Ian M. Goodyer

Clinical and psychosocial predictors of suicide attempts and nonsuicidal self-injury in the Adolescent Depression Antidepressants and Psychotherapy Trial (ADAPT)

OBJECTIVE The authors assessed whether clinical and psychosocial factors in depressed adolescents at baseline predict suicide attempts and nonsuicidal self-injury over 28 weeks of follow-up. METHOD Participants were 164 adolescents with major depressive disorder taking part in the Adolescent Depression Antidepressants and Psychotherapy Trial (ADAPT). Clinical symptoms, family function, quality of current personal friendships, and suicidal and nonsuicidal self-harm were assessed at baseline. Suicidal and nonsuicidal self-harm thoughts and behaviors were assessed during 28 weeks of follow-up. RESULTS High suicidality, nonsuicidal self-injury, and poor family function at entry were significant independent predictors of suicide attempts over the 28 weeks of follow-up. Nonsuicidal self-injury over the follow-up period was independently predicted by nonsuicidal self-injury, hopelessness, anxiety disorder, and being younger and female at entry. CONCLUSIONS Both suicidal and nonsuicidal self-harm persisted in depressed adolescents receiving treatment in the ADAPT study. A history of nonsuicidal self-injury prior to treatment is a clinical marker for subsequent suicide attempts and should be as carefully assessed in depressed youths as current suicidal intent and behavior.

Do Corticosteroids Damage the Brain

Corticosteroids are an essential component of the bodys homeostatic system. In common with other such systems, this implies that corticosteroid levels in blood and, more importantly, in the tissues remain within an optimal range. It also implies that this range may vary according to circumstance. Lack of corticosteroids, such as untreated Addisons disease, can be fatal in humans. In this review, we are principally concerned with excess or disturbed patterns of circulating corticosteroids in the longer or shorter term, and the effects they have on the brain.

Exposure to postnatal depression predicts elevated cortisol in adolescent offspring

BACKGROUND Animal research shows that early adverse experience results in altered glucocorticoid levels in adulthood, either raised basal levels or accentuated responses to stress. If a similar phenomenon operates in humans, this suggests a biological mechanism whereby early adversity might transmit risk for major depression, glucocorticoid elevations being associated with the development of this disorder. METHODS We measured salivary cortisol at 8:00 am and 8:00 pm over 10 days in 13-year-old adolescents who had (n = 48) or had not (n = 39) been exposed to postnatal maternal depression. RESULTS Maternal postnatal depression was associated with higher, more variable morning cortisol in offspring, a pattern previously found to predict major depression. CONCLUSIONS Early adverse experiences might alter later steroid levels in humans. Because maternal depression confers added risk for depression to children, these alterations might provide a link between early events and later psychopathology.

A genomewide scan identifies two novel loci involved in specific language impairment

Approximately 4% of English-speaking children are affected by specific language impairment (SLI), a disorder in the development of language skills despite adequate opportunity and normal intelligence. Several studies have indicated the importance of genetic factors in SLI; a positive family history confers an increased risk of development, and concordance in monozygotic twins consistently exceeds that in dizygotic twins. However, like many behavioral traits, SLI is assumed to be genetically complex, with several loci contributing to the overall risk. We have compiled 98 families drawn from epidemiological and clinical populations, all with probands whose standard language scores fall > or =1.5 SD below the mean for their age. Systematic genomewide quantitative-trait-locus analysis of three language-related measures (i.e., the Clinical Evaluation of Language Fundamentals-Revised [CELF-R] receptive and expressive scales and the nonword repetition [NWR] test) yielded two regions, one on chromosome 16 and one on 19, that both had maximum LOD scores of 3.55. Simulations suggest that, of these two multipoint results, the NWR linkage to chromosome 16q is the most significant, with empirical P values reaching 10(-5), under both Haseman-Elston (HE) analysis (LOD score 3.55; P=.00003) and variance-components (VC) analysis (LOD score 2.57; P=.00008). Single-point analyses provided further support for involvement of this locus, with three markers, under the peak of linkage, yielding LOD scores >1.9. The 19q locus was linked to the CELF-R expressive-language score and exceeds the threshold for suggestive linkage under all types of analysis performed-multipoint HE analysis (LOD score 3.55; empirical P=.00004) and VC (LOD score 2.84; empirical P=.00027) and single-point HE analysis (LOD score 2.49) and VC (LOD score 2.22). Furthermore, both the clinical and epidemiological samples showed independent evidence of linkage on both chromosome 16q and chromosome 19q, indicating that these may represent universally important loci in SLI and, thus, general risk factors for language impairment.

