Tatja Hirvikoski

Visuo-Spatial Working Memory Span: A Sensitive Measure of Cognitive Deficits in Children With ADHD

Working memory (WM) has been hypothesised to be impaired in attention-deficit/hyperactivity disorder (ADHD). However, there are few studies reported on tests measuring visuo-spatial WM (VSWM) in ADHD. Some of these studies used paradigms including episodic memory, others only used low memory loads. In the present study we used a VSWM test that has not been used previously in ADHD research. The sensitivity of the VSWM test and a choice reaction time (CRT) test was evaluated in a pilot study by comparing them to two commonly used tests in ADHD-research; the Continuous Performance Test (CPT) and a Go/no-go test, in children with and without ADHD. The groups differed significantly in performance on the VSWM test (P<.01) and CRT (P<.05) but not on the CPT (P>.1) or on the Go/no-go test (P>.1). The results from the VSWM and CRT tests were replicated in a larger sample of participants (80 boys; 27 boys with ADHD and 53 controls, mean age 11.4 years). The difference between the groups was significant for both the VSWM test (P<.01) and the CRT test (P<.01). The effect size (ES) of the VSWM test was 1.34. There was a significant age-by-group interaction on the VSWM test, with larger group differences for the older children (P<.01). Our results show that the VSWM test is a sensitive measure of cognitive deficits in ADHD and it supports the hypothesis that deficits in VSWM is a major component of ADHD.

Attention Deficit Hyperactivity Disorder (ADHD) among longer-term prison inmates is a prevalent, persistent and disabling disorder

BackgroundADHD is a common and disabling disorder, with an increased risk for coexisting disorders, substance abuse and delinquency. In the present study, we aimed at exploring ADHD and criminality. We estimated the prevalence of ADHD among longer-term prison inmates, described symptoms and cognitive functioning, and compared findings with ADHD among psychiatric outpatients and healthy controls.MethodsAt Norrtälje Prison, we approached 315 male inmates for screening of childhood ADHD by the Wender Utah Rating Scale (WURS-25) and for present ADHD by the Adult ADHD Self-Report Screener (ASRS-Screener). The response rate was 62%. Further, we assessed 34 inmates for ADHD and coexisting disorders. Finally, we compared findings with 20 adult males with ADHD, assessed at a psychiatric outpatient clinic and 18 healthy controls.ResultsThe estimated prevalence of adult ADHD among longer-term inmates was 40%. Only 2 out of 30 prison inmates confirmed with ADHD had received a diagnosis of ADHD during childhood, despite most needed health services and educational support. All subjects reported lifetime substance use disorder (SUD) where amphetamine was the most common drug. Mood and anxiety disorders were present among half of subjects; autism spectrum disorder (ASD) among one fourth and psychopathy among one tenth. Personality disorders were common; almost all inmates presented conduct disorder (CD) before antisocial personality disorder (APD). Prison inmates reported more ADHD symptoms during both childhood and adulthood, compared with ADHD psychiatric outpatients. Further, analysis of executive functions after controlling for IQ showed both ADHD groups performed poorer than controls on working memory tests. Besides, on a continuous performance test, the ADHD prison group displayed poorer results compared with both other groups.ConclusionsThis study suggested ADHD to be present among 40% of adult male longer-term prison inmates. Further, ADHD and coexisting disorders, such as SUD, ASD, personality disorders, mood- and anxiety disorders, severely affected prison inmates with ADHD. Besides, inmates showed poorer executive functions also when controlling for estimated IQ compared with ADHD among psychiatric outpatients and controls. Our findings imply the need for considering these severities when designing treatment programmes for prison inmates with ADHD.

Reduced ADHD symptoms in adults with ADHD after structured skills training group: results from a randomized controlled trial.

OBJECTIVE Feasibility, acceptability, and efficacy of a Dialectical Behavioral Therapy (DBT) -based method developed in Germany were evaluated in a Swedish outpatient psychiatric context. METHOD Fifty-one adults with ADHD on stable medical treatment or on no medication were randomized to the DBT-based skills training (n=26) or a parallel loosely structured discussion group (n=25). Self-rating scales were administered before randomization and after the treatment. RESULTS Feasibility and participant satisfaction were good in both groups while skills training was perceived as more logical and effective for ADHD-related problems. The analyses of the individuals who completed the treatment and remained stable with regard to medication (n=19 in skills training; n=18 in control group) showed a significant reduction in ADHD symptoms in the skills training group, but not in the control group. No reduction of comorbidity was observed in any of the groups. CONCLUSIONS The treatment was feasible in an outpatient psychiatric context, well tolerated, and significantly reduced ADHD symptoms in on-treatment individuals who remained stable regarding medication status.

Long-term follow-up of prenatally treated children at risk for congenital adrenal hyperplasia : Does dexamethasone cause behavioural problems?

