Active and placebo transcranial magnetic stimulation effects on external and internal auditory hallucinations of schizophrenia.

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) over the left temporo-parietal region has been proposed as a treatment for resistant auditory verbal hallucinations (AVH), but which patients are more likely to benefit from rTMS is still unclear. This study sought to assess the effects of rTMS on AVH, with a focus on hallucination phenomenology. METHOD: Twenty-seven patients with schizophrenia and medication-resistant AVH participated to a randomized, double-blind, placebo-controlled, add-on rTMS study. The stimulation targeted a language-perception area individually determined using functional magnetic resonance imaging and a language recognition task. AVH were assessed using the hallucination subscale of the Scale for the Assessment of Positive Symptoms (SAPS). The spatial location of AVH was assessed using the Psychotic Symptom Rating Scales. RESULTS: A significant improvement in SAPS hallucination subscale score was observed in both actively treated and placebo-treated groups with no difference between both modalities. Patients with external AVH were significantly more improved than patients with internal AVH, with both modalities. CONCLUSIONS: A marked placebo effect of rTMS was observed in patients with resistant AVH. Patients with prominent external AVH may be more likely to benefit from both active and placebo interventions. Cortical effects related to non-magnetic stimulation of the auditory cortex are suggested.

[Depression and the elderly]. / Dépression et personnes âgées.

"Depression" and "old age" are often associated among our contemporaries. In this case, "depression" is understood to be "existential despair" and not a "depressive disease": an amalgam is made of the tragedy of the patient's existence and a pathological condition. Clinical pictures of depression, the pathological nature of which is obvious, are frequent in the elderly; however, the line between normal and pathological becomes less clear above a certain symptomatic threshold, in the presence of chronic evolutions and in situations of comorbidity. The nosographical tool, in spite of its limits, is precious. Epidemiological studies that include the comorbidities of the depressive episode with cognitive and/or somatic affections permit better estimations of the prevalence of the symptoms and the depressive problems among elderly populations. The formula "depression is depression at whatever age" harbours a certain truth if one takes into account the multiple factors that modify the symptomatic expression of depression in later life. The most documented factor is the comorbidity of depression with somatic affections that is present in the majority of those aged over 80. Other psychological or sociocultural factors are also apparent, but their influence has been studied less. The decline in cognitive performance observed during depression is not exclusive to the elderly but is undeniably more marked in this population. Making an early diagnosis of Alzheimer's disease or, conversely, eliminating this diagnosis in a depressed patient complaining of diminished cognition is an essential step in the subsequent management. Together with the neuropsychological assessment and brain imaging, required for diagnosis, a neuropsychogeriatric pluridisciplinary assessment is obviously required. The management of geriatric depression is based on various approaches that include somatic care, psychotropic drugs, brain stimulation techniques and psychotherapy, but also requires medicosocial care. The coordination of care is incumbent on the general practitioner in the heart of the plan. However, this theoretical mission may appear impossible for the management of complex cases. Based on this, reflections on were initiated on the modalities of adapting the Anglo-Saxon "collaborative care" to France: coordination of the various therapeutic interventions by a care manager would offer greater efficacy than that of the usual care modalities.

[Paradoxical aggressive reactions to benzodiazepine use: a review]. / Réactions d'agressivité sous benzodiazépines: une revue de la littérature.

INTRODUCTION: With growing prescription and availability, benzodiazepine usage in France is on the increase among the general population. Although its anxiolytic action has long been proven, many side effects can be observed. TYPOLOGY AND PREVALENCE: Paradoxical reactions of aggressiveness under benzodiazepines have been discussed in the scientific literature since the 1960s. This term was introduced to describe reactions of agitation and disinhibition occurring during anxiolytic or hypnotic treatment. Physical aggression, rape, impulsive decision-making and violence have been reported, as well as autoaggressiveness and suicide. General population studies indicate a prevalence of these reactions of less than 1%, and meta-analysis has shown that use of benzodiazepines generates aggressiveness more frequently than it reduces it. It has also been shown that long-term memory (anterograde amnesia) can be impaired following the ingestion of a benzodiazepine. RISK FACTORS: Benzodiazepine-linked disinhibition, auto and heteroaggressiveness, anxiety and criminal acts have been associated with various vulnerability factors. Although the risk of these paradoxical reactions depends on the number of such factors present in a single patient, the effects of the type and dose of benzodiazepine on the frequency and the intensity of paradoxical symptoms are not clear. In terms of personality, several studies have demonstrated the role of low-stress control (specifically high-trait anxiety) on aggressiveness under benzodiazepines. Other authors underline the role of borderline personality disorder as a major risk factor predicting paradoxical reactions. Results of a study on borderline patients show a prevalence of benzodiazepine-linked disinhibition of 58%. On a neuropharmacological level, the influence of the GABA system on the serotonin control and the impact of alcohol seem to be established. Benzodiazepines, specifically when associated with alcohol, seem to facilitate GABAergic transmission, which can be at the origin of the disinhibited behaviours that have been reported. DISCUSSION: In 2000, France was the first country in terms of benzodiazepine use 17.4% of the adult population had been prescribed an anxiolytic. Implications for medicolegal and clinical practice are discussed.

