[Psychometric approach of metacognition: Pilot study in clinical population]. / Approche psychométrique de la métacognition : étude pilote en population clinique.

BACKGROUND: Metacognition describes the process of thinking about one's own thought processes. This concept was introduced by Flavell in 1979 and has since been widely developed in the cognitive approach to mood and anxiety disorders. As it happens, many recent studies have underlined the links between metacognition and anxio-depressive symptoms, pointing out the interest of assessing its various dimensions. The short form of the Metacognitions Questionnaire is a brief multidimensional measure of a range of metacognitive processes and metacognitive beliefs about worry and cognition relevant to the vulnerability to and the maintenance of emotional disorders. The aim of this study was twofold: firstly to adapt and validate a French version of the short form of the Metacognitions Questionnaire (MCQ-30) and to assess its psychometric properties in a clinical sample, and secondly to investigate metacognitive predictors of anxiety and depression in this sample. METHOD: The sample included 55 clinical participants (24 men, 31 women, mean age=51.33±14.62) with DSM-IV-TR psychiatric disorders (major depression, bipolar disorder and obsessive-compulsive disorder). Instrument reliability (internal consistency), construct validity (confirmatory factor analysis), and convergent validity were measured. The total score and the five subscale scores were also compared with previous results in non-clinical samples. RESULTS: Reliability analyses indicated that the French version of the MCQ-30 possessed satisfactory internal consistency (Cronbach α=0.84), and confirmatory factor analysis supported the MCQ's original five-factor structure. Correlation with measurements of depression, anxiety and pathological worry demonstrated convergent validity (r=0.62, P<0.01 for anxiety; r=0.47, P<0.01 for rumination; r=0.33, P<0.05 for depression). Moreover, our clinical sample scored higher on the global scale when compared to previous non-clinical samples (mean score=71.85±13.57 while previous studies global scores ranged from 48.41±13.31 to 65.89±17.17). Consistent with others studies, negative beliefs about worry concerning uncontrollability and danger, as well as beliefs about the need to control thoughts were the strongest predictors of pathological worry (respectively r=0.68, P<0.01 and r=0.48, P<0.01) and depression (respectively r=0.45, P<0.01 and r=0.39, P<0.01), providing further support for the validity of the measure. CONCLUSION: These findings provide general support for the internal consistency of the French version of the MCQ-30, as well as its five-factor structure and its good concurrent validity in a clinical sample. They also confirm that this version is a valuable tool for the assessment of various dimensions of metacognition, in relation to the anxio-depressive symptomatology and the subsequent management of patients.

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.

[Validation of EHD self questionnaire in multiple sclerosis]. / Validation de l'Echelle d'Humeur Dépressive (EHD), version autoquestionnaire, dans la sclérose en plaques.

Depressive Mood Scale (EHD) aims at assessing the various depressive mood dimensions as "blunted affect" and "lack of emotional control". It is an 18 items hetero-evaluation scale. The aim of this study was the validation of an EHD self questionnaire version. Self questionnaire items were generated from genuine scale items. As in the former version, response format was a Lickert 5 point scale. This validation study was carried out on 77 Multiple Sclerosis (MS) patients. Mood disorders are frequent during the course of MS and might be triggered or worsened by immuno-modulation therapies. Principal Component Analysis (ACP) with Varimax rotation revealed a two factors structure. The first one, corresponding to a "blunted affect" dimension, explained 33.5% of the scale variance and was composed of 7 items. The second one, corresponding to a "lack of emotional control" dimension, explained 20% of total scale variance and was composed of 4 items. The questionnaire internal coherence coefficient (Cronbach alpha) was excellent (=0.87) and the two sub-scales ones were satisfactory [0.89 for "blunted affect" dimension and 0.71 for "lack of emotional control" dimension. The questionnaire's external validity was confirmed by a positive correlation between "lack of control" sub-score and state sub-score of the Stait-Trait Anger eXpression Inventory (STAXI)] (r=0.55, p<0.01). Moreover we found a positive correlation between the total EHD autoquestionnaire score and both sub-scores on the one hand, and the Beck Depression Inventory score on the second hand (EHD/BDI: r=0.76, p<0.01; "lack of emotional control"/BDI: r=0.68, p<0.01; "blunted affect"/BDI: r=0.63, p<0.01). Test-retest reliability was good with a positive correlation between all the initial scores and their retests, a week later. Secondarily, a structural equation modeling analysis confirmed the two-factors structure model suggested by ACP. Various indicators showed a good fit between theoretical variance-covariance matrix and the observed one (chi(2)=41.55, p=0.49, ddl=42, Goodness Fit Index GFI=0.91, Root Mean Square Residual RMSEA=0.00). Thus, we proposed a well validated self questionnaire that allows the assessment of "blunted affect" and "lack of emotional control". It should be challenging to correlate those dimensions with neuro-psycho-logical testing and neuro-imagery, in patients affected by CNS diseases. Moreover, the assessment of those dimensions during interferon treatment in MS could allow a more precise evaluation of the emotional changes potentially induced by immuno-modulatory treatments.

