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If this is the between RD and MD was confirmed in several studies cheap 1000 mg carafate mastercard gastritis eating plan. A case, there may be 'double-deficit' readers who are im- strong link of Tourette syndrome, ADHD, and LD has paired in both phonologic and rapid naming processes (23). Evidence has accumu- tions that address phonologic processing and would require lated that locations on the short arm of chromosome 6 TABLE 44. GENETICS OF LEARNING DISORDERS Study Subjects Method Comment Comings and Comings, 47 normal controls, 246 TS Comparison of TS and 27% of TS had LD vs 4. However, these reviews also call attention to discrepancies Odds for linkage to chromosome 15 are reported as being in findings, possibly the result of small cohorts, variations 1,000 to 1, with evidence that 30% of an extended series of in sampling, and heterogeneity of the LDs. Many studies confirm earlier findings of trait markers. The excess of affected males with LDs identi- abnormalities of the microstructure of the planum tempor- fied in clinic and referred samples disappears in research- ale from autopsy studies, but conflicting data emerge, possi- based samples (25). Although most studies implicate abnormalities in left temporal-parietal ana- tomic areas, additional findings have identified white mat- NEUROIMAGING ter, right hemisphere anomalies, motor cortex, cingulate gyrus, and the splenium of the corpus callosum. The neuroanatomic and functional pathways in the brain One of the older controversies regarding the functional involved in LDs were greatly clarified in the 1990s by a brain basis of dyslexia is whether dyslexia represents a visual variety of neuroimaging techniques. Reviews of neuroimag- (orthographic) disorder or a language-based (phonologic ing of LDs describe rapid progress in identifying the brain processing) disorder. Neuroimaging studies now appear to regions and functional pathways involved (20,26–29). NEUROIMAGING IN LEARNING DISORDERS Study Method Subjects Results Klingberg et al. White matter diffusion anisotropy in the temporoparietal region of the left hemisphere was significantly correlated with reading scores within the reading-impaired adults and within the control group. The anisotropy reflects microstructure of white matter tracts, which may contribute to reading ability by determining the strength of communication between cortical areas involved in visual, auditory, and language processing. Dyslexics with a history of many symptoms of ADHD in childhood (high ADHD) accounted for the group differences in P300; the dyslexics with a history of few or no such symptoms (low ADHD) were indistinguishable from the controls at all electrode sites. The results are interpreted as suggesting that a distinct brain organization may characterize dyslexic men with a history of concomitant deficits in attention. In contrast, the letter-string–specific responses peaking around 150 ms predominantly in the left inferior occipitotemporal cortex in fluent readers were undetectable in dyslexic readers. Thus, while the early visual processing seems intact in dyslexic adults, the pattern of cortical activation starts to differ from that of fluent readers at the point where letter-string–specific signals first emerge during reading. Best and Demb, Sagittal magnetic resonance Dyslexics with documented Dyslexic subjects did not deviate from 1999 (32) images of PT and MC deficits and controls normal leftward PT asymmetry, magnocellular visual but both groups became less pathway left-lateralized with methods that excluded sulcul tissue. Results suggest that dyslexic subjects with a magnocellular deficit do not always have abnormal symmetry of the PT. PT symmetry may instead be related to a different subtype of dyslexia. In addition, PT asymmetry in any subject group depends on the measurement method. In contrast, no group main or interaction effects for the subcortical or callosal structures. No significant differences were observed in the nonlanguage tasks. These results preclude an explanation of deep dyslexia in terms of purely right-hemisphere word processing. These results support the separation of the reading disabled into a group that has difficulty translating orthography into phonology and a group that is slower functioning and has reduced capacity in preparing for a response. These results support a conclusion that the impairment in dyslexia is phonologic and that these brain activation patterns may provide a neural signature for this impairment. Given the heterogeneity of the dyslexic population, some subgroup of dyslexic individuals (i.
