Pain, mood, and suicidal behavior among injured working adults in Chile.

BACKGROUND: Chronic pain is comorbid with psychiatric disorders, but information on the association of chronic pain with depressive symptoms, generalized anxiety, and suicidal behavior among occupational cohorts is inadequate. We investigated these associations among employed Chilean adults. METHODS: A total of 1946 working adults were interviewed during their outpatient visit. Pain was assessed using the Short Form McGill Pain questionnaire (SF-MPG) while depression and generalized anxiety were examined using the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), respectively. The Columbia-Suicide Severity Rating Scale was used to assess suicidal behavior and suicidal ideation. Multivariable logistic regression models were used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (95%CI) for the association of chronic pain with mood disorders, as well as suicidal behavior. RESULTS: High chronic pain (SF-MPG > 11) was reported by 46% of participants. Approximately two-fifths of the study participants (38.2%) had depression, 23.8% generalized anxiety, 13.4% suicidal ideation, and 2.4% suicidal behavior. Compared to those with low pain (SF-MPG ≤11), participants with high chronic pain (SF-MPG > 11) had increased odds of experiencing depression only (aOR = 2.87; 95% CI: 2.21-3.73), generalized anxiety only (aOR = 2.38; 95% CI: 1.42-3.99), and comorbid depression and generalized anxiety (aOR = 6.91; 95% CI: 5.20-9.19). The corresponding aOR (95%CI) for suicidal ideation and suicidal behavior were (aOR = 2.20; 95% CI: 1.58-3.07) and (aOR = 2.18 = 95% CI: 0.99-4.79), respectively. CONCLUSIONS: Chronic pain is associated with increased odds of depression, generalized anxiety, and suicidal behavior. Mental health support and appropriate management of patients experiencing chronic pain are critical.

Poor sleep Quality and Obstructive Sleep Apnea are Associated with Maternal Mood, and Anxiety Disorders in Pregnancy.

BACKGROUND: Previous studies suggest sleep quality and obstructive sleep apnea (OSA) may be associated with psychiatric symptoms, including depression, anxiety, and posttraumatic stress disorder (PTSD). However, few studies have examined the relationship between sleep quality and OSA with maternal psychiatric symptoms during pregnancy, a state of vulnerability to these disorders. OBJECTIVE: The objective of our study is to examine the association between poor sleep quality and sleep apnea with antepartum depression, anxiety, and PTSD among pregnant women. METHODS: A cross-sectional study was conducted among women seeking prenatal care in Lima, Peru. Sleep quality was measured using the Pittsburgh Sleep Quality Index, and the Berlin questionnaire was used to identify women at high risk for OSA. Depression, generalized anxiety, and PTSD symptoms were measured using the Patient Health Questionnaire-9, Generalized Anxiety Disorder Assessment, and PTSD Checklist - Civilian Version. Multivariate logistic regression procedures were used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (95% CI). RESULTS: Approximately 29.0X% of women had poor sleep quality, and 6.2% were at high risk for OSA. The prevalence of psychiatric symptoms was high in this cohort with 25.1%, 32.5%, and 30.9% of women reporting symptoms of antepartum depression, antepartum anxiety, and PTSD, respectively. Women with poor sleep quality had higher odds of antepartum depression (aOR = 3.28; 95%CI: 2.64-4.07), generalized anxiety (aOR = 1.94; 95%CI: 1.58-2.38), and PTSD symptoms (aOR = 2.81; 95% CI: 2.28-3.46) as compared with women who reported good sleep quality. Women with a high risk of OSA had higher odds of antepartum depression (aOR = 2.36; 95% CI: 1.57-3.56), generalized anxiety (aOR = 2.02, 95% CI: 1.36-3.00), and PTSD symptoms (aOR = 2.14; 95%CI: 1.43-3.21) as compared with those with a low risk of sleep apnea. CONCLUSIONS: Poor sleep quality and high risk of OSA are associated with antepartum depression, generalized anxiety, and PTSD symptoms among pregnant women. Further characterizations of the associations of these prevalent sleep, mood, and anxiety conditions among pregnant women could aid in evaluating and delivering optimal perinatal care to women with these comorbidities.

Commentary: Global Alzheimer's disease and Alzheimer's disease related dementia research funding organizations support and engage the research community throughout the COVID-19 pandemic.

