Age and sex differences in the impact of the COVID-19 pandemic on mental health and coping mechanisms in Latin American youth.

BACKGROUND: The COVID-19 pandemic has had negative effects on mental health. Understanding sex and age differences in the perception of stressors, the use of coping strategies, and the prevalence of depression and anxiety can lead to detecting at-risk groups. METHODS: A cross-sectional online study surveyed perceived stressors, coping strategies, and the PHQ-9 and GAD-7 rating scales for symptoms of depression and anxiety. The study was open from Spring 2020 to Spring 2021 and was aimed at children, adolescents and young adults of Latin America. RESULTS: The survey was completed by 3965 participants (63.8% females). The sample was divided into children (N = 621, 15.7%), adolescents (N = 1123, 28.3%) and young adults (N = 2021, 56%). Moderate to severe symptoms of depression and anxiety were found in 43.53% and 27%, respectively, being more frequent in females. Children of both sexes showed the lowest scores in rating scales. Adult females reported a higher level of stress in regards to pandemic news, having someone close diagnosed with COVID-19,the possibility of getting sick, academic delays, economic impact, and depression, while female adolescents reported a higher level of stress regarding the lockdown, losing contact with peers and anxiety. In juxtaposition, females also reported a higher frequency of positive coping strategies. A multivariate analysis confirmed the association of several variables with the presence of depression and anxiety. CONCLUSION: A high prevalence of depression and anxiety was found among young people. Specific intervention programs must be created taking into account age and sex differences.

Neuropsychological screening with TOWI: Performance in 6- to 12-year-old children.

Videogames represent an exciting development in neuropsychological assessment of cognitive function. Here, we used TOWI, a series of games based on standardized tests, to evaluate the cognitive performance of a large sample of school-age children. We compared the metrics produced by TOWI with the performance metrics reported for the standardized tests that inspired each of these tasks. We found ascending values together with age for scores reflecting correct answers and descending values together with age for scores reflecting completion times, mistakes or missed entries. Sensitivity to developmental changes, similarities with standardized tests of task metrics contribute to the validity of TOWI as a screening tool.

Similarities and Differences in Associations Between Duration of Untreated Psychosis (DUP) and Demographic, Premorbid, and Symptom Severity Measures in Two Samples of First-Episode Psychosis Patients from Mexico and the United States.

Early-psychosis researchers have documented that duration of untreated psychosis (DUP) is an important predictor of outcomes in first-episode psychosis. Very few cross-national studies have been conducted, and none have been carried out involving patients from both Mexico and the U.S. We collaborated to answer three questions: (1) Are DUP estimates similar in two very different settings and samples? (2) Are demographic variables, premorbid adjustment, and symptom severity similarly related to DUP in the two different settings? (3) Does the same set of variables account for a similar proportion of variance in DUP in the two settings? Data on sociodemographic characteristics, premorbid adjustment, symptom severity, and DUP were available for 145 Mexican and 247 U.S. first-episode psychosis patients. DUP was compared, and bivariate analyses and multiple linear regressions were carried out in each sample. DUP estimates were similar (medians of 35 weeks in Mexico and 38 weeks in the U.S.). In the Mexican sample, DUP was associated with gender, employment status, premorbid social adjustment, and positive symptom severity (explaining 18% of variance). In the U.S. sample, DUP was associated with age, employment status, premorbid social adjustment, and positive symptom severity (but in the opposite direction of that observed in the Mexican sample), accounting for 25% of variance. Additional cross-national collaborations examining key facets of early-course psychotic disorders, including DUP, will clarify the extent of generalizability of findings, strengthen partnerships for more internationally relevant studies, and support the global movement to help young people struggling with first-episode psychosis and their families.

Cognitive impairment and its improvement after six months in adolescents with schizophrenia.

Studies evaluating the cognitive impairment in schizophrenic adolescents reported a variable course following antipsychotic treatment, with improvement being associated to patients' demographic or clinical characteristics. OBJECTIVES: To examine the cognitive impairments of a Mexican sample of adolescents with schizophrenia using the MATRICS Consensus Cognitive Battery (MCCB) before and after six months of antipsychotic treatment and to determine which demographic or clinical characteristics could be associated to cognitive improvement. METHODS: A sample of 87 Mexican patients was evaluated with the MCCB. Domain scores for three age groups (12-13, 14-15 and 16-17 y.o.) were obtained at baseline, and after 3 and 6 months of treatment. The groups were compared for demographic and clinical variables (sex, school attendance, years of education, being on their first psychotic episode, duration of illness and mean dose of antipsychotic), and a logistic regression analysis was performed to determine which variables predicted larger improvement. RESULTS: The baseline performance showed scores below the standardized mean, with improvement in all domains except for social cognition; female adolescents showed a larger improvement in attention/vigilance and visual learning domains. CONCLUSIONS: We observed cognitive impairments on schizophrenic adolescents, which improved after six months of treatment in almost all domains.

