Negative symptom severity at discharge from an index hospitalization and subsequent use of psychiatric care resources: A retrospective 1-year follow-up study on 450 patients with schizophrenia spectrum disorders.

Negative symptoms of schizophrenia have a great impact on patients' functioning and are among the most important contributors to subject's disability. However, few studies have assessed the role of type and severity of symptomatology of schizophrenia on the psychiatric care resource utilization. We investigated if the clinical profile of patients at discharge from an index hospitalization might be associated with a different use of psychiatric care resources in the subsequent 1-year period in a large population of patients with schizophrenia spectrum disorders. Clinical records of 450 patients with schizophrenia spectrum disorders admitted in an acute psychiatric inpatient service and subsequently followed in the outpatient services of the same Department were reviewed. Patients with more severe negative symptoms at discharge from hospital showed a higher number and duration of hospitalizations in the 1-year follow-up, as well as a higher number of rehabilitative residential admissions than patients with milder severity of negative symptoms. The same was true for patients with predominant negative symptoms. A global resource utilization index indicated a higher use of psychiatric resources in patients with higher severity of negative symptoms. In conclusion, showing moderate to severe negative symptoms versus positive symptoms at discharge from a hospitalization for an acute exacerbation of schizophrenia spectrum disorder does predict a higher use of psychiatric care resources. This underlines the importance of relieving negative symptoms even in the acute phase of treatment and the need to develop more effective treatments for this symptom dimension.

Do dogs exhibit jealous behaviors when their owner attends to their companion dog?

Jealousy appears to have clear adaptive functions across species: it emerges when an important social relationship with a valued social partner is threatened by third-party that is perceived as a rival. Dyads of dogs living together and their owners were tested adapting a procedure devised to study jealousy in young human siblings. Owners at first ignored both dogs while reading a magazine (Control episode), and then petted and praised one of the dogs while ignoring the other, and vice versa (Experimental episodes). We found several differences in the dogs' behavior between the Experimental episodes and the Control episode, even though only monitoring (gazing at the owner) was exhibited for a significantly greater amount of time in the Experimental episodes. Remarkable individual behavioral differences emerged, suggesting that the dogs' reactions could be influenced by the relationships that they establish with their owner and the companion dog. Overall, current results do not clearly support our prediction that the ignored dogs would exhibit more behaviors aimed at regaining the owner's attention when their owner directed attention and care to a companion dog, compared to the control situation. The great intra- and inter-dyad behavioral variability and the choice to test cohabiting dogs could have prevented the emergence of a clear jealous reaction. These findings do not exclude that dogs may exhibit a primordial form of jealousy in a realistic situation, but an additional research is needed to fully gauge which situations, if any, could trigger jealousy in dogs and to rule out alternative explanations.

The GRM7 gene, early response to risperidone, and schizophrenia: a genome-wide association study and a confirmatory pharmacogenetic analysis.

The search for biomarkers of response to antipsychotic medications is hindered by difficulties inherent in the topic or related to persistent methodological difficulties, such as high rates of anticipated discontinuation and consequent distortions in the imputation of missing data. Because early response to antipsychotics represents a sufficiently reliable index of the subsequent treatment response in patients with schizophrenia, we undertook a real-world, genome-wide association study (GWAS) with the aim of identifying genetic predictors of response to risperidone after 2 weeks in 86 patients with schizophrenia. Limited to the associations reaching significance in the GWAS, confirmatory analysis relative to risperidone response over 9 months was also designed involving 97 patients (European only) enroled in the CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) genetic substudy. The GWAS revealed a significant association (false discovery rate 0.02) of the single-nucleotide polymorphism rs2133450 inside the GRM7 gene with Emsley's positive domain derived from the positive and negative syndrome scale (PANSS). Patients with the rs2133450 CC genotype presented poorer improvement in the positive domain over 2 weeks, with odds ratios of 12.68 (95% CI, 3.51-45.76) and 6.95 (95% confidence interval (CI), 2.37-20.37) compared with patients with the AA and AC genotypes, respectively. Compared with A homozygotes, rs2133450 C homozygotes enroled in the CATIE-derived confirmatory analysis showed less improvement in Emsley's positive, excited and depression domains, positive and general PANSS subtypes, and total PANSS after 9 months of treatment with risperidone. The original GWAS and the CATIE-derived confirmatory analysis support the proposal that the rs2133450 may have translational relevance as a predictor of response to risperidone.

Patterns of brain structural changes in first-contact, antipsychotic drug-naive patients with schizophrenia.

