Test of variables of attention (TOVA) as a predictor of early attention complaints, an antecedent to dementia.

The goal of this study was to determine if impairments detected by the test of variables of attention (TOVA) may be used to predict early attention complaints and memory impairments accurately in a clinical setting. We performed a statistical analysis of outcomes in a patient population screened for attention deficit hyperactivity disorder or attention complaints, processing errors as measured by TOVA and the Wechsler Memory Scale (WMS-III) results. Attention deficit disorder (ADD) checklists, constructed using the Diagnostic and Statistical Manual of Mental Disorders 4th Edition criteria, which were completed by patients at PATH Medical, revealed that 72.8% of the patients had more than one attention complaint out of a total of 16 complaints, and 41.5% had more than five complaints. For the 128 males with a significant number of ADD complaints, individuals whose scores were significantly deviant or borderline (SDB) on TOVA, had a significantly greater number of attention complaints compared with normals for omissions (P < 0.02), response time (P < 0.015), and variability (P < 0.005), but not commissions (P > 0.50). For males, the mean scores for auditory, visual, immediate, and working memory scores as measured by the WMS-III were significantly greater for normals versus SDBs on the TOVA subtest, ie, omission (P < 0.01) and response time (P < 0.05), but not variability or commissions. The means for auditory, visual, and immediate memory scores were significantly greater for normals versus SDBs for variability (P < 0.045) only. In females, the mean scores for visual and working memory scores were significantly greater for normals versus SDBs for omissions (P < 0.025). The number of SDB TOVA quarters was a significant predictor for "impaired" or "normal" group membership for visual memory (P < 0.015), but not for the other three WMS-III components. For males, the partial correlation between the number of attention complaints and the number of SDB TOVA quarters was also significant (r = 0.251, P < 0.005). For the 152 females with a significant number of attention complaints, no significant differences between SDBs and normals were observed (P > 0.15). This is the first report, to our knowledge, which provides evidence that TOVA is an accurate predictor of early attention complaints and memory impairments in a clinical setting. This finding is more robust for males than for females between the ages of 40 and 90 years.

Healing enhancement of chronic venous stasis ulcers utilizing H-WAVE(R) device therapy: a case series.

INTRODUCTION: Approximately 15% (more than 2 million individuals, based on these estimates) of all people with diabetes will develop a lower-extremity ulcer during the course of the disease. Ultimately, between 14% and 20% of patients with lower-extremity diabetic ulcers will require amputation of the affected limb. Analysis of the 1995 Medicare claims revealed that lower-extremity ulcer care accounted for $1.45 billion in Medicare costs. Therapies that promote rapid and complete healing and reduce the need for expensive surgical procedures would impact these costs substantially. One such example is the electrotherapeutic modality utilizing the H-Wave(R) device therapy and program.It has been recently shown in acute animal experiments that the H-Wave(R) device stimulation induces a nitric oxide-dependent increase in microcirculation of the rat Cremaster skeletal muscle. Moreover, chronic H-wave(R) device stimulation of rat hind limbs not only increases blood flow but induces measured angiogenesis. Coupling these findings strongly suggests that H-Wave(R) device stimulation promotes rapid and complete healing without need of expensive surgical procedures. CASE PRESENTATION: We decided to do a preliminary evaluation of the H-Wave(R) device therapy and program in three seriously afflicted diabetic patients. Patient 1 had chronic venous stasis for 6 years. Patient 2 had chronic recurrent leg ulcerations. Patient 3 had a chronic venous stasis ulcer for 2 years. All were dispensed a home H-Wave(R) unit. Patient 1 had no other treatment, patient 2 had H-Wave(R) therapy along with traditional compressive therapy, and patient 3 had no other therapy.For patient 1, following treatment the ulcer completely healed with the H-Wave(R) device and program after 3 months. For patient 2, by one month complete ulcer closure occurred. Patient 3 had a completely healed ulcer after 9 months. CONCLUSIONS: While most diabetic ulcers can be treated successfully on an outpatient basis, a significant proportion will persist and become infected. Based on this preliminary case series investigation we found that three patients prescribed H-Wave(R) home treatment demonstrate accelerated healing with excellent results. While these results are encouraging, additional large scale investigation is warranted before any interpretation is given to these interesting outcomes.

