Proportion and predictors of remission and recovery in first-episode psychosis: Systematic review and meta-analysis.

BACKGROUND: To determine the proportion of patients in symptomatic remission and recovery following a first-episode of psychosis (FEP). METHODS: A multistep literature search using the Web of Science database, Cochrane Central Register of Reviews, Ovid/PsychINFO, and trial registries from database inception to November 5, 2020, was performed. Cohort studies and randomized control trials (RCT) investigating the proportion of remission and recovery following a FEP were included. Two independent researchers searched, following PRISMA and MOOSE guidelines and using a PROSPERO protocol. We performed meta-analyses regarding the proportion of remission/recovery (symptomatic plus functional outcomes). Heterogeneity was measured employing Q statistics and I2 test. To identify potential predictors, meta-regression analyses were conducted, as well as qualitative reporting of studies included in a systematic review. Sensitivity analyses were performed regarding different times of follow-up and type of studies. RESULTS: One hundred articles (82 cohorts and 18 RCTs) were included in the meta-analysis. The pooled proportion of symptomatic remission was 54% (95%CI [30, 49-58]) over a mean follow-up period of 43.57 months (SD = 51.82) in 76 studies. After excluding RCT from the sample, the proportion of remission remained similar (55%). The pooled proportion of recovery was 32% (95%CI [27-36]) over a mean follow-up period of 71.85 months (SD = 73.54) in 40 studies. After excluding RCT from the sample, the recovery proportion remained the same. No significant effect of any sociodemographic or clinical predictor was found. CONCLUSIONS: Half of the patients are in symptomatic remission around 4 years after the FEP, while about a third show recovery after 5.5 years.

Community Violence Exposure and Conduct Problems in Children and Adolescents with Conduct Disorder and Healthy Controls.

Exposure to community violence through witnessing or being directly victimized has been associated with conduct problems in a range of studies. However, the relationship between community violence exposure (CVE) and conduct problems has never been studied separately in healthy individuals and individuals with conduct disorder (CD). Therefore, it is not clear whether the association between CVE and conduct problems is due to confounding factors, because those with high conduct problems also tend to live in more violent neighborhoods, i.e., an ecological fallacy. Hence, the aim of the present study was: (1) to investigate whether the association between recent CVE and current conduct problems holds true for healthy controls as well as adolescents with a diagnosis of CD; (2) to examine whether the association is stable in both groups when including effects of aggression subtypes (proactive/reactive aggression), age, gender, site and socioeconomic status (SES); and (3) to test whether proactive or reactive aggression mediate the link between CVE and conduct problems. Data from 1178 children and adolescents (62% female; 44% CD) aged between 9 years and 18 years from seven European countries were analyzed. Conduct problems were assessed using the Kiddie-Schedule of Affective Disorders and Schizophrenia diagnostic interview. Information about CVE and aggression subtypes was obtained using self-report questionnaires (Social and Health Assessment and Reactive-Proactive aggression Questionnaire (RPQ), respectively). The association between witnessing community violence and conduct problems was significant in both groups (adolescents with CD and healthy controls). The association was also stable after examining the mediating effects of aggression subtypes while including moderating effects of age, gender and SES and controlling for effects of site in both groups. There were no clear differences between the groups in the strength of the association between witnessing violence and conduct problems. However, we found evidence for a ceiling effect, i.e., individuals with very high levels of conduct problems could not show a further increase if exposed to CVE and vice versa. Results indicate that there was no evidence for an ecological fallacy being the primary cause of the association, i.e., CVE must be considered a valid risk factor in the etiology of CD.

COMT haplotypes, catecholamine metabolites in plasma and clinical response in schizophrenic and bipolar patients.

AIM: We examined the association of COMT haplotypes and plasma metabolites of catecholamines in relation to the clinical response to antipsychotics in schizophrenic and bipolar patients. PATIENTS & METHODS: We studied 165 patients before and after four weeks of treatment, and 163 healthy controls. We assessed four COMT haplotypes and the plasma concentrations of HVA, DOPAC and MHPG. RESULTS: Bipolar patients: haplotypes are associated with age at onset and clinical evolution. In schizophrenic patients, an haplotype previously associated with increased risk, is related to better response of negative symptoms. CONCLUSION: Haplotypes would be good indicators of the clinical status and the treatment response in bipolar and schizophrenic patients. Larger studies are required to elucidate the clinical usefulness of these findings.

