The future of cognitive and behavioral therapies in the prevention and early management of psychosis: Opportunities and risks

Behavioral and cognitive interventions for people with psychosis have a long and distinguished history, although the evidence for their application to young people remains limited. We anticipate that the next decades will show substantial research into psychological intervention for this population. Important targets will include the management of environmental stressors, reduction of substance misuse, and promotion of early treatment. Psychological management of positive symptoms, depression, and suicidal behavior will continue to be critical objectives. Important secondary prevention goals will be the retention of cognitive functioning, vocational options, social skills, and social network support, including appropriate family support. We expect primary prevention to include both universal programs and interventions for adolescents at particularly high risk. Technical innovations will include increasing use of Internet-based intervention and behavior cueing devices. Pressures for intervention brevity will continue, as will problems with the systematic delivery of effective procedures.

Outpatient cognitive behavioural therapy programme for alcohol dependence impact of naltrexone use on outcome

Objective: Cognitive-behavioural therapy (CBT) has been effectively used in the treatment of alcohol dependence. Clinical studies report that the anticraving drug naltrexone, is a useful adjunct to treatment. Currently, few data are available on the impact of adding this medication to programmes in more typical, outpatient, and rehabilitation settings. The objective of this study was to examine the impact on outcome of adding naltrexone to an established outpatient alcohol rehabilitation program which employed CBT. Method: Fifty patients participated in an established 12-week, outpatient, 'contract'-based alcohol abstinence programme which employed CBT. They also received naltrexone 50 mg orally daily (CBT + naltrexone). Outcomes were compared with 50 historical, matched controls, all of whom participated in the same programme without an anticraving medication (CBT alone). All patients met DSM-IV criteria for alcohol dependence. Results: Programme attendance across the eight treatment sessions was lower in the CBT alone group (p < 0.001). Relapse to alcohol use occurred sooner and more frequently in the CBT alone group (p < 0.001). Rehabilitation programme completion at 12 weeks was 88% (CBT + naltrexone) compared with 36% for (CBT alone) (p < 0.001). Alcohol abstinence at 12 weeks was 76% (CBT + naltrexone) compared with 18% (CBT alone) (p < 0.001). Conclusion: When employing the same outpatient rehabilitation programme and comparing outcomes using matched historical controls, the addition of naltrexone substantially improves programme attendance, programme completion and reported alcohol abstinence. In a typical outpatient programme, naltrexone addition was associated with significantly improved programme participation, better outcomes and was well tolerated.

Lexical decision in Parkinson's disease: A reply to Brown, McDonald, and Spicer (1999)

Recent semantic priming investigations in Parkinsons disease (PD) employed variants of Neelys (1977) lexical decision paradigm to dissociate the automatic and attentional aspects of semantic activation (McDonald, Brown, Gorell, 1996; Spicer, Brown, Gorell, 1994). In our earlier review, we claimed that the results of Spicer, McDonald and colleagues normal control participants violated the two-process model of information processing (Posner Snyder, 1975) upon which their experimental paradigm had been based (Arnott Chenery, 1999). We argued that, even at the shortest SOA employed, key design modifications to Neelys original experiments biased the tasks employed by Spicer et al. and McDonald et al. towards being assessments of attention-dependent processes. Accordingly, we contended that experimental procedures did not speak to issues of automaticity and, therefore, Spicer, McDonald and colleagues claims of robust automatic semantic activation in PD must be treated with caution.

Semantic priming in Alzheimer's dementia: Evidence for dissociation of automatic and attentional processes

The nature of the semantic memory deficit in dementia of the Alzheimer's type (DAT) was investigated in a semantic priming task which was designed to assess both automatic and attention-induced priming effects. Ten DAT patients and 10 age-matched control subjects completed a word naming semantic priming task in which both relatedness proportion (RP) and stimulus-onset asynchrony (SOA) were varied. A clear dissociation between automatic and attentional priming effects in both groups was demonstrated; however, the DAT subjects pattern of priming deviated significantly from that of the normal controls. The DAT patients failed to produce any priming under conditions which encouraged automatic semantic processing and produced facilitation only when the RP was high. In addition, the DAT group produced hyperpriming, with significantly larger facilitation effects than the control group. These results suggest an impairment of automatic spreading activation in DAT and have implications for theories of semantic memory impairment in DAT as well as models of normal priming. (C) 2001 Academic Press.

