Long-term medication for ADHD (LMA) trial: 2-year prospective observational study in children and adolescents. Core symptoms, daily functioning, and comorbidity outcomes.

More knowledge is needed about long-term ADHD medication and symptom, daily functioning, comorbidity, and tolerability outcomes. This "Long-term Medication for ADHD (LMA) trial" was a prospective observational 2-year trial in children and adolescents aged 6-18 years (extension of 1-year trial). Participants met criteria for DSM-5 ADHD (inattentive or combined), with complex comorbidities; autism spectrum disorder (31%), autistic traits (24%), oppositional symptoms (59%), anxiety (32%), dyslexia/language disorder (16%), borderline intellectual functioning (17%). Medication was individually tailored and followed-up at clinical visits (1, 2, 3, 6, 12, 18, 24 months). Primary outcome: Clinical Global Impression-Severity and Improvement scales (CGI-S, CGI-I). Secondary outcomes: Investigator-rated ADHD-Rating Scale, Weiss Functional Impairment Rating Scale-Parent report (WFIRS-P; Family, School Learning and Behavior, Life Skills, Self-Concept, Social Activities, and Risky Activities domains), comorbidity symptoms and adverse events (AEs). One hundred twenty-eight participants were enrolled (1-year trial only n = 27, LMA trial n = 101). Of these 29 (23%) discontinued, mainly due to AEs (n = 7), moving (n = 7), or no longer needing medication (n = 6). Main AEs were poor appetite, low mood, anxiety, irritability, fatigue. Improvements from baseline to 2 years were large in CGI-S (effect size (ES) 2.28), ADHD-RS (ES 2.06), and moderate to large in WFIRS-P (ES total 0.73, learning 0.4, family 0.67). Overall, the trial showed robust and sustained improvements in ADHD symptom severity and daily functioning over a period of 2 years of ADHD medication in children and adolescents with ADHD and complex comorbidities. Most AEs were mild. Comorbidity symptoms were improved after 1 year, particularly oppositional symptoms, depression, and anxiety.

Monitoring medication response in ADHD: what can continuous performance tests tell us?

Documenting effectiveness of ADHD medication is essential throughout the course of treatment. A rating scale and a continuous performance test (CPT) with motion tracking were used to study the effect of ADHD medication including compliance during one year. Children (N = 78, age 6-18 years) with ADHD were tested with the QbTest at baseline, visit 1 (1 month after baseline) and visit 5 (12 months after baseline). The ADHD-Rating scale was rated by investigator interview at the same visits. QbTest results and ADHD-RS ratings showed reductions in symptoms on all cardinal parameters of the QbTest and on all ADHD-RS subscales between baseline and 1 month and between baseline and 12 months. There was a weak but significant correlation between the total change scores on the two measures from baseline to 1 month. Eighteen participants dropped out of the study before visit 5; at baseline, these children showed significantly lower results on the inattention parameter of the QbTest, with faster reaction time and lower variation in reaction time, suggesting they suffered less problems with inattention. Both the QbTest and the ADHD-RS showed robust ADHD symptom improvements indicative of medication effect, and the QbTest results might also predict non-compliance of medication. Further research is warranted to increase knowledge about reliable monitoring of long-term medication and compliance.

Biomarker support for ADHD diagnosis based on Event Related Potentials and scores from an attention test.

ADHD is a heterogeneous neurodevelopmental disorder associated with dysfunctions in several brain systems. Objective markers of brain dysfunction for clinical assessment are lacking. Many studies applying electroencephalography (EEG) and neuropsychological tests find significant differences between ADHD and controls, but the effect sizes (ES) are often too small for diagnostic purposes. This study aimed to compute a diagnostic index for ADHD by combining behavioral test scores from a cued visual go/no-go task and Event Related Potentials (ERPs). Sixty-one children (age 9-12 years) diagnosed with ADHD and 69 age- and gender-matched typically developing children (TDC) underwent EEG-recording while tested on a go/no-go task. Based on comparisons of ERP group-means and task-performance, variables that differed significantly between the groups with at least moderate ES were converted to a five points percentile scale and multiplied by the ES of the variable. The sum-scores of the variables constituted the diagnostic index. The index discriminated significantly between patients and TDC with a large ES. This index was applied to an independent sample (20 ADHD, 21 TDC), distinguishing the groups with an even larger ES. The diagnostic index described has the potential to support assessment. Further research establishing diagnostic indexes for differential diagnoses is needed.

