Fabry disease in genetic counseling practice: recommendations of the National Society of Genetic Counselors

The objective of this document is to provide health care professionals with recommendations for genetic counseling and testing of individuals with a suspected or confirmed diagnosis of Fabry disease, with a family history of Fabry disease, and those identified as female carriers of Fabry disease. These recommendations are the opinions of a multicenter working group of genetic counselors, medical geneticists, and other health professionals with expertise in Fabry disease counseling, as well as an individual with Fabry disease who is a founder of a Fabry disease patient advocacy group in the United States. The recommendations are U.S. Preventive Task Force Class III, and they are based on clinical experience, a review of pertinent English-language articles, and reports of expert committees. This document reviews the genetics of Fabry disease, the indications for genetic testing and interpretation of results, psychosocial considerations, and references for professional and patient resources. These recommendations should not be construed as dictating an exclusive course of management, nor does use of such recommendations guarantee a particular outcome. The professional judgment of a healthcare provider, familiar with the facts and circumstances of a specific case, will always supersede these recommendations.     

Rapid adaptation to auditory-visual spatial disparity

The so-called ventriloquism aftereffect is a remarkable example of rapid adaptative changes in spatial localization caused by visual stimuli. After exposure to a consistent spatial disparity of auditory and visual stimuli, localization of sound sources is systematically shifted to correct for the deviation of the sound from visual positions during the previous adaptation period. In the present study, this aftereffect was induced by presenting, within 17 min, 1800 repetitive noise or pure-tone bursts in combination with synchronized, and 20° disparate flashing light spots, in total darkness. Post-adaptive sound localization, measured by a method of manual pointing, was significantly shifted 2.4° (noise), 3.1° (1 kHz tones), or 5.8° (4 kHz tones) compared with the pre-adaptation condition. There was no transfer across frequencies; that is, shifts in localization were insignificant when the frequencies used for adaptation and the post-adaptation localization test were different. It is hypothesized that these aftereffects may rely on shifts in neural representations of auditory space with respect to those of visual space, induced by intersensory spatial disparity, and may thus reflect a phenomenon of neural short-term plasticity.     

Place learning in scopolamine-treated rats: the roles of distal cues and catecholaminergic mediation

Experiments 1 and 2 tested the hypothesis that cholinergic receptor antagonists impair place learning in a water maze by interfering with the processing of distal, visual cues. Extramaze cues were offered to rats in the form of geometrical patterns arranged on the inner circumference of a curtain surrounding the water maze. In Experiment 1 the animals were offered both the distal cues and proximal cues in the form of pingpong balls in fixed positions on the surface of the water while only distal cues were present in Experiment 2. Animals were injected with either scopolamine (0.5 mg/kg body wt) or saline 20 min prior to the daily place learning sessions. Upon reaching criterion level performance the animals were tested on "rotation" sessions on which the distal cues were displaced. The outcome of such "rotations" demonstrated that-regardless of the presence or absence of proximal cues-scopolamine-treated rats relied at least as much as normal animals on the distal cues. The acquisition phase of both Experiments 1 and 2 demonstrated an almost complete lack of scopolamine-associated impairment in acquisition and performance of the place learning task. In Experiment 3 (when scopolamine was no longer administered) the subjects of Experiment 2 were exposed to a series of pharmacological "challenges" of their place learning performance and eventually to surgical ablation of the anteromedial prefrontal cortex. The outcome of the pharmacological challenges and the postoperative test of task performance demonstrated that the place learning performance of animals which had acquired the task under scopolamine was mediated by a neural substrate dissimilar to the substrate of task performance in normal animals. Rats acquiring the task while deprived of the cholinergic system demonstrated above-normal contributions to task mediation from catecholaminergic-probably dopaminergic-mechanisms and tentative results pointed to a "shift" toward prefrontal task mediation.     

