To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
To better characterize brain-based mechanisms of polygenic liability for psychopathology and psychological traits, we extended our previous report (Liu et al. Psychophysiological endophenotypes to characterize mechanisms of known schizophrenia genetic loci. Psychological Medicine, 2017), focused solely on schizophrenia, to test the association between multivariate psychophysiological candidate endophenotypes (including novel measures of θ/δ oscillatory activity) and a range of polygenic scores (PGSs), namely alcohol/cannabis/nicotine use, an updated schizophrenia PGS (containing 52 more genome-wide significant loci than the PGS used in our previous report) and educational attainment.
A large community-based twin/family sample (N = 4893) was genome-wide genotyped and imputed. PGSs were constructed for alcohol use, regular smoking initiation, lifetime cannabis use, schizophrenia, and educational attainment. Eleven endophenotypes were assessed: visual oddball task event-related electroencephalogram (EEG) measures (target-related parietal P3 amplitude, frontal θ, and parietal δ energy/inter-trial phase clustering), band-limited resting-state EEG power, antisaccade error rate. Principal component analysis exploited covariation among endophenotypes to extract a smaller number of meaningful dimensions/components for statistical analysis.
Endophenotypes were heritable. PGSs showed expected intercorrelations (e.g. schizophrenia PGS correlated positively with alcohol/nicotine/cannabis PGSs). Schizophrenia PGS was negatively associated with an event-related P3/δ component [β = −0.032, nonparametric bootstrap 95% confidence interval (CI) −0.059 to −0.003]. A prefrontal control component (event-related θ/antisaccade errors) was negatively associated with alcohol (β = −0.034, 95% CI −0.063 to −0.006) and regular smoking PGSs (β = −0.032, 95% CI −0.061 to −0.005) and positively associated with educational attainment PGS (β = 0.031, 95% CI 0.003–0.058).
Evidence suggests that multivariate endophenotypes of decision-making (P3/δ) and cognitive/attentional control (θ/antisaccade error) relate to alcohol/nicotine, schizophrenia, and educational attainment PGSs and represent promising targets for future research.
The Cal-DSH Diversion Guidelines provide 10 general guidelines that jurisdictions should consider when developing diversion programs for individuals with a serious mental illness (SMI) who become involved in the criminal justice system. Screening for SMI in a jail setting is reviewed. In addition, important treatment interventions for SMI and substance use disorders are highlighted with the need to address criminogenic risk factors highlighted.
A new wood-boring ichnospecies is described from transgressive (lagoonal) deposits of the Lower Cretaceous Sparky Formation (Mannville Group) in west-central Saskatchewan, Canada. Apectoichnus lignummasticans new ichnospecies is a trace fossil that occurs in a thin coal bed and that was emplaced in an in situ xylic substratum (woodground). The ichnofossil is thin, elongate, unbranched, and straight to gently curved with a circular cross section and uniform diameter. Apectoichnus lignummasticans n. isp. is similar in many respects to modern borings in wood that are produced by marine isopods, e.g., Limnoria lignorum Rathke, 1799, for feeding and refugia. The recognition of Apectoichnus lignummasticans n. isp. in the rock record aligns with the modern observation that fossilized wood-boring assemblages should display higher ichnofossil diversities than commonly reported. Additionally, the stratigraphic occurrence of Apectoichnus lignummasticans n. isp. in association with other evidence of marine deposition reaffirms that certain wood boring morphologies (i.e., ichnotaxa) are useful as indicators of marine transgressions.
While negative affect reliably predicts binge eating, it is unknown how this association may decrease or ‘de-couple’ during treatment for binge eating disorder (BED), whether such change is greater in treatments targeting emotion regulation, or how such change predicts outcome. This study utilized multi-wave ecological momentary assessment (EMA) to assess changes in the momentary association between negative affect and subsequent binge-eating symptoms during Integrative Cognitive Affective Therapy (ICAT-BED) and Cognitive Behavior Therapy Guided Self-Help (CBTgsh). It was predicted that there would be stronger de-coupling effects in ICAT-BED compared to CBTgsh given the focus on emotion regulation skills in ICAT-BED and that greater de-coupling would predict outcomes.
Adults with BED were randomized to ICAT-BED or CBTgsh and completed 1-week EMA protocols and the Eating Disorder Examination (EDE) at pre-treatment, end-of-treatment, and 6-month follow-up (final N = 78). De-coupling was operationalized as a change in momentary associations between negative affect and binge-eating symptoms from pre-treatment to end-of-treatment.
There was a significant de-coupling effect at follow-up but not end-of-treatment, and de-coupling did not differ between ICAT-BED and CBTgsh. Less de-coupling was associated with higher end-of-treatment EDE global scores at end-of-treatment and higher binge frequency at follow-up.
Both ICAT-BED and CBTgsh were associated with de-coupling of momentary negative affect and binge-eating symptoms, which in turn relate to cognitive and behavioral treatment outcomes. Future research is warranted to identify differential mechanisms of change across ICAT-BED and CBTgsh. Results also highlight the importance of developing momentary interventions to more effectively de-couple negative affect and binge eating.
Individuals with tardive dyskinesia (TD) who completed a long-term study (KINECT 3 or KINECT 4) of valbenazine (40 or 80 mg/day, once-daily for up to 48 weeks followed by 4-week washout) were enrolled in a subsequent study (NCT02736955) that was primarily designed to further evaluate the long-term safety of valbenazine.
Participants were initiated at 40 mg/day (following prior valbenazine washout). At week 4, dosing was escalated to 80 mg/day based on tolerability and clinical assessment of TD; reduction to 40 mg/day was allowed for tolerability. The study was planned for 72 weeks or until termination due to commercial availability of valbenazine. Assessments included the Clinical Global Impression of Severity-TD (CGIS-TD), Patient Satisfaction Questionnaire (PSQ), and treatment-emergent adverse events (TEAEs).
At study termination, 85.7% (138/161) of participants were still active. Four participants had reached week 60, and none reached week 72. The percentage of participants with a CGIS-TD score ≤2 (normal/not ill or borderline ill) increased from study baseline (14.5% [23/159]) to week 48 (64.3% [36/56]). At baseline, 98.8% (158/160) of participants rated their prior valbenazine experience with a PSQ score ≤2 (very satisfied or somewhat satisfied). At week 48, 98.2% (55/56) remained satisfied. Before week 4 (dose escalation), 9.4% of participants had ≥1 TEAE. After week 4, the TEAE incidence was 49.0%. No TEAE occurred in ≥5% of participants during treatment (before or after week 4).
Valbenazine was well-tolerated and persistent improvements in TD were found in adults who received once-daily treatment for >1 year.
Group psychotherapy for older adults with generalised anxiety disorder is an under-researched area.
This report describes a mixed method evaluation of the acceptability and feasibility of an Overcoming Worry Group.
The Overcoming Worry Group was a novel adaptation of a cognitive behavioural therapy protocol targeting intolerance-of-uncertainty for generalised anxiety disorder, tailored for delivery to older adults in a group setting (n = 13).
The adapted protocol was found to be acceptable and feasible, and treatment outcomes observed were encouraging.
This proof-of-concept study provides evidence for an Overcoming Worry Group as an acceptable and feasible group treatment for older adults with generalised anxiety disorder.
The Minnesota Center for Twin and Family Research (MCTFR) comprises multiple longitudinal, community-representative investigations of twin and adoptive families that focus on psychological adjustment, personality, cognitive ability and brain function, with a special emphasis on substance use and related psychopathology. The MCTFR includes the Minnesota Twin Registry (MTR), a cohort of twins who have completed assessments in middle and older adulthood; the Minnesota Twin Family Study (MTFS) of twins assessed from childhood and adolescence into middle adulthood; the Enrichment Study (ES) of twins oversampled for high risk for substance-use disorders assessed from childhood into young adulthood; the Adolescent Brain (AdBrain) study, a neuroimaging study of adolescent twins; and the Siblings Interaction and Behavior Study (SIBS), a study of adoptive and nonadoptive families assessed from adolescence into young adulthood. Here we provide a brief overview of key features of these established studies and describe new MCTFR investigations that follow up and expand upon existing studies or recruit and assess new samples, including the MTR Study of Relationships, Personality, and Health (MTR-RPH); the Colorado-Minnesota (COMN) Marijuana Study; the Adolescent Brain Cognitive Development (ABCD) study; the Colorado Online Twins (CoTwins) study and the Children of Twins (CoT) study.
Children vary in the extent to which they benefit from parenting programs for conduct problems. How does parental mental health change if children benefit less or more? We assessed whether changes in conduct problems and maternal depressive symptoms co-occur following participation in the Incredible Years parenting program. We integrated individual participant data from 10 randomized trials (N = 1280; children aged 2–10 years) and distinguished latent classes based on families' baseline and post-test conduct problems and maternal depressive symptoms, using repeated measures latent class analysis (RMLCA) and latent transition analysis (LTA). Classes differed mainly in severity of conduct problems and depression (RMLCA; 4 classes). Conduct problems reduced in all classes. Depressive symptoms did not change in most classes, except in a class of families where conduct problems and depression were particularly severe. Incredible Years led to a greater likelihood of families with particularly severe conduct problems and depression moving to a class with mild problems (LTA; 3 classes). Our findings suggest that for the majority of families, children's conduct problems reduce, but maternal depressive symptoms do not, suggesting relative independence, with the exception of families with severe depression and severe conduct problems where changes for the better do co-occur.
Music and sporting events are mass gatherings with unique risks related to participation. “All-ages” events, which include participants below the age of majority (18 in many jurisdictions), have been observed to have an over-representation of patient presentations in the youth category. Peer helpers may lower the barrier to seeking on-site care. Youth (peer-aged) volunteerism provides opportunities for exposure to new environments, skills, and mentorship. Medical volunteerism may promote personal satisfaction through prosocial behavior (i.e., helping others), community engagement and immersion into a potential health professions career path.
We conducted an observational pilot feasibility study with feedback forms and semi-structured interviews. The pilot program paired youth with parents/guardians/responsible adults as health care volunteers at special events.
Youth/adult dyads volunteered for a variety of events in Canada during the 2018 event season. All participants in the “Juniors Program” completed at least a Standard First Aid course, including orientation to personal safety and confidentiality. Each pair worked in one of two areas: first aid or Festival Health (the harm reduction space at music events) providing peer-to-peer and “all-ages” support. Post-event feedback from the dyads revealed many positive experiences and universally called for more opportunities.
A strong volunteer base is an asset to any community. In this pilot study, the volunteer experiences were supervised by a team of credentialed health care professionals. The authors report on qualitative feedback in themes based on patient perspective, volunteer perspective, team perspective, and event management perspective. More research is needed to measure the outcomes of the Junior’s Program. More Investigation is needed to determine not only the long-term benefits of participation on event medical teams, but also to identify factors that shape a positive experience for youth, their parents, and the event participants that they support.
A large dataset of word recognition behavior from nonnative speakers (NNS) of English was collected using an online crowdsourced lexical decision task. Lexical features were used to predict NNS lexical decision latencies and accuracies. Predictors of NNS latencies and accuracy included contextual diversity, age of acquisition, and contextual distinctiveness, while length moderated the impact of contextual diversity and neighborhood size on accuracy. Results have implications for second language word recognition and demonstrate that NNS behavioral data collected through large crowdsourcing projects can afford a rich source for SLA research.
Patients treated with antipsychotics, regardless of psychiatric diagnosis, are at risk for developing tardive dyskinesia (TD), a potentially debilitating drug-induced movement disorder. Valbenazine (INGREZZA; VBZ) is a novel vesicular monoamine transporter 2 (VMAT2) inhibitor approved to treat TD in adults. Data from KINECT 4 (NCT02405091) were analyzed to evaluate the long-term effects of VBZ in adults with schizophrenia/schizoaffective disorder (SZD) or mood disorder (MD) and moderate or severe TD.
KINECT 4 included open-label treatment (48weeks) followed by washout (4weeks). Entry requirements included: moderate or severe TD, qualitatively assessed at screening by a blinded, external reviewer; DSM diagnosis of SZD or MD; psychiatric stability (Brief Psychiatric Rating Scale score <50). Stable concomitant psychiatric medications were allowed. Dosing was initiated at 40mg, with escalation to 80mg at Wk4 if participants had a Clinical Global Impression of Change-TD score of ≥3 (minimally improved to very much worse) and tolerated 40mg. A reduction to 40mg was allowed if 80mg was not tolerated (80/40mg); participants unable to tolerate 40mg were discontinued. Safety was the primary focus, but the Abnormal Involuntary Movement Scale (AIMS) total score (sum of items 1–7) was used to evaluate changes in TD. Mean changes from baseline (BL) in AIMS total score (rated by on-site investigators) were analyzed descriptively. Safety assessments included treatment-emergent adverse events (TEAEs) and psychiatric scales (Positive and Negative Syndrome Scale [PANSS], Calgary Depression Scale for Schizophrenia [CDSS], Montgomery-Åsberg Depression Rating Scale [MADRS], Young Mania Rating Scale [YMRS], and Columbia-Suicide Severity Rating Scale [C SSRS]).