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For example generic carafate 1000 mg with visa gastritis problems, Gur and associates (8) found ferent time points in the disorder. EXPERT OPINION Our summary relies on a combination of these ap- VERSUS COUNTINGVERSUS proaches. Accordingly, we have followed a sug- field) relies on reviews with essentially three main ap- gestion of Rosenthal (11), and computed the probability of proaches, which can be combined. This is simply done by using a two-tailed alpha level of p. The resulting overall probability does not assume a nor- and findings, with specific citations to drive home the mal distribution, but does assume comparability of the stud- points. Many reviews, in fact, adopt this approach of 'trust ies. We see this as an im- This approach tabulates the number of studies with findings provement on simply saying 'some studies find... The disadvantage of this approach is that the subject the weight of evidence from peer-reviewed studies based on N of each study and the effect size are not taken into ac- a probability of. Metaanalysis Metaanalysis essentially involves weighting each individual CURRENT STRUCTURAL FINDINGS IN study by a function of its N and effect size, and then using SCHIZOPHRENIA this information to produce an estimate of the combined effect size (9–11). If all studies used equivalent technology A complete review is not appropriate here because the ex- and subject populations, this would be the method of choice. However, because it seemed essential to MR scanner technology in the past decade has been chang- us that the reader have at least an overview of structural ing rapidly; therefore, studies are not quantitatively compa- results in schizophrenia (with references), we have drawn rable; (b) the extent of detail varies in anatomically based on data from a recent comprehensive review (13). This cov- ROI information used in the measurement of images; (c) ered all peer-reviewed schizophrenia studies with control there is a wide difference in moderator variables of subject groups during the time period 1987 to May 1998, and to gender, chronicity (age of onset), medication, parental SES, our knowledge is the most recently published comprehen- etc. Another disadvantage is that many studies must Most studies (81% of 31) did not find abnormalities 762 763 764 Neuropsychopharmacology: The Fifth Generation of Progress of whole brain/intracranial contents, but lateral ventricle except for the fourth ventricle and cerebellum (p. Again, caution should be exercised on the strength three studies evaluating the fourth ventricle found abnor- of these probability estimates because comparability is not malities. Of Clinical Symptom Implications all cortical areas surveyed, the superior temporal gyrus most consistently showed volume reduction (81% of 16 studies) Clinical scale data suggest that positive symptoms (and dis- and, if the gray matter of this structure was evaluated sepa- organization in a three-factor model) may be most closely rately from white matter, all seven studies showed a volume related to temporal lobe volumetric abnormalities, whereas reduction. Fully 77% of the 30 studies of the medial tem- more limited evidence supports, in some studies, a relation- poral lobe reported abnormalities in one or more of its con- ship between negative symptoms and frontal lobe MRI ab- stituent structures (hippocampus, amygdala, or parahippo- normalities. Finally, there now appears to be growing evi- campal gyrus). Neuropathologic studies in general support dence that MRI abnormalities differ in affective (bipolar) the presence of temporal lobe limbic system abnormalities psychosis and schizophrenia, with reductions in neocortical in schizophrenia (14,15), although some do not (16). Un- gray matter, especially in temporal and prefrontal neocortex fortunately, there is a lack of quantitative postmortem stud- being especially prominent in schizophrenia. In a postmortem quantitative study, Sele- the latter, see Kikinis and colleagues) (18) and abnormalities mon and associates (17) found only a small (8%) reduction in first-episode patients all suggest a possible developmental in prefrontal cortical thickness, a reduction that was not origin. However, there are growing (although still limited) statistically significant, although noteworthy abnormalities data pointing to progression of volumetric abnormalities in density of various cell types were present in schizophrenia. This suggests that both developmental and pro- This and the MRI findings suggest that frontal lobe volume gressive features may be present in schizophrenia; these are reductions may be small, and near the threshold for MRI consistent with, we hypothesize, a 'two-hit' model of schiz- detection. The parietal and occipital lobes have been much ophrenia. Most of the seven studies of cortical gray matter (86%) find that volume re- AUTOMATINGSTRUCTURAL MRI ductions are not diffuse, but are more pronounced in certain ANALYSIS: BRAIN WARPINGAND VOXEL- areas, as might be anticipated from the preceding statistics BASED ANALYSIS on individual regions of interest. About two-thirds of the studies of subcortical structures The tedious task of manual definition of regions of interest report positive findings, including the six studies of the thal- by tracing outlines—even if assisted by automated segmen- amus, 18 studies of the corpus callosum, and 17 studies of tation—has prompted interest in using automated methods the basal ganglia. Basal ganglia tended to show increased of MRI analysis. The two (closely related) major classes of volume when patients were on typical but not on atypical methods are: (a) brain warping, using a standard or 'atlas neuroleptics. The cerebellum had mainly negative findings brain' to compare and define features on subject brains, and (in four of the six studies), but was not studied with the (b) voxel-based analyses. Because these techniques, although same volumetric precision as other ROI. Almost all (91%) promising, are new and thus far have limited data on valid- of the 11 studies of cavum septi pellucidi (CSP) showed ity, we have not included the studies in the summary table that schizophrenics have less fusion of the septum, a devel- of ROI findings. This section concludes with a brief discus- opmental abnormality probably linked to limbic system pa- sion of shape analysis, often based on the brain warping thology.
