[Teraligen in the complex treatment of anxiety-phobic, behavioral and depressive syndromes in children and adolescents with schizotypal disorder]. / Teralidzhen v kompleksnoi terapii trevozhno-fobicheskikh, povedencheskikh i depressivnykh narushenii u detei i podrostkov s shizotipicheskim rasstroistvom.

OBJECTIVE: To determine the frequency of prescribing and the main therapeutic targets of Teraligen in the treatment of Schizotypal disorder (STD) in childhood and adolescence. MATERIAL AND METHODS: The sample consisted of 151 patients aged 7 to 16 years with a diagnosis of STD (F 21), of which 31.1% (n=47) of female patients and 68.9% (n=104) of male patients who received inpatient or outpatient treatment at the FSBI NCPZ from 2008 to 2020. The study was conducted by clinical-psychopathological, clinical-catamnestic, and statistical methods. RESULTS: Teraligen was prescribed by psychiatrists to patients with STD in 74.2% of cases, of which in 46.4% of cases patients received Teraligen even before the diagnosis of STD in connection with complaints of neurotic disorders (anxiety, fears and sleep disorders) (n=30), as well as in connection with autistic-like behavior (n=22). At the time of follow-up, 55% (n=83) of patients received Teraligen, of which 63.9% (n=53) of patients were prescribed it for the first time. The applied schemes of prescribing Teraligen for the treatment of anxiety-phobic, depressive and behavioral syndromes within the framework of the STD in a relatively age-related aspect are presented. CONCLUSION: The high frequency of prescribing Teraligen by psychiatrists and neurologists to children and adolescents with STD at different stages of observation is shown, which reflects the confidence of specialists in this drug. Teraligen has demonstrated a multidimensional pharmacological effect, including a mild antipsychotic effect, providing reduction of a wide range of psychopathological symptoms, with good tolerability and drug interaction. The study of the possibilities of Teraligen, both for monotherapy and for augmentation of the treatment of mental pathology in childhood, remains relevant.

Psychedelic drug use and schizotypy in young adults.

Despite recently resurrected scientific interest in classical psychedelics, few studies have focused on potential harms associated with abuse of these substances. In particular, the link between psychedelic use and psychotic symptoms has been debated while no conclusive evidence has been presented. Here, we studied an adult population (n = 1032) with a special focus on young (18-35 years) and healthy individuals (n = 701) to evaluate the association of psychedelic drug use with schizotypy and evidence integration impairment typically observed in psychosis-spectrum disorders. Experimental behavioural testing was performed in a subsample of the subjects (n = 39). We observed higher schizotypy scores in psychedelic users in the total sample. However, the effect size was notably small and only marginally significant when considering young and healthy subjects (Cohen's d = 0.13). Controlling for concomitant drug use, none of our analyses found significant associations between psychedelic use and schizotypal traits. Results from experimental testing showed that total exposure to psychedelics (frequency and temporal proximity of use) was associated with better evidence integration (Cohen's d = 0.13) and a higher sensitivity of fear responses (Cohen's d = 1.05) to the effects instructed knowledge in a reversal aversive learning task modelled computationally with skin conductance response and pupillometry. This effect was present even when controlling for demographics and concomitant drug use. On a group level, however, only difference in sensitivity of fear responses to instructed knowledge reached statistical significance. Taken together, our findings suggest that psychedelic drug use is only weakly associated with psychosis-like symptoms, which, in turn, is to a large extent explained by psychiatric comorbidities and use of other psychoactive substances. Our results also suggest that psychedelics may have an effect on flexibility of evidence integration and aversive learning processes, that may be linked to recently suggested therapeutic effects of psychedelic drugs in non-psychotic psychiatric populations.

