Association of adolescent depression with subsequent prescriptions of anti-infectives and anti-inflammatories in adulthood: A longitudinal cohort study.

New insights into how depression is linked to physical health throughout the lifespan could potentially inform clinical decision making. The aim of this study was to explore the association of adolescent depression with subsequent prescriptions of anti-infectives and anti-inflammatories in adulthood. The study was based on the Uppsala Longitudinal Adolescent Depression Study (ULADS), a Swedish prospective cohort study initiated in 1991. Depressed (n = 321) and non-depressed (n = 218) adolescents were followed prospectively using patient registries. The associations of adolescent depression (age 16-17 years) with subsequent prescription of anti-infectives and anti-inflammatories (age 30-40 years), were analysed using generalized linear models. Sub-analyses explored the impact of diagnostic characteristics in adolescence and reception of anti-depressants prescriptions in adulthood. The results suggest that females with persistent depressive disorder in adolescence have a higher rate of future prescriptions than non-depressed peers, with adjusted incidence rate ratio of 1.42 (1.06 to 1.92) for anti-infectives and 1.72 (1.10 to 2.70) for anti-inflammatories. These associations were mainly driven by those who were also prescribed antidepressants during the same period. Associations were less robust for females with episodic or subsyndromal depression in adolescence and for males. These findings emphasize the importance of integrated mental health services at the primary healthcare level.

Adolescent depression, early psychiatric comorbidities, and adulthood welfare burden: a 25-year longitudinal cohort study.

PURPOSE: Depression at all ages is recognized as a global public health concern, but less is known about the welfare burden following early-life depression. This study aimed to (1) estimate the magnitude of associations between depression in adolescence and social transfer payments in adulthood; and (2) address the impact of major comorbid psychopathology on these associations. METHODS: This is a longitudinal cohort study of 539 participants assessed at age 16-17 using structured diagnostic interviews. An ongoing 25-year follow-up linked the cohort (n = 321 depressed; n = 218 nondepressed) to nationwide population-based registries. Outcomes included consecutive annual data on social transfer payments due to unemployment, work disability, and public assistance, spanning from age 18 to 40. Parameter estimations used the generalized estimating equations approach. RESULTS: Adolescent depression was associated with all forms of social transfer payments. The estimated overall payment per person and year was 938 USD (95% CI 551-1326) over and above the amount received by nondepressed controls. Persistent depressive disorder was associated with higher recipiency across all outcomes, whereas the pattern of findings was less clear for subthreshold and episodic major depression. Moreover, depressed adolescents presenting with comorbid anxiety and disruptive behavior disorders evidenced particularly high recipiency, exceeding the nondepressed controls with an estimated 1753 USD (95% CI 887-2620). CONCLUSION: Adolescent depression is associated with considerable public expenditures across early-to-middle adulthood, especially for those exposed to chronic/persistent depression and psychiatric comorbidities. This finding suggests that the clinical heterogeneity of early-life depression needs to be considered from a longer-term societal perspective.

Asylum-seeking children with resignation syndrome: catatonia or traumatic withdrawal syndrome?

In the beginning of the 2000s, an increasing number of asylum-seeking children in Sweden fell into a stuporous condition. In the present study, we report 46 consecutive children with the most severe form of this illness where the children were unable to give any response at all, did not react to pain, cold or touching, could not be supported to sit or stand on their feet, could not do anything when requested, and in most cases had enuresis/encopresis. A minority of the children came from war zones (n = 8, 17.4%). A majority belonged to an ethnic or religious minority (n = 32, 69.6%) in their homeland and almost all were persecuted (n = 43, 93.5%). All had either experienced violence themselves or had witnessed or heard about violence against close family members. The age of onset of the first symptom of illness for boys was 11.2 years [CI 9.6-12.8], for girls 11.8 yrs.[CI 10.4-13.2], and the age for falling into stupor for boys was 12.9 years [CI 11.6-14.1] years and was the same for girls, 12.9 years [CI 11.6-14.2] years. Girls tended to have depression before entering the stuporous condition, while the boys tended to have PTSD first (Chi-square = 3.73, p = 0.054). A majority of the children had one (n = 13, 28.3%) or both parents (n = 14, 30.4%) suffering from mental or severe physical disorder. It is discussed whether the presented condition is a separate entity or if the syndrome should be regarded as a variant of catatonia, and whether benzodiazepines should be tried.