BACKGROUND AND PURPOSE: Previous studies have suggested that structural changes do occur in the brain of patients with schizophrenia compared with healthy control participants. However, findings from such studies are inconclusive, probably because of the different methodologic approaches, the clinical heterogeneity of patient samples, and also the fact that patients enrolled were treated with antipsychotic drugs. The aim of this study was to investigate brain GM volumes and intrinsic structural WM changes in first-contact, antipsychotic drug-naïve patients with schizophrenia. MATERIALS AND METHODS: A total of 43 first-contact, drug-naïve, patients with schizophrenia and 17 age-matched control participants were studied. All participants underwent T1-weighted MR imaging and DTI scans. Voxel-based morphometry and tract-based spatial statistics were used to compare GM volumes and WM DTI metrics between groups. MR imaging measures were correlated with the duration of the untreated psychosis and the clinical positive and negative symptoms. RESULTS: Compared with control participants, patients with schizophrenia showed smaller volumes of the temporal, parietal, and occipital GM, and a pattern of decreased mean diffusivity and increased fractional anisotropy in the brain stem and cerebellum bilaterally, interhemispheric and cortico-cortical connections bilaterally, and right anterior and posterior limb of the internal capsule. In patients, decreased mean diffusivity and increased fractional anisotropy in several brain regions were related to a longer duration of the untreated psychosis and the severity of positive symptoms. CONCLUSIONS: First-contact, drug-naïve, patients with schizophrenia present with volumetric and DTI changes, which correlated with their clinical features. This study increases our knowledge on the neural networks involved in the pathophysiologic mechanisms of schizophrenia.

The effect of preferential paw usage on dogs' (Canis familiaris) performance in a manipulative problem-solving task.

In a number of species, individuals showing lateralized hand/paw usage (i.e. the preferential use of either the right or left paw) compared to ambilateral individuals have been shown to be more proactive in novel situations. In the current study we used an established test to assess preferential paw usage in dogs (the Kong test) and then compared the performance of ambilateral and lateralized dogs as well as left- vs. right-pawed dogs in a novel manipulative problem solving task. Results showed an equal proportion of ambilateral and lateralized dogs but contrary to predictions non-lateralized dogs were faster at accessing the apparatus in test trials. No differences emerged between right- and left-pawed dogs. Results are discussed in relation to previous studies on lateralization.

Are dogs (Canis familiaris) misled more by their owners than by strangers in a food choice task?

Dogs are highly skilled in understanding a large variety of human social cues and use them appropriately to solve a number of different cognitive tasks. They rely on human signals even when these are contradictory or misleading and ultimately prevent them from correctly solving a task. In the following two experiments, we investigated whether the owner and a stranger differently influenced dogs' choices in food discrimination tasks. In Experiment 1, 48 dogs were tested in 3 different conditions: (1) choice between a large and a small amount of dog pellets with no demonstration; (2) choice between a large and a small amount of dog pellets after having witnessed the owner/stranger favouring the small quantity; (3) choice between two single food pellets after observing the owner/stranger choosing one of them. In Experiment 2, 48 dogs could choose between two foods of different palatability: in Condition 1, dogs chose between a slice of sausage and a dry pellet with no demonstration. In Condition 2, the same choice was available but with a person (owner/stranger) showing a preference for the dry pellet. In Condition 3, dogs chose between a single dry pellet and 8 slices of sausage, with the person (owner/stranger) showing a preference for the pellet. In both experiments, dogs conformed to the human's indications even though these led to the selection of the less advantageous option (i.e. the smaller amount of food in Experiment 1 or the low quality food in Experiment 2). However, the owner and the stranger did not differently influence the dogs' behaviour. Results show that dogs are willing to follow a person's indication even when this is visibly (if perhaps only mildly) counterproductive to them and that they are socially prepared to rely equally on cues given by the owner and an unfamiliar friendly person.

Comment on "Differential sensitivity to human communication in dogs, wolves, and human infants".

Topál et al. (Reports, 4 September 2009, p. 1269) showed that dogs, like infants but unlike wolves, make perseverative search errors that can be explained by the use of ostensive cues from the experimenter. We suggest that a simpler learning process, local enhancement, can account for errors made by dogs.

Is your choice my choice? The owners' effect on pet dogs' (Canis lupus familiaris) performance in a food choice task.

