Long-acting injectable antipsychotics (LAIs) reduce relapses in schizophrenia; however, most healthcare professionals (HCPs) reserve LAIs for nonadherence to oral antipsychotics (OAs) or severe disease.

US HCPs were surveyed regarding attitudes and perceptions toward LAIs for schizophrenia and LAI selection preferences. Respondents were grouped by LAI use (high [≥31% of patients using LAIs], low [≤14% using LAIs]; mid not analyzed) and archetype based on response to, “Which of the following best fits the current way you view your use of [LAIs] for your patients with schizophrenia?” (see responses below).

Respondents (106 high, 130 low LAI use) were distributed across early LAI use (n=123), severity-reserved (n=88), adherence-reserved (n=113), and LAI-hesitant (n=56) archetypes.

Across all groups, HCPs estimated OA nonadherence in their practice (21%– 32%) to be lower than for patients nationwide (50%– 56%). Overall, 27% were dissatisfied with their LAI:OA use ratio, most thinking their OA use was too high. In all groups, side effects/tolerability was ranked as most important when choosing an LAI and “preference for the molecule” was ranked least important. Overall, 71%– 77% of HCPs were somewhat/much more likely to use a particular LAI based on multiple injection site options, small/on par needle, and price, and 63%– 82% of HCPs were somewhat/much more likely to select an LAI dosed once monthly or less often compared with an LAI dosed once every 2 weeks (8%). HCPs with high LAI use or early LAI use archetype were more likely to disagree that managing patients with schizophrenia increased their stress (64% and 63% vs 27%-45%, P<.05 each) and/or left them feeling “burned out” (77% and 79% vs 50%– 64%, P<.05 each).

Compared with other groups, greater proportions with high LAI use or early LAI use archetype consistently read new LAI publications (18% and 19% vs 0%– 5%, P<.01) and were confident in key aspects of LAI treatment (ie, dosing, managing side effects, access; 67%– 74% and 59%– 70% vs 11%– 57%, P<.05 each).

HCPs with low LAI use estimated the proportion of patients who initially refuse LAIs to be higher (mean, 55%) than those with low LAI use (44%, P<.01); there were no differences among archetypes (49%– 54%). HCPs with high LAI use or early LAI use archetype were more likely to “use any means necessary to ensure that a patient is on an LAI” vs other groups (44% and 51% vs 5%– 22%, P<.01 each) or had used guardianship to assist with treatment (70% and 69% vs 32%– 56%, P<.05 each); greater proportions with high LAI use or early LAI use archetype strongly agreed it was “worth [their] time to resolve issues with the insurance company” (42% and 45% vs 16%– 30%, P<.05 each) and were confident they would be able to do so (23% and 20% vs 2%– 11%, P<.05 each). Greater proportions of HCPs with early LAI use archetype vs the severity-reserved archetype strongly agreed that they attempt to determine the patient’s/caregiver’s preferred role before involving them (43% vs 27%, P<.05) and encourage them to participate (72% vs 57%, P<.05) in shared decision-making.

Comparing HCPs with high LAI use or early LAI use archetype vs other groups, multiple factors (eg, attitudes, preferences, training, knowledge base) combine to influence LAI use. These results highlight considerations for developing educational materials to increase LAI use in this population.

Teva Branded Pharmaceutical Products R&D, Inc.

Healthcare professionals (HCPs) face unique challenges when managing patients with schizophrenia. Educational initiatives targeting common clinical dilemmas encountered by clinicians, including partial or nonadherence, may alleviate knowledge gaps and clarify the role of long-acting injectable antipsychotic agents (LAIs) in treating this population.

4 experts in schizophrenia management used empirical evidence to identify 11 key clinical dilemmas where LAIs may be useful. These experts then developed a heuristic, educational tool (S.C.O.P.E.™: Schizophrenia Clinical Outcome Scenarios and Patient-Provider Engagement) based on empirical evidence and expert opinion for clinicians to use when encountering similar scenarios to optimize schizophrenia care.