[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.

Psychiatric genetics: search for phenotypes.

Failure to obtain convincing results in psychiatric genetics can partly be attributed to the fact that progress in molecular biology and genetic epidemiology has not been followed by an equivalent development in phenotypic description. Instead of relying entirely on classical nosological approaches, we argue that identifying more homogeneous forms of diseases through a'candidate symptom approach' among affected subjects and an endophenotype approach that identifies sub-clinical traits among non-affected relatives might yield better results. Examples where these strategies have already been fruitful when applied to complex diseases are presented in this review. Focusing on vulnerability traits might stimulate the redefinition of traditional psychiatric syndromes and help to bridge the gap between clinical and experimental approaches.

Directed forgetting in PTSD: a comparative study versus normal controls.

The most characteristic feature of Post-Traumatic Stress Disorder (PTSD) is the reexperiencing syndrome. The patient's memory seems to be fixed on the traumatic event, which may be due to disturbance of the autobiographic memory. To retrieve memories, others have to be inhibited. These inhibition mechanisms have been studied using the Directed Forgetting Paradigm, which measures the capacity to forget recently processed information and to retain the relevant information. Our hypothesis is that during PTSD, the memory is saturated with traumatic memories, so that the patients are no longer able to use the inhibitory processes. Therefore, during a Directed Forgetting Task (DFT) in which words "to remember" and words "to forget" are given, PTSD patients cannot inhibit the words "to forget", and so recall more words than the controls. We studied 30 patients with PTSD and compared them with 30 healthy controls, using DFT. The results show that the patients remembered significantly fewer words overall, and fewer of the words "to remember" than the controls, both for immediate and final recall. Our results are in favor of a reduction in directed forgetting in patients suffering from PTSD, resulting in difficulty in inhibiting irrelevant information from the overall information. There seems to be a deficit in the inhibitory processes in the memory in PTSD.

[Episodic autobiographical memory in depression: a review]. / Mémoire autobiographique épisodique et dépression.

