Adults with attention-deficit/hyperactivity disorder - a diffusion-tensor imaging study of the corpus callosum.

The objective of the present study was to investigate the microstructure and the macrostructure of the corpus callosum (CC) in adults with Attention-Deficit/Hyperactivity Disorder (ADHD) by means of magnetic resonance imaging (MRI). Twenty-nine participants with ADHD and 37 controls were included from the Norwegian ADHD project in Bergen. We measured the fractional anisotropy (FA) values, as well as the size of different subdivisions of the CC, using diffusion tensor imaging (DTI) and anatomical MRI. The isthmus/splenium part of the CC in the ADHD group showed reduced FA values compared to the control group, whereas the size of the CC did not differ across groups. Our findings thus demonstrate a divergence between microstructural and macrostructural measures in the CC of adults with ADHD. This contrasts with findings in children demonstrating callosal abnormalities in both microstructure and macrostructure. Our results may indicate that adults with ADHD in part have succeeded in passing by an earlier developmental delay of the CC, resulting in a normalization of callosal macrostructure into adulthood. However, microstructural differences are still present in adults, which may point to an abnormal lateralization in adults with ADHD, or could be a sign of a persisting impairment.

A critical re-examination of sexual dimorphism in the corpus callosum microstructure.

Recent diffusion-tensor imaging (DTI) studies suggest sexual dimorphism in the micro-structural architecture of the corpus callosum. However, the corpus callosum is also found to be larger in males than in females, a fact that might introduce a systematic bias to the analysis of DTI parameters. Diffusion parameters obtained in the larger male corpus callosum could be less affected by partial-volume averaging with surrounding non-callosal tissue than respective parameters obtained in the smaller female corpus callosum, i.e. the sex of the subject and partial-volume effects would be confounded. The objective of the present DTI study was to re-examine microstructural sex differences in the corpus callosum, while controlling for corpus callosum size differences between sexes. We compared 41 female and 34 male participants using regional tract-based spatial statistics (TBSS) analysis. Clusters of significantly higher fractional anisotropy (FA) and lower diffusion strength in males compared to females were detected in the genu and truncus of the corpus callosum. However, only the sex difference located in the anterior genu subregions could be unequivocally interpreted. This was the only cluster where the diffusion parameters did not correlate with regional callosal size. The present results indicate a stronger inter-hemispheric connectivity between the frontal lobes in males than females, which might be related to sex differences in hemispheric asymmetry and brain size.

Cognitive control in adults with attention-deficit/hyperactivity disorder.

The objective of the present study was to investigate the ability of adults with Attention-Deficit/Hyperactivity Disorder (ADHD) to direct their attention and exert cognitive control in a forced instruction dichotic listening (DL) task. The performance of 29 adults with ADHD was compared with 58 matched controls from the Bergen Dichotic Listening Database (N>1500). Participants in the Bergen DL task listen to and report from conflicting consonant-vowel combinations (two different syllables presented simultaneously, one to each ear). They are asked to report the syllable they hear (non-forced condition), or to focus and report either the right- or left-ear syllable (forced-right and forced-left condition). This procedure is presumed to tap distinct cognitive processes: perception (non-forced condition), orienting of attention (forced-right condition), and cognitive control (forced-left condition). Adults with ADHD did not show significant impairment in the conditions tapping perception and attention orientation, but were significantly impaired in their ability to report the left-ear syllable during the forced-left instruction condition, whereas the control group showed the expected left-ear advantage in this condition. This supports the hypothesis of a deficit in cognitive control in the ADHD group, presumably mediated by a deficit in a prefrontal neuronal circuitry. Our results may have implications for psychosocial adjustment for persons with ADHD in educational and work environments.

Subcortical brain volume differences in participants with attention deficit hyperactivity disorder in children and adults: a cross-sectional mega-analysis.

