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Olanzapine long-acting injections (OLAIs) are often prescribed to patients with severe schizophrenia who are typically excluded from randomized clinical trials. To date, no mirror-image study has examined the impact of OLAIs on healthcare resource utilizations in these patients. We conducted a retrospective, one-year mirror-image study of OLAIs on 40 patients with severe schizophrenic disorder. Illness severity was defined by failure to respond to two sequential antipsychotics. Outcomes included: (i) healthcare resource utilizations via hospitalization admissions, bed days, outpatient visits, and inpatient service costs computations (ii) clinical efficacy through changes in the Brief Psychiatric Rating Scale (BPRS) and in the Clinical Global Impression-Schizophrenia Scale (CGI-SCH), and (iii) adverse effects. After one year, OLAIs were associated with significant decreases of 65.7%, 86.2% and 86.2% in hospitalization admissions, bed days, and inpatient service costs respectively. A significant mean change of -0.47 and -0.63 was determined the BPRS and the CGI-SCH scores, respectively. There were no significant differences in the number of outpatient visits and adverse effects, except for post-injection sedation/delirium syndrome whose incidence was 0.30% per injection. This mirror-image study provides the first evidence that prescribing OLAIs reduces in a cost-effective manner average bed days and hospital admissions in patients with severe schizophrenia., (Copyright © 2018. Published by Elsevier B.V.)

Background: Understanding the relationship between psychopathology and major domains of human neurobehavioral functioning may identify new transdiagnostic treatment targets. However, studies examining the interrelationship between psychopathological symptoms, sensorimotor, cognitive, and global functioning in a transdiagnostic sample are lacking. We hypothesized a close relationship between sensorimotor and cognitive functioning in a transdiagnostic patient sample., Methods: We applied network analysis and community detection methods to examine the interplay and centrality [expected influence (EI) and strength] between psychopathological symptoms, sensorimotor, cognitive, and global functioning in a transdiagnostic sample consisting of 174 schizophrenia spectrum (SSD) and 38 mood disorder (MOD) patients. All patients (n = 212) were examined with the Positive and Negative Syndrome Scale (PANSS), the Heidelberg Neurological Soft Signs Scale (NSS), the Global Assessment of Functioning (GAF), and the Brief Cognitive Assessment Tool for Schizophrenia consisted of trail making test B (TMT-B), category fluency (CF) and digit symbol substitution test (DSST)., Results: NSS showed closer connections with TMT-B, CF, and DSST than with GAF and PANSS. DSST, PANSS general, and NSS motor coordination scores showed the highest EI. Sensory integration, DSST, and CF showed the highest strength., Conclusions: The close connection between sensorimotor and cognitive impairment as well as the high centrality of sensorimotor symptoms suggests that both domains share aspects of SSD and MOD pathophysiology. But, because the majority of the study population was diagnosed with SSD, the question as to whether sensorimotor symptoms are really a transdiagnostic therapeutic target needs to be examined in future studies including more balanced diagnostic groups., (© 2024. The Author(s).)

Objective: To examine the criminological circumstances of homicide in a group of French murderers with and without major mental disorders (MMD) stratified by the perpetrator's gender., Methods: Sociodemographic, clinical, and criminological variables were collected from the psychiatric expert reports of 210 cases of homicide heard at the High Court of Angers, France. Murderers were categorized according to MMD diagnosis and gender., Results: Among 210 murderers, 17.6% (n = 37) had a MMD (20% of the female perpetrators). Logistic regression models showed that being a murderer with a MMD was associated with younger age (adjusted Odds Ratio OR = 1.03, P = 0.034), high school education (OR = 2.48, P = 0.036), previous use of psychiatric services (OR = 4.75, P = 0.003), alcohol intoxication (OR = 2.71, P = 0.027), and delusional state (OR = 3.96, P = 0.002) at the time of the homicide. Multiple correspondence analyses showed that female murderers with a MMD were more prone to have depression and to use drowning as a method than those without a MMD, and that male murderers with a MMD more often had a high school education and delusional beliefs at the time of the homicide than those without a MMD., Conclusion: Specific profiles of criminological circumstances of homicide could help to explore the risk of homicide in female and male patients with a MMD., (Copyright © 2016 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.)

Background: The development of neuroimaging biomarkers in patients with schizophrenia (SCZ) requires a refined clinical characterization. A limitation of the neuroimaging literature is the partial uptake of progress in characterizing disease-related features, particularly negative symptoms (NS) and cognitive impairment (CI). In the present study, we assessed NS and CI using up-to-date instruments and investigated the associations of abnormalities in brain restingstate (rs)-activity with disease-related features. Methods: Sixty-two community-dwelling SCZ subjects participated in the study. Multiple regression analyses were performed with the rs-activity of nine regions of interest as dependent variables and disease-related features as explanatory variables. Results: Attention/vigilance deficits were negatively associated with dorsal anterior cingulate rs-activity and, together with depression, were positively associated with right dorsolateral prefrontal cortex rs-activity. These deficits and impairment of Reasoning/problem-solving, together with conceptual disorganization, were associated with right inferior parietal lobule and temporal parietal junction rs-activity. Independent of other features, the NS Expressive Deficit domain was associated with the left ventral caudate, while the Motivational Deficit was associated with the dorsal caudate rs-activity. Conclusion: Neurocognitive deficits and the two negative symptom domains are associated with different neural markers. Replications of these findings could foster the identification of clinically actionable biomarkers of poor functional outcomes. [ABSTRACT FROM AUTHOR]

Objective: This study aimed at determining brain structural imaging correlates of neurological soft signs (NSS) in patients suffering from a first-episode psychosis., Method: Fifty-two patients with a DSMIV diagnosis of first-episode psychosis (schizophrenia or schizophrenia spectrum disorder) were consecutively included. Subjects were assessed using a standardized neurological examination for motor coordination, motor integration and sensory integration. Anatomical magnetic resonance images (MRI) were analysed in the whole brain using optimized voxel-based morphometry., Results: Neurological soft signs (NSS) total score (P-corrected = 0.013) and motor integration subscore (P-corrected = 0.035) were found to negatively correlate with grey matter structure of the dorsolateral prefrontal cortices. Motor coordination subscore was positively correlated with grey matter structure of the thalami (P-corrected = 0.002) and negatively with white matter structure of the cerebellum (P-corrected = 0.034). The addition of age and gender as covariate yielded similar results. We did not find any correlation between neither sensory integration subscore and grey matter structure nor NSS total score, motor integration subscore and voxel-based morphometry (VBM) white matter structure., Conclusion: Structural alteration in the cerebello-thalamo-prefrontal network is associated with neurological soft signs in schizophrenia, a candidate network for 'cognitive dysmetria'., (© 2011 John Wiley & Sons A/S.)