Of 163 participants in the analyses, 103 completed the study. Adverse events (n=26) was the most common reason for discontinuation. Analyses included 119 participants with SZD (40mg=37; 80mg=76; 80/40mg=6) and 44 with MD (40mg=8; 80mg=31; 80/40mg=5). At Wk48, mean improvements from BL in AIMS total score were: SZD (40mg, –10.1; 80mg,–10.7); MD (40mg, 10.2; 80mg: –11.6). AIMS total scores at Wk52 (end of washout) indicated a return toward BL levels. Compared to SZD, the MD subgroup had a higher incidence of any TEAE (84% vs 61% [all doses]) but fewer TEAEs leading to discontinuation (7% vs 18%). Urinary tract infection was the most common TEAE in the MD subgroup (18%); somnolence and headache were most common in the SZD subgroup (7% each). Psychiatric status remained stable from BL to Wk48: SZD (PANSS positive, –0.7, PANSS negative, –0.6; CDSS, –0.7); MD (MADRS, –0.3; YMRS, –0.3). Most participants (95%) had no change in C-SSRS score during the study.
Sustained and clinically meaningful TD improvements were observed with VBZ, regardless of primary psychiatric diagnosis. VBZ was generally well tolerated and no notable changes in psychiatric status were observed.
Funding Acknowledgements: Supported by Neurocrine Biosciences, Inc.
To evaluate the long-term safety and tolerability of once-dailyvalbenazine in adults with tardive dyskinesia(TD).
Data were pooled from KINECT 3 (NCT02274558: 6-week double-blind placebo-controlled period, followed by a 42-week double-blind extension and 4-week drug-free washout) and KINECT 4 (NCT02405091: 48-week open-label treatment period and 4-week drug-free washout). KINECT 3/4 study completers could enroll in a subsequent rollover study (NCT02736955: up to 72weeks of open-label treatment or until valbenazine became commercial available); data from this study were described separately for this analysis. Valbenazine dose groups (40 and 80mg) were pooled for analysis. Safety assessments included treatment-emergent adverse events (TEAEs) and the Columbia-Suicide Severity Rating Scale (C-SSRS). Psychiatric status was assessed in KINECT 3 and KINECT 4 using the following measures: Positive and Negative Syndrome Scale (PANSS) total score and Calgary Depression Scale for Schizophrenia (CDSS) in participants with schizophrenia/schizoaffective disorder; Montgomery-Åsberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) in participants with a mood disorder.
Analyses included 304 KINECT 3/4 participants and 160 rollover participants. In KINECT 3/4, the summary of TEAEs was as follows: any TEAE (71.7%), serious TEAE (16.8%), and discontinuation due to TEAE (15.5%). TEAEs reported in ≥5% of all KINECT 3/4 participants were headache (8.9%), urinary tract infection (8.9%), somnolence (7.9%), fatigue (6.3%), dizziness (5.9%), and suicidal ideation (5.6%). The summary of TEAEs from the rollover study was as follows: any TEAE (53.1%), serious TEAE (10.0%), and discontinuation due to TEAE (5.6%). The most common TEAEs in the rollover study were back pain and urinary tract infection (4.4%, each); no TEAE was reported in ≥5% of participants. Minimal changes in psychiatric status were observed in KINECT 3/4, as indicated by mean score changes from baseline to Week 48 in participants with schizophrenia/schizoaffective disorder (PANSS total, –3.2; CDSS total, –0.5) or a mood disorder (MADRS total, 0.3; YMRS total, –1.0). Over one-third of study participants had a lifetime history of suicidal ideation or behavior (KINECT 3/4, 41%; rollover, 38%). Most participants had no C-SSRS suicidal ideation at study baseline; of these, >90% had no emergence of suicidal ideation at any time during the study (KINECT 3/4, 93% [276/296]; rollover, 98% [153/156]).
Valbenazine was well tolerated and no unexpected safety signals were found in adults who received >1 year of once-daily treatment. Psychiatric stability was maintained, and few participants experienced any emergence of suicidal ideation during the studies despite 35–40% having a lifetime history of suicidality. These results indicate that once-daily valbenazine may be an appropriate treatment for the long-term management of TD.
Funding Acknowledgements: Neurocrine Biosciences, Inc.
Valbenazine (VBZ) is a novel vesicular monoamine transporter 2 (VMAT2) inhibitor approved to treat tardive dyskinesia (TD) in adults. It has been evaluated in 2 long-term studies (KINECT 3, KINECT 4) in which participants received VBZ (40 or 80mg) for up to 48weeks. This long-term rollover study (NCT02736955) was conducted to evaluate global TD improvement and patient satisfaction with once-daily VBZ.
Key eligibility criteria: age 18 to 85 years; completion of KINECT 3 or KINECT 4; maintenance medications (for schizophrenia, schizoaffective disorder, or mood disorder) at stable doses; Brief Psychiatric Rating Scale score <50; no significant risk of active suicidal ideation or behavior. Following washout of prior VBZ treatment (Weeks 48 to 52 of KINECT 3 and KINECT 4), participants were re-initiated at 40mg (4weeks) and escalated to 80mg based on tolerability and clinical assessment of TD; dose was reduced to 40mg if 80mg was not tolerated (80/40mg). If unable to tolerate the 40mg dose, the participant was discontinued. Participants received open-label VBZ for up to 72weeks or until commercial availability. Assessments included Clinical Global Impression of Severity-TD (CGIS-TD: range, 1[“normal, not at all ill”] to 7[“among the most extremely ill patient”]) and Patient Satisfaction Questionnaire (PSQ: range, 1[“very satisfied”] to 5[“very dissatisfied”]).
160 participants with available data were included in analyses (40mg =35; 80mg =117; 80/40mg =8); 138 were receiving treatment when VBZ became commercially available. The percentages of participants who completed visits at Wks 12, 24, 36, and 48 were 96.3%, 78.1%, 56.9% and 35.0%, respectively. Few reached Wk 60 (n=4) or Wk 72 (n=0) due to commercial availability. The percentage of participants with CGIS-TD score ≤2 (“normal, not at all ill” or “borderline ill”) increased from baseline (before restarting VBZ) (40mg, 5.7%; 80mg, 18.1%) to Wk 48 (40mg , 41.7%; 80mg , 74.4%). At baseline, almost all participants rated their prior VBZ experience with a PSQ score ≤2 (“very satisfied” or “somewhat satisfied”) (40mg , 100%, 80mg , 99.1%). Similar results were seen at the Wk 48 visit, with most participants continuing to express satisfaction with VBZ (40mg , 100%; 80mg , 97.4%).
A clinician-based global assessment indicated ongoing, meaningful TD improvements in adults who received once-daily VBZ in the current study. In participants treated for >1 year, continued patient satisfaction rates with VBZ were high.
Funding Acknowledgements: Neurocrine Biosciences, Inc.
A number of longitudinal studies of L2 production have reported frequency effects wherein learners' produce more frequent words as a function of time. The current study investigated the spoken output of English L2 learners over a four-month period of time using both native and non-native English speaker frequency norms for both word types and word tokens. The study also controlled for individual differences such as first language distance, English proficiency, gender, and age. Results demonstrated that lower level L2 learners produced more infrequent tokens at the beginning of the study and that high intermediate learners, when compared to advanced learners, produced more infrequent tokens at the beginning of the study and more frequent tokens toward the end of the study. Main effects were also reported for proficiency level, age, and language distance. These results provide further evidence that L2 production may not follow expected frequency trends (i.e., that more infrequent tokens are produced as a function of time).
The low (high) abnormal returns of stocks with high (low) beta, which we refer to as the beta anomaly, is one of the most persistent anomalies in empirical asset pricing research. This article demonstrates that investors’ demand for lottery-like stocks is an important driver of the beta anomaly. The beta anomaly is no longer detected when beta-sorted portfolios are neutralized to lottery demand, regression specifications control for lottery demand, or factor models include a lottery demand factor. The beta anomaly is concentrated in stocks with low levels of institutional ownership and it exists only when the price impact of lottery demand is concentrated in high-beta stocks.