Teacher-reported emotional and behavioural problems and ethnic background associated with children's psychosocial care use: a longitudinal population-based study.

Approximately, 15% of children in Western countries suffer from emotional and behavioural problems. However, not all children receive the psychosocial care they need, especially children with a non-Western background experience an unmet need for care. This might be because parents of non-Western children report a lower need for care than parents of Western children, unrelated to the actual need. This study examined the association between teacher-reported problems and psychosocial care use, independent of mother-reported problems. Further, the role of ethnic background in this association was investigated. The study sample of 9-year-old children was retrieved from the Generation R Study (N = 3084), a prospective, population-based cohort of children born in Rotterdam, the Netherlands. Teacher- and mother-reported problems were measured via questionnaire when the children were  6/7 years old. Psychosocial care use was mother-reported at the research centre when children were 9 years old (8.1%). Hierarchical logistic regressions showed significant positive associations between teacher-reported total, externalising and internalising problems and later psychosocial care use. These associations were independent of mother-reported problems. Children with a non-Western background used less care, but ethnic background did not moderate the association between teacher-reported problems and care use. Our findings suggest that teachers might have an important role, next to parents, in the identification of problems and children's access to care. This may be particularly important for non-Western children, as they use less psychosocial care than Western children, despite other research showing that they generally display higher levels of problems. Directions for future research and implications are discussed.

Children's use of psychosocial care in a population-based longitudinal study: less likely for girls, children with a non-Western background and children with a high quality of life.

Knowledge on determinants of children's psychosocial care use is important to improve their access to care. This study examined the independent contributions of need and predisposing factors to psychosocial care use in 9-year-old children, guided by the Gateway Provider Model. Data of the Generation R Study, a prospective cohort of children born in Rotterdam, the Netherlands, were analysed using multivariable logistic regression (n = 4714). Need (quality of life, presence and type of emotional/behavioural problems) and predisposing factors (sex, ethnic background and maternal educational level) were measured using parent questionnaires at multiple time points between ages 1.5 and 9 years. Psychosocial care use was parent-reported at 9 years old (9.6% among children with Western background, 7.3% among children with non-Western background). Having emotional/behavioural problems at 5 and 9 years old was associated with more care use, while having a higher quality of life, being a girl and having a Moroccan/Turkish or other non-Western background were associated with less care use. Externalising and internalising problems, as well as several types of problems, at 5 and 9 years old were associated with psychosocial care use. Stratified analyses revealed that, in children with non-Western backgrounds, only a poorer psychosocial quality of life was associated with psychosocial care use. To conclude, girls with a Western background and children with a non-Western background were less likely to receive care compared to their peers. Children with parent-reported emotional/behavioural problems at 5 and 9 years old and decreased quality of life at 5 years old were more likely to receive psychosocial care use at 9 years old. Our findings hold relevance for preventive policies.

[Psychopathology, risk factors and possible interventions in the early years: Dutch cohort research]. / Risicofactoren voor psychische problemen en mogelijke interventies in de jonge jaren: Nederlands cohortonderzoek.

Background Multiple factors contribute to the development of psychiatric disorders. Aim To discuss factors in pregnancy and early childhood that contribute to the development of psychiatric problems. Method Overview of the findings of four major Dutch child cohorts. Results Based on findings of four major Dutch child cohorts, we describe risk factors during pregnancy and early childhood that contribute to the development of psychopathology. Conclusion The identified risk factors and mechanisms can serve as targets for follow-up research, prevention, and intervention. Tijdschrift voor psychiatrie 63(2021)2, 107-110.

Effective psychological therapies to improve lifestyle behaviors in (pre)pregnant women: A systematic review.

Poor lifestyle behaviors impact (pre)pregnant women by affecting pregnancy outcomes and offspring health. This systematic review provides an overview of psychological therapies to support lifestyle behavior changes among (pre)pregnant women. Scientific databases were searched from their inception to 20 December 2020 for studies investigating the effects of psychological therapies on improvements in lifestyle behaviors. Studies were eligible if they included (pre)pregnant women, examined the effects of a psychological therapy on at least one lifestyle behavior and used a control group receiving usual pregnancy care or a non-psychological intervention. Lifestyle behaviors of interest were dietary intake, physical activity, smoking, alcohol consumption, drug use, body weight loss and body weight gain during pregnancy. Pregnancy complications were included as outcome measures. Motivational interviewing (MI) (n = 21), cognitive behavioral therapy (CBT) (n = 8), incentive-based contingency management (IBCM) (n = 9), mindfulness (n = 1) and hypnosis (n = 1) were investigated as lifestyle behavior interventions. The findings revealed that MI was effective in reducing (self-reported) smoking and alcohol consumption and restricting gestational weight gain (GWG). CBT was only studied as an intervention to restrict GWG and the results predominantly confirmed its effectiveness. IBCM showed the strongest effect on reducing smoking and substance use. The studies using hypnosis or mindfulness to reduce smoking or restrict GWG, respectively, showed no associations. The use of psychological therapies to improve lifestyle behaviors among (pre)pregnant women is new and the scientific proof is promising. Before wide implementation is legitimated, more evidence is needed on the consequences of lifestyle change for pregnancy outcomes.

