Childhood correlates and young adult outcomes of trajectories of emotional problems from childhood to adolescence.

BACKGROUND: Emotional problems, especially anxiety, have become increasingly common in recent generations. Few population-based studies have examined trajectories of emotional problems from early childhood to late adolescence or investigated differences in psychiatric and functional outcomes. METHODS: Using the Avon Longitudinal Study of Parents and Children (ALSPAC, n = 8286, 50.4% male), we modeled latent class growth trajectories of emotional problems, using the parent-reported Strength and Difficulties Questionnaire emotional scale (SDQ-E) on seven occasions (4-17 years). Psychiatric outcomes in young adulthood (21-25 years) were major depressive disorder (MDD), generalized anxiety disorder (GAD), and self-harm. Functional outcomes were exam attainment, educational/occupational status, and social relationship quality. RESULTS: We identified four classes of emotional problems: low (67.0%), decreasing (18.4%), increasing (8.9%), and persistent (5.7%) problems. Compared to those in the low class, individuals with decreasing emotional problems were not at elevated risk of any poor adult outcome. Individuals in the increasing and persistent classes had a greater risk of adult MDD (RR: 1.59 95% CI 1.13-2.26 and RR: 2.25 95% CI 1.49-3.41) and self-harm (RR: 2.37 95% CI 1.91-2.94 and RR: 1.87 95% CI 1.41-2.48), and of impairment in functional domains. Childhood sleep difficulties, irritability, conduct and neurodevelopmental problems, and family adversity were associated with a persistent course of emotional problems. CONCLUSIONS: Childhood emotional problems were common, but those whose symptoms improved over time were not at increased risk for adverse adult outcomes. In contrast, individuals with persistent or adolescent-increasing emotional problems had a higher risk of mental ill-health and social impairment in young adulthood which was especially pronounced for those with persistent emotional problems.

Investigating the genetic underpinnings of early-life irritability.

Severe irritability is one of the commonest reasons prompting referral to mental health services. It is frequently seen in neurodevelopmental disorders that manifest early in development, especially attention-deficit/hyperactivity disorder (ADHD). However, irritability can also be conceptualized as a mood problem because of its links with anxiety/depressive disorders; notably DSM-5 currently classifies severe, childhood-onset irritability as a mood disorder. Investigations into the genetic nature of irritability are lacking although twin studies suggest it shares genetic risks with both ADHD and depression. We investigated the genetic underpinnings of irritability using a molecular genetic approach, testing the hypothesis that early irritability (in childhood/adolescence) is associated with genetic risk for ADHD, as indexed by polygenic risk scores (PRS). As a secondary aim we investigated associations between irritability and PRS for major depressive disorder (MDD). Three UK samples were utilized: two longitudinal population-based cohorts with irritability data from childhood (7 years) to adolescence (15-16 years), and one ADHD patient sample (6-18 years). Irritability was defined using parent reports. PRS were derived from large genome-wide association meta-analyses. We observed associations between ADHD PRS and early irritability in our clinical ADHD sample and one of the population samples. This suggests that early irritability traits share genetic risk with ADHD in the general population and are a marker of higher genetic loading in individuals with an ADHD diagnosis. Associations with MDD PRS were not observed. This suggests that early-onset irritability could be conceptualized as a neurodevelopmental difficulty, behaving more like disorders such as ADHD than mood disorders.

Explaining risk for suicidal ideation in adolescent offspring of mothers with depression.

BACKGROUND: It is well-established that offspring of depressed mothers are at increased risk for suicidal ideation. However, pathways involved in the transmission of risk for suicidal ideation from depressed mothers to offspring are poorly understood. The aim of this study was to examine the contribution of potential mediators of this association, including maternal suicide attempt, offspring psychiatric disorder and the parent-child relationship. METHOD: Data were utilized from a population-based birth cohort (ALSPAC). Three distinct classes of maternal depression symptoms across the first 11 years of the child's life had already been identified (minimal, moderate, chronic-severe). Offspring suicidal ideation was assessed at age 16 years. Data were analysed using structural equation modelling. RESULTS: There was evidence for increased risk of suicidal ideation in offspring of mothers with chronic-severe depression symptoms compared to offspring of mothers with minimal symptoms (odds ratio 3.04, 95% confidence interval 2.19-4.21). The majority of this association was explained through maternal suicide attempt and offspring psychiatric disorder. There was also evidence for an independent indirect effect via the parent-child relationship in middle childhood. There was no longer evidence of a direct effect of maternal depression on offspring suicidal ideation after accounting for all three mediators. The pattern of results was similar when examining mechanisms for maternal moderate depression symptoms. CONCLUSIONS: Findings highlight that suicide prevention efforts in offspring of depressed mothers should be particularly targeted at both offspring with a psychiatric disorder and offspring whose mothers have made a suicide attempt. Interventions aimed at improving the parent-child relationship may also be beneficial.