Depressive disorders in adolescence, recurrence in early adulthood, and healthcare usage in mid-adulthood: A longitudinal cost-of-illness study.

BACKGROUND: Depression in adolescence is associated with increased healthcare consumption in adulthood, but prior research has not recognized the heterogeneity of depressive disorders. This paper investigated the additional healthcare usage and related costs in mid-adulthood for individuals with adolescent depression, and examined the mediating role of subsequent depression in early adulthood. METHODS: This study was based on the Uppsala Longitudinal Adolescent Depression Study, initiated in Sweden in the early 1990s. Depressive disorders were assessed in adolescence (age 16-17) and early adulthood (age 19-30). Healthcare usage and related costs in mid-adulthood (age 31-40) were estimated using nationwide population-based registries. Participants with specific subtypes of adolescent depression (n = 306) were compared with matched non-depressed peers (n = 213). RESULTS: Women with persistent depressive disorder (PDD) in adolescence utilized significantly more healthcare resources in mid-adulthood. The association was not limited to psychiatric care, and remained after adjustment for individual and parental characteristics. The total additional annual cost for a single age group of females with a history of PDD at a population level was estimated at 3.10 million USD. Depression recurrence in early adulthood mediated the added costs for psychiatric care, but not for somatic care. LIMITATIONS: Primary health care data were not available, presumably resulting in an underestimation of the true healthcare consumption. Estimates for males had limited precision due to a relatively small male proportion. CONCLUSIONS: On a population level, the additional healthcare costs incurred in mid-adulthood in females with a history of adolescent PDD are considerable. Early treatment and prevention should be prioritized.

Uppsala Longitudinal Adolescent Depression Study (ULADS).

PURPOSE: To present the Uppsala Longitudinal Adolescent Depression Study, initiated in Uppsala, Sweden, in the early 1990s. The initial aim of this epidemiological investigation was to study the prevalence, characteristics and correlates of adolescent depression, and has subsequently expanded to include a broad range of social, economic and health-related long-term outcomes and cost-of-illness analyses. PARTICIPANTS: The source population was first-year students (aged 16-17) in upper-secondary schools in Uppsala during 1991-1992, of which 2300 (93%) were screened for depression. Adolescents with positive screening and sex/age-matched peers were invited to a comprehensive assessment. A total of 631 adolescents (78% females) completed this assessment, and 409 subsequently completed a 15-year follow-up assessment. At both occasions, extensive information was collected on mental disorders, personality and psychosocial situation. Detailed social, economic and health-related data from 1993 onwards have recently been obtained from the Swedish national registries for 576 of the original participants and an age-matched reference population (N≥200 000). FINDINGS TO DATE: The adolescent lifetime prevalence of a major depressive episode was estimated to be 11.4%. Recurrence in young adulthood was reported by the majority, with a particularly poor prognosis for those with a persistent depressive disorder or multiple somatic symptoms. Adolescent depression was also associated with an increased risk of other adversities in adulthood, including additional mental health conditions, low educational attainment and problems related to intimate relationships. FUTURE PLANS: Longitudinal studies of adolescent depression are rare and must be responsibly managed and utilised. We therefore intend to follow the cohort continuously by means of registries. Currently, the participants are approaching mid-adulthood. At this stage, we are focusing on the overall long-term burden of adolescent depression. For this purpose, the research group has incorporated expertise in health economics. We would also welcome extended collaboration with researchers managing similar datasets.

Early risk factors for adult bipolar disorder in adolescents with mood disorders: a 15-year follow-up of a community sample.