Nutrigenomic targeting of carbohydrate craving behavior: can we manage obesity and aberrant craving behaviors with neurochemical pathway manipulation by Immunological Compatible Substances (nutrients) using a Genetic Positioning System (GPS) Map?

Genetic mediated physiological processes that rely on both pharmacological and nutritional principles hold great promise for the successful therapeutic targeting of reduced carbohydrate craving, body-friendly fat loss, healthy body recomposition, and overall wellness. By integrating an assembly of scientific knowledge on inheritable characteristics and environmental mediators of gene expression, we review the relationship of genes, hormones, neurotransmitters, and nutrients as they correct unwanted weight gain coupled with unhappiness. In contrast to a simple one-locus, one-mechanism focus on pharmaceuticals alone, we hypothesize that the use of nutrigenomic treatment targeting multi-physiological neurological, immunological, and metabolic pathways will enable clinicians to intercede in the process of lipogenesis by promoting lipolysis while attenuating aberrant glucose cravings. In turn, this approach will enhance wellness in a safe and predictable manner through the use of a Genetic Positioning System (GPS) Map. The GPS Map, while presently incomplete, ultimately will serve not only as a blueprint for personalized medicine in the treatment of obesity, but also for the development of strategies for reducing many harmful addictive behaviors and promoting optimal health by using substances compatible with the body's immune system.

Hypothesizing that brain reward circuitry genes are genetic antecedents of pain sensitivity and critical diagnostic and pharmacogenomic treatment targets for chronic pain conditions.

While it is well established that the principal ascending pathways for pain originate in the dorsal horn of the spinal cord and in the medulla, the control and sensitivity to pain may reside in additional neurological loci, especially in the mesolimbic system of the brain (i.e., a reward center), and a number of genes and associated polymorphisms may indeed impact pain tolerance and or sensitivity. It is hypothesized that these polymorphisms associate with a predisposition to intolerance or tolerance to pain. It is further hypothesized that identification of certain gene polymorphisms provides a unique therapeutic target to assist in the treatment of pain. It is hereby proposed that pharmacogenetic testing of certain candidate genes (i.e., mu receptors, PENK etc.) will result in pharmacogenomic solutions personalized to the individual patient, with potential improvement in clinical outcomes.

Activation instead of blocking mesolimbic dopaminergic reward circuitry is a preferred modality in the long term treatment of reward deficiency syndrome (RDS): a commentary.

BACKGROUND AND HYPOTHESIS: Based on neurochemical and genetic evidence, we suggest that both prevention and treatment of multiple addictions, such as dependence to alcohol, nicotine and glucose, should involve a biphasic approach. Thus, acute treatment should consist of preferential blocking of postsynaptic Nucleus Accumbens (NAc) dopamine receptors (D1-D5), whereas long term activation of the mesolimbic dopaminergic system should involve activation and/or release of Dopamine (DA) at the NAc site. Failure to do so will result in abnormal mood, behavior and potential suicide ideation. Individuals possessing a paucity of serotonergic and/or dopaminergic receptors, and an increased rate of synaptic DA catabolism due to high catabolic genotype of the COMT gene, are predisposed to self-medicating any substance or behavior that will activate DA release, including alcohol, opiates, psychostimulants, nicotine, gambling, sex, and even excessive internet gaming. Acute utilization of these substances and/or stimulatory behaviors induces a feeling of well being. Unfortunately, sustained and prolonged abuse leads to a toxic" pseudo feeling" of well being resulting in tolerance and disease or discomfort. Thus, a reduced number of DA receptors, due to carrying the DRD2 A1 allelic genotype, results in excessive craving behavior; whereas a normal or sufficient amount of DA receptors results in low craving behavior. In terms of preventing substance abuse, one goal would be to induce a proliferation of DA D2 receptors in genetically prone individuals. While in vivo experiments using a typical D2 receptor agonist induce down regulation, experiments in vitro have shown that constant stimulation of the DA receptor system via a known D2 agonist results in significant proliferation of D2 receptors in spite of genetic antecedents. In essence, D2 receptor stimulation signals negative feedback mechanisms in the mesolimbic system to induce mRNA expression causing proliferation of D2 receptors. PROPOSAL AND CONCLUSION: The authors propose that D2 receptor stimulation can be accomplished via the use of Synapatmine, a natural but therapeutic nutraceutical formulation that potentially induces DA release, causing the same induction of D2-directed mRNA and thus proliferation of D2 receptors in the human. This proliferation of D2 receptors in turn will induce the attenuation of craving behavior. In fact as mentioned earlier, this model has been proven in research showing DNA-directed compensatory overexpression (a form of gene therapy) of the DRD2 receptors, resulting in a significant reduction in alcohol craving behavior in alcohol preferring rodents. Utilizing natural dopaminergic repletion therapy to promote long term dopaminergic activation will ultimately lead to a common, safe and effective modality to treat Reward Deficiency Syndrome (RDS) behaviors including Substance Use Disorders (SUD), Attention Deficit Hyperactivity Disorder (ADHD), Obesity and other reward deficient aberrant behaviors. This concept is further supported by the more comprehensive understanding of the role of dopamine in the NAc as a "wanting" messenger in the meso-limbic DA system.