Modulation of the adrenocortical stress response in marine turtles (Cheloniidae): evidence for a hormonal tactic maximizing maternal reproductive investment

The relationships between reproductive condition, level of reproductive investment and adrenocortical modulation to capture stress in marine turtles form the basis of this study. When subjected to either capture or ecological stressors, nesting marine turtles have demonstrated adrenocortical responses that are both small in magnitude, and slow in responsiveness. These observations were further investigated to determine whether this minimal stress response was a physiological strategy to maximize reproductive investment in adult green Chelonia mydas and hawksbill Eretmochelys imbricata turtles. Female green and hawksbill turtles exhibited a decrease in adrenocortical responsiveness with progressive reproductive condition. Breeding turtles exhibited most suppression of their adrenocortical response to capture compared to both non-breeding and pre-breeding female counterparts. Nesting green turtles maintained a suppressed adrenocortical response to capture throughout the nesting season despite decreased reproductive investment. In contrast, male green and hawksbill turtles were less able to modulate their corticosterone (B) response to acute capture stress. During breeding, male turtles possessed significantly greater adrenocortical responses to capture than females. These results could indicate that the large reproductive investment necessary for female marine turtle reproduction might underlie the marked decrease in adrenocortical responsiveness. This hormonal mechanism could function as one strategy by which female marine turtles maximize their current reproductive event, even though under certain situations this mechanism could entail costs to female survival.

Phylogenetic classification of Eudorylini (Diptera: Pipunculidae)

The phylogenetic relationships of members of Eudorylini (Diptera: Pipunculidae: Pipunculinae) were explored. Two hundred and fifty-seven species of Eudorylini from all biogeographical regions and all known genera were examined. Sixty species were included in an exemplar-based phylogeny for the tribe. Two new genera are described, Clistoabdominalis and Dasydorylas. The identity of Eudorylas Aczél, the type genus for Eudorylini, has been obscure since its inception. The genus is re-diagnosed and a proposal to stabilize the genus and tribal names is discussed. An illustrated key to the genera of Pipunculidae is presented and all Eudorylini genera are diagnosed. Numerous new generic synonyms are proposed. Moriparia nigripennis Kozánek & Kwon is preoccupied by Congomyia nigripennis Hardy when both are transferred to Claraeola, so Cla. koreana Skevington is proposed as a new name for Mo. nigripennis.

Vascular smooth muscle cell phenotypic modulation in culture is associated with reorganisation of contractile and cytoskeletal proteins

Smooth muscle cells (SMC) exhibit a functional plasticity, modulating from the mature phenotype in which the primary function is contraction, to a less differentiated state with increased capacities for motility, protein synthesis, and proliferation. The present study determined, using Western analysis, double-label immunofluorescence and confocal microscopy, whether changes in phenotypic expression of rabbit aortic SMC in culture could be correlated with alterations in expression and distribution of structural proteins. Contractile state SMC (days 1 and 3 of primary culture) showed distinct sorting of proteins into subcellular domains, consistent with the theory that the SMC structural machinery is compartmentalised within the cell. Proteins specialised for contraction (alpha -SM actin, SM-MHC, and calponin) were highly expressed in these cells and concentrated in the upper central region of the cell. Vimentin was confined to the body of the cell, providing support for the contractile apparatus but not co-localising with it. In line with its role in cell attachment and motility, beta -NM actin was localised to the cell periphery and basal cortex. The dense body protein alpha -actinin was concentrated at the cell periphery, possibly stabilising both contractile and motile apparatus. Vinculin-containing focal adhesions were well developed, indicating the cells' strong adhesion to substrate. In synthetic state SMC (passages 2-3 of culture), there was decreased expression of contractile and adhesion (vinculin) proteins with a concomitant increase in cytoskeletal proteins (beta -non-muscle [NM] actin and vimentin). These quantitative changes in structural proteins were associated with dramatic chan-es in their distribution. The distinct compartmentalisation of structural proteins observed in contractile state SMC was no longer obvious, with proteins more evenly distributed throughout die cytoplasm to accommodate altered cell function. Thus, SMC phenotypic modulation involves not only quantitative changes in contractile and cytoskeletal proteins, but also reorganisation of these proteins. Since the cytoskeleton acts as a spatial regulator of intracellular signalling, reorganisation of the cytoskeleton may lead to realignment of signalling molecules, which, in turn, may mediate the changes in function associated with SMC phenotypic modulation. (C) 2001 Wiley-Liss, Inc.

