Spatial relational learning and memory abilities do not differ between men and women in a real-world, open-field environment

This study assesses gender differences in spatial and non-spatial relational learning and memory in adult humans behaving freely in a real-world, open-field environment. In Experiment 1, we tested the use of proximal landmarks as conditional cues allowing subjects to predict the location of rewards hidden in one of two sets of three distinct locations. Subjects were tested in two different conditions: (1) when local visual cues marked the potentially-rewarded locations, and (2) when no local visual cues marked the potentially-rewarded locations. We found that only 17 of 20 adults (8 males, 9 females) used the proximal landmarks to predict the locations of the rewards. Although females exhibited higher exploratory behavior at the beginning of testing, males and females discriminated the potentially-rewarded locations similarly when local visual cues were present. Interestingly, when the spatial and local information conflicted in predicting the reward locations, males considered both spatial and local information, whereas females ignored the spatial information. However, in the absence of local visual cues females discriminated the potentially-rewarded locations as well as males. In Experiment 2, subjects (9 males, 9 females) were tested with three asymmetrically-arranged rewarded locations, which were marked by local cues on alternate trials. Again, females discriminated the rewarded locations as well as males in the presence or absence of local cues. In sum, although particular aspects of task performance might differ between genders, we found no evidence that women have poorer allocentric spatial relational learning and memory abilities than men in a real-world, open-field environment.

Manifestations neurologiques des troubles musculosquelettiques [Neurological manifestations in musculoskeletal disorders].

Musculoskeletal disorders are a crossroad among diverse specialties: neurology, rehabilitation, orthopedics, occupational medicine and psycho-traumatology. They are integrated into occupational medicine and encompass overuse syndromes, repeated micro-trauma and focal compressive neuropathies linked with professional or sports' activity. Neurological manifestations are omnipresent. Yet, their importance is not always recognized despite frequent resort to neurologists specialized in peripheral nervous system disorders and neurophysiology, as well as, to behavioral cognition specialists. Therapeutic approaches require preventive and work organization measures, neurophysiologic investigations and imaging in expert hands, and conservative treatment with physiotherapy, with or without paraneural and intra-articular injections.

The Beck Cognitive Insight Scale in outpatients with psychotic disorders: further evidence from a French-speaking sample.

OBJECTIVE: The Beck Cognitive Insight Scale (BCIS) evaluates patients' self-report of their ability to detect and correct misinterpretation. Our study aims to confirm the factor structure and the convergent validity of the original scale in a French-speaking environment. METHOD: Outpatients (n = 158) suffering from schizophrenia or schizoaffective disorders fulfilled the BCIS. The 51 patients in Montpellier were equally assessed with the Positive and Negative Syndrome Scale (PANSS) by a psychiatrist who was blind of the BCIS scores. RESULTS: The fit indices of the confirmatory factor analysis validated the 2-factor solution reported by the developers of the scale with inpatients, and in another study with middle-aged and older outpatients. The BCIS composite index was significantly negatively correlated with the clinical insight item of the PANSS. CONCLUSIONS: The French translation of the BCIS appears to have acceptable psychometric properties and gives additional support to the scale, as well as cross-cultural validity for its use with outpatients suffering from schizophrenia or schizoaffective disorders. The correlation between clinical and composite index of cognitive insight underlines the multidimensional nature of clinical insight. Cognitive insight does not recover clinical insight but is a potential target for developing psychological treatments that will improve clinical insight.

gp100(209-2M) peptide immunization of human lymphocyte antigen-A2+ stage I-III melanoma patients induces significant increase in antigen-specific effector and long-term memory CD8+ T cells.