Hypothesizing that marijuana smokers are at a significantly lower risk of carcinogenicity relative to tobacco-non-marijuana smokers: evidenced based on statistical reevaluation of current literature.

A hypothetical link between marijuana smoking and cancer has been established based on a number of misleading assumptions. However, recent studies tend to suggest, if anything, an inverse association between marijuana use and cancers. To test the hypothesis that marijuana smoking significantly lowers the risk of developing cancer in humans, we analyzed published data from a prospective cohort study on cancer incidence among nonsmokers (NS), marijuana-only smokers (MS), tobacco-only smokers (TS), and marijuana and tobacco smokers (MTS). Using the log linear model to calculate the probability of developing each cancer form as a function of the interaction between marijuana and tobacco smoking, as well as functions of marijuana and tobacco smoking main effects whereby chi square statistics were calculated for the interaction and main effect estimates, we found that in all cases tested there was a significantly lower risk for MS compared to TS. Male and female TS had a greater probability of developing lung cancer than did MS. Males and females TS had a greater probability of developing lung cancer compared with NS. Males and female MTS had a slightly higher probability of developing lung cancer than did MS. This difference was statistically significant: chi2 = 30.51, p < .00001, with a correlation coefficient of -0.75, Z = -7.84, p < .05. Male and female MTS had a lower probability of developing lung cancer than did TS. This difference was statistically significant: chi2 = 71.61, p = .00003, with a correlation coefficient of 0.61, Z = 5.06, p < .05.

LG839: anti-obesity effects and polymorphic gene correlates of reward deficiency syndrome.

INTRODUCTION: This study systematically assessed the weight management effects of a novel experimental DNA-customized nutraceutical, LG839 (LifeGen, Inc., La Jolla, CA, USA). METHODS: A total of 1058 subjects who participated in the overall D.I.E.T. study were genotyped and administered an LG839 variant based on polymorphic outcomes. A subset of 27 self-identified obese subjects of Dutch descent, having the same DNA pattern of four out of the five candidate genes tested (chi-square analysis) as the entire data set, was subsequently evaluated. Simple t tests comparing a number of weight management parameters before and after 80 days of treatment with LG839 were performed. RESULTS: Significant results were observed for weight loss, sugar craving reduction, appetite suppression, snack reduction, reduction of late night eating (all P<0.01), increased perception of overeating, enhanced quality of sleep, increased happiness (all P<0.05), and increased energy (P<0.001). Polymorphic correlates were obtained for a number of genes (LEP, PPAR-gamma2, MTHFR, 5-HT2A, and DRD2 genes) with positive clinical parameters tested in this study. Of all the outcomes and gene polymorphisms, only the DRD2 gene polymorphism (A1 allele) had a significant Pearson correlation with days on treatment (r=0.42, P=0.045). CONCLUSION: If these results are confirmed in additional rigorous, controlled studies, we carefully suggest that DNA-directed targeting of certain regulator genes, along with customized nutraceutical intervention, provides a unique framework and strategic modality to combat obesity.

Attention-deficit-hyperactivity disorder and reward deficiency syndrome.