Associations of eczema phenotypes with emotional and behavioural problems from birth until school age. The Generation R Study.

BACKGROUND: Eczema phenotypes and emotional and behavioural problems are highly prevalent in childhood, but their mutual relationship is not fully clear. OBJECTIVES: To examine the associations of eczema phenotypes with school-age emotional and behavioural problems, and the bidirectional associations of eczema and emotional and behavioural problems from birth until 10 years. METHODS: This study among 5265 individuals was embedded in a prospective population-based cohort study. Never, early transient, mid-transient, late transient and persistent eczema phenotypes were identified based on parent-reported, physician-diagnosed eczema from age 6 months until 10 years. Emotional (internalizing) and behavioural (externalizing) problems were measured repeatedly using the Child Behavior Checklist from age 1·5 to 10 years. Cross-lagged models were applied for bidirectional analyses. RESULTS: All eczema phenotypes were associated with more internalizing problems and attention problems at age 10 years, compared with never having eczema: range of Z-score differences 0·14 [95% confidence interval (CI) 0·01-0·27] to 0·39 (95% CI 0·18-0·60). Children with early transient eczema had more aggressive behaviour symptoms at age 10 years (Z = 0·16, 95% CI 0·05-0·27). Bidirectional analysis showed that eczema at 0-2 years was associated with more internalizing and externalizing problems at ages 3-6 and 10 years, while, inversely, only internalizing problems at 0-2 years were associated with an increased risk of eczema at age 10 years. CONCLUSIONS: Eczema phenotypes are very modestly associated with more somatic symptoms and attention problems at school age. Early transient eczema is associated with more aggressive behaviour symptoms. Directional effects seem to occur from early-life eczema to later-life internalizing and externalizing problems, rather than the reverse.

ADHD symptoms and body composition changes in childhood: a longitudinal study evaluating directionality of associations.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is linked to increased risk of overweight/obesity among children and adults. Studies have also implicated obesity as a risk factor for ADHD. However, no studies have evaluated bidirectional, longitudinal associations between childhood fat mass and ADHD symptom severity. OBJECTIVES: We investigate bidirectional associations between ADHD symptoms and measures of body composition between ages 1.5 and 9. We further examine effects of specific eating patterns linked to ADHD on associations between symptom severity and body composition. METHODS: The study utilized data from children (N = 3903) participating in the Generation R cohort (Netherlands). Children were enrolled at birth and retained regardless of ADHD symptoms over time. Cross-lagged and change models examined bidirectional associations between body composition (body mass index/dual-energy X-ray absorptiometry) and ADHD symptoms at four time points in childhood. RESULTS: A child with a clinically concerning ADHD symptom z-score two standard deviations above the mean at age 6 would be expected to experience about 0.22 kg greater fat mass gain measured via dual-energy x-ray absorptiometry between ages 6 and 9, even if they displayed healthy eating patterns (95% CI: 0.11 - 0.28, p < 0.001). Conversely, fat mass at any age did not predict worse ADHD symptoms later. CONCLUSIONS: Beginning in early childhood, more ADHD symptoms predict higher fat mass at later ages. We did not find evidence of a reverse association. Based on these and prior findings, lifestyle counselling during treatment for children with a diagnosis of ADHD should be considered, even if they are diagnosed in early childhood and do not yet have a body mass index of clinical concern.

Self-reported problem behavior in young children with and without a DSM-disorder in the general population.