BACKGROUND: We aimed to outline the early risk factors for adult bipolar disorder (BPD) in adolescents with mood disorders. METHODS: Adolescents (16-17 years old) with mood disorders (n = 287; 90 participants with hypomania spectrum episodes and 197 with major depressive disorder [MDD]) were identified from a community sample. Fifteen years later (at 30-33 years of age), mood episodes were assessed (n = 194). The risk of developing BPD (n = 22), compared with MDD (n = 104) or no mood episodes in adulthood (n = 68), was estimated via logistic regression. Adolescent mood symptoms, non-mood disorders, and family characteristics were assessed as potential risk factors. RESULTS: Among the adolescents with mood disorders, a family history of BPD was the strongest predictor of developing BPD compared with having no mood episodes in adulthood (OR = 5.94; 95% CI = 1.11-31.73), whereas disruptive disorders significantly increased the risk of developing BPD compared with developing MDD (OR = 2.94; CI = 1.06-8.12). The risk that adolescents with MDD would develop adult BPD, versus having no mood episodes in adulthood, was elevated among those with an early disruptive disorder (OR = 3.62; CI = 1.09-12.07) or multiple somatic symptoms (OR = 6.60; CI = 1.70-25.67). Only disruptive disorders significantly predicted adult BPD among adolescents with MDD versus continued MDD in adulthood (OR = 3.59; CI = 1.17-10.97). Only a few adolescents with hypomania spectrum episodes continued to have BPD as adults, and anxiety disorders appeared to increase this risk. CONCLUSIONS: Although most of the identified potential risk factors are likely general predictors of continued mood disorders, disruptive disorders emerged as specific predictors of developing adult BPD among adolescents with MDD.

Hypomania spectrum disorder in adolescence: a 15-year follow-up of non-mood morbidity in adulthood.

BACKGROUND: We investigated whether adolescents with hypomania spectrum episodes have an excess risk of mental and physical morbidity in adulthood, as compared with adolescents exclusively reporting major depressive disorder (MDD) and controls without a history of adolescent mood disorders. METHODS: A community sample of adolescents (N = 2 300) in the town of Uppsala, Sweden, was screened for depressive symptoms. Both participants with positive screening and matched controls (in total 631) were diagnostically interviewed. Ninety participants reported hypomania spectrum episodes (40 full-syndromal, 18 with brief episode, and 32 subsyndromal), while another 197 fulfilled the criteria for MDD without a history of a hypomania spectrum episode. A follow up after 15 years included a blinded diagnostic interview, a self-assessment of personality disorders, and national register data on prescription drugs and health services use. The participation rate at the follow-up interview was 71% (64/90) for the hypomania spectrum group, and 65.9% (130/197) for the MDD group. Multiple imputation was used to handle missing data. RESULTS: The outcomes of the hypomania spectrum group and the MDD group were similar regarding subsequent non-mood Axis I disorders in adulthood (present in 53 vs. 57%). A personality disorder was reported by 29% of the hypomania spectrum group and by 20% of the MDD group, but a statistically significant difference was reached only for obsessive-compulsive personality disorder (24 vs. 14%). In both groups, the risk of Axis I disorders and personality disorders in adulthood correlated with continuation of mood disorder. Prescription drugs and health service use in adulthood was similar in the two groups. Compared with adolescents without mood disorders, both groups had a higher subsequent risk of psychiatric morbidity, used more mental health care, and received more psychotropic drugs. CONCLUSIONS: Although adolescents with hypomania spectrum episodes and adolescents with MDD do not differ substantially in health outcomes, both groups are at increased risk for subsequent mental health problems. Thus, it is important to identify and treat children and adolescents with mood disorders, and carefully follow the continuing course.

Pharmacological treatment and demographic characteristics of pediatric patients with Attention Deficit Hyperactivity Disorder, Sweden.

The aim of this study was to describe the pediatric population with ADHD and their pharmacological treatment. Using the Swedish National Patient Register and the Prescribed Drug Register we identified individuals below 19 years of age who were diagnosed or medically treated for ADHD for the first time 2006-2007. The unique patient identifiers were used to link information from the two registers to describe demographic characteristics, hospital care and drug treatments. Logistic regression model estimated the association between age, sex, frequency of hospitalization, diagnosis or treatment for other mental disorders and risk of gap in the treatment. Totally the study included 7931 patients of whom 74% were males. The mean age at first diagnosis was 12 years. Some 84% were medically treated for ADHD and approximately 90% received methylphenidate as the first substance. Combination therapy was rare and the most common combination was methylphenidate and atomoxetine. More than 55% of the patients, which could be followed up for two years after start of treatment, had at least one treatment gap of six months. Older age at diagnosis, lower number of hospitalizations and comorbidity with other mental disorders increased risks of gaps in medication. Approximately one fifth of the patients recorded in the National Patient Register as diagnosed with ADHD did not receive pharmacological treatment. Medication adherence seems to be low, when measured as gaps in treatment.