Novel evidence that attributing affectively salient signal to random noise is associated with psychosis.

We wished to replicate evidence that an experimental paradigm of speech illusions is associated with psychotic experiences. Fifty-four patients with a first episode of psychosis (FEP) and 150 healthy subjects were examined in an experimental paradigm assessing the presence of speech illusion in neutral white noise. Socio-demographic, cognitive function and family history data were collected. The Positive and Negative Syndrome Scale (PANSS) was administered in the patient group and the Structured Interview for Schizotypy-Revised (SIS-R), and the Community Assessment of Psychic Experiences (CAPE) in the control group. Patients had a much higher rate of speech illusions (33.3% versus 8.7%, ORadjusted: 5.1, 95% CI: 2.3-11.5), which was only partly explained by differences in IQ (ORadjusted: 3.4, 95% CI: 1.4-8.3). Differences were particularly marked for signals in random noise that were perceived as affectively salient (ORadjusted: 9.7, 95% CI: 1.8-53.9). Speech illusion tended to be associated with positive symptoms in patients (ORadjusted: 3.3, 95% CI: 0.9-11.6), particularly affectively salient illusions (ORadjusted: 8.3, 95% CI: 0.7-100.3). In controls, speech illusions were not associated with positive schizotypy (ORadjusted: 1.1, 95% CI: 0.3-3.4) or self-reported psychotic experiences (ORadjusted: 1.4, 95% CI: 0.4-4.6). Experimental paradigms indexing the tendency to detect affectively salient signals in noise may be used to identify liability to psychosis.

The influence of the Val158Met catechol-O-methyltransferase polymorphism on the personality traits of bipolar patients.

INTRODUCTION: Certain personality traits and genetic polymorphisms are contributing factors to bipolar disorder and its symptomatology, and in turn, this syndrome influences personality. The aim of the present study is to compare the personality traits of euthymic bipolar patients with healthy controls and to investigate the effect of the catechol-O-methyltransferase (COMT) Val158Met genotype on those traits. We recruited thirty seven bipolar I patients in euthymic state following a manic episode and thirty healthy controls and evaluated their personality by means of the Cloninger's Temperament and Character Inventory (version TCI-R-140). We assessed the influence of the polymorphism Val158Met in the COMT gene on the personality of these patients. The patients scored higher than controls in harm avoidance (61.3±12.5 vs. 55.3±8.1) and self-transcendence (45.3±12.8 vs. 32.7±8.2) and scored lower than controls in self-directedness (68.8±13.3 vs. 79.3±8.1), cooperativeness (77.1±9.1 vs. 83.9±6.5) and persistence (60.4±15.1 vs. 67.1±8.9). The novelty seeking dimension associates with the Val158Met COMT genotype; patients with the low catabolic activity genotype, Met/Met, show a higher score than those with the high catabolic activity genotype, Val/Val. CONCLUSIONS: Suffering from bipolar disorder could have an impact on personality. A greater value in harm avoidance may be a genetic marker for a vulnerability to the development of a psychiatric disorder, but not bipolar disorder particularly, while a low value in persistence may characterize affective disorders or a subgroup of bipolar patients. The association between novelty seeking scores and COMT genotype may be linked with the role dopamine plays in the brain's reward circuits.

La opinión de los residentes de psiquiatría sobre la formación que reciben / The opinion of psychiatric residents on the training they receive

Se presentan y comentan los resultados de una encuesta llevada a cabo por la Comisión Nacional de Psiquiatría entre los MIR de psiquiatría de tercer y cuarto año. La encuesta tuvo por objeto conocer la opinión de los residentes sobre la formación que recibieron, así como el grado de satisfacción que experimentaron. Los resultados indican que la mayoría cumplieron con los requisitos del Programa Nacional de Formación Psiquiátrica y que su grado de satisfacción fue bueno. No obstante un porcentaje pequeño pero sustancial de residentes no cumplieron el programa de forma adecuada, particularmente en relación con la formación en psicoterapia, metodología de la investigación, gerontopsiquiatría, neurología y medicina general. Basándose en estos resultados la Comisión Nacional expone su opinión y presenta unas recomendaciones dirigidas a las partes interesadas en la formación de los residentes de psiquiatría en España (AU)