Thirty-five HLA-A2(+) patients with completely resected stage I-III melanoma were vaccinated multiple times over 6 months with a modified melanoma peptide, gp100(209-2M), emulsified in Montanide adjuvant. Direct ex vivo gp100(209-2M) tetramer analysis of pre- and postvaccine peripheral blood mononuclear cells (PBMCs) demonstrated significant increases in the frequency of tetramer(+) CD8(+) T cells after immunization for 33 of 35 evaluable patients (median, 0.36%; range, 0.05-8.9%). Ex vivo IFN-gamma cytokine flow cytometry analysis of postvaccine PBMCs after brief gp100(209-2M) in vitro activation showed that for all of the patients studied tetramer(+) CD8(+) T cells produced IFN-gamma; however, some patients had significant numbers of tetramer(+) IFN-gamma(-) CD8(+)T cells suggesting functional anergy. Additionally, 8 day gp100(209-2M) in vitro stimulation (IVS) of pre- and postvaccine PBMCs resulted in significant expansion of tetramer(+) CD8(+) T cells from postvaccine cells for 34 patients, and these IVS tetramer(+) CD8(+) T cells were functionally responsive by IFN-gamma cytokine flow cytometry analysis after restimulation with either native or modified gp100 peptide. However, correlated functional and phenotype analysis of IVS-expanded postvaccine CD8(+) T cells demonstrated the proliferation of functionally anergic gp100(209-2M)- tetramer(+) CD8(+) T cells in several patients and also indicated interpatient variability of gp100(209-2M) stimulated T-cell proliferation. Flow cytometry analysis of cryopreserved postvaccine PBMCs from representative patients showed that the majority of tetramer(+) CD8+ T cells (78.1 +/- 4.2%) had either an "effector" (CD45 RA(+)/CCR7(-)) or an "effector-memory" phenotype (CD45RA(-)/CCR7(-)). Notably, analysis of PBMCs collected 12-24 months after vaccine therapy demonstrated the durable presence of gp100(209-2M)-specific memory CD8(+) T cells with high proliferation potential. Overall, this report demonstrates that after vaccination with a MHC class I-restricted melanoma peptide, resected nonmetastatic melanoma patients can mount a significant antigen-specific CD8(+) T-cell immune response with a functionally intact memory component. The data further support the combined use of tetramer binding and functional assays in correlated ex vivo and IVS settings as a standard for immunomonitoring of cancer vaccine patients.

Prevalence and correlates of DSM-5 bipolar and related disorders and hyperthymic personality in the community.

BACKGROUND: To 1) establish the lifetime and 12-month prevalence of DSM-5 bipolar and related disorders including the new algorithmically defined conditions grouped within Other Specified Bipolar and Related Disorders (OSBARD) as well as hyperthymic personality in a randomly selected community sample, and 2) determine the clinical relevance of the OSBARD category in terms of sociodemographic characteristics, course, comorbidity and treatment patterns by comparing the subjects of this category to those with bipolar-I (BP-I), bipolar-II (BP-II), major depressive disorder (MDD), and those with no history of mood disorders. METHODS: The semi-structured Diagnostic Interview for Genetic Studies was administered by masterslevel psychologists to a random sample of an urban area (n=3'719). RESULTS: The lifetime prevalence was 1.0% for BP-I, 0.8% for BP-II, 1.0% for OSBARD and 3% for hyperthymic personality. Subjects with OSBARD were more severely affected than subjects without a history of mood disorders regarding almost all clinical correlates. Compared to those with MDD, they also revealed an elevated risk of suicidal attempts, lower global functioning, more treatment seeking and more lifetime comorbidity including anxiety, substance use and impulse-control disorders. However, they did not differ from subjects with BP-II. LIMITATIONS: Small sample sizes for bipolar and related disorders and potential inaccurate recall of symptoms. CONCLUSIONS: The modifications of diagnostic criteria for manic/hypomanic episodes according to the DSM-5 only marginally affect the prevalence estimates for BP-I and BP-II. The new DSM-5 OSBARD category is associated with significant clinical burden, is hardly distinct from BP-II with respect to clinical correlates and deserves similar clinical attention.

Development of mental disorders one year after exposure to psychosocial stressors; a cohort study in primary care patients with a physical complaint.