Selective serotonin reuptake inhibitors (SSRIs) and routine specialist care with and without cognitive behaviour therapy in adolescents with major depression: randomised controlled trial

Objective To determine whether a combination of a selective serotonin reuptake inhibitor (SSRIs) and cognitive behaviour therapy (CBT) together with clinical care is more effective in the short term than an SSRI and clinical care alone in adolescents with moderate to severe major depression. Design Pragmatic randomised controlled superiority trial. Setting 6 outpatient clinics in Manchester and Cambridge. Participants 208 adolescents, aged 11-17, with moderate to severe major or probable major depression who had not responded to a brief initial intervention. Adolescents with suicidality, depressive psychosis, or conduct disorder were included. Interventions 103 adolescents received an SSRI and routine care; 105 received an SSRI, routine care, and CBT. The trial lasted 12 weeks, followed by a 16 week maintenance phase. Main outcome measures Change in score on the Health of the Nation outcome scales for children and adolescents (primary outcome) from baseline with 12 weeks as the primary and 28 weeks as the follow-up end point. Secondary measures were change in scores on the mood and feelings questionnaire, the revised childrens depression rating scale, the childrens global assessment scale, and the clinical global impression improvement scale. Results At 12 weeks the treatment effect for the primary outcome was −0.64 (95% confidence interval −2.54 to 1.26, P=0.50). In a longitudinal analysis, there was no difference in effectiveness of treatment for the primary (average treatment effect 0.001, −1.52 to 1.52, P=0.99) or secondary outcome measures. On average there was a decrease in suicidal thoughts and self harm. There was no evidence of a protective effect of cognitive behaviour therapy on suicidal thinking or action. By 28 weeks, 57% were much or very much improved with 20% remaining unimproved. Conclusions For adolescents with moderate to severe major depression there is no evidence that the combination of CBT plus an SSRI in the presence of routine clinical care contributes to an improved outcome by 28 weeks compared with the provision of routine clinical care plus an SSRI alone. Trial registration Current Controlled Trials ISRCNT 83809224.

Adrenal secretion during major depression in 8- to 16-year-olds, I. Altered diurnal rhythms in salivary cortisol and dehydroepiandrosterone (DHEA) at presentation.

The association between basal cortisol, dehydroepiandrosterone (DHEA), its sulphate (DHEAS) and major depression was investigated in 8- to 16-year-olds. Eighty-two subjects with major depression, 25 non-depressed psychiatric cases and 40 community controls were systematically assessed for current mental state and hormone levels at 08.00, 12.00 and 20.00 h, assayed from salivary samples collected over a 48 h period. The average mean of the two time points was compared between the three groups. Evening cortisol hypersecretion and morning DHEA hyposecretion were significantly, and independently, associated with major depression. High evening cortisol (> 0.594 ng/mL) and low morning DHEA (< 0.200 ng/mL) identified subgroups of depressives with different types of adrenal hormone dysregulation. The association between high evening cortisol or low morning DHEA and MDD was not affected by either age or gender.

Maternal Postnatal Depression and the Development of Depression in Offspring Up to 16 Years of Age

OBJECTIVE The aim of this study was to determine the developmental risk pathway to depression by 16 years in offspring of postnatally depressed mothers. METHOD This was a prospective longitudinal study of offspring of postnatally depressed and nondepressed mothers; child and family assessments were made from infancy to 16 years. A total of 702 mothers were screened, and probable cases interviewed. In all, 58 depressed mothers (95% of identified cases) and 42 nondepressed controls were recruited. A total of 93% were assessed through to 16-year follow-up. The main study outcome was offspring lifetime clinical depression (major depression episode and dysthymia) by 16 years, assessed via interview at 8, 13, and 16 years. It was analysed in relation to postnatal depression, repeated measures of child vulnerability (insecure infant attachment and lower childhood resilience), and family adversity. RESULTS Children of index mothers were more likely than controls to experience depression by 16 years (41.5% versus 12.5%; odds ratio = 4.99; 95% confidence interval = 1.68-14.70). Lower childhood resilience predicted adolescent depression, and insecure infant attachment influenced adolescent depression via lower resilience (model R(2) = 31%). Family adversity added further to offspring risk (expanded model R(2) = 43%). CONCLUSIONS Offspring of postnatally depressed mothers are at increased risk for depression by 16 years of age. This may be partially explained by within child vulnerability established in infancy and the early years, and by exposure to family adversity. Routine screening for postnatal depression, and parenting support for postnatally depressed mothers, might reduce offspring developmental risks for clinical depression in childhood and adolescence.