Some of the cognitive impairments of schizophrenia are already detectable before the onset of the disease, and could help to identify individuals at higher risk of psychosis. In patients with schizophrenia, semantic verbal fluency (VF) is more impaired than phonological fluency. We investigated whether the same profile is present in young patients at Ultra High Risk of psychosis (UHR). One hundred and fifty six young patients (15-30y.o.) consecutively seeking help at our specialized youth mental health center with no definite psychiatric diagnoses were recruited and assessed with the CAARMS. Individuals meeting the criteria for UHR were compared to the remaining patients considered as Help Seeker Controls (HSCo). UHR individuals had a lower mean total semantic fluency score than HSCo. This effect was significant for each semantic category ('animals' and 'fruits'). By contrast, there were no differences in phonological fluency scores between UHR and HSCo either in the total score or when each letter ('P' and 'R') was considered separately. Semantic but not phonological VF differentiated UHR individuals from non-psychotic help-seeking young adults. These results suggest that semantic deficits are present during the prodromal phase, prior to clinical expression of full-blown psychosis, and suggest that prodromes could be associated with alteration in temporal brain areas., (Copyright © 2010 Elsevier B.V. All rights reserved.)

The psychiatrist is confronted by a variety of emotional states, ranging from sadness to exaltation. The term "psychache "has been used to describe depression with melancholic features. But can such mental pain be defined without reference to visible lesions or precise physical symptoms? We report pathophysiological evidence supporting this concept and show that it has implications for both treatment and prognosis. Cognitive studies have shown that the neurological substrate of physical pain is also activated by mental pain. Mental pain is associated with a risk of suicide and can be improved by analgesics, including opiates and ketamine.

Introduction: Tragic and high profile killings by people with mental illness have been used to suggest that the community care model for mental health services has failed. It is also generally thought that schizophrenia predisposes subjects to homicidal behaviour., Objective: The aim of the present paper was to estimate the rate of mental disorder in people convicted of homicide and to examine the relationship between definitions. We investigated the links between homicide and major mental disorders., Methods: This paper reviews studies on the epidemiology of homicide committed by mentally disordered people, taken from recent international academic literature. The studies included were identified as part of a wider systematic review of the epidemiology of offending combined with mental disorder. The main databases searched were Medline. A comprehensive search was made for studies published since 1990., Results: There is an association of homicide with mental disorder, most particularly with certain manifestations of schizophrenia, antisocial personality disorder and drug or alcohol abuse. However, it is not clear why some patients behave violently and others do not. Studies of people convicted of homicide have used different definitions of mental disorder. According to the definition of Hodgins, only 15% of murderers have a major mental disorder (schizophrenia, paranoia, melancholia). Mental disorder increases the risk of homicidal violence by two-fold in men and six-fold in women. Schizophrenia increases the risk of violence by six to 10-fold in men and eight to 10-fold in women. Schizophrenia without alcoholism increased the odds ratio more than seven-fold; schizophrenia with coexisting alcoholism more than 17-fold in men. We wish to emphasize that all patients with schizophrenia should not be considered to be violent, although there are minor subgroups of schizophrenic patients in whom the risk of violence may be remarkably high. According to studies, we estimated that this increase in risk could be associated with a paranoid form of schizophrenia and coexisting substance abuse. The prevalence of schizophrenia in the homicide offenders is around 6%. Despite this, the prevalence of personality disorder or of alcohol abuse/dependence is higher: 10% to 38% respectively. The disorders with the most substantially higher odds ratios were alcohol abuse/dependence and antisocial personality disorder. Antisocial personality disorder increases the risk over 10-fold in men and over 50-fold in women. Affective disorders, anxiety disorders, dysthymia and mental retardation do not elevate the risk. Hence, according to the DMS-IV, 30 to 70% of murderers have a mental disorder of grade I or a personality disorder of grade II. However, many studies have suffered from methodological weaknesses notably since obtaining comprehensive study groups of homicide offenders has been difficult., Conclusions: There is an association of homicide with mental disorder, particularly with certain manifestations of schizophrenia, antisocial personality disorder and drug or alcohol abuse. Most perpetrators with a history of mental disorder were not acutely ill or under mental healthcare at the time of the offence. Homicidal behaviour in a country with a relatively low crime rate appears to be statistically associated with some specific mental disorders, classified according to the DSM-IV-TR classifications.

