Efficacy and specificity of computer-assisted cognitive remediation in schizophrenia: a meta-analytical study.

BACKGROUND: Cognitive remediation is frequently based on computerized training methods that target different cognitive deficits. The aim of this article was to assess the efficacy of computer-assisted cognitive remediation (CACR) in schizophrenia and to determine whether CACR enables selective treatment of specific cognitive domains. METHOD: A meta-analysis was performed on 16 randomized controlled trials evaluating CACR. The effect sizes of differences between CACR and control groups were computed and classified according to the cognitive domain assessed. The possible influences of four potential moderator variables were examined: participants' age, treatment duration, weekly frequency, and control condition type. To test the domain-specific effect, the intended goal of each study was determined and the effect sizes were sorted accordingly. The effect sizes of the cognitive domains explicitly targeted by the interventions were then compared with those that were not. RESULTS: CACR enhanced general cognition with a mean effect size of 0.38 [confidence interval (CI) 0.20-0.55]. A significant medium effect size of 0.64 (CI 0.29-0.99) was found for Social Cognition. Improvements were also significant in Verbal Memory, Working Memory, Attention/Vigilance and Speed of Processing with small effect sizes. Cognitive domains that were specifically targeted by the interventions did not yield higher effects than those that were not. CONCLUSIONS: The results lend support to the efficacy of CACR with particular emphasis on Social Cognition. The difficulty in targeting specific domains suggests a 'non-specific' effect of CACR. These results are discussed in the light of the possible bias in remediation tasks due to computer interface design paradigms.

Psychometric properties of a French version of the junior temperament and character inventory.

The junior temperament and character inventory (JTCI) has been developed for the assessment of temperament and character dimensions in childhood based on Cloninger's model of personality. We evaluated the psychometric proprieties of a French child and parent-rated version of the JTCI based on a previous German version, and assessed the correlations between the JTCI dimension scores and the scores on the child behavior checklist (CBCL) in a community sample of French children and adolescents aged 10-16 years. We used data from 452 child-rated and 233 -parent-rated JCTI. The psychometric properties (internal consistency and external validity in relation to the emotionality activity sociability (EAS) questionnaire) of the French JTCI were adequate in the parent-rated version. The parent-rated JTCI had overall better psychometric qualities than the child-rated version, but for both versions of the JTCI the confirmatory factor analysis showed low fit between the observed data and the original model. Dimensions of the EAS model were significantly correlated with the temperament scales of the JTCI. Further studies are required to improve the psychometric properties of the child-rated JTCI, and to provide insight about lacking fit of our data with the theoretical model.

[Dimensional approach of emotion in psychiatry: validation of the Positive and Negative Emotionality scale (EPN-31)]. / Evaluation dimensionnelle des émotions en psychiatrie: validation du questionnaire Emotionnalité positive et négative à 31 items (EPN-31).

