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PubMed2005

Familial clustering of executive functioning in affected sibling pair families with ADHD.

OBJECTIVE: To investigate familial clustering of executive functioning (i.e., response inhibition, fine visuomotor functioning, and attentional control) in attention-deficit/hyperactivity disorder (ADHD)-affected sibling pairs. METHOD: Fifty-two affected sibling pairs aged 6 to 18 years and diagnosed with ADHD according to DSM-IV performed the Stroop test, go/no-go task, two different fine visuomotor tracking tasks, and a sustained-, divided-, and focused attention task. RESULTS: Significant correlations (r = 0.4) were found between siblings for response inhibition and attentional control and for fine visuomotor skills that made high demands on executive functioning. CONCLUSIONS: Response inhibition, higher order controlled fine visuomotor functioning, and attentional control seem to cluster in ADHD-affected siblings. This suggests that these aspects of executive dysfunctioning may reflect an endophenotype of ADHD. Measurement of these executive functions may facilitate the identification of genes involved in ADHD by forming more homogeneous subgroups.

Adolescent↗

PubMed2006

Genetic dissection of the common epilepsies.

PURPOSE OF REVIEW: Only two functionally validated susceptibility genes, CACNA1H and GABRD, have so far been identified in the common epilepsies using a candidate gene approach. The difficulty with the alternative statistical approach, where none of the suggested candidates has been functionally validated, may partly be due to the posited genetic architecture of the common epilepsies, such as the idiopathic generalized epilepsies. A subset of both rare and common variants from a much larger pool of susceptibility genes may contribute to disease risk. We review methods and designs for the genetic dissection of common epilepsies. RECENT FINDINGS: Genetic association studies, though theoretically more powerful than linkage analysis, have not yet delivered validated susceptibility genes. Methodological flaws can undermine such studies but are correctable. Concerns remain, however, about the extent of underlying genetic heterogeneity in common epilepsies. Genome-wide association studies are increasingly feasible, but issues remain about their conduct and analysis. Meta-analysis may resolve conflicting association studies, facilitated by the establishment of databases of genetic association studies. Newer multi-locus and admixture mapping approaches are attractive alternatives to traditional association studies and may offer new insights into identifying epilepsy genes. SUMMARY: We conclude by emphasizing the importance of deeper endophenotyping using electroclinical, imaging, and molecular approaches to dissect the common epilepsies.

Chromosome Mapping↗

PubMed2006

Cognitive deficits in the families of patients with schizophrenia.

PURPOSE OF REVIEW: Studies of first-degree relatives of patients with schizophrenia over the past 25 years have reported a number of cognitive deficits, primarily in the domains of memory and executive function. Nevertheless, due to a number of methodological issues, such as including different types of relatives and not controlling for possible psychopathology, it is not yet clear that these findings can fully support a conclusion of heritability of cognitive dysfunction associated with a schizophrenia genotype. RECENT FINDINGS: Several recent meta-analyses have shown that the most consistent deficit shown by relatives is impaired performance on 'maintenance plus' frontal-lobe tasks requiring increased effort and higher central executive processing. Studies of multiplex families (multiple diagnoses in one family) also report that family members tend to have more difficulty on executive function tasks. Another interesting trend is research on subgroups of patients and relatives displaying distinct cognitive syndromes, particularly a subgroup with a generalized cognitive deficit. SUMMARY: As methodological designs improve, this field of study holds promise not only for understanding the neurobiological mechanisms of schizophrenia and the associated cognitive deficits, but also for possibly describing endophenotypes that may lead to identifying at-risk patients and relatives.

Cognition Disorders↗

PubMed2006

Association analysis of the NrCAM gene in autism and in subsets of families with severe obsessive-compulsive or self-stimulatory behaviors.