Effectiveness of a treatment guideline for schizophrenia in adolescents: Lessons from a middle-income country.

INTRODUCTION: Treatment guidelines for schizophrenia represent a standard way to manage patients, especially in countries with limited staff resources. However, they have not been compared on their efficacy with treatment as usual, despite adult studies suggesting they can be more effective. METHODS: Inpatient and outpatient adolescents with schizophrenia were randomly allocated to be either treated according to a guideline-based treatment ( n = 43) or treatment as usual ( n = 44). The effects on symptoms, psychosocial functioning and cognition were compared in a 6-month follow-up. RESULTS: There were no differences between groups in the pharmacological treatment, reduction in symptom severity or cognition. The guideline-based treatment group showed a better functioning at months 3 and 6. CONCLUSION: The guideline-based treatment had a greater effect than the treatment as usual in the psychosocial functioning of adolescent patients ( www.clinicaltrials.gov ; II3/02/0811).

Validity and reliability of the Spanish version of the Personal and Social Performance scale in adolescents with schizophrenia.

BACKGROUND: The Personal and Social Performance (PSP) scale is a widely used tool to evaluate adults with schizophrenia; however, more studies are needed regarding its usefulness in the assessment of adolescent patients, since the evaluation of their functioning could require adaptations according to development. OBJECTIVE: To examine construct validity, convergent validity, internal consistency and interrater reliability of the PSP in a sample of Mexican adolescents with schizophrenia. METHODS: A total of 40 patients with a DSM-IV diagnosis of schizophrenia or schizophreniform disorder were evaluated with PSP, CGAS, PANSS and the MATRICS battery. Construct and convergent validity were determined by the correlation between PSP with PANSS factors, MATRICS dimensions and CGAS. In addition, reliability was evaluated with Cronbach's alpha and intraclass correlation coefficients. RESULTS: PSP scores correlated with negative, excitement and cognitive factors of PANSS, CGAS as well as MATRICS domains. The PSP also showed high internal consistency and interrater reliability. CONCLUSIONS: The PSP is a valid and reliable instrument for the assessment of adolescent patients.

Registro Electrónico de Adherencia al Tratamiento de Esquizofrenia en Latinoamérica (e-STAR): Resultados clínicos del uso de risperidona inyectable de liberación prolongada a dos años de seguimiento / Electronic Schizophrenia Treatment Adherence Registry in Latin America (e-STAR): Clinical outcomes of long-acting injectable risperidone in a 2-year follow up

Schizophrenia is a chronic psychiatric disorder associated to high healthcare costs mainly driven by inpatient care. Lack of adherence to antipsychotic treatment is a common reason for relapse and rehospitalization leading to poor prognosis and global functional impairment of patients. Risperidone long-acting injection (RLAI) has demonstrated its efficacy in treating symptoms of schizophrenia and offers the potential to improve adherence to treatment. Objective To determine clinical and functional efficacy of RLAI and use of health resources (eg., hospitalizations) in a 2-year follow up study among patients with schizophrenia from Latin America. Method The electronic Schizophrenia Treatment Adherence Registry (e-STAR) is an observational study of patients who start treatment with RLAI. Data from patients recruited in Mexico, Colombia and Brazil were collected retrospectively for one year prior to baseline, at baseline and every three months for 24 months. Hospitalization rates and treatment regime were registered. Efficacy was assessed using the Clinical Global Impression of Illness-Severity Scale (CGI-S), while the Global Assessment of Functioning (GAF) and the Personal and Social Performance (PSP) were used for the evaluation of functioning. Results Seventy-three patients completed the two-year follow-up. The proportion of patients hospitalized declined from 16.4% before treatment to 4.1% after 2 years of treatment with RLAI. Only 2.7% discontinued the treatment due to lack of efficacy. Significant improvements were reported in illness severity as well as in global functioning assessed by the CGI-S, GAF and PSP scales, respectively. Discussion Our results give further support of the efficacy of RLAI for the treatment of schizophrenia. Additional to symptom severity reduction and functional recovery, improved treatment adherence and reduced hospitalization rates were observed with the use of RLAI. In a real world clinical setting, RLAI offer an effective long-term treatment for patients with schizophrenia, with a lower use of healthcare resources.