INTRODUCTION: Autobiographical memory and personal identity (self) are linked by a reciprocal relationship. Autobiographical memory is critical for both grounding and changing the self. Individuals' current self-views, beliefs, and goals influence their recollections of the past. According to Tulving, episodic memory is characterized by autonoetic consciousness, which is associated with a sense of the self in the past (emotions and goals) and mental reliving of an experience. Its close relationship with self and emotion strongly involves episodic autobiographical memory in the psychopathology of depression. However, due to methodological and conceptual issues, little attention has been paid to episodic autobiographical memory in depression. Since the seminal work of Williams et al. 15 years ago, there is now growing interest around this issue. LITERATURE FINDINGS: We reviewed the evidence for three major features of autobiographical memory functioning in depression: an increase in general memory retrieval (overgenerality), a mood-congruent memory effect and the high occurrence of intrusive memories of stressful events. Although it was first observed among suicidal patients, overgenerality is actually associated with both depression and post-traumatic stress disorder. Overgenerality is not associated with anxious disorders other than post-traumatic stress disorder, obsessive-compulsive disorder, or borderline personality disorder. Most of controlled studies carried out on autobiographical memory in depression rely on the Williams' Autobiographical Memory Test (AMT). When presented with positive and negative cue words and asked to retrieve specific personal events, depressed patients (unlike matched controls) are less specific in their memories. They tend to recall repeated events (categorical overgeneral memories) rather than single episodes (specific memories). Overgenerality in depression is: 1) more evident with positive than with negative events (mood-congruent memory effect); 2) related to avoidance of intrusive memories; 3) quite stable over time, ie, remaining after remission; and 4) related to short-term prognosis in depression. Although it is not clear whether overgenerality is a cause or an effect of depression, there is some evidence to suggest that overgenerality is a trait marker indicating vulnerability to persistent depression. Mood-congruent effect, a well-known effect in depression, has been addressed in both autobio-graphical and non-autobiographical memory. Depressed patients spontaneously recall more negative than positive memories. With the AMT, depressed patients take longer to respond to positive than to negative cues, whereas controls do the opposite. Depression is also associated with a high occurrence of spontaneous intrusive memories of stressful life events. Studies found intrusions and related avoidance, as measured by the Impact of Event Scale, to be positively correlated with overgenerality, whereas there was no direct link between performance on the Autobiographical Memory Test and stressful life events per se. Both Williams' mnemonic interlock model and Conway's self-memory system are useful models to address the complexity of findings regarding autobiographical memory and depression. DISCUSSION: According to Williams, repeated avoidance of stressful memories leads depressed patients to have an autobiographical memory functioning characterized by iterative retrievals of categorical overgeneral memories, producing an enduring overgeneral retrieval style. According to Conway, the recollection of autobiographical memories requires a retrieval process that provides access to sensory/perceptual event-specific knowledge (ie perceptions and feelings) via a personal semantic knowledge base (ie lifetime periods and generic events). This retrieval process (generative retrieval mode) relies on both executive functioning and current self-view, namely the working-self. Spontaneous memories, usually vivid, result from a direct retrieval mode in which event-specific knowledge is directly triggered. In line with this model, episodic autobiographical memory impairment in state depression may arise from the working self rather than from autobiographical knowledge. The mood-congruent effect may be explained by the current (depressed) self. The high occurrence of intrusive memories may be explained by lack of executive control during direct retrieval. Overgenerality may rely on the interaction of both executive dysfunction and current (depressed) self, within the working-self, during generative retrieval. Our review suggests that further evidence is needed to address the relationship between executive functioning, self and autobiographical memory in depression.

Eye deviation during rotation in darkness in trait anxiety: an early expression of perceptual avoidance?

BACKGROUND: Patients with dizziness and patients with panic disorder and agoraphobia share a common symptomatology. Numerous studies have investigated a potential link between anxiety and the vestibular system, but few of them have addressed the specific topic of spatial representation. METHODS: Passive whole-body rotations in the horizontal plane were imposed on two groups of subjects who differed in their level of trait anxiety. Subjects were seated on a mobile robot in darkness. After each passive rotation, subjects were asked to reproduce the stimulus by driving the robot with a joystick and to perform a rotation of the same magnitude. Eye movements were recorded and analyzed. RESULTS: No difference in either perception (accuracy in the reproduction task) or in VOR gain was found between the two groups of subjects. Mean eye deviation, caused by fast phases of the nystagmus, differed in the two groups. It was typically in the anticompensatory direction in the non-anxious group, and in the compensatory direction the anxious group. Such compensatory movement may be explained by an egocentric orientation strategy, that may in turn indicate a lack of interest toward the visual surroundings. CONCLUSIONS: An egocentric strategy for self-orientation exhibited at a level below the threshold of awareness could reveal the existence of a physiological mode of processing leading to agoraphobic avoidance.

Heterogeneity of information-processing alterations according to dimensions of depression: an event-related potentials study.

To identify alterations in elementary cognitive operations according to dimensions of depression, two stages of information processing, namely the response choice and the motor preparation stages, were explored using an event-related potential paradigm in two subgroups of depressed patients (retarded and blunted affect versus anxious-agitated and impulsive) compared to controls. Two results are common to all depressed patients: a slow encoding of stimuli (P1 wave) and a prolonged processing of stimulus-response compatibility (after P3b). This is compensated by a global velocity increase in stimulus evaluation or decision making (P3b) in anxious-agitated patients or, on the contrary, cumulated with its velocity decrease in retarded-blunted-affect patients. Such results could provide an explanation for the massive retardation observed in blunted-affect patients, contrary to anxious-agitated patients, whose normal reaction times may come from a very high energetical involvement at the P3b level. Results as a whole suggest that impairments in blunted-affect patients concern effort mechanisms, whereas those in anxious-agitated patients concern perceptual processes.

