Efficacy of clonidine in 24 patients with acute mania.

The authors treated 24 newly hospitalized patients suffering from acute mania with 450-900 micrograms/day of clonidine, an alpha 2-adrenergic agonist, for 2 weeks. A marked decrease in manic symptoms was observed after 5 and 13 days of treatment in about half of the patients. Early response seemed to predict the final result. Patients with a family history of affective disorder and patients who had had a good response to neuroleptics during a previous manic episode tended not to respond to clonidine. At the doses given, the patients' tolerance to clonidine was excellent: sedation was markedly lower than it is with neuroleptic treatment.

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).

The measurement of retardation in depression.

The description of clinical features helps to distinguish between depressive illness and nondepressive psychic pain and enables the clinician to decide whether prescription of an antidepressant is beneficial. Psychomotor retardation is probably a central feature of depression, and this review discusses the methods available for measuring it. The Salpêtrière Retardation Rating Scale (SRRS) specifically measures psychomotor retardation; the scale and applications are described. Means of measuring motor and speech activity and an experimental approach for understanding the process underlying psychomotor retardation are reviewed. Comparison of the SRRS and other rating scale scores demonstrates that retardation is related to depression severity and therapeutic change and is a good criterion for prediction of therapeutic effect. The SRRS has been used to show that selective antidepressants target specific clinical dimensions of depression depending on the patient subgroup treated. Measures of motor and speech activity are sensitive to therapeutic response. Choice Reaction Time and Simple Reaction Time tasks are particularly suited for examining psychomotor retardation because they test the decision process while avoiding motivation and attention interference. Psychomotor retardation is a constant and probably central feature of depression. Means available for measuring it can be used to assess the effects of antidepressants on specific clinical dimensions.

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.

Attribution of intentions to others in people with schizophrenia: a non-verbal exploration with comic strips.

Several clinical and experimental data suggest that some people with schizophrenia have an impaired ability to attribute relevant mental states to other people. We tested this notion in 24 schizophrenic patients and two control groups, who performed a task devised to test understanding of the intentions of nonverbal comic strip characters. Only the schizophrenic subjects with thought and speech disorganization had specific difficulties attributing mental states to others. The findings support cognitive models which postulate a link between planning process disorders and a deficit in mentalizing skills. The hypothesis that the more frequent an action is in everyday life, the more easily it is understood by schizophrenic subjects, is discussed.

Investigating theory of mind in schizophrenia: influence of verbalization in disorganized and non-disorganized patients.

The ability to attribute intentions to others was studied in 13 disorganized and 13 non-disorganized schizophrenic patients, 13 depressed and 13 normal controls. Subjects were asked to complete 28 comic strips requiring theory of mind skills by choosing one out of three answer cards. The answer cards were simple pictures in a first condition and short sentences in a second condition. This study, which used the cognitive neuropsychological approach, underlies the existence of a link between disorganization patterns in schizophrenia and a deficit in the attribution of intentions to others, independently of the pictorial or verbal form of the mode of answering. In addition, results show that the non-disorganized schizophrenic group, depressed and normal controls perform similarly in both pictorial/verbal conditions. The influence of the absence/presence of verbal material on a task investigating theory of mind in schizophrenia is discussed.

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.

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.

Emotional and psychopathological disturbances in HIV-infection.

1. The evaluation of emotional disturbances, depression and anxiety in 25 HIV-Positive paired with 25 HIV-Negative male homosexuals and a control group of 15 HIV-Negative male heterosexual have shown the presence of emotional perturbations and especially of an emotional blunting, in absence of depressive or anxious episode in HIV-Positive subjects. 2. Emotional perturbations were the lowest in the HIV-Negative heterosexual group. 3. These results raise the question of the emotional deficit as an adaptative process or as the direct action of the virus. 4. Its relationship with the other emotional perturbations and their impact on the evolution of the disease are discussed.

Loss of control of pre-motor activation in anxious agitated and impulsive depressives. A clinical and ERP study.

