ADHD in Adults: Does Age at Diagnosis Matter?

OBJECTIVE: To provide additional information about clinical features associated with adult ADHD in patients diagnosed in childhood compared to those first diagnosed in adulthood. METHOD: We stratified a sample of adults with ADHD into patients diagnosed in childhood versus adulthood and compared demographic and clinical characteristics. RESULTS: We found similar clinical features in adults diagnosed in childhood and adults diagnosed in adulthood. Among those diagnosed in adulthood, 95% reported symptom onset in youth. Our results do not support the hypothesis that ADHD diagnosed in adulthood is due to misinterpreting symptoms of other disorders as ADHD. They also suggest incorporating behavioral signs of executive dysfunction into diagnostic criteria for ADHD in adults may increase diagnostic sensitivity. CONCLUSION: These results support the validity of ADHD diagnoses in adulthood, as these adults show similar clinical profiles to those diagnosed in youth. Our results also suggest that if adult-onset ADHD exists, it is rare.

Circular RNAs in the human brain are tailored to neuron identity and neuropsychiatric disease.

Little is known about circular RNAs (circRNAs) in specific brain cells and human neuropsychiatric disease. Here, we systematically identify over 11,039 circRNAs expressed in vulnerable dopamine and pyramidal neurons laser-captured from 190 human brains and non-neuronal cells using ultra-deep, total RNA sequencing. 1526 and 3308 circRNAs are custom-tailored to the cell identity of dopamine and pyramidal neurons and enriched in synapse pathways. 29% of Parkinson's and 12% of Alzheimer's disease-associated genes produced validated circRNAs. circDNAJC6, which is transcribed from a juvenile-onset Parkinson's gene, is already dysregulated during prodromal, onset stages of common Parkinson's disease neuropathology. Globally, addiction-associated genes preferentially produce circRNAs in dopamine neurons, autism-associated genes in pyramidal neurons, and cancers in non-neuronal cells. This study shows that circular RNAs in the human brain are tailored to neuron identity and implicate circRNA-regulated synaptic specialization in neuropsychiatric diseases.

Circular RNAs in the human brain are tailored to neuron identity and neuropsychiatric disease.

Little is known about circular RNAs (circRNAs) in specific brain cells and human neuropsychiatric disease. Here, we systematically identified over 11,039 circRNAs expressed in vulnerable dopamine and pyramidal neurons laser-captured from 190 human brains and non-neuronal cells using ultra-deep, total RNA sequencing. 1,526 and 3,308 circRNAs were custom-tailored to the cell identity of dopamine and pyramidal neurons and enriched in synapse pathways. 88% of Parkinson's and 80% of Alzheimer's disease-associated genes produced circRNAs. circDNAJC6, produced from a juvenile-onset Parkinson's gene, was already dysregulated during prodromal, onset stages of common Parkinson's disease neuropathology. Globally, addiction-associated genes preferentially produced circRNAs in dopamine neurons, autism-associated genes in pyramidal neurons, and cancers in non-neuronal cells. This study shows that circular RNAs in the human brain are tailored to neuron identity and implicate circRNA- regulated synaptic specialization in neuropsychiatric diseases.

Hepatic connexin 32 associates with nonalcoholic fatty liver disease severity.

Emerging data highlight the critical role for the innate immune system in the progression of nonalcoholic fatty liver disease (NAFLD). Connexin 32 (Cx32), the primary liver gap junction protein, is capable of modulating hepatic innate immune responses and has been studied in dietary animal models of steatohepatitis. In this work, we sought to determine the association of hepatic Cx32 with the stages of human NAFLD in a histologically characterized cohort of 362 patients with NAFLD. We also studied the hepatic expression of the genes and proteins known to interact with Cx32 (known as the connexome) in patients with NAFLD. Last, we used three independent dietary mouse models of nonalcoholic steatohepatitis to investigate the role of Cx32 in the development of steatohepatitis and fibrosis. In a univariate analysis, we found that Cx32 hepatic expression associates with each component of the NAFLD activity score and fibrosis severity. Multivariate analysis revealed that Cx32 expression most closely associated with the NAFLD activity score and fibrosis compared to known risk factors for the disease. Furthermore, by analyzing the connexome, we identified novel genes related to Cx32 that associate with NAFLD progression. Finally, we demonstrated that Cx32 deficiency protects against liver injury, inflammation, and fibrosis in three murine models of nonalcoholic steatohepatitis by limiting initial diet-induced hepatoxicity and subsequent increases in intestinal permeability. Conclusion: Hepatic expression of Cx32 strongly associates with steatohepatitis and fibrosis in patients with NAFLD. We also identify novel genes associated with NAFLD and suggest that Cx32 plays a role in promoting NAFLD development. (Hepatology Communications 2018;2:786-797).