Data from two major government-funded studies of comparative antipsychotic effectiveness in schizophrenia contradict the widely prevalent belief that the newer second-generation medications are vastly superior to the older first-generation drugs. This has caused uncertainty among patients, clinicians and policy-makers about the relative utility of first- and second- generation antipsychotic agents in its treatment. To reduce confusion and provide a contextual understanding of the new data, the World Psychiatry Association Section on Pharmacopsychiatry comprehensively reviewed the literature on the comparative effectiveness of different antipsychotic treatments for schizophrenia and developed this update. Utilizing data from the approximately 1,600 randomized controlled trials of antipsychotic treatment in schizophrenia, we applied the two indirect and one direct method to comparing the effectiveness of 62 currently-available antipsychotic agents. The subclasses of 51 first-generation and 11 second-generation antipsychotics were both found to be very heterogeneous, with substantial differences in side-effect profiles among members. Second-generation antipsychotic agents were found to be inconsistently more effective than first-generation agents in alleviating negative, cognitive, and depressive symptoms and had a lower liability to cause tardive dyskinesia; these modest benefits were principally driven by the ability of second-generation antipsychotics to provide equivalent improvement in positive symptoms along with a lower risk of causing extrapyramidal side-effects. Clozapine was found to be more efficacious than other agents in treatment-refractory schizophrenia. There were no consistent differences in efficacy among other second-generation antipsychotic agents; if such differences exist, they are likely small in magnitude. Dosing was found to be a key variable in optimizing effectiveness of both first- and second- generation antipsychotic agents. There was enormous individual variability in antipsychotic response and vulnerability to various adverse effects. In contrast to their relatively similar efficacy in treating positive symptoms, there were substantial differences among both first- and second- generation antipsychotic agents with regard to their propensity to cause extrapyramidal, metabolic and other adverse effects; second-generation agents have a lower liability to cause acute extrapyramidal symptoms and tardive dyskinesia along with a tendency to cause greater metabolic side-effects than first-generation agents. Based on these data about the comparative effectiveness of different antipsychotic treatment options, we summarize elements of current best antipsychotic practice for the treatment of schizophrenia and discuss the role of government and the pharmaceutical industry in obtaining and disseminating information which can facilitate best practice.

The conflicting results reported by genetic studies with the variants of the genes coding for the dopaminergic system in cocaine addicts could be partially explained by the difficulties to constitute homogenous sample of patients. Childhood attention-deficit/hyperactivity disorder (ADHD), and/or impulsivity are frequently associated with cocaine addiction and could participate in the heterogeneity of the samples in cocaine addicts. Accordingly, it is hypothesized that cocaine addiction would be associated with the variants of the genes coding for the dopamine system in an homogenized sample of cocaine addicts, especially in individuals with childhood ADHD comorbidity, or with a high impulsivity score. The potential association of the variants TaqI A of the DRD2, BalI of the DRD3, exon III repeat of the DRD4, and 3' UTR VNTR of the DAT was examined in African-Caribbean males, smoked-cocaine dependents. All the subjects were assessed with the Diagnostic Interview of Genetic Studies, the Barratt's impulsivity scale, and the Wender Utah rating scale for childhood ADHD. A positive association was found with the DRD2 and DRD4 polymorphisms in the subgroups of patients with childhood ADHD, or with a high impulsivity score, which represented, respectively, 53.3 and 73.0% of the patients. Conversely, no positive association was found for any of the polymorphisms studied when the group of patients was examined as a whole. Therefore, our results suggest that the clinical dimensions of childhood ADHD and of impulsivity could be taken into account to homogenize the samples of patients in cocaine association studies., (2007 Wiley-Liss, Inc.)

Introduction: There is evidence that there is a small group of people with schizophrenia spectrum disorders who are more likely to commit homicide than those in the general population. However, there is limited knowledge about the psychopathology that leads to homicide in this group. The aim of this study was to examine two commonly used definitions of the Threat/Control-Override (TCO) concept, which aims to identify a certain risk of serious violence in patients with schizophrenia spectrum disorders. Methods: This is a sub analysis of a file-based, retrospective and exploratory cross-sectional study. All forensic homicide offenders with schizophrenia spectrum disorders who were detained at the Forensic Hospital Berlin as of 31 December 2014 were examined for the occurrence of TCO according to two commonly used definitions. Results: Of a total of 419 forensic patients with schizophrenia spectrum disorders, 78 committed homicide (18.6%). The forensic homicide offenders with schizophrenia spectrum disorders were characterised by being male, unemployed, single and having committed (attempted) manslaughter. Irrespective of the definition used, the entire TCO complex was present in less than a third of the sample. In both definitions, Threat symptoms were slightly less frequent than Control-Override symptoms. While Threat symptoms occurred less frequently in Stompe et al.'s definition, Control-Override symptoms were the most common. With regard to Kröber's definition of Threat and Control-Override, the situation is exactly the opposite. Discussion: Regarding the entire TCO complex, Kröber's definition seems a little more open and Stompe et al.'s more strict (38.5% vs. 35.9%). Since TCO only occurs in about one third of the subjects in both definitions, neither definition appears to be conclusive. A combination with proportions from both definitions could be a contribution to a future definition of TCO. The present study provides scarcely published primary data on psychopathology in homicide offenders with schizophrenia spectrum disorders, especially on the much discussed TCO concept in two definitions. In order to determine the most useful definition of TCO, to avoid false positives and to identify clear psychopathological risk symptoms, larger samples and comparative studies with offenders and nonoffenders should be conducted in the future. [ABSTRACT FROM AUTHOR]

Clinical signs and symptoms preceding the onset of dementia are sometimes acute, such as mood disorders often associated with hypochondriacal traits and cognitive slowing, sudden and serious suicide attempts, character and conduct disorders contrasting with the previous state, and psychotic disorders presenting as pathological mistrust, or ill-structured prejudice or persecution. Most forerunning symptoms reflect a progressive deterioration of cognitive functions over a long period, that have been masked by various coping strategies used by the patient with the spouse's help. Progressive cognitive deficits may develop over years before dementia can be diagnosed with confidence. Quantitative tools can help to detect dementia incipiens, such as the Folstein Mini Mental Test, the Mattis Dementia Scale, the five-word learning test, the clock drawing test, and the brief cognitive battery. The profile of early cognitive deterioration varies according to the type of dementia (Alzheimer's disease, fronto-temporal dementia, Lewy body dementia, and vascular dementia). The symptoms of dementia may be interlinked with symptoms of other disorders. Neuropsychological tests and brain imaging are needed to validate the diagnosis.

