ABSTRACT
Attention deficit hyperactivity disorder (ADHD) is a common neuropsychiatric condition that has been strongly associated with changes in sleep and circadian rhythms. Circadian rhythms are near 24-h cycles that are primarily generated by an endogenous circadian timekeeping system, encoded at the molecular level by a panel of clock genes. Stimulant and non-stimulant medication used in the management of ADHD has been shown to potentially impact on circadian processes and their behavioral outputs. In the current study, we have analyzed circadian rhythms in daily activity and sleep, and the circadian gene expression in a cohort of healthy controls (N = 22), ADHD participants not using ADHD-medication (N = 17), and participants with ADHD and current use of ADHD medication (N = 17). Rhythms of sleep/wake behavior were assessed via wrist-worn actigraphy, whilst rhythms of circadian gene expression were assessed ex-vivo in primary human-derived dermal fibroblast cultures. Behavioral data indicate that patients with ADHD using ADHD-medication have lower relative amplitudes of diurnal activity rhythms, lower sleep efficiency, more nocturnal activity but not more nocturnal wakenings than both controls and ADHD participants without medication. At the molecular level, there were alterations in the expression of PER2 and CRY1 between ADHD individuals with no medication compared to medicated ADHD patients or controls, whilst CLOCK expression was altered in patients with ADHD and current medication. Analysis of fibroblasts transfected with a BMAL1:luc reporter showed changes in the timing of the peak expression across the three groups. Taken together, these data support the contention that both ADHD and medication status impact on circadian processes.
Subject(s)
Attention Deficit Disorder with Hyperactivity/genetics , Attention Deficit Disorder with Hyperactivity/physiopathology , Circadian Rhythm Signaling Peptides and Proteins/genetics , Circadian Rhythm , Sleep/physiology , Actigraphy , Adult , Attention Deficit Disorder with Hyperactivity/drug therapy , CLOCK Proteins/genetics , Cells, Cultured , Circadian Clocks/genetics , Cryptochromes/genetics , Female , Fibroblasts/metabolism , Gene Expression , Humans , Male , Middle Aged , Period Circadian Proteins/geneticsABSTRACT
The diagnosis of adult attention-deficit/hyperactivity disorder (ADHD) requires evidence for a persistence of core symptoms of the disorder since childhood, the differential diagnostic assessment of other psychiatric or neurologic disorders that might have elicited the current symptoms, an assessment of symptom relevance in terms of clinical impairment, as well as a survey of comorbid psychiatric disorders. Methods used within the diagnostic procedure are clinical questionnaires and interviews, personality questionnaires, and tests of intellectual and cognitive functioning. However, the diagnostic procedure is complicated by a myriad of available measures which are based on differing theoretical concepts of the disorder. These concepts and measures are summarized in the present paper, finally underscoring the significance of an integrated diagnostic master plan based on clinically relevant dimensions.
Subject(s)
Attention Deficit Disorder with Hyperactivity/diagnosis , Adult , Attention Deficit Disorder with Hyperactivity/psychology , Humans , Neuropsychological Tests , Surveys and QuestionnairesABSTRACT
Other than in children diagnosed with attention deficit hyperactivity disorder (ADHD), the connection between ADHD and lipids has not been sufficiently investigated so far in adults. Blood serum lipoproteins and fatty acids (FA) composition were measured and analyzed by colorimetry and gaschromatography in eight male and seven female adults diagnosed with ADHD as well as in 15 age- and gender-matched healthy control subjects. In ADHD patients, polyunsaturated FAs [docosahexaenoic, arachidonic and dihomogammalinolenic acid (p = 0.048; 0.003; 0.012)] showed lower concentrations, while monounsaturated acids (palmitoleic and oleic acid) as well as total and LDL cholesterol showed higher concentrations (p = 0.011; 0.005). ADHD scores positively correlated with palmitoleic (R = -0.56; p = 0.032), stearic (R = 0.53; p = 0.044), eicosapentaenoic (R = 0.62; p = 0.014), docosahexaenoic (R = 0.51; p = 0.050), gammalinolenic (R = 0.62; p = 0.018) and alphalinolenic acid (R = 0.56; p = 0.031) concentration. Even though the total and LDL cholesterol concentrations in blood serum were significantly higher among the ADHD patients than in controls, none of the ADHD symptom scores were significantly associated with any of the lipoproteine measures. We could demonstrate that a lack of polyunsaturated FAs in blood serum of subjects with ADHD persists into adulthood. Furthermore, we could show that adult ADHD symptomatology positively correlates with elevated levels of saturated stearic and monounsaturated FAs.