BACKGROUND: Problem behavior of young children is generally not assessed with structured child interviews. This paper examined how information about problem behavior, obtained by structured interviews with six-year-old children, relates to DSM-disorders obtained from parents and to treatment referral. METHODS: In a population-based cohort, caregivers of 1084 young children (mean age 6.7 years) were interviewed with the DSM-based Diagnostic Interview Schedule-Young Child version (DISC-YC), and they scored the Child Behavior Checklist (CBCL). Children themselves were interviewed about problem behavior using the semi-structured Berkeley Puppet Interview (BPI). Information regarding treatment referral to mental health services was obtained by parent-reported questionnaire when children were on average eight years old. RESULTS: DSM-disorders and CBCL problems in the clinical range were cross-sectionally associated with higher levels of child self-reported problems. Associations were strongest in the externalizing domain (e.g. DISC-YC externalizing disorders with BPI externalizing scores: F(1, 416)=19.39, P<0.001; DISC-YC internalizing disorders with BPI internalizing scores: F(1, 312)=3.75, P=0.054). Moreover, higher BPI internalizing and externalizing problem scores predicted treatment referral two years later. CONCLUSIONS: We conclude that systematically interviewing preschool and young elementary school-aged children should be an integral part of child assessment. This approach may contribute to a better understanding of child development and may predict future problems.

Bidirectional associations between circulating vitamin D and cholesterol levels: The Rotterdam Study.

OBJECTIVES: Higher levels of vitamin D have been associated with lower rates of cardiovascular disease perhaps through improved lipid profiles. However, results are inconsistent and the direction of the association between vitamin D and lipid levels remains unknown. We examined bidirectional associations between serum 25-hydroxyvitamin D (25(OH)D) and cholesterol concentrations. STUDY DESIGN: We used data from 1165 participants aged 55 to 88 years from the Rotterdam Study, a population-based prospective cohort study. MAIN OUTCOME MEASURES: Serum concentrations of 25(OH)D, total cholesterol (TC) and HDL cholesterol (HDL-C) were measured at two time points with a median time difference of 6 years. Bidirectional associations between 25(OH)D and each of the blood lipids was examined with path analyses in cross-lagged models. All models were adjusted for baseline age, sex, BMI, smoking status, and diet quality. RESULTS: The best-fit model for 25(OH)D and TC indicated that higher baseline TC concentrations were associated with lower 25(OH)D concentrations (standardized regression coefficient -0.05 (SE 0.02)), but 25(OH)D at baseline did not predict TC. For HDL-C, the best-fit model suggested a bidirectional inverse association between HDL-C and 25(OH)D (standardized regression coefficients of -0.03 (SE 0.02)) for both directions. CONCLUSIONS: Our results from path analyses on repeatedly measured 25(OH)D and lipid levels suggest that total cholesterol may be associated with decreased in 25(OH)D concentrations, but not the other way around, whereas the observed inverse association between HDL-C and 25(OH)D may be bidirectional.

CBFB-MYH11/RUNX1 together with a compendium of hematopoietic regulators, chromatin modifiers and basal transcription factors occupies self-renewal genes in inv(16) acute myeloid leukemia.

Different mechanisms for CBFß-MYH11 function in acute myeloid leukemia with inv(16) have been proposed such as tethering of RUNX1 outside the nucleus, interference with transcription factor complex assembly and recruitment of histone deacetylases, all resulting in transcriptional repression of RUNX1 target genes. Here, through genome-wide CBFß-MYH11-binding site analysis and quantitative interaction proteomics, we found that CBFß-MYH11 localizes to RUNX1 occupied promoters, where it interacts with TAL1, FLI1 and TBP-associated factors (TAFs) in the context of the hematopoietic transcription factors ERG, GATA2 and PU.1/SPI1 and the coregulators EP300 and HDAC1. Transcriptional analysis revealed that upon fusion protein knockdown, a small subset of the CBFß-MYH11 target genes show increased expression, confirming a role in transcriptional repression. However, the majority of CBFß-MYH11 target genes, including genes implicated in hematopoietic stem cell self-renewal such as ID1, LMO1 and JAG1, are actively transcribed and repressed upon fusion protein knockdown. Together these results suggest an essential role for CBFß-MYH11 in regulating the expression of genes involved in maintaining a stem cell phenotype.

Bidirectional associations between overweight and health-related quality of life from 4-11 years: Longitudinal Study of Australian Children.