To date, no one antidepressant medication has been proven to be more efficient than another. Physicians are still waiting for good criteria to select which antidepressant has more chances of being effective in certain patients. Nevertheless, guidelines for antidepressant prescription could improve the rate of success in treating depression. All antidepressant medications share the same indication: a major depressive episode. Some compounds have indications other than a major depressive episode, which may be taken into account by the prescribing physician. Many researchers have tried to identify predictive criteria of response to antidepressants. The predictive clinical criteria include: endogeneity, early response, severity and duration of depression, pathological personality traits, quality of the environment, and co-morbid organic abnormalities. Paraclinical criteria have also been studied: levels of monoamines, neuro-endocrinological parameters, enzymatic activities, polysomnography, and brain imaging. Different recommendations have been proposed to guide therapeutic strategies from the acute period to the post-acute period, but three items have been mentioned most often: risk of negative side effects, patient expectations, and level of proof of efficacy of the compounds. Mild to moderate major depressive episodes raise a difficult question: can psychotherapy be an alternative option to antidepressant medication?

Background: Neurological soft signs (NSS) and minor physical anomalies (MPA) are frequent in patients with schizophrenia and their biological relatives. We examined whether the NSS and MPA are related to the genetic loading in schizophrenia., Methods: Patients with schizophrenia (DSM-IV) (n=61), nonpsychotic parents of these patients (n=76) and healthy comparison subjects (n=44) took part in the study. Parents were further classified as "presumed carriers" of the genetic loading (n=26) if they had a second relative with schizophrenia in their ascendants and/or collaterals (first or second degree) or as "presumed noncarriers" (n=50). NSS and MPA were compared in these groups., Results: A multivariate analysis indicated that total NSS and MPA scores, adjusted for age and gender, were significantly related to group status. Univariate tests showed higher scores in motor coordination and integration subscores (p=0.005 and 0.008, respectively) in presumed carriers than in presumed noncarriers. In addition, a discriminant function analysis based on total NSS and MPA scores correctly classified 71% of nonpsychotic parents in presumed carriers or presumed noncarriers., Conclusions: Neurological impairments and slight morphological anomalies seem to be associated with the genetic risk for schizophrenia, even when the disease itself is absent. Their presence might be a valuable composite intermediate phenotype for genetic studies.

Markers of vulnerability have been identified in schizophrenia, and among them, neurological soft-signs (NSS) and minor physical anomalies (MPAs) also seem to occur in biological relatives. The similarities of these developmental markers within families may depend on either genetic or non-genetic factors. The aim of the study was to investigate the intra-familial similarities of NSS and MPAs within 18 nuclear families (18 probands with schizophrenia and 36 of their non-psychotic parents). A general linear model showed similarities within families for NSS (intra-class coefficient [ICC] = 0.64; F = 2.6; df = 17.17; p = 0.02) but not for MPAs (ICC = -0.10; F = 0.7; df = 17.17; ns). We thus found a direct evidence for the intra-familial transmission of NSS but not of MPAs, suggesting that this morphological phenotypic trait could be more dependent on epigenetic influences.

Unlabelled: Over the past 10 years researches and clinicians have made substantial progress in understanding and treating nicotine dependence. To demonstrate the effectiveness of these treatments, reliable and sensitive measures of change and outcome must be used. In the nicotine dependence treatment literature numerous outcome have been used: frequencies drug use, problems associated with substance use, psychiatric comorbidity, withdrawal severity, and craving. The term craving reflects the subjective reports of addicts regarding their attempts to abstain from drug use and the state of their minds at the point at which they attempt to fail. Exposure to cues previously associated with nicotine play a role in precipitating relapse in eliciting a conditioned craving/withdrawal response and can be measures by the Questionnaire of Smoking Urge (QSU)., Objective of the Study: Validation in a French translated version of the QSU published in 1991 by Tiffany and Drobes., Methodology: 42 male and 62 female participated in the study with the translated questionnaire: mean age was 36.7 years, mean age at starting and mean duration of tobacco consumption was respectively 20.2 years old and 16.5 years, daily consumption was 16.6 cigarettes per day. The French translation of the QSU was administered to smokers instructed to abstain from smoking one hour and a half to three hours., Results: The back translation has been accepted by Tiffany because more than 85% of the items are similar to the original questionnaire. We founded the same factor analysis with two factors, "desire to smoke" and "intention to smoke" accounting for 34% and 11% of the items variance, respectively. These two factors were the same than those of the original questionnaire., Conclusion: The validation of the French translation of the QSU gives the opportunity to use a sensitive instrument to assess craving.

1. Plasma Homovanillic Acid (p HVA) levels were measured by HPLC (high performance liquid chromatography) in 5 schizo-affective depressed patients receiving a standardized treatment. (lithium, chlorpromazine and clomipramine) during 4 weeks. 2. Four patients were pretreated, without a washout period. 3. No significant difference was observed between patients and normal controls at baseline. Under treatment, pHVA levels increased (p<0.02) with clinical improvement (MADRS and PANSS scores). 4. Although effects of medications prior to the study period were not controlled, these findings suggest that depressed schizo-affective patients may have normal pHVA levels that increase with clinical improvement, unlike schizophrenic patients whose increased pHVA concentrations decline with neuroleptic treatment.

Schizophrenia is a heterogeneous disease involving genetic and environmental factors. The frequency of structural brain abnormalities or physical anomalies supports a neurodevelopmental etiology, especially in early onset schizophrenia. Brain-Derived-Neurotrophic-Factor (BDNF) is involved in the neurodevelopment of dopaminergic (DA)-related systems and interacts with the meso-limbic DA systems, involved in the therapeutic response to antipsychotic drugs and substance abuse. In addition, BDNF promotes and maintains dopamine D3 receptor (DRD3) expression. In a French Caucasian population, we found no statistical difference in allele or genotype distribution of the BDNF gene dinucleotide repeat polymorphism (166-174 bp) between the whole group of schizophrenic patients and controls. By contrast, an excess of the 172-176 bp alleles was found in patients with late onset, in neuroleptic-responding patients and in non-substance-abusing patients. BDNF gene variants thus appear to be associated with developmental features of schizophrenia. In addition, this association with good treatment responding was independent from the association found with the DRD3 Ball gene polymorphism in the same population. These results suggest an independent contribution of each gene to a treatment-sensitive form of schizophrenia.