Prognostic significance of functional somatic symptoms in adolescence: a 15-year community-based follow-up study of adolescents with depression compared with healthy peers.

BACKGROUND: There is a lack of population-based long-term longitudinal research on mental health status and functional physical/somatic symptoms. Little is known about the long-term mental health outcomes associated with somatic symptoms or the temporal relationship between depression and such symptoms. This 15-year study followed up adolescents with depression and matched controls, screened from a population-based sample, who reported different numbers of somatic symptoms. METHODS: The total population of 16-17-year-olds in Uppsala, Sweden, was screened for depression in 1991-1993. Adolescents who screened positive and an equal number of healthy controls took part in a semi-structured diagnostic interview. In addition, 21 different self-rated somatic symptoms were assessed. Sixty-four percent of those adolescents participated in a follow-up structured interview 15 years later. RESULTS: Somatic symptoms in adolescence predicted depression and other adult mental disorders regardless of the presence of adolescent depression. In adolescents with depression, the number of functional somatic symptoms predicted, in a dose response relationship, suicidal behavior, bipolar episodes, and psychotic episodes as well as chronic and recurrent depression. Contrary to expectations, the somatic symptoms of abdominal pain and perspiration without exertion better predicted depression than all DSM-IV depressive symptoms. Abdominal pain persisted as an independent strong predictor of depression and anxiety, even after controlling for other important confounders. CONCLUSIONS: Somatic symptoms in adolescence can predict severe adult mental health disorders. The number of somatic symptoms concurrent with adolescent depression is, in a stepwise manner, linked to suicidal attempts, bipolar disorders, psychotic disorders, and recurrent and chronic depression. These findings can be useful in developing treatment guidelines for patients with somatic symptoms.

School performance and hospital admission due to unipolar depression: a three-generational study of social causation and social selection.

PURPOSE: Both "social causation" and "social selection" offer plausible explanations for an association between education and mental health. We aimed to explore these processes in unipolar depression, with a specific focus on school performance and family tradition of education. METHOD: Grandchildren (N = 28,089, 49% female, aged 13-47 years in 2002) of a cohort born in Uppsala, Sweden, in 1915-1929 were studied in national registers. We obtained data on final grade point average (GPA) in compulsory school, hospitalizations for unipolar depression, grandparental/parental education and other parental social characteristics. Hospitalization in adolescence and adulthood were studied separately, as were hospitalization for depression with or without a lifetime externalizing disorder. RESULTS: Low compulsory school GPA (1-2 SD or >2 SD below average vs. average GPA) was associated with increased rate of adolescent hospitalization for unipolar depression, both with externalizing comorbidity [hazard ratio (HR) point estimates of 66-80] and without (HR point estimates of 4-6). By contrast, low GPA was only associated with first-time hospitalization in adulthood for the subgroup with externalizing comorbidity (HR point estimates of 4-6). These associations were largely independent of family education and social characteristics. Overall, low parental/grandparental education was not related to increased rates of hospitalization. CONCLUSION: The association between school performance and hospitalization for depression depended on adolescent hospitalization or externalizing comorbidity, suggesting that disorders with an early onset are decisive. Contrary to the social patterning of many health outcomes, low grandparental/parental education did not appear to increase the rate of hospitalization for unipolar depression in the offspring.

Drug prescriptions of adults with adolescent depression in a community sample.

PURPOSE: The prescription drugs have, to our knowledge, not been much studied in epidemiological samples with long-term follow-up. Accordingly, our purpose was to analyze the use of prescription drugs in adults with adolescent depression. METHODS: A population-based cohort of adolescents (n = 2465) was screened for the presence of depressive symptoms and diagnosed according to a structured interview. Totally, 362 individuals were identified as depressed and compared with 250 non-depressed controls. The prescription drugs were evaluated at the age of 29-31 years from a register kept by the National Health and Welfare Board. RESULTS: The formerly depressed females received significantly more prescription drugs, such as antidepressants, antiepileptics, antibacterials, antimycotics, and antihistamines for systemic use as well as other drugs, compared with controls (15.6 ± 27.4 vs 8.2 ± 7.4 recipes, p < 0.001). Formerly depressed males did not differ from controls regarding prescription drugs. CONCLUSIONS: The females but not males with adolescent depression subsequently received more prescription drugs than non-depressed peers. Depressed female adolescents received more psychotropic and non-psychotropic drugs later in life compared to the non-depressed. This might be as a result of physical illnesses, different treatment-seeking behaviors, or somatizing reactions.