BACKGROUND: Temporal pathways of known associations between overweight and poor health-related quality of life (HRQoL) in adolescents remain poorly documented. This study aims to (1) examine timing and strength of the association between HRQoL and body mass index (BMI) in childhood, and (2) investigate directionality and impact of cumulative burden in any observed HRQoL-BMI associations. DESIGN, SETTING AND PARTICIPANTS: Participants were 3898 children in the population-based Longitudinal Study of Australian Children (LSAC) assessed at four biennial waves from ages 4-5 (2004) to 10-11 years (2010). MAIN MEASURES: At every wave, parents completed the Pediatric Quality of Life Inventory, and measured BMI (kg m(-2)) was converted into BMIz and overweight using international norms. ANALYSES: Linear and logistic regressions. RESULTS: Overweight first became cross-sectionally associated with HRQoL at 6-7 years of age, with linear associations between poorer HRQoL (physical and psychosocial health) and higher BMI developing by 8-9 years and strengthening by 10-11 years. Longitudinal analyses revealed cumulative relationships such that the number of times a child was overweight between the ages 4 and 11 years predicted progressively poorer scores on both physical and psychosocial health at 10-11 years (P-values for trend <0.001). In the weaker reverse associations, children with poor (vs persistently good) physical health at any wave had slightly higher mean BMIz at age 10-11 years, but this difference was small (0.14, 95% confidence interval (CI): 0.04, 0.24) and not cumulative; results for psychosocial health were even weaker, with mixed subscale findings. CONCLUSIONS: Middle childhood appears to be the critical period in which HRQoL-BMI comorbidities emerge and strengthen, first among children with clinically relevant conditions, that is, overweight or poor HRQoL, and then more generally across the whole range of BMI. Poorer HRQoL seemed predominantly a consequence of higher BMI, rather than a cause, suggesting that effective promotion of healthy weight could benefit multiple aspects of children's well-being.

Perinatal outcomes and gestational weight gain in women with eating disorders: a population-based cohort study.

OBJECTIVE: To investigate adverse perinatal outcomes and gestational weight gain trajectories in women with lifetime (current/past) eating disorders (ED: anorexia nervosa [AN] and bulimia nervosa [BN]). DESIGN: A longitudinal population-based birth cohort. SETTING: Rotterdam, the Netherlands. SAMPLE: Women who enrolled prenatally, had complete information on exposure (lifetime ED), and gave birth to a live singleton (n = 5256). Four groups of exposed women: lifetime AN (n = 129), lifetime BN (n = 209), lifetime AN + BN (n = 100), other lifetime psychiatric disorder (n = 1002) were compared with unexposed women (n = 3816). METHODS: Perinatal outcomes and gestational weight gain were obtained from obstetric and midwifery records, self-report and objective measurements. Exposed women were compared with unexposed women within the cohort using linear, logistic regression and mixed models. MAIN OUTCOME MEASURES: Any pregnancy, delivery and postnatal complications. Birthweight adjusted for gestational age, prematurity (born <37 weeks), small-for-gestational age; maternal weight gain during pregnancy. RESULTS: Maternal AN was positively associated with suspected fetal distress. No differences were found in mean birthweight, prevalence of a small-for-gestational-age, or premature birth. Relative to unexposed women, women with AN had, on average, a lower body weight but a higher rate of weight gain subsequently; whereas women with BN had a higher body weight but a lower rate of weight gain. CONCLUSIONS: Maternal lifetime ED is associated with few adverse perinatal outcomes in this sample. Differential gestational weight gain patterns in women with AN and BN are consistent with possible biological compensatory mechanisms aimed at protecting the fetus.

Perinatal complications increase the risk of postpartum depression. The Generation R Study.

OBJECTIVE: To examine whether specific pregnancy and delivery complications are risk factors for postpartum depression. DESIGN: A prospective longitudinal study. SETTING: Rotterdam, the Netherlands. POPULATION: A cohort of 4941 pregnant women who enrolled in the Generation R Study. METHODS: Information on perinatal complications was obtained from the midwife and hospital registries or by questionnaire. Logistic regression analyses were used to calculate the risk of postpartum depression for the separate perinatal complications. MAIN OUTCOME MEASURES: Postpartum psychiatric symptoms were assessed 2 months after delivery using the Edinburgh postnatal depression scale. RESULTS: Several perinatal complications were significantly associated with postpartum depression, namely: pre-eclampsia (adjusted OR, aOR 2.58, 95% CI 1.30-5.14), hospitalization during pregnancy (aOR 2.25, 95% CI 1.19-4.26), emergency caesarean section (aOR 1.53, 95% CI 1.02-2.31), suspicion of fetal distress (aOR 1.56, 95% CI 1.08-2.27), a medically indicated delivery provided by an obstetrician (aOR 2.43, 95% CI 1.56-3.78), and hospital admission of the baby (aOR 1.45, 95% CI 1.10-1.92). Unplanned pregnancy, thrombosis, meconium-stained amniotic fluid, and Apgar score were not associated with postpartum depression after adjustment for confounding factors, such as pre-existing psychopathological symptoms and sociodemographic characteristics. The risk of postpartum depression increased with the number of perinatal complications women experienced (P < 0.001). CONCLUSIONS: We showed that several pregnancy and delivery complications present a risk for women's mental health in the postpartum period. Obstetricians, midwives, general practitioners, and staff at baby well clinics should be aware that women who experienced perinatal complications-especially those with a number of perinatal complications-are at risk for developing postpartum depression.