Women remain a small minority of homicide offenders and appear to be understudied in the scientific literature. Gender-specific characteristics are however identified by existing studies. The aim of the study was to explore homicides committed by women with mental disorders, by analyzing their sociodemographic, clinical features, and criminological circumstances of the homicide. We conducted a retrospective and descriptive study among all female homicide offenders with mental disorders hospitalized in a French high-secure unit over a 20-year period (n = 30). We found that the female patients we studied were a diverse group in terms of their clinical profiles, backgrounds, and criminological characteristics. Confirming previous studies, we observed an over-representation of young women, unemployed, with a destabilized family situation and history of adverse childhood experiences. Prior self- and hetero-aggressive behavior were frequent. We found a history of suicidal behavior in 40% of cases. Their homicidal acts often occurred impulsively at home, in the evening or at night and were mainly directed toward family members (60%), especially their child(ren) (46.7%), then acquaintances (36.7%), and rarely a stranger. We found symptomatic and diagnostic heterogeneity: schizophrenia (40%), schizoaffective disorder (10%), delusional disorder (6.7%), mood disorders (26.7%), and borderline personality disorder (16.7%). Mood disorders were exclusively unipolar or bipolar depressions, often with psychotic features. The majority of patients had received psychiatric care prior to the act. We identified four subgroups, according to psychopathology and criminal motives: delusional (46.7%), melancholic (20%), homicide-suicide dynamic (16.7%), and impulsive outbursts (16.7%). We consider that further studies are necessary., (© 2023 American Academy of Forensic Sciences.)

Eye movement anomalies are more frequent in schizophrenic patients than in healthy subjects. This study deals with visually guided saccadic eye movements in seventeen schizophrenic patients [ten untreated (neuroleptic-naive or free), seven treated patients] and their correlations between symptoms presented by patients and oculomotor performances. There was no significant difference between the patients and the control group in visually guided saccades tasks. However, negative correlations between oculomotor performance and positive or disorganisation symptomatology were found. Thus, although no major oculomotor dysfunction in response to external stimulus was seen in schizophrenic patients, some symptoms were linked to oculomotor performance impairment. Thus psychiatric symptoms might share some common cerebral circuits which those involved in oculomotor tasks.

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.

The concept of pseudo-obsessive schizophrenia has been often used in the past. Clinically, severe obsessive-compulsive disorders (OCD) are closed from psychotic symptoms and ask questions about differential diagnosis with schizophrenia. Moreover some characterized schizophrenia may present in some cases obsessive compulsive symptoms (OCS). Finally, schizophrenia treated by atypical antipsychotics can be complicated by obsessive compulsive symptoms following the onset of the drug. Until now, there have been no control trials on this specific topic. Reviewing data of studies exploring the prevalence of OCD in schizophrenia this current article summarizes the different pharmaceutical approaches used in treating this disorder. In addition, a review about antipsychotics causing either emergence or exacerbation of OCS is presented.

Medical information for the general public, patients and their families is a current Public Health priority. What information can be given to a patient suffering from schizophrenia, whose understanding and judgement capacities are supposedly affected by this mental disease? In the United States, 70% of psychiatrists inform patients of schizophrenia and diagnosis of schizophreniform disorder, while in Japan less than 30% do this. The lack of information given to the general public on the disease may contribute to reinforcing the difficulty in announcing the diagnosis. Indeed, the beliefs and attitudes of the patient, his/her family, the general population and health carers concerning the disease do not match up. However, the first two years seem to be a main issue for the subsequent evolution of the disease. No specific data on the attitude of French clinicians with respect to the announcement of the diagnosis is available. In the current legal context and in view of the advances in treatment, we have carried out a survey among French psychiatrists. It is an auto-questionnaire, transversal epidemiological, descriptive and analytical. The questionnaire was sent to a population of 12,958 psychiatrists. It comprised 48 questions: 7 referred to the socio-demographic and professional characteristics of the subjects, 22 to the attitude with respect to the announcement of the diagnosis to the patients, and the last 18 concerned the attitude with respect to the announcement of the diagnosis to the families. 1,691 questionnaires were returned by free post and analysed. The socio-demographic characteristics of the sample are close to those of French psychiatrists as a whole. The number of patients suffering from schizophrenia in the active files of the psychiatrists is 24% (+/- 21.4) on the entire sample. Approximately a third (37.8%) of psychiatrists deem it necessary to announce the schizophrenia diagnosis and approximately two thirds (69.5%) declare that they sometimes announce it. Among the patients suffering from schizophrenia in the active files of the psychiatrists who responded, approximately a third (34%) were informed of their diagnosis. The main reasons for not announcing the diagnosis are firstly the "reticence to give a diagnosis label" and secondly "the functional incapacity of the patient to understand the concept". The alternative diagnosis term most commonly used is "psychosis" (46.5%). However, 48.1% of practitioners state that the announcement of a specific diagnosis allows a better therapeutic combination. Depending on the proportion of patients suffering from schizophrenia in their active file presented in two categories (< 10% and > 10%), psychiatrists significantly most frequently announce the specific diagnosis (17.3% vs 25.3%, p < 10(-3). A statistically significant proportion of younger psychiatrists (44.4 vs 46.3, p < 10(-3) with fewer years of practice (14.1 vs 15.8), more often believe that it is necessary to announce the diagnosis. The rate of response (13.5%) for this type of survey seems high, which could indicate a high interest among psychiatrists with respect to this question. Our data showed the existence of a correlation between age, number of years in practice, type of practice and the proportion of patients suffering from schizophrenia in the active file on the one hand and the attitude of the psychiatrists with respect to the announcement of the diagnosis on the other hand. It is possible that the multi-disciplinary team work of public practice psychiatrists and the fact that they are more often confronted with schizophrenic disease facilitate the announcement of this diagnosis. In the survey population, the inability to give a diagnosis may be related to the questions of the practitioners about the capacity of the subjects to understand, the lack of precision of this diagnosis, the fear of disheartening the patients and the absence of curative treatment. The risk of suicide does not seem to be one

