Deborah N. Black

Cree leukoencephalopathy and CACH/VWM disease are allelic at the EIF2B5 locus

Cree leukoencephalopathy is a rapidly fatal infantile autosomal recessive leukodystrophy of unknown cause observed in the native North American Cree and Chippewayan indigenous population. We found in the brain of affected individuals the typical foamy cells with the oligodendroglial phenotype described in central hypomyelination syndrome/vanishing white matter, a syndrome related to mutations in the genes encoding the five subunits of the eucaryotic translation initiation factor eIF2B. In three patients of two Cree families, we found a homozygous missense mutation resulting in a histidine substitution at arginine 195 of ε‐eIF2B.

Neuroanatomy of Dopamine: Reward and Addiction

Abnormalities of the physiological reward system are believed to play a major part in many serious psychiatric disorders, such as substance abuse, pathological gambling, and major depression. Motivation that involves liking, wanting, craving, and learning about pleasurable events and behavior is heavily influenced by the circuitry of the dopamine reward system, which plays a major role in both normal reward behavior and pathological behavior and addiction. In this Windows to the Brain article, the authors elucidate the mechanisms of this system.

Leukotomy revisited: late cognitive and behavioral effects in chronic institutionalized schizophrenics

BACKGROUND In the 1940s and 1950s, prefrontal lobotomy was widely used to treat aggressive, disruptive and psychotic behavior in schizophrenics. Subsequent observations have confirmed its ineffectiveness in schizophrenia. Few studies have addressed its long-term consequences. METHODS We conducted tests of frontal function, behavior (Frontal Behavioral Inventory), psychopathology (PANSS), neurological examinations and CT scans in 19 chronically institutionalized schizophrenic patients (mean age 74) who had undergone orbitofrontal leukotomy between 1948 and 1972 and 11 controls (mean age 74) matched for age, length of hospitalization, education, and diagnosis. RESULTS There were no significant differences between leukotomized patients and controls on: Folstein Mini-Mental score (leuko 22.13+/-5.66; controls 23.55+/-5.93), utilization behavior, Luria alternating written and motor sequences, verbal fluency, imitation behavior, motor impersistence, primitive reflexes, or psychopathology. Significant differences were found on clock drawing and on the go/no-go test, which may reflect the presence of an orbitofrontal lesion in the leukotomized group. There was a tendency for the leukotomized group to have fewer indices of frontal behavioral dysfunction. Both groups showed comparable impairment on the Stroop test and cognitive rigidity on the Odd Man Out test of category shifting. CONCLUSIONS With few exceptions, elderly leukotomized and nonleukotomized schizophrenic patients show varying degrees of distractibility, difficulty in set shifting, poor planning and organization, susceptibility to interference, primitive reflexes and signs of global cognitive impairment. Allowing for the small sample size, variability in the surgical frontal lesion, and the long interval from surgery to testing, these observations likely reflect the long-term consequences of severe schizophrenia in both groups.

Long-term effect of prefrontal lobotomy on verbal fluency in patients with schizophrenia.

OBJECTIVE This study investigated the long-term effects of bilateral prefrontal leukotomy on lexical abilities in schizophrenia subjects. METHOD we compared performances of leukotomized (LSP), non-leukotomized schizophrenia patients (NLSP) and normal controls, using a test of verbal fluency. Multiple case and triple comparison design were implemented. i.e., the performance of each LSP was compared to that of NLSP and that of a normal control. The sample consisted of four LSP, four NLSP, and four normal subjects. Subjects were matched in sex, age, handedness, and schooling. In Addition, schizophrenia groups were matched in diagnosis and years of hospitalization. Quantitative and qualitative analyses of generated words and errors produced by subjects were carried out. RESULTS A deficiency in both groups of schizophrenia was observed, although a better performance in LSP patients was detected. CONCLUSION Intact Lexical ability in LSP indicates its poor relation to the frontal lobe.

Book Review: Épilepsie: Syndromes épileptiques et troubles psychotiquesSyndromes épileptiques et troubles psychotiques. de ToffolBertrand. Paris: Éditions John Libbey Eurotext; 2001. US

Ceux qui ont peu de temps à consacrer à ce petit livre dense de 178 pages seraient bien servis de lire la dernière partie, consacrée à la physiopathologie. On y trouve une analyse approfondie des hypothèses neurophysiologiques, une revue de la structure et de la fonction du système limbique, des altérations génétiques et synaptiques en conséquence d’une crise ou d’une série de crises, une revue critique du concept de « l’embrasement » (kindling) dans la genèse des psychoses, des données pharmacologiques et neurochimiques, y compris le rôle non négligeable des anticonvulsivants, et une considération du rôle de la dysgénésie corticale dans l’épilepsie et dans la schizophrénie. Quoique l’orientation neurobiologique de l’auteur soit explicite, les hypothèses psychodynamiques des états psychotiques sont dûment exposées. En raison de l’analyse de différentes hypothèses — fonctionnelles, pharmacologiques, structurales et psychogénétiques — nous nous attendons à une synthèse, un mot final, regroupant ces contributions diverses. Le professeur de Toffol résiste à ce piège : « Il nous semble impossible, en l’état actuel des connaissances, de regrouper les faits hétérogènes à partir de méthodes d’études très variées, qui éclairent chacune un aspect très partiel des problèmes. » Tout au plus, de Toffol se permet la réflexion « que l’existence d’une dysfonction amygdalienne unilatérale sévère évoluant au sein d’un cerveau porteur de lésions bi-hémisphériques représente une situation particulièrement à risque de psychose ».