The 24-2 Visual Field Test Misses Central Macular Damage Confirmed by the 10-2 Visual Field Test and Optical Coherence Tomography.

PURPOSE: To determine the extent to which the 24-2 visual field (VF) misses macular damage confirmed with both 10-2 VF and optical coherence tomography (OCT) tests and to evaluate the patterns of damage missed. METHODS: One hundred forty-one eyes of 141 glaucoma patients or suspects underwent 24-2 VF (mean deviation [MD] better than -6 dB), 10-2 VF, and OCT testing. Retinal nerve fiber layer (RNFL) and retinal ganglion cell plus inner plexiform (RGC+) probability plots were combined with 10-2 VF probability plots. Eyes were classified as "abnormal macula" if abnormal regions on both the 10-2 VF and OCT plots agreed. The number of abnormal eyes missed (i.e., false negatives) was determined for the following 24-2 VF metrics: MD; pattern standard deviation (PSD); glaucoma hemifield test (GHT); cluster criteria (CC); and abnormal points within ± 10°. Eyes that were missed on one or more of the 24-2 metrics were classified by damage type based upon circumpapillary RNFL thickness plots. RESULTS: Fifty-nine (41.8%) eyes were classified as "abnormal macula," and comprised the reference standard. Of the 59, 31 (52.5%) were missed by one or more of the 24-2 metrics. The individual 24-2 metrics missed between 7 (CC) and 20 (MD) eyes. The eyes missed had widespread macular damage, as well as both shallow and deep local defects. CONCLUSIONS: Eyes with macular glaucomatous damage may be classified as normal based on the 24-2 VF alone. TRANSLATIONAL RELEVANCE: To detect macular damage with perimetry, the 10-2 VF test (or a modified 24-2 VF test) is essential.

A Test of a Model of Glaucomatous Damage of the Macula With High-Density Perimetry: Implications for the Locations of Visual Field Test Points.

PURPOSE: To use high-density perimetry to test a model of local glaucomatous damage to the macula (central visual field [VF]) and to assess the optimal placement of stimuli used to detect this damage. METHODS: Thirty-one eyes of 31 patients showing glaucomatous arcuate damage within the upper hemifield of the central 10° were tested with a customized VF with double the density of the 10-2 (2° grid) test. Individual plots of total deviation (TD) values were generated. A model, which predicts a "vulnerable macular region" (VMR) and a "less vulnerable macular region" (LVMR), was compared with the TD values without (standard model) and with (aligned model) scaling and rotating to align it with the patient's fovea-to-disc axis. Computer simulations assessed alternative VF locations for adding two points to the 6° grid pattern (e.g., 24-2 VF) typically used in the clinic. RESULTS: There were significantly more abnormal points in the VMR than in the LVMR. However, the aligned model did no better than the standard model in describing the data. The optimal locations for adding two points to the 24-2 (6° grid) test were (-1°, 5°) and (1°, 5°), both within the VMR. CONCLUSIONS: The model describes the region of the superior VF vulnerable to arcuate damage. TRANSLATIONAL RELEVANCE: The model can be used to determine the optimal locations for adding test points to the commonly used VF test pattern (24-2). It does not seem necessary to adjust the location of VF test points based upon interindividual differences in the fovea-to-disc axis.

Modifying the Conventional Visual Field Test Pattern to Improve the Detection of Early Glaucomatous Defects in the Central 10°

PURPOSE: To simulate modified versions of the 24-2 (6° grid) visual field (VF) test pattern by adding points from the 10-2 (2° grid) test pattern, and to assess their ability to detect early glaucomatous defects in the central 10°. METHODS: One hundred forty-four eyes of 144 glaucoma patients and suspects with 24-2 mean deviations better than -6 dB were tested with 10-2 and 24-2 VFs. Based upon both 10-2 VF and optical coherence tomography probability plots, 63 hemifields were defined as abnormal, while 121 hemifields were defined as normal. Three modified 24-2 VF test patterns, called 24-2 +4, 24-2 +16 (Even), and 24-2 +16 (Empirical), were simulated by adding 4 or 16 test points from the 10-2 VF. RESULTS: Based upon the number of abnormal points (P ≤ 5%), the area under the ROC curves (AROC scores) of the three modified 24-2 VFs were significantly greater than that of the 24-2 VF for both the upper and lower VF. For a specificity of 85%, the number of true positives was 25 (24-2), 30 (24-2 +4), 31 (24-2 +16, even), and 32 (24-2 +16, empirical) of 34 total true positives for the upper VF and 23, 26, 27, and 28 of 29 for the lower VF. CONCLUSIONS: Adding points from the 10-2 test pattern to the 24-2 test pattern significantly improved its ability to detect macular defects without employing more test points than a single 10-2 test. TRANSLATIONAL RELEVANCE: Additional central points should be added to the 24-2 pattern to improve the detection of macular damage.