[Personality tests and gender identification in male transsexuals]. / Tests de personnalité et identification sexuée chez des transsexuels masculins.

The aim of this research project was to study gender identification in male transsexuals compared to male and female controls, using the Rorschach test and the MMPI. In the international literature, many researches have shown that the nature of the human response on Rorschach card III is linked to gender identification, as is the MMPI Mf scale. Ten untreated male homosexual transsexuals and 18 treated and operated male homosexual transsexuals were compared to 10 male and 12 female controls regarding verbal IQ, human content on Rorschach card III and the MMPI Mf scale. Absence of hormonal treatment for the first group of transsexuals was checked by a blood test at the time of the psychological testing. Responses on Rorschach card III were scored according to different kinds of human contents: male (M), female (F), gender-unidentified/neutral (N), bisexual (B), feminine then masculine or the opposite (M/F), and nonhuman (NH). N, B, M/F and NH responses were rare in all Rorschach protocols. As expected, responses given by participants in the control group were significantly more consistent with their anatomical sex than with the opposite sex. Untreated transsexuals do not differ from treated and operated transsexuals on Rorschach data, and both transsexual groups give significantly more female human representations than male controls. Transsexuals' results are similar to female controls. Untreated transsexuals' mean score on the MMPI Mf scale is significantly higher than that of treated and operated transsexuals' score, in the male profile (biological sex). Both groups of transsexuals score higher on the Mf scale in the male profile than in the female profile. The mean Mf score in the male profile is significantly higher than that of male controls, whereas, in the female profile, the mean Mf score is similar to that of female controls. This study shows that for both groups of transsexuals, results are homogenous in respect of Rorschach and MMPI, showing hyper-conformism to self-perceived gender. Results in both groups are similar to results of female controls, but tend to show even more feminine gender identification. The absence of any significant difference between untreated and treated and operated transsexuals seems surprising, suggesting that the hormonal treatment has not had a major impact on gender identification processes. It would doubtless be interesting to study gender identification using even more kinds of data: all human contents in the Rorschach protocol (not just the responses given to card III), MMPI Mf scale, Draw-A-Person Test and Animal-and-Opposite Drawing Test. This would enhance result liability and could provide useful information about how gendter identification processes evolve after surgical sex reassigment.

Antidepressant efficacy and cognitive effects of repetitive transcranial magnetic stimulation in vascular depression: an open trial.

BACKGROUND: Beneficial effects of repetitive transcranial magnetic stimulation (rTMS) were demonstrated by many controlled studies in major depression. Moreover, this promising and non invasive therapeutic tool seems to be better tolerated than electroconvulsive therapy.Vascular depression is a subtype of late-life depression, associated with cerebrovascular disease and means a poorer response to antidepressant treatment. We employed rTMS over the left prefrontal cortex in 11 patients with late-onset resistant vascular depression. The primary purpose of this two-week open study was to examine antidepressant efficacy of rTMS in vascular depression. The secondary aim was to evaluate cognitive effects of rTMS in our sample. METHODS: Clinical status, as measured with the Hamilton Depression Rating Scale (HDRS), and cognitive effects, as evaluated by neuropsychological tests, were assessed at baseline and after two weeks of rTMS. Brain measurements to obtain an index of prefrontal atrophy were performed at both the motor cortex and prefrontal cortex. RESULTS: Five out of 11 resistant patients with late-onset vascular depression were responders. They showed a clinically meaningful improvement in HDRS scores, with a decrease of 11, 4 points (p<0.01). Antidepressant response is correlated to the relative degree of prefrontal atrophy (p = 0.05). After two weeks, verbal fluency and visuospatial memory improved. No cognitive performance deteriorated except for verbal memory, as the delayed recall decreased significantly in the responders' group. CONCLUSIONS: Our preliminary observations prompt to perform a subsequent controlled study to examine if rTMS may constitute an alternative to electroconvulsive therapy.

Phenomenological and comorbid features associated in obsessive-compulsive disorder: influence of age of onset.