'The risks of playing it safe': a prospective longitudinal study of response to reward in the adolescent offspring of depressed parents.

BACKGROUND: Alterations in reward processing may represent an early vulnerability factor for the development of depressive disorder. Depression in adults is associated with reward hyposensitivity and diminished reward seeking may also be a feature of depression in children and adolescents. We examined the role of reward responding in predicting depressive symptoms, functional impairment and new-onset depressive disorder over time in the adolescent offspring of depressed parents. In addition, we examined group differences in reward responding between currently depressed adolescents, psychiatric and healthy controls, and also cross-sectional associations between reward responding and measures of positive social/environmental functioning. Method We conducted a 1-year longitudinal study of adolescents at familial risk for depression (n = 197; age range 10-18 years). Reward responding and self-reported social/environmental functioning were assessed at baseline. Clinical interviews determined diagnostic status at baseline and at follow-up. Reports of depressive symptoms and functional impairment were also obtained. RESULTS: Low reward seeking predicted depressive symptoms and new-onset depressive disorder at the 1-year follow-up in individuals free from depressive disorder at baseline, independently of baseline depressive symptoms. Reduced reward seeking also predicted functional impairment. Adolescents with current depressive disorder were less reward seeking (i.e. bet less at favourable odds) than adolescents free from psychopathology and those with externalizing disorders. Reward seeking showed positive associations with social and environmental functioning (extra-curricular activities, humour, friendships) and was negatively associated with anhedonia. There were no group differences in impulsivity, decision making or psychomotor slowing. CONCLUSIONS: Reward seeking predicts depression severity and onset in adolescents at elevated risk of depression. Adaptive reward responses may be amenable to change through modification of existing preventive psychological interventions.

Predictors of suicidality across the life span: the Isle of Wight study.

BACKGROUND: Data from a representative community sample were used to explore predictors of lifetime suicidality and to examine associations between distal adolescent and more proximal adult risks. METHOD: Data are from a midlife follow-up of the Isle of Wight study, an epidemiological sample of adolescents assessed in 1968. Ratings of psychiatric symptoms and disorder, relationships and family functioning and adversity were made in adolescence; adult assessments included lifetime psychiatric history and suicidality, neuroticism and retrospective reports of childhood sexual abuse and harsh parenting. RESULTS: A wide range of measures of childhood psychopathology, adverse experiences and interpersonal difficulties were associated with adult suicidality; associations were particularly strong for adolescent irritability, worry and depression. In multivariate analyses, substantial proportions of these effects could be explained by their association with adult psychopathology and neuroticism, but additional effects remained for adolescent irritability and worry. CONCLUSIONS: Factors of importance for long-term suicidality risk are evident in adolescence. These include family and experiential adversities as well as psychopathology. In particular, markers of adolescent worry and irritability appeared both potent risks and ones with additional effects beyond associations with adult disorder and adult neuroticism.

Persistence of literacy problems: spelling in adolescence and at mid-life.

BACKGROUND: Developmental reading problems show strong persistence across the school years; less is known about poor readers' later progress in literacy skills. METHOD: Poor (n = 42) and normally developing readers (n = 86) tested in adolescence (ages 14/15 years) in the Isle of Wight epidemiological studies were re-contacted at mid-life (ages 44/45 years). Participants completed a spelling test, and reported on educational qualifications, perceived adult spelling competence, and problems in day-to-day literacy tasks. RESULTS: Individual differences in spelling were highly persistent across this 30-year follow-up, with correlations between spelling at ages 14 and 44 years of r = .91 (p < .001) for poor readers and r = .89 (p < .001) for normally developing readers. Poor readers' spelling remained markedly impaired at mid-life, with some evidence that they had fallen further behind over the follow-up period. Taking account of adolescent spelling levels, continued exposure to reading and literacy demands in adolescence and early adulthood was independently predictive of adult spelling in both samples; family social background added further to prediction among normally developing readers only. CONCLUSIONS: By adolescence, individual differences in spelling and its related sub-skills are highly stable. Encouraging young people with reading disabilities to maintain their exposure to reading and writing may be advantageous in the longer term.