Antipsicóticos inyectables de liberación prolongada para el tratamiento de la esquizofrenia en España / Long-acting injectable antipsychotics for the treatment of schizophrenia in Spain

Los antipsicóticos son un componente esencial del tratamiento de la esquizofrenia. Las formulaciones inyectables de liberación prolongada (ILP) surgen para mejorar la adherencia con el potencial asociado de reducir el riesgo de recaídas. El objetivo de este artículo es analizar el uso de antipsicóticos ILP en España -que es similar al de otros países europeos pero con un predominio de la utilización de ILP de segunda generación-, discutir las posibles causas de las diferencias de prescripción respecto a otros países de nuestro entorno (entre otras, aspectos organizativos, actitudes de psiquiatras, pacientes y familiares, guías de práctica clínica), y discutir su utilización en unidades de agudos, primeros episodios, y en niños y adolescentes. A nuestro juicio, aunque es necesario aumentar las pruebas existentes respecto a las ventajas de los antipsicóticos ILP y la diferenciación entre aquellos disponibles actualmente, su utilización seguirá probablemente creciendo impulsada por la experiencia clínica

Antipsychotics are an essential component in the treatment of schizophrenia. Long-acting injectable formulations (LAI) arose to improve adherence with the associated potential of reducing the risk of relapse. The objective of this article is to analyze the use of LAI antipsychotics in Spain, which is similar to other European countries but with a predominance of the use of second generation LAI, to discuss the possible causes of prescribing differences with respect to other countries (including organizational aspects, attitudes of psychiatrists, patients and family members, and clinical practice guidelines), and to discuss their use in acute psychiatric units, first episode, and in children and adolescents. In our view, while it is necessary to increase existing evidence regarding the advantages of LAI antipsychotics and the differentiation between LAI antipsychotics currently available, their use will likely continue to grow driven by clinical experience

Predictors of falls and fractures leading to hospitalization in people with schizophrenia spectrum disorder: A large representative cohort study.

AIM: To investigate predictors of falls/fractures leading to hospitalisation in people with schizophrenia-spectrum disorders. METHODS: A historical cohort of people with schizophrenia-spectrum disorders (ICD F20-29) from 01/2006-12/2012 was assembled using data from the South London and Maudsley NHS Biomedical Research Centre Case Register. Falls/fractures were ascertained from a linkage to national hospitalisation data. Separate multivariate Cox regression analyses were employed to identify predictors of falls and fractures. RESULTS: Of 11,567 people with schizophrenia-spectrum disorders (mean age 42.6 years, 43% female), 579 (incidence rate 12.79 per 1000 person-years) and 528 (11.65 per 1000 person-years) had at least one reported hospital admission due to a fall or fracture respectively and 822 patients had at least either a recorded fall or a fracture during this period (i.e. 7.1% of sample). Overall, 6.69 and 10.74 years of inpatient hospital stay per 1000-person years of follow-up occurred due to a fall and fracture respectively. 14(0.12%) and 28(0.24%) died due to a fall and fracture respectively. In Multivariable analysis, increasing age, white ethnicity, analgesics, cardiovascular disease, hypertension, diseases of the genitourinary system, visual disturbance and syncope were significant risk factor for both falls and fractures. A previous fracture (HR 2.05, 95% CI 1.53-2.73) and osteoporosis (HR 6.79, 95% CI 4.71-9.78) were strong risk factors for consequent fractures. CONCLUSION: Comorbid physical health conditions and analgesic medication prescription were associated with higher risk of falls and fractures. Osteoporosis and previous fracture were strong predictors for subsequent fractures. Interventions targeting bone health and falls/fractures need to be developed and evaluated in these populations.

[The efficacy and tolerability of pericyazine in the treatment of patients with schizotypal disorder, organic personality disorders and pathocharacterological changes within personality disorders]. / Éffektivnost' i perenosimost' terapii peritsiazinom bol'nykh shizotipicheskim rasstroistvom, organicheskim rasstroistvom lichnosti i patsientov s patokharakterologicheskimi narusheniiami v ramkakh rasstroistv lichnosti.

AIM: To assess the efficacy and tolerability of pericyazine in the treatment of patients with mental disorders manifesting with psychopathic-like symptoms and correction of pathocharacterological disorders in patients with personality disorders during the short-term admission to the hospital or the long-term outpatient treatment. MATERIAL AND METHODS: Sixty-three patients with schizotypal personality disorder and organic personality disorder with psychopathic-like symptoms and pathocharacterological changes within the diagnosis of dissocial personality disorder and borderline personality disorder were examined. Patients received pericyazine during the short-term admission to the hospital (6 weeks) or the long-term outpatient treatment (6 month). Efficacy, tolerability and compliance were assessed in the study. RESULTS AND CONCLUSION: Treatment with pricyazine was effective in all patients. The improvement was seen in patients with organic personality disorders and patients with personality disorders (psychopathy). The maximal effect was observed in inpatients and this effect remained during outpatient treatment. The improvement of mental state of patients with schizotypal personality disorder achieved during inpatient treatment with pericyazine continued during the long-term outpatient treatment. Side-effects were restricted to extrapyramidal symptoms, the frequency of metabolic syndrome was low. During outpatient treatment, the compliance was higher if the patient was managed by the same psychiatrist during inpatient- and outpatient treatment.