The results of a survey carried out by the Spanish National Board for Psychiatric Training among psychiatric trainees in their third and fourth year of training are presented and discussed. The aim of the survey was to know the resident’s opinion and level of satisfaction on the training they had received. The results indicate that the majority of residents had complied with the National Program for Psychiatric Training requirements and that their level of satisfaction was fair. However a small but substantial percentage did not comply adequately with the program, particularly in relation with the training in psychotherapy, research methodology, old age psychiatry, neurology and general medicine. Based on these results the National Board puts forward some recommendations meant for those involved in the training of psychiatrists in Spain (AU)

The opinion of psychiatric residents on the training they receive.

The results of a survey carried out by the Spanish National Board for Psychiatric Training among psychiatric trainees in their third and fourth year of training are presented and discussed. The aim of the survey was to know the resident's opinion and level of satisfaction on the training they had received. The results indicate that the majority of residents had complied with the National Program for Psychiatric Training requirements and that their level of satisfaction was fair. However a small but substantial percentage did not comply adequately with the program, particularly in relation with the training in psychotherapy, research methodology, old age psychiatry, neurology and general medicine. Based on these results the National Board puts forward some recommendations meant for those involved in the training of psychiatrists in Spain.

Variability of plasma homovanillic acid over 13 months in patients with schizophrenia; relationship with the clinical response and the Wisconsin card sort test.

In the present study we have measured, on a monthly basis, the concentration of plasma homovanillic acid (pHVA) in schizophrenic patients during 13 months of their pharmacological treatment. The average pHVA values of each patient were within the range of 7.30-17.70 ng/ml and the coefficients of variation for each patient (CV %) were within the range of 13-33%. Half of the patients that showed higher pHVA CV% values also showed higher scores on the Brief Psychiatric Rating Scale at the beginning of the study, and improved more after 6 months, when compared to the remaining 50% with lower CV% values. There was no significant relationship between the scores of the Wisconsin Card Sort Test and the concentration or the CV% of the pHVA of each patient. A greater variability in the pHVA may be associated with a greater plasticity of the dopaminergic system and a better clinical response.

Catechol O-methyltransferase and monoamine oxidase A genotypes, and plasma catecholamine metabolites in bipolar and schizophrenic patients.

Metabolites of dopamine and norepinephrine measured in the plasma have long been associated with symptomatic severity and response to treatment in schizophrenic, bipolar and other psychiatric patients. Plasma concentrations of catecholamine metabolites are genetically regulated. The genes encoding enzymes that are involved in the synthesis and degradation of these monoamines are candidate targets for this genetic regulation. We have studied the relationship between the Val158Met polymorphism in catechol O-methyltransferase gene, variable tandem repeat polymorphisms in the monoamine oxidase A gene promoter, and plasma concentrations of 3-methoxy-4-hydroxyphenylglycol, 3,4-dihydroxyphenylacetic acid and homovanillic acid in healthy control subjects as well as in untreated schizophrenic and bipolar patients. We found that the Val158Met substitution in catechol O-methyltransferase gene influences the plasma concentrations of homovanillic and 3,4-dihydroxyphenylacetic acids. Although higher concentrations of plasma homovanillic acid were found in the high-activity ValVal genotype, this mutation did not affect the plasma concentration of 3-methoxy-4-hydroxyphenylglycol. 3,4-dihydroxyphenylacetic acid concentrations were higher in the low-activity MetMet genotype. Interestingly, plasma values 3-methoxy-4-hydroxyphenylglycol were greater in schizophrenic patients and in bipolar patients than in healthy controls. Our results are compatible with the previously reported effect of the Val158Met polymorphism on catechol O-methyltransferase enzymatic activity. Thus, our results suggest that this polymorphism, alone or associated with other polymorphisms, could have an important role in the genetic control of monoamine concentration and its metabolites.

GABA and homovanillic acid in the plasma of Schizophrenic and bipolar I patients.