BACKGROUND: To explore clinical features of symptoms and comorbidity according to the age of onset of patients suffering from obsessive-compulsive disorder (OCD). METHODS: The survey involved collecting data from both patient members of an OCD association, and a sample of 175 OCD patients seen in OCD specialty practice. All the patients (n=617) responded to a questionnaire on family and personal psychiatric OCD history, phenomenological features of OCD and comorbidity. They were classified according to OCD age at onset [group early age of onset (EO): under 15, group late age of onset (LO): older than 15]. RESULTS: A higher percentage of patients from Group LO complained of OCD triggering by factors such as professional difficulties and childbirth (P<0.05); also they more often had (P=0.05) a sudden onset of symptoms. On the other hand, clinical features, such as superstition and magic thoughts, parasite obsessions and repeating, counting, hoarding, tapping/rubbing and collecting compulsions were significantly more frequent (P<0.05) in EO; likewise, history of tics was more frequent in this group. The existence of comorbid depression (at least one episode) did not show any significant difference between groups. However, depression preceding OCD was more frequent in LO. There was no significant difference in treatment response according to age of onset OCD. CONCLUSIONS: The results showed a clear association of EO with obsessions of superstition and parasites, repetitive compulsions and motor and vocal tics, whereas a sudden onset, triggering factors and a more frequent depression preceding OCD characterized LO.

[Validation of the Short Cognitive Battery (B2C). Value in screening for Alzheimer's disease and depressive disorders in psychiatric practice]. / Validation de la batterie cognitive courte (B2C). Intérêt pour le dépistage précoce de la maladie d'Alzheimer et des troubles dépressifs en pratique psychiatrique.

UNLABELLED: Alzheimer's disease (AD) is a major healthcare challenge due to the increasing longevity of the population. Clinically prominent neuropsychological and neurological impairments, together with behavioral disorders characterize Alzheimer's disease (AD). In the past, behavioural and emotional disturbances received less attention than cognitive symptoms in studies of dementia. The association between cognitive and behavioural symptoms is complicated by the fact that such association could also occur with different patterns during depressive episode without dementia. Because Alzheimer's disease (AD) tends to be under diagnosed, there is an increasing need for accurate neuropsychological screening tools that are easy to administer by psychiatrists. The aim of the present study was to validate, in French, a sensitive and specific screening battery (B2C) designed to improve the discrimination between patients with AD, patients with depression, and healthy elderly subjects. POPULATION AND METHOD: The B2C was administered to 123 ambulatory subjects (mean age 76.4 2.3 years): divided in three groups of subjects. AD subjects were included (n=49) with a Mini-Mental Status Examination (MMSE) score of between 18 and 26, and a confirmed diagnosis (DSM IV) of mild to moderate AD. Subjects were not included if they were receiving treatment with an acetylcholinesterase inhibitor. The depressive group comprised elderly subjects (n=27) with at least two DSM IV criteria for a major depressive episode including the depressive mood criterion and a score of more than 17 on the Montgomery-Asberg Depression Rating Scale (MADRS). The healthy control group (n=47) comprised age-matched subjects with no neurological or psychiatric pathology. The B2C consists of four individual tasks derived from classical neuropsychological tests. Tasks were presented in the following order: temporal orientation test (knowledge of month, date, year, day of the week and time of day), 5 word test (task is originally derived from the Enhanced Cued Recall test), clock drawing test (In this widely used test, the subject had to draw a clock with all the numbers and then draw the clock hands at twenty minutes to four), and the semantic verbal fluency test (the subject was asked to generate as many words as possible from a given category in a fixed time period of 60 seconds). During the pre-study investigator meeting, the test procedure was adapted to ensure uniformity of practice in all centres. The B2C was administered one week to one month after the study inclusion date by a psychologist blinded to the patient groups and who had not participated in the subject's inclusion. Multivariate analysis was performed using a forced model of all four tests. Due to the nature of the dependent variable (AD vs controls and depressive vs control), the chosen discrimination model was a binary logistical regression model. Explanatory variables were limited to the variables of the test battery, and the dependent variable was the subject's status (AD, depressive or control). RESULTS: The mean results for each test are presented in Table II. The time taken to perform the tests was significantly higher (p=0.0001) for the AD group (11.2 minutes) when compared with both the control (7.6 minutes) and depressive group (8.2 minutes). In each of the four subtests, the AD subjects were significantly more impaired than the two other groups. Multivariate analysis was performed using a forced model of all four tests which provided correct classification of a high percentage of subjects (88.5%). The analysis followed a normal distribution and demonstrated that the AD patients were significantly impaired in all four tests of the B2C compared with controls. Depressive, elderly subjects were only impaired in verbal fluency. Multivariate analysis showed that, compared with controls, patients with mild AD were significantly impaired for all four tests. Response operating characteristics (ROC) analysis of the B2C showed: 93.8% sensitivity and 85% specificity for discriminating AD from control patients (table III), and 63% sensitivity and 96% specificity for discriminating AD from depressive patients (table IV). DISCUSSION: The main objective of this study was to demonstrate that the Short Cognitive Evaluation Battery developed in the French language is able to discriminate between patients suffering from AD and healthy elderly subjects. The results clearly demonstrate that AD patients were significantly impaired in all four tests of the B2C compared with the control group. The present study also supports the use of the screening battery for discriminating between AD and depressive subjects. The SCEB was less discriminatory for AD versus depressive patients than for AD versus controls. This could be due to the limited size of the depressive group. The verbal fluency test was the most sensitive for discriminating between AD and depression but this was at the expense of specificity. Other brief screening tests have already been developed in English speaking countries, In French language, the B2C appears to be a highly sensitive and specific tool for discriminating between patients with mild AD and healthy elderly individuals. Furthermore, in combination with clinical evaluation, the B2C could improve the specificity of the difficult discrimination between mild AD and depression. The next step of the validation process will include concurrent validity study and inclusion of a higher number of subjects with depressive symptoms.

