Francis M. Crinella

Effect of Stimulant Medication on Children with Attention Deficit Disorder: A “Review of Reviews”

The University of California, Irvine ADD Center recently conducted a synthesis of the literature on the use of stimulants with children with attention deficit disorder (ADD), using a unique “review of reviews” methodology. In this article, we compare three reviews from each of three review types (traditional, meta-analytic, general audience) and illustrate how coding variables can highlight sources of divergence. In general, divergent conclusions stemmed from variations in goal rather than from variations in the sources selected to review. Across quantitative reviews, the average effect size for symptomatic improvement (.83) was twice that for benefits on IQ and achievement measures (.35). A summary of what should and should not be expected of the use of stimulants with ADD children, derived from the literature synthesis, is provided.

Reaction time, evoked brain potentials, and psychometric g in the severely retarded

Measurements derived from reaction time (RT), movement time (MT), and an index of neural adaptability (NA) derived from averaged evoked potentials are significantly related to each other as well as to g factor scores extracted from a battery of 15 psychometric tests in a sample of 54 severely retarded adults. The RT-MT and NA variables show a shrunken multiple R of .64 (p < .001) with psychometric g.

Effect of High Dietary Manganese Intake of Neonatal Rats on Tissue Mineral Accumulation, Striatal Dopamine Levels, and Neurodevelopmental Status

Mn is an essential element, but may become neurotoxic at high levels. Recent reports of high Mn levels in hair of children with neurodevelopmental deficits suggest that these deficits could be due to Mn-induced neurotoxic effects on brain dopamine (DA) systems, although the mechanism is not well understood. Infant formulas contain considerably higher concentrations of Mn than human milk. Thus, formula-fed infants are exposed to high levels of Mn at a time when Mn homeostasis is incompletely developed. We studied the effects of dietary Mn supplementation of rat pups on tissue Mn accumulation, brain dopamine levels, infant neurodevelopmental status, and behavior at maturity. Newborn rats were supplemented daily with 0, 50, 250, or 500 microg Mn given orally from day 1 to day 20. Mineral analysis of small intestine and brain at day 14 showed a significant increase of tissue Mn in supplemented rats. Neurodevelopmental tests conducted at various ages showed significant delays as a function of Mn supplementation. At day 32, there was a significant positive relationship between passive avoidance errors and Mn supplementation levels. Brains of animals killed on day 40 showed a significant inverse relationship between Mn supplementation level and striatal dopamine concentration. These observations suggest that dietary exposure to high levels of Mn during infancy can be neurotoxic to rat pups and result in developmental deficits.

Effects of Neonatal Dietary Manganese Exposure on Brain Dopamine Levels and Neurocognitive Functions

Neonatal exposure to high levels of manganese (Mn) has been indirectly implicated as a causal agent in attention deficit hyperactivity disorder (ADHD), since Mn toxicity and ADHD both involve dysfunction in brain dopamine (DA) systems. This study was undertaken to examine this putative relationship in an animal model by determining if levels of neonatal dietary Mn exposure were related to brain DA levels and/or behavioral tests of executive function (EF) when the animals reached maturity. We used 32 newborn male Sprague-Dawley rats and randomly assigned them to one of the four dietary Mn supplementation conditions: 0, 50, 250 and 500 microg per day, administered daily in water from postnatal days 1-21. During days 50-64, the animals were given a burrowing detour test and a passive avoidance test. At day 65, the animals were killed and brains were assayed for DA. There was a statistically significant relationship (P = 0.003) between dietary Mn exposure and striatal DA. On the burrowing detour and passive avoidance, greater deficits were observed for animals subjected to higher Mn exposure, but these differences did not reach statistical significance. However, tests for heterogeneity of variance between groups were statistically significant for all measures, with positive relationship between Mn exposure and degree of within-group behavioral variability. Kendalls nonparametric test of the relationship between the three behavioral measures and striatal DA levels was also statistically significant (P = 0.02). These results lend support to the hypothesis that neonatal Mn exposure is related to brain DA levels and neurocognitive deficit in the rodent.

Why Children with ADHD Do Not Have Low IQs.

The major cognitive deficit of children with attention-deficit/hyperactivity disorder (ADHD) is impaired executive function (EF), a cognitive component that some theorists believe to be the primary substrate for the general intelligence (g) factor. We review the constructs of g and EF and the relevant research findings on ADHD. We then analyze the results of a battery of diverse tests, including measures of EF, administered to 123 boys with ADHD. The correlations among the EF measures, two well-accepted measures of IQ, and the g factor extracted from the entire battery are trivial at best. These results are discussed in the context of collateral evidence supporting the independence of g and EF and its clinical and theoretical implications.

Naltrexone reduces self-injury and improves learning.

Author(s): Sandman, CA; Hetrick, WP; Taylor, DV; Barron, JL; Touchette, P; Lott, I; Crinella, F; Martinazzi, V | Abstract: A cross-over study of 24 Ss with self-injurious behavior (SIB) was conducted over a continuous 10-week period. Treatment with naltrexone (NTX) was provided for 3 weeks in a randomized, reversal design with different doses or placebo each week. Videotaped observations (20 hr/subject), neurological examinations, and ratings of adaptive and maladaptive behavior were collected. Treatment with 2 mg/kg NTX produced at least a 50% reduction in SIB in a significant (p l.01) number of Ss. The 1.0 mg/kg was less effective (p l.02), and no significant change was observed at 0.5 mg/kg. Eighteen of 21 Ss achieved at least a 25% reduction in SIB after treatment of at least 1 dose of NTX (p l.0001). More than half of the Ss (52%) had a l 50% reduction (p l.001), and a significant number of Ss (33%) decreased SIB by more than 75% after at least 1 dose of NTX. Significant improvement was measured after NTX on measures of learning and attention.