La esquizofrenia genera elevados costos al sistema de salud. La falta de adherencia al tratamiento es una de las principales causas de recaídas y hospitalizaciones en la esquizofrenia. Lo anterior conduce a un pobre pronóstico y deterioro funcional de los pacientes. La risperidona inyectable de liberación prolongada (RILP) ha demostrado su eficacia en el tratamiento de la esquizofrenia, ofreciendo la posibilidad de que los pacientes tengan una mayor adherencia terapéutica. Objetivo Determinar la eficacia y efecto sobre la funcionalidad y el uso de recursos hospitalarios de la RILP en una muestra de pacientes con esquizofrenia de América Latina a dos años de seguimiento. Método El Registro Electrónico de Adherencia al Tratamiento de Esquizofrenia en Latinoamérica (e-STAR) es un estudio observacional del uso de la RILP en la esquizofrenia. Se reclutaron pacientes de México, Colombia y Brasil. Se registró la información clínica del paciente un año previo al inicio del tratamiento con la RILP y de forma prospectiva cada tres meses hasta cumplir los 24 meses de seguimiento. Se registraron las hospitalizaciones y el esquema de tratamiento con la RILP. La escala de Impresión Clínica Global-Gravedad (CGI-S) se utilizó como indicador de eficacia mientras que la Escala Global de Funcionamiento (GAF) y la Escala de Desempeño Personal y Social (PSP) se utilizaron para evaluar el funcionamiento. Resultados Setenta y tres pacientes completaron los dos años de seguimiento. La proporción de pacientes hospitalizados disminuyó del 16.4 al 4.1% después de dos años de tratamiento con la RILP. El 2.7% descontinuó el tratamiento debido a falta de eficacia. Se observó una mejoría significativa en cuanto a la gravedad del padecimiento y el funcionamiento global. Discusión En la práctica clínica cotidiana, la RILP resulta ser un tratamiento a largo plazo efectivo para la esquizofrenia con el beneficio adicional de una menor utilización de recursos del sistema de salud.

Association study of DRD3 gene in schizophrenia in Mexican sib-pairs.

Schizophrenia is a heritable, complex mental disorder. We analysed the DRD3 gene as a candidate to be related to schizophrenia and clinical features in affected sib-pairs. A positive association with the -250A/Ser9 haplotype and a trend toward an association with formal thought disorder were observed. A synergic effect of DRD3 polymorphisms on schizophrenia susceptibility is suggested.

Clinical outcomes of long-acting injectable risperidone in patients with schizophrenia: six-month follow-up from the Electronic Schizophrenia Treatment Adherence Registry in Latin America.

BACKGROUND: Risperidone long-acting injection (RLAI) has been shown to be efficacious, improve compliance, and increase long-term retention rate on therapy. The aim of this work was to determine the effect of RLAI on clinical outcome and hospitalization rate in patients with schizophrenia or schizoaffective disorder enrolled in the electronic Schizophrenia Treatment Adherence Registry in Latin America. METHODS: Data were collected at baseline, retrospectively for the 12 months prior to baseline, and prospectively every three months for 24 months. Hospitalization prior to therapy was assessed by a retrospective chart review. Efficacy and functioning were evaluated using Clinical Global Impression of Illness Severity (CGI-S), Personal and Social Performance (PSP), and Global Assessment of Functioning (GAF) scores. Relapse and treatment were also registered. RESULTS: Patients were recruited in Mexico (n = 53), Brazil (n = 11), and Colombia (n = 15). Sixty-five percent (n = 52) were male, and mean age was 32.9 years. Patients were classified as having schizophrenia (n = 73) or schizoaffective disorder (n = 6). The mean dose of RLAI at six months was 34.1 mg (standard deviation = 10.2 mg). The percentage of hospitalized patients before treatment was 28.2% and 5.1% at six months after initiating RLAI (P < 0.001). Significant changes were registered on CGI-S, GAF, and PSP scores. CONCLUSIONS: RLAI was associated with an improvement in clinical symptoms and functioning, and a greater reduction in hospitalization.

APOE-epsilon3 and APOE-219G haplotypes increase the risk for schizophrenia in sibling pairs.

To investigate the role of the apolipoprotein E (APOE) gene in schizophrenia, the authors analyzed 60 families with this mental disorder. An association in the presence of linkage test (APL) and haplotypes analysis were undertaken using the APL v1.1 software. A global allelic transmitted was significant for APOE-epsilon3 (chi(2)=6.24, p=0.01); this allele is mainly carried by female patients (chi(2)=8.33, p=0.003), whereas APOE-219G is preferentially transmitted in males (p=0.02). Furthermore, our results show that haplotypes APOE-epsilon3/APOE-219G are associated with schizophrenia (chi(2)=11.61, p=0.01). These results provide evidence that the APOE gene may play a significant role in the etiology of schizophrenia in the Mexican population.

Validity of the Spanish version of the Personal and Social Performance scale in schizophrenia.

BACKGROUND: The Personal and Social Performance (PSP) scale is a reliable and valid instrument that utilizes objective parameters for the assessment of social functioning in patients with schizophrenia. OBJECTIVE: The aim of this study was to determine the validity and reliability of the Spanish version of the PSP scale. METHOD: In total, 100 patients with DSM-IV diagnoses of schizophrenia and schizoaffective disorder were recruited and assessed with the PSP, the GAF, the PANSS, and the CGI. Internal consistency for the PSP was obtained and discriminant validity was assessed by comparing PSP scores between inpatients and outpatients; correlations between PSP scores, the GAF, and the five factors of the PANSS were used to evaluate the convergent validity of the scale; reliability was evaluated with intra-class correlation coefficients and temporal stability was obtained using correlation coefficients between the PSP and CGI scores on a follow up assessment. RESULTS: The Cronbach's alpha coefficient of the PSP was 0.843. Inpatients showed lower scores on the PSP than did outpatients. Patients with low scores on the PSP reported fewer years of education, were more frequently unemployed, had a longer duration of illness, and had a shorter duration of antipsychotic treatment. The PSP scores showed a positive correlation with the GAF and a negative correlation with the cognitive, negative, and positive factors derived from the PANSS. The PSP scores showed significant correlations with the severity and improvement CGI scores at follow-up. Good inter-rater reliability was obtained. CONCLUSION: These findings support the Spanish version of PSP to be a reliable and valid instrument for the assessment of social functioning in patients with schizophrenia.