Salivary cortisol and dehydroepiandrosterone in relation to puberty and gender

This study investigates basal levels of cortisol and dehydroepiandrosterone (DHEA), and their relation to gender and pubertal development, in healthy children and adolescents. Salivary cortisol and DHEA levels were examined in 129 normally developing subjects aged eight to 16 years. Subjects provided morning (08:00 h) and evening (20:00 h) saliva samples over four consecutive days. Pubertal stage was assessed using Tanner stage sketches, and subjects were grouped according to their general status of pubertal development (pre-early puberty: Tanner stageII). Results showed that morning salivary cortisol in mid-postpubertal girls was greater than in mid-postpubertal boys, but not pre-early pubertal girls and boys. Mean levels of salivary DHEA were greater in mid-postpubertal boys and girls than in pre-early pubertal boys and girls. Changes in hypothalamic-pituitary-adrenal (HPA) axis function that occur during puberty may have implications for immediate and long-term adolescent health.

Non-suicidal self-injury

Self-injury is a relatively common phenomenon in adolescence. Often there is no suicidal intent; rather, the action is used for one or more reasons that relate to reducing distressing affect, inflicting self-punishment and/or signalling personal distress to important others. Non-suicidal self-injury (NSSI) is both deliberate and contains no desire to die and therefore aetiology is likely to be at least partly different to suicidal behaviour per se. Interestingly, NSSI is associated with subsequent suicide attempts suggesting that these behaviours and their related psychology may lie on the same risk trajectory. NSSI neither appears in DSM-IV or ICD 10 as a disorder nor does it constitute a component of any current anxious or depressive syndrome. This lack of nosological recognition coupled with clear psychopathological importance is to be recognised in the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), with NSSI being classified as a syndrome in its own right. We agree that this is appropriate and is likely to have several positive consequences including: (1) improving communication between professionals and patients; (2) informing treatment and management decisions; (3) increasing research into the nature, course and outcome of NSSI. We agree with the proposed DSM-5 diagnostic criteria, although believe the impairment criterion would be better phrased if it stated that self-injury is associated with, rather than causal for, intense distress.

Adrenal steroid secretion and major depression in 8- to 16-year-olds, III. Influence of cortisol/DHEA ratio at presentation on subsequent rates of disappointing life events and persistent major depression.

BACKGROUND An investigation of the association between diurnal changes in cortisol and DHEA levels, or in the cortisol/DHEA ratio at five different time points at presentation, and the occurrence of undesirable life events (losses, dangers to self and others, disappointments) during follow-up, and the outcome of major depression at 36 weeks were investigated. METHODS Psychosocial and endocrine assessment of a consecutive cohort (N = 68) of 8- to 16-year-old subjects with first episode major depression reassessed 12 months after presentation using a repeat measures design. RESULTS Higher cortisol/DHEA ratios at 20.00 or 24.00 h predicted persistent major depression. Basal levels of either hormone alone or cortisol/DHEA ratios at the other three time points (08.00, 12.00 or 16.00 h) did not. High cortisol/DHEA ratios (i.e. values greater than the 60th percentile) at both evening points (20.00 and 24.00 h) also predicted the occurrence of subsequent disappointing life events but no other category of undesirable event. Both high evening cortisol/DHEA ratio at 20.00 h and one or more severely disappointing life events between presentation and follow-up predicted persistent major depression: 86% of subjects with both of these factors were still depressed at 36 weeks whereas 81% with neither factor were not. CONCLUSIONS The finding that it is depressed subjects with high cortisol/DHEA ratios at presentation who are specifically at risk for subsequent disappointing life events suggests a putative role for these adrenal steroids in abnormal cognitive or emotional processes associated with disturbed interpersonal behaviour.