The COVID-19 pandemic has disproportionately affected more vulnerable populations, including those living with dementia. Over 50 million individuals worldwide are living with Alzheimer's disease (AD) or other dementia, and it is crucial to continue the fight against the condition during the global pandemic. Since the start of mandated lockdowns in March 2020, charity and non-profit organizations that fund AD and related dementia research continue to respond to the needs of the AD research community, ensuring the momentum continues and accelerates. Members of the International Alzheimer's and Related Dementia Research Funder Consortium, a group of nearly 40 funding organizations that informally convene throughout the year to share updates and information, have taken a number of steps to ensure the continued support of the research community. Even during times of uncertainty, it is essential that the field moves forward to uncover preventions, diagnoses, and treatments for these diseases that affect many millions globally.

Learning Disorder Confers Setting-Specific Treatment Resistance for Children with ADHD, Predominantly Inattentive Presentation.

Attention deficit/hyperactivity disorder-predominantly inattentive presentation (ADHD-I) and specific learning disorder (SLD) are commonly co-occurring conditions. Despite the considerable diagnostic overlap, the effect of SLD comorbidity on outcomes of behavioral interventions for ADHD-I remains critically understudied. The current study examines the effect of reading or math SLD comorbidity in 35 children with comorbid ADHD-I+SLD and 39 children with ADHD-I only following a behavioral treatment integrated across home and school (Child Life and Attention Skills [CLAS]). Pre- and posttreatment outcome measures included teacher-rated inattention, organizational deficits, and study skills and parent-rated inattention, organizational deficits, and homework problems. A similar pattern emerged across all teacher-rated measures: Children with ADHD-I and comorbid ADHD-I+SLD did not differ significantly at baseline, but between-group differences were evident following the CLAS intervention. Specifically, children with ADHD-I and comorbid ADHD-I+SLD improved on teacher-rated measures following the CLAS intervention, but children with ADHD-I only experienced greater improvement relative to those with a comorbid SLD. No significant interactions were observed on parent-rated measures-all children improved following the CLAS intervention on parent-rated measures, regardless of SLD status. The current results reveal that children with ADHD-I+SLD comorbidity benefit significantly from multimodal behavioral interventions, although improvements in the school setting are attenuated significantly. A treatment-resistant fraction of inattention was identified only in the SLD group, implying that this fraction is related to SLD and becomes apparent only when behavioral intervention for ADHD is administered.

The Use of Wearable Technology to Objectively Measure Sleep Quality and Physical Activity Among Pregnant Women in Urban Lima, Peru: A Pilot Feasibility Study.

INTRODUCTION: Sleep quality and physical activity can affect the mental and physical health of pregnant women and their babies in utero. METHODS: We investigated the feasibility of objectively assessing sleep quality and physical activity among resource-constrained, pregnant women in urban Lima, Peru. Twenty pregnant women were asked to complete written sleep logs and wear ActiSleep, a wristwatch-like device that records sleep quality (consecutive minutes of uninterrupted sleep) and physical activity (steps), for seven consecutive days. Sociodemographic data and pregnancy characteristics were also collected. RESULTS: Of twenty women, 13 (65%) had sufficient data collected for analysis. The mean age of study participants was 26.3 years (SD = 3.9), with a mean sleep duration of 6.9 h (SD = 1.4). The median time for sleep onset was 21:15. The mean time for sleep latency was 17.3 min; and wake after sleep onset was 116 min. The mean number of awakenings was 20.4 (SD = 6.7); and sleep efficiency was 77.9%. For physical activity, participants averaged of 6,029 steps per day (SD = 3,087). DISCUSSION: Objective assessment of sleep quality and physical activity among pregnant women in a resource-constrained setting was promising, despite modest data collection completeness. Wearable technology could be used in health interventions to improve sleep quality and physical activity among this population.

Systematic review of burnout among healthcare providers in sub-Saharan Africa.