[Association study and meta-analysis of the apolipoprotein gene and schizophrenia]. / Estudio de asociación y metaanálisis del gen de la apolipoproteína E y esquizofrenia.

BACKGROUND: Schizophrenia is a mental disorder of unknown etiology. Epidemiological, association and linkage studies suggest the presence of genetic factors in the development of this disorder. Numerous studies have been undertaken to gain insight on the role of the ApoE gene in schizophrenia. However, findings remain controversial. OBJECTIVE: The current study analyzed the ApoE gene among schizophrenic patients of Mexican origin. RESULTS AND CONCLUSIONS: No significant differences were found in the distribution of alleles (chi2=0.94, df=2, p=0.62), or genotypes (chi2=1.02, df=2, p=0.59). The meta-analysis comprising 19 association studies (including the present one) showed that the risk allele epsilon4 of ApoE is not associated with the development of schizophrenia (OR 1.04, CI 95%=0.90-1.21, p=0.184) in the absence of heterogeneity (chi2=18.8, df=18, p=0.4).

Estudio de asociación y metaanálisis del gen de la apolipoproteína E y esquizofrenia / Association study and meta-analysis of the apolipoprotein gene and schizophrenia

Antecedentes: La esquizofrenia es una enfermedad mental cuyas causas etiológicas son desconocidas. Los estudios de epidemiología genética, de asociación y de ligamiento, han sugerido la presencia de factores genéticos involucrados en el desarrollo de la esquizofrenia. Existen numerosos estudios dirigidos a comprender la participación del gen de la apolipoproteína E (ApoE) en la esquizofrenia, sin embargo, los resultados son controversiales por la falta de replicación de los hallazgos. Objetivo: Para conocer el efecto del alelo ε4 de ApoE en esquizofrenia, se analizó la frecuencia de genotipos y alelos de ApoE en pacientes de origen mexicano. Resultados y conclusiones: No observamos diferencias estadísticamente significativas en los pacientes con esquizofrenia comparados con el grupo control en las frecuencias por alelos (χ2=0.94, gl=2, p=0.62) ni por genotipos (χ2=1.02, gl=2, p=0.59). Finalmente, el metaanálisis de 19 estudios de asociación, incluyendo el presente estudio, mostró que el alelo de riesgo ε4 de ApoE no está asociado con el desarrollo de la esquizofrenia (OR=1.04, IC 95%=0.90-1.21, p=0.184), sin la presencia de heterogeneidad (χ2=18.8, gl=18, p=0.4).

BACKGROUND: Schizophrenia is a mental disorder of unknown etiology. Epidemiological, association and linkage studies suggest the presence of genetic factors in the development of this disorder. Numerous studies have been undertaken to gain insight on the role of the ApoE gene in schizophrenia. However, findings remain controversial. OBJECTIVE: The current study analyzed the ApoE gene among schizophrenic patients of Mexican origin. RESULTS AND CONCLUSIONS: No significant differences were found in the distribution of alleles (chi2=0.94, df=2, p=0.62), or genotypes (chi2=1.02, df=2, p=0.59). The meta-analysis comprising 19 association studies (including the present one) showed that the risk allele epsilon4 of ApoE is not associated with the development of schizophrenia (OR 1.04, CI 95%=0.90-1.21, p=0.184) in the absence of heterogeneity (chi2=18.8, df=18, p=0.4).

The P50 auditory evoked potential in violent and non-violent patients with schizophrenia.

BACKGROUND: Emotionally driven violence is facilitated by increased arousal. It may be a consequence of an information-processing deficit and the cognitive attributions for the stimuli given by the subject. The aim of this study was to compare the P50 evoked potential responses of violent patients with schizophrenia with non-violent patients with schizophrenia and healthy controls. METHOD: Patients were classified into violent and non-violent in accordance to the Overt Aggression Scale. P50 auditory evoked potentials of 32 unmedicated patients with schizophrenia (violent=14, non-violent=18) and 17 healthy controls were recorded during five runs of 30 click pairs. RESULTS: Healthy controls exhibited a lower S2/S1 ratio when compared to violent (p<0.001) and non-violent (p=0.04) patients. Using a cutoff point of 0.50 for S2/S1 ratio to define abnormal gating a significant proportion of violent patients did not show P50 suppression (71.4%) in comparison to non-violent patients (38.9%) and healthy controls (23.5%) (p=0.02). CONCLUSIONS: Violent behavior in patients with schizophrenia could be associated with a disturbed information sensory gating. Violence in patients with schizophrenia may be facilitated by an increased arousal which may in turn be the result of an information-processing deficit.

