Primary and secondary caregiver depressive symptoms and family functioning following a pediatric cancer diagnosis: an exploration of the buffering hypothesis.

OBJECTIVE: After diagnosis, caregivers of children with cancer, particularly mothers or primary caregivers (PCs), often show elevated depressive symptoms which may negatively impact family functioning. We tested PC and secondary caregiver (SC) depressive symptoms as predictors of family, co-parenting, and marital functioning and whether having a non-depressed SC buffers against potential negative effects of PC depressive symptoms. METHODS: Families (N = 137) were recruited from two major children's hospitals following a diagnosis of pediatric cancer. Caregivers completed self-report measures of depressive symptoms (Center for Epidemiological Studies-Depression Scale; Depression, Anxiety, and Stress Scale) and marital functioning (Dyadic Adjustment Scale) at 1-month post-diagnosis. A subset of families (n = 75) completed videotaped interaction tasks at approximately 3-months post-diagnosis that were coded for family and co-parenting interactions. RESULTS: Higher PC depressive symptoms at 1-month post-diagnosis was associated with higher adaptability and lower conflict in family functioning. PC depressive symptoms were also associated lower dyadic consensus and lower dyadic satisfaction. SC depressive symptoms were not significantly associated with any family/co-parenting/marital functioning variables. Significant interaction analyses suggested that SC depressive symptoms moderated the effect of PC depressive symptoms on family cohesion, withdrawn parenting, and affective expression in the marriage, such that the relationship between PC depressive symptoms and poorer functioning was attenuated when SC depressive symptoms were at low or average levels. CONCLUSIONS: Having a nondepressed SC buffered against negative effects of PC depressive symptoms on certain domains of family, coparenting, and marital functioning. SCs may play a protective role for families of children with cancer.

Stress and marital adjustment in families of children with cancer.

OBJECTIVE: Pediatric cancer is highly stressful for parents. The current prospective study examines the impact of several stressors (financial strain, life threat, treatment intensity, treatment-related events, and negative life events) on the trajectory of marital adjustment across the first year following diagnosis. We examined whether average level of stressors across the year was related to (1) levels of marital adjustment at the end of the first year of treatment and () the rate of change in marital adjustment. METHOD: One hundred and thirty families of children newly diagnosed with cancer (M age = 6.33 years, SD = 3.61) participated. Primary caregivers provided 12 monthly reports on marital adjustment and stressors. RESULTS: Multilevel models indicated that although marital adjustment was stable across the first year on average, random effect estimates suggested that this was the result of differing trajectories between families (eg, some increasing and others decreasing). Five individual stress constructs and a cumulative stress composite were then used to predict this variability. Higher average economic strain was related to consistently poorer marital adjustment across time. Higher average frequency of treatment-related events and negative life events were associated with decreasing adjustment over time and lower adjustment at the end of the first year of treatment. Perception of life threat and treatment intensity were not associated with final levels or trajectory of adjustment. Finally, higher cumulative stress was associated with consistently poorer marital adjustment across time. CONCLUSION: Implications for identification of at-risk families are discussed, and importance of delivering tailored interventions for this population.

Patterns of Spillover Between Marital Adjustment and Parent-Child Conflict During Pediatric Cancer Treatment.

Objective: When a child is diagnosed with cancer, problems may arise in family relationships and negatively affect child adjustment. The current study examined patterns of spillover between marital and parent-child relationships to identify targets for intervention aimed at ameliorating family conflict. Method: Families (N = 117) were recruited from two US children's hospitals within 2-week postdiagnosis to participate in a short-term prospective longitudinal study. Children with cancer were 2-10 years old (M = 5.42 years, SD = 2.59). Primary caregivers provided reports of marital and parent-child conflict at 1-, 6-, and 12-month postdiagnosis. Results: Results indicated that a unidirectional model of spillover from the marital to the parent-child relationship best explained the data. In terms of specific temporal patterns, lower marital adjustment soon after diagnosis was associated with an increase in parent-child conflict 6 months later, though this pattern was not repeated in the latter 6 months of treatment. Conclusion: Targeting problems in marital relationships soon after diagnosis may prevent conflict from developing in the parent-child relationship.