Trends in the prescription of clozapine in a psychiatric hospital: a 5-year observational study / Tendência na prescrição de clozapina em um hospital psiquiátrico: estudo observacional de 5 anos

Abstract Introduction Clozapine is a well-recognized effective treatment for some patients with treatment-resistant schizophrenia (TRS). Although it has potential benefits and approximately 30% of patients have a clinical indication for clozapine use, prescription rates are low. Objective To evaluate clozapine prescription trends over a 5-year period in a tertiary psychiatric hospital. Methods In this observational study, data prospectively collected by the Medical and Statistical File Service (Serviço de Arquivo Médico e Estatístico) and the Pharmacy Division of Instituto de Psiquiatria de Santa Catarina between January 2010 and December 2014 were summarized and analyzed by investigators blinded to data collection. The number of 100 mg clozapine pills dispensed by the Pharmacy Division to the inpatient units was the outcome and considered a proxy measure of clozapine prescriptions. The number of occupied inpatient unit beds and the number of patients admitted with F20-F29 (ICD-10) diagnoses during the study period were considered to be possible confounders. Results A multiple linear regression model showed that time in months was independently associated with an increase in the number of clozapine pills dispensed by the Pharmacy Division (β coefficient = 15.82; 95% confidence interval 10.88-20.75). Conclusion Clozapine prescriptions were found to have increased during the 5-year period studied, a trend that is opposite to reports from several other countries.

Resumo Introdução Clozapina é um medicamento reconhecidamente eficaz para alguns pacientes com esquizofrenia refratária ao tratamento. Apesar dos seus potenciais benefícios e de sua indicação clínica para aproximadamente 30% dos pacientes, a frequência de prescrição de clozapina é baixa. Objetivos Avaliar a tendência na prescrição de clozapina durante um período de 5 anos em um hospital psiquiátrico. Métodos Neste estudo observacional, dados coletados prospectivamente pelo Serviço de Arquivo Médico e Estatístico e pela Divisão de Farmácia (DF) do Instituto de Psiquiatria de Santa Catarina foram analisados por pesquisadores cegos para a coleta de dados. O número de comprimidos de clozapina 100 mg dispensados pela DF às enfermarias foi considerado a variável dependente e a medida de prescrição de clozapina. Número de leitos de internação ocupados e número de pacientes admitidos com diagnósticos F20-F29 (CID-10) durante o período de estudo foram considerados possíveis confundidores. Resultados Após análise com modelo de regressão linear múltipla, tempo em meses foi independentemente associado com aumento do número de comprimidos de clozapina 100 mg dispensados pela DF (coeficiente β = 15,82; intervalo de confiança de 95% 10,88-20,75). Conclusão Houve um aumento na prescrição de clozapina durante o período de 5 anos estudado, uma tendência oposta à relatada em vários outros países.

Trends in the prescription of clozapine in a psychiatric hospital: a 5-year observational study.

INTRODUCTION: Clozapine is a well-recognized effective treatment for some patients with treatment-resistant schizophrenia (TRS). Although it has potential benefits and approximately 30% of patients have a clinical indication for clozapine use, prescription rates are low. OBJECTIVE: To evaluate clozapine prescription trends over a 5-year period in a tertiary psychiatric hospital. METHODS: In this observational study, data prospectively collected by the Medical and Statistical File Service (Serviço de Arquivo Médico e Estatístico) and the Pharmacy Division of Instituto de Psiquiatria de Santa Catarina between January 2010 and December 2014 were summarized and analyzed by investigators blinded to data collection. The number of 100 mg clozapine pills dispensed by the Pharmacy Division to the inpatient units was the outcome and considered a proxy measure of clozapine prescriptions. The number of occupied inpatient unit beds and the number of patients admitted with F20-F29 (ICD-10) diagnoses during the study period were considered to be possible confounders. RESULTS: A multiple linear regression model showed that time in months was independently associated with an increase in the number of clozapine pills dispensed by the Pharmacy Division (ß coefficient = 15.82; 95% confidence interval 10.88-20.75). CONCLUSION: Clozapine prescriptions were found to have increased during the 5-year period studied, a trend that is opposite to reports from several other countries.