BACKGROUND: This paper reports the first validation study of the EPN-31 scale (Positive and Negative Emotionality scale, 31 items) in a French psychiatric sample. This questionnaire has been adapted by Rolland from an emotion inventory developed by Diener, and is also in accordance with Watson and Clark's tripartite model of affects. METHODOLOGICAL ASPECTS: Respondents were asked to rate the frequency with which they had experienced each affect (31 basic emotional states) during the last month. The answer format was a 7-point scale, ranging from 1 "Not experienced at all" to 7 "Experienced this affect several times each day". Three main scores were calculated (positive affects, negative affects, and surprise affects), as well as six sub-scores (joy, tenderness, anger, fear, sadness, shame). Four hundred psychiatric patients were included in this study, and completed the EPN-31 scale and the Hospital Anxiety and Depression (HAD) scale. The Global Assessment of Functioning (GAF) scale was rated, as well as DSM IV diagnostic criteria. We performed a principal component analysis, with Varimax orthogonal transformation, and explored the factorial structure of the questionnaire, the internal consistency of each dimension, and the correlations between EPN-31 scores and HAD scores. RESULTS: The factorial structure of the EPN-31 was well-defined as expected, with a three-factor (positive, negative and surprise affects) solution accounting for 58.2% of the variance of the questionnaire. No correlation was obtained between positive and negative affects EPN-31 scores (r=0.006). All alpha Cronbach coefficients were between 0.80 and 0.95 for main scores, and between 0.72 and 0.90 for sub-scores. GAF scores were significantly correlated with EPN-31 positive affects scores (r=0.21; p=0.001) and with EPN-31 negative affects scores (r=- 0.45; p=0.001). We obtained significant correlations between positive affects score and HAD depression score (r=- 0.45; p<0.001), and between negative affects score and HAD anxiety (r=0.56; p<0.001) and depression (r=0.45; p<0.001) scores. This pattern of correlation was in accordance with the Watson tripartite model of emotionality. Significantly higher EPN-31 positive affect mean scores were observed in females when compared to males (p<0.001). The third factor of the EPN-31 is less robust than the others and, the validity of the surprise score could hence be discussed. CONCLUSION: In all, this study confirmed the validity and the interest of the EPN-31 use in psychiatric patients. Various clinical and research applications can be considered, such as infra-symptomatic studies of emotions in affective disorders and during treatment protocols or definition of phenotypic markers in genetic or neuro-imagery studies.

[Is age at onset associated with executive dysfunction in obsessive-compulsive disorder?]. / Fonctions exécutives dans le trouble obsessionnel compulsif: effet de l'âge de début des troubles.

In obsessive-compulsive disorder (OCD), clinical, neurobiological and genetic differences have been reported according to age at onset (AAO). Given the importance of identifying homogeneous subtypes in complex hete-rogeneous disorders such as OCD, it would be particularly useful to identify a specific cognitive profile associated with early-onset OCD. Although impaired cognition has repea-tedly been demonstrated in OCD patients, discrepancies between studies have hampered the identification of a precise cognitive dysfunction. Executive dysfunction has often been reported, but findings have not always been replicated. The aim of this study was to assess executive functions in 30 patients according to their AAO. The sample consisted of 15 early-onset and 15 late-onset OCD patients and 22 normal controls, matched for age, sex and socio-economic status. Various aspects of executive function were assessed with five neuropsychological tests: Tower of London, Trail Making Test, Verbal Fluency, Design Fluency and Association Fluen-cy. The 30 OCD patients obtained lower total scores than the controls in the Tower of London test and association fluen-cy task (p<0.05 and p<0.001, respectively). Impairments were more marked for the early-onset group, with no effect of gender or age at interview. Deficits in specific aspects of frontal lobe function were found in the OCD group and were particularly pronounced within the early-onset group. These findings confirm clinical data suggesting that OCD patients can be subtyped according to age at onset and that OCD patients present unusual cognitive characteristics. They also support the hypothesis that early-onset OCD might be a rele-vant subgroup characterised both by a particular clinical profile and by specific cognitive characteristics.

Influence of prepartum chronic ultramild stress on maternal pup care behavior in mice.

BACKGROUND: Stress administered to pregnant rodents has been shown to lead to biological and behavioral alterations in both mother and pups. Most of these stress procedures use noxious stressors. Chronicity is obtained by simple repetition of one or two stressors and may be more representative of moderate daily stress experienced during normal life than stress during severe life events. The effects of this procedure were assessed by observing maternal pup-care behavior and testing maternal aggression. METHODS: The subjects included eight controls and eight stressed B6D2F1 females. Chronic ultramild stress was applied from mating to postpartum day (PD) 0. Pup-care behavior was observed on PD 1. Maternal aggression against a male intruder was tested on PD 8, which corresponds to the peak in the display of this behavior. RESULTS: Prenatal stress did not affect basic pup-care behavior, but dramatically impaired defense behavior designed to protect the pups from an external attacker. CONCLUSIONS: The results suggest that gestating females subjected to chronic ultramild stress suffer from a long-lasting decline in recognition of external distress cues either from a resident intruder and/or their own litter. It is assumed these effects are due to the chronicity of the stress rather than its severity.