Molecular genetic studies have identified several genes that may mediate susceptibility to attention deficit hyperactivity disorder (ADHD). A consensus of the literature suggests that when there is a dysfunction in the "brain reward cascade," especially in the dopamine system, causing a low or hypo-dopaminergic trait, the brain may require dopamine for individuals to avoid unpleasant feelings. This high-risk genetic trait leads to multiple drug-seeking behaviors, because the drugs activate release of dopamine, which can diminish abnormal cravings. Moreover, this genetic trait is due in part to a form of a gene (DRD(2) A1 allele) that prevents the expression of the normal laying down of dopamine receptors in brain reward sites. This gene, and others involved in neurophysiological processing of specific neurotransmitters, have been associated with deficient functions and predispose individuals to have a high risk for addictive, impulsive, and compulsive behavioral propensities. It has been proposed that genetic variants of dopaminergic genes and other "reward genes" are important common determinants of reward deficiency syndrome (RDS), which we hypothesize includes ADHD as a behavioral subtype. We further hypothesize that early diagnosis through genetic polymorphic identification in combination with DNA-based customized nutraceutical administration to young children may attenuate behavioral symptoms associated with ADHD. Moreover, it is concluded that dopamine and serotonin releasers might be useful therapeutic adjuncts for the treatment of other RDS behavioral subtypes, including addictions.

Gene \Narcotic Attenuation Program attenuates substance use disorder, a clinical subtype of reward deficiency syndrome.

This study evaluated the effects of a putative activator of brain reward circuitry on outcomes in a 1-y prospective comprehensive outpatient clinical program. As part of the Gene Narcotic Attenuation Program, Haveos (Synaptamine)(TM) was administered for the treatment of substance use disorder. Seventy-six patients (45 males and 31 females; mean age, 33 y [standard deviation, 7.0]) who had been given a diagnosis of serious substance use disorder were recruited. After exclusion of 15 patients who dropped out before the end of the study, self-reported craving decreased from program entrance to 12 wk (visual analog scale whereby 0 represents no craving and 5, the strongest craving) for 61 compliant patients (mean decrease, 2.85, 95% confidence interval [CI], 2.65, 3.05); this improvement was significant (P<.001). Building up to relapse scores (each of 5 individual items and summary value) showed similar improvement after 1 y of treatment; the mean decrease in scores was significant for stress (t=3.3; P=.002), depression (t=4.0; P<.001), anger (t=4.4; P<.001), anxiety (t=4.5, P<.001), drug craving (t=5.4, P<.001), and summary building up to relapse (t=4.1; P<.001). Also, recovery score measures of energy level (t=8.4; P<.001) and ability to refrain from drug-seeking behavior (t=7.4; P<.001) showed significant mean increases from entry to 1 y. During the study, the alcoholic dropout rate was only 7% (4 of 57), which was significantly (Fisher's exact test, P<.001) lower than the 73% (11 of 15) dropout rate reported for psychostimulant users. Although these results are significant, any interpretation must await the performance of rigorous double-blind studies.

Manipulation of catechol-O-methyl-transferase (COMT) activity to influence the attenuation of substance seeking behavior, a subtype of Reward Deficiency Syndrome (RDS), is dependent upon gene polymorphisms: a hypothesis.

There are common genetic mechanisms responsible for both drug effects and subsequent seeking behavior. In 1996, we coined the term Reward Deficiency Syndrome (RDS). Past and current treatment of substance seeking behavior, a subtype of Reward Deficiency Syndrome (RDS), is considered by most to be inadequate. Recently, we evaluated a complex named Synaptamine [Haveos (SG8839R)]. The main difference with an older studied variant and the latest variant is the inclusion of a proprietary form of Rhodiola rosea, a known catechol-O-methyl-transferase inhibitor (COMT) to potentially enhance the activity of presynaptic released dopamine. In this regard, based on the current literature we hypothesize that manipulation of catechol-O-methyl-transferase (COMT) activity to influence the attenuation of substance seeking behavior, is dependent upon gene polymorphisms. In this regard we hypothesize that carrying the LL genotype with low COMT activity should as theorized, increase the reward induced by substance-induced dopamine release and may indeed increase the propensity to type 1 alcoholism and possibly other drugs that activate the dopaminergic system. Thus when alcohol is present in low COMT LL genotype, increasing COMT activity, not inhibiting it should assist in the reduction of social consumption or abuse. Alternatively, under physiological conditions (no psychoactive substances present (e.g. alcohol) carrying the DRD2 A1 allele with associated low D2 receptors should, as theorized, increase craving behavior because of a low or hypodopaminergic state causing the individual to seek out substances that increase the release of dopamine for subsequent activation of unbound D2 sites in the nucleus accumbens. Thus, in the absence of alcohol or other psychoactive drugs (dopamine releasers), especially during recovery or rehabilitation, decreasing, not increasing COMT activity, should result in enhanced synaptic dopamine as physiologically released, thereby proliferating D2 receptors while reducing stress, increasing well-being, reducing craving behavior and preventing relapse. Based on this hypothesis, we believe that adding the COMT inhibitor R. rosea (as Rhodimin) to our amino-acid and chromium combination in DUI offenders and other illegal drug-related crimes, increases the potential for more targeted neurochemical rebalancing and enhanced relapse prevention. Finally, we hypothesize that these data coupled together provide evidence that the combination of enkephalinase inhibition, neurotransmitter precursor loading, brain tryptophan enhancing and COMT inhibition as well as DNA analysis of the individual's genome, may be useful as an adjunct to therapy when used in outpatient recovery, specifically to assist in reducing craving behavior and preventing relapse.