Antipsychotic treatment of schizotypy and schizotypal personality disorder: a systematic review.

Schizotypal personality disorder (SPD) is characterised by thought disorders, experiences of illusions, obsessive ruminations, bizarre or eccentric behaviour, cognitive problems and deficits in social functioning - symptoms that SPD shares with schizophrenia. Efforts have been undertaken to investigate the relationship between these conditions regarding genetics, pathophysiology, and phenomenology. However, treatment of SPD with antipsychotics has received less scientific attention. Embase and PubMed databases were searched using all known generic names of antipsychotics as search terms in combination with the following diagnostic terms: latent schizophrenia, schizotypal disorder, latent type schizophrenia, or SPD. Studies were categorised according to evidence level on the basis of their methodology from A, being the best, to E, being the worst. Five hundred and nine studies were retrieved and scrutinised. Sixteen studies, from the period 1972 to 2012, on antipsychotic treatment of SPD were extracted. Four studies were categorised as evidence level A, two as level B, six as level C and three as level D, with one study level E. Only four randomised, double-blind, placebo-controlled trials, on subjects with well-defined diagnoses, exists. Only amisulpride, risperidone and thiothixene have been studied according to evidence level A. This result warrants further high quality studies of the effects of antipsychotic treatment of SPD.

The coupling of low-level auditory dysfunction and oxidative stress in psychosis patients.

Patients diagnosed with schizophrenia often present with low-level sensory deficits. It is an open question whether there is a functional link between these deficits and the pathophysiology of the disease, e.g. oxidative stress and glutathione (GSH) metabolism dysregulation. Auditory evoked potentials (AEPs) were recorded from 21 psychosis disorder patients and 30 healthy controls performing an active, auditory oddball task. AEPs to standard sounds were analyzed within an electrical neuroimaging framework. A peripheral measure of participants' redox balance, the ratio of glutathione peroxidase and glutathione reductase activities (GPx/GR), was correlated with the AEP data. Patients displayed significantly decreased AEPs over the time window of the P50/N100 complex resulting from significantly weaker responses in the left temporo-parietal lobe. The GPx/GR ratio significantly correlated with patients' brain activity during the time window of the P50/N100 in the medial frontal lobe. We show for the first time a direct coupling between electrophysiological indices of AEPs and peripheral redox dysregulation in psychosis patients. This coupling is limited to stages of auditory processing that are impaired relative to healthy controls and suggests a link between biochemical and sensory dysfunction. The data highlight the potential of low-level sensory processing as a trait-marker of psychosis.

Neurophysiological evidence of impaired self-monitoring in schizotypal personality disorder and its reversal by dopaminergic antagonism.

BACKGROUND: Schizotypal personality disorder (SPD) is a schizophrenia-spectrum disorder characterized by odd or bizarre behavior, strange speech, magical thinking, unusual perceptual experiences, and social anhedonia. Schizophrenia proper has been associated with anomalies in dopaminergic neurotransmission and deficits in neurophysiological markers of self-monitoring, such as low amplitude in cognitive event-related brain potentials (ERPs) like the error-related negativity (ERN), and the error positivity (Pe). These components occur after performance errors, rely on adequate fronto-striatal function, and are sensitive to dopaminergic modulation. Here we postulated that analogous to observations in schizophrenia, SPD individuals would show deficits in self-monitoring, as measured by the ERN and the Pe. We also assessed the capacity of dopaminergic antagonists to reverse these postulated deficits. METHODS: We recorded the electroencephalogram (EEG) from 9 SPD individuals and 12 healthy controls in two separate experimental sessions while they performed the Eriksen Flanker Task, a classical task recruiting behavioral monitoring. Participants received a placebo or 1 mg risperidone according to a double-blind randomized design. RESULTS: After placebo, SPD individuals showed slower reaction times to hits, longer correction times following errors and reduced ERN and Pe amplitudes. While risperidone impaired performance and decreased ERN and Pe in the control group, it led to behavioral improvements and ERN amplitude increases in the SPD individuals. CONCLUSIONS: These results indicate that SPD individuals show deficits in self-monitoring analogous to those in schizophrenia. These deficits can be evidenced by neurophysiological measures, suggest a dopaminergic imbalance, and can be reverted by dopaminergic antagonists.