Since the discovery of the neuroleptics in 1952, french psychiatrists have proposed a classification of neuroleptics taking into account the pharmalogical and therapeutic differences between these drugs. They distinguished three different clinical effects of neuroleptics: sedative effects, effects on the positive symptoms of schizophrenia and effects on the negative symptoms. However these agents have many side effects including the extrapyramidal syndrome (EPS), akathisia, dystonia and parkinsonism. These side effects occur in up to 75% of patients receiving typical neuroleptics and are the main cause of non-compliance. Since the eighties, clozapine was introduced for use in refractory patients because it has a better efficacy (than haloperidol) specifically on negative symptoms, a better tolerance and fewer effects. After clozapine, several new antipsychotic agents are now available, such as risperidone, olanzapine, sertindole, quietapine, ziprasidone ... Their therapeutical effects are probably linked with a dual antagonist effect on 5HT2 and D2 receptors. The present article reviews the evolution of the use of these new agents, their real efficacy, their adverse effects and their expanding indications. Future research will more clearly establish appropriate treatment guidelines for their use. These new antipsychotics should add a positive modification in schizophrenia care and in some mood disorders. The approach consisting on individualizing dimensions and clusters analysis might be useful to test the efficiency of each antipsychotic on a syndromic dimension.

The current classification system of anxiety disorders allows us to match treatment with the particular form of disorder presented. The first part of this paper presents the main features of each anxiety disorder with the approved pharmacological treatment. Despite progress in this field, treatment has to be improved to resolve resistant symptoms and to eliminate adverse side effects of the drugs currently used. The efficacy of antidepressants in chronic anxiety disorders as compared to classic 'anxiolytics' has been shown. For treatment of acute phase of anxiety, new drugs have been proposed as an alternative to benzodiazepines (BZD), but to date, no individual agent has demonstrated a better effectiveness. Interesting results may be provided by drugs acting on CCK receptors or with 5HT blockers. Preliminary results are listed and prospects in the field are proposed. The discussion focuses on an improved definition of anxiety and on the overlap of anxiety symptoms with those of depression.

Tardive dystonia is one of the most serious adverse events of typical neuroleptic treatments. They differ from tardive dyskinesia by their clinical and evolutive features. The occurrence of tardive dystonia due to new antipsychotics remained unknown. For the first time in the literature, we report a case of typical tardive dystonia occurring in a young male schizophrenic patient treated for 8 months with risperidone. No remission was observed despite several therapeutics including botulinic toxin.

"Subsyndromic" or "subthreshold" mood disorders belong to the category of mood disorders. Because newly studied, few informations are available up to date. The Appendix B of the DSM IV introduces six categories of research criteria which characterize these disorders and give us the thread of our study. From Hippocrate to contemporary specialists, many authors reported mild forms of mood disorders, including the Kraepelin or the psychoanalyst authors views. Dysthymic Disorder, Minor Depressive Disorder and Brief Recurrent Depressive Disorder are different categories of subthreshold unipolar disorders. During their course, these disorders overlap each other and with major mood disorders. Many studies, carried out in primary care practice, pointed out the severe impairment in social functioning, experienced by these patients. We propose a review of "Minor Depressive Disorders", focusing on some points: definitions, epidemiologic studies, "functional impact" of this kind of disorders, comorbidity and therapeutical considerations. Prevalence of suicide is extensive in non major depressive disorders. We discuss interest of "subsyndromic concept" aiming at the prevention of major mood disorders. Moreover, this concept leads to a new clinical approach in the care of mood disorders and provides new fields for psychopathological research.

Twenty-two patients suffering from intractable recurrent unipolar or bipolar mood disorders were enrolled in a maintenance-ECT protocol (ECT-M) for more than 18 months, with a treatment at approximately monthly intervals. Eleven have continued treatment for > 2 years. Whereas 44% of the year had been spent in the hospital with at least three episodes a year prior to ECT-M, only 7% of the year was spent in the hospital during ECT-M with only one relapse every 16 months requiring admission (p < 0.001). Forty-five percent of the patients were in full remission and 27% in partial remission according to DSM-III-R criteria. ECT-M responsiveness of rapid-cyclers and delusional depressed patients usually drug refractory has been very encouraging with full or partial remission for 100% of rapid-cyclers and 80% of delusional depressed patients.

The authors present a review of literature and their personal experience concerning the practice of methadone substitutive therapy for heroin addicts in France. In their experience, the use of methadone, within the frame of a controlled administration and in the perspective of a specific pharmaco-therapeutic profile, is a valuable therapeutical option. Otherwise, methadone could only induce a new and further pharmacological dependence. The use of methadone has often been the subject of controversies overlooking the clinical reality of drug addiction. Therefore, a controlled use of methadone remains a valuable therapeutic tool if its indications are strictly delimited.

