Maternal prenatal stress and postnatal depressive symptoms: discrepancy between mother and teacher reports of toddler psychological problems.

PURPOSE: Maternal prenatal stress and postnatal depression are reported to increase the risk for early offspring psychological problems. We examined whether these two stressors predicted toddler emotional or behavioral problems based on the mother and teacher reports, respectively. METHODS: A longitudinal study within the Odense Child Cohort (OCC). Prenatal stress was assessed (gestation week 28) using Cohen's Perceived Stress Scale (PSS). Depressive symptoms were assessed (3 months after birth) using the Edinburgh Postnatal Depression Scale (EPDS). Behavioral and emotional problems were assessed by mothers using the preschool version of Child Behaviour Checklist (CBCL) and by teachers using the caregiver-teacher report form (CTR-F). RESULTS: N = 1302 mother-child dyads were included. CBCL (N = 1302) was collected at 29 months (SD 5.3) and C-TRF (N = 989) at 32.6 months (SD 6.9). N = 70 mothers (5.4%) were at high risk for postnatal depression (EPDS score > 12). Generalized additive models showed that prenatal stress (increase of + 1 on PSS-10 total score) predicted an increase in CBCL (+ 0.011) and C-TRF (+ 0.015) total scores. Postnatal depressive symptoms (increase of + 1 on EPDS total score) only predicted an increase in CBCL total score (+ 0.026). CONCLUSION: Prenatal maternal stress was a significant predictor of both mother and teacher reported toddler emotional and behavioral problems, although effect sizes were small. Postnatal depressive symptoms were associated with increased maternal (but not teacher) reporting of toddler problems. Mothers reported more toddler psychological problems than teachers, and the mother-teacher discrepancy was positively correlated to maternal postnatal depressive symptoms.

Trends in antidepressant use among children and adolescents: a Scandinavian drug utilization study.

OBJECTIVE: To compare antidepressant utilization in individuals aged 5-19 years from the Scandinavian countries. METHODS: A population-based drug utilization study using publicly available data of antidepressant use from Denmark, Norway, and Sweden. RESULTS: In the study period from 2007 to 2017, the proportion of antidepressant users increased markedly in Sweden (9.3-18.0/1000) compared to Norway (5.1-7.6/1000) and Denmark (9.3-7.5/1000). In 2017, the cumulated defined daily doses (DDD) of selective serotonin reuptake inhibitors were 5611/1000 inhabitants in Sweden, 2709/1000 in Denmark, and 1848/1000 in Norway. The use of 'other antidepressants' (ATC code N06AX) also increased in Sweden with a higher DDD in 2017 (497/1000) compared to Denmark (225/1000) and Norway (170/1000). The use of tricyclic antidepressants was generally low in 2017 with DDDs ranging between 30-42 per 1000. The proportion of antidepressant users was highest among 15- to 19-year-old individuals. Girls were more likely to receive treatment than boys, and the treated female/male ratios per 1000 were similar in Sweden (2.39), Denmark (2.44), and Norway (2.63). CONCLUSION: Even in highly comparable healthcare systems like the Scandinavian countries', variation in antidepressant use is considerable. Swedish children and adolescents have a markedly higher and still increasing use of antidepressants compared to Danish and Norwegian peers.

Changing relationships between smoking and psychiatric disorders across twentieth century birth cohorts: clinical and research implications.