OBJECTIVES: An autism susceptibility locus (AUTS1, MIM#608636) has been identified in chromosome 7q31. NrCAM is a candidate gene for AUTS1 because it is expressed in the brain and encodes a receptor involved in nervous system development. Polymorphisms in NrCAM have been reported to be associated with autism susceptibility and with substance abuse, implicating NrCAM in reward circuitry. Self-stimulatory, perseverative behavior in autism might be due to defects in reward circuitry. In addition, models of drug addiction have also borrowed from models of obsessive-compulsive behavior designed to reduce anxiety. Thus, our goals were to replicate previous associations of NrCAM with autism, making use of a large cohort, and to clarify whether NrCAM was associated with a specific endophenotype of autism in the repetitive behaviors and stereotyped interests domains. METHODS: We genotyped six NrCAM single nucleotide polymorphisms in 352 families and we tested for association between these polymorphisms and autism in the entire cohort and in two subsets, one with severe obsessive-compulsive behaviors and one with pronounced self-stimulatory behaviors. RESULTS: We found no association between single nucleotide polymorphisms of NrCAM and autism in our large cohort, or in the severe obsessive-compulsive behavior and self-stimulatory behavior subsets. However, we observed a significant overtransmission (21 transmitted vs 6 nontransmitted, chi2=12.054, P=0.0005) of the haplotype G-G-A-G-C-A of rs722519-rs1269622-rs405945-rs6958498-rs401433-rs439587 in the severe obsessive-compulsive behavior subset, likely driven by the G-C haplotype of rs6958498-rs401433, which itself showed significant overtransmission (31 transmitted vs 13 nontransmitted, chi2=8.844, P=0.003). CONCLUSIONS: Overtransmission of particular haplotypes of NrCAM, that may relate to the expression level of NrCAM in the brain, appeared to be associated with autism in the severe obsessive-compulsive behavior subset.

Autistic Disorder↗

PubMed2004

Interleukin (IL)-10, IL-1ra and IL-12 profiles in active and quiescent systemic lupus erythematosus: could longitudinal studies reveal patient subgroups of differing pathology?

Several cytokines have been implicated individually in the pathogenesis of systemic lupus erythematosus (SLE) and some, including interleukin (IL)-10, IL-12 and IL-1ra are raised during flares of disease activity. Few studies have been directed at examining the interactions between these cytokines and how their combined profile relates to disease activity. We have examined serum levels of IL-10, IL-12 and IL-1ra in a cohort of SLE patients obtained from the Queen Elizabeth Hospital, Birmingham in cross-sectional and, in a smaller group, longitudinal analyses. In the cross-sectional study, there were significant correlations between levels of the three cytokines. There were also significant correlations between levels of each cytokine and measures of disease activity. IL-10 levels correlated with ESR, anti-dsDNA antibody titres and C3D, IL-12 levels with anti-dsDNA antibody titres and IL-1ra levels with ESR, anti-dsDNA antibody titres and C3D. IL-1ra levels also correlated with CRP. Circulating IL-10 and IL-1ra levels were higher in patients with SLE than in normal controls, although in this study group they did not reach significance. Circulating IL-12 levels were, however, significantly higher in SLE compared to controls. This was true both in patients with active disease and those sampled during a quiescent phase. These data add to the evidence that cytokines such as IL-10, IL-12 and IL-1ra are important in SLE pathogenesis. In a retrospective study of serial serum samples from seven patients, we found two patients whose cytokine profile was very different from the rest of the group. In most patients normalized IL-10, IL-12 and IL-1ra levels mirrored BILAG scores closely, but in these two patients, IL-10, IL-12 and IL-1ra levels did not fluctuate with disease activity. It is possible that there is a subgroup of SLE patients whose cytokine profile could be an important indicator of their pathology. In order to confirm this and determine the frequency of such patients this study needs to be repeated with a much larger subject group. The coexistence of patient groups with different patterns of cytokine activity might explain conflicting reports of associations of levels of particular cytokines with SLE. As the observed differences could reflect different aetiologies of SLE, this information could reveal valuable endophenotypes for genetic and functional studies of SLE and might, ultimately, inform therapeutic management.

Adult↗

PubMed2004

Neurocognitive function in unaffected first-degree relatives of patients with bipolar disorder: a preliminary report.

OBJECTIVE: Patients with remitted bipolar disorder (BD) have persistent impairments in neuropsychological function, particularly in the domains of executive control and declarative memory [Br J Psychiatry 180 (2002) 293]. If these were the phenotypic expression of genetic vulnerability to BD, then healthy subjects with a genetic predisposition to BD would be expected to display the same deficits. This study, therefore, examined neuropsychological function in healthy first-degree relatives of patients with BD. METHOD: A cross-sectional design was employed to compare the performance of 17 unaffected first-degree relatives of BD patients and 17 demographically matched controls on a range of neuropsychological tests. RESULTS: Relatives were significantly impaired on Backward Digit Span, Spatial Span and on tasks of visuospatial declarative memory in comparison with controls. Psychomotor performance and verbal declarative memory were intact, as were non-working memory aspects of executive performance. CONCLUSION: The selective deficits in executive control and declarative memory exhibited by relatives in this study have previously been reported in euthymic BD patients suggesting they may be useful endophenotypic markers of genetic vulnerability to BD.