Background: The cerebellum contributes to the precise timing of non-motor and motor functions, and cerebellum abnormalities have been implicated in psychosis pathophysiology. In this study, we explored the effects of cerebellar theta burst stimulation (TBS), an efficient transcranial magnetic stimulation protocol, on temporal discrimination and self-reported mood and psychotic symptoms. Methods: We conducted a case-crossover study in which patients with psychosis (schizophrenias, schizoaffective disorders, or bipolar disorders with psychotic features) were assigned to three sessions of TBS to the cerebellar vermis: one session each of intermittent (iTBS), continuous (cTBS), and sham TBS. Of 28 enrolled patients, 26 underwent at least one TBS session, and 20 completed all three. Before and immediately following TBS, participants rated their mood and psychotic symptoms and performed a time interval discrimination task (IDT). We hypothesized that cerebellar iTBS and cTBS would modulate these measures in opposing directions, with iTBS being adaptive and cTBS maladaptive. Results: Reaction time (RT) in the IDT decreased significantly after iTBS vs. Sham (LS-mean difference = -73.3, p = 0.0001, Cohen's d = 1.62), after iTBS vs. cTBS (LSmean difference = -137.6, p < 0.0001, d = 2.03), and after Sham vs. cTBS (LS-mean difference = -64.4, p < 0.0001, d = 1.33). We found no effect on IDT accuracy. We did not observe any effects on symptom severity after correcting for multiple comparisons. Conclusion: We observed a frequency-dependent dissociation between the effects of iTBS vs. cTBS to the cerebellar midline on the reaction time of interval discrimination in patients with psychosis. iTBS showed improved (adaptive) while cTBS led to worsening (maladaptive) speed of response. These results demonstrate behavioral target engagement in a cognitive dimension of relevance to patients with psychosis and generate testable hypotheses about the potential therapeutic role of cerebellar iTBS in this clinical population. [ABSTRACT FROM AUTHOR]

Spa therapy (aka crenobalneotherapy) has been the object of criticism due to insufficient evidence of its effectiveness. While further effectiveness studies are needed, others are also required to better evaluate the curative factors involved during spa therapy that may contribute to the effectiveness. The current study used specific scales to investigate two possible curative factors: the psychosomatic state and the letting-go of patients with mental disorders after 3 weeks of spa therapy. The Saujon Psychosomatic Questionnaire (SPQ) and the Quantified Assessment of Fluidity of Consciousness Questionnaire (QACF) evaluate psychosomatic state and letting-go, respectively. The Hospital Anxiety and Depression Scale (HAD) and the Insomnia Severity Index (ISI) evaluate depression and anxiety symptoms and insomnia symptoms, respectively. Sixty-five subjects (57 women (87.69%); 8 men), with a mean age of 56.9 (± 9.7) years, were included. SPQ and QAFC scores improved significantly before and after the 3 weeks of spa therapy. Improvement in HAD and ISI scores was significantly correlated with SPQ and QACF scores. These preliminary results suggest that the induced psychosomatic state and the letting-go induced by spa treatment with bubbling baths, jet showers, pool bathing and massage could help patients to become more available and more able to change their psychophysiological state. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate neurocognitive functioning, quality of life, and global functional performance in Ultra-High Risk (UHR) individuals compared to Familial High-Risk (FHR) individuals for developing schizophrenia. Method: An observational cross-sectional study was conducted using a convenient sampling method at Roozbeh Hospital in Tehran, Iran, from June 2017 to January 2020. The study included 40 UHR individuals based on the Structured Interview for Psychosis Syndrome (SIPS) interview, as well as 34 FHR individuals due to genetic risk. Neurocognitive functioning, quality of life, and global functional performance were assessed by using the Cambridge Automated Neuropsychological Test Battery (CANTAB) and Controlled Oral Word Association Test (COWAT), Quality of Life Scale (QLS), and Global Assessment of Functioning (GAF). Results: UHR individuals for schizophrenia demonstrated significant lower scores in phonemic and semantic verbal fluency (t = 6.218, P < 0.001; t = 4.184, P < 0.001, respectively), more total errors for spatial working memory (t = -5.874, P < 0.001), and fewer problems solved in minimum moves in Stocking of Cambridge (SOC) (t = -2.706, P < 0.01) compared to FHR individuals. Intra-Extra Dimension (IED) did not differ significantly between the two groups. Moreover, the study indicated significant GAF decline (F = 79.257, P < 0.001) and lower total score on the QLS (t = -10.655, P < 0.001) in UHR compared to FHR individuals. Conclusion: It is possible to differentiate UHR individuals from FHR individuals through neurocognitive, quality of life, and global functioning assessment. [ABSTRACT FROM AUTHOR]

Background: Attention deficit hyperactivity disorder (ADHD) is commonly associated with developmental dyslexia (DD), which are both prevalent and complicated pediatric neurodevelopmental disorders that have a significant influence on children's learning and development. Clinically, the comorbidity incidence of DD and ADHD is between 25 and 48%. Children with DD and ADHD may have more severe cognitive deficiencies, a poorer level of schooling, and a higher risk of social and emotional management disorders. Furthermore, patients with this comorbidity are frequently treated for a single condition in clinical settings, and the therapeutic outcome is poor. The development of effective treatment approaches against these diseases is complicated by their comorbidity features. This is often a major problem in diagnosis and treatment. In this study, we developed bioinformatical methodology for the analysis of the comorbidity of these two diseases. As such, the search for candidate genes related to the comorbid conditions of ADHD and DD can help in elucidating the molecular mechanisms underlying the comorbid condition, and can also be useful for genotyping and identifying new drug targets. Results: Using the ANDSystem tool, the reconstruction and analysis of gene networks associated with ADHD and dyslexia was carried out. The gene network of ADHD included 599 genes/proteins and 148,978 interactions, while that of dyslexia included 167 genes/proteins and 27,083 interactions. When the ANDSystem and GeneCards data were combined, a total of 213 genes/proteins for ADHD and dyslexia were found. An approach for ranking genes implicated in the comorbid condition of the two diseases was proposed. The approach is based on ten criteria for ranking genes by their importance, including relevance scores of association between disease and genes, standard methods of gene prioritization, as well as original criteria that take into account the characteristics of an associative gene network and the presence of known polymorphisms in the analyzed genes. Among the top 20 genes with the highest priority DRD2, DRD4, CNTNAP2 and GRIN2B are mentioned in the literature as directly linked with the comorbidity of ADHD and dyslexia. According to the proposed approach, the genes OPRM1, CHRNA4 and SNCA had the highest priority in the development of comorbidity of these two diseases. Additionally, it was revealed that the most relevant genes are involved in biological processes related to signal transduction, positive regulation of transcription from RNA polymerase II promoters, chemical synaptic transmission, response to drugs, ion transmembrane transport, nervous system development, cell adhesion, and neuron migration. Conclusions: The application of methods of reconstruction and analysis of gene networks is a powerful tool for studying the molecular mechanisms of comorbid conditions. The method put forth to rank genes by their importance for the comorbid condition of ADHD and dyslexia was employed to predict genes that play key roles in the development of the comorbid condition. The results can be utilized to plan experiments for the identification of novel candidate genes and search for novel pharmacological targets. [ABSTRACT FROM AUTHOR]