BACKGROUND: Mental disorders, common in primary care, are often associated with physical complaints. While exposure to psychosocial stressors and development or presence of principal mental disorders (i.e. depression, anxiety and somatoform disorders defined as multisomatoforme disorders) is commonly correlated, temporal association remains unproven. The study explores the onset of such disorders after exposure to psychosocial stressors in a cohort of primary care patients with at least one physical symptom. METHOD: The cohort study SODA (SOmatization, Depression and Anxiety) was conducted by 21 private-practice GPs and three fellow physicians in a Swiss academic primary care centre. GPs included patients via randomized daily identifiers. Depression, anxiety or somatoform disorders were identified by the full Patient Health Questionnaire (PHQ), a validated procedure to identify mental disorders based on DSM-IV criteria. The PHQ was also used to investigate exposure to psychosocial stressors (before the index consultation and during follow up) and the onset of principal mental disorders after one year of follow up. RESULTS: From November 2004 to July 2005, 1020 patients were screened for inclusion. 627 were eligible and 482 completed the PHQ one year later and were included in the analysis (77%). At one year, prevalence of principal mental disorders was 30/153 (19.6% CI95% 13.6; 26.8) for those initially exposed to a major psychosocial stressor and 26/329 (7.9% CI95% 5.2; 11.4) for those not. Stronger association exists between psychosocial stressors and depression (RR = 2.4) or anxiety (RR = 3.5) than multisomatoforme disorders (RR = 1.8). Patients who are "bothered a lot" (subjective distress) by a stressor are therefore 2.5 times (CI95% 1.5; 4.0) more likely to experience a mental disorder at one year. A history of psychiatric comorbidities or psychological treatment was not a confounding factor for developing a principal mental disorder after exposure to psychosocial stressors. CONCLUSION: This primary care study shows that patients with physical complaints exposed to psychosocial stressors had a higher risk for developing mental disorders one year later. This temporal association opens the field for further research in preventive care for mental diseases in primary care patients.

Associations of serum uric acid and SLC2A9 variant with depressive and anxiety disorders: a population-based study

Background: Limited information exists regarding the association between serum uric acid (SUA) and psychiatric disorders. We explored the relationship between SUA and subtypes of major depressive disorder (MDD) and specific anxiety disorders. Additionally, we examined the association of SLC2A9 rs6855911 variant with anxiety disorders. Methods: We conducted a cross-sectional analysis on 3,716 individuals aged 35-66 years previously selected for the population-based CoLaus survey and who agreed to undergo further psychiatric evaluation. SUA was measured using uricase-PAP method. The French translation of the semi-structured Diagnostic Interview for Genetic Studies was used to establish lifetime and current diagnoses of depression and anxiety disorders according to the DSM-IV criteria. Results: Men reported significantly higher levels of SUA compared to women (357}74 μmol/L vs. 263}64 μmol/L). The prevalence of lifetime and current MDD was 44% and 18% respectively while the corresponding estimates for any anxiety disorders were 18% and 10% respectively. A quadratic hockey-stick shaped curve explained the relationship between SUA and social phobia better than a linear trend. However, with regards to the other specific anxiety disorders and other subtypes of MDD, there was no consistent pattern of association. Further analyses using SLC2A9 rs6855911 variant, known to be strongly associated with SUA, supported the quadratic relationship observed between SUA phenotype and social phobia. Conclusions: A quadratic relationship between SUA and social phobia was observed consistent with a protective effect of moderately elevated SUA on social phobia, which disappears at higher concentrations. Further studies are needed to confirm our observations.

Evaluer les troubles de la marche des personnes âgées au cabinet [Assessment of gait disorders in older people]

Gait disorders are frequent and important to assess in older people because they provide unique diagnostic and prognostic information. Gait disorders can be regarded as a marker of frailty because they are associated with several adverse consequences, including falls, cognitive disorders, functional decline, institutionalization, hospitalization, and death. Using structured instruments, gait assessment could be performed in primary care practice to classify the level of sensorimotor deficit and provide the necessary information to decide how to best intervene to improve gait performances, prevent falls as well as functional decline.