Featured Article: Caregiver Perceptions of Stress and Sibling Conflict During Pediatric Cancer Treatment.

Objective: The current study examined the effect of stress on sibling conflict during the first year of pediatric cancer treatment. Method: Families (N = 103) included a child with cancer (aged 2-17 years, Mage = 6.46, SD = 3.52) and at least one sibling aged <5 years of the child with cancer (Mage = 8.34, SD = 5.61). Primary caregivers completed monthly questionnaires throughout the first year of treatment assessing five sources of stress (i.e., general life, cancer-related, financial, perceived treatment intensity, and life threat) and level of sibling conflict. Using multilevel modeling, we explored the effects of these stressors on conflict both at the within- and between-family levels to examine if changes in stress resulted in concurrent changes in conflict within an individual family, and whether greater average stress affected the trajectory of conflict between families, respectively. Results: At the between-family level, higher average levels of cancer-related stress, general life stress, and financial stress were associated with higher sibling conflict at the end of the first year of treatment. Perceived treatment intensity and life threat were not associated with conflict. No stressors were associated with conflict at the within-family level. Conclusions: During pediatric cancer treatment, some stressors may spill over into family relationships and contribute to increases in sibling conflict.

Maternal directiveness in childhood survivors of acute lymphoblastic leukemia.

Parental intrusiveness is associated with internalizing problems in healthy children. Given the unique demands that childhood cancer places on parents, it is important to determine whether intrusiveness operates differently in survivors of childhood cancer. The current study tested whether cancer survivorship moderates the relation between maternal directiveness-one aspect of intrusiveness-and children's internalizing problems. Survivors (7-12 years old) of acute lymphoblastic leukemia (ALL) (n = 25) and their mothers, and healthy controls (n = 22) and their mothers engaged in parent-child interactions. Mothers completed a measure of children's psychosocial adjustment, and observations of 10-min parent-child interactions were obtained. Cancer survivorship moderated the relation between directiveness and children's withdrawn/depressed symptoms. Maternal directiveness was associated with increased withdrawn/depressed symptoms for children in the control group. This association was not significant for survivors of ALL. Findings suggest that childhood cancer may alter the context in which children experience maternal directiveness.

HHV-6 reactivation and its effect on delirium and cognitive functioning in hematopoietic cell transplantation recipients.

Human herpesvirus 6 (HHV-6) is detected in the plasma of approximately 40% of patients undergoing hematopoietic cell transplantation (HCT) and sporadically causes encephalitis in this population. The effect of HHV-6 reactivation on central nervous system function has not been fully characterized. This prospective study aimed to evaluate associations between HHV-6 reactivation and central nervous system dysfunction after allogeneic HCT. Patients were enrolled before HCT. Plasma samples were tested for HHV-6 at baseline and twice weekly after transplantation until day 84. Delirium was assessed at baseline, 3 times weekly until day 56, and weekly on days 56 to 84 using a validated instrument. Neurocognitive testing was performed at baseline and at approximately day 84. HHV-6 was detected in 111 (35%) of the 315 included patients. Patients with HHV-6 were more likely to develop delirium (adjusted odds ratio = 2.5; 95% confidence interval, 1.2-5.3) and demonstrate neurocognitive decline (adjusted odds ratio = 2.6; 95% confidence interval, 1.1-6.2) in the first 84 days after HCT. Cord blood and unrelated transplantation increased risk of HHV-6 reactivation. These data provide the basis to conduct a randomized clinical trial to determine whether prevention of HHV-6 reactivation will reduce neurocognitive morbidity in HCT recipients.

Caregiver emotion regulation predicts trajectories of psychopathology during pediatric cancer treatment.

