defining region in the cognitive control network of the brain and implicated in executive functions such as attention and working memory, we lack knowledge about whether TMS improves cognitive function independent of depression symptoms. This exploratory analysis sought to address this gap in knowledge by assessing changes in attention before and after completion of a standard treatment with TMS in Veterans with TRD.

Participants consisted of 7 Veterans (14.3% female; age M = 46.14, SD = 7.15; years education M = 16.86, SD = 3.02) who completed a full 30-session course of TMS treatment and had significant depressive symptoms at baseline (Patient Health Questionnaire-9; PHQ-9 score >5). Participants were given neurocognitive assessments measuring aspects of attention [Wechsler Adult Intelligence Scale 4th Edition (WAIS-IV) subtests: Digits Forward, Digits Backward, and Number Sequencing) at baseline and again after completion of TMS treatment. The relationship between pre and post scores were examined using paired-samples t-test for continuous variables and a linear regression to covary for depression and posttraumatic stress disorder (PTSD), which is often comorbid with depression in Veteran populations.

There was a significant improvement in Digit Span Forward (p=.01, d=-.53), but not Digit Span Backward (p=.06) and Number Sequencing (p=.54) post-TMS treatment. Depression severity was not a significant predictor of performance on Digit Span Forward (f(1,5)=.29, p=.61) after TMS treatment. PTSD severity was also not a significant predictor of performance on Digit Span Forward (f(1,5)=1.31, p=.32).

Findings suggested that a standard course of TMS improves less demanding measures of working memory after a full course of TMS, but possibly not the more demanding aspects of working memory. This improvement in cognitive function was independent of improvements in depression and PTSD symptoms. Further investigation in a larger sample and with direct neuroimaging measures of cognitive function is warranted.

Clinical implementation of risk calculator models in the clinical high-risk for psychosis (CHR-P) population has been hindered by heterogeneous risk distributions across study cohorts which could be attributed to pre-ascertainment illness progression. To examine this, we tested whether the duration of attenuated psychotic symptom (APS) worsening prior to baseline moderated performance of the North American prodrome longitudinal study 2 (NAPLS2) risk calculator. We also examined whether rates of cortical thinning, another marker of illness progression, bolstered clinical prediction models.

Participants from both the NAPLS2 and NAPLS3 samples were classified as either ‘long’ or ‘short’ symptom duration based on time since APS increase prior to baseline. The NAPLS2 risk calculator model was applied to each of these groups. In a subset of NAPLS3 participants who completed follow-up magnetic resonance imaging scans, change in cortical thickness was combined with the individual risk score to predict conversion to psychosis.

The risk calculator models achieved similar performance across the combined NAPLS2/NAPLS3 sample [area under the curve (AUC) = 0.69], the long duration group (AUC = 0.71), and the short duration group (AUC = 0.71). The shorter duration group was younger and had higher baseline APS than the longer duration group. The addition of cortical thinning improved the prediction of conversion significantly for the short duration group (AUC = 0.84), with a moderate improvement in prediction for the longer duration group (AUC = 0.78).

These results suggest that early illness progression differs among CHR-P patients, is detectable with both clinical and neuroimaging measures, and could play an essential role in the prediction of clinical outcomes.