As the risks of tobacco use become recognized and smoking becomes stigmatized, new smokers may be increasingly driven to smoke by biological or genetic vulnerabilities rather than social desirability. Given that genetic risk for deviant proneness is shared across other psychiatric and addictive disorders, we predicted that as rates of smoking decreased through the latter half of the twentieth century, associations between smoking and psychopathology would increase. Participants (N=25 412) from a large US study-the National Epidemiologic Survey on Alcohol and Related Conditions, NESARC-were interviewed using the Alcohol Use Disorder and Associated Disabilities Interview Schedule - DSM-IV Version (AUDADIS-IV) and classified into one of five birth cohort decades (1940s to 1980s) and three smoking history (nonsmokers, never-dependent smokers and ever-dependent smokers) groups. We found that the prevalence of smoking decreased across the five birth cohorts, but associations of smoking with drug and AUDs, attention-deficit hyperactivity disorder, bipolar disorder and antisocial personality disorder, each increased monotonically in more recently born cohorts, even after adjusting for concurrent demographic and socioeconomic changes. For drug and AUDs, increases were observed among smokers both with and without a history of nicotine dependence; for other outcomes, increases were entirely driven by nicotine-dependent smokers. Findings suggest that smokers in more recent cohorts have disproportionately high psychiatric vulnerability, and may benefit from greater mental health screenings. Differentiating between casual and dependent smokers may further help prioritize those at greatest risk. Researchers should also be aware of potential variation in psychiatric comorbidity based on cohort of birth when defining groups of smokers, to minimize confounding.

Prenatal depression outcomes in the next generation: A critical review of recent DOHaD studies and recommendations for future research.

Prenatal depression, a common pregnancy-related risk with a prevalence of 10-20 %, may affect in utero development and socioemotional and neurodevelopmental outcomes in the next generation. Although there is a growing body of work that suggests prenatal depression has an independent and long-lasting effect on offspring outcomes, important questions remain, and findings often do not converge. The present review examines work carried out in the last decade, with an emphasis on studies focusing on mechanisms and leveraging innovative technologies and study designs to fill in gaps in research. Overall, the past decade of research continues to suggest that prenatal depression increases risk for offspring socioemotional problems and may alter early brain development by affecting maternal-fetal physiology during pregnancy. However, important limitations remain; lack of diversity in study samples, inconsistent consideration of potential confounders (e.g., genetics, postnatal depression, parenting), and restriction of examination to narrow time windows and single exposures. On the other hand, exciting work has begun uncovering potential mechanisms underlying transmission, including alterations in mitochondria functioning, epigenetics, and the prenatal microbiome. We review the evidence to date, identify limitations, and suggest strategies for the next decade of research to detect mechanisms as well as sources of plasticity and resilience to ensure this work translates into meaningful, actionable science that improves the lives of families.

Depression and cognition are associated with lipid dysregulation in both a multigenerational study of depression and the National Health and Nutrition Examination Survey.

Chronic dysregulation of peripheral lipids has been found to be associated with depression and cognition, but their interaction has not been investigated. Growing evidence has highlighted the association between peripheral lipoprotein levels with depression and cognition with inconsistent results. We assessed the association between peripheral lipids, depression, and cognition while evaluating their potential interactions using robust clinically relevant predictors such as lipoprotein levels and chronic medical disorders that dysregulate lipoproteins. We report an association between peripheral lipids, depression, and cognition, suggesting a common underlying biological mechanism driven by lipid dysregulation in two independent studies. Analysis of a longitudinal study of a cohort at high or low familial risk for major depressive disorder (MDD) (n = 526) found metabolic diseases, including diabetes, hypertension, and other cardiovascular diseases, were associated with MDD and cognitive outcomes. Investigating a cross-sectional population survey of adults in the National Health and Nutrition Examination Survey 2011-2014 (NHANES) (n = 2377), depression was found to be associated with high density lipoprotein (HDL) and cognitive assessments. In the familial risk study, medical conditions were found to be associated with chronic lipid dysregulation and were significantly associated with MDD using the structural equation model. A positive association between chronic lipid dysregulation and cognitive scores was found in an exploratory analysis of the familial risk study. In a complementary study, analysis of NHANES revealed a positive association of HDL levels with cognition. Further analysis of the NHANES cohort indicated that depression status mediated the interaction between HDL levels and cognitive tests. Importantly, the protective effect of HDL on cognition was absent in those with depressive symptoms, which may ultimately result in worse outcomes leading to cognitive decline. These findings highlight the potential for the early predictive value of medical conditions with chronic lipid dyshomeostasis for the risk of depression and cognitive decline.

Panic disorder is associated with the serotonin transporter gene (SLC6A4) but not the promoter region (5-HTTLPR).