This study investigates the influence of owners on their dogs' performance in a food choice task using either different or equal quantities of food. Fifty-four pet dogs were tested in three different conditions. In Condition 1 we evaluated their ability to choose between a large and small amount of food (quantity discrimination task). In Condition 2 dogs were again presented with a choice between the large and small food quantity, but only after having witnessed their owner favouring the small quantity. In Condition 3 dogs were given a choice between two equally small quantities of food having witnessed their owner favouring either one or the other. A strong effect of the owner on the dogs' performance was observed. In Condition 1 dogs as a group chose significantly more often the large food quantity, thus showing their ability to solve the quantity discrimination task. After observing their owner expressing a preference for the small food quantity they chose the large quantity of food significantly less than in the independent choice situation. The tendency to conform to the owner's choice was higher when the dogs had to choose between equally small quantities of food (Condition 3) rather than between a large and a small one (Condition 2). These results provide evidence that dogs can be influenced by their owners even when their indications are clearly in contrast with direct perceptual information, thus leading dogs to ultimately make counterproductive choices.

Chronic exposure to low doses bisphenol A interferes with pair-bonding and exploration in female Mongolian gerbils.

Estrogenic endocrine disruptors, synthetic or naturally occurring substances found in the environment, can interfere with the vertebrate endocrine system and, mimicking estrogens, interact with the neuroendocrine substrates of behavior. Since species vary in their sensitivity to steroids, it is of great interest to widen the range of species included in the researches on neurobehavioral effects of estrogenic endocrine disruptors. We examined socio-sexual and exploratory behavior of Mongolian gerbil females (Meriones unguiculatus), a monogamous rodent, in response to chronic exposure to the estrogenic endocrine disruptor bisphenol A. Paired females were daily administered with one of the following treatments: bisphenol A (2 or 20 microg/kg body weight/day); 17alpha-ethynil estradiol (0.04 microg/kg body weight/day 17alphaE); oil (vehicle). Females were treated for 3 weeks after pairing. Starting on day of pairing, social interactions within pairs were daily recorded. Three weeks after pairing, females were individually tested in a free exploratory paradigm. Bisphenol A and 17alphaE affected male-female social interactions by increasing social investigation. Bisphenol A reduced several exploratory parameters, indicating a decreased exploratory propensity of females. These results highlight the sensitivity of adult female gerbils to bisphenol A during the hormonally sensitive period of pair formation, also considering that the bisphenol A doses tested are well below the suggested human tolerable daily intake.

How to study boron biodistribution in liver metastases from colorectal cancer.

The purpose of this study was to evaluate boron distribution for a safe and effective BNCT (Boron Neutron Capture Therapy) of liver metastases. Samples both from healthy and tumour liver parenchyma were analysed, after i.v. boron administration, by: alpha particles counting under neutron irradiation; morphological analysis by standard haematoxylin-eosin staining; neutron autoradiography. Our method was unaffected by the cytological heterogeneity inside tumour nodules; it demonstrated selective boron distribution in tumour tissue and predicted estimated mean therapeutic doses in tumour and safety doses in healthy tissue. The time interval for efficient BNCT was 2 to 4 hours after i.v. boron administration.

AFLP to assess genetic variation in laboratory gerbils (Meriones unguiculatus).

The amplified fragment length polymorphism (AFLP) technique has been increasingly employed for characterizing inbred breeds of animals and detecting strain-specific polymorphisms. The majority of animals studies conducted in biomedical research are performed on rodent species, among which laboratory-reared Mongolian gerbils can be included. Despite the wide use of gerbils in scientific studies, their genetics has rarely been studied. Therefore we investigated the genetic differentiation of laboratory bred gerbils by means of AFLP markers. Six EcoRI/TaqI primer combinations were selected among 13 different combinations to assess the genetic polymorphisms in four stocks of animals: Charles River (CR), Harlan (Ha), Parma (Pr), and Crossbred (Cb). CR and Ha gerbils were purchased from commercial vendors, while Pr and Cb were derived from animals bred in our animal colony. A total of 228 fragments ranging between 70 and 650 bp were obtained. The mean percentage of polymorphic loci across primer combinations was 7.5%. Calculation of genetic distances through application of different algorithms (Nei's, BSI, and Jaccard's indexes) confirmed the poor genetic diversity between stocks. Nevertheless, a differentiation of the Pr and Cb stocks from the more homogeneous CR and Ha was revealed, in agreement with the different breeding derivation and management of the stocks.

Quetiapine, clozapine, and olanzapine in the treatment of tardive dyskinesia induced by first-generation antipsychotics: a 124-week case report.