S.C.O.P.E.™ is a freely-available resource comprising an interactive digital platform providing educational materials for HCPs involved in continued care for patients with schizophrenia. S.C.O.P.E.™ provides HCPs with considerations in common clinical scenarios met in inpatient and outpatient settings, as well as questions to consider when patients present to the emergency department. The potential usefulness of LAIs is explored in each scenario. Clinical education videos prepare nurse practitioners, social workers, and case managers to address patient concerns and communicate the benefits of LAI treatment. S.C.O.P.E.™ will not replace clinical judgment, guidelines, or continuing medical education, and is not a platform for recording patient-level data, nor intended for payer negotiations or access-related questions by HCPs.

S.C.O.P.E.™ is an educational tool for HCPs to use alongside standard psychiatric evaluations to improve understanding of how to manage common clinical dilemmas when treating patients with schizophrenia and the role of LAIs in schizophrenia management.

Teva Branded Pharmaceutical Products R&D, Inc.

Healthcare professionals (HCPs) face unique challenges when managing patients with schizophrenia. Educational initiatives targeting common clinical dilemmas encountered by clinicians, such as unfamiliarity with prescribing information for long-acting injectable antipsychotics (LAIs), may assist clinicians when treating patients with schizophrenia.

Four experts in schizophrenia management used empirical evidence to identify 11 key clinical dilemmas where LAIs may be useful. These experts then developed a heuristic, educational tool (S.C.O.P.E.™: Schizophrenia Clinical Outcome Scenarios and Patient-Provider Engagement) based on empirical evidence and expert opinion for clinicians to use when encountering similar scenarios to optimize schizophrenia care. S.C.O.P.E.™ also includes supportive elements such as an LAI selector.

S.C.O.P.E.™ is a freely available resource comprising an interactive digital platform providing educational materials for HCPs involved in continued care for patients with schizophrenia. To acquaint HCPs with characteristics of common LAIs used in schizophrenia treatment, S.C.O.P.E.™ offers a selector that filters LAIs by approved indication(s), initiation regimen, reconstitution, dosing strengths and frequency, injection volumes and routes, and supply and storage information based on approved product labels. The LAI selector does not provide LAI safety and efficacy data, so HCPs should visit individual product websites for this information. Therefore, S.C.O.P.E.™ will not replace clinical judgment, guidelines, or continuing medical education, and is not a platform for recording patient-level data, nor intended for payer negotiations or access-related questions by HCPs.

S.C.O.P.E.™ is an educational tool for HCPs to use alongside standard psychiatric evaluations to improve understanding of how to manage common clinical dilemmas when treating patients with schizophrenia, the role of LAIs in schizophrenia management, and the product characteristics of available LAIs.

Teva Branded Pharmaceutical Products R&D, Inc.

The brain can be represented as a network, with nodes as brain regions and edges as region-to-region connections. Nodes with the most connections (hubs) are central to efficient brain function. Current findings on structural differences in Major Depressive Disorder (MDD) identified using network approaches remain inconsistent, potentially due to small sample sizes. It is still uncertain at what level of the connectome hierarchy differences may exist, and whether they are concentrated in hubs, disrupting fundamental brain connectivity.

We utilized two large cohorts, UK Biobank (UKB, N = 5104) and Generation Scotland (GS, N = 725), to investigate MDD case–control differences in brain network properties. Network analysis was done across four hierarchical levels: (1) global, (2) tier (nodes grouped into four tiers based on degree) and rich club (between-hub connections), (3) nodal, and (4) connection.

In UKB, reductions in network efficiency were observed in MDD cases globally (d = −0.076, pFDR = 0.033), across all tiers (d = −0.069 to −0.079, pFDR = 0.020), and in hubs (d = −0.080 to −0.113, pFDR = 0.013–0.035). No differences in rich club organization and region-to-region connections were identified. The effect sizes and direction for these associations were generally consistent in GS, albeit not significant in our lower-N replication sample.

Our results suggest that the brain's fundamental rich club structure is similar in MDD cases and controls, but subtle topological differences exist across the brain. Consistent with recent large-scale neuroimaging findings, our findings offer a connectomic perspective on a similar scale and support the idea that minimal differences exist between MDD cases and controls.

Face-to-face administration is the “gold standard” for both research and clinical cognitive assessments. However, many factors may impede or prevent face-to-face assessments, including distance to clinic, limited mobility, eyesight, or transportation. The COVID19 pandemic further widened gaps in access to care and clinical research participation. Alternatives to face-to-face assessments may provide an opportunity to alleviate the burden caused by both the COVID-19 pandemic and longer standing social inequities. The objectives of this study were to develop and assess the feasibility of a telephone- and video-administered version of the Uniform Data Set (UDS) v3 cognitive batteries for use by NIH-funded Alzheimer’s Disease Research Centers (ADRCs) and other research programs.