Building hippocampal circuits to learn and remember: insights into the development of human memory

The hippocampal formation is essential for the processing of episodic memories for autobiographical events that happen in unique spatiotemporal contexts. Interestingly, before 2 years of age, children are unable to form or store episodic memories for recall later in life, a phenomenon known as infantile amnesia. From 2 to 7 years of age, there are fewer memories than predicted based on a forgetting function alone, a phenomenon known as childhood amnesia. Here, we discuss the postnatal maturation of the primate hippocampal formation with the goal of characterizing the development of the neurobiological substrates thought to subserve the emergence of episodic memory. Distinct regions, layers and cells of the hippocampal formation exhibit different profiles of structural and molecular development during early postnatal life. The protracted period of neuronal addition and maturation in the dentate gyrus is accompanied by the late maturation of specific layers in different hippocampal regions that are located downstream from the dentate gyrus, particularly CA3. In contrast, distinct layers in several hippocampal regions, particularly CA1, which receive direct projections from the entorhinal cortex, exhibit an early maturation. In addition, hippocampal regions that are more highly interconnected with subcortical structures, including the subiculum, presubiculum, parasubiculum and CA2, mature even earlier. These findings, together with our studies of the development of human spatial memory, support the hypothesis that the differential maturation of distinct hippocampal circuits might underlie the differential emergence of specific "hippocampus-dependent" memory processes, culminating in the emergence of episodic memory concomitant with the maturation of all hippocampal circuits.

A study compared nine patient-specific indices for musculoskeletal disorders.

BACKGROUND AND OBJECTIVE: Patient-specific quality of life indices show great potential, but certain conceptual and methodological concerns have yet to be fully addressed. The present study reviewed nine patient-specific instruments used in musculoskeletal disorders: the Canadian Occupational Performance Measure (COPM), Juvenile Arthritis Quality of life Questionnaire (JAQQ), McMaster-Toronto Arthritis questionnaire (MACTAR), Measure Yourself Medical Outcome Profile (MYMOP), Patient-Specific Index (PASI) for total hip arthroplasty, Problem Elicitation Technique (PET), Patient Generated Index (PGI) of quality of life, Patient-Specific Functional Scale (PSFS), and Schedule for the Evaluation of Individual Quality of Life (SEIQoL). STUDY DESIGN AND SETTING: Each tool was evaluated for purpose, content validity, face validity, feasibility, psychometric properties, and responsiveness. RESULTS: This critical appraisal revealed important differences in terms of the concept underlying these indices, the domains covered, the item-generation techniques and the scoring (response scale, methods) in each scale. The nine indices would generate different responses and likely scores for the same patient, despite the fact that they all include patient-generated items. CONCLUSION: Although the value of these indices in treatment planning and monitoring at an individual level is strong, more studies are needed to improve our understanding of how to interpret the numeric scores of patient-specific indices at both an individual and a group level.

Electroconvulsive therapy-induced brain plasticity determines therapeutic outcome in mood disorders.

There remains much scientific, clinical, and ethical controversy concerning the use of electroconvulsive therapy (ECT) for psychiatric disorders stemming from a lack of information and knowledge about how such treatment might work, given its nonspecific and spatially unfocused nature. The mode of action of ECT has even been ascribed to a "barbaric" form of placebo effect. Here we show differential, highly specific, spatially distributed effects of ECT on regional brain structure in two populations: patients with unipolar or bipolar disorder. Unipolar and bipolar disorders respond differentially to ECT and the associated local brain-volume changes, which occur in areas previously associated with these diseases, correlate with symptom severity and the therapeutic effect. Our unique evidence shows that electrophysical therapeutic effects, although applied generally, take on regional significance through interactions with brain pathophysiology.

Genetic Association of Recovery from Eating Disorders: The Role of GABA Receptor SNPs.