Emotional contagion for pain is intact in autism spectrum disorders.

Perceiving others in pain generally leads to empathic concern, consisting of both emotional and cognitive processes. Empathy deficits have been considered as an element contributing to social difficulties in individuals with autism spectrum disorders (ASD). Here, we used functional magnetic resonance imaging and short video clips of facial expressions of people experiencing pain to examine the neural substrates underlying the spontaneous empathic response to pain in autism. Thirty-eight adolescents and adults of normal intelligence diagnosed with ASD and 35 matched controls participated in the study. In contrast to general assumptions, we found no significant differences in brain activation between ASD individuals and controls during the perception of pain experienced by others. Both groups showed similar levels of activation in areas associated with pain sharing, evidencing the presence of emotional empathy and emotional contagion in participants with autism as well as in controls. Differences between groups could be observed at a more liberal statistical threshold, and revealed increased activations in areas involved in cognitive reappraisal in ASD participants compared with controls. Scores of emotional empathy were positively correlated with brain activation in areas involved in embodiment of pain in ASD group only. Our findings show that simulation mechanisms involved in emotional empathy are preserved in high-functioning individuals with autism, and suggest that increased reappraisal may have a role in their apparent lack of caring behavior.

A 37-year prospective study of neuroticism and extraversion in women followed from mid-life to late life.

OBJECTIVE: Personality traits are presumed to endure over time, but the literature regarding older age is sparse. Furthermore, interpretation may be hampered by the presence of dementia-related personality changes. The aim was to study stability in neuroticism and extraversion in a population sample of women who were followed from mid-life to late life. METHOD: A population-based sample of women born in 1918, 1922 or 1930 was examined with the Eysenck Personality Inventory (EPI) in 1968-1969. EPI was assessed after 37 years in 2005-2006 (n = 153). Data from an interim examination after 24 years were analysed for the subsample born in 1918 and 1922 (n = 75). Women who developed dementia at follow-up examinations were excluded from the analyses. RESULTS: Mean levels of neuroticism and extraversion were stable at both follow-ups. Rank-order and linear correlations between baseline and 37-year follow-up were moderate ranging between 0.49 and 0.69. Individual changes were observed, and only 25% of the variance in personality traits in 2005-2006 could be explained by traits in 1968-1969. CONCLUSION: Personality is stable at the population level, but there is significant individual variability. These changes could not be attributed to dementia. Research is needed to examine determinants of these changes, as well as their clinical implications.

Secular trends in the prevalence of dementia and depression in Swedish septuagenarians 1976-2006.

BACKGROUND: It is not clear whether the prevalence of dementia and depression among the elderly has changed during the past 30 years. METHOD: Population-based samples from Gothenburg, Sweden were examined with identical psychiatric and neuropsychiatric examinations at age 70 years in 1976-1977 (n = 404, response rate 78.8%) and 2000-2001 (n = 579, response rate 66.4%), and at age 75 in 1976-1977 (n = 303, response rate 78%) and 2005-2006 (n = 753, response rate 63.4%). Depression was diagnosed according to DSM-IV and dementia according to Kay's criteria. General linear models (GLMs) were used to test for differences between groups. RESULTS: Dementia was related to age but not to birth cohort or sex. Major depression was related to sex (higher in women) but not to birth cohort or age. Minor depression was related to birth cohort, sex (higher in women), age (higher at age 75) and the interaction effect of birth cohort × age; that is, the prevalence of minor depression increased with age in the 2000s but not in the 1970s. Thus, the prevalence of minor depression was higher in 2005-2006 than in 1976-1977 among 75-year-olds for both men (12.4% v. 3.7%) and women (19.1% v. 5.6%) whereas there were no birth cohort differences at age 70. CONCLUSIONS: Secular changes were observed only for minor depression, which is considered to be related more to psychosocial factors than major depression. The high prevalence of minor depression in later-born birth cohorts emphasizes the importance of detecting minor depression in the elderly.

Secular changes in personality: study on 75-year-olds examined in 1976-1977 and 2005-2006.