Modulation of ligand selectivity by mutation of the first extracellular loop of the human C5a receptor

The cyclic C5a receptor antagonist, phenylalanine [L-ornithine-proline-D-cyclohexylalanine-tryptophan-arginine] (F-[OPchaWR]), has similar to 1000-fold less affinity for the C5a receptor (C5aR) on murine polymorphonuclear leukocytes than on human. Analysis of C5aR from different species shows that a possible cause of this difference is the variation in the sequence of the first extracellular loop of the receptor. The mouse receptor contains Y at a position analogous to P-103 in the human receptor, and D at G(105). To test this hypothesis, we expressed human C5aR mutants ((PY)-Y-103, G(105)D and the double mutant, (PY)-Y-103/G(105)D) in RBL-2H3 cells and investigated the effects of these mutations on binding affinity and receptor activation. All three mutant receptors had a higher affinity for human C5a than the wild-type receptor, but showed no significant difference in the ability of F-[OPchaWR] to inhibit human C5a binding. However, all of the mutant receptors had substantially lower affinities for the weak agonist, C5a des Arg(74) (C5adR(74)), and two altered receptors (G(105)D and (PY)-Y-103/G(105)D) had much lower affinities for the C-terminal C5a agonist peptide analogue, L-tyrosine-serine-phenylalanine-lysine-proline-methionine-proline-leucine-D-alanine-arginine (YSFKPMPLaR). Although it is unlikely that differences at these residues are responsible for variations in the potency of F-[OPchaWR] across species, residues in the first extracellular loop are clearly involved in the recognition of both C5a and C5a agonists. The complex effects of mutating these residues on the affinity and response to C5a, C5adR(74), and the peptide analogues provide evidence of different binding modes for these ligands on the C5aR. (C) 2001 Elsevier Science Inc. All rights reserved.

Childhood neglect and cognitive development in extremely low birth weight infants: A prospective study

Objective. To examine the relationship between child maltreatment and cognitive development in extremely low birth weight infants, adjusting for perinatal and parental risk factors. Methods. A total of 352 infants with birth weight of

The effects of pregnancy on myelin basic protein-induced experimental autoimmune encephalomyelitis in Lewis rats: Suppression of clinical disease, modulation of cytokine expression in the spinal cord inflammatory infiltrate and suppression of lymphocyte p

Problem: The present study was performed to explore the effects of pregnancy on experimental autoimmune encephalomyelitis (EAE) induced in Lewis rats by inoculation with myelin basic protein (MBP) (MBP-EAE). Method of study: MBP-EAE was induced in pregnant and non-pregnant rats and severity of disease evaluated. Serum from pregnant and non-pregnant rats was used in standard lymphocyte proliferation assays. Real-time polymerase chain reaction (PCR) was used to investigate the expression of cytokine mRNA in the inflammatory cells obtained from the spinal cord of rats on day 15 after inoculation. Results: Pregnant rats developed less severe disease than non-pregnant rats. Serum from pregnant rats suppressed the proliferation of T lymphocytes in response to MBP. There was significantly increased expression of IL-4. IL-10 and TNF-alpha mRNA in the spinal cord infiltrate of pregnant rats. Conclusion: Circulating humoral factors and alteration in cytokine production by inflammatory cells may contribute to the suppression of EAE in pregnant rats.

Transcriptional modulation of mouse mu-opioid receptor distal promoter activity by Sox18

Previously, we reported the presence of dual promoters, referred to as distal (DP) and proximal, with a negative regulatory element between them in the mouse mu -opioid receptor (mor) gene. Here we have identified a positive regulatory element influencing mor DP transcription, which contains multiple consensus binding motifs for Sox factors (sex-determining Sry-like high mobility group box-containing genes). In gel supershift assays, the Sox family member Sox18 bound directly to the multiple Sox consensus binding motifs of the mor DP enhancer. Overexpression of Sox18 cDNA increased luciferase activity regulated by the mor DP, and did so in a Sox18 concentration-dependent manner. In contrast, overexpression of another Sox member, Sox5, triggered no such trans-activation of mor DP-driven luciferase activity or DNA-protein binding activity. These results suggest that Sox18 directly and specifically stimulates mor gene expression, by trans-activating the mor DP enhancer.

A classification of subantarctic Heard Island vegetation

The vascular and bryophyte floras of subantarctic Heard Island were classified using cluster analysis into six vegetation communities: Open Cushion Carpet, Mossy Feldmark, Wet Mixed Herbfield, Coastal Biotic Vegetation, Saltspray Vegetation, and Closed Cushion Carpet. Multidimensional scaling indicated that the vegetation communities were not well delineated but were continua. Discriminant analysis and a classification tree identified altitude, wind, peat depth, bryophyte cover and extent of bare ground, and particle size as discriminating variables. The combination of small area, glaciation, and harsh climate has resulted in reduced vegetation variety in comparison to those subantarctic islands north of the Antarctic Polar Front Zone. Some of the functional groups and vegetation communities found on warmer subantarctic islands are not present on Heard Island, notably ferns and sedges and fernbrakes and extensive mires, respectively.