BACKGROUND: Burnout is characterized by physical and emotional exhaustion from long-term exposure to emotionally demanding work. Burnout affects interpersonal skills, job performance, career satisfaction, and psychological health. However, little is known about the burden of burnout among healthcare providers in sub-Saharan Africa. METHODS: Relevant articles were identified through a systematic review of PubMed, Web of Science (Thomson Reuters), and PsycINFO (EBSCO). Studies were selected for inclusion if they examined a quantitative measure of burnout among healthcare providers in sub-Saharan Africa. RESULTS: A total of 65 articles met our inclusion criteria for this systematic review. Previous studies have examined burnout in sub-Saharan Africa among physicians (N = 12 articles), nurses (N = 26), combined populations of healthcare providers (N = 18), midwives (N = 2), and medical or nursing students (N = 7). The majority of studies assessed burnout using the Maslach Burnout Inventory. The highest levels of burnout were reported among nurses, although all healthcare providers showed high burnout. Burnout among healthcare providers is associated with their work environments, interpersonal and professional conflicts, emotional distress, and low social support. CONCLUSIONS: Available studies on this topic are limited by several methodological challenges. More rigorously designed epidemiologic studies of burnout among healthcare providers are warranted. Health infrastructure improvements will eventually be essential, though difficult to achieve, in under-resourced settings. Programs aimed at raising awareness and coping with burnout symptoms through stress management and resilience enhancement trainings are also needed.

Association of antepartum suicidal ideation during the third trimester with infant birth weight and gestational age at delivery.

Antepartum suicidal behaviors are a leading cause of maternal injury and death. Previous research has not investigated associations between antepartum suicidal ideation and perinatal complications. Our study objective was to evaluate the relationship of antepartum suicidal ideation with low infant birthweight, small for gestational age, and preterm birth. A cohort study was conducted among 1,108 women receiving prenatal care in Peru. Suicidal ideation was measured using the Patient Health Questionnaire-9 during pregnancy. Birth outcomes were extracted from medical records. Linear regressions and multivariable logistic regressions were used to estimate were used to investigate associations between suicidal ideation and pregnancy outcomes. The prevalence of suicidal ideation was 8.7%, preterm delivery was 5.7%, low birthweight was 4.4%, and small for gestational age was 3.4%. In an adjusted model, infant birthweight was 94.2 grams lower for mothers with antepartum suicidal ideation (95% CI: -183.0, -5.5, p = 0.037) compared with those without suicidal ideation. After adjusting for confounders including depression, participants with suicidal ideation had a nearly four-fold increased odds of delivering a small for gestational age infant (OR: 3.73; 95% CI: 1.59-8.74). These findings suggest suicidal ideation during pregnancy is associated with adverse perinatal outcomes, especially low infant birthweight.

Association Between Migraine and Suicidal Behaviors: A Nationwide Study in the USA.

BACKGROUND: Recent studies show migraineurs are at an increased risk of developing suicidal behaviors, even after controlling for comorbid depression. However, previous research has not examined the impact of psychiatric mood disorders on suicidal behaviors in migraineurs within a nationally representative sample. OBJECTIVE: A cross-sectional study was used to investigate the association between migraine and suicidal behaviors and determine whether psychiatric comorbidities modify this association in a nationwide inpatient cohort. METHODS: We analyzed the Nationwide Inpatient Sample of hospitalizations compiled from USA billing data. Migraine, suicidal behaviors, and psychiatric disorders were identified based on the International Classification of Diseases, 9th Revision, Clinical Modification diagnosis codes from hospitalization discharges (2007-2012). Weighted national estimates were used to estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: 156,172,826 hospitalizations were included, of which 1.4% had a migraine diagnosis and 1.6% had a diagnosis of suicidal behavior. Migraineurs had a 2.07-fold increased odds of suicidal behaviors (95%CI: 1.96-2.19) compared with non-migraineurs. We repeated analyses after stratifying by depression, anxiety, or posttraumatic stress disorder (PTSD). Among hospitalizations with depression, migraine was associated with a 20% reduced odds of suicidal behaviors (95%CI: 0.76-0.85). Among hospitalizations without depression, migraine was associated with 2.35-fold increased odds of suicidal behaviors (95%CI: 2.20-2.51). In stratified analyses, we noted that among hospitalizations with anxiety, migraineurs had slightly increased odds of suicidal behaviors (OR: 1.07, 95%CI: 1.02-1.13). Among hospitalizations without anxiety, migraine was associated with a 2.06-fold increased odds of suicidal behaviors (95%CI: 1.94-2.20). Similarly, in analyses stratified by PTSD, migraine was not associated with an increased risk of suicidal behaviors (OR: 1.00, 95%CI: 0.94-1.07) among those with PTSD. However, the odds of suicidal behaviors were increased among hospitalizations without PTSD (OR: 1.95, 95%CI: 1.84-2.08). CONCLUSION: Chronic conditions that do not affect the current hospitalization may not have been reported. The presence of psychiatric diagnoses influences associations of suicidal behaviors with migraine in a national inpatient sample. Migraineurs with diagnosed comorbid psychiatric disorders may be receiving care that mitigates their risk for suicidal behaviors.

Association between migraine and suicidal behavior among Ethiopian adults.

BACKGROUND: Despite the significant impact of migraine on patients and societies, few studies in low- and middle-income countries (LMICs) have investigated the association between migraine and suicidal behavior. The objective of our study is to examine the extent to which migraines are associated with suicidal behavior (including suicidal ideation, plans, and attempts) in a well-characterized study of urban dwelling Ethiopian adults. METHODS: We enrolled 1060 outpatient adults attending St. Paul hospital in Addis Ababa, Ethiopia. Standardized questionnaires were used to collect data on socio-demographics, and lifestyle characteristics. Migraine classification was based on the International Classification of Headache Disorders-2 diagnostic criteria. The Composite International Diagnostic Interview (CIDI) was used to assess depression and suicidal behaviors (i.e. ideation, plans and attempts). Multivariable logistic regression models were used to estimate adjusted odds ratio (AOR) and 95% confidence intervals (95% CIs). RESULTS: The prevalence of suicidal behavior was 15.1%, with a higher suicidal behavior among those who had migraines (61.9%). After adjusting for confounders including substance use and socio-demographic factors, migraine was associated with a 2.7-fold increased odds of suicidal behavior (AOR = 2.7; 95% CI 1.88-3.89). When stratified by their history of depression in the past year, migraine without depression was significantly associated with suicidal behavior (AOR: 2.27, 95% Cl: 1.49-3.46). The odds of suicidal behavior did not reach statistical significance in migraineurs with depression (AOR: 1.64, 95% CI: 0.40-6.69). CONCLUSION: Our study indicates that migraine is associated with increased odds of suicidal behavior in this population. Given the serious public health implications this has, attention should be given to the treatment and management of migraine at a community level.

Migraine and the risk of post-traumatic stress disorder among a cohort of pregnant women.

BACKGROUND: Individually both migraine and post-traumatic stress disorder (PTSD) prevalence estimates are higher among women. However, there is limited data on the association of migraine and PTSD in women during pregnancy. METHODS: We examined the association between migraine and PTSD among women attending prenatal clinics in Peru. Migraine was characterized using the International Classification of Headache Disorders (ICHD)-III beta criteria. PTSD was assessed using the PTSD Checklist-Civilian Version (PCL-C). Multivariable logistic regression analyses were performed to estimate odds ratios (OR) and 95% confidence intervals (CI) after adjusting for confounders. RESULTS: Of the 2922 pregnant women included, 33.5% fulfilled criteria for any migraine (migraine 12.5%; probable migraine 21.0%) and 37.4% fulfilled PTSD criteria. Even when controlling for depression, women with any migraine had almost a 2-fold increased odds of PTSD (OR: 1.97; 95% CI: 1.64-2.37) as compared to women without migraine. Specifically, women with migraine alone (i.e. excluding probable migraine) had a 2.85-fold increased odds of PTSD (95% CI: 2.18-3.74), and women with probable migraine alone had a 1.61-fold increased odds of PTSD (95% CI: 1.30-1.99) as compared to those without migraine, even after controlling for depression. In those women with both migraine and comorbid depression, the odds of PTSD in all migraine categories were even further increased as compared to those women without migraine. CONCLUSION: In a cohort of pregnant women, irrespective of the presence or absence of depression, the odds of PTSD is increased in those with migraine. Our findings suggest the importance of screening for PTSD, specifically in pregnant women with migraine.

Association of Migraine Headaches With Suicidal Ideation Among Pregnant Women in Lima, Peru.

BACKGROUND: Suicide is a leading cause of maternal death globally, and suicide prevalence rates have been shown to be increased in those with migraine. No previous study has examined the association between migraine and suicidal ideation during pregnancy. OBJECTIVE: To examine the association between migraine and suicidal ideation among a cohort of pregnant women. METHODS: A cross-sectional study was conducted among 3372 pregnant women attending prenatal care clinics in Lima, Peru. Suicidal ideation and depression were assessed using the Patient Health Questionnaire-9 (PHQ-9) scale during early pregnancy. Migraine classification (including migraine and probable migraine) was based on International Classification of Headache Disorders-III beta criteria. Multivariable logistic regression analyses were performed to estimate odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: Suicidal ideation was more common among those with migraine (25.6%) as compared to those with probable migraine (22.1%, P < .001) or non-migraineurs (12.3%, P < .001). After adjusting for confounders, including depression, those with migraine or probable migraine had a 78% increased odds of suicidal ideation (OR = 1.78; 95% CI: 1.46-2.17), as compared with non-migraineurs. Women with both migraine and depression had a 4.14-fold increased odds of suicidal ideation (OR = 4.14; 95% CI: 3.17-5.42) compared to those with neither condition. CONCLUSION: Migraine is associated with increased odds of suicidal ideation in pregnant women even when controlling for depression. These findings support the consideration of screening women with comorbid migraine and depression for suicidal behavior during pregnancy.

Guidelines to improve animal study design and reproducibility for Alzheimer's disease and related dementias: For funders and researchers.

The reproducibility of laboratory experiments is fundamental to the scientific process. There have been increasing reports regarding challenges in reproducing and translating preclinical experiments in animal models. In Alzheimer's disease and related dementias, there have been similar reports and growing interest from funding organizations, researchers, and the broader scientific community to set parameters around experimental design, statistical power, and reporting requirements. A number of efforts in recent years have attempted to develop standard guidelines; however, these have not yet been widely implemented by researchers or by funding agencies. A workgroup of the International Alzheimer's disease Research Funder Consortium, a group of over 30 research funding agencies from around the world, worked to compile the best practices identified in these prior efforts for preclinical biomedical research. This article represents a consensus of this work group's review and includes recommendations for researchers and funding agencies on designing, performing, reviewing, and funding preclinical research studies.

The Cognistat (neurobehavioural cognitive status exam): Administering the full test in stroke patients for optimal results.

BACKGROUND: One of the most commonly administered tools occupational therapists use for stroke patients is the Cognistat, which was designed as a brief screening tool of cognitive functioning. Evaluations in samples of patients have identified a high false-negative rate if the Cognistat is administered using the 'screen metric' approach. Assessing the Cognistat based on its intended design can ensure consistency and accuracy among occupational therapists for this commonly administered tool. Thus, this study examined the accuracy of administering the entire Cognistat in comparison to the screen-metric approach and the factor analytic structure within stroke patients. METHODS: The full Cognistat was administered to stroke patients receiving inpatient rehabilitation. RESULTS: Seventy-five patients who experienced a recent stroke met inclusion criteria. An inconsistency between the screen and metric items was found for five of 10 subscales. Additionally, a principal component analysis (PCA) found the Cognistat to be a two factor structure with six of the subscales loading on Factor 1, while the remaining subscales loaded on Factor 2. CONCLUSIONS: Our findings confirm that occupational therapists should administer the full Cognistat to stroke patients rather than the original screen-metric approach. A two-factor structure was also supported in our results, suggesting that occupational therapists' scoring practices should reflect this finding and use the differentiated score out of 10 rather than a global sum. However, additional research is necessary to consider the clinical and theoretical significance of the Cognistats' subscale clustering.

Working and short-term memory in children with ADHD: an examination of prefrontal cortical functioning using functional Near-Infrared Spectroscopy (fNIRS).

Working memory impairments are an oft-reported deficit among children with ADHD, and complementary neuroimaging studies implicate reductions in prefrontal cortex (PFC) structure and function as a neurobiological explanation. Most imaging studies, however, rely on costly, movement-intolerant, and/or invasive methods to examine cortical differences. This is the first study to use a newer neuroimaging tool that overcomes these limitations, functional Near Infrared Spectroscopy (fNIRS), to investigate hypothesized prefrontal differences. Children (aged 8-12) with ADHD (N = 22) and typically developing (N = 18) children completed phonological working memory (PHWM) and short-term memory (PHSTM) tasks. Children with ADHD evinced poorer performance on both tasks, with greater differences observed in PHWM (Hedges' g = 0.67) relative to PHSTM (g = 0.39). fNIRS revealed reduced hemodynamic response among children with ADHD in the dorsolateral PFC while completing the PHWM task, but not within the anterior or posterior PFC. No between-group fNIRS differences were observed during the PHSTM task. Findings suggest that children with ADHD exhibit an inadequate hemodynamic response in a region of the brain that underlies PHWM abilities. The study also highlights the use of fNIRS as a cost-effective, noninvasive neuroimaging technique to localize/quantify neural activation patterns associated with executive functions.

Disrupted autophagy leads to dopaminergic axon and dendrite degeneration and promotes presynaptic accumulation of α-synuclein and LRRK2 in the brain.

Parkinson's disease (PD) is characterized pathologically by the formation of ubiquitin and α-synuclein (α-syn)-containing inclusions (Lewy bodies), dystrophic dopamine (DA) terminals, and degeneration of midbrain DA neurons. The precise molecular mechanisms underlying these pathological features remain elusive. Accumulating evidence has implicated dysfunctional autophagy, the cell self-digestion and neuroprotective pathway, as one of the pathogenic systems contributing to the development of idiopathic PD. Here we characterize autophagy-deficient mouse models and provide in vivo evidence for the potential role that impaired autophagy plays in pathogenesis associated with PD. Cell-specific deletion of essential autophagy gene Atg7 in midbrain DA neurons causes delayed neurodegeneration, accompanied by late-onset locomotor deficits. In contrast, Atg7-deficient DA neurons in the midbrain exhibit early dendritic and axonal dystrophy, reduced striatal dopamine content, and the formation of somatic and dendritic ubiquitinated inclusions in DA neurons. Furthermore, whole-brain-specific loss of Atg7 leads to presynaptic accumulation of α-syn and LRRK2 proteins, which are encoded by two autosomal dominantly inherited PD-related genes. Our results suggest that disrupted autophagy may be associated with enhanced levels of endogenous α-syn and LRRK2 proteins in vivo. Our findings implicate dysfunctional autophagy as one of the failing cellular mechanisms involved in the pathogenesis of idiopathic PD.

Development of a Web-Based Training Platform for School Clinicians in Evidence-Based Practices for ADHD.

Lack of training for school clinicians in evidence-based practices (EBPs) contributes to underutilization of such services for youth with attention-deficit/hyperactivity disorder (ADHD). Advances in web-based technology and videoconferencing have allowed for expanded access to and optimization of training. We describe the development and outcomes of a novel web-based platform for training school clinicians to gain skills in EBPs for school-age youth with ADHD. The training platform is adapted from an empirically supported, in-person training for a school-home behavioral intervention (Collaborative Life Skills program) and includes skill modules for working with teachers, parents, and students. Training methods include web-accessed manuals/handouts, skill example video clips, automated progress monitoring tools, and consultation/in-session coaching via videoconferencing. We gathered stakeholder qualitative and quantitative feedback during discovery and design phases of the iterative development. We then evaluated the usability, acceptability, fidelity and clinician and student outcomes of the remote training program. Focus group themes and qualitative feedback identified clinician preferences for remote training features (e.g., interactive, brief, role-plays/coaching methods), video tools (recorded samples of skills and therapy sessions), and progress monitoring tools (e.g., clear, easy to use). Clinician usability ratings of the platform were high with most components rated as moderately to very useful/easy to use. Clinician ratings of usability, fidelity implementing the treatment, and their EBP knowledge and confidence following training were favorable. Student's outcomes were similar to those achieved in prior studies of clinician in-person training. Results support the promise of remote, web-based clinician training for the dissemination of evidence-based practices.

Development of prefrontal corticostriatal connectivity in mice.