Adult↗

PubMed2005

Neuroanatomical abnormalities as risk factors for bipolar disorder.

OBJECTIVE: Neuroimaging studies show structural brain abnormalities in bipolar patients. Some of the abnormalities may represent biological risk factors conveying vulnerability for the disease. This paper aims to identify neuroanatomical risk factors for bipolar disorder (BD). METHODS: We reviewed magnetic resonance imaging (MRI) findings in populations in which the effects of the disease or treatment are minimal or where the chances of finding genetically coded risk factors shared within the families are increased. Such populations include unaffected relatives of bipolar patients, first-episode patients, children or adolescents with BD and patients with familial BD. RESULTS: MEDLINE search revealed 30 relevant scientific papers. Abnormalities in the volume of the striatum, left hemispheric white matter, thalamus and anterior cingulate as well as quantitative MRI signal hyperintensities were identified already in unaffected relatives of bipolar patients. Subjects in the early stages of the disease showed volume changes of the ventricles, white matter, caudate, putamen, amygdala, hippocampus and the subgenual prefrontal cortex. Reduction in the subgenual prefrontal cortex volume was replicated in three of four studies in patients with familial BD. CONCLUSIONS: Possible candidates for neuroanatomical risk factors for BD are volumetric abnormalities of the subgenual prefrontal cortex, striatum, white matter, and probably also the hippocampus and amygdala. Qualitative finding of white matter hyperintensities was already utilized as an endophenotype.

Adolescent↗

PubMed2006

Neurocognitive impairment in euthymic young adults with bipolar spectrum disorder and recurrent major depressive disorder.

OBJECTIVE: Patients with remitted major depressive disorder (MDD) and bipolar disorder have persistent impairments in executive function and verbal memory that may represent endophenotypic abnormalities. In this study, we examine neurocognitive function in a sample of euthymic young adults with bipolar spectrum disorder (BSD) (Can J Psychiatry 2002; 47: 125-134) and compare this to well-matched samples of young adults with recurrent MDD and controls. METHOD: Twenty-one euthymic young adult patients with BSD were compared with 42 young adult patients with MDD and 33 controls on a neuropsychological battery assessing attention, executive function and verbal memory. RESULTS: Patients with BSD were significantly more impaired than MDD patients and controls on tests of executive function and verbal memory. MDD patients did not differ significantly from controls on verbal memory function but performed less well on a test of executive function. CONCLUSION: Euthymic young adults with BSD had greater impairment on neurocognitive measures associated with prefrontal and hippocampal function than MDD patients and controls. This is a reflection of a strong bipolar diathesis in the BSD group rather than being a consequence of a more severe unipolar illness.

Adult↗

PubMed2006

Differential working memory impairment in bipolar disorder and schizophrenia: effects of lifetime history of psychosis.

BACKGROUND: Although bipolar disorder and schizophrenia have long been viewed as distinct illnesses, there is growing evidence that these two complex diseases share some common genes, which may manifest as overlapping neuropsychological impairments. Although working memory dysfunction has been proposed to be central to the pathophysiology of schizophrenia, it has received less attention in studies of bipolar disorder. METHOD: We applied measures of working memory to patients with schizophrenia (n = 15), patients with schizoaffective disorder (n = 15), patients with psychotic (n = 11) and non-psychotic (n = 15) bipolar disorder, and demographically matched healthy subjects (n = 32), in order to determine the extent to which these groups show common or unique impairments. RESULTS: While patients with bipolar disorder (with and without psychotic features) and those with schizophrenia/schizoaffective disorder were impaired on backward digit span, only patients with a lifetime history of psychotic features, regardless of diagnosis, were impaired on spatial delayed response task. CONCLUSIONS: Backward digit span performance is comparable in bipolar disorder and schizophrenia, and may be an appropriate endophenotypic marker that cuts across diagnostic categories. In contrast, spatial working memory performance clearly distinguishes non-psychotic bipolar disorder patients from patients with functional psychosis.

Adult↗

PubMed2006

Prefrontal cognition in schizophrenia and bipolar illness in relation to Val66Met polymorphism of the brain-derived neurotrophic factor gene.