Panic disorder (PD) and social anxiety disorder (SAD) are moderately heritable anxiety disorders. We analyzed five genes, derived from pharmacological or translational mouse models, in a new case-control study of PD and SAD in European Americans: (1) the serotonin transporter (SLC6A4), (2) the serotonin receptor 1A, (3) catechol-O-methyltransferase, (4) a regulator of g-protein signaling and (5) the gastrin-releasing peptide receptor. Cases were interviewed using the schedule for affective disorders and schizophrenia and were required to have a probable or definite lifetime diagnosis of PD (N=179), SAD (161) or both (140), with first onset by age 31 and a family history of anxiety. Final diagnoses were determined using the best estimate procedure, blind to genotyping data. Controls were obtained from the National Institute of Mental Health Human Genetics Initiative; only subjects above 25 years of age who screened negative for all psychiatric symptoms were included (N=470). A total of 45 single nucleotide polymorphisms were successfully genotyped over the five selected genes using Applied Biosystems SNPlex protocol. SLC6A4 provided strong and consistent evidence of association with the PD and PD+SAD groups, with the most significant association in both groups being at rs140701 (chi(2)=10.72, P=0.001 with PD and chi(2)=8.59, P=0.003 in the PD+SAD group). This association remained significant after multiple test correction. Those carrying at least one copy of the haplotype A-A-G constructed from rs3794808, rs140701 and rs4583306 have 1.7 times the odds of PD than those without the haplotype (95% confidence interval: 1.2-2.3). The SAD only group did not provide evidence of association, suggesting a PD-driven association. The findings remained after adjustment for age and sex, and there was no evidence that the association was due to population stratification. The promoter region of the gene, 5-HTTLPR, did not provide any evidence of association, regardless of whether analyzed as a triallelic or biallelic locus, nor did any of the other four candidate genes tested. Our findings suggest that the serotonin transporter gene may play a role in PD; however, the findings require replication. Future studies should attend to the entire genetic region rather than the promoter.

A randomized trial of intravenous acetaminophen versus indomethacin for treatment of hemodynamically significant PDAs in VLBW infants.

Objective was to compare the rate of successful treatment of hsPDA based on echocardiogram criteria after use of IV acetaminophen or IV indomethacin in very low-birthweight infants. The study was a multi-center, randomized controlled trial. Infants born prior to 32 weeks with birthweight ≤ 1500 g were included if PDA treatment was indicated within the 21 days after birth. hsPDA was defined by strict echocardiogram criteria. Eligible infants were randomized to treatment with either IV acetaminophen or IV indomethacin. Of 86 eligible infants, 17 infants were randomized to acetaminophen and 20 to indomethacin. One (5.9%) hsPDA in the acetaminophen group had successful treatment compared to 11 (55%) in the indomethacin group (p = 0.002). Eight (47%) in the acetaminophen group and 3 (15%) in the indomethacin group received transcatheter PDA closure (p = 0.07). IV indomethacin was more effective than IV acetaminophen for treatment of hsPDAs. More infants in the acetaminophen group received transcatheter closure.

Reduced narcotic and sedative utilization in a NICU after implementation of pain management guidelines.

OBJECTIVE: To assess the opioid and benzodiazepine usage in a level IV NICU after implementation of pain guidelines. STUDY DESIGN: Guidelines were developed for infants undergoing surgical procedures and infants on mechanical ventilation. Data collected for period 1 (July to December 2013) and period 2 (March to August 2014). RESULTS: Gestational age, birth weight and infants with hypoxic respiratory failure or requiring major procedures were comparable in two periods. Number of patients exposed to opioids decreased from 62.9% (129/205) in period 1 to 32.8% (82/250) in period 2, P=<0.001. Cumulative dose exposure decreased, opioids in morphine equivalent dose, mg kg-1 (1.64 (0.38 to 6.94) vs 0.51 (0.04 to 2.33), P=0.002), sedatives in midazolam equivalent, mg kg-1 (0.16 (0.03 to 7.39) vs 0.10 (0.00 to 4.00), P=0.03). Ten patients required treatment for iatrogenic opioid withdrawal versus only three in post guideline, P=0.02. CONCLUSIONS: Evidence-based guidelines led to significant reduction in opioids and sedatives exposure, and in the number of infants requiring methadone for iatrogenic narcotic dependence.