Mortality of eating disorders: a follow-up study of treatment in a specialist unit 1974-2000.

OBJECTIVE: To study excess mortality, causes of death, and co-morbidity in patients with eating disorder (ED), treated in a Swedish specialist facility. METHOD: A retrospective cohort study of 201 patients with ED followed from 1974 to year 2001 in the Swedish Causes of Death Register (SCODR). Standardized mortality ratio (SMR) was calculated with respect to the Swedish population, by gender, age, and calendar time. RESULTS: In the complete follow-up of 201 patients, 23 had died. At a mean follow-up of 14.3 years the overall SMR was 10. Patients with body mass index (BMI) over 11.5 had an average SMR of about 7 and for those with BMI lower than 11.5 had SMR above 30. Six patients died from AN/starvation, nine due to suicide, and eight from other causes. DISCUSSION: SMR in anorexia nervosa (AN) is high but not in bulimia nervosa. A risk stratification of AN, based on BMI is suggested.

Somatic symptoms as a marker for severity in adolescent depression.

AIM: This study aims to investigate the prevalence of somatic symptoms in depressed adolescents and in their healthy peers. A second aim is to investigate the correlation, in the depressed adolescents, between the number of somatic symptoms and severe concurrent symptoms, signs and life events. METHODS: The total population of 16-17 year olds - in the city of Uppsala - was screened for depression and then interviewed using a structured interview questionnaire. Depressed subjects and matched controls were identified. A total of 177 pairs were used for pair-wise analyses of somatic symptoms. Severe symptoms, signs and life events were selected for analysing their relation to depression with somatic symptoms. RESULTS: The adolescents with depressive disorders experienced considerably more somatic symptoms than their healthy controls. The duration and depth of the depression correlated with the number of somatic symptoms. There was a strong correlation between depression with many somatic symptoms and suicidal plans/thoughts, suicidal attempts, disruptive behaviour, as well as multiple stressful relationships. CONCLUSION: This study demonstrates that somatic symptoms are common in adolescent depression. Multiple somatic symptoms within depression imply a higher severity in terms of duration, depth and psychiatric comorbidity. The strong correlation with suicidal plans, suicidal attempts and disruptive behaviour is concerning.

Long-term follow-up of adolescent depression. A population-based study.

Adolescent depression is common. Earlier studies indicate that relapses and recurrences are common. But many questions are still unanswered. The aim of the present study has been to follow subjects with adolescent depressions, identified in a population-based study, over a 15-year period. Subjects with adolescent depression (n = 362) and a comparison group (n = 250) were followed in the National Swedish registers. The formerly depressed females had significantly more out-patient visits, and a significantly higher proportion (78.4% versus 69.6%) had at least one out-patient visit. Among the males, no significant differences were found as concerns out-patient visits. The formerly depressed females had significantly more in-patient stays (3.6 versus 2.4) and a significantly higher total number of in-patient days (27.4 versus 10.1). A significantly higher proportion had in-patient days due to mental disorders (9.5% versus 4.6%), in particular anxiety disorders (4.9% versus 1.0%). As concerns the males, a significantly higher proportion had in-patient days due to mental disorders (16.5% versus 1.8%), in particular alcohol and drug abuse (7.6% versus 0%). Among the formerly depressed females there were no significant differences against the comparison group as concerns the proportion of being a mother, number of children per woman, or age at first child. However, a significantly higher proportion of the formerly depressed females had had different, usually mild, disorders related to pregnancy (8.6% versus 0.6%). The children of the women with adolescent depressions were not affected.

Thicker carotid intima layer, thinner media layer and higher intima/media ratio in women with recurrent depressive disorders: A pilot study using non-invasive high frequency ultrasound.