Association analysis of exon III and exon I polymorphisms of the dopamine D4 receptor locus in Mexican psychotic patients.

In this study, we investigated whether polymorphisms of the dopamine D4 receptor (DRD4) gene were associated with psychotic symptomatology rather than with a unique diagnosis such as schizophrenia. A number of association studies between the DRD4 gene 48 bp-VNTR polymorphism at exon 3 and psychotic disorders have been reported, but the results have been controversial. Both 48 bp-VNTR and the 12 bp-VNTR (at exon 1) polymorphisms of this gene were analyzed in a group of 149 unrelated Mexican subjects with a diagnosis of schizophrenia, schizoaffective disorder, schizophreniform disorder, major depression and bipolar disorder, both with psychotic symptoms, brief psychotic disorder, delusional disorder and non-specific psychotic disorder, and in 169 individuals free of psychiatric illnesses. There were no differences in allele or genotype frequencies between groups for the 12 bp-VNTR polymorphisms. However, a significant excess of "rare" alleles (3-, 5-, 6- and 8-48 bp repeats alleles) was found in the group of psychotics. Moreover, haplotypes 3-A1, 5-A1, 6-A1 and 8-A1 were significantly more frequently associated with cases. This positive association supports a role of this molecule as a genetic risk factor in psychotic disorders.

Association study of MAO-A and DRD4 genes in schizophrenic patients with aggressive behavior.

Genes involved in dopamine neurotransmission are interesting candidates to be analyzed in schizophrenia and aggressive behavior. Therefore, we analyzed the functional polymorphisms of the dopamine receptor D4 (DRD4) and monoamine oxidase A (MAO-A) genes in a sample of 71 schizophrenic patients assessed with the Overt Aggression Scale to measure aggressive behavior. CLUMP analysis of the DRD4 48-bp repeat-exon III polymorphism in schizophrenic patients showed significant differences between the aggressive behavior and the nonaggressive groups (T1 = 18.77, d.f. = 6, p = 0.0046; T3 = 6.54, p = 0.0195). However, analysis of the promoter polymorphism of the MAO-A gene revealed no significant association between aggressive and nonaggressive patients. Finally, analysis of Overt Aggression Scale dimensions exhibited significant differences for the DRD4 and MAO-A genes. Our preliminary findings suggest that the DRD4 and MAO-A genes may be involved in aggressive schizophrenic patients.

Association between violent behavior and psychotic relapse in schizophrenia: once more through the revolving door? / Asociación de la conducta violenta y la recída psicótica en la esquizofrenia: ¿una vez más a través de la puerta revolvente?

Summary: The potential for violence in a number of persons with mental illnesses stimulates public fear and prevents general acceptance of persons with psychiatric disabilities. Schizophrenia has been the diagnosis most often associated with violence as it has been taken as a paradigm of insanity, incompetence and dangerousness. Clinicians' efforts to prevent violence through conventional external patient treatment are impede by several situational variables and patients become trapped in a costly cycle of repeated institutional admissions (revolving door phenomenon) in the most restrictive settings, going through involuntary in-patient treatment. The major hypothesis proposed in this review is that violence in schizophrenia can become a part of a self-perpetuating cycle, in which the combination of non-adherence to treatment and an inadequate management of illness from families and caregivers leads to violent behavior and deteriorated social relationships, finally resulting in institutional recidivism. As some of the initial symptoms of the illness, such as irritability and agitation may not be detected by the patient and his/her family, these symptoms eventually can easily escalate into open hostility, and the accompanying behavior is frequently violent. Disturbed moods secondary to psychotic symptoms, such as fear and anger apparently can also activate violent psychotic action. Accordingly, the path from the characteristics of the illness to violence leads to them through psychotic symptoms and lack of insight, and results in symptom-consistent violence. When psychotic symptoms and violent behavior cannot be managed by caregivers, patients are brought to the attention of psychiatric services and frequently admitted to patient service. During admission for a psychotic episode, there are more violent incidents than later on in the disease. As patients respond to medication and hospital environment, violent incidents and psychotic symptoms decrease in frequency and severity. After hospital discharge, patients may assume greater autonomy and control over several aspects of their daily lives. Nevertheless, this process may be hampered by familial reactions to the burden of living with a family member with schizophrenia. This burden can also be exacerbated because many patients have a history of violent behavior and families may experience negative attitudes towards them. In line with this, there is evidence of significant differences between the professionals' perception about symptoms and illness, and that of the patient and his/her family. Sometimes, these different conceptions may reflect a lack of awareness regarding illness and treatment that may lead to discontinue medication. Medication suspension can lead to an eventual relapse which most obvious sign is the emergence of positive psychotic symptoms. Nevertheless if a patient has a past history of violent behavior, it is very likely that these behaviors will appear during relapse and it may be necessary to consider hospitalization. Although treatment with antipsychotics may be useful when violence is secondary to psychotic symptoms, violence might be indirectly reduced through clinical programs aimed at increasing insight into illness and treatment. A psychoeducational strategy may improve antipsychotic treatment compliance by helping the patients to work through their ambivalence regarding antipsychotic medication. For families, a psychoeducation strategy can lead to a change in attitudes toward the disorder, as well as to promote problem-solving skills for violence. The model presented here suggests that violence in schizophrenia is conditioned by several factors such as psychotic symptoms, medication non-compliance and lack of social support. The prevention of violent behavior in schizophrenia should include attention to other areas, such as the quality of the social environment surrounding the patient. For the "revolving door" patients, violence may be a key factor that complicates treatment. Health professionals have the responsibility to work in partnership with patients and their families for the prevention of violence.