We have determined the plasma (p) concentration of gamma-aminobutyric acid (GABA) and the dopamine metabolite homovanillic acid (HVA), and the pHVA/pGABA ratio in schizophrenic and bipolar patients. The research was undertaken in a geographic area with an ethnically homogeneous population. The HVA plasma concentrations were significantly elevated in the schizophrenic patients compared to the bipolar patients. The levels of pGABA was significantly lower in the two groups of patients compared to the control group, while the pHVA/pGABA ratio was significantly greater in the both groups of patients compared to the controls. As the levels of pHVA and pGABA are partially under genetic control it is better to compare their concentrations within an homogeneous population. The values of the ratio pHVA/pGABA are compatible with the idea of an abnormal dopamine-GABA interaction in schizophrenic and bipolar patients. The pHVA/pGABA ratio may be a good peripheral marker in psychiatric research.

Estudio sobre aceptabilidad, preferencia y efectividad de una nueva formulación bucodispersable de mirtazapina, en pacientes con depresión (episodio depresivo mayor, según criterios del DSM-IV) / Acceptability, patient preference, and effectiveness of the new fast dissolving, orally disintegrating mirtazapine tablet formulation in patients with a major depressive episode (DSM-IV criteria)

Objetivo: Valorar la aceptabilidad, efectividad y cumplimiento terapéutico de una nueva formulación bucodispersable de mirtazapina en pacientes con depresión (según criterios del DSM-IV). Método: Estudio clínico multicéntrico, prospectivo, abierto, no controlado, en 49 pacientes provenientes de consultas externas de 7 servicios de psiquiatría, durante 6 semanas. Se realizaron evaluaciones mediante la escala de Hamilton para la Depresión de 17 ítems y la escala de Impresión Clínica Global, subescalas de gravedad y de cambio (ICG-G, ICG-C), y se valoraron los efectos adversos, el cumplimiento terapéutico de los pacientes y el Cuestionario de aceptabilidad y preferencia (Soltab Patient Preference Survey). Resultados: La puntuación media total de la escala Hamilton para la Depresión de 17 ítems (HAMD-17) fue de 23,27 en la visita basal y disminuyó a 12,84 el día 15 (p < 0,0001) y a 6,81 el día 45 (p < 0,0001), con una mejoría estadísticamente significativa y clínicamente relevante. Al finalizar el estudio, el 70% de los pacientes había mejorado mucho o bastante según la subescala de Impresión Clínica Global de cambio (ICG-C). Las principales razones para preferir la nueva forma bucodispersable de mirtazapina fueron: la facilidad de uso, el hecho de que no sea necesario ingerir agua, la posibilidad de tomarla en cualquier momento y lugar, y la sensación de estar menos medicado. ConclusiÓn: Éste es el primer estudio realizado en España en el que se valora la aceptabilidad de la nueva formulación bucodispersable de mirtazapina, además de la eficacia, la seguridad, la tolerabilidad y el cumplimiento terapéutico en pacientes con depresión

Objective: To assess the acceptability and effectiveness of the new fast dissolving, orally disintegrating mirtazapine tablet formulation and therapeutic compliance with this treatment in patients with a major depressive episode (DSM-IV criteria). Method: A multicenter, observational, prospective, open, and non-controlled study was performed. Forty-nine patients from seven outpatient psychiatric clinics in Spain were evaluated over a 6-week period. Evaluation was performed using the following scales: the 17-item Hamilton Depression Scale (HAM-D-17), the severity and improvement subscales of the Clinical Global Impression scale (CGI-S and CGI-I), and an acceptability questionnaire (Soltab Patient Preference Survey). Results: The total average HAM-D-17 score decreased from 23.27 at baseline to 12.84 on day 15 (p<0.0001) and 6.81 on day 45 (p<0.0001). This decrease was statistically significant and clinically relevant. Seventy percent of the patients showed "much" or "some" improvement at day 45 (CGI-I). The main reasons for preferring fast dissolving mirtazapine tablets were that they are easy to take, there is no need to drink water, they can be swallowed at any time and place, and there is no feeling of being on medication. Conclusion: This is the first study performed in Spain that assesses the acceptability, effectiveness, and tolerability of the new orally disintegrating mirtazapine formulation, as well as drug compliance, in patients with depression