Diagnostic criteria for major depressive disorder allow for heterogeneous symptom profiles but genetic analysis of major depressive symptoms has the potential to identify clinical and etiological subtypes. There are several challenges to integrating symptom data from genetically informative cohorts, such as sample size differences between clinical and community cohorts and various patterns of missing data.

We conducted genome-wide association studies of major depressive symptoms in three cohorts that were enriched for participants with a diagnosis of depression (Psychiatric Genomics Consortium, Australian Genetics of Depression Study, Generation Scotland) and three community cohorts who were not recruited on the basis of diagnosis (Avon Longitudinal Study of Parents and Children, Estonian Biobank, and UK Biobank). We fit a series of confirmatory factor models with factors that accounted for how symptom data was sampled and then compared alternative models with different symptom factors.

The best fitting model had a distinct factor for Appetite/Weight symptoms and an additional measurement factor that accounted for the skip-structure in community cohorts (use of Depression and Anhedonia as gating symptoms).

The results show the importance of assessing the directionality of symptoms (such as hypersomnia versus insomnia) and of accounting for study and measurement design when meta-analyzing genetic association data.

Therapeutics targeting frontotemporal dementia (FTD) are entering clinical trials. There are challenges to conducting these studies, including the relative rarity of the disease. Remote assessment tools could increase access to clinical research and pave the way for decentralized clinical trials. We developed the ALLFTD Mobile App, a smartphone application that includes assessments of cognition, speech/language, and motor functioning. The objectives were to determine the feasibility and acceptability of collecting remote smartphone data in a multicenter FTD research study and evaluate the reliability and validity of the smartphone cognitive and motor measures.

A diagnostically mixed sample of 207 participants with FTD or from familial FTD kindreds (CDR®+NACC-FTLD=0 [n=91]; CDR®+NACC-FTLD=0.5 [n=39]; CDR®+NACC-FTLD>1 [n=39]; unknown [n=38]) were asked to remotely complete a battery of tests on their smartphones three times over two weeks. Measures included five executive functioning (EF) tests, an adaptive memory test, and participant experience surveys. A subset completed smartphone tests of balance at home (n=31) and a finger tapping test (FTT) in the clinic (n=11). We analyzed adherence (percentage of available measures that were completed) and user experience. We evaluated Spearman-Brown split-half reliability (100 iterations) using the first available assessment for each participant. We assessed test-retest reliability across all available assessments by estimating intraclass correlation coefficients (ICC). To investigate construct validity, we fit regression models testing the association of the smartphone measures with gold-standard neuropsychological outcomes (UDS3-EF composite [Staffaroni et al., 2021], CVLT3-Brief Form [CVLT3-BF] Immediate Recall, mechanical FTT), measures of disease severity (CDR®+NACC-FTLD Box Score & Progressive Supranuclear Palsy Rating Scale [PSPRS]), and regional gray matter volumes (cognitive tests only).

Participants completed 70% of tasks. Most reported that the instructions were understandable (93%), considered the time commitment acceptable (97%), and were willing to complete additional assessments (98%). Split-half reliability was excellent for the executive functioning (r’s=0.93-0.99) and good for the memory test (r=0.78). Test-retest reliabilities ranged from acceptable to excellent for cognitive tasks (ICC: 0.70-0.96) and were excellent for the balance (ICC=0.97) and good for FTT (ICC=0.89). Smartphone EF measures were strongly associated with the UDS3-EF composite (ß's=0.6-0.8, all p<.001), and the memory test was strongly correlated with total immediate recall on the CVLT3-BF (ß=0.7, p<.001). Smartphone FTT was associated with mechanical FTT (ß=0.9, p=.02), and greater acceleration on the balance test was associated with more motor features (ß=0.6, p=0.02). Worse performance on all cognitive tests was associated with greater disease severity (ß's=0.5-0.7, all p<.001). Poorer performance on the smartphone EF tasks was associated with smaller frontoparietal/subcortical volume (ß's=0.4-0.6, all p<.015) and worse memory scores with smaller hippocampal volume (ß=0.5, p<.001).

