The paradox of quetiapine in obsessive-compulsive disorder

Schizophrenia and obsessive-compulsive disorder (OCD) have historical, clinical, and epidemiological links. The clinical use of atypical neuroleptics (ie, dual serotonin-dopamine antagonists) to treat both conditions sheds a new light on them. We report the first two cases of obsessive-compulsive symptoms (OCS) induced by quetiapine in schizophrenia patients. A case of successful augmentation by quetiapine in refractory OCD is also presented. A review of the literature on OCS induced by atypical neuroleptics follows. This paradoxically induced OCD symptomology in schizophrenia patients administered atypical neuroleptics is discussed from new pathophysiological and clinical perspectives. The discussion emphasizes the prognostic implications of OCS in schizophrenia and available therapies for this comorbidity.     

Development of subtype selective GABAA modulators

Drugs modulating gamma-aminobutyric acid (GABA) transmission via the benzodiazepine (BZ) site on the gamma-aminobutyric acid type A (GABAA) receptor have been in widespread use for more than 40 years to treat anxiety, epilepsy, and sleep disorders. These drugs have been shown to be safe, well tolerated, and effective although the mechanism by they produce a myriad of pharmacologic effects remains elusive. In recent years it has been discovered that, although the GABAA receptor is widely distributed in the brain, the substructure and composition of the receptor differs from between brain regions. Termed "GABAA receptor subtypes" their discovery leads to speculation that different subtypes may mediate specific effects of BZs such as anxiety or sedation. The phenotypic analysis of transgenic knock-in and knock-out mice in which particular GABAA receptors were rendered insensitive to the effects of BZ while others were unaffected confirmed this speculation. Subsequently, subtype-specific GABAA ligands were developed that, for example, retained the anxiolytic effects of BZs but were devoid of their sedative effects. Therefore, it may be possible to develop effective anxiolytic compounds that have a much reduced side-effect profile compared with existing drugs.     

Laboratory measured behavioral impulsivity relates to suicide attempt history

The purpose of this study was to examine the relationship between laboratory behavioral measured impulsivity (using the Immediate and Delayed Memory Tasks) and suicidal attempt histories. Three groups of adults were recruited, those with either: no previous suicide attempts (Control, n = 20), only a single suicide attempt (Single, n = 20), or multiple suicidal attempts (Multiple, n = 10). As hypothesized, impulsive responses increased with the number of suicide attempts (Control < Single < Multiple). This study helps to demonstrate how laboratory behavioral measures of impulsivity can be used to discriminate groups based on suicidal histories among samples not currently exhibiting significant suicidal behaviors.     

A formal model for structuring local perceptions of environmental space

The problem of constructing computational models of space that mimic those found in human spatial reasoning is addressed. This paper extends a formal model that addressed point objects in a 2D world to include the presence of line objects and barriers. The problem consists of determining an appropriate global model for the spatial configuration given a sequence of local views or observations. A formal model is proposed based on constraint network theory. The model leads to the identification of stable regions within which perceptual information about the environment changes slowly, and zones of transition within which the perceptual information changes more quickly. A special case of transition zones is a gateway, which may be viewed as a kind of discontinuity or singularity in the model. It is expected that the model obtained will be used to mimic human mental representations of navigable outdoor environments.     

Do age of onset and course of illness define biologically distinct groups within atypical depression?

Illness course separates patients with atypical depression into tricyclic responders and nonresponders as does perceptual asymmetry. The authors therefore investigated whether the course-of-illness parameters would define groups within atypical depression differing in brain laterality. Patients with atypical depression were assessed for illness course and brain laterality. Two patient groups were defined, 1 with onset prior to age 20 plus a very chronic course, and a 2nd group having later onset or less chronic illness. Patients reporting early onset of very chronic dysphoria showed significantly less right-ear (left-hemisphere) accuracy and also differed in characteristic perceptual asymmetry when compared to patients with later onset or less chronicity. Course of illness may usefully define more homogeneous depressive subgroups within atypical depression.     

Commission error rates on a continuous performance test are related to deficits measured by the Benton Visual Retention Test

This study is one in a series investigating the relationship between impulsive behavior on a Continuous Performance Test (i.e., the Immediate and Delayed Memory Task) and other cognitive deficits measured by clinical instruments. Forty-two adolescents were selected for two groups, controls and hospitalized patients with disruptive behavior disorders. Each adolescent completed the Immediate and Delayed Memory Task and the Benton Visual Retention Test. Our main findings were that, even when controlling for IQ, the Immediate and Delayed Memory Task commission errors were associated with adverse Benton performance, but only in the patient group. These results may be explained by a shared association between processes of impulsivity and other deficits of executive control that may interfere with successful performance of the Benton.     

Perirhinal cortex lesions impair context aversion learning

Rats with perirhinal cortex lesions were compared with sham controls on a conditional discrimination in which saccharin was paired with LiCl in context 1, but paired with saline in context 2. Perirhinal-lesioned rats were slightly slower to acquire the discrimination but reached control levels by the end of acquisition. Both groups showed transfer to familiar tap water, consuming less in context 1 than in context 2. Unlike sham rats, perirhinal rats failed to show an aversion to context 1 on a place choice test. These data provide neuroanatomical support for the postulated difference between Pavlovian conditioning and conditional learning.     

A Kripke Semantics for the Logic of Gelfand Quantales

Gelfand quantales are complete unital quantales with an involution, *, satisfying the property that for any element a, if a b a for all b, then a a* a = a. A Hilbert-style axiom system is given for a propositional logic, called Gelfand Logic, which is sound and complete with respect to Gelfand quantales. A Kripke semantics is presented for which the soundness and completeness of Gelfand logic is shown. The completeness theorem relies on a Stone style representation theorem for complete lattices. A Rasiowa/Sikorski style semantic tableau system is also presented with the property that if all branches of a tableau are closed, then the formula in question is a theorem of Gelfand Logic. An open branch in a completed tableaux guarantees the existence of an Kripke model in which the formula is not valid; hence it is not a theorem of Gelfand Logic.