Elevated child and caregiver psychopathology are observed in families of children with cancer, with a subset developing clinically significant symptoms. This study examines whether caregivers' resting respiratory sinus arrhythmia (RSA) and observed emotion regulation (ER) are protective against caregiver and child psychopathology during the first year of pediatric cancer treatment. Primary caregivers of children recently diagnosed with cancer (N = 159; child Mage = 5.6 years; children 48% male, 52% female) completed 12 monthly questionnaires. At Month 3, primary caregivers were interviewed about their experiences of emotions, and their resting RSA was measured. Data were analyzed using multilevel models. Observed ER was associated with lower caregiver anxiety, depression, and posttraumatic stress symptoms (PTSS) 1 year postdiagnosis but was not associated with children's symptoms. Resting RSA had a significant positive association with child depression/anxiety at the start of treatment and Month 12 child PTSS. Findings suggest that caregivers would benefit from interventions to manage their negative emotions at the start of cancer treatment. Additionally, caregivers who are more physiologically regulated may be more attuned to their children's negative emotions. Our findings highlight the importance of taking a multimethod approach to understanding how ER impacts functioning. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Caregiver perceived financial strain during pediatric cancer treatment: Longitudinal predictors and outcomes.

OBJECTIVE: Previous work has examined family income and material hardship in pediatric cancer. However, few studies have focused on perceived financial strain (PFS), or the extent to which caregivers perceive financial stress and worry related to their child's cancer. The current study addresses this gap by a) describing the trajectory of perceived financial strain over the first year of pediatric cancer treatment; b) examining sociodemographic predictors of that trajectory; and c) examining associations between PFS and caregiver and child psychological adjustment. METHOD: Primary caregivers of children (Mage = 6.31) recently diagnosed with cancer provided 12 monthly reports of their own perceived financial strain and depression, anxiety, and posttraumatic stress symptoms, as well as their child's internalizing and externalizing symptoms. Data were analyzed using multilevel models. RESULTS: Caregiver PFS decreased over the first year of treatment. Nonmarried caregivers and those with lower income reported higher levels of PFS over time. Caregivers with higher PFS relative to other caregivers and relative to their own average PFS in a given month experienced psychological maladjustment. PFS was not associated with child adjustment. CONCLUSIONS: On average caregivers perceive less financial strain over the first year of treatment; however, nonmarried caregivers and those with lower income are at risk for higher PFS over time, and PFS may contribute to psychological maladjustment in caregivers. Caregivers may benefit from psychosocial support focused on managing financial strain. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

A comparison of neurocognitive functioning in children previously randomized to dexamethasone or prednisone in the treatment of childhood acute lymphoblastic leukemia.

In previous clinical trials of childhood acute lymphoblastic leukemia (ALL), dexamethasone resulted in higher event-free survival rates than prednisone, presumably due to greater central nervous system penetration. Dexamethasone's association with long-term neurocognitive toxicity is unknown. In this multisite study, we measured neurocognitive functioning in 92 children with standard-risk ALL, 1 to 9.99 years at diagnosis, at a mean of 9.8 years after randomization to prednisone (n = 41) or dexamethasone (n = 51) on Children's Cancer Group (CCG) 1922. No significant overall differences in mean neurocognitive and academic performance scores were found between the prednisone and dexamethasone groups after adjusting for age, sex, and time since diagnosis. The exception was that patients receiving dexamethasone scored one-third of a standard deviation worse on word reading (98.8 +/- 1.7 vs 104.9 +/- 1.8; P = .02). There were no group differences in the distribution of test scores or the parents' report of neurologic complications, psychotropic drug use, and special education. Further analyses suggested for the dexamethasone group, older age of diagnosis was associated with worse neurocognitive functioning; for the prednisone group, younger age at diagnosis was associated with worse functioning. In conclusion, our study did not demonstrate any meaningful differences in long-term cognitive functioning of childhood ALL patients based on corticosteroid randomization. This study is registered with http://www.clinicaltrials.gov under NCT00085176.

Pediatric cancer and the quality of children's dyadic peer interactions.