Clinical and neurochemical effect of acute tryptophan depletion in unaffected relatives of patients with bipolar affective disorder.

BACKGROUND: The lowering of mood induced by an acute tryptophan depletion (ATD) has been proposed as a candidate endophenotype for the vulnerability to manic-depressive illness. This study tests this hypothesis in relatives of probands from well-characterized multiplex families affected with bipolar affective disorder (BAD). METHODS: In a double-blind, crossover design, 20 unaffected relatives (URs) and 19 control subjects received either a 100-g amino acid (AA) drink devoid of tryptophan or a placebo, respectively. Clinical and biochemical effects of ATD were compared between unaffected relatives of BAD probands and age- and sex-matched control subjects. RESULTS: At 5 hours after AA drink ingestion, relative to the placebo, ATD resulted in 74% and 84% decreases in total plasma tryptophan concentrations in control subjects and relatives of patients with BAD, respectively. Unlike control subjects unaffected relatives experienced a lowering of mood during ATD but not with the placebo. Furthermore, URs tended to show increased impulsivity in the ATD condition. Measurements obtained before ingestion of the AA drink indicated that, relative to control subjects URs exhibited lower serotonin platelet concentrations, lower affinity, and fewer binding sites of the serotonin transporter for imipramine; these differences were unaffected by ATD. CONCLUSION: These results replicate and extend previous findings suggesting that URs of patients with BAD are more susceptible to low tryptophan availability. This finding may bear significance in the purported role of serotonergic mechanisms in the vulnerability to depressive syndrome and/or illness.

Long-term treatment with the antioxidant drug EGb 761 at senescence restored some neurobehavioral effects of chronic ultramild stress exposure seen in young mice.

In this study, we compared the effects of chronic ultramild stress (CUMS) exposure on decision-making behavior in a validated test, and on the stress responsive serotoninergic and dopaminergic systems in four age groups of B6D2F1 female mice (5-6, 11-12, 17-18 and 23-24 months old). The levels of serotonin (5-HT) and its metabolite 5-hydroxyindolacetic acid (5-HIAA) were measured in the brain stem, the cortex, the striatum and the hippocampus; the levels of dopamine (DA) and its metabolite dihydroxyphenylacetic acid (DOPAC) were measured in the brain stem and the striatum. The influence of a long-term treatment with the extract of Ginkgo biloba leaves EGb 761 (Tanakan) on age- and stress-related changes was also investigated in the two oldest age groups. In the absence of drug treatment, middle-age mice were the least efficient in making a decision, and senescent mice exhibited reduced levels of both 5-HT and DA and their metabolites in all the brain areas examined. CUMS facilitated evaluation and choice behavior in all age groups, but induced age-dependent reduction of hesitation, acceleration of information processing and reduction in serotoninergic neurotransmission. In senescent mice, EGb 761 reduced the impact of stress on evaluation and hesitation, and restored some stress-related neurobehavioral changes that were only seen in young mice, i.e. acceleration of information processing and reduction in brain 5-HIAA levels. Restoration of some plasticity of the serotoninergic systems might contribute to the stress alleviating influence of EGb 761 in old age.

Decreased platelet serotonin transporter sites and increased platelet inositol triphosphate levels in patients with unipolar depression: effects of clomipramine and fluoxetine.