Bone tissue formation from human embryonic stem cells in vivo.

Although the use of embryonic stem cells in the assisted repair of musculoskeletal tissues holds promise, a direct comparison of this cell source with adult marrow-derived stem cells has not been undertaken. Here we have compared the osteogenic differentiation potential of human embryonic stem cells (hESC) with human adult-derived stem cells in vivo. hESC lines H7, H9, the HEF-1 mesenchymal-like, telomerized H1 derivative, the human embryonic kidney epithelial cell line HEK293 (negative control), and adult human mesenchymal stem cells (hMSC) were either used untreated or treated with osteogenic factors for 4 days prior to injection into diffusion chambers and implantation into nude mice. After 11 weeks in vivo chambers were removed, frozen, and analyzed for evidence of bone, cartilage, and adipose tissue formation. All hESCs, when pretreated with osteogenic (OS) factors gave rise exclusively to bone in the chambers. In contrast, untreated hESCs (H9) formed both bone and cartilage in vivo. Untreated hMSCs did not give rise to bone, cartilage, or adipose tissue in vivo, while pretreatment with OS factors engendered both bone and adipose tissue. These data demonstrate that hESCs exposed to OS factors in vitro undergo directed differentiation toward the osteogenic lineage in vivo in a similar fashion to that produced by hMSCs. These findings support the potential future use of hESC-derived cells in regenerative medicine applications.

Selective estrogen receptor modulator inhibits osteocyte apoptosis during abrupt estrogen withdrawal: implications for bone quality maintenance.

Estrogens exert positive effects on the quantity and quality of bone, including the maintenance of osteocytes through the inhibition of their apoptosis. Ideally, selective estrogen receptor modulators (SERMs) confer all of the positive bone-associated effects of estrogens without any adverse effects. In a similar way to estrogen, the raloxifene analog LY 117018 has been shown to prevent bone loss in ovariectomized (OVX) rats. In this study, we investigated whether the osteocyte-sparing effect of 17beta-estradiol can be mimicked by the SERM LY 117018 in a rat model of OVX. Twenty-four juvenile female rats were divided into four treatment groups: sham-operated (SHAM), OVX, OVX + 17beta-estradiol (OVX+E(2)), and OVX + LY 117018 (OVX+SERM). At 7 or 14 days following the start of treatment, the radius and ulna were removed. The percentage of apoptotic osteocytes, determined using an in situ nick-translation method, was increased (2.5-fold at 7 days and sixfold at 14 days) in the OVX group compared with SHAM in both the radius and ulna. Treatment of OVX animals with either 17beta-estradiol at a dose rate of 0.125 mg/kg/day or LY 117018 at a dose rate of 3 mg/kg/day prevented these increases in osteocyte apoptosis similarly. These observations demonstrate that LY 117018 exerts a powerful inhibitory effect upon osteocyte apoptosis directly after estrogen loss, in a similar way to the known effect of 17beta-estradiol replacement. These results point to the potential benefits of SERMs on both the quantity and quality of bone in E(2)-depleted rats.

Featural and configurational processes in the recognition of faces of different familiarity.

Previous research suggests that face recognition may involve both configurational and piecemeal (featural) processing. To explore the relationship between these processing modes, we examined the patterns of recognition impairment produced by blurring, inversion, and scrambling, both singly and in various combinations. Two tasks were used: recognition of unfamiliar faces (seen once before) and recognition of highly familiar faces (celebrities). The results provide further support for a configurational-featural distinction. Recognition performance remained well above chance if faces were blurred, scrambled, inverted, or simultaneously inverted and scrambled: each of these manipulations disrupts either configurational or piecemeal processing, leaving the other mode available as a route to recognition. However, blurred/scrambled and blurred/inverted faces were recognised at or near chance levels, presumably because both configurational processing and featural processing were disrupted. Similar patterns of effects were found for both familiar and unfamiliar faces, suggesting that the relationship between configurational and featural processing is qualitatively similar in both cases.

Validity of the Malaise Inventory in general population samples.