1. Current research uses a variety of traditional validation methods in order to test the clinical expression of biological models in psychiatry. The application of these methods has resulted in a paradoxical situation which requires the definition of new objectives in biological and pharmacoclinical research: the biological specificity of new psychotropic drugs does not assume any congruence between their pharmacological and their therapeutic effects, but raises the question of the relationship between biological systems and clinical symptomatology. The dimensional description of psychopathological disorders may be more appropriate to biological studies in psychiatry. 2. A study was undertaken on a population of twenty-one in-patients fulfilling the DSM III-R criteria for major depressive episode. They were divided into two groups on the basis of contrasting clinical dimensions: anxious-agitation and impulsiveness versus retardation and affective blunting. 3. Significant clinical differences between the two groups on mood profiles were echoed by contrasts in event-related potentials during a go-nogo task: only anxious agitated and impulsive patients developed an abnormal cortical activity, as measured by contingent negative variation (CNV), in the nogo condition. 4. This paper suggests how a paradigm with control of motor action leads to specify premotor activation abnormalities in the agitated impulsive depression subtype.

Speech pause time and the retardation rating scale for depression (ERD). Towards a reciprocal validation.

Sixteen depressed inpatients were studied before the onset of treatment and within 48 h of discharge or of a change in medication. Patients' evaluation included clinical ratings with the Hamilton Depression Rating Scale (HDRS) and the Retardation Rating Scale for Depression (ERD), and measure of Speech Pause Time (SPT). The main results are a confirmation in French-speaking patients of Szabadi et al.'s and Greden et al.'s findings and the strong correlation between SPT changes and ERD score changes. The latter point constitutes a reciprocal validation of SPT and ERD.

Antiparkinsonian and antidepressant effects of high doses of bromocriptine. An independent comparison.

Ten depressed parkinsonian patients were treated with high doses of bromocriptine (rang 85-220 mg/day). Changes in the parkinsonian and depressive symptomatologies were independently evaluated by a neurologist and a psychiatrist. Rating took place before treatment after wash-out and again 8 days later. Results show a significant mean improvement of both depressive and parkinsonian symptomatologies. However, there was no correlation between the two therapeutic effects in the 10 patients. Clinical and biological implications of these heterogeneous patterns are discussed.

Discrimination and response bias in memory: effects of depression severity and psychomotor retardation.

Although memory disorders have been well documented in depression, there is controversy concerning depressives' performance on recognition memory tasks; e.g. whether they have impaired discrimination and conservative or liberal response bias according to signal detection theory. In addition, symptomatic correlates of discrimination and response bias indices have been lacking. A word recognition memory task analyzed according to the two high threshold theory was administered to 26 depressives and 26 controls. Depressives obtained a lower index of discrimination (Pr) than controls. The index of response bias (Br) was not different between groups. In the depressed group, overall severity of depression was related to discrimination, whereas psychomotor retardation level was related to response bias. Cognitive performance of depressives could be advantageously analyzed in terms of these two dimensions of symptomatology.

Circadian pattern of motor activity in major depressed patients undergoing antidepressant therapy: relationship between actigraphic measures and clinical course.

The 24-hour motor activity pattern was evaluated in 26 inpatients with major depression at treatment onset and after 4 weeks of antidepressant therapy. Clinical state, depression, and psychomotor retardation, as well as motor activity level and circadian rhythm, were simultaneously assessed. Treatment responders and nonresponders were also considered. Diurnal hypoactivity and reduced 24-hour rhythm amplitude were found at treatment onset. Activity level increased significantly on discharge. The rest-activity cycle for each depressed patient fit a cosine function of 24-hour periodicity. Data tended to show no phase shift but a large intragroup phase variability. Preliminary findings of a negative correlation between basic activity level and clinical improvement, and a trend toward responders having a lower activity level than nonresponders, suggest that activity could be used to predict therapeutic response.

Clinical subtypes and age at onset in schizophrenic siblings.

This study examines the concordance of clinical subtypes and age at onset of schizophrenia in 42 sibships of multiply affected schizophrenic patients. Subtypes were defined by four major diagnostic systems (DSM-III, DSM-III-R, ICD-10, and Tsuang-Winokur criteria) and rated both for the first hospitalization and long-term diagnosis. When a sibship method was used, no concordance for subtypes was found in siblings. Age at onset, analyzed as a continuous variable with the intraclass correlation method, was found to be correlated in siblings. This finding suggest that the search for continuous traits distributed in families of schizophrenic patients might constitute an alternative to discrete category-based family studies.