Effects of the D1 dopamine receptor agonist dihydrexidine (DAR-0100A) on working memory in schizotypal personality disorder.

Pharmacological enhancement of prefrontal D1 dopamine receptor function remains a promising therapeutic approach to ameliorate schizophrenia-spectrum working memory deficits, but has yet to be rigorously evaluated clinically. This proof-of-principle study sought to determine whether the active enantiomer of the selective and full D1 receptor agonist dihydrexidine (DAR-0100A) could attenuate working memory impairments in unmedicated patients with schizotypal personality disorder (SPD). We performed a randomized, double-blind, placebo-controlled trial of DAR-0100A (15 mg/150 ml of normal saline administered intravenously over 30 min) in medication-free patients with SPD (n=16) who met the criteria for cognitive impairment (ie, scoring below the 25th percentile on tests of working memory). We employed two measures of verbal working memory that are salient to schizophrenia-spectrum cognitive deficits, and that clinical data implicate as being associated with prefrontal D1 availability: (1) the Paced Auditory Serial Addition Test (PASAT); and (2) the N-back test (ratio of 2-back:0-back scores). Study procedures occurred over four consecutive days, with working memory testing on Days 1 and 4, and DAR-0100A/placebo administration on Days 2-4. Treatment with DAR-0100A was associated with significantly improved PASAT performance relative to placebo, with a very large effect size (Cohen's d=1.14). Performance on the N-back ratio was also significantly improved; however, this effect rested on both a non-significant enhancement and diminution of 2-back and 0-back performance, respectively; therefore interpretation of this finding is more complicated. DAR-0100A was generally well tolerated, with no serious medical or psychiatric adverse events; common side effects were mild to moderate and transient, consisting mainly of sedation, lightheadedness, tachycardia, and hypotension; however, we were able to minimize these effects, without altering the dose, with supportive measures, eg, co-administered normal saline. Although preliminary, these findings lend further clinical support to the potential of D1 receptor agonists to treat schizophrenia-spectrum working memory impairments. These data suggest a need for further studies with larger group sizes, serum DAR-0100A levels, and a more comprehensive neuropsychological battery.

Hemispheric language asymmetry in first episode psychosis and schizotypy: the role of cannabis consumption and cognitive disorganization.

Cannabis use has been related to an elevated psychosis risk and attenuated cognitive functioning. Cannabis-related cognitive impairments are also observed in populations along the psychosis dimension. We here investigated whether a potential behavioral marker of the psychosis dimension (attenuated functional hemispheric asymmetry) is even further attenuated in individuals using cannabis (CU) vs those not using cannabis (nCU). We tested 29 patients with first-episode psychosis (FEP; 11 CU) and 90 healthy controls (38 CU) on lateralized lexical decisions assessing left-hemisphere language dominance. In patients, psychotic symptoms were assessed by Positive & Negative Symptom Scale (PANSS). In controls, self-reported schizotypy was assessed (The Oxford-Liverpool Inventory of Feelings and Experiences: O-LIFE). Results indicated that nCU FEP patients had a relative reduced hemispheric asymmetry, as did controls with increasing cognitive disorganization (CogDis) scores, in particular when belonging to the group of nCU controls. Positive, disorganized and negative PANSS scores in patients and negative and positive schizotypy in controls were unrelated to hemispheric asymmetry. These findings suggest that cannabis use potentially balances rather than exacerbates uncommon hemispheric laterality patterns. Moreover, in healthy populations, the potential stabilization of typical hemispheric asymmetry in CU might be most relevant to individuals with elevated CogDis. We discuss the potential beneficial and harmful effects of cannabis use along the psychosis dimension together with propositions for future studies that should account for the mediating role of additional substances (eg nicotine), cannabis composition (eg cannabidiol content), and individual differences (eg physical health, or absence of significant polysubstance use).

Neuropsychological deficits in the prodromal phase and course of an early-onset schizophrenia. A case report.