Rational decision making is grounded in learning to associate actions with outcomes, a process that depends on projections from prefrontal cortex to dorsomedial striatum. Symptoms associated with a variety of human pathological conditions ranging from schizophrenia and autism to Huntington's and Parkinson's disease point toward functional deficits in this projection, but its development is not well understood, making it difficult to investigate how perturbations in development of this circuitry could contribute to pathophysiology. We applied a novel strategy based on Hotspot Analysis to assess the developmental progression of anatomical positioning of prefrontal cortex to striatal projections. Corticostriatal axonal territories established at P7 expand in concert with striatal growth but remain largely unchanged in positioning through adulthood, indicating they are generated by directed, targeted growth and not modified extensively by postnatal experience. Consistent with these findings, corticostriatal synaptogenesis increased steadily from P7 to P56, with no evidence for widescale pruning. As corticostriatal synapse density increased over late postnatal ages, the strength of evoked PFC input onto dorsomedial striatal projection neurons also increased, but spontaneous glutamatergic synaptic activity was stable. Based on its pattern of expression, we asked whether the adhesion protein, Cdh8, influenced this progression. In mice lacking Cdh8 in PFC corticostriatal projection neurons, axon terminal fields in dorsal striatum shifted ventrally. Corticostriatal synaptogenesis was unimpeded, but spontaneous EPSC frequency declined and mice failed to learn to associate an action with an outcome. Collectively these findings show that corticostriatal axons grow to their target zone and are restrained from an early age, do not undergo postnatal synapse pruning as the most dominant models predict, and that a relatively modest shift in terminal arbor positioning and synapse function has an outsized, negative impact on corticostriatal-dependent behavior.

Development and cadherin-mediated control of prefrontal corticostriatal projections in mice.

Action-outcome associations depend on prefrontal cortex (PFC) projections to the dorsal striatum. To assess how these projections form, we measured PFC axon patterning, synapse formation, and functional maturation in the postnatally developing mouse striatum. Using Hotspot analysis, we show that PFC axons form an adult-like pattern of clustered terminations in the first postnatal week that remains largely stable thereafter. PFC-striatal synaptic strength is adult-like by P21, while excitatory synapse density increases until adulthood. We then tested how the targeted deletion of a candidate adhesion/guidance protein, Cadherin-8 (Cdh8), from corticostriatal neurons regulates pathway development. Mutant mice showed diminished PFC axon targeting and reduced spontaneous glutamatergic synaptic activity in the dorsal striatum. They also exhibited impaired behavioral performance in action-outcome learning. The data show that PFC-striatal axons form striatal territories through an early, directed growth model and they highlight essential contributions of Cdh8 to the anatomical and functional features critical for the formation of action-outcome associations.

Association of morningness-eveningness with psychiatric symptoms among pregnant women.

In the present study, we examined associations between circadian preference and psychiatric symptoms among 1,796 pregnant women from Lima, Peru. One quarter were classified as evening types. Compared to morning types, evening type pregnant women had increased odds of generalized anxiety (OR = 1.44; 95%CI: 1.12-1.86) and posttraumatic stress disorder (OR = 1.38; 95%CI: 1.07-1.78). Although there was a positive trend, evening chronotype was not significantly associated with elevated odds of depression (OR = 1.23; 95%CI: 0.94-1.61). Future studies are warranted to help understand the underlying behavioral, biological, and genetic pathways of these associations. Assessing circadian preference may help clinicians identify pregnant women at risk for psychiatric symptoms.

Verbal Memory Interference in Attention-Deficit Hyperactivity Disorder: A Meta-Analytic Review.

OBJECTIVE: Interference control is used to overcome conflict among competing memory representations and may contribute to memory difficulties in ADHD. This meta-analytic review examined memory interference to evaluate susceptibility to proactive, retroactive, and memory control interference among those with ADHD. METHOD: Twenty studies (1987-2019) examining verbal memory interference in ADHD met inclusion criteria (age: 8-36 years). Proactive and retroactive interference indices were extracted from list-learning tasks, and memory control indices were extracted from experimental paradigms (e.g., directed-forgetting). RESULTS: Children with ADHD were less affected by proactive interference (g=-0.53, 95% CI [-0.75, -0.31]), whereas no significant differences were found in adults (g=0.13, 95% CI [-0.02, 0.28]). Adults and children with ADHD exhibited more retroactive interference (g=0.17, 95% CI [0.05, 0.29]) and performed worse on memory control tasks (g=0.35, 95% CI [0.08, 0.62]) relative to controls. CONCLUSION: Differences in verbal memory interference control in ADHD were observed but effects were different depending upon interference type and participant age.