Resumen: La esquizofrenia ha sido el principal diagnóstico psiquiátrico asociado con la violencia. La prevención de la violencia a través del tratamiento ambulatorio se ha visto obstaculizada por diversas variables situacionales y muchos pacientes llegan a verse inmersos en un ciclo de continuas admisiones hospitalarias (fenómeno de la puerta revolvente). La hipótesis central de la presente revisión es que la violencia en la esquizofrenia puede formar parte de un ciclo recurrente de hospitalizaciones psiquiátricas, en el que, combinados la falta de adhesión al tratamiento y el manejo inadecuado de la enfermedad por parte de los familiares, dan por resultado la manifestación del comportamiento violento. Diversas investigaciones han mostrado que tanto los síntomas psicóticos, como las alteraciones del ánimo secundarias a su presencia y la falta de una conciencia de enfermedad, son las principales características de la esquizofrenia, asociadas con la manifestación de la violencia en dicho padecimiento. Cuando los familiares no pueden manejar los síntomas psicóticos y el comportamiento violento del paciente, se busca la atención en un servicio especializado de psiquiatría, y con frecuencia, el paciente tiene que ser hospitalizado. La manifestación de conductas violentas ha sido considerada como una de las principales causas de hospitalización psiquiátrica. Diversas investigaciones han documentado que los actos violentos se presentan con mayor frecuencia durante la admisión hospitalaria por un episodio psicótico que en otros momentos durante el curso del padecimiento. Asimismo, la hospitalización psiquiátrica pos sí misma reduce la frecuencia e intensidad de la violencia, debido probablemente al tratamiento con antipsicóticos y al entorno restrictivo de las instalaciones. Tras la alta hospitalaria, los pacientes viven un proceso de transición mediante el cual van asumiendo mayor autonomía y control sobre diversos aspectos de su vida cotidiana. Sin embargo, este proceso se puede ver obstaculizado por las reacciones familiares secundarias al desgaste físico y emocional de vivir con un familiar con esquizofrenia. Asimismo, este desgaste puede verse exacerbado debido al antecedente de violencia en muchos de estos pacientes. Se ha descrito que la percepción que tienen los pacientes y sus familiares con respecto a los síntomas de la enfermedad difiere significativamente de la de los especialistas de la salud mental. A veces, estas diferencias se asocian con falta de discernimiento y conciencia sobre la enfermedad y con la necesidad de tratamiento médico, lo que a su vez puede llevar a la suspensión del mismo. La suspensión del tratamiento farmacológico induce a una eventual recaída cuyos signos más evidentes son los síntomas psicóticos. No obstante, si un paciente tiene antecedentes de comportamiento violento, es muy probable que este comportamiento surja durante la recaída y que sea necesario considerar nuevamente la hospitalización. En estos pacientes, en quienes la violencia tiene un importante papel en las hospitalizaciones recurrentes, es necesario considerar el establecimiento de programas clínicos, que incluyan la psicoeducación, dirigidos a incrementar la conciencia del paciente y de los familiares, sobre la enfermedad y la necesidad del tratamiento farmacológico. El modelo presentado en esta revisión sugiere que la violencia en la esquizofrenia es una condición generada por diversos factores tales como los síntomas psicóticos, la falta de adherencia al tratamiento y el inadecuado apoyo social. La prevención de la conducta violenta en la esquizofrenia no sólo debe fundamentarse en el uso de antipsicóticos, ya que existen otras áreas en las que intervienen las características propias del individuo y su entorno social. Los profesionales de la salud mental tienen la responsabilidad de trabajar en conjunto con los pacientes y sus familiares para prevenir la manifestación de conductas violentas. Es necesario realizar futuros estudios dirigidos a evaluar la forma en la que los servicios de salud mental pueden ser más efectivos en la reducción y prevención de la violencia en la esquizofrenia.