The measures of prefrontal cognition have been used as endophenotype in molecular-genetic studies. Brain-derived neurotrophic factor (BDNF) has been implicated in cognitive functions and in the pathogenesis of major psychoses. This study investigates the relationship between Val66Met polymorphisms of the BDNF gene and prefrontal cognitive function in 129 patients with schizophrenia and 111 patients with bipolar mood disorder. Cognitive tests included the Wisconsin Card Sorting Test (WCST), with such domains as number of perseverative errors, non-perseverative errors, completed corrected categories, conceptual level responses, and set to the first category, and the N-back test, where mean reaction time and percent of correct reactions were measured. Genotyping for Val66Met BDNF polymorphism was done by polymerase chain reaction method. In schizophrenia, no relationship between Val66Met polymorphism of the BDNF gene and the results of the WCST was observed. Patients with Val/Val genotype had a higher percentage of correct reactions in the N-back test than those with the remaining genotypes. Bipolar patients with Val/Val genotype obtained significantly better results on three of five domains of the WCST. No relationship between BDNF polymorphism and the results of the N-back test was found in this group. A limitation to the results could be variable psychopathological state and medication during cognitive testing and lack of Hardy-Weinberg equilibrium in schizophrenia group. Val66Met polymorphism of the BDNF gene may be associated with cognitive performance on the WCST in bipolar mood disorder but not in schizophrenia. An association of this polymorphism with performance on the N-back test in schizophrenia and not in bipolar illness may suggest that in schizophrenia, the BDNF system may be connected with early phases of information processing.

Adolescent↗

PubMed2005

Characterizing the ADHD phenotype for genetic studies.

The genetic study of ADHD has made considerable progress. Further developments in the field will be reliant in part on identifying the most appropriate phenotypes for genetic analysis. The use of both categorical and dimensional measures of symptoms related to ADHD has been productive. The use of multiple reporters is a valuable feature of the characterization of psychopathology in children. It is argued that the use of aggregated measures to characterize the ADHD phenotype, particularly to establish its pervasiveness, is desirable. The recognition of the multiple comorbidities of ADHD can help to isolate more specific genetic influences. In relation to both reading disability and conduct disorder there is evidence that genes may be involved in the comorbid condition that are different from pure ADHD. To date, progress with the investigation of endophenotypes for ADHD has been disappointing. It is suggested that extending such studies beyond cognitive underpinnings to include physiological and metabolic markers might facilitate progress.

Attention Deficit Disorder with Hyperactivity↗

PubMed2004

The factor structure of autistic traits.

BACKGROUND: Although DSM-IV requires symptoms in three criterion domains for a diagnosis of autistic disorder, the extent to which those domains are phenotypically independent is an unanswered and important question. The identification of 'endophenotypes' of the autistic syndrome may be very useful for genetic and neurobiologic studies of autism, but only if they represent truly independent sub domains of the disorder. METHODS: In this study we examined the factor structure of autistic traits using data from 226 child psychiatric patients with and without pervasive developmental disorders, employing cluster analysis of data from the Autism Diagnostic Interview-Revised (ADI-r) and principal components factor analysis of data from the Social Responsiveness Scale (SRS, a quantitative genetic measure of autistic traits formerly known as the Social Reciprocity Scale). RESULTS: The results were consistent with the existence of a singular, continuously distributed underlying factor, resulting in disparate phenotypic manifestations across the three criterion domains for autistic disorder (social deficits, language deficits, and repetitive/stereotypic behaviors). CONCLUSION: The analyses generally failed to support the existence of independent sub domains of dysfunction in autism spectrum conditions. Future studies of the association between genetic/neurobiologic markers and autistic symptomatology may be enhanced by approaches which consider autistic symptoms as quantitative traits, and which are informed by ongoing research on the development and phenomenology of core deficiencies in reciprocal social behavior.

Adolescent↗

PubMed2006

Fine-motor skill deficits in childhood predict adulthood tic severity and global psychosocial functioning in Tourette's syndrome.