Plasma growth hormones, P300 event-related potential and test of variables of attention (TOVA) are important neuroendocrinological predictors of early cognitive decline in a clinical setting: evidence supported by structural equation modeling (SEM) parameter estimates.

A review of the literature in both animals and humans reveals that changes in sex hormone have often been associated with changes in behavioral and mental abilities. Previously published research from our laboratory, and others, provides strong evidence that P300 (latency) event-related potential (ERP), a marker of neuronal processing speed, is an accurate predictor of early memory impairment in both males and females across a wide age range. It is our hypothesis, given the vast literature on the subject, that coupling growth hormones (insulin-like growth factor-I, (IGF-I) and insulin-like growth factor binding protein 3 (IGF-BP3)), P300 event-related potential and test of variables of attention (TOVA) are important neuroendocrinological predictors of early cognitive decline in a clinical setting. To support this hypothesis, we utilized structural equation modeling (SEM) parameter estimates to determine the relationship between aging and memory, as mediated by growth hormone (GH) levels (indirectly measured through the insulin-like growth factor system), P300 latency and TOVA, putative neurocognitive predictors tested in this study. An SEM was developed hypothesizing a causal directive path, leading from age to memory, mediated by IGF-1 and IGF-BP3, P300 latency (speed), and TOVA decrements. An increase in age was accompanied by a decrease in IGF-1 and IGF-BP3, an increase in P300 latency, a prolongation in TOVA response time, and a decrease in memory functioning. Moreover, independent of age, decreases in IGF-1 and IGF-BP3, were accompanied by increases in P300 latency, and were accompanied by increases in TOVA response time. Finally, increases in P300 latency were accompanied by decreased memory function, both directly and indirectly through mediation of TOVA response time. In summary, this is the first report utilizing SEM to reveal the finding that aging affects memory function negatively through mediation of decreased IGF-1 and IGF-BP3, and increased P300 latency (delayed attention and processing speed).

The H-Wave small muscle fiber stimulator, a nonpharmacologic alternative for the treatment of chronic soft-tissue injury and neuropathic pain: an extended population observational study.

In a previous study, the H-Wave small-muscle fiber stimulator significantly reduced chronic pain and restored physical function among patients with pain in the lower and upper extremities and spine. In this extended population observational study, a cross-sectional,computer-administered 10-item survey was administered to 6774 patients (3367 men [49.7%], 3406 women [50.3%], and 1 sex not reported [<1%]; mean+/-SD age, 45.28+/-10.08 y; range, 18-65 y) with chronic soft-tissue injury or neuropathic pain to assess their therapeutic response. The mean+/-SE duration of self-administered H-Wave treatment before the survey was completed was 87.35+/-1.39 d. Sixty-five percent of study participants reported a reduced or eliminated need for pain medication; 79% reported improved functional capacity or activity; and 78% reported 25% or greater reduction of pain. This cross-sectional evaluation represents the largest outcome study on the benefits of the H-Wave device in patients with chronic soft-tissue injury or neuropathic pain. The results suggest that this nonpharmacologic approach may provide an important alternative to standard pharmacologic treatment.

Delayed P300 latency correlates with abnormal Test of Variables of Attention (TOVA) in adults and predicts early cognitive decline in a clinical setting.