Explaining educational inequalities in preterm birth: the generation r study.

BACKGROUND: Although a low socioeconomic status has consistently been associated with an increased risk of preterm birth, little is known about the pathways through which socioeconomic disadvantage influences preterm birth. AIM: To examine mechanisms that might underlie the association between the educational level of pregnant women as an indicator of socioeconomic status, and preterm birth. METHODS: The study was nested in a population-based cohort study in the Netherlands. Information was available for 3830 pregnant women of Dutch origin. FINDINGS: The lowest-educated pregnant women had a statistically significant higher risk of preterm birth (odds ratio (OR) = 1.89 (95% CI 1.28 to 2.80)) than the highest educated women. This increased OR was reduced by up to 22% after separate adjustment for age, height, preeclampsia, intrauterine growth restriction, financial concerns, long-lasting difficulties, psychopathology, smoking habits, alcohol consumption, and body mass index (BMI) of the pregnant women. Joint adjustment for these variables resulted in a reduction of 89% of the increased risk of preterm birth among low-educated pregnant women (fully adjusted OR = 1.10 (95% CI 0.66 to 1.84)). CONCLUSIONS: Pregnant women with a low educational level have a nearly twofold higher risk of preterm birth than women with a high educational level. This elevated risk could largely be explained by pregnancy characteristics, indicators of psychosocial well-being, and lifestyle habits. Apparently, educational inequalities in preterm birth go together with an accumulation of multiple adverse circumstances among women with a low education. A number of explanatory mechanisms unravelled in the present study seem to be modifiable by intervention programmes.

Behavioral problems in relation to intelligence in children with 22q11.2 deletion syndrome: a matched control study.

The 22q11.2 deletion syndrome (22q11DS) is a genetic disorder associated with palatal abnormalities, cardiac defects, a characteristic facial appearance, learning difficulties, and delays in speech and language development. Various behavioral disorders and psychiatric illnesses have also been reported. There is much debate as to whether the behavioral problems are caused by factors such as medical discomfort, facial abnormalities or a lower intelligence, or whether they are independently related to the genetic abnormality ("behavioral phenotype"). We examined the relationship between intelligence level and behavioral problems. A group of 69 children with 22q11DS was compared with 69 children with craniofacial anomalies (CFA) using the child behavior checklist (CBCL). The matches between individual children were based on their total IQ scores. Use of the CBCL norm scores covered the corrections for age and sex. The group of 22q11DS children showed significantly more behavioral problems than the CFA group: this was especially apparent on the CBCL subscales "withdrawn," "anxious/depressed," "delinquent behavior," "aggressive behavior," "somatic complaints," and "social problems." We found no correlation between IQ score and behavioral problems in the 22q11DS group, which was remarkable because, comparable with the general population, intellectual disabilities were a predictor of behavioral problems in the CFA group. 22q11DS children with relatively higher IQs showed more problems of an internalizing than an externalizing nature, whereas the 22q11DS children with lower IQs showed various behavioral problems. The absence of a statistically significant correlation between intelligence and behavior problems in the group of 22q11DS children is tentative evidence for a 22q11DS behavioral phenotype.

Intravenous immunoglobulin as therapy for pediatric Guillain-Barré syndrome.

Seven children with Guillain-Barré syndrome were treated with intravenous immunoglobulin. Median patient age was 5.8 years. A standard dosage of 0.4 g/kg/day for 5 days was administered. Clinical improvement occurred on average within 2.4 +/- 1.3 days of beginning intravenous immunoglobulin. One child required mechanical ventilation for 7 days. Eight comparable children with Guillain-Barré syndrome at our institution in a prior study treated with plasmapheresis alone had similar clinical results. However, the need for admission to the pediatric intensive care unit and duration of pediatric intensive care unit stay were lower in the intravenous immunoglobulin treated group (P < .05). There were no complications with intravenous immunoglobulin therapy except for a brief episode of hypotension in one patient. Review of the literature identified 74 additional children with Guillain-Barré syndrome successfully receiving intravenous immunoglobulin therapy. We suggest intravenous immunoglobulin as initial therapy for pediatric Guillain-Barré syndrome, because it appears equally as effective as plasmapheresis and is associated with fewer complications.