Current concepts on the neurobiology of Attention-Deficit/Hyperactivity Disorder

Attention-Deficit/Hyperactivity Disorder (ADHD) is an early onset, clinically heterogeneous disorder of inattention, hyperactivity, and impulsivity. In contrast to the widespread acceptance of ADHD as a childhood diagnosis, Its prevalence In adults and its implications for clinical practice remain a source of controversy. Throughout the lifecycle, a key clinical feature observed in ADHD patients is comorbidity with Conduct Depressive, Bipolar, and Anxiety disorders. Family studies consistently support the assertion that ADHD runs in families. Heritability data from twin studies of ADHD attribute about 80 percent of the etiology of ADHD to genetic factors. Adoption studies of ADHD also implicate genes in its etiology. Molecular genetic data are bolstered by considerations suggesting that DRD4 and DAT genes may be relevant for ADHD. Independently of genes, prenatal exposure to nicotine and psychosocial adversity have also been identified as risk factors for ADHD. Structural and functional imaging studies consistently implicate catecholamine-rich fronto-subcortical systems in the pathophysiology of ADHD. The effectiveness of stimulants, along with animal models of hyperactivity, point to catecholamine disruption as at least one source of ADHD brain dysfunction. Although not entirely sufficient, changes in dopaminergic and noradrenergic function appear necessary for the clinical efficacy of pharmacological treatments for ADHD, providing support for the hypothesis that alteration of monoaminergic transmission in critical brain regions may be the basis for therapeutic action in ADHD.     

Methylphenidate in treatment of adults with Attention-Deficit/Hyperactivity Disorder

Attention-Deficit/Hyperactivity Disorder (ADHD) can persist into adulthood with a continuation of the pattern of childhood psychopathology, cognition and functioning. Adult comorbidities include substance use disorders, antisocial personality disorder, anxiety, and depression. Studies have shown that as in children, methylphenidate treatment for adults can lead to a robust, dose-dependent improvement in ADHD symptoms. Future research is needed to evaluate the safety and efficacy of long-term treatment with methylphenidate (MPH).     

Psychological and family factors associated with suicidal ideation in pre-adolescents

To assess the psychological and family factors associated with suicidal ideation in pre-adolescent children, we studied a sample of 361 students, average age 9 years old. Two groups were formed, on the basis of the presence (n = 34) or absence (n = 44) of suicidal ideation. Suicidal ideation was assessed with the Children's Depression Inventory and the Children's Depression Rating Scale-Revised. Depression, hopelessness, self-esteem, and perceived family environment were compared in both the suicidal ideation and the control groups. Students with suicidal ideation generally presented greater depressive symptoms and hopelessness, and lower self-esteem and family expressiveness, although there were differences both between sexes, and when the variable depression was controlled. Identifying these risk factors in pre-adolescents may have an impact on prevention of suicidal behavior at higher risk ages.     

The continuing need for disinterested research

For scientific knowledge to be trustworthy, it needs to be dissociated from material interests. Disinterested research also performs other important non-instrumental roles. In particular, academic science has traditionally provided society with reliable, imaginative public knowledge and independent, self-critical expertise. But this type of science is not compatible with the practice of instrumental research, which is typically proprietary, prosaic, pragmatic and partisan. With ever-increasing dependence on commercial or state funding, all modes of knowledge production are merging into a new, ‘post-academic’ research culture which is dominated by utilitarian goals. Growing concern about conflicts of interest is thus a symptom of deep-seated malaise in science and medicine. An expanded version of this paper was presented at an International Conference on “Conflict of Interest and its Significance in Science and Medicine” held in Warsaw, Poland on 5–6 April, 2002.     

How (and where) does moral judgment work?

Moral psychology has long focused on reasoning, but recent evidence suggests that moral judgment is more a matter of emotion and affective intuition than deliberate reasoning. Here we discuss recent findings in psychology and cognitive neuroscience, including several studies that specifically investigate moral judgment. These findings indicate the importance of affect, although they allow that reasoning can play a restricted but significant role in moral judgment. They also point towards a preliminary account of the functional neuroanatomy of moral judgment, according to which many brain areas make important contributions to moral judgment although none is devoted specifically to it.