Brain mechanisms and intelligence. Psychometric g and executive function.

Abstract Sternberg [Sternberg, R.J. (1985). Beyond IQ: a triarchic theory of human intelligence. New York: Cambridge Univ. Press.] has proposed that the general intelligence, or the g factor, obtained when batteries of mental tests are factor analyzed, is a reflection of the fact that executive functions (EF) are common to all cognitive tests. Three lines of evidence that fail to support Sternbergs formulation are presented. First, in animal problem solving studies, there is only a modest degree of overlap between brain structures that are critical for g, and brain structures that have been identified as the rodent EF system. Second, children with attention deficit-hyperactivity disorder (ADHD), characterized by EF dysfunction, do not have IQ scores that are lower, on average, than children in the test standardization populations. Third, human frontal lobe patients often have clear EF deficits, but IQ (a next-best estimate of g) may be preserved. These findings cast serious doubt on the plausibility of Sternbergs formulation. Clarifying the distinction between psychometric g and EF can be important for understanding the differences between practical and psychometric intelligence.

Chapter 20 Attention and Hyperactivity

More than a decade ago, in response to persuasive arguments by Douglas (1972) and others that children diagnosed with Hyperkinetic Reaction of Childhood (DSM-II, 1968) might have a primary deficit in attention processes, the diagnostic criteria and label for this disorder were changed to emphasize attention deficits [e.g., Attention Deficit Disorder with (ADDH) or without (ADD) Hyperactivity in DSM-III (1980), and Attention Deficit-Hyperactivity Disorder (ADHD) in DSM-III-R (1987)] A great deal of research has been devoted to searching for a core attention deficit in these children. Among researchers involved in this search, there is an emerging opinion that children with ADD/ADHD may not have a specific information processing deficit that can be attributed to a defect in attention. The empirical support for this view has emerged in recent investigations which have used paradigms from cognitive psychology to measure attention based on performance on laboratory tasks. This research has shown that some theoretically important components of attention do not distinguish ADD/ADHD patients from normal subjects, and this has convinced many investigators that “attention deficit” is not the core defect of the ADD/ADHD syndrome. Several issues about diagnosis and labeling of ADD/ADHD are discussed in this chapter. Based on new models of attention, we present a position in favor of retention of the term “attention deficit” as part of the psychiatric label, but we recommend restricting this label to a smaller, more homogeneous group of children than specified by DSM-III or DSM-III-R criteria.

Long-Term Effects of Naltrexone on Self-Injurious Behavior.

A subgroup of self-injuring patients responds positively to the opiate-blocking agent naltrexone in acute, double-blind studies. In this study we examined the effects of naltrexone after acute treatment and the long-term effects of naltrexone on SIB. Rates of SIB were collected from pretreatment baseline; a second baseline a year after the acute trial; and a subsequent 12-month double-blind, placebo-controlled treatment. A subgroup of patients decreased SIB for a year without treatment after acute exposure to naltrexone. Five participants who decreased SIB by 70% after acute treatment increased SIB to the long-term treatment with naltrexone. In contrast, those for whom SIB increased over the one-year treatment hiatus decreased their SIB after the first long-term treatment. Discussion of these complex effects considered the role of background opioid levels, dosing, and treatment regimen of naltrexone and other factors limiting receptor adaptation among patients who exhibit SIB.

Brain mechanisms in problem solving and intelligence: A replication and extension

Abstract Anderson (1993, 1995) recently reported the extraction of a general intelligence (g) factor from a battery of tests administered to laboratory rats, conflicting with historical evidence and our more recent study of rat problem-solving behavior ( Thompson, Crinella, & Yu, 1990) . Andersons findings are most likely due to use of an outbred strain, whereas we and others used inbred rats. However, it has been suggested that these unique findings may be due to Andersons use of a more g-loaded test battery. We tested this hypothesis by analyzing the performance of 120 adult male Sprague-Dawley rats on seven laboratory tests, selected for diversity and g saturation. At 21 to 23 days of age, 96 of the animals were bilaterally lesioned in one of 48 brain sites, and 24 remained unlesioned. Testing began at 42 to 45 days of age. Analysis of data from the 24 unlesioned animals showed no evidence of a g factor. When data from unlesioned and lesioned animals were combined, uniformly positive correlations were obtained, and an unrotated first principal component accounted for 34% of the variance. This component had psychometric properties analogous to g factors extracted from human test batteries. The results support our contention that the disparity between Andersons findings and ours are due to strain differences, and not psychometric properties of the respective test batteries. The results also show that the g loading of a test is directly related to the number of brain structures required to mediate its performance—biological support for the view that tests with higher g loadings sample a proportionately greater number of elementary processes than tests with lower g loadings. Because the psychometric g factor is sensitive to the widest array of brain lesions, it may be the best measure for detecting neuropsychological deficit irrespective of lesion location.