Severe rattlesnake envenomation with anaphylaxis and rhabdomyolysis.

A 7-year-old boy presented to the emergency department with severe hypotension and lethargy after a rattlesnake bite. He developed anaphylaxis to antivenom and required intubation, epinephrine, antihistamines, and steroids. Severe rhabdomyolysis and myoglobinuric kidney failure developed over 24 hours, with a peak creatine phosphokinase level of 214,500 units/L. Severe hypocalcemic tetany was treated with replacement therapy. Local wound swelling was never severe and the patient had no coagulopathies. Marked motor weakness improved with antivenom administration. Because of the myotoxic and neurologic effects in the absence of fibrinogenolysis/thrombocytopenia and minimal tissue signs, as well as the similarity to a previously reported case from our area, the envenomation was most likely caused by a Mojave rattlesnake.

Guillain-Barré syndrome in childhood: natural course and efficacy of plasmapheresis.

Eight children with Guillain-Barré syndrome were treated with plasmapheresis. Retrospective comparisons were made with 11 historic control patients. Eight children required mechanical ventilation, 4 of whom were in the plasmapheresis group. One week after the last plasmapheresis treatment, patients receiving plasmapheresis within 7 days of symptom onset had improved by one Guillain-Barré syndrome score. Discharge Guillain-Barré syndrome scores were significantly lower for those receiving plasmapheresis (P < .05). Patients in the plasmapheresis group had a decrease in the number of days of mechanical ventilation, time until motor recovery, and overall cost. Our results are consistent with published literature and indicate that plasmapheresis for childhood Guillain-Barré syndrome is a safe and effective treatment to shorten the time to recovery.

Mojave rattlesnake envenomation: prolonged neurotoxicity and rhabdomyolysis.

An 11-year-old girl presented to the emergency department with hypoventilation and shock after being bitten by a Mojave rattlesnake. Intubation was required, and she improved rapidly after fluid resuscitation and antivenom administration. She was extubated four hours after envenomation and did well. The patient subsequently developed increased weakness and cranial nerve paresis and required reintubation for respiratory failure at 30 hours after envenomation despite administration of 30 vials of antivenom. She improved after administration of additional antivenom and was extubated ten hours later. Twenty-four hours after envenomation, signs of rhabdomyolysis were noted with myoglobinuria and a creatine phosphokinase level of 96,400 units/L. Myoglobinuric renal failure was treated with mannitol, hydration, and alkalinization of the urine. The patient's renal and neurological functions improved steadily during the following three to four days. Neurotoxic and myotoxic effects of Mojave venom are known to occur but are not well documented in human beings. Recognition of potential complications from envenomation such as respiratory paralysis and rhabdomyolysis with myoglobinuric renal failure is critical.

Glucocorticoid receptors and cell cycle progression in human melanoma cell lines.

Proliferation of six established human melanoma cell lines was inhibited after treatment for 1 h with a high dose of glucocorticoid. Four of the lines with the capacity of colony formation were used to quantify final plating efficiency. Specific glucocorticoid binding sites in these cell lines ranged from 51,000 to 170,000 sites per cell as measured with a whole-cell assay. Growth inhibition was completely reversible in one cell line, irreversible in another, and partially reversible in two lines. Receptor content per cell correlated with the reduction in final plating efficiency of glucocorticoid-treated cells, suggesting a receptor-mediated event. A more than 90% growth inhibition and a 40% reduction in cell survival in the most sensitive cell line, M-5A, was accompanied by a dual blockage in G1 and G2/M phase that lasted till at least 96 h after treatment with 2.5 microM dexamethasone for 1 h. Evidence is presented of a real arrest of M-5A cells in G1 phase and a markedly retarded progression through G2; the blockage of G1-S transition was immediate and complete. Accumulation of G1 cells was observed in two other cell lines but was inconsistent in the fourth line studied by flow cytometry; in none of the three cell lines was G2/M accumulation observed. Stimulated melanogenesis after glucocorticoid treatment of M-5A and NKI-26 cells suggested differentiation of the cells during glucocorticoid-induced arrest.