Ninety-three individuals (M age: 72.8 years; education: 15.6 years; 72% female; 84% White) enrolled in our ADRC were included. Their most recent adjudicated cognitive status was normal cognition (N=44), MCI (N=35), mild dementia (N=11) or other (N=3). They completed portions of the UDSv3 cognitive battery, plus the RAVLT, either by telephone or video-format within approximately 6 months (M:151 days) of their annual in-person visit, where they completed the same in-person cognitive assessments. Some measures were substituted (Oral Trails for TMT; Blind MoCA for MoCA) to allow for phone administration. Participants also answered questions about the pleasantness, difficulty level, and preference for administration mode. Cognitive testers provided ratings of perceived validity of the assessment. Participants’ cognitive status was adjudicated by a group of cognitive experts blinded to most recent inperson cognitive status.

When results from video and phone modalities were combined, the remote assessments were rated as pleasant as the inperson assessment by 74% of participants. 75% rated the level of difficulty completing the remote cognitive assessment the same as the in-person testing. Overall perceived validity of the testing session, determined by cognitive assessors (video = 92%; phone = 87.5%), was good. There was generally good concordance between test scores obtained remotely and in-person (r = .3 -.8; p < .05), regardless of whether they were administered by phone or video, though individual test correlations differed slightly by mode. Substituted measures also generally correlated well, with the exception of TMT-A and OTMT-A (p > .05). Agreement between adjudicated cognitive status obtained remotely and cognitive status based on in-person data was generally high (78%), with slightly better concordance between video/in-person (82%) vs phone/in-person (76%).

This pilot study provided support for the use of telephone- and video-administered cognitive assessments using the UDSv3 among individuals with normal cognitive function and some degree of cognitive impairment. Participants found the experience similarly pleasant and no more difficult than inperson assessment. Test scores obtained remotely correlated well with those obtained in person, with some variability across individual tests. Adjudication of cognitive status did not differ significantly whether it was based on data obtained remotely or in-person. The study was limited by its’ small sample size, large test-retest window, and lack of randomization to test-modality order. Current efforts are underway to more fully validate this battery of tests for remote assessment. Funded by: P30 AG072947 & P30 AG049638-05S1

Delayed cerebral ischemia (DCI) is a complication of aneurysmal subarachnoid hemorrhage (aSAH) and is associated with significant morbidity and mortality. There is little high-quality evidence available to guide the management of DCI. The Canadian Neurosurgery Research Collaborative (CNRC) is comprised of resident physicians who are positioned to capture national, multi-site data. The objective of this study was to evaluate practice patterns of Canadian physicians regarding the management of aSAH and DCI.

We performed a cross-sectional survey of Canadian neurosurgeons, intensivists, and neurologists who manage aSAH. A 19-question electronic survey (Survey Monkey) was developed and validated by the CNRC following a DCI-related literature review (PubMed, Embase). The survey was distributed to members of the Canadian Neurosurgical Society and to Canadian members of the Neurocritical Care Society. Responses were analyzed using quantitative and qualitative methods.

The response rate was 129/340 (38%). Agreement among respondents was limited to the need for intensive care unit admission, use of clinical and radiographic monitoring, and prophylaxis for the prevention of DCI. Several inconsistencies were identified. Indications for starting hyperdynamic therapy varied. There was discrepancy in the proportion of patients who felt to require IV milrinone, IA vasodilators, or physical angioplasty for treatment of DCI. Most respondents reported their facility does not utilize a standardized definition for DCI.

DCI is an important clinical entity for which no homogeneity and standardization exists in management among Canadian practitioners. The CNRC calls for the development of national standards in the definition, identification, and treatment of DCI.

Clinical high-risk states for psychosis (CHR) are associated with functional impairments and depressive disorders. A previous PRONIA study predicted social functioning in CHR and recent-onset depression (ROD) based on structural magnetic resonance imaging (sMRI) and clinical data. However, the combination of these domains did not lead to accurate role functioning prediction, calling for the investigation of additional risk dimensions. Role functioning may be more strongly associated with environmental adverse events than social functioning.