OBJECTIVE: To use observational methods to assess the quality of peer relationships in 51 7- to 12-year-old acute lymphoblastic leukemia survivors as compared to healthy children. METHODS: Children were audiotaped as they engaged in free play with their best friend and interactions were coded to assess their ability to maintain engagement with one another during play as well as the affective dimension of their play. RESULTS: Results indicated that dyads with survivors of childhood cancer were less likely to be highly engaged with their best friend and more likely to experience disengagement than dyads with healthy participants. There were no group differences in positive or negative affect. CONCLUSIONS: Overall, these data suggest that survivors of childhood cancer's relationships with their best friend may be compromised in some specific areas when compared to the relations of healthy children. Implications for intervention are discussed.

Stress and psychological adjustment in caregivers of children with cancer.

OBJECTIVE: To examine effects of stress on caregiver psychological adjustment during the first year of pediatric cancer. METHOD: Caregivers (N = 159) of children with cancer completed monthly questionnaires assessing domains of caregiver psychological adjustment (depression, anxiety, and posttraumatic stress symptoms) and stress (general life stress, treatment-related stress, caregiver perceptions of treatment intensity and life threat). Effects of stress were assessed at two levels to examine whether within-person changes in stress predicted concurrent changes in caregiver adjustment and whether average stress was associated with between-person differences in caregiver adjustment trajectories. RESULTS: Overall, higher levels of stress factors were associated with poorer caregiver adjustment at both the between- and within-person levels, with high average levels of treatment-related stress and general life stress emerging as leading predictors of worse adjustment. CONCLUSIONS: Both types of stressors, those directly related as well as unrelated to a child's cancer, contribute uniquely to caregiver distress. Caregiver distress is impacted by both overall levels of stress over time as well as month-to-month changes in stress. Implications for informing care for at-risk caregivers are discussed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Diagnostic Classification of ADHD Versus Control: Support Vector Machine Classification Using Brief Neuropsychological Assessment.

Objective: Common methods for clinical diagnosis include clinical interview, behavioral questionnaires, and neuropsychological assessment. These methods rely on clinical interpretation and have variable reliability, sensitivity, and specificity. The goal of this study was to evaluate the utility of machine learning in the prediction and classification of children with ADHD-Combined presentation (ADHD-C) using brief neuropsychological measures (d2 Test of Attention, Children with ADHD-C and typically developing control children completed semi-structured clinical interviews and measures of attention/concentration and parents completed symptom severity questionnaires. Method: We used a forward feature selection method to identify the most informative neuropsychological features for support vector machine (SVM) classification and a decision tree model to derive a rule-based model. Results: The SVM model yielded excellent classification accuracy (100%) of individual children with and without ADHD (1.0). Decision tree algorithms identified individuals with and without ADHD-C with 100% sensitivity and specificity. Conclusion:This study observed highly accurate statistical diagnostic classification, at the individual level, in a sample of children with ADHD-C. The findings suggest data-driven behavioral algorithms based on brief neuropsychological data may present an efficient and accurate diagnostic tool for clinicians.

Differential trajectories of neurocognitive functioning in females versus males following treatment for pediatric brain tumors.

BACKGROUND: Female and male trajectories of cerebellar and lobar brain structures are sexually dimorphic, making sex a potential candidate moderator of neurocognitive late effects from radiation treatment. We sought to evaluate longitudinal neurocognitive functioning in male versus female children treated for posterior fossa brain tumors. METHODS: Fifty-one female and 63 male survivors of posterior fossa tumors completed neuropsychological testing at 2 timepoints. We included patients treated with surgical resection, chemotherapy, and radiation therapy. Multilevel mixed modeling was used to predict IQ score as a function of patient sex following treatment (~2 or ~4 years post treatment). Effect sizes were used as a measure of clinical significance. RESULTS: Multilevel models resulted in a significant sex by time interaction (F = 6.69, P = 0.011). Females' cognitive scores were considerably higher compared with males at 4 years posttreatment. Females demonstrated an average improvement of 7.61 standard score IQ points compared with a decline of 2.97 points for males at 4 years follow-up. Effect sizes for female IQ compared with male IQ at 4 years posttreatment were between 0.8 and 0.9. CONCLUSION: Trajectories of neurocognitive functioning following posterior fossa tumor treatment differed between female and male children. Sexual dimorphism in radiation late effects may alter treatment decisions in children. Research into sex-specific neuroprotective mechanisms underlying neurocognitive development following pediatric brain tumor treatments is warranted.