BACKGROUND: The central serotonergic system has been implicated in the pathophysiology of depression and in the mechanism of the action of antidepressant drugs. The human platelet has been proposed as a peripheral model of central serotonergic neurons. METHODS: Six peripheral serotonergic parameters were determined simultaneously in 27 patients with unipolar depression before and after 2, 4, and 12 weeks of clomipramine or fluoxetine treatment according to the psychiatrist. RESULTS: In patients with depression versus matched control subjects, platelet [3H]paroxetine binding sites were found to be significantly decreased (2.10 +/- 0.70 versus 3.88 +/- 0.77 fmol/10(9) platelets; P = .0001), platelet serotonin (5-HT) content was found to be significantly decreased (1.90 +/- 1.52 versus 2.74 +/- 1.12 nmol/10(9) platelets; P = .001), and platelet inositol triphosphate levels were found to be significantly increased (2.85 +/- 0.70 versus 1.85 +/- 0.77 fmol/10(9) platelets; P = .0001). No significant difference between patients and control subjects was found for platelet [3H]-lysergic acid diethylamide ([3H]LSD) binding sites, aggregation tests with 5-HT or adenosine diphosphate and plasma 5-HT levels. Treatment with both clomipramine and fluoxetine gradually further reduced the density of platelet [3H]paroxetine binding sites and induced a dramatic decrease in platelet and plasma 5-HT levels. With clomipramine, the decreased blood 5-HT levels are associated with increased platelet [3H]LSD binding sites and aggregation responses. After 12 weeks, nonresponders to both treatments had platelet inositol triphosphate levels that were still increased (2.81 +/- 0.75 fmol/10(9) platelets) when responders levels were not different from those of control subjects (1.41 +/- 0.45 versus 1.70 +/- 0.25 fmol/10(9) platelets). CONCLUSIONS: Drug-free patients with depression had simultaneously decreased 5-HT transporter (5-HTT) sites and overstimulated phosphoinositide signaling systems. Clomipramine and fluoxetine treatments, which further decreased the density of 5-HTT sites, allowed platelet inositol triphosphate levels to return to normal values only in responders.

In vivo regulation of cerebral monoamine oxidase activity in senescent controls and chronically stressed mice by long-term treatment with Ginkgo biloba extract (EGb 761).

It is well recognized that Ginkgo biloba extract (EGb 761) exert beneficial effects against various age-related changes and is able to reduce the negative influence of stress. In view of the age-dependent increase in the activity of the B form of monoamine oxidase (MAO-B) and in view of the anti-stress action of EGb 761 hypothetically attributed to an inhibition of monoamine oxidase by this substance, we investigated the effects of long-term treatment with EGb 761 upon in vivo cerebral MAO-A and -B activities of stressed and unstressed 17- and 18-month-old mice. The stress was a 'chronic mild stress' regimen whose behavioral impact is known to be reduced by EGb 761. The results showed that: (1) EGb761 induced reductions in MAO activity in 18-month-old, but not in 17-month-old mice; the older animals having higher basal MAO activity; (2) in unstressed mice, EGb 761 appeared to reduce the age-induced increase in cerebral MAO activity; (3) MAO-A and -B activities of stressed and treated 18-month-old mice did not differ significantly from the levels observed in unstressed and untreated 17-month-old mice. These results may shed light on the anti-stress effects of Ginkgo biloba extract.

Is a dot-filling group test a good tool for assessing manual performance in children?

A dot-filling test was used to assess hand performance in two populations of French children. In the first experiment, the effect of sex, age and handedness on hand performance was examined (1742 children). Age was related to the degree of laterality, but girls were less lateralized than boys. The second experiment (200 children) showed that the surprising sex differences cannot be explained by the group testing procedure. Underlying processes leading to performance in the dot-filling task are probably different from those involved in other tests generally used for children.

Lack of startle modulation by smoking cues in smokers.

RATIONALE: The startle reflex methodology has been used to study the effects of nicotine in humans and the motivational effects of smoking cues in smokers. However, no other studies investigate startle modulation by smoking cues in smokers compared to non-smokers. In the other studies, smoking deprivation was manipulated in smokers or smokers were not compared directly to non-smokers. OBJECTIVE: The goal of this study was to examine the temporal course of information processing following the presentation of a smoking-related cue using the startle probe methodology in smokers compared to non-smokers. METHODS: Thirty-four smokers were selected on the basis of nicotinic dependence according to the DSM-IV, and compared to 34 non-smokers. During testing, subjects viewed neutral pictures and smoking related pictures displayed on a computer screen. Acoustic startle stimuli were delivered at various times after picture onset (60, 120 or 5000 ms) to examine inhibition by lead stimulus and the affective modulation of startle. RESULTS: The magnitude of startle reflex inhibition increased in smokers compared to non-smokers, at 60 and 120 ms. In all, there was no PicturexGroup interaction effect. CONCLUSION: We showed that smoking cues have no impact on the startle reflex of either group, even if, in line with previous results, prepulse inhibition was higher in smokers than non-smokers. These results suggest that smoking cues have no effect on the positive reinforcement of nicotine consumption, and that cognitive factors play a primary role in the development and maintenance of tobacco dependence.