OBJECTIVES To investigate the long-term effects of prenatal treatment of congenital adrenal hyperplasia (CAH) with emphasis on behavioural problems and temperament. DESIGN A population-based long-term follow-up study of Swedish children at risk for virilising CAH, who had received treatment prenatally with dexamethasone (DEX). The questionnaire-based follow-up was performed when the children had reached school age. METHODS Standardised parent-completed questionnaires were used to evaluate adaptive functioning, behavioural/emotional problems and psychopathology, social anxiety and temperament in DEX-exposed school-aged children (n=26) and matched controls (n=35). In addition, the association between parental questionnaires and childrens self-ratings was investigated. RESULTS There were no statistically significant differences between DEX-exposed children and controls in measures of psychopathology, behavioural problems and adaptive functioning. In a questionnaire on temperamental traits, DEX-exposed children were described by their parents as being more sociable than controls (P=0.042). The correlation analysis showed only modest parent-child agreement on social anxiety, i.e. the increased social anxiety in childrens self-ratings was not confirmed by their parents. CONCLUSIONS DEX-treated children showed good overall adjustment. The parent-child agreement with respect to social anxiety was modest, highlighting the importance of multiple information sources and assessment methods. The clinical significance of the observed difference in sociability cannot be determined within the frameworks of this study. Additional studies of larger cohorts are essential to make more decisive conclusions on the safety of the treatment. Until then, it is important that parents are thoroughly informed about the benefits and potential risks and uncertainties of this controversial treatment.

Premature mortality in autism spectrum disorder

BACKGROUND Mortality has been suggested to be increased in autism spectrum disorder (ASD). AIMS To examine both all-cause and cause-specific mortality in ASD, as well as investigate moderating role of gender and intellectual ability. METHOD Odds ratios (ORs) were calculated for a population-based cohort of ASD probands (n = 27,122, diagnosed between 1987 and 2009) compared with gender-, age- and county of residence-matched controls (n = 2,672,185). RESULTS During the observed period, 24,358 (0.91%) individuals in the general population died, whereas the corresponding figure for individuals with ASD was 706 (2.60%; OR = 2.56; 95% CI 2.38-2.76). Cause-specific analyses showed elevated mortality in ASD for almost all analysed diagnostic categories. Mortality and patterns for cause-specific mortality were partly moderated by gender and general intellectual ability. CONCLUSIONS Premature mortality was markedly increased in ASD owing to a multitude of medical conditions.

High self-perceived stress and many stressors, but normal diurnal cortisol rhythm, in adults with ADHD (attention-deficit/hyperactivity disorder).

Attention-deficit/hyperactivity disorder (ADHD) in adults is associated with significant impairment in many life activities and may thus increase the risk of chronic stress in everyday life. We compared adults with a DSM-IV ADHD diagnosis (n=28) with healthy controls (n=28) regarding subjective stress and amounts of stressors in everyday life, diurnal salivary cortisol in the everyday environment and salivary cortisol before and after cognitive stress in a laboratory setting. The association between cortisol concentrations and impulsivity was also investigated. Consistent with assumptions, individuals with ADHD reported significantly more self-perceived stress than controls, and subjective stress correlated with the amount of stressors in everyday life. The two groups were comparable with respect to overall diurnal cortisol levels and rhythm, as well as in pre- and post-stress cortisol concentrations. Post-stress cortisol (but not baseline cortisol) concentration was positively correlated with impulsivity. The group with high post-stress cortisol also reported more symptoms of depression and anxiety, as well as self-perceived stress and stressors in every-day life. The diagnosis of ADHD significantly increased the risk of belonging to the group with high post-stress cortisol levels. The results in this study warrant a focus not only on the primary diagnosis of ADHD, but also calls for a broader assessment of stressors and subjective stress in everyday life, as well as support comprising stress management and coping skills.

Long-term outcome of prenatal treatment of congenital adrenal hyperplasia.

Prenatal treatment of congenital adrenal hyperplasia (CAH) with dexamethasone to minimize the genital virilization of external genitalia of affected girls has been in use since the mid-1980s. The positive effect of reducing virilization is now established. However, experimental data from animal studies and observations on adverse medical events in human newborns have raised concerns about the long-term safety of the treatment. Most animal studies on prenatal treatment with synthetic glucocorticoids have been designed to mimic treatment for lung maturation in preterm infants. The primary focus has been on a possible impact on fetal programming and the development of the metabolic syndrome with insulin resistance, type 2 diabetes, and high blood pressure. Altered reactivity to stress as a function of differences in reactivity of the HPA axis and glucocorticoid receptor function have been assayed. Effects on cognition, especially memory, have been observed. In children at risk for CAH and treated prenatally with dexamethasone, no overall effects on full-scale IQ have been observed, but a negative effect on verbal working memory has been reported. Contradictory effects on social behavior with respect to shyness and inhibition have been discussed. There is an urgent need for in-depth studies of long-term outcome in prenatal treatment of CAH regarding both maternal side effects and possible negative metabolic as well as cognitive and behavioral effects in the growing fetus and the child in her development into adulthood.

