Structural correlates of intellectual impairment and autistic features in adolescents

Intellectual disability, a common but under-researched condition, is strongly associated with autism spectrum disorders (ASD). Although studies have investigated the neural correlates of intelligence quotient (IQ) and ASD in intellectually unimpaired subjects, these issues have not been addressed in intellectually impaired subjects. We studied 63 intellectually disabled adolescents receiving additional learning support and 72 controls using whole brain tissue volumes extracted from native space and voxel-based morphometry (VBM) in normalised space. We applied a qualitative and quantitative review of VBM preprocessing and modified the optimised method to establish optimum co-registration of the brains in normalised space. We report tissue density differences at cluster level with adjustment for underlying smoothness. Individuals with intellectual disability had smaller total white matter and total brain tissue volumes than controls, as well as reduced grey matter density in the right cerebellar hemisphere and left temporo-parietal cortex, and reduced white matter density in the posterior corpus callosum. Intellectually disabled subjects were additionally subgrouped according to their degree of reported autistic features. Reduced grey matter density was detected in the thalamus of subjects with autistic features scoring within the pervasive developmental disorder range as compared to subjects below the threshold for ASD, and increased white matter density was detected in the left superior temporal gyrus of subjects scoring above the threshold for autism as compared to subjects below the threshold for ASD.     

Neural correlates of adjunctive rivastigmine treatment to antipsychotics in schizophrenia: a randomized, placebo-controlled, double-blind fMRI study

Facilitation of central cholinergic activity may form a potential treatment strategy for cognitive impairment in schizophrenia. In a randomized, placebo-controlled, double-blind, parallel-group design, we investigated the neural correlates of cognitive effects of rivastigmine, an acetylcholinesterase inhibitor, given as an add-on therapy to antipsychotic-treated schizophrenia patients. Thirty-six chronic schizophrenia patients with mild cognitive impairment took part. After 1 week on placebo (baseline), all patients entered a double-blind protocol; 18 were allocated to receive rivastigmine and 18 placebo for the next 12 weeks (final sample with usable imaging data: 11 patients on rivastigmine, 10 on placebo). All patients underwent functional magnetic resonance imaging during a parametric 'n-back' task, involving monitoring of dots in particular locations on a screen at a given delay from the original occurrence, twice: at baseline and 12 weeks post-rivastigmine/placebo treatment. Compared to placebo, rivastigmine produced only a small and non-significant improvement in task accuracy across all conditions with no change in response latency, and increased activity in the extrastriate visual cortex in areas associated with visual and spatial attention but not in any region within the working memory network. Our observations suggest that cholinergic enhancement with rivastigmine at doses known to be effective in Alzheimer's disease does not produce strong and clinically meaningful cognitive and neural changes in schizophrenia patients treated with atypical antipsychotics although the neural effects in terms of enhanced neuronal activity in regions associated with visual and spatial attention are consistent with those reported previously with cholinergic enhancement in healthy subjects.     

An acquired translocation in JAK2 Val617Phe-negative essential thrombocythemia associated with autosomal spread of X-inactivation

The acquired mutation Val617Phe in the tyrosine kinase JAK2 was recently identified in most but not all patients with classical myeloproliferative disorders. We describe a cytogenetic and molecular study of a JAK2Val617Phe-negative case of essential thrombocythemia harboring the acquired translocation t(X;5)(q13;q33). We show that this involves the inactive X-chromosome and is associated with silencing of autosomal genes within the adjacent 5q minus syndrome common deleted region. This is the first documented example of autosomal gene silencing adjacent to an X-autosome breakpoint in human malignancy and such a mechanism may underlie the pathogenesis of related disorders with translocations involving Xq13.     

Managed Care Organizations’ Use of Treatment Management Strategies for Outpatient Mental Health Care

A nationally representative sample of managed care organizations was surveyed (response rate=92%) regarding use of treatment management techniques for outpatient mental health care in their commercial products in 1999. Bivariate tests and logistic regression models were used to examine the relationship between product type, behavioral health contracting arrangement and treatment management techniques (prior authorization, standards for time to initial appointment, concurrent review, standards for follow-up after discharge, case management, practice guidelines). Prevalence varied from 43% to 87% depending on the technique. HMO products and products with specialty behavioral health contracts were more likely to use the techniques. Product type and contracting arrangement had independent effects.     

Neural dysfunction and violence in schizophrenia: an fMRI investigation

Contemporary theories and evidence implicate frontal lobe dysfunction in violent behaviour as well as in schizophrenia. We applied functional magnetic resonance imaging (fMRI) to investigate and compare brain activation during an 'n-back' working memory task in groups of men with (i) schizophrenia and a history of serious physical violence (VS; n=13), (ii) schizophrenia without a history of violence (NVS: n=12), (iii) antisocial personality disorder (APD) and a history of serious physical violence (n=10), and (iv) no history of violence or a mental disorder (n=13). We observed comparable performance in all four groups during the control (0-back) condition. Subtle working memory deficits were seen in the NVS and APD groups but severe deficits emerged in the VS group relative to the healthy group. The VS group showed activation deficit bilaterally in the frontal lobe and precuneus when compared to the healthy group, and in the right inferior parietal region when compared to the NVS group during the working memory load condition. Frontal (bilateral) as well as right inferior parietal activity was negatively associated with the ratings of violence across all schizophrenia patients, with the right parietal region showing this association most strongly. APD patients, relative to healthy subjects, showed activation deficit in the left frontal gyrus, anterior cingulate and precuneus. It is concluded that reduced functional response in the frontal and inferior parietal regions leads to serious violence in schizophrenia perhaps via impaired executive functioning.