OBJECTIVES: Although clear advances have been achieved in the study of early-onset schizophrenia (EOS), little is known to date about premorbid and prodromal neuropsychological functioning in EOS. METHOD: Here, we report on a case of an adolescent male with EOS who underwent neuropsychological testing before and after illness onset. RESULTS: Marked cognitive deficits in the domains of attention, set-shifting, and verbal memory were present both pre-onset and during the course of schizophrenia, though only deficits in verbal memory persisted after illness-onset and antipsychotic treatment. CONCLUSION: The findings of this case study suggest that impairments in the verbal memory domain are particularly prominent symptoms of cognitive impairment in prodromal EOS and persist in the course of the disorder, which further demonstrates the difficult clinical situation of adequate schooling opportunities for adolescent patients with EOS.

Marked elevation of transaminases and pancreatic enzymes in severe malnourished male with eating disorder.

We report a case of a 45 year old Caucasian malnourished male with an history of eating disorder who developed severe liver and pancreatic damage and multiorgan disfunction. At admission to our department, his body mass index (BMI) was 11.1. Biochemical evaluation showed elevated serum levels of transaminases (AST= 2291 U/L, ALT= 1792 U/L), amylase (3620 U/L), lipase (4102 U/L), CPK= 1370 U/L, LDH= 2082 U/L. No other cause of acute liver and pancreatic damage was evidenced. Haematological disorders (anemia, thrombocytopenia, leukopenia) found on admission seem related to bone marrow hypoplasia and to gelatinous marrow transformation described in severe state of malnutrition. Although a moderate increase in liver and pancreatic enzymes are a common finding in malnourished patients, only a small number of reports describes severe liver injury and multiorgan dysfunction. After a few days of treatment (hydration and nutritional support) a marked decrease of serum transaminases, lipase, amylase, CPK, LDH occurred, despite a transient increase in these levels secondary to refeeding syndrome. The association of chronic malnutrition and a decrease in systemic perfusion may be responsible for multiorgan dysfunction. In our patient the high levels of transaminases and pancreatic enzymes were the most important biochemical abnormalities normalized after refeeding.

Pituitary gland volume in patients with schizophrenia, subjects at ultra high-risk of developing psychosis and healthy controls: a systematic review and meta-analysis.

BACKGROUND: A larger pituitary size is thought to reflect a greater activation of the hypothalamic-pituitary-adrenal (HPA) axis, which may be related to an increase in the number and size of corticotroph cells. Some studies, but not all, indicate that pituitary volume increases before or at the onset of psychosis. There is a need for at critical appraisal of the literature on this topic accompanied by a meta-analytical evaluation of the data. METHODS: We included studies comparing the volume of the pituitary gland in healthy controls and patients with schizophrenia, first episode of psychosis (FEP), schizotypal disorder or ultra high-risk (UHR) subjects. We defined three groups of subjects for the analyses: healthy controls; UHR and schizotypal patients; and patients diagnosed with first episode of psychosis, schizophrenia or schizoaffective disorder. RESULTS: Ten studies were included in the meta-analysis. We found a trend of a larger pituitary volume in both UHR subject who had transition to psychosis (p=0.05) and in FEP subjects (p=0.09) compared to healthy controls. There was no difference in pituitary volume between patients with schizophrenia combined with FEP versus healthy controls (p=0.52) or between UHR (with and without transition) and healthy controls (p=0.24). In a regression analysis, we demonstrated that the number of subjects receiving antipsychotics and pituitary volume were positively correlated. As previously reported in other samples, gender also had an impact on pituitary volume with females presenting with a larger mean volume. CONCLUSION: Results from this meta-analysis suggest that the pituitary gland could be increasing before the onset of psychosis. Both gender and use of antipsychotics have a major impact on the pituitary volume.

[Cognitive deficits in first episode psychosis patients and people at risk for psychosis: from diagnosis to treatment]. / Troubles cognitifs des sujets présentant un premier épisode psychotique et à haut risque de transition vers la psychose: du repérage à la prise en charge.