We aimed to predict role functioning in CHR, ROD and transdiagnostically, by adding environmental adverse events-related variables to clinical and sMRI data domains within the PRONIA sample.

Baseline clinical, environmental and sMRI data collected in 92 CHR and 95 ROD samples were trained to predict lower versus higher follow-up role functioning, using support vector classification and mixed k-fold/leave-site-out cross-validation. We built separate predictions for each domain, created multimodal predictions and validated them in independent cohorts (74 CHR, 66 ROD).

Models combining clinical and environmental data predicted role outcome in discovery and replication samples of CHR (balanced accuracies: 65.4% and 67.7%, respectively), ROD (balanced accuracies: 58.9% and 62.5%, respectively), and transdiagnostically (balanced accuracies: 62.4% and 68.2%, respectively). The most reliable environmental features for role outcome prediction were adult environmental adjustment, childhood trauma in CHR and childhood environmental adjustment in ROD.

Findings support the hypothesis that environmental variables inform role outcome prediction, highlight the existence of both transdiagnostic and syndrome-specific predictive environmental adverse events, and emphasise the importance of implementing real-world models by measuring multiple risk dimensions.

Substantial clinical heterogeneity of major depressive disorder (MDD) suggests it may group together individuals with diverse aetiologies. Identifying distinct subtypes should lead to more effective diagnosis and treatment, while providing more useful targets for further research. Genetic and clinical overlap between MDD and schizophrenia (SCZ) suggests an MDD subtype may share underlying mechanisms with SCZ.

The present study investigated whether a neurobiologically distinct subtype of MDD could be identified by SCZ polygenic risk score (PRS). We explored interactive effects between SCZ PRS and MDD case/control status on a range of cortical, subcortical and white matter metrics among 2370 male and 2574 female UK Biobank participants.

There was a significant SCZ PRS by MDD interaction for rostral anterior cingulate cortex (RACC) thickness (β = 0.191, q = 0.043). This was driven by a positive association between SCZ PRS and RACC thickness among MDD cases (β = 0.098, p = 0.026), compared to a negative association among controls (β = −0.087, p = 0.002). MDD cases with low SCZ PRS showed thinner RACC, although the opposite difference for high-SCZ-PRS cases was not significant. There were nominal interactions for other brain metrics, but none remained significant after correcting for multiple comparisons.

Our significant results indicate that MDD case-control differences in RACC thickness vary as a function of SCZ PRS. Although this was not the case for most other brain measures assessed, our specific findings still provide some further evidence that MDD in the presence of high genetic risk for SCZ is subtly neurobiologically distinct from MDD in general.

Chromosome 22q11.2 deletion syndrome (22q11DS) is associated with high rates of psychiatric disorders, including schizophrenia in up to 30% of individuals with the syndrome. Despite this, we know relatively little about trajectories and predictors of persistence of psychiatric disorders from middle childhood to early adulthood. Accordingly, we followed youth over four timepoints, every 3 years, to assess long-term trajectories of attention-deficit hyperactivity disorder (ADHD), anxiety, mood, and psychosis-spectrum disorders (PSDs), as well as medication usage.

Eighty-seven youth with 22q11DS and 65 controls between the ages of 9 and 15 years at the first timepoint (T1; mean age 11.88 ± 2.1) were followed for 9 years (mean age of 21.22 ± 2.01 years at T4). Baseline cognitive, clinical, and familial predictors of persistence were identified for each class of psychiatric disorders.

Baseline age and parent-rated hyperactivity scores predicted ADHD persistence [area under curve (AUC) = 0.81]. The presence of family conflict predicted persistence of anxiety disorders (ADs) whereas parent ratings of child internalizing symptoms predicted persistence of both anxiety and mood disorders (MDs) (AUC = 0.84 and 0.83, respectively). Baseline prodromal symptoms predicted persistent and emergent PSDs (AUC = 0.83). Parent-reported use of anti-depressants/anxiolytics increased significantly from T1 to T4.

Psychiatric, behavioral, and cognitive functioning during late childhood and early adolescence successfully predicted children with 22q11DS who were at highest risk for persistent psychiatric illness in young adulthood. These findings emphasize the critical importance of early assessments and interventions in youth with 22q11DS.