Filtrado sensorial y P50: implicaciones para la neurobiología de la esquizofrenia

Resumen: El estudio del filtrado sensorial mediante potenciales evocados ha marcado una línea de investigación en la esquizofrenia que plantea explicaciones alternativas a la presencia de la sintomatología, y que bien merecen atención y estudio. La P50 es un potencial evocado con respuesta de latencia media que se origina en el lóbulo temporal medio, en el hipocampo y cerca de éste. Mediante estudios con magnetoencefalografía, se ha propuesto que las células piramidales situadas en el giro temporal son la fuente más probable de la P50 en el registro electroencefalográfico, correspondiente al electrodo CZ situado en el vértex, de acuerdo con el sistema internacional 10-20. En este paradigma se presentan ensayos con dos estímulos auditivos con sonido de "clic": el primero es condicionante (E1) y el segundo, de prueba (E2), y pueden tener parámetros variables de duración, intensidad, intervalo interestímulo e intervalo interensayo. Cuando existe variación en los valores de estos parámetros, se obtiene como resultado una respuesta facilitada o suprimida al segundo estímulo. La P50 es una onda con amplitud no mayor a 50 -i.V ni menor a 0.5 -i.V. Para su análisis, se saca un promedio de entre 30 y 180 ensayos de cada estímulo y finalmente se analiza mediante la comparación del porcentaje de disminución de la amplitud de E1 y de E2, también con el resultado de la diferencia de E1 menos E2, o con el porcentaje de disminución en el área de la P50 de E2 comparada con la disminución de Et Los estudios que documentan la eficacia de los antipsicóticos para normalizar el defecto en el filtrado sensorial no brindan información concluyente. Algunos estudios han observado que los pacientes sin medicación antipsicótica no presentan supresión de la respuesta a E2, o la presentan muy disminuida. Otros estu dios han documentado la repuesta no suprimida de la P50 en un grupo de esquizofrénicos bajo tratamiento antipsicótico. En ellos se observó un aumento en las latencias y amplitudes del trazo casi idénticas que las presentadas por los controles sanos. Se ha descri to que la mejoría en el déficit sensorial que presentan los esquizofrénicos bajo tratamiento antipsicótico se debe al bloqueo de la transmisión dopaminérgica. Se ha observado que algunos de los familiares en primer grado de los pacientes con esquizofrenia muestran también alteraciones en la inhibición del segundo estímulo auditivo del paradigma P50. Asimismo, en familiares sanos no fumadores que presentaban el defecto de filtrado se ha reportado una normalización transitoria del déficit sensorial registrado después de dosificar nicotina me diante goma de mascar. De acuerdo con estos datos, se ha propuesto la importancia que tiene la nicotina para el filtrado sensorial. En el paradigma de la P50, el fenómeno de habituación se produce cuando E1 activa las interneuronas a través de los receptores nicotínicos, que provocan la liberación de GABA, con la cual las células piramidales del hipocampo no logran ser excitadas por E2 y por lo tanto no responden a éste. En la esquizofrenia, la falta de habituación puede explicarse por una disminución en el número de interneuronas inhibitorias que muestran una alta ex presión de receptores nicotínicos.