BACKGROUND: Most children with Tourette's syndrome (TS) experience a significant decline in tic symptoms during adolescence. Currently no clinical measures have been identified that can predict whose tic symptoms will persist into adulthood. Patients with TS have deficits on neuropsychological tests involving fine-motor coordination and visual-motor integration. We seek to determine if these neuropsychological tests are useful in predicting future symptom severity. METHODS: Thirty-two children, aged 8-14, with TS underwent clinical evaluation and a focused neuropsychological testing battery consisting of the Purdue Pegboard, Beery Visual-Motor Integration (VMI) Test and the Rey-Osterreith Complex Figure Task (RCFT). A follow-up clinical assessment was performed on these children an average of 7.5 years later. Ordinal logistic regression analysis was used to correlate neuropsychological testing at Time 1 with tic severity, OCD severity and global psychosocial functioning at Time 2. RESULTS: Poor performance with the dominant hand on the Purdue Pegboard test predicted worse adulthood tic severity and correlated with tic severity at the time of childhood assessment. Poor performance on the VMI and Purdue Pegboard tests (both dominant and non-dominant hand) also predicted worse adulthood global psychosocial functioning. None of the neuropsychological tests were useful in predicting the future course of OCD symptoms in TS patients. CONCLUSION: Fine motor skill deficits may be a predictor of future tic severity and global psychosocial function in children with TS. We hypothesize that performance on the Purdue Pegboard test may serve as a useful endophenotype in the study of TS and provide a rough measure of the degree of basal ganglia dysfunction present in TS patients.

Adolescent↗

PubMed2004

P300 amplitude in nonalcoholic adolescent twin pairs who become discordant for alcoholism as adults.

Past reports suggest that reduced P300 amplitude is associated with risk for alcoholism. We examined whether visual P300 amplitude could identify familial risk for alcohol disorders in individuals not known to be at risk at the time P300 was recorded. These individuals were twins from pairs where neither twin had an alcohol disorder at age 17 but familial risk was established at age 20 when one twin developed an alcohol disorder whereas the other did not. Of special interest was the P300 of the unaffected twin recorded at age 17 when both twins were alcoholism free. We found reduced P300 in the unaffected twin compared to pairs where both members were continuously disorder free. Hence, P300 was reduced in alcohol disorder-free individuals whose twin siblings subsequently developed alcoholism, further supporting reduced P300 amplitude as an endophenotype indexing familial risk for alcoholism.

Adolescent↗

PubMed2006

Heritability of P300 amplitude development from adolescence to adulthood.

Early adulthood is a period of late brain development corresponding to the age of onset for psychopathology associated with P300 amplitude reductions. Although amplitude from a single occasion is heritable, little is known about genetic influences on change during this period. This is the first study of P300 change to combine latent growth and twin models. P300 at Pz was measured up to three times at approximately ages 17, 20, and 23 in monozygotic and dizygotic male twins using a visual task. P300 decreased with age. Correlations indexing the stability of amplitude over time were high (median r=.72) and almost 90% of the stable variance (i.e., the model intercept) was attributable to genetic influences. The rate of decrease was heritable, and the genes influencing intercept may be the same ones influencing change. Finally, intercept was more heritable than amplitude at any single time point. Intercept may be a more useful aid in the search for genes associated with relevant psychopathology than single measures of P300. Over a broader age range growth indices may be useful "developmental" endophenotypes.

Adolescent↗

PubMed2006

Contribution of serotonin transporter gene polymorphisms to pediatric migraine.

BACKGROUND: The serotonin transporter gene is a promising candidate locus for the genetic susceptibility of migraine. OBJECTIVE: Two functional polymorphisms of the serotonin transporter gene (5-HTTLPR and STin2) were analyzed to assess whether these variants are associated with pediatric migraine. METHODS: Eighty-seven Hungarian pediatric migraine patients and 464 controls were genotyped using polymerase chain reaction. Patients suffering from migraine with (n = 38) or without aura (n = 49) were interviewed regarding the clinical symptoms before or during the attacks. RESULTS: There was no difference between genotype or allele distribution of 5-HTTLPR and STin2 polymorphisms in the entire group of migraineurs and controls. Analysis of subgroups showed an association between STin2 and migraine with aura, as the 12,12 homozygote genotype was overrepresented in this group of patients. Furthermore, similar allele and genotype patterns were found in cases with severe vomiting and abdominal pain. CONCLUSIONS: These results confirm and extend the association between the STin2 polymorphism of 5-HTT gene and migraine with aura using pediatric probands. Our data also suggest a novel endophenotype for pediatric migraine characterized by excessive vomiting and abdominal pain during the attack.

Child↗

PubMed2006

Measuring craving: an attempt to connect subjective craving with cue reactivity.