BACKGROUND: The Malaise Inventory is a commonly used self-completion scale for assessing psychiatric morbidity. There is some evidence that it may represent two separate psychological and somatic subscales rather than a single underlying factor of distress. This paper provides further information on the factor structure of the Inventory and on the reliability and validity of the total scale and two sub-scales. METHODS: Two general population samples completed the full Inventory: over 11,000 subjects from the National Child Development Study at ages 23 and 33, and 544 mothers of adolescents included in the Isle of Wight epidemiological surveys. RESULTS: The internal consistency of the full 24-item scale and the 15-item psychological subscale were found to be acceptable, but the eight-item somatic sub-scale was less reliable. Factor analysis of all 24 items identified a first main general factor and a second more purely psychological factor. Receiver operating characteristic (ROC) analysis indicated that the validity of the scale held for men and women separately and for different socio-economic groups, by reference to external criteria covering current or recent psychiatric morbidity and service use, and that the psychological sub-scale had no greater validity than the full scale. CONCLUSIONS: This study did not support the separate scoring of a somatic sub-scale of the Malaise Inventory. Use of the 15-item psychological sub-scale can be justified on the grounds of reduced time and cost for completion, with little loss of reliability or validity, but this approach would not significantly enhance the properties of the Inventory by comparison with the full 24-item scale. Inclusion of somatic items may be more problematic when the full scale is used to compare particular sub-populations with different propensities for physical morbidity, such as different age groups, and in these circumstances it would be a sensible precaution to utilise the 15-item psychological sub-scale.

Mild mental retardation: psychosocial functioning in adulthood.

BACKGROUND: Evidence on the adult adaptation of individuals with mild mental retardation (MMR) is sparse, and knowledge of the factors associated with more and less successful functioning in MMR samples yet more limited. METHOD: Prospective data from the National Child Development Study were used to examine social circumstances and psychosocial functioning in adulthood in individuals with MMR and in a non-retarded comparison group. RESULTS: For many individuals with MMR, living circumstances and social conditions in adulthood were poor and potential stressors high. Self-reports of psychological distress in adulthood were markedly elevated, but relative rates of psychiatric service use fell between childhood and adulthood, as reflected in attributable risks. Childhood family and social disadvantage accounted for some 20-30% of variations between MMR and non-retarded samples on a range of adult outcomes. Early social adversity also played a significant role in contributing to variations in functioning within the MMR sample. CONCLUSIONS: MMR appears to be associated with substantial continuing impairment for many individuals.

School achievement and adult qualifications among adoptees: a longitudinal study.

Data from the National Child Development study (NCDS) were used to examine predictors of attainment among adoptees, nonadopted children from similar birth circumstances, and other members of this national birth cohort. Adoptees performed more positively than nonadopted children from similar birth circumstances on childhood tests of reading, mathematics, and general ability, and retained this advantage in school-leaving and later adult qualifications. In addition to family SES and material circumstances, measures of the educational environment of the home and of parental interest in education emerged as central predictors of these variations. Further analyses suggested possible differences in the mode of operation of these variables between boys and girls, and at different stages of young people's educational careers.

Infant adoption: psychosocial outcomes in adulthood.

Adoption studies are able to provide important insights into the impact of changed rearing environments for children's development. A number of studies reporting on the childhood adjustment of adoptees have found an increased risk for disruptive behaviour problems when compared with children brought up in intact families. The long-term implications of adoption for psychosocial adjustment in adult life are less clear. We have used data from the National Child Development Study (NCDS) to examine the psychosocial functioning over a number of life-domains of an unselected sample of adoptees, non-adopted children from similar birth circumstances, and other members of the cohort. Adopted women showed very positive adult adjustment across all the domains examined in this study, whilst our findings suggest some difficulty in two specific domains (employment and social support) for adopted men. Implications of the findings are discussed.

Maternal serum free alpha- and free beta-human chorionic gonadotrophin in pregnancies with insulin-dependent diabetes mellitus: implications for screening for Down's syndrome.

A study was performed to investigate the concentrations of the alpha and beta free sub-units of human chorionic gonadotrophin (free alpha-hCG and free beta-hCG) in maternal serum between 15 and 22 weeks of pregnancy in 126 pregnancies among 92 women with insulin-dependent diabetes mellitus (IDDM). Each IDDM pregnancy was matched with two control singleton pregnancies for gestational age (same completed week) and duration of sample storage (same calendar quarter). The median free alpha-hCG level in the IDDM pregnancies was 0.86 multiples of the median (MOM) for pregnancies without IDDM at the same gestational age (P < 0.002) (95 per cent confidence interval 0.80-0.94). The corresponding free beta-hCG level was 0.96 MOM (95 per cent confidence interval 0.85-1.09). These results enable free alpha-hCG values to be adjusted so that antenatal screening for Down's syndrome can be performed using this marker in IDDM pregnancies as well as in non-diabetic pregnancies.