These results suggest remote digital data collection of cognitive and motor functioning in FTD research is feasible and acceptable. These findings also support the reliability and validity of unsupervised ALLFTD Mobile App cognitive tests and provide preliminary support for the motor measures, although further study in larger samples is required.

The Test of Memory Malingering (TOMM) is a performance validity test (PVT) that aims to assess whether participants are giving adequate effort to perform well on tasks of memory performance (Tombaugh, 1996). Other PVTs, specifically the Forced Choice Recognition Trial in the California Verbal Learning Test, have shown that even single errors may indicate invalid performance (Erdodi et al., 2018). Finally, youth are often understudied in the PVT literature, and athletes are at increased risk of invalid performance on baseline testing due to many wanting to return to play following concussion (Erdal, 2012). Therefore, the objective of the current study is to examine whether single errors on TOMM Trial 1 are indicative of lower, and possibly invalid, cognitive performance in a youth sample, given that cognitive performance declines with even small decreases in effort (Green, 2007).

Healthy youth athletes (n=174) aged 8-16 years (M=12.07) completed the TOMM as well as other neuropsychological measures during baseline neuropsychological evaluation in a clinical research program for sports concussion. Independent samples t-tests compared youth athletes who scored 49 points on the TOMM (n=28) to youth athletes who scored a perfect 50 (n=50) across several groupings of neuropsychological measures. Participants who scored less than 49 or who didn’t complete the TOMM were excluded from the analyses.

Participants scoring 50/50 on TOMM Trial 1 scored significantly higher on Stroop Color Naming task (p=0.036), Verbal Learning Delayed task from the second edition of the Wide Range Assessment of Learning and Memory (WRAML-2, p=0.018), and Letter Number Sequencing task from the Weschler Intelligence Scale for Children (WISC-IV, p=0.025), relative to participants scoring 49/50. Though not statistically significant, results also showed a trend toward participants scoring 50/50 scoring higher on nearly every test in the battery.

Participants with a single error on TOMM Trial 1, as compared to participants with a perfect score, performed significantly worse on a processing speed task, a verbal learning task, and a working memory task as part of a comprehensive neuropsychological battery. The single-error group also trended toward scoring lower on nearly all of the remaining attention, processing speed, perceptual ability, memory, and executive functioning tasks in the battery. The results could lead to a more liberal interpretation of TOMM scores, given that the trend towards lower performance may be due to putting forth significantly less effort. These results point to the need for a similar comparison of the TOMM in a larger sample size, as greater power may reveal even more significant differences in performance. Findings also emphasize the importance of viewing performance validity on a continuum rather than as a dichotomous pass/fail. Understanding the TOMM and how single errors may be indicative of poorer performance in a youth sample could help to reframe the way PVT results are interpreted in clinical and forensic settings.

Performance validity testing (PVT) is important in neuropsychological evaluations to ensure accurate interpretation of performance. While research shows children pass PVTs with adult cut-offs, PVTs are more commonly used with adults (Lippa, 2018). The Test of Memory Malingering (TOMM), a standalone PVT, is commonly used with adults and children (DeRight & Carone, 2015). The Reliable Digit Span (RDS), an embedded PVT derived from the Digit Span subtest of the Wechsler Intelligence Scales (Wechsler Intelligence Scale for Children-4th Edition, WISC-IV; Wechsler, 2003), is less commonly used with children (DeRight & Carone, 2015). RDS cut-off scores are associated with an increased rate of false positives in children, indicating mixed results regarding the clinical utility in pediatric populations (Welsh et al., 2012). Research shows that youth with a history of concussion (HOC) may demonstrate suboptimal effort for many reasons (e.g., external incentives, boredom, pressure), thus highlighting the need to investigate the utility of PVTs in this population (Araujo et al., 2014; DeRight & Carone, 2015). The present study aimed to examine the clinical utility of RDS in detecting poor effort on the TOMM in youth athletes with a HOC.