OBJECTIVE: In order to study secular changes in personality factors neuroticism and extroversion, representative population samples of non-demented 75-year-olds underwent psychiatric examinations in 1976-1977 (total n = 223, 138 women, 85 men) and 2005-2006 (total n = 556, 322 women and 234 men). METHODS: Eysenck Personality Inventory was used at both occasions. Demographic factors (educational level, marital status, having children) were registered. RESULTS: Seventy-five-year-olds examined in 2005-2006 had higher values on extroversion and lower values on the Lie scale compared with those examined in 1976-1977. Neuroticism did not differ between the two birth cohorts. Neuroticism scores were higher in women than in men both in 1976-1977 and 2005-2006, and Lie score was higher in women than in men in 2005-2006. CONCLUSIONS: Our findings suggest that present cohorts of 75-year-olds are more extroverted and less prone to respond in a socially desirable manner than those born three decades earlier. Neuroticism levels remained unchanged, suggesting this trait may be less influenced by environmental factors than the other traits studied.

The sociocommunicative deficit subgroup in anorexia nervosa: autism spectrum disorders and neurocognition in a community-based, longitudinal study.

BACKGROUND: A subgroup of persons with anorexia nervosa (AN) have been proposed to have sociocommunicative problems corresponding to autism spectrum disorders [ASDs, i.e. DSM-IV pervasive developmental disorders (PDDs): autistic disorder, Asperger's disorder, PDD not otherwise specified (NOS)]. Here, clinical problems, personality traits, cognitive test results and outcome are compared across 16 subjects (32%) with teenage-onset AN who meet or have met ASD criteria (AN+ASD), 34 ASD-negative AN subjects and matched controls from a longitudinal Swedish study including four waves of independent assessments from the teens to the early thirties. METHOD: The fourth wave included the Structured Clinical Interview for DSM-IV (SCID)-I and the SCID-II (cluster C, i.e. 'anxious' PDs) interviews, the Asperger Syndrome Diagnostic Interview, self-assessments by the Autism Spectrum Quotient and the Temperament and Character Inventory, neurocognitive tests by subscales from the Wechsler scales, continuous performance tests, Tower of London, and Happé's cartoons. RESULTS: The ASD assessments had substantial inter-rater reliability over time (Cohen's κ between 0.70 and 0.80 with previous assessments), even if only six subjects had been assigned a diagnosis of an ASD in all four waves of the study, including retrospective assessments of pre-AN neurodevelopmental problems. The AN+ASD group had the highest prevalence of personality disorders and the lowest Morgan-Russell scores. The non-ASD AN group also differed significantly from controls on personality traits related to poor interpersonal functioning and on neurocognitive tests. CONCLUSIONS: A subgroup of subjects with AN meet criteria for ASDs. They may represent the extreme of neurocognitive and personality problems to be found more generally in AN.

Neurocognitive stability in Asperger syndrome, ADHD, and reading and writing disorder: a pilot study.

Boys with Asperger syndrome (n=20), attention-deficit-hyperactivity disorder (n=20), and reading and writing disorder (n=20) were followed up and retested on several neuropsychological measures 1 to 2 years after initial assessments. Wechsler Intelligence Scale for Children (WISC-III) Full Scale, Verbal, and Performance IQ scores remained stable for all diagnostic groups. Kaufman factors and 'fluid' and 'crystallized' abilities were also stable measures. Subtest stability over time, was slightly more variable. There was a tendency for the group with Asperger syndrome to deteriorate over time with respect to logical reasoning abilities. Measures of executive function/attention ('go-no-go' and 'conflict' tests) showed good test-retest stability in all diagnostic groups. This is the first study of its kind.

Autism and Asperger syndrome: coexistence with other clinical disorders.

OBJECTIVE: : To provide a clinically useful analysis of the extent to which autism and Asperger syndrome coexist with other disorders. METHOD: Selective review of the literature detailing data pertaining to symptoms and disorders sometimes encountered in connection with autism or Asperger syndrome. RESULTS: A large number of medical conditions, psychiatric disorders and behavioural and motor dyscontrol symptoms are associated with autism and Asperger syndrome. CONCLUSION: Comorbidity is to be expected in autism spectrum disorders -directly or indirectly. Comorbid conditions may be markers for underlying pathophysiology and suggest a more varied treatment approach. There is a great need for in-depth research into this area, meaning that the exclusion criteria of current diagnostic manuals, i.e. those that rule out a diagnosis of autism in some disorders, and a diagnosis of certain other disorders in autism may have to be revised.