BACKGROUND: Neuroimaging studies have shown structural alterations in several brain regions in children and adults with attention deficit hyperactivity disorder (ADHD). Through the formation of the international ENIGMA ADHD Working Group, we aimed to address weaknesses of previous imaging studies and meta-analyses, namely inadequate sample size and methodological heterogeneity. We aimed to investigate whether there are structural differences in children and adults with ADHD compared with those without this diagnosis. METHODS: In this cross-sectional mega-analysis, we used the data from the international ENIGMA Working Group collaboration, which in the present analysis was frozen at Feb 8, 2015. Individual sites analysed structural T1-weighted MRI brain scans with harmonised protocols of individuals with ADHD compared with those who do not have this diagnosis. Our primary outcome was to assess case-control differences in subcortical structures and intracranial volume through pooling of all individual data from all cohorts in this collaboration. For this analysis, p values were significant at the false discovery rate corrected threshold of p=0·0156. FINDINGS: Our sample comprised 1713 participants with ADHD and 1529 controls from 23 sites with a median age of 14 years (range 4-63 years). The volumes of the accumbens (Cohen's d=-0·15), amygdala (d=-0·19), caudate (d=-0·11), hippocampus (d=-0·11), putamen (d=-0·14), and intracranial volume (d=-0·10) were smaller in individuals with ADHD compared with controls in the mega-analysis. There was no difference in volume size in the pallidum (p=0·95) and thalamus (p=0·39) between people with ADHD and controls. Exploratory lifespan modelling suggested a delay of maturation and a delay of degeneration, as effect sizes were highest in most subgroups of children (<15 years) versus adults (>21 years): in the accumbens (Cohen's d=-0·19 vs -0·10), amygdala (d=-0·18 vs -0·14), caudate (d=-0·13 vs -0·07), hippocampus (d=-0·12 vs -0·06), putamen (d=-0·18 vs -0·08), and intracranial volume (d=-0·14 vs 0·01). There was no difference between children and adults for the pallidum (p=0·79) or thalamus (p=0·89). Case-control differences in adults were non-significant (all p>0·03). Psychostimulant medication use (all p>0·15) or symptom scores (all p>0·02) did not influence results, nor did the presence of comorbid psychiatric disorders (all p>0·5). INTERPRETATION: With the largest dataset to date, we add new knowledge about bilateral amygdala, accumbens, and hippocampus reductions in ADHD. We extend the brain maturation delay theory for ADHD to include subcortical structures and refute medication effects on brain volume suggested by earlier meta-analyses. Lifespan analyses suggest that, in the absence of well powered longitudinal studies, the ENIGMA cross-sectional sample across six decades of ages provides a means to generate hypotheses about lifespan trajectories in brain phenotypes. FUNDING: National Institutes of Health.

Adults with attention-deficit/hyperactivity disorder - a brain magnetic resonance spectroscopy study.

BACKGROUND: Impaired cognitive control in individuals with attention-deficit/hyperactivity disorder (ADHD) may be related to a prefrontal cortical glutamatergic deficit. We assessed the glutamate level in the left and the right midfrontal region including the anterior cingulate cortex in adults with ADHD and healthy controls. METHODS: Twenty-nine adults with ADHD and 38 healthy controls were included. We used Proton Magnetic Resonance Imaging with single voxel point-resolved spectroscopy to measure the ratio of glutamate to creatine (Glu/Cre) in the left and the right midfrontal region in the two groups. RESULTS: The ADHD group showed a significant reduction of Glu/Cre in the left midfrontal region compared to the controls. CONCLUSION: The reduction of Glu/Cre in the left midfrontal region in the ADHD group may reflect a glutamatergic deficit in prefrontal neuronal circuitry in adults with ADHD, resulting in problems with cognitive control.

Bipolar symptoms in adult attention-deficit/hyperactivity disorder: a cross-sectional study of 510 clinically diagnosed patients and 417 population-based controls.

OBJECTIVE: Bipolar spectrum disorders (BSD) have several symptoms and features in common with attention-deficit/hyperactivity disorder (ADHD). Here we explored the prevalence of BSD and the relationship between symptoms of BSD and ADHD in adult ADHD patients. METHOD: Norwegian adults diagnosed with DSM-IV ADHD during 1997 through 2007 (n = 510) and a random sample of 417 controls from the general population (aged 18-40 years) were recruited and responded to 85 questions rating symptoms of ADHD, lifetime symptoms of mood disorders, other comorbid conditions, and sociodemographic data. RESULTS: According to the Mood Disorder Questionnaire (MDQ), 50.6% of the ADHD patients screened positive for BSD, compared to 8.3% of the controls. In comparison, the prevalence of BSD according to DSM-IV in a subsample of interviewed patients (n = 50) was 32%. In the whole study sample (N = 927), an ADHD diagnosis was the strongest predictor for screening positive on the MDQ (OR = 5.0, P < .001), but the correlation between dimensional symptom levels of ADHD and of BSD was strongest in the control group (Pearson correlation r = 0.7, P < .001 vs r = 0.3, P < .001). Patients screening positive on the MDQ had significantly more drug problems, higher ADHD symptom scores, and lower educational and occupational levels. CONCLUSIONS: Our findings illustrate the close relationship between some symptoms of BSD and ADHD in adults. In clinical and research settings, patients screening positive for BSD should be assessed for a possible underlying or coexisting ADHD condition and vice versa.