Sensation seeking, nicotine dependence, and smoking motivation in female and male smokers.

Sensation-seeking scores in female (n = 36) and male (n = 60) French smokers were compared with those for a control group of female (n = 23) and male (n = 45) nonsmokers. The findings clearly show that smokers of both sexes are higher in sensation seeking than their nonsmoking counterparts: they score higher on the Disinhibition, Experience Seeking, and Boredom Susceptibility components of sensation seeking. Smoking women were particularly high on Experience Seeking. The relationships among the sensation-seeking components, nicotine dependence, and motives for smoking were assessed in the smokers. Disinhibition and Experience Seeking moderately correlated with nicotine dependence in females, as assessed by the Fagerström questionnaire and the Addictive factor of the Russell Classification of Smoking by Motives. Women high in Experience Seeking may be at particular risk for smoking and possibly for dependence. Further research is needed to state that the high sensation seeker is a person who might be expected to be particularly sensitive to the stimulating reward of smoking, and thus particularly vulnerable to becoming a dependent smoker.

Emotional deficit: an adaptative and evolutive process in HIV infection.

The objective of the present study was to evaluate emotional disturbances and psychopathological symptoms in early stages of human immunodeficiency virus (HIV) infection. Seventy-one homosexual subjects, positive to HIV and two groups of HIV-negative subjects (32 homosexuals and 26 heterosexuals) were evaluated in a semi-structured interview by two trained raters. The results showed the presence of emotional perturbations already in asymptomatic HIV-positive individuals even in the absence of caracterized depression and/or anxiety. This emotional deficit seemed to be more important in more advanced stages of the disease. Depressive and anxious symptoms appeared to be slightly but significantly present in both groups of homosexual men. This emotional deficit could be the reflect of an adaptative process to the threatening consequences of HIV-infection. Emotional perturbations, even mild should not be neglected, because their reduction contributes to the psychological well being of HIV-positive subjects.

Semantic inhibition disorders in schizophrenic patients assessed by a lexical decision task.

Lexical decision tasks were used in 17 schizophrenic subjects and 11 control subjects, to evaluate the so-called automatic priming of semantic links, and the controlled processes which involve longer lexical anticipation strategies. In this type of trial, inhibition in the recognition of the target word, when the preceding priming word is not semantically linked to it, indicates the activation of such controlled processes. Postulating that patients in the schizophrenic group were heterogeneous in terms of cognition, we compared the resultant scores in two subtypes of schizophrenic patients: paranoid and hebephrenic (CIM-9 criteria). The study demonstrated that there was a difference in performance between the schizophrenic subtypes. Although these findings need to be confirmed, they demonstrate the necessity of determining individual profiles of patients entering the trial, to take into account those of their phenomenological differences that may correspond to differences in cognitive functioning. The results indicate an absence of inhibition, but only in the paranoid group. In these subjects, results were consistent with the hypothesis of a failure to set up controlled processes rather than a stronger "automatic" activation of the semantic links. However, as the results were not significant, the hypothesis remains open to further investigation. The reasons for the nonsignificance of the results and alternative hypotheses are discussed.

Are there differential effects of fluoxetine in retarded/blunted affect versus agitated/anxious depressives? A clinical study.

BACKGROUND: Clinical selectivity of antidepressants with pharmacological specificity still remains under debate. METHOD: In the open trial presented below, the effects of fluoxetine, a selective serotonin re-uptake inhibitor (SSRI), were compared across two groups of depressive inpatients contrasted on their symptomatological expression (agitated/anxious versus retarded/blunted affect). Sixteen patients (8 in each groups) were included in the 4-weeks treatment period and submitted to a weekly-based evaluation. Global depression, retardation, emotional blunting, agitation, anxiety and mood profile were assessed. RESULTS: Significant improvements of the HDRS and MADRS scores were observed in both groups. Although no group x treatment interaction was found on the global scores of depression, a differential effect according to the group was observed on anxiety, agitation, irritability and emotional lability. DISCUSSION: These preliminary results support the hypothesis that the effect of fluoxetine on positive clinical dimensions could lead to a differential effect in patients with agitation/anxiety when compared with patients with retardation/blunted affect.