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.

Decreased presynaptic dopamine function in the left caudate of depressed patients with affective flattening and psychomotor retardation.

OBJECTIVE: The study assessed striatal presynaptic dopamine function in patients with different subtypes of depression. METHOD: Magnetic resonance imaging and positron emission tomography with [(18)F]fluorodopa ([(18)F]DOPA) were used to compare six depressed patients with marked affective flattening and psychomotor retardation, six depressed patients with marked impulsivity and anxiety, and 10 healthy comparison subjects. Depressed patient groups were matched for severity of depression. RESULTS: [(18)F]DOPA uptake K(i) values in the left caudate were significantly lower in patients with psychomotor retardation than in patients with high impulsivity and in comparison subjects. CONCLUSIONS: These results suggest that left caudate dopamine function differs between depressed patients with psychomotor retardation and those with impulsivity and provide direct evidence of a link between dopamine hypofunction and psychomotor retardation in depression.

Body image perception among men in three countries.

OBJECTIVE: The authors tested the hypothesis that men in modern Western societies would desire to have a much leaner and more muscular body than the body they actually had or perceived themselves to have. METHOD: The height, weight, and body fat of college-aged men in Austria (N=54), France (N=65), and the United States (N=81) were measured. Using the somatomorphic matrix, a computerized test devised by the authors, the men chose the body image that they felt represented 1) their own body, 2) the body they ideally would like to have, 3) the body of an average man of their age, and 4) the male body they believed was preferred by women. The men's actual fat and muscularity was compared with that of the four images chosen. RESULTS: Only slight demographic and physical differences were found among the three groups of men. Modest differences were found between the men's measured fat and the fat of the images chosen. However, measures of muscularity produced large and highly significant differences. In all three countries, men chose a ideal body that was a mean of about 28 lb (13 kg) more muscular than themselves and estimated that women preferred a male body about 30 lb (14 kg) more muscular than themselves. In a pilot study, however, the authors found that actual women preferred an ordinary male body without added muscle. CONCLUSIONS: The wide discrepancy between men's actual muscularity and their body ideals may help explain the apparent rise in disorders such as muscle dysmorphia and anabolic steroid abuse.

Cognitive function in recent-onset demyelinating diseases.

To determine cognitive disturbances in recent demyelinating disease, we studied 21 patients with definite or probable multiple sclerosis (MS) of less than two years' duration and nine patients with recently isolated optic neuritis. None had any clinical or social evidence of cognitive impairment. Mild to moderate cognitive impairment. Mild to moderate cognitive impairment was present in 18 (60%) of 30 cases, affecting visual and/or verbal efficiency. These abnormalities were statistically significant when compared with the results of a control group of 29 patients. There was no correlation with a depressive status, between the presence of cognitive impairment and either the degree of handicap or the activity of the disease. The frequency of cognitive dysfunction (60%) appears to be comparable to that reported in other series in which MS evolution is over ten years. The natural history of cognitive functions in MS has to be identified. Neuropsychologic tests could be useful in the diagnosis of monosymptomatic or paucisymptomatic forms of MS (ie, visual or medullary).

Affective disturbances in Alzheimer's disease.