Outcomes of neonates with birth weight⩽500 g: a 20-year experience.

OBJECTIVE: Ethical dilemmas continue regarding resuscitation versus comfort care in extremely preterm infants. Counseling parents and making decisions regarding the care of these neonates should be based on reliable, unbiased and representative data drawn from geographically defined populations. We reviewed survival and morbidity data for our population at the edge of viability. STUDY DESIGN: A retrospective review of our perinatal database was carried out to identify all infants born alive and admitted to the neonatal intensive care unit (NICU) with BW⩽500 g between 1989 and 2009. Data from the initial hospital stay and follow-up at 24 months were collected. RESULT: Out of 22 672 NICU admissions, 273 were eligible: 212 neonates were reviewed after excluding infants with comfort care. BW ranged from 285 to 500 g (mean 448 g) and gestational age range 22 to 28 weeks (median 24 week). Sixty-one (28.8%) survived until discharge. Only 13.8% males survived compared with 39.2% females (P<0.05). Half (49%) were discharged with home oxygen/monitor. Fifty (82%) patients' charts were available to review at the 24-month follow-up. Thirty-three percent of surviving infants had a normal neurodevelopmental assessment at 24 months. Forty-three percent had weight/head circumference<5th percentile at 24 months. CONCLUSION: About a third of neonates admitted to NICU with ⩽500 g BW survived, with 33% of those surviving, demonstrating age-appropriate development at a 24-month follow-up visit.

Immunomodulation by exogenous surfactant: effect on TNF-alpha secretion and luminol-enhanced chemiluminescence activity by murine macrophages stimulated with group B streptococci.

Group B streptococci (GBS) are important pathogens in neonatal sepsis and pneumonia. GBS stimulate alveolar macrophages to produce inflammatory cytokines and free oxygen radicals, which can damage the lungs. In several studies, use of exogenous surfactant in term babies has improved outcome related to sepsis and respiratory failure. The role(s) of exogenous surfactant in modulating the inflammatory response produced by this microbe was examined. Tumor necrosis factor alpha (TNF-alpha) production and luminol-enhanced chemiluminescence (LCL), a measure of respiratory burst, were investigated. For measuring TNF-alpha release, RAW 264.7 murine macrophages were pre-incubated with bovine surfactant and stimulated with either lipopolysaccharide, live or heat-killed GBS type Ia. LCL was measured after macrophages were pre-incubated with or without surfactant overnight, then stimulated with GBS or phorbol myristate acetate. Lipopolysaccharide and GBS stimulated TNF-alpha secretion from macrophages that was suppressed by exogenous surfactant in a dose-dependent fashion. GBS and phorbol myristate acetate also increased LCL from macrophages, which was significantly suppressed by pre-incubation of macrophages with exogenous surfactant. We conclude that GBS type Ia stimulates TNF-alpha release and LCL from RAW 264.7 cells and that these responses are suppressed by surfactant. Suppression of inflammatory mediators by exogenous surfactant might improve respiratory disease associated with GBS.

Representation of nociceptive stimuli in primary sensory cortex.

Using fMRI, we observed cortical activity associated with nociceptive hot and cold sensations applied to hand and foot that are not spatially restricted to the corresponding regions of the primary somatosensory cortex (SI). Hot (55-57 degrees C) and cold (0-2 degrees C) tactile stimuli were applied separately to the right hand and foot of eight right-handed subjects. Although somatotopic mapping of hand and foot was observed as expected based on the Penfield homunculus, activations associated with hot during both hand and foot stimulation and subsequently, cold, activated regions unique to each thermal modality irrespective of the body part. This distributed system for thermal information is present at both nociceptive and more neutral thermal intensities (i.e. warm and cool sensations) indicating the presence of distributed sensory processing associated with thermal-related sensations in human primary sensorimotor cortex.

Multidrug-resistant typhoid fever.

One hundred children (consecutive) with positive blood culture for Salmonella typhi were studied for clinical profile and complications. The common clinical features were fever (100%), vomiting (58%), abdominal pain (48%), cough (22%) and loose stools (14%) and the Widal test was positive in 75% patients. Eighty per cent of the salmonella isolates were resistant to amoxycillin, chloramphenicol and co-trimoxazole drugs, but all were sensitive to ciprofloxacin and ceftriaxone. Forty patients developed complications: encephalopathy (18), melaena (12), haematemesis (10), epistaxis (4), hepatitis (4), acalculous cholecystitis (4), bowel perforation (3) and nephritis (2). Complications were more frequent in children with multidrug-resistant typhoid. The final antibiotic required to render the children afebrile included ciprofloxacin (80), ceftriaxone, amoxycillin (4), chloramphenicol (4), amoxycillin and gentamicin (4), amoxycillin with chloramphenicol (2), and furazolidone (2). The defervesence time was least with ceftriaxone and greatest with amoxycillin. All the affected children made a complete recovery.

Genotyping serotonin transporter polymorphisms 5-HTTLPR and rs25531 in European- and African-American subjects from the National Institute of Mental Health's Collaborative Center for Genomic Studies.

A number of studies have suggested DNA sequence variability in the serotonin transporter gene (SLC6A4) between European-American (EA) and African-American (AA) populations, which could be clinically important, given the central role SLC6A4 has in serotonin transmission. However, these studies have had relatively small samples, used self-reported measures of race, and have only tested the promoter-linked polymorphism 5-HTTLPR. Here we genotype 5-HTTLPR and rs25531, a neighboring functional polymorphism, in 954 AA and 2622EA subjects from a National Institute of Mental Health repository sample. Genotyping was performed using fragment analysis by capillary electrophoresis. AA, as compared with EA, groups had lower frequencies of the S allele (0.25 vs 0.43) and SS genotype (0.06 vs 0.19) at 5-HTTLPR, and higher rates of the G allele at rs25531 (0.21 vs 0.075). A rare xL variant at 5-HTTLPR was also more common among AAs (0.017 vs 0.008). When the polymorphisms were redefined into a high- and low-transcription haplotypes, the AA group showed significantly fewer low-transcription variants (χ(2)=4.8, P=0.03). No genotypes were associated with major depression, any anxiety disorder, or neuroticism in either EA or AA populations. This is the largest study to show SLC6A4 genotype differences between EA and AA populations, and the first to include rs25531. Lack of associations with clinical outcomes may reflect untested moderating environmental influences.

A comparison between screened NIMH and clinically interviewed control samples on neuroticism and extraversion.

The National Institute of Mental Health (NIMH) has supported the collection of DNA samples on over 4000 subjects for use primarily as controls in psychiatric genetic studies. These subjects, though screened online, were not directly interviewed or assessed on family history. We compared this sample to one that was directly interviewed using structured diagnostic assessments on comparable measures of neuroticism and extraversion. The screened sample completed an online self-report based on the Composite International Diagnostic Instrument Short-Form (CIDI-SF). The interviewed sample was assessed by clinically trained personnel using the Schedule for Affective Disorders and Schizophrenia (SADS-LA-IV) and Family History Screen; final diagnoses were made blind to trait scores by a clinician using the best-estimate procedure. Neuroticism and extraversion were assessed on the NEO five-factor inventory (NEO-FFI) and the revised Eysenck Personality Questionnaire short form (EPQ-R). We found that subjects in the NIMH-screened sample who did not report any psychiatric symptoms on the self-report were indistinguishable from interviewed diagnosis free and family history negative controls on neuroticism and extraversion. Subjects in the screened sample who screened positive for anxiety disorders, however, deviated significantly on these measures both from the screened subjects with no self-reported symptoms, as well as from subjects in the interviewed sample diagnosed with comparable disorders. These findings suggest that control groups generated from the NIMH sample should ideally be restricted to subjects free of any self-reported symptoms, regardless of the disorder being addressed, in order to maximize their reflection of diagnosis-free populations.