[Biological therapies of behavioral and psychological symptoms of dementia: update and prospects]. / Les thérapeutiques biologiques des signes et symptômes comportementaux et psychologiques de la démence: mise au point et perspectives.

In addition to cognitive deficits, dementia is characterized by noncognitive behavioral disorders that are highly prevalent as the disease progresses into its later stages. These "behavioral and psychological signs and symptoms of dementia" are probably more important on a day to day basis than the cognitive deficits: in some patients, they are not a source of major disability but rather just a nuisance and may not require active pharmacological treatment; in others, they can be source of substantial anxiety and distress. Among the many behavioral symptoms of dementia, the group of behaviors included under the label of depression, anxiety, agitation, aggressiveness or uncooperativeness are the most burdensome and frequently lead to the prescription of an antipsychotic drug. They often precipitate institutional placement. The rationale for the use of psychotropic drugs is partially based upon phenomenological similarities of some behaviors observed in elderly demented patients to signs and symptoms of psychiatric disorders such as depressive illnesses, anxiety or psychotic disorders in non-elderly patients. In fact, the "psychiatric symptoms" in Alzheimer's disease or other dementia are often qualitatively different from those that characterize depressive, anxious or psychotic disorders. Many monoaminergic acquired deficits in dementia may also explain why treatment outcome studies suggest that the psychotropic drugs are less effective in patients with Alzheimer's disease or frontal lobe dementia than in patients with psychiatric disorders. The role of cholinesterase inhibitors in the treatment of neuropsychiatric symptoms in Alzheimer's disease may represent a novel and promising therapeutical approach.

[Alzheimer's disease and depression]. / Maladie d'Alzheimer et dépression.

Alzheimer's disease is the most frequent cause of dementia (60% of all dementias) and affects nearly 300,000 people in France. Alzheimer's disease is a disease of the elderly which generally begins after 60 years and whose prevalence increases markedly after age 75 years. The elderly population is increasing in all Western countries. Alzheimer's disease thus constitutes a veritable emergent public health problem. The rapid inflation of the epidemiological and etiopathogenetic data have contributed to enhanced nosographic definition and finer semiological characterization of the disease. Thus, the classic concept of senile dementia has been totally abandoned. In contrast, the concept of depressive pseudodementia as defined by Kiloh (1961) remains present in the "psychiatric culture". The concept refers to rare clinical situations in which the controversial concept of "test therapy" with antidepressants retains, in the author's opinion, some utility. Depressive or psychobehavioral signs and symptoms frequently inaugurate Alzheimer's disease giving rise to first-line psychiatric management. The use of multidimensional evaluation instruments such as the neuropsychiatric inventory (NPI) has enabled demonstration of the signs and symptoms and their quantification through the course of the disease. In the dementia stage, the psychobehavioral symptoms are related to the patient's awareness of the degradation in his intellectual functions and the loss of independence and to specific neuropathological lesions responsible for "frontal deafferentation". Certain clinical forms of depression of late onset are also characterized by symptoms reflecting hypofrontal signs (blunted affect, apathy, defective initiative, etc.) and severe cognitive disorders. Those depressions are associated with risk factors shared with Alzheimer's disease (sex, age, vascular function, APOE 4) and constitute a risk factor for progression to dementia, requiring regular clinical and neuropsychological follow-up. Now that we are entering the era of therapy for Alzheimer's disease, the psychiatrist must contribute to the collective effort of early diagnosis and treatment. In close collaboration with all the medical and social professionals involved, the psychiatrist has a fundamental role throughout the disease, towards the patient but also in providing support and psychological assistance for caregivers.