Cerebellar Cognitive Affective Syndrome in Costa da Morte Ataxia (SCA36).

SCA36 is an autosomal dominant spinocerebellar ataxia (SCA) affecting many families from Costa da Morte, a northwestern region of Spain. It is caused by an intronic GGCCTG repeat expansion in NOP56. In order to characterize the cognitive and affective manifestations of this cerebellar disease, a group of 30 SCA36 mutation carriers (11 preataxic and 19 ataxic patients) were assessed with a comprehensive battery of standardized tests. Phonological verbal fluency - but not semantic fluency - was already mildly impaired in preataxic subjects. In ataxic patients, both phonological and semantic fluencies were significantly below normal. Depression, while more frequent and prominent in ataxic patients, was also often present in the preataxic stage. This is the first systematic study supporting the presence of a mild cerebellar cognitive and affective syndrome in SCA36. Routine evaluation of cognitive and emotional spheres in SCA36 patients as well as asymptomatic mutation carriers should allow early detection and timely therapeutic intervention.

Cognitive and clinical predictors of a long-term course in obsessive compulsive disorder: A machine learning approach in a prospective cohort study.

BACKGROUND: Obsessive compulsive disorder (OCD) is a disabling illness with a chronic course, yet data on long-term outcