Longitudinal transactional relationships between caregiver and child mental health during the COVID-19 global pandemic

Background Emerging work examining the psychological impact of COVID-19 on children and families suggests that the relationship between pandemic-related stress, child psychosocial functioning, and caregiver mental health are interrelated. However, much of this research is unidirectional and thus little is known about the bidirectional cascading effects children and caregivers may experience. The current study examined the transactional relationships between caregiver and child mental health over time during the COVID-19 pandemic. Methods Linguistically, racially, and ethnically diverse caregivers (N = 286) of young children completed measures of caregiver mental health, caregiver pandemic-related stress, and child mental health (i.e., externalizing, internalizing, prosocial behavior) across three time points in the spring of 2020. Results Using autoregressive cross-lagged analyses, impaired caregiver mental health at Time 1 (April 2020) predicted increased caregiver pandemic-related stress at Time 2 (May 2020). Caregiver pandemic-related stress at Time 1 predicted increased child internalizing symptoms at Time 2 which, in turn, predicted increased caregiver pandemic-related stress at Time 3 (July 2020). Lastly, impaired caregiver mental health at Time 2 (May 2020) predicted increased child externalizing symptoms at Time 3 (July 2020). Conclusions Assessing transactional relationships between child and caregiver mental health during the COVID-19 pandemic is important to inform models of risk and resilience. Interventions at the level of the caregiver, the child, and/or the family should be considered as a way to interrupt potential negative developmental cascades

Neonatal Cardiac Arrest Following Lacosamide Treatment: A Case Report

Lacosamide is an antiepileptic drug with FDA approval for treatment of partial-onset seizures in patients above the age of 1 month. Lacosamide works by selective enhancement of proteins which induce preferential slow promotion of sodium channels to the hyperpolarized inactive state. Lacosamide is generally well tolerated; however, clinical and nonclinical studies have linked its use with cardiac side effects including PR Prolongation and AV block. We present the case of a 3-week-old female neonatal patient born at 25 weeks gestation who developed 2nd degree AV heart block and cardiac arrest after initiating lacosamide therapy. The patient was being treated for neonatal seizure complicated by intraventricular hemorrhage (grade II) and electrolyte disturbances with phenobarbital, levetiracetam, and phenytoin. Prior to addition of lacosamide therapy, the patient had an unremarkable EKG and no known cardiac risk factors for lacosamide. After medication discontinuation, the patient experienced no reoccurring episodes or other cardiac events. Use of lacosamide for neonatal populations is currently under evaluation. To our knowledge, this is the first report of adverse cardiac event (AV block) in the setting of neonatal lacosamide use. Risk of future adverse cardiac events should be evaluated when determining the safety and efficacy of lacosamide in the neonatal population

Longitudinal transactional relationships between caregiver and child mental health during the COVID-19 global pandemic

Abstract Background Emerging work examining the psychological impact of COVID-19 on children and families suggests that the relationship between pandemic-related stress, child psychosocial functioning, and caregiver mental health are interrelated. However, much of this research is unidirectional and thus little is known about the bidirectional cascading effects children and caregivers may experience. The current study examined the transactional relationships between caregiver and child mental health over time during the COVID-19 pandemic. Methods Linguistically, racially, and ethnically diverse caregivers (N = 286) of young children completed measures of caregiver mental health, caregiver pandemic-related stress, and child mental health (i.e., externalizing, internalizing, prosocial behavior) across three time points in the spring of 2020. Results Using autoregressive cross-lagged analyses, impaired caregiver mental health at Time 1 (April 2020) predicted increased caregiver pandemic-related stress at Time 2 (May 2020). Caregiver pandemic-related stress at Time 1 predicted increased child internalizing symptoms at Time 2 which, in turn, predicted increased caregiver pandemic-related stress at Time 3 (July 2020). Lastly, impaired caregiver mental health at Time 2 (May 2020) predicted increased child externalizing symptoms at Time 3 (July 2020). Conclusions Assessing transactional relationships between child and caregiver mental health during the COVID-19 pandemic is important to inform models of risk and resilience. Interventions at the level of the caregiver, the child, and/or the family should be considered as a way to interrupt potential negative developmental cascades

Effects of Anticholinergic Burden on Verbal Memory Performance in First-Episode Psychosis.

OBJECTIVES: Antipsychotics are widely used to treat first-episode psychosis but may have an anticholinergic burden, that is, a cumulative effect of medications that block the cholinergic system. Studies suggest that a high anticholinergic burden negatively affects memory in psychosis, where cognitive deficits, particularly those in verbal memory, are a core feature of the disease. The present study sought to replicate this in a large cohort of well-characterized first-episode psychosis patients. We expected that patients in the highest anticholinergic burden group would exhibit the poorest verbal memory compared to those with low anticholinergic burden and healthy controls at baseline (3 months following admission). We further hypothesized that over time, at month 12, patients verbal memory performance would improve but would remain inferior to controls. METHODS: Patients (n  =  311; low anticholinergic burden [n  =  241] and high anticholinergic burden [n  =  70], defined by a Drug Burden Index cut-off of 1) and healthy controls (n  =  128) completed a clinical and neurocognitive battery including parts of the Wechsler Memory Scale at months 3 and 12. RESULTS: Cross-sectionally, using an analysis of variance, patients in the highest anticholinergic burden group had the poorest performance in verbal memory when compared to the other groups at month 3, F(2,430)  =  52.33, P < 0.001. Longitudinally, using a Generalized Estimating Equation model, the verbal memory performance of all groups improved over time. However, patients performance overall remained poorer than the controls. CONCLUSION: These findings highlight the importance of considering the anticholinergic burden when prescribing medications in the early stages of the disease

Effects of Anticholinergic Burden on Verbal Memory Performance in First-Episode Psychosis

Antipsychotics are widely used to treat first-episode psychosis but may have an anticholinergic burden, i.e., a cumulative effect of medications that block the cholinergic system. Studies suggest that a high anticholinergic burden negatively affects memory in psychosis, where cognitive deficits, particularly those in verbal memory, are a core feature of the disease. The present study sought to replicate this in a large cohort of well-characterized first-episode psychosis patients. We expected that patients in the highest anticholinergic burden group would exhibit the poorest verbal memory compared to those with low anticholinergic burden and to healthy controls at baseline (3 months following admission). We further hypothesized that over time, at month 12, patients' verbal memory performance would improve but would remain inferior to controls. Patients (n=311; low anticholinergic burden [n=241] and high anticholinergic burden [n=70], defined by a Drug Burden Index cut-off of 1) and controls (n=128) completed a clinical and neurocognitive battery including parts of the Wechsler Memory Scale at month 3 and 12. Cross-sectionally, using an ANOVA, patients in the highest anticholinergic burden group had the poorest performance in verbal memory when compared to the other groups at month 3 (F(2,430)=52.33, P<0.001). Longitudinally, using a Generalized Estimating Equation model, the verbal memory performance of all groups improved over time. However, patients' performance overall remained poorer than the controls. These findings highlight the importance of considering the anticholinergic burden when prescribing medications in the early stages of the disease

Postprint: Sex-Specific Associations in Verbal Memory Brain Circuitry in Early Psychosis

Abstract: Hippocampal circuitry and related cortical connections are altered in first episode psychosis (FEP) and are associated with verbal memory deficits, as well as positive and negative symptoms. There are robust sex differences in the clinical presentation of psychosis, including poorer verbal memory in male patients. Consideration of sex differences in hippocampal-cortical circuitry and their associations with different behavioral dimensions may be useful for understanding the underlying pathophysiology of verbal memory deficits and related symptomatology in psychosis. Here, we use a data-driven approach to simultaneously capture the complex links between sex, verbal memory, symptoms, and cortical-hippocampal brain metrics in FEP. Structural magnetic resonance imaging and behavioral data were acquired from 100 FEP patients (75 males, 25 females) and 87 controls (55 males, 32 females). Multivariate brain-behavior associations were examined in FEP using partial least squares to map sociodemographic, verbal memory, and clinical data onto brain morphometry. The analysis identified two sex-dependent patterns of verbal memory, symptoms, and brain structure. In male patients, verbal memory deficits and core psychotic symptoms were associated with both increased and decreased frontal and temporal cortical thickness and reductions in CA2/3 hippocampal subfield and fornix volumes. In female patients, fewer negative/depressive symptoms were associated with a more attenuated cortical thickness pattern and more diffuse reductions in hippocampal white matter regions. Taken together, the results contribute towards better understanding the underlying pathophysiology of psychosis by highlighting the unique contribution of specific hippocampal subfields and surrounding white matter and their connections with broader cortical networks in a sex-dependent manner

Risk and resilience of well-being in caregivers of young children in response to the COVID-19 pandemic

The COVID-19 pandemic is impacting communities worldwide, with direct effects of illness and mortality, and indirect effects on economies, workplaces, schools/daycares, and social life. However, we understand very little about the effects of this pandemic on families of young children. We used a risk and resilience model to evaluate the effects of the pandemic on mental health in diverse caregivers (N = 286) with children ages birth to 5. We evaluated the hypotheses that (a) pandemic stress and caregiver-reported child psychosocial concerns correlate with caregivers' mental health symptoms and (b) caregivers' pandemic-related self-efficacy and coping mediate these relationships. Caregivers completed surveys in April-May 2020 assessing pandemic stress (e.g., health, finances, and housing), child psychosocial problems, coping strategies, and self-efficacy to manage family needs. Our primary outcome was caregivers' self-reported changes in mental health symptoms since the outbreak. Path analysis revealed that higher pandemic stress was associated with caregivers' reduced confidence in meeting their family's needs related to COVID-19, which correlated with worse caregiver mental health symptoms. Greater child psychosocial problems also predicted worse caregiver mental health symptoms. Findings suggest that pandemic stress, child psychosocial problems, and caregiver self-efficacy are interrelated in their influence on caregivers' mental health. While further research is needed to examine strategies to foster resilience and buffer the pandemic's effects on caregiver mental health, this is a first step in evaluating the psychosocial effects of this pandemic in families of young children. Clinical implications are discussed for a tiered response to mitigate the pandemic's impacts on family functioning

Altered hippocampal centrality and dynamic anatomical covariance of intracortical microstructure in first episode psychosis

Hippocampal circuitry has been posited to be fundamental to positive symptoms in psychosis, but its contributions to other factors important for outcome remains unclear. We hypothesized that longitudinal changes in the hippocampal circuit and concomitant changes of intracortical microstructure are altered in first episode psychosis (FEP) patients and that such changes are associated with negative symptoms and verbal memory. Longitudinal brain scans (2–4 visits over 3–15 months) were acquired for 27 FEP and 29 age- and sex-matched healthy controls. Quantitative T1 maps, sensitive to myelin content, were used to sample the microstructure of the hippocampal subfields and output circuitry (fimbria, alveus, fornix, mammillary bodies), and intracortical regions. Dynamic anatomical covariance in pair-wise regional trajectories were assessed for each subject, and graph theory was used to calculate a participation coefficient metric that quantifies the similarity/divergence between hippocampal and intracortical microstructure. The mean participation coefficient of the hippocampus was significantly reduced in FEP patients compared with controls, reflecting differences in output hippocampal regions. Importantly, lower participation coefficient of the hippocampal circuit was associated with worse negative symptoms, a relationship that was mediated by changes in verbal memory. This study provides evidence for reduced hippocampal centrality in FEP and concomitant changes in intracortical anatomy. Myelin-rich output regions of the hippocampus may be an important biological trigger in early psychosis, with cascading effects on broader cortical networks and resultant clinical profiles

Latent clinical-anatomical dimensions of schizophrenia

Widespread structural brain abnormalities have been consistently reported in schizophrenia, but their relation to the heterogeneous clinical manifestations remains unknown. In particular, it is unclear whether anatomical abnormalities in discrete regions give rise to discrete symptoms or whether distributed abnormalities give rise to the broad clinical profile associated with schizophrenia. Here, we apply a multivariate data-driven approach to investigate covariance patterns between multiple-symptom domains and distributed brain abnormalities in schizophrenia. Structural magnetic resonance imaging and clinical data were derived from one discovery sample (133 patients and 113 controls) and one independent validation sample (108 patients and 69 controls). Disease-related voxel-wise brain abnormalities were estimated using deformation-based morphometry. Partial least-squares analysis was used to comprehensively map clinical, neuropsychological, and demographic data onto distributed deformation in a single multivariate model. The analysis identified 3 latent clinical-anatomical dimensions that collectively accounted for 55% of the covariance between clinical data and brain deformation. The first latent clinical-anatomical dimension was replicated in an independent sample, encompassing cognitive impairments, negative symptom severity, and brain abnormalities within the default mode and visual networks. This cognitive-negative dimension was associated with low socioeconomic status and was represented across multiple races. Altogether, we identified a continuous cognitive-negative dimension of schizophrenia, centered on 2 intrinsic networks. By simultaneously taking into account both clinical manifestations and neuroanatomical abnormalities, the present results open new avenues for multi-omic stratification and biotyping of individuals with schizophrenia