Our report of a patient with severe tardive dyskinesia (TD) who has been exposed to both typical antipsychotic and clozapine, olanzapine and quetiapine during a 124-week follow-up period supports the possible beneficial effect of atypical antipsychotics on pre-existing symptoms of TD. Persistently high AIMS scores during all the periods of treatment with typical antipsychotics contrast strongly with the drop in scores that occurs in strict chronological sequence after switching to both clozapine (45%), olanzapine (27.8%) and quetiapine (85%). Since the reversal to haloperidol from the three atypical agents was systemically associated with a return to high AIMS scores, it seems likely that the improvement noted with clozapine, olanzapine and quetiapine represents a temporary symptomatic effect rather than a sustained resolution of the disorder. The olanzapine-clozapine-quetiapine rank order of increasing effectiveness against TD symptoms suggests that this property, although shared by the atypical antipsychotics, is to some degree drug-specific. Patient- and/or drug-dependent mechanisms may be involved in this gradient of effect.

How to decrease the non-compliance in a clinical trial.

BACKGROUND: A high compliance is an important scientific objective for a multicenter clinical trial and also an ethical responsibility. Some of non-compliance causes can be prevented during the enrollment phase by an accurate selection of subjects (quality of recruitment), other can be controlled after the recruitment, by a good organization of follow-up tests and visits (quality of organization). METHODS: The policy adopted in the Operative Center of the Delegazione Alto Lario della Lega Italiana per la Lotta contro i Tumori di Gravedona (Como) for obtaining a high compliance of women recruited in the Italian Tamoxifen Prevention Study are illustrated. RESULTS: The non-compliance rate of this center is low: 5.6 vs 23.3% of the whole Italian trial. CONCLUSIONS: The low non-compliance demonstrates the efficacy of the policy adopted.

Learning to cope with two different food distributions: the performance of house mice (Mus musculus domesticus).

Search abilities of mice (Mus musculus domesticus) were evaluated using an arena closed by a ceiling in which 9 food sources (which mice could reach standing on their hind legs) could be arranged according to 2 configurations: a 3 x 3 square matrix and 3 clusters each containing 3 food sources. Testing conditions prevented olfactory and visual cues from being left after visits to food sources, and mice were able to choose alternative routes between food sources. Results showed that mice were more efficient with the matrix than with the cluster configuration. Sex differences were observed: Females improved their performance with both configurations, whereas males improved only with the matrix one. Mice did not develop evident search strategies that would minimize task complexity. Comparison with data published on capuchin monkeys revealed differences, with monkeys performing better with the cluster configuration than with the matrix and applying searching strategies.

Sex differences in conditioned taste aversion and in the effects of exposure to a specific pulsed magnetic field in deer mice Peromyscus maniculatus.

Although conditioned taste aversion (CTA) has been investigated and described in laboratory rodents and domestic animals, less is known regarding wild rodents. Here, we describe CTA in males and females of a "wild" species of rodent, the deer mouse (Peromyscus maniculatus). In addition, as CTA has often been induced by exposure to intense electromagnetic, X or gamma, radiation, in a second study, we also investigated the effects of a specifically designed, pulsed extremely low-frequency and low-intensity magnetic field on the flavor preferences of male and female deer mice. The results of these investigations showed that: (i) deer mice quickly developed a marked CTA for a novel flavor after a single pairing with LiCl; (ii) although the intensity of the CTA was the same in males and females, there was a sex difference in the duration of the flavor aversion, with males displaying it for a longer period (4 days) than females (3 days); (iii) both males and females showed a rapid and complete extinction of the aversion, in contrast to what has been reported for laboratory rodents; (iv) there was no recovery of CTA on re-test 10 days after extinction; (v) neither male or female deer mice developed a taste aversion as a consequence of exposure to a weak electromagnetic field; and (vi) there was a sex difference in response to the magnetic field, with exposure to the magnetic field significantly enhancing novel taste preference in male but not in female deer mice. Overall, our results show that there are several sex differences in the behavior of deer mice, both in the characteristics of the CTA and in the response to magnetic field exposure. The sex differences are discussed in terms of a sexually dimorphic sensitivity to experimental manipulation and the induction of stress and/or anxiety.

Opioid modulation of socially transmitted and spontaneous food preferences in female mice.