Abstract: In the search for etiologic and physiologic keys to increase the knowledge about schizophrenia, research focused in the assessment of sensory gating by the use of event-related potentials has been considered an alternative to explain the presence of cognitive and positive symptoms. The P50 is a middlelatency-evoked potential originated in the temporal lobe, in the hippocampus and close to this. Through magnetoencephalographic studies, it has been hypothesized that piramidal cells located in the temporal gyrus are the most suitable source of the P50 wave present in electroencephalographic recordings. Therefore, the main wave for the obtention of the P50 is located in the vertex, which corresponds to the CZ electrode, in agreement with the 10-20 International System. The P50 paradigm is evoked by two auditory stimuli with the sound of a click, where the first stimulus is labelled conditioning (S1) and the second one, testing (S2). Both of them may have variable values for duration, intensity, inter-stimulus interval and inter-testing interval. Any variation on these parameter values leads to a suppressed or a facilitated response of the second stimulus. The amplitude established for the P50 paradigm is smaller than 50 [íV and greater than 0.5 -iV. Once the recording is acquired, the analysis of the P50 wave must be done with an average of 30 to 180 tests of S1 and S2. Results from the average can be analyzed by: a) a comparison of the amplitude's diminution percentage of S1 and S2, b) the difference between the substraction of the S1 value minus the S2 value, or c) the mean reduction of the P50 area of S1 compared with the mean reduction of the P50 area of S2. Different pharmacological assays had shown evidence of changes in sensory gating performance by means of the mechanism of action of some antipsychotics. Although some studies had shown a normalizing effect of antipsychotics over the sensory gating deficit in schizophrenic patients, the results are not conclusive. Some studies have reported that schizophrenic patients under antipsychotic treatment suppress the S2, while patients without antipsychotic treatment showed a lack of suppression of the S2. Nevertheless, other studies had reported a minor suppression of the second stimulus in groups of schizophrenic patients under antipsychotic treatment. Moreover, other studies had observed increased latencies and almost identical amplitudes of the outline between schizophrenic patients and normal healthy controls. The dopamine hypothesis has been one of the most important physiopathologic explanations for schizophrenia and the dopaminergic transmission blockade has also been implicated in the improvement of sensory gating in schizophrenic patients under antipsychotic treatment. Furthermore, a familiar pattern of sensory gating dysfunction has been found in healthy first-degree relatives of schizophrenic patients, whose response to the P50 paradigm has shown the lack of inhibition to the second auditory stimulus. This deficit is mainly observed in the parent having a greater familiar history for schizophrenia and also in half of the patient's healthy sibs. It is important to consider that although some relatives display an abnormal performance of the P50 wave, in general their cognitive performance is higher than the one showed by the schizophrenic patient. Likewise, some healthy non-smoker relatives, whose previous recordings displayed abnormal P50 waves, showed a transitory normalization of their sensory gating after nicotine administration by means of a nicotine chewing gum. It has been postulated that nicotine has a primary effect over the sensory gating performance. Hippocampal neurons receiving the originating stimuli from the medial septal nucleus are densely concentrated with nicotinic receptors. This inervation has been described as the main filter of repetitive auditory stimuli in the hippocampus. Following the hypothesis of the influence of nicotine over the sensory gating performance, it has been proposed that the habituation phenomenon occuring in the P50 paradigm takes place when interneurons are activated by nicotinic receptors after the first auditory stimuli. This activation causes a liberation of GABA, which avoids hippocampal piramidal cells excitation by S2, and therefore they do not respond to this stimulus. In schizophrenic patients, the lack of habituation can be explained by histochemical evidencies which suggest a smaller number of inhibitory interneurons with a higher expression of OC-7 nicotinic receptors. Based on these data, the actual background of the P50 paradigm brings out the possibility of including it as an important biological marker for the early detection of schizophrenia between high-risk relatives of schizophrenic patients. Further research is required to fully understand the potential advantages offered by the P50 sensory gating study. It is important to develop pharmacological studies focused on the role of specific antipsychotics over cognitive functions in schizophrenic patients. Also, future research should be addressed to the assessment of the influence of nicotinic receptors in attentional proceses and in the etiopathology of schizophrenia in order to explore O -7 nicotinic receptor selective agonists as candidates for the treatment of cognitive and perceptual disturbances in schizophrenia. The aim of this review is to give an introduction to the auditory sensory gating studies applied to schizophrenia research by means of event-related potentials.

Amoxapine as an atypical antipsychotic: a comparative study vs risperidone.

Amoxapine is marketed as an antidepressant. However, its in-vitro profile, receptor occupancy and preclinical effects are very similar to atypical antipsychotics. Amoxapine has also shown efficacy as an atypical antipsychotic in open trials. The objective of this study was to compare the antipsychotic and side effect profile of amoxapine and risperidone in a randomised assignment, standardized dosing, double-blind trial of acutely psychotic patients with schizophrenia. A total of 48 schizophrenic patients were enrolled and randomized in a double-blind 6-week trial to receive either risperidone (up to 5 mg/day) or amoxapine (up to 250 mg/day). Positive, negative, affective symptoms and motor side effects were measured using standardized weekly assessments. Prolactin levels were also determined at baseline and at the end of the study. A total of 39 patients (amoxapine, n=22; risperidone, n=21) completed the trial. Both pharmacological treatments, amoxapine 228.0 mg/day (SD=34.6) and risperidone 4.5 mg/day (SD=0.7), showed equivalent improvement in positive, negative, and depressive symptoms. Amoxapine was associated with less EPS and less prolactin elevation than risperidone. These data support previous reports about the efficacy of amoxapine as an atypical antipsychotic. Since amoxapine is off-patent, it may be a valuable low-cost alternative to new atypical antipsychotics, particularly in low-income countries where the majority of the patients are still treated with typical antipsychotics.

The effects of amisulpride on five dimensions of psychopathology in patients with schizophrenia: a prospective open-label study.

BACKGROUND: The efficacy of antipsychotics can be evaluated using the dimensional models of schizophrenic symptoms. The D2/D3-selective antagonist amisulpride has shown similar efficacy and tolerability to other atypical antipsychotics. The aim of the present study was to determine the efficacy of amisulpride on the dimensional model of schizophrenic symptoms and tolerability in latin schizophrenic patients. METHOD: Eighty schizophrenic patients were enrolled and 70 completed a prospective open-label 3-month study with amisulpride. The schizophrenic symptoms, psychosocial functioning and side-effects were evaluated with standardized scales. RESULTS: The patients showed significant improvement in the five dimensions evaluated. Amisulpride (median final dose 357.1 mg/d) was well-tolerated without treatment-emergent extrapyramidal side-effects. CONCLUSION: Amisulpride showed efficacy on different psychopathological dimensions and was well tolerated, leading to consider this drug a first line choice for the treatment of schizophrenia.