Background: We performed a pilot study on whether tablet-based measures of manual dexterity can provide behavioral markers for detection of first-episode psychosis (FEP), and whether cortical excitability/inhibition was altered in FEP. Methods: Behavioral and neurophysiological testing was undertaken in persons diagnosed with FEP (N = 20), schizophrenia (SCZ, N = 20), autism spectrum disorder (ASD, N = 20), and in healthy control subjects (N = 20). Five tablet tasks assessed different motor and cognitive functions: Finger Recognition for effector (finger) selection and mental rotation, Rhythm Tapping for temporal control, Sequence Tapping for control/memorization of motor sequences, Multi Finger Tapping for finger individuation, and Line Tracking for visuomotor control. Discrimination of FEP (from other groups) based on tablet-based measures was compared to discrimination through clinical neurological soft signs (NSS). Cortical excitability/inhibition, and cerebellar brain inhibition were assessed with transcranial magnetic stimulation. Results: Compared to controls, FEP patients showed slower reaction times and higher errors in Finger Recognition, and more variability in Rhythm Tapping. Variability in Rhythm Tapping showed highest specificity for the identification of FEP patients compared to all other groups (FEP vs. ASD/SCZ/Controls; 75% sensitivity, 90% specificity, AUC = 0.83) compared to clinical NSS (95% sensitivity, 22% specificity, AUC = 0.49). Random Forest analysis confirmed FEP discrimination vs. other groups based on dexterity variables (100% sensitivity, 85% specificity, balanced accuracy = 92%). The FEP group had reduced short-latency intra-cortical inhibition (but similar excitability) compared to controls, SCZ, and ASD. Cerebellar inhibition showed a non-significant tendency to be weaker in FEP. Conclusion: FEP patients show a distinctive pattern of dexterity impairments and weaker cortical inhibition. Easy-to-use tablet-based measures of manual dexterity capture neurological deficits in FEP and are promising markers for detection of FEP in clinical practice. [ABSTRACT FROM AUTHOR]

Objective: Antipsychotics have conflicting data with respect to obsessive–compulsive disorder/symptoms (OCD/OCS), with some reporting causality and some reporting treatment benefits. This pharmacovigilance study aimed to investigate reporting of OCD/OCS in association with the use of antipsychotics in comparison to one another, as well as treatment failure using data derived from the FDA Adverse Event Reporting System (FAERS). Methods: Data from January 1st, 2010 to December 31st, 2020 on suspected adverse drug reactions (ADRs) including OCD/OCS was obtained. The information component (IC) was used to determine a disproportionality signal, and reporting odds ratio (ROR) calculations were performed via intra‐class analyses to discern differences between the evaluated antipsychotics. Results: A total of 1454 OCD/OCS cases were utilized in IC and ROR calculations and 385,972 suspected ADRs were used as non‐cases. A significant disproportionality signal was seen with all second generation antipsychotics. Relative to other antipsychotics, only aripiprazole had a significant ROR of 23.87 (95% CI: 21.01–27.13; p < 0.0001). The ROR for antipsychotic treatment failure in those with OCD/OCS was highest with aripiprazole, and lowest with risperidone and quetiapine. Sensitivity analyses were largely in favor of the primary findings. Our analysis appears to implicate the 5‐HT1A receptor or an imbalance between this receptor and the D2‐receptor in antipsychotic treatment‐emergent OCD/OCS. Conclusions: In contrast to prior reports noting clozapine as the antipsychotic most commonly associated with de novo or exacerbated OCD/OCS, this pharmacovigilance study found aripiprazole was most frequently reported for this adverse effect. While these findings from FAERS offer a unique perspective on OCD/OCS with different antipsychotic agents, due to the inherent limitations of pharmacovigilance studies they should ideally be validated through alternative prospective research studies involving direct comparisons of antipsychotic agents. [ABSTRACT FROM AUTHOR]

Introduction: Tianeptine is approved in some countries to treat depression and anxiety. In addition to its activity on serotonin and glutamate neurotransmission, tianeptine has been proven to be a mu-opioid receptor (MOR) agonist, but only a few preclinical studies have characterized the opioid-like behavioral effects of tianeptine. Methods: In this study, we tested tianeptine activity on G protein activation using the [S35] GTPgS binding assay in brain tissue from MOR+/+ and MOR-/- mice. Then, to determine whether tianeptine behavioral responses areMOR-dependent, we characterized the analgesic, locomotor, and rewarding responses of tianeptine in MOR+/+ and MOR-/- mice using tail immersion, hot plate, locomotor, and conditioned place preference tests. Results: Using the [S35] GTPgS binding assay, we found that tianeptine signaling is mediated by MOR in the brain with properties similar to those of DAMGO (a classic MOR agonist). Furthermore, we found that the MOR is necessary for tianeptine's analgesic (tail immersion and hot plate), locomotor, and rewarding (conditioned place preference) effects. Indeed, these behavioral effects could only bemeasured in MOR+/+ mice but not in MOR-/- mice. Additionally, chronic administration of tianeptine induced tolerance to its analgesic and hyperlocomotor effects. Discussion: These findings suggest that tianeptine's opioid-like effects require MOR and that chronic use could lead to tolerance. [ABSTRACT FROM AUTHOR]