The present experiments were conducted to investigate the possible role of endogenous opioid peptides in the social transmission of food preferences in female mice. In the first experiment, observer animals were injected with 0.5 mg kg(-1) naltrexone, a long-lasting opioid receptor antagonist, 30 min prior to a 15-min period of social interaction with a familiar conspecific (demonstrator) fed either with a cocoa-flavoured or a plain diet. Afterwards, observers underwent a 30-min two-choice test between the cocoa and a more palatable, unfamiliar cinnamon diet. The results showed that opioid receptor blockade decreased the amount of cocoa diet consumed by the animals whose demonstrators ate cocoa diet. Experiment 2 showed that naltrexone, administered after the social interaction, strongly attenuated the expression of both a socially acquired preference for the cocoa diet and the spontaneous preference for the cinnamon diet. A third experiment was then conducted using the shorter-lasting opioid antagonist naloxone. Naloxone (0.5 mg kg(-1)) administered prior to the social interaction did not impair the acquisition of the food preference. Hence, results indicate that a blockade of opioid activity is sufficient to impair the expression of a socially acquired food preference but not its acquisition.

Radioimmunoassisted surgery for lung metastases from colorectal cancer: results and perspectives.

The high incidence of resectable lung metastases from colorectal cancer and the very poor prognosis of untreated patients (less than 24-month survival) has promoted the surgical approach to treatment. Since the main aims of this kind of surgery are the complete resection of the tumor, the preservation of tumor-free parenchyma, and a minimal surgical trauma, innovative surgical techniques have been developed. We report on our experience in the radioimmunoassisted pulmonary metastasectomy by the use of a hand-held gamma-detecting probe (GDP) and describe the application of the intraoperative radioimmunolocalization of tumor to video-assisted minimally invasive surgery.

Social learning of a food preference in male and female Mongolian gerbils is facilitated by the anxiolytic, chlordiazepoxide.

Social transmission of a food preference in Mongolian gerbils (Meriones unguiculatus) depends on the presence of a social bond between the interacting animals. An "observer" gerbil can acquire a preference for a novel food item from a familiar and, or related "demonstrator" animal. However, exposure to an unfamiliar and unrelated demonstrator gerbil does not lead to acquisition of a food preference, even though the extent of social interaction and likelihood of transmission of food information is unaffected. Likewise, individual preexposure to a novel food does not affect diet preference in individual animals. Here we show that oral, nongavage, administration of the benzodiazepine anxiolytic, chlordiazcpoxide (CDP, 2.5, 5, and 10 mg/kg) has significant dose-associated differential facilitatory effects on social learning in male and female gerbils, while having no significant effects on either individual learning or total food consumption. These results suggest that the CDP mediated reduction of the anxiety associated with the interactions between unfamiliar/unrelated gerbils facilitates social learning. These findings also rise the possibility of sex differences in socially related anxiety and the effects of CDP on social learning in gerbils.

The effect of demonstrator age and number on duration of socially-induced food preferences in house mouse (Mus domesticus).

Present research was undertaken to investigate whether the transfer of food preference from a demonstrator mouse to an observer can be influenced by their relative age. In experiment 1 an adult female mouse, the observer, was allowed to interact with a recently-fed demonstrator which was a pup of her litter or an adult female mouse. The observer was then tested to assess whether it acquired a preference for the demonstrator's diet. The results showed that a pup demonstrator's influence on an adult's food preference is shorter-lasting than an adult demonstrator's influence. Experiment 2 was aimed to investigate whether many demonstrators have an additive effect in influencing their observer's choice. The results indicated that multiple pup demonstrations do not increase longevity of food preferences induced by pup demonstrators. Moreover, the longevity of an adult observer's preference for its demonstrator's food is reduced by the exposure to multiple adult demonstrators. Results are discussed in terms of demonstrator's reliability and of social constraints that could affect social transfer of food information in the house mouse.

Kinship and familiarity as factors affecting social transfer of food preferences in adult Mongolian gerbils (Meriones unguiculatus).

Experiments were carried out with Mongolian gerbils (Meriones unguiculatus) to assess whether a socially mediated acquisition of diet selection exists in this species. Results showed that a gerbil was influenced in its diet choices by information extracted during a brief period of interaction with a familiar conspecific that had recently eaten a novel food. Data revealed that the acquisition of a food preference from a conspecific depends on the existence of a social bond between the interacting gerbils. Either genetic relatedness (being brother or sister raised in different litters) or familiarity (being bred in the same litter or being member of a reproductive pair) is necessary for the transfer of information. Unfamiliar and unrelated observer gerbils did not selectively choose their demonstrator's food.