Follow-up studies of eating disorders (EDs) suggest outcomes ranging from recovery to chronic illness or death, but predictors of outcome have not been consistently identified. We tested 5151 single-nucleotide polymorphisms (SNPs) in approximately 350 candidate genes for association with recovery from ED in 1878 women. Initial analyses focused on a strictly defined discovery cohort of women who were over age 25 years, carried a lifetime diagnosis of an ED, and for whom data were available regarding the presence (n=361 ongoing symptoms in the past year, ie, 'ill') or absence (n=115 no symptoms in the past year, ie, 'recovered') of ED symptoms. An intronic SNP (rs17536211) in GABRG1 showed the strongest statistical evidence of association (p=4.63 × 10(-6), false discovery rate (FDR)=0.021, odds ratio (OR)=0.46). We replicated these findings in a more liberally defined cohort of women age 25 years or younger (n=464 ill, n=107 recovered; p=0.0336, OR=0.68; combined sample p=4.57 × 10(-6), FDR=0.0049, OR=0.55). Enrichment analyses revealed that GABA (γ-aminobutyric acid) SNPs were over-represented among SNPs associated at p<0.05 in both the discovery (Z=3.64, p=0.0003) and combined cohorts (Z=2.07, p=0.0388). In follow-up phenomic association analyses with a third independent cohort (n=154 ED cases, n=677 controls), rs17536211 was associated with trait anxiety (p=0.049), suggesting a possible mechanism through which this variant may influence ED outcome. These findings could provide new insights into the development of more effective interventions for the most treatment-resistant patients.

De la perception à l'apprentissage [From perception to learning]

Dans le domaine de la perception, l'apprentissage est contraint par la présence d'une architecture fonctionnelle constituée d'aires corticales distribuées et très spécialisées. Dans le domaine des troubles visuels d'origine cérébrale, l'apprentissage d'un patient hémi-anopsique ou agnosique sera limité par ses capacités perceptives résiduelles, mais un déficit de reconnaissance visuelle de nature apparemment perceptive, peut également être associé à une altération des représentations en mémoire à long terme. Des réseaux neuronaux distincts pour la reconnaissance - cortex temporal - et pour la localisation des sons - cortex pariétal - ont été décrits chez l'homme. L'étude de patients cérébro-lésés confirme le rôle des indices spatiaux dans un traitement auditif explicite du « where » et dans la discrimination implicite du « what ». Cette organisation, similaire à ce qui a été décrit dans la modalité visuelle, faciliterait les apprentissages perceptifs. Plus généralement, l'apprentissage implicite fonde une grande partie de nos connaissances sur le monde en nous rendant sensible, à notre insu, aux règles et régularités de notre environnement. Il serait impliqué dans le développement cognitif, la formation des réactions émotionnelles ou encore l'apprentissage par le jeune enfant de sa langue maternelle. Le caractère inconscient de cet apprentissage est confirmé par l'étude des temps de réaction sériels de patients amnésiques dans l'acquisition d'une grammaire artificielle. Son évaluation pourrait être déterminante dans la prise en charge ré-adaptative. [In the field of perception, learning is formed by a distributed functional architecture of very specialized cortical areas. For example, capacities of learning in patients with visual deficits - hemianopia or visual agnosia - from cerebral lesions are limited by perceptual abilities. Moreover a visual deficit in link with abnormal perception may be associated with an alteration of representations in long term (semantic) memory. Furthermore, perception and memory traces rely on parallel processing. This has been recently demonstrated for human audition. Activation studies in normal subjects and psychophysical investigations in patients with focal hemispheric lesions have shown that auditory information relevant to sound recognition and that relevant to sound localisation are processed in parallel, anatomically distinct cortical networks, often referred to as the "What" and "Where" processing streams. Parallel processing may appear counterintuitive from the point of view of a unified perception of the auditory world, but there are advantages, such as rapidity of processing within a single stream, its adaptability in perceptual learning or facility of multisensory interactions. More generally, implicit learning mechanisms are responsible for the non-conscious acquisition of a great part of our knowledge about the world, using our sensitivity to the rules and regularities structuring our environment. Implicit learning is involved in cognitive development, in the generation of emotional processing and in the acquisition of natural language. Preserved implicit learning abilities have been shown in amnesic patients with paradigms like serial reaction time and artificial grammar learning tasks, confirming that implicit learning mechanisms are not sustained by the cognitive processes and the brain structures that are damaged in amnesia. In a clinical perspective, the assessment of implicit learning abilities in amnesic patients could be critical for building adapted neuropsychological rehabilitation programs.]