Adult Adhd Animal Model

Attention defect hyperactivity disorder (ADHD) affects 3-7% of school-aged children, and reports suggest similar percentages in adults. Children and adults manifest the symptoms of hyperactivity, impulsivity, and inattention differently, however, and diagnostic criteria are typically oriented around the children's core symptoms. While diagnostic criteria have developed significantly since the 1970s, underdiagnosis is a key issue with regard to adult ADHD. In addition, many of the controlled clinical studies have largely ignored the use of therapeutics in populations other than school-aged Caucasian males. On the positive side, it is clear that, once diagnosed, medical treatment is often very effective in ameliorating the effects of ADHD, conferring strong benefits to those who have struggled with ADHD-related problems at work, with family, and with social issues.

There are no objective laboratory measures of ADHD, and there is no one definitive animal model. There are a number of evolving animal models of aspects of ADHD, which have greatly furthered research directed toward the development of novel therapeutics for treating symptoms of ADHD. Perhaps one of the most relevant animal assays is the five-choice serial reaction time test (5-CSRTT), originally designed as a preclinical correlate of the continuous performance test (CPT) of attention used in clinical studies. In addition, while imaging measures currently lack specificity for use in diagnosing ADHD, it is clear that recent imaging studies are shedding light on the etiology of the disorder.

The biological underpinnings of ADHD focus largely on monoamine neurotransmitter systems, including dopamine and norepinephrine. Imaging studies show decreased activation in frontal brain regions (areas involved in attention and working memory). Genetic studies indicate heritability for ADHD of about 70%. Genetic variants related to genes coding for dopamine and norepinephrine neurotransmission may confer susceptibility to ADHD. Stimulant medications, which are still among the most effective treatments for ADHD, act on the dopaminergic system.

Of the available treatments, the stimulants (a class that includes methylphenidate) are first-line agents for both children and adults diagnosed with ADHD. About 70-80% of children respond to methylphenidate, and, with appropriate dosing regimens, adults often respond as well as children to treatment. Long-acting formulations are a key new area in the treatment of ADHD, as these permit once-a-day dosing that eliminates interruptions during the school day for dosing. Other treatment options include the newly approved drug atomoxetine, which is the first nonscheduled drug approved for this disorder. Off-label use of antidepressants and antihypertensive medications may be effective in patients who do not respond to(or cannot tolerate the side effects of) stimulant medications.

Future research will need to consider associated comorbidities with ADHD, which, if properly identified, may influence successful treatment options. New therapeutics with the efficacy of stimulants but without the scheduling concerns would clearly be advantageous in the treatment of ADHD. Finally, emphasis should be given to appropriate diagnostic criteria for children, adolescents, and adults.

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