Participants included 174 youth athletes aged 8 to 18 (20.1% female; 42.5% people of color (POC)) who completed a baseline neuropsychological battery that included the TOMM and WISC-IV Digit Span. Of the sample, 29 youth athletes reported a HOC (13.8% female; 37.9 POC). RDS was calculated for each Digit Span administration, and sensitivity (SN) and specificity (SP) were calculated for RDS when invalid performance was operationalized by a more stringent cut-off score of <49 to increase the SN of the TOMM Trial 1 (Stenclik et al., 2013). Receiver operator characteristics (ROC) curve analysis determined whether RDS performance accurately predicted participants’ performance on the TOMM.

The ROC curve analysis resulted in an area under the curve (AUC) of just 0.427 for RDS. A cut-off score of <7 (as suggested by Kirkwood et al. (2011)) for RDS results in 100% SN, 8.3% SP, 5% positive predictive validity (PPV), and 95% negative predictive validity (NPV). However, a cut-off score of <9 for RDS results in 75% SN, 15% SP, 25% PPV, and 75% NPV.

Little research shows the utility of different PVTs predicting children’s performance on other PVTs, despite evidence that children with a HOC are vulnerable to variable or insufficient effort (Araujo et al., 2014; DeRight & Carone, 2015). In a sample of 29 youth athletes with a HOC, RDS predicted TOMM performance at rates worse than chance. While RDS has advantages as an embedded PVT, its limited ability to predict performance on a standalone PVT suggests interpreting with great caution. These findings highlight the importance of implementing multiple PVTs throughout testing to ensure accurate findings and interpretations, particularly in youth with a HOC. The small sample size is a limitation that possibly impacted the ability of RDS to predict TOMM performance. Further research is needed to understand the utility of RDS as a predictor of PVT performance in different populations. Replication of these findings with a larger sample size is needed to provide confirmatory evidence of poor predictive performance of the RDS.

The impact of the coronavirus disease 2019 (COVID-19) pandemic on mental health is still being unravelled. It is important to identify which individuals are at greatest risk of worsening symptoms. This study aimed to examine changes in depression, anxiety and post-traumatic stress disorder (PTSD) symptoms using prospective and retrospective symptom change assessments, and to find and examine the effect of key risk factors.

Online questionnaires were administered to 34 465 individuals (aged 16 years or above) in April/May 2020 in the UK, recruited from existing cohorts or via social media. Around one-third (n = 12 718) of included participants had prior diagnoses of depression or anxiety and had completed pre-pandemic mental health assessments (between September 2018 and February 2020), allowing prospective investigation of symptom change.

Prospective symptom analyses showed small decreases in depression (PHQ-9: −0.43 points) and anxiety [generalised anxiety disorder scale – 7 items (GAD)-7: −0.33 points] and increases in PTSD (PCL-6: 0.22 points). Conversely, retrospective symptom analyses demonstrated significant large increases (PHQ-9: 2.40; GAD-7 = 1.97), with 55% reported worsening mental health since the beginning of the pandemic on a global change rating. Across both prospective and retrospective measures of symptom change, worsening depression, anxiety and PTSD symptoms were associated with prior mental health diagnoses, female gender, young age and unemployed/student status.

We highlight the effect of prior mental health diagnoses on worsening mental health during the pandemic and confirm previously reported sociodemographic risk factors. Discrepancies between prospective and retrospective measures of changes in mental health may be related to recall bias-related underestimation of prior symptom severity.

Suicide is the second leading cause of death in all youth and among adults with bipolar disorder (BD). The risk of suicide in BD is among the highest of all psychiatric conditions. Self-harm, including suicide attempts and non-suicidal self-injury, is a leading risk factor for suicide. Neuroimaging studies suggest reward circuits are implicated in both BD and self-harm; however, studies have yet to examine self-harm related resting-state functional connectivity (rsFC) phenotypes within adolescent BD.

