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SPECT Functional Neuroimaging Distinguishes Adult Attention Deficit Hyperactivity Disorder From Healthy Controls in Big Data Imaging Cohorts.

ABSTRACT: Background: The diagnosis of attention deficit hyperactivity disorder (ADHD) relies on history and observation, as no reliable biomarkers have been identified. In this study, we compared a large single diagnosis group of patients with ADHD (combined, inattentive, and hyperactive) to healthy controls using brain perfusion single-photon emission computed tomography (SPECT) imaging to determine specific brain regions which could serve as potential biomarkers to reliably distinguish ADHD. Methods: In a retrospective analysis, subjects (n = 1,135) were obtained from a large multisite psychiatric database, where resting state (baseline) and on-task SPECT scans were obtained. Only baseline scans were analyzed in the present study. Subjects were separated into two groups - Group 1 (n = 1,006) was composed of patients who only met criteria for ADHD with no comorbid diagnoses, while a control group (n = 129) composed of individuals who did not meet criteria for any psychiatric diagnosis, brain injury, or substance use served as a non-matched control. SPECT regions of interests (ROIs) and visual readings were analyzed using binary logistic regression. Predicted probabilities from this analysis were inputted into a Receiver Operating Characteristic analysis to identify sensitivity, specificity, and accuracy. Results: The baseline ROIs and visual readings show significant separations from healthy controls. Sensitivity of the visual reads was 100% while specificity was >97%. The sensitivity and specificity of the post-hoc ROI analysis were both 100%. Decreased perfusion was primarily seen in the orbitofrontal cortices, anterior cingulate gyri, areas of the prefrontal cortices, basal ganglia, and temporal lobes. In addition, ROI analysis revealed some unexpected areas with predictive value in distinguishing ADHD, such as cerebellar subregions and portions of the temporal lobes. Conclusions: Brain perfusion SPECT distinguishes adult ADHD patients without comorbidities from healthy controls. Areas which were highly significantly different from control and thus may serve as biomarkers in baseline SPECT scans included: medial anterior prefrontal cortex, left anterior temporal lobe, and right insular cortex. Future studies of these potential biomarkers in ADHD patients with comorbidities are warranted.

SUBMITTER: Amen DG

PROVIDER: S-EPMC8653781 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:A challenge facing clinical neuroscientists is how best to synthesize diverse and sometimes inconsistent evidence for neuropsychological deficits and brain system dysfunction found in psychiatric disorders into models that guide etiological and treatment research. Multiple-pathway models suggest that psychiatric symptoms might arise from pathophysiology in different neural systems. This study tested dual-pathway model predictions for attention-deficit/hyperactivity disorder (ADHD) that reward and executive function cognitive deficits should be related to abnormalities in corresponding functionally specialized neural systems. METHODS:Behavioral inhibition and preference for immediate rewards were assessed in N = 251 adolescent boys and girls ages 12 to 18 diagnosed with DSM-IV combined-subtype ADHD or non-ADHD control subjects. Following taxometric analyses of test performance, the resulting subgroups were compared on a functional magnetic resonance imaging monetary incentive delay task probing reward anticipation and go/no-go task of motor response inhibition. RESULTS:Three ADHD subgroups were identified consistent with different proposed pathways-ADHD with executive function/motor inhibition deficits, ADHD with both executive and reward deficits, and ADHD with relatively normal test performance. Each cognitive domain mapped to different ADHD brain dysfunction features as expected. However, no brain abnormalities were found common to all ADHD subgroups despite the fact they had nearly identical ADHD-related clinical characteristics. CONCLUSIONS:The results suggest that combined-subtype ADHD is a collection of discrete disorders for which a comparable behavioral end point arises through different neurobiological pathways. The findings raise caution about applying common cause, single-deficit conceptual models to individual ADHD patients and should prompt researchers to consider biologically defined, multifactorial etiological models for other psychiatric diagnoses.

Project description:Attention Deficit Hyperactivity Disorder (ADHD) is characterized clinically by hyperactive/impulsive and/or inattentive symptoms which determine diagnostic subtypes as Predominantly Hyperactive-Impulsive (ADHD-HI), Predominantly Inattentive (ADHD-I), and Combined (ADHD-C). Neuroanatomically though we do not yet know if these clinical subtypes reflect distinct aberrations in underlying brain organization. We imaged 34 ADHD participants defined using DSM-IV criteria as ADHD-I (n = 16) or as ADHD-C (n = 18) and 28 matched typically developing controls, aged 8-17 years, using high-resolution T1 MRI. To quantify neuroanatomical organization we used graph theoretical analysis to assess properties of structural covariance between ADHD subtypes and controls (global network measures: path length, clustering coefficient, and regional network measures: nodal degree). As a context for interpreting network organization differences, we also quantified gray matter volume using voxel-based morphometry. Each ADHD subtype was distinguished by a different organizational profile of the degree to which specific regions were anatomically connected with other regions (i.e., in "nodal degree"). For ADHD-I (compared to both ADHD-C and controls) the nodal degree was higher in the hippocampus. ADHD-I also had a higher nodal degree in the supramarginal gyrus, calcarine sulcus, and superior occipital cortex compared to ADHD-C and in the amygdala compared to controls. By contrast, the nodal degree was higher in the cerebellum for ADHD-C compared to ADHD-I and in the anterior cingulate, middle frontal gyrus and putamen compared to controls. ADHD-C also had reduced nodal degree in the rolandic operculum and middle temporal pole compared to controls. These regional profiles were observed in the context of no differences in gray matter volume or global network organization. Our results suggest that the clinical distinction between the Inattentive and Combined subtypes of ADHD may also be reflected in distinct aberrations in underlying brain organization.

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SPECT Functional Neuroimaging Distinguishes Adult Attention Deficit Hyperactivity Disorder From Healthy Controls in Big Data Imaging Cohorts.

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