BACKGROUND: Better insight into craving may contribute to the development of more efficient relapse prevention strategies. Inconsistent findings on the relation between craving and relapse may be due to difficulties in the measurement of craving. These difficulties are accounted for by 3 interrelated problems: lack of consensus regarding the definition of craving, the use of different time frames (craving now vs craving in the past), and lack of concordance between self-reported craving and psychophysiological measures of cue reactivity. The aim of this study is to develop and validate a new self-report questionnaire for the assessment of the core aspects of craving, taking into account different time frames and emphasizing the psychophysiological aspects of craving. It is hypothesized that this questionnaire will show higher concordance with measures of cue reactivity than existing self-report craving questionnaires. METHODS: Based on a semantic mapping sentence, a 24-item self-report questionnaire was developed: the Jellinek Alcohol Craving Questionnaire (JACQ). The questionnaire was tested in 2 samples of treatment-seeking alcohol-dependent patients (sample A, n = 251; sample B, n = 48). Psychometric properties were examined in sample A and cross-validated in sample B. The associations with psychophysiological and neuroendocrine measures of cue reactivity were studied in sample B. RESULTS: The JACQ consists of 1 dimension with the following 4 aspects: (1) emotional urge, (2) physical sensations, (3) temptation to drink, and (4) uncontrolled thoughts. All (sub)scales had a good internal consistency (alpha = 0.77-0.95) and were highly intercorrelated (r = 0.57-0.86). Craving-past correlated low with craving-now (r = 0.32). Craving-now (sub)scales showed a moderate association with heart rate (0.46-0.49), but not with respiration rate, skin conductance, or cortisol production in saliva following cue exposure. In contrast, craving-past (sub)scales showed a moderate association with cortisol production in saliva (0.15-0.42) following cue exposure. Remarkably, the physical symptoms scale did not show stronger association with psychophysiological and neuroendocrine measures than the other subscales. CONCLUSIONS: The JACQ reliably measures 1 dimension including 4 aspects of craving for distinct time frames. Despite the presence of a special subscale for physical sensations, only moderate relationships were found between self-reported craving and biological indicators of cue reactivity. These findings suggest individual differences between alcoholics in the detection and/or reporting of cue-related psychophysiological signs as indicators of cue reactivity. Further research should focus on the nature of these individual differences. In addition, more research is needed on the relative predictive validity of subjective phenotypic indicators of craving (such as self-reported craving) versus objective endophenotypic indicators of craving (such as physiological measures of cue reactivity) for example in the prediction of relapse.

Adult↗

PubMed2007

Reduced frontal lobe activity in subjects with high impulsivity and alcoholism.

OBJECTIVE: Impulsivity is an important characteristic of many psychiatric disorders, including substance-related disorders. These disinhibitory disorders have a similar underlying genetic diathesis, with each disorder representing a different expression of the same underlying genetic liability. This study assessed whether there is a relationship between impulsivity and alcohol dependence, and their correlations with P3 (P300) amplitude, a proposed endophenotype of alcoholism. METHODS: Healthy control subjects (n=58) and subjects with DSM-IV diagnosis of alcohol dependence (n=57) were assessed with a visual oddball task. Event-Related Potentials (ERPs) were recorded from 61 scalp electrodes and P3 amplitudes measured. Barratt Impulsiveness Scale (BIS), version 11, was used to evaluate impulsivity. Source localization of P3 was computed using low-resolution brain electromagnetic tomography (LORETA). RESULTS: Alcoholic subjects manifested reductions in target P3 amplitudes (p<0.0001). Using LORETA, significantly reduced activation was mapped in the cingulate, medial, and superior frontal regions in alcoholic subjects and highly impulsive subjects. Alcoholic subjects had significantly higher scores on the BIS (p<0.0001) than nonalcoholic individuals. There were significant negative correlations between total scores on BIS and P3 amplitude (r=-0.274, p=0.003, on Pz; r=-0.250, p=0.007, on Cz). CONCLUSIONS: Our results demonstrate a strong frontal focus of reduced activation during processing of visual targets in alcoholic subjects and individuals with higher impulsivity. The findings suggest that impulsivity may be an important factor that underlies the pathogenesis of alcohol dependence. Studies are underway to examine the relationship between impulsivity and ERPs in offspring of alcoholic subjects, and to identify genes associated with the underlying predisposition involved in disinhibitory disorders.

Adult↗