Balance control and posture differences in the anxious BALB/cByJ mice compared to the non anxious C57BL/6J mice.

A relation between anxiety disorders and balance control dysfunctions has been observed in many studies in humans. A mismatch in the integration of sensory inputs could trigger these disturbances. Very few experimental animal procedures have been designed to study the functional link between anxiety and balance control. A task was therefore developed, challenging the visual, vestibular and somesthesic sensory systems in mice. The test, called the 'rotating beam', gave an accurate assessment of balance control and the posture, using sensitive measures (number of falls and imbalances, position of tail and trunk). Striking differences were observed between the two inbred strains of mice known to have radically different anxiety-related behaviour. The highly anxious strain, BALB/cByJ, performed poorly compared to the non anxious strain, C57BL/6J. Balance control and postural abilities of anxious mice were improved by acute anxiolytic diazepam treatment. Lower behavioural performance level was registered in non anxious mice given anxiogenic beta-CCM treatment. The findings account for a strong relationship between anxiety and balance control in mice. Finally, the highly sensitive procedure proved to be well suited to the study of functional links between anxiety and sensorimotor processes.

Quantitative trait loci implicated in corpus callosum midsagittal area in mice.

The midsagittal area of the corpus callosum expressed as the percentage of the hemispheric surface is smaller in the NZB/BlNJ than in the C57BL/6By inbred strain of mice. We performed a QTL mapping analysis using 284 F2s. Two loci linked to this measure were found: the CCrSQTL1 and CCrSQTL2 at 87 and 67 centiMorgans from the centromere on chromosomes 1 and 4 respectively. The two loci interacted significantly. The total source of genetic variation contributed to 25% of the observed variance.

Age-dependent effects of a chronic ultramild stress procedure on open-field behaviour in B6D2F1 female mice.

Few studies have been devoted to the interaction between age and stress. However, in view of the age-related changes in various components of the stress responses, the effects of stress may not be constant with age. In this study, we used a dimensional approach to compare open-field behaviour of B6D2F1 female mice, aged 5-6, 11-12, 17-18 and 23-24 months, exposed to a chronic ultramild stress (CUMS) procedure, solely based on nonnociceptive socioenvironmental stressors. Three behavioural dimensions emerged from the principal-component analysis; these were labelled as motor reactivity, exploratory activity, and emotional reactivity. Despite a major effect of age on the three dimensions, we could not conclude that CUMS had any influence as a function the age of the subjects. At all ages, CUMS increased motor activity and had no clear-cut effect on emotional reactivity and exploratory activity. The results are discussed in terms of the influence of the nature of the stressors on behavioural responses to novelty.

An assessment of handedness in mice.

Mice from a pool of inbred strains (384 males and 329 females) were tested for handedness according to Collins' protocol in order to assess the reliability of this measurement. As previously reported by Collins these data revealed that a) approximately half of the mice were right-handed and half left-handed, b) most of the mice were strongly lateralized and c) females were more lateralized than males. The study of the psychometric characteristics of the test suggested that this measurement of behavioral asymmetry is both stable and observer independent. The test of paw preference also appeared to measure preexisting lateralization and was not a function of training during the test.

Factorial structure of the 20-item Toronto Alexithymia Scale: confirmatory factorial analyses in nonclinical and clinical samples.