Prenatal Dexamethasone Treatment of Children at Risk for Congenital Adrenal Hyperplasia: The Swedish Experience and Standpoint

Congenital adrenal hyperplasia (CAH) refers to rare ( 1:10,000), recessively inherited disorders of adrenal steroidogenesis. 21-Hydroxylase deficiency, the most common form, results in virilization of external genitalia in severely affected female fetuses. Prenatal treatment of CAH with dexamethasone (DEX) has been administered since the mid-1980s and is effective in reducing virilization in CAH-affected girls (1). The treatment has to be initiated early in pregnancy, before prenatal testing is possible. Consequently, seven of eight fetuses (all boys and CAH-unaffected girls) are treated in early pregnancy without any benefit of the treatment per se, until prenatal testing can determine the sex and diagnostic status at the end of the first trimester. CAH-affected girls are treated until term. Prenatal DEX treatment of fetuses at risk for CAH is controversial. Results from animal studies, as well as studies on prenatal glucocorticoid therapy in other contexts, have raised concerns regarding possible negative effects on behavioral and somatic development (2, 3). Adult corticosteroid-exposed rodent offspring are characterized by hypertension (via reduced nephron number); hyperinsulinemia and hyperglycemia (via permanently increased levels of the hepatic enzyme phosphoenolpyruvate carboxylase); fatty liver but not obesity when given a high-fat diet; and hyperactivity of the hypothalamic-pituitaryadrenal axis and altered affective behavior, reminiscent of anxiety, as well as impaired learning and memory functions. In the rhesus monkey, prenatal DEX during the last trimester resulted in offspring with elevated basaland stress-stimulated cortisol at the age of 10 months as well as smaller hippocampal volume. In the African vervet monkey, high-dose DEX exposure (120–200 g/kg) from midgestation until term resulted in offspring with an exaggerated cortisol response to stress already prepubertally, and adult animals exhibited hypertension, impaired glucose tolerance, and hyperinsulinemia (4). A long-term follow-up of individuals treated prenatally with betamethasone due to a risk of preterm birth shows that 30 yr after exposure the individuals exhibit insulin resistance, particularly in women, and 7% of the adults had elevated basal, morning cortisol levels (5). Other authors consider the prenatal treatment of CAH to be safe (1), but the recent Endocrine Society Guidelines state that such treatment should only be done within the frames of ethically approved clinical studies (6). The prenatal treatment of CAH is considered to be safe in the short-term perspective, although there are few longterm follow-up studies. In Sweden, prenatal treatment of CAH has been administered within the frameworks of a clinical study since 1999. The study, which is ongoing, is designed as a prospective, nonrandomized, multicenter trial in several participating European countries, including both follow-up of the mothers and long-term follow-up of the children. In Sweden, 31 cases have been enrolled during the last 10 yr. Hence, it will take several years before the first results from the long-term follow-up assessments will be available. We have also conducted retrospective follow-up studies of mothers and 43 children treated in Sweden and Nor-

Family history of suicide and exposure to interpersonal violence in childhood predict suicide in male suicide attempters

BACKGROUND Family studies, including twin and adoption designs, have shown familial transmission of suicidal behaviors. Early environmental risk factors have an important role in the etiology of suicidal behavior. The aim of the present study was to assess the impact of family history of suicide and childhood trauma on suicide risk and on severity of suicide attempt in suicide attempters. METHODS A total of 181 suicide attempters were included. Family history of suicide was assessed with the Karolinska Suicide History Interview or through patient records. Childhood trauma was assessed with the Karolinska Interpersonal Violence Scale (KIVS) measuring exposure to violence and expressed violent behavior in childhood (between 6 and 14 years of age) and during adult life (15 years or older). Suicide intent was measured with the Freeman scale. RESULTS Male suicide attempters with a positive family history of suicide made more serious and well planned suicide attempts and had a significantly higher suicide risk. In logistic regression, family history of suicide and exposure to interpersonal violence as a child were independent predictors of suicide in male suicide attempters. LIMITATIONS The information about family history of suicide and exposure to interpersonal violence as a child derives from the patients only. In the first part of the inclusion period the information was collected from patient records. CONCLUSIONS The results of this study imply that suicides among those at biological risk might be prevented with the early recognition of environmental risks.

Gender role behaviour in prenatally dexamethasone-treated children at risk for congenital adrenal hyperplasia--a pilot study.

Aim:  To investigate the effects of prenatal dexamethasone (DEX) exposure on gender role behaviour.