OBJECTIVES: Growing evidence indicates that depression is an important risk factor for coronary heart disease. Thus, the aim of the present study has been to investigate if young women with adolescent onset and recurrent depressive disorders have signs of carotid intima and media changes already at the age of 30. METHODS: Fifteen subjects with adolescent onset recurrent depressive disorders, mean age 31.5 years, were compared to 20 healthy women with a mean age of 39.6 years. The thickness of carotid artery intima and media was assessed, using non-invasive high-frequency ultrasound (25MHz). RESULTS: The subjects with recurrent depressive disorders had significantly thicker carotid intima, significantly thinner carotid media and significantly higher intima/media ratio despite the fact that they were about 10 years younger than the healthy women. Hypertension, obesity or smoking could not explain the results. CONCLUSION: Already at the age of 30, subjects with recurrent depressive disorders with adolescent onset do have early signs of carotid intima and media changes, indicating a less healthy artery wall, despite otherwise no clinical signs of cardiovascular disease.

Central stimulants in the treatment of attention-deficit hyperactivity disorder (ADHD) in children and adolescents. A naturalistic study of the prescription in Sweden, 1977-2007.

BACKGROUND: An increased prescription of central stimulants (CS) for treatment of attention-deficit hyperactivity disorder (ADHD) in children and adolescents has been reported in Sweden. AIMS: To follow-up the treatment with CS as concerns total as well as regional differences in prescription rate. Efficacy and side-effects reported and gender differences in prescription over time also have been summarized. METHODS: Data from the Swedish Medical Products Agency (MPA) of individual licences, annual reports about patients on individual or clinic licences from the MPA and sales statistics from the National Pharmacy (Apoteket AB) have been used. RESULTS: The number of new licences and prescriptions increased dramatically from 1992 to 2007 and a change of preparations was seen. Great differences (fivefold) between the 21 counties of Sweden were noticed. In the follow-up reports to the MPA, a good/moderate treatment effect was reported in 92% and adverse effects were reported in 4% leading to discontinuation of medication in 46% of them. Abuse/misuse of the preparation was suspected in 0.2% of the reports. A tendency of a reduction of the proportion of boys to girls treated through individual licences has been seen. CONCLUSIONS: The study, although observational, supports good efficacy, limited adverse effects and a low degree of misuse in clinical use of CS for children and adolescents with ADHD.

Traumatic experiences and post-traumatic stress disorder in Kurdistanian children and their parents in homeland and exile: an epidemiological approach.

The prevalence and correlates of post-traumatic stress disorder (PTSD) were assessed in random samples of school-aged Kurdistanian children and their parents in homeland and exile. Of the 376 eligible children at the two sites, 312 children and their parents (293 mothers and 248 fathers) completed the Harvard-Uppsala Trauma Questionnaire and Posttraumatic Stress Symptom interviews for children, and Harvard Trauma Questionnaire for parents. Unlike their children, fathers showed significantly higher PTSD frequencies in exile than in the homeland. The fathers' PTSD negatively correlated with the living standard and fathers' education, while child PTSD mostly correlated with maternal education and living in exile. Living in exile seems to have a negative impact on fathers' post-traumatic reactions, despite its positive influence on children. High drop-outs in exile limit the conclusions.

Massage decreases aggression in preschool children: a long-term study.

AIM: To evaluate the effects of massage in 4- to 5-year-old children with aggression and deviant behaviour at day-care centres. METHOD: The children received daily massage in preschool at the midday rest (n = 60). The controls were listening to a story (n = 50). The Child Behaviour Checklist (CBCL) was used to rate the children's behaviour by parents and staff before the treatment started, and after 3 and 6 months. A long-term evaluation was also carried out. It included all massaged children still in daycare after 12 months (n = 34). RESULTS: Children with high scores of behaviour problems, receiving massage and/or extra attention showed significant decrease in aggression scores after 3 months, but after 6 months significantly lowered scores were only found in massage-treated deviant children. Parents of the children receiving massage rated a significant decrease of somatic problems of their children. Staff rated that the massaged children's social problems decreased, compared to the control children. Attention problems tended to decrease, especially at home. A continuous decrease in aggressive behaviour and somatic problems over a 12-month period was observed in the children receiving massage. CONCLUSION: Daily touching by massage lasting for 5-10 min could be an easy and inexpensive way to decrease aggression among preschool children.