OBJECTIVE: The 20-item Toronto Alexithymia Scale (TAS-20) measures three intercorrelated dimensions of alexithymia: (1) difficulties identifying feelings (DIF), (2) difficulties describing feelings (DDF), and (3) externally oriented thinking (EOT). The aim of the study was to test the three-factor model of the TAS-20 using confirmatory factorial analyses (CFA). METHOD: 769 healthy subjects and 659 patients meeting the DSM-IV criteria for substance use disorders or eating disorders completed the TAS-20. The correlation matrices for each of the samples were analyzed with LISREL 7.16. RESULTS: In each sample, the three-factor model was found to be replicable. CONCLUSION: The three TAS-20 subcales can be used to explore the distinct facets of the alexithymia construct.

Age at onset and gender resemblance in bipolar siblings.

In order to measure the intrafamilial correlation for age at onset and to examine gender resemblance among bipolar siblings, we assessed a sample of 130 bipolar patients belonging to 59 multiple affected sibships. To study the intrafamilial resemblance for age at onset and gender, we used the intraclass correlation and the sibship method, respectively. Within the whole sample, age at onset for affected siblings was correlated (rho = 0.42, P = 0.0001). Gender was randomly distributed among bipolar sibships, demonstrating the absence of gender resemblance among affected siblings. The existence of an intrafamilial correlation for age at onset among bipolar siblings suggests that this variable may assist in the identification of more heritable forms of the illness. No intrafamilial correlation was found for the gender of affected siblings, suggesting that familial vulnerability factors are not gender-specific.

Differences in anxiety-related behavior and response to diazepam in BALB/cByJ and C57BL/6J strains of mice.

The study in an ethological perspective of inbred strains of mice offers a more accurate description of anxiety-related behavior. In this context, behavioral performances of the BALB/cByJ and C57BL/6J strains were systematically compared in the staircase test, the light/dark test and the elevated plus maze test. A rarely used variable, the latency of the first entry in the dark box, was also recorded in the light/dark test. A new statistical approach to this measure meant that specific avoidance strategies could be differentiated in the two strains. A study of the behavioral responses of the two strains given treatment with diazepam, a widely used anxiolytic compound, was also carried out. Results showed substantial differences between BALB/cByJ and C57BL/6J strains. C57BL/6J mice had high baseline activity and exploration of a new environment, suggesting a low level of anxiety. BALB/cByJ mice displayed defensive and protective behavior, with limited exploration of the new environment together with low locomotor activity. The response to diazepam was also different for each strain: C57BL/6J mice showed higher sensitivity to diazepam treatment than did BALB/cByJ mice.

Alexithymia and anxiety: compounded relationships? A psychometric study.

This study is a careful examination of the relationships between different components of the alexithymia construct and state versus trait anxiety. In order to study the relations between anxiety and alexithymia in a subclinical population, we administered to 125 female college students a test battery including measures of alexithymia (TAS26), state and trait anxiety (STAI) and depression (QD2A). Results indicated positive correlations between depression, anxiety (state and trait) and alexithymia scores. Partial correlations revealed a tight link between trait anxiety and alexithymia. Furthermore, in agreement with the view that alexithymia is a multidimensional construct, the various alexithymia dimensions were found to be diversely correlated with anxiety. On the basis of partial correlation analyses, a descriptive model of the relationships between depression, state anxiety, trait anxiety and alexithymia was postulated. This model was confirmed by pathways analyses.

Gender and activation level in smokers.

Studies on the enhancing effects of nicotine on performance are usually pharmacological challenges using deprived male smokers. However, gender may be a factor that influences nicotine/smoking effects upon information processing. We investigated gender differences in contingent negative variation (CNV) amplitude in non-deprived dependent smokers performing a go-no go reaction time paradigm. Female smokers did not differ from female non-smokers in both early and late CNV, whereas male smokers presented greater early and late CNV compared to male non-smokers and an alteration in inhibiting processes responsible for CNV development in the no go condition. Consistent with the evidence of gender differences in nicotine/smoking sensitivity, these preliminary results emphasize the need for taking into account gender in psychophysiological research of nicotine/smoking effects.