Genetic variables of the glutamatergic system associated with treatment-resistant depression: A review of the literature.

Depression is a common, recurrent mental disorder and one of the leading causes of disability and global burden of disease worldwide. Up to 15%-40% of cases do not respond to diverse pharmacological treatments and, thus, can be defined as treatment-resistant depression (TRD). The development of biomarkers predictive of drug response could guide us towards personalized and earlier treatment. Growing evidence points to the involvement of the glutamatergic system in the pathogenesis of TRD. Specifically, the N-methyl-D-aspartic acid receptor (NMDAR) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), which are targeted by ketamine and esketamine, are proposed as promising pathways. A literature search was performed to identify studies on the genetics of the glutamatergic system in depression, focused on variables related to NMDARs and AMPARs. Our review highlights GRIN2B, which encodes the NR2B subunit of NMDAR, as a candidate gene in the pathogenesis of TRD. In addition, several studies have associated genes encoding AMPAR subunits with symptomatic severity and suicidal ideation. These genes encoding glutamatergic receptors could, therefore, be candidate genes for understanding the etiopathogenesis of TRD, as well as for understanding the pharmacodynamic mechanisms and response to ketamine and esketamine treatment.

Classification of subtypes of patients with eating disorders by correspondence analysis.

BACKGROUND: Grouping eating disorders (ED) patients into subtypes could help improve the establishment of more effective diagnostic and treatment strategies. AIM: To identify clinically meaningful subgroups among subjects with ED using multiple correspondence analysis (MCA). METHODS: A prospective cohort study was conducted of all outpatients diagnosed for an ED at an Eating Disorders Outpatient Clinic to characterize groups of patients with ED into subtypes according to sociodemographic and psychosocial impairment data, and to validate the results using several illustrative variables. In all, 176 (72.13%) patients completed five questionnaires (clinical impairment assessment, eating attitudes test-12, ED-short form health-related quality of life, metacognitions questionnaire, Penn State Worry Questionnaire) and sociodemographic data. ED patient groups were defined using MCA and cluster analysis. Results were validated using key outcomes of subtypes of ED. RESULTS: Four ED subgroups were identified based on the sociodemographic and psychosocial impairment data. CONCLUSION: ED patients were differentiated into well-defined outcome groups according to specific clusters of compensating behaviours.

Predictors of change in psychosocial impairment secondary to an eating disorder.

Eating disorders (ED) can significantly impair psychosocial health in patients. However, no published studies have so far used a standardized and specific instrument to evaluate predictive factors in ED-related psychosocial impairment. This prospective cohort study involved 177 patients receiving outpatient treatment for an ED at baseline and 115 patients at the 1-year follow-up. Patients completed three self-administered questionnaires: the Clinical Impairment Assessment (CIA), the Eating Attitudes Test-12 (EAT-12), and the Health-Related Quality of Life in ED-short form (HeRQoLED-s). Descriptive statistics, ANOVA, chi-square, and Fisher's exact test were applied to examine intervariable relationships. Multivariate linear regression was used to determine predictors of change in CIA scores. An improvement was reported by patients with restrictive anorexia nervosa (AN) compared to those with purgative AN. In the multivariate analysis, employment status, subtype of ED, and the bulimia and food preoccupation factor of the EAT-12 were significant predictors of change in the CIA scores.

Adaptation and validation of the Spanish version of the Clinical Impairment Assessment Questionnaire.

The Clinical Impairment Assessment (CIA) assesses psychosocial impairment secondary to an eating disorder. The aim of this study was to create and validate a Spanish-language version of the CIA. Using a forward-backward translation methodology, we translated the CIA into Spanish and evaluated its psychometric characteristics in a clinical sample of 178 ED patients. Cronbach's alpha values, confirmatory factor analysis (CFA), and correlations between the CIA and the Eating Attitudes Test-12 and the Health-Related Quality of Life in ED-short form questionnaires evaluated the reliability, construct validity, and convergent validity, respectively. Known-groups validity was also studied comparing the CIA according to different groups; responsiveness was assessed by means of effect sizes. Data revealed a three-factor structure similar to that of the original CIA. Cronbach alpha coefficient of 0.91 for the total CIA score supported its internal consistency and correlations with other instruments demonstrated convergent validity. The total CIA score and factor scores also significantly discriminated between employment status, evidencing known-groups validity. Responsiveness parameters showed moderate changes for patients with restrictive eating disorders. These findings suggest that the CIA can be reliably and validly used in Spain in a number of different clinical contexts, by researchers and clinicians alike.

Adaptation and validation of the Metacognition Questionnaire (MCQ-30) in Spanish clinical and nonclinical samples.

BACKGROUND: The short form of the Metacognitions Questionnaire is a brief multidimensional measure of a range of metacognitive processes and metacognitive beliefs about worry and cognition relevant to vulnerability to and maintenance of emotional disorders. The aim of the study was adapt and validate a Spanish version of the short form of the Metacognitions Questionnaire (MCQ-30) and to evaluate its psychometric properties in clinical and nonclinical samples. METHOD: The MCQ-30 was administered to a sample of 316 patients with psychiatric disorders (anxiety, depression, and eating disorders) and to a sample of 169 individuals belonging to the general population. Instrument reliability (internal consistency), construct validity (confirmatory factor analysis [CFA], convergent validity, known groups) and responsiveness were measured. RESULTS: The clinical sample scored the highest on all factors when compared to nonclinical sample. The exploratory factor analysis supported the MCQ׳s original five-factor solution. The CFA suggested a good fit of the model. Correlation with measure of worry demonstrated convergent validity. Known-groups validity was supported by significant differences in the MCQ-30 mean scores according to certain variables, such as educational level and employment status. LIMITATIONS: This study did not assess the test-retest reliability. CONCLUSIONS: The MCQ-30 has good psychometric properties and can be used to evaluate several dimensions of metacognition in both clinical and nonclinical samples.