Delayed P300 latency identifies dementia better than the Mini-Mental Status Exam and, in some cases, the Wechsler Memory Scale (WMS-III). The purpose of this study was to determine whether the outcome of an objective Test of Variables of Attention (TOVA) correlates with the findings of an electrophysiologic test-P300 latency-in patients 40 y of age or older. Adult attention deficit disorder may be an important premorbid marker of memory dysfunction or dementia. In males, the means for P300 latency and age-adjusted P300 latency were significantly greater for patients classified as SD-BL (significantly deviant or borderline: TOVA<-1.0) than for those categorized as normal (TOVA(3)0) for attention failure (ie, omissions [P<.010] and commissions [P<.005]) but not for response time or for variability. Males with >2 SD-BL quarters had significantly delayed P300 latency and age-adjusted P300 latency compared with males who had 0 SD-BL quarters (P<.020) and 1 SD-BL quarter (P<.005). In females, the means for P300 latency and age-adjusted P300 latency were significantly delayed for those grouped as SD-BL than for those labeled normal for response time (P<.001) and variability (P<.010), but not for omissions or for commissions. Females with >2 SD-BL quarters had significantly delayed P300 latency and age-adjusted P300 latency compared with females who had 0 SD-BL quarters (P<.005) and 1 SD-BL quarter (P<.010). Results suggest that TOVA abnormalities may be an indicator of delayed P300 and attention disorder. Recent research correlates TOVA abnormalities with impaired WMS scores of early dementia. Coupling of TOVA assessment findings with results of P300, Mini-Mental Status Exam, and WMS-III may allow for enhanced accuracy in the diagnosis and evaluation of the complex pathway of failing attention, memory, and cognition that leads to dementia.

H-Wave, a nonpharmacologic alternative for the treatment of patients with chronic soft tissue inflammation and neuropathic pain: a preliminary statistical outcome study.

The burden of chronic soft tissue inflammation and neuropathic pain on individuals and society is substantial. This study was conducted to evaluate the H-wave device--an innovative form of treatment for chronic pain and inflammation--in patients with persistent pain associated with injuries or conditions affecting the upper or lower extremities or the back. Patients with at least moderate pain despite conventional therapy were included in a systematic survey after they had been given 2 to 6 wk of treatment with the H-wave device. Measures of improvement involved the proportion of patients with diminished medication requirements, improved function, or pain relief greater than 25%. More than 60% of patients with pain in the lower extremities, upper extremities, or back experienced pain relief exceeding 25%. The proportion of patients whose function improved and who were able to perform a new activity was consistently greater than 50% across the 3 anatomic subgroups. More than 40% of patients in each group were able to reduce or completely eliminate the use of pain medications. These benefits of treatment were independent of the type of pain therapy administered previously. In each anatomic subgroup, the proportion of patients who reported improvement on more than 1 of the 3 endpoints was significantly higher than the expected response to placebo therapy (P<.001). Results suggest that the H-wave device provided important benefits to patients with chronic soft tissue inflammation and neuropathic pain.

Neurogenetic interactions and aberrant behavioral co-morbidity of attention deficit hyperactivity disorder (ADHD): dispelling myths.

BACKGROUND: Attention Deficit Hyperactivity Disorder, commonly referred to as ADHD, is a common, complex, predominately genetic but highly treatable disorder, which in its more severe form has such a profound effect on brain function that every aspect of the life of an affected individual may be permanently compromised. Despite the broad base of scientific investigation over the past 50 years supporting this statement, there are still many misconceptions about ADHD. These include believing the disorder does not exist, that all children have symptoms of ADHD, that if it does exist it is grossly over-diagnosed and over-treated, and that the treatment is dangerous and leads to a propensity to drug addiction. Since most misconceptions contain elements of truth, where does the reality lie? RESULTS: We have reviewed the literature to evaluate some of the claims and counter-claims. The evidence suggests that ADHD is primarily a polygenic disorder involving at least 50 genes, including those encoding enzymes of neurotransmitter metabolism, neurotransmitter transporters and receptors. Because of its polygenic nature, ADHD is often accompanied by other behavioral abnormalities. It is present in adults as well as children, but in itself it does not necessarily impair function in adult life; associated disorders, however, may do so. A range of treatment options is reviewed and the mechanisms responsible for the efficacy of standard drug treatments are considered. CONCLUSION: The genes so far implicated in ADHD account for only part of the total picture. Identification of the remaining genes and characterization of their interactions is likely to establish ADHD firmly as a biological disorder and to lead to better methods of diagnosis and treatment.