OBJECTIVE: To evaluate the emotional disturbances in patients with Alzheimer's disease (AD) using both a categorical and a dimensional approach. DESIGN: Prospective study. SETTING: Outpatient clinic in a neurological department from a general University Teaching Hospital. MEASURES: A semi-structured interview was used to fill in the Hamilton Depression Rating Scale, the Retardation Rating Scale for depression, the Tyrer and Covi scales for anxiety, and the Depressive Mood Scale for emotional disturbances. The cognitive status was assessed by the Mini-Mental State Examination and the Mattis Dementia Rating Scale. PATIENTS: One hundred eighteen consecutive AD outpatients fitting the criteria for probable or possible AD, according to the National Institute of Neurological and Communication Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association, were compared with 34 community-dwelling healthy older controls and with 20 inpatients meeting the diagnostic criteria for depression according to the Diagnostic and Statistical Manual of Mental Disorders, 3rd Edition-Revised. RESULTS: No AD patient met the criteria for Major Depressive Episode or Generalized Anxiety Disorder, but 10 (8%) met the criteria for Dysthymic Disorder. AD patients scored significantly higher than the control group but lower than the depressed group for depressive and anxious symptomatology. Depressive symptomatology was correlated negatively to the cognitive status and positively to anxious symptomatology. Two main dimensions in emotional disturbances were described using the Depressive Mood Scale: Emotional Deficit (anhedonia, hypoexpressiveness) and Loss of Control (felt irritability, hyperexpressiveness). Emotional Deficit was correlated positively to the depressive symptomatology and correlated negatively to the cognitive status and the Loss of Control dimension. Loss of Control was correlated positively to the severity of the depressive and anxious symptomatology and weakly to cognitive performance. CONCLUSION: Affective changes were found frequently in AD patients, but no major affective disorder was found. The dimensional approach seems to be more appropriate than the categorical approach to describe the emotional disturbances in these patients.

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.

Theoretical considerations and perspectives on the onset of action of moclobemide.

The aim of this paper is to focus on methodological problems related to clinical studies on the onset of action of antidepressants, especially moclobemide. The methodological discussion proposed focuses on: --global efficacy as a function of time; --proposals for a specific approach to the study of the onset of action; --quality of the response and onset of action; --the dimensional level and the onset of action.

Attention deficits in depression: an electrophysiological marker.

EVENT-RELATED POTENTIALS were recorded in young depressed subjects and compared with results from controls. Subjects were required to respond to targets (rare high-frequency sounds) presented to a designated ear, and to ignore targets presented to the non-designated ear as well as standards (frequent low-frequency sounds) presented to either ear. The results confirm those previously obtained with elderly depressed patients, showing the same general profile of electrophysiological and behavioural differences, and in particular a substantial reduction of the N200 amplitude in response to attended targets in depressed subjects. It is suggested that the N200 component could be a marker of depression.

Balance control and posture in anxious mice improved by SSRI treatment.

A task requiring dynamic postural stabilisation during locomotion in a conflicting visual vestibular environment (rotating beam), has been devised to assess anxiety-related balance impairments and postural changes in mice. The model, already validated with acutely administered diazepam, was used to assess the action of two chronically administered selective serotonin reuptake inhibitors (SSRIs), fluoxetine and paroxetine. On three behavioural measures (imbalance, elevation of trunk and angle of tail), observed in anxious BALB/cByJ mice, both compounds had the same diazepam-like effects: reduction in number of imbalances, higher elevation of trunk and increase in tail angle. These data suggest, for the first time, that SSRIs should be useful in the treatment of anxiety-induced balance impairments.

Decrease of complexity in EEG as a symptom of depression.

Nonlinear dynamic analysis provides new methods for the processing of the electroencephalogram (EEG). We demonstrate here that the EEG dynamics of major depressive subjects is more predictable, that is less complex, than that of control subjects. Moreover, the consequence of treatment upon the EEG dynamics seems to be dependent on the appearance of the illness. Although the specificity of this dynamic signature for different stages of depression is to be confirmed, the assumption of a strong link between a healthy system and a high level of complexity in dynamics is further supported.

Apolipoprotein E gene polymorphism in early and late onset bipolar patients.

To explore the involvement of apolipoprotein E gene (APO E) in major depression, we studied the APO E gene polymorphism in a sample of 156 unrelated bipolar patients and 91 healthy volunteers. This population was stratified for age at onset of the affective disorder (onset before 18 years, after 45 years and between 18 and 45 years). Early onset bipolar patients with psychotic symptoms exhibited a significant increase of epsilon4 allele frequency (28.9%) compared to either other bipolar patients (13.1%, chi2 = 6.52, df = 1, P < 0.02) or controls (12.1%, chi2 = 7.01, df = 1, P < 0.01). The association between epsilon4 and early onset bipolar disorder (BPD) with psychotic symptoms suggests that APO E gene is a risk factor for a subgroup of BPD, or influences the phenotypic expression (i.e. psychotic symptoms or age at onset) of manic depressive illness.