BACKGROUND: Up to now, studies have not demonstrated significant efficacy of antipsychotics on cognitive impairments in patients with psychotic disorders. These cognitive deficits are of particular interest since they traditionally start early before the diagnosis of psychosis. They are observed during premorbid and prodromal stages, and during the first episode of psychosis. Moreover, cognitive impairments may be detected without any psychotic symptoms (such as positive symptoms) suggesting their development independently of the psychotic symptoms. Cognitive disturbances consist of impairments of episodic and working memories, intellectual functioning, executive functions (planning, inhibition, and cognitive flexibility), selective and sustained attentions and social cognition (emotion, recognition, theory of mind). The altered cognitive functions observed in schizophrenia are the same as in earlier stages but at a lower level of severity. LITERATURE FINDINGS: Data suggest that cognitive deficits can be considered as vulnerability markers of psychosis since they have been described in healthy relatives of psychotic patients with high genetic risk. Cognitive deficits might also be considered as predictive of the occurrence of the disease after the first episode of psychosis. Indeed, retrospective studies suggest cognitive impairments in patients with schizophrenia during premorbid and prodromal phases but not in bipolar patients. Cognitive assessment might be of particular interest in people at risk for psychosis, in order to differentiate diagnostic outcomes. Cognitive functioning impairs until the diagnosis of first episode psychosis, even though cognitive profiles are quite heterogeneous in these patients. Once the diagnosis of schizophrenia is considered, cognitive deficits may be stable, although the literature is still controversial. Several factors such as symptoms and gender can contribute in diversifying the cognitive profiles. Moreover, age of onset might worsen the prognosis because of a disruption of the cognitive development and the disturbance of scholarship in young individuals. DISCUSSION: Considering these results, the treatment of cognitive deficits should be initiated as soon as possible, e.g. in people at risk for psychosis in order to reinforce the normal cognitive development, prevent cognitive decline and to preserve the educational, professional and social status. Since antipsychotic medications do not impact on cognitive functioning, alternative therapeutics should be developed such as cognitive remediation. Several studies and meta-analyses have shown that cognitive remediation programs are particularly efficient in patients with schizophrenia or bipolar disorders. Contrary to antipsychotics, these techniques should be used in patients with a first psychotic episode, but also in individuals with subpsychotic symptoms, subthreshold to the diagnosis of schizophrenia.

Are neurocognitive, clinical and social dysfunctions in schizotaxia reversible pharmacologically?: Results from the Changsha study.

The Changsha study identifies adult, non-psychotic relatives of patients with schizophrenia who show deficits in neurocognitive, social, clinical and other dimensions, and who meet provisional criteria for a liability syndrome for schizophrenia ('schizotaxia'). In this study, we investigated whether negative symptoms, neurocognitive deficits, or other measures of clinical and social function in subjects who met our research criteria for schizotaxia were amenable to pharmacological remediation with a low dose (2.0 mg) of risperidone, a second generation antipsychotic medication. One hundred eighty nine relatives were assessed at the Mental Health Institute, Second Xiangya Hospital of Central South University, Changsha (Hunan Province, China), between 12/06 - 12/08. Eighty six of these individuals met modified criteria for schizotaxia, and 36 agreed to enter a 6-week, double-blind, placebo-controlled protocol. ANCOVAs using age and gender as covariates showed significant improvement in the risperidone group (n=20) on neurocognitive function (Wisconsin Card Sorting Test Total Errors and Perseverative Errors) and on a self-report measure of social function (Social Adjustment Scale), compared to the placebo-control group (n=16). Effect sizes were small to medium. Notably, risperidone effect sizes were larger (medium to large) in a subset of subjects (risperidone=15; placebo=10) whose membership in the schizotaxic group was supported empirically by cluster analysis. Negative symptoms did not change significantly in either analysis. The results are generally consistent with previous open-label investigations of risperidone administration in subjects with schizotaxia, and provide evidence that some neurocognitive and clinical problems are amenable to remediation in non-psychotic relatives of people with schizophrenia.

Visual masking in schizophrenia: overview and theoretical implications.

Visual masking provides several key advantages for exploring the earliest stages of visual processing in schizophrenia: it allows for control over timing at the millisecond level, there are several well-supported theories of the underlying neurobiology of visual masking, and it is amenable to examination by electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI). In this paper, we provide an overview of the visual masking impairment schizophrenia, including the relevant theoretical mechanisms for masking impairment. We will discuss its relationship to clinical symptoms, antipsychotic medications, diagnostic specificity, and presence in at-risk populations. As part of this overview, we will cover the neural correlates of visual masking based on recent findings from EEG and fMRI. Finally, we will suggest a possible mechanism that could explain the patterns of masking findings and other visual processing findings in schizophrenia.