Resting-state fMRI data were analyzed for 141 adolescents, ages 13–20 years, including 38 with BD and lifetime self-harm (BDSH+), 33 with BD and no self-harm (BDSH−), and 70 healthy controls (HC). The dorsolateral prefrontal cortex (dlPFC), orbitofrontal cortex (OFC) and amygdala were examined as regions of interest in seed-to-voxel analyses. A general linear model was used to explore the bivariate correlations for each seed.

BDSH− had increased positive rsFC between the left amygdala and left lateral occipital cortex, and between the right dlPFC and right frontal pole, and increased negative rsFC between the left amygdala and left superior frontal gyrus compared to BDSH+ and HC. BDSH+ had increased positive rsFC of the right OFC with the precuneus and left paracingulate gyrus compared to BDSH− and HC.

This study provides preliminary evidence of altered reward-related rsFC in relation to self-harm in adolescents with BD. Between-group differences conveyed a combination of putative risk and resilience connectivity patterns. Future studies are warranted to evaluate changes in rsFC in response to treatment and related changes in self-harm.

Irregular hospital discharge is highly prevalent among people admitted to hospital for mental health reasons. No study has examined the relationship between irregular discharge, post-discharge mortality and treatment setting (i.e. mortality after patients are discharged from acute in-patient or residential mental health settings).

To understand the relationship between irregular discharge and mortality among patients discharged from acute in-patient and residential settings.

A retrospective study was conducted in members of the US veteran population discharged from acute in-patient or residential settings of the US Department of Veterans Affairs between 2003 and 2018. Multivariate Cox proportional hazards were used to evaluate associations between irregular discharge and suicide, external-cause (as defined by ICD-10 Codes: V01-Y98) and all-cause mortality in the first 30-, 90- and 180-days post-discharge.

There were over 1.5 million mental health discharges between 2003 and 2018. Patients with an irregular discharge were at increased risk for suicide, external-cause and all-cause mortality in the first 180 days after discharge. In the first 30 days after discharge, patients with irregular discharge had more than three times greater suicide risk than patients with regular discharge (adjusted hazard ratio (HR) = 3.41, 95% CI 2.21–5.25). Suicide risk was higher among patients with irregular discharge in the first 30 days after acute in-patient discharge (adjusted HR = 1.55, 95% CI 1.11–2.16). In both settings, the mortality risk associated with irregular discharge attenuated but remained elevated within 90 and 180 days.

Irregular discharge after an acute in-patient or residential stay poses a large risk for mortality soon after discharge. Clinicians must identify effective interventions to mitigate harms associated with irregular discharge in these settings.

Patients admitted to the hospital may unknowingly carry severe acute respiratory coronavirus virus 2 (SARS-CoV-2), and hospitals have implemented SARS-CoV-2 admission screening. However, because SARS-CoV-2 reverse-transcription polymerase chain reaction (RT-PCR) assays may remain positive for months after infection, positive results may represent active or past infection. We determined the prevalence and infectiousness of patients who were admitted for reasons unrelated to COVID-19 but tested positive for SARS-CoV-2 on admission screening.

We conducted an observational study at the University of Iowa Hospitals & Clinics from July 7 to October 25, 2020. All patients admitted without suspicion of COVID-19 were included, and medical records of those with a positive admission screening test were reviewed. Infectiousness was determined using patient history, PCR cycle threshold (Ct) value, and serology.

In total, 5,913 patients were screened and admitted for reasons unrelated to COVID-19. Of these, 101 had positive admission RT-PCR results; 36 of these patients were excluded because they had respiratory signs/symptoms on admission on chart review. Also, 65 patients (1.1%) did not have respiratory symptoms. Finally, 55 patients had Ct values available and were included in this analysis. The median age of the final cohort was 56 years and 51% were male. Our assessment revealed that 23 patients (42%) were likely infectious. The median duration of in-hospital isolation was 5 days for those likely infectious and 2 days for those deemed noninfectious.

SARS-CoV-2 was infrequent among patients admitted for reasons unrelated to COVID-19. An assessment of the likelihood of infectiousness using clinical history, RT-PCR Ct values, and serology may help in making the determination to discontinue isolation and conserve resources.