Trajectories of child and caregiver psychological adjustment in families of children with cancer.

OBJECTIVE: To describe the trajectory of patient and caregiver mental health from diagnosis through the first year of treatment for pediatric cancer and assess whether rates of clinically relevant symptoms were elevated compared with norms. We examined mean levels of internalizing and externalizing symptoms and posttraumatic stress symptoms (PTSS) in children with cancer, and depression, anxiety, and PTSS in caregivers during the first year of treatment; the proportion of patients and caregivers that scored in the clinical range at each time point; and the typical trajectory of symptoms in patients and caregivers and whether trajectories differed between individuals. METHOD: Families (N = 159) of children newly diagnosed with cancer (Mage = 5.6 years; range = 2-18 years) participated in a short-term prospective study. Primary caregivers provided monthly reports of their own and their children's psychological adjustment. RESULTS: On average, children were well-adjusted. However, compared with norms, there was a higher than expected proportion of children with clinically relevant internalizing symptoms around the time of diagnosis. On average children's symptoms declined over time, though variability was observed. Caregivers were less well-adjusted on average, with a high proportion reporting clinically relevant symptoms over time for depression and anxiety. Caregiver symptoms also declined over time, though considerable variability was observed. CONCLUSION: Although most children remain well-adjusted during the first year of treatment, many caregivers experience clinically relevant symptoms of psychological distress. Implications for development of interventions targeting at-risk patients and caregivers are discussed. Identifying processes that predict between-family variability in trajectories of psychopathology is an important next step. (PsycINFO Database Record

Trajectories of marital, parent-child, and sibling conflict during pediatric cancer treatment.

OBJECTIVE: The stress of having a child with cancer can impact the quality of relationships within the family. The current study describes the longitudinal trajectory of marital, parent-child, and sibling conflict beginning around the time of diagnosis through the first year of treatment. We examined the average level of marital, parent-child, and sibling conflict at each monthly time point in the first year of treatment; the proportion of families that fall into the distressed range of marital, parent-child, and sibling conflict at each time point; the typical trajectory of conflict during the first year of treatment and whether there are differences in trajectories across families. METHOD: A total of 160 families of children newly diagnosed with cancer (Mage = 5.6 years; range = 2-18 years) participated in a short-term prospective longitudinal study. Primary caregivers provided monthly reports of marital, parent-child, and sibling conflict. RESULTS: Using multilevel modeling (MLM), most families showed stability in quality of family relationships, although considerable between-family variability was observed. For married couples, 25-36% of couples were in the distressed range at one time point over the first year of treatment. For married couples, more distress occurred at earlier months, particularly month 3. For parent-child and sibling dyads, the most difficult time periods were during later months. CONCLUSION: Implications for development of interventions that target at-risk family relationships are discussed. Identifying processes that predict between-family variability in trajectories of family relationships is an important next step, particularly for the marital relationship. (PsycINFO Database Record

GABA alterations in pediatric sport concussion.

OBJECTIVE: To evaluate whether frontal-lobe magnetic resonance spectroscopy measures of γ-aminobutyric acid (GABA) would be altered in a sample of adolescents scanned after sport concussion because mild traumatic brain injury is often associated with working memory problems. METHODS: Eleven adolescents (age 14-17 years) who had sustained a first-time sport concussion were studied with MRI/magnetic resonance spectroscopy within 23 to 44 days after injury (mean 30.4 ± 6.1 days). Age- and sex-matched healthy controls, being seen for sports-related injuries not involving the head and with no history of concussion, were also examined. GABA/creatine + phosphocreatine (Cre) was measured in left-sided frontal lobe and central posterior cingulate regions. The frontal voxel was positioned to overlap with patient-specific activation on a 1-back working memory task. RESULTS: Increased GABA/Cre was shown in the frontal lobe for the concussed group. A decreased relationship was observed in the parietal region. High correlations between GABA/Cre and task activation were observed for the control group in the frontal lobe, a relationship not shown in the concussed participants. CONCLUSIONS: GABA/Cre appears increased in a region colocalized with working memory task activation after sport concussion. Further work extending these results in larger samples and at time points across the injury episode will aid in refining the clinical significance of these observations.

Multiagent chemotherapy and deferred radiotherapy in infants with malignant brain tumors: a report from the Children's Cancer Group.

PURPOSE: To evaluate response rate, event-free survival (EFS), and toxicity of two chemotherapeutic regimens for treatment of children younger than 36 months with malignant brain tumors and to estimate control intervals without irradiation in children with no residual tumor after initial surgery and induction chemotherapy and with delayed irradiation in patients with residual tumor or metastatic disease at diagnosis. PATIENTS AND METHODS: Patients were randomly assigned to one of two regimens of induction chemotherapy (vincristine, cisplatin, cyclophosphamide, and etoposide v vincristine, carboplatin, ifosfamide, and etoposide). Maintenance chemotherapy began after induction in children without progressive disease. Children with no residual tumors after induction therapy and no metastatic disease at diagnosis were not to receive radiation therapy unless their tumors progressed. RESULTS: Two hundred ninety-nine infants were enrolled. Forty-two percent of patients responded to induction chemotherapy. At 5 years from study entry, the EFS rate was 27% +/- 3%, and the survival rate was 43% +/- 3%. There was no significant difference between the two arms in terms of response rate or EFS. For medulloblastoma, supratentorial primitive neuroectodermal tumor, ependymoma, and rhabdoid tumors, 5-year EFS rates were 32% +/- 5%, 17% +/- 6%, and 32% +/- 6%, and 14% +/- 7%, respectively. Fifty-eight percent of patients who were alive 5 years after study entry had not received radiation therapy. CONCLUSION: Intensified induction chemotherapy resulted in a high response rate of malignant brain tumors in infants. Survival was comparable to that of previous studies, and most patients who survived did not receive radiation therapy.

Neurodevelopmental implications of "deformational" plagiocephaly.

Over the past decade there has been a dramatic increase in referrals to specialty clinics, craniofacial centers, plastic surgeons, and neurosurgeons for assessment and treatment of deformational plagiocephaly (DP). Though considered a medically benign condition, preliminary reports suggest that DP may be associated with developmental problems. However, mechanisms to account for this association have not been hypothesized or empirically tested. Although treatment justifications often center on prevention of atypical appearance, little is known about the cosmetic outcomes of treated and untreated children. In this review we hypothesize different etiological pathways linking DP with neurodevelopment (e.g., environmental positioning limitations with and without underlying CNS pathology). We outline directions for research on incidence and prevalence, developmental outcomes, sex differences, determinants of treatment participation, and craniofacial appearance. Despite the paucity of existing research, preliminary findings suggest that children with this condition should be screened and monitored for developmental delays or deficits, as we await more conclusive information from future studies.

Neuropsychological functioning in early onset psychotic disorders.

This paper examines whether neuropsychological profiles of youth with early onset psychotic disorders predicted diagnostic or clinical status. Youth with schizophrenia (n=27), bipolar disorder (n=22), and psychosis NOS (n=20) were included. Subjects received an extensive neuropsychological evaluation, including measures of general cognition, attention, memory, and executive functioning. Medication status was not controlled. No statistically significant neurocognitive differences across diagnostic groups were found. Compared to standardized norms, youth with schizophrenia demonstrated deficits in general cognition, verbal learning, recall, sustained effort, and social knowledge. Subjects with bipolar disorder and psychosis NOS exhibited deficits on measures of verbal learning, recall, and sustained effort similar to those of youth with schizophrenia. Neurocognitive deficits in memory and attention appeared to be common among youth with psychotic illnesses, regardless of diagnosis. Those with schizophrenia may have greater global cognitive deficits and problems with social knowledge. Across diagnoses, subjects demonstrated relative strengths on tests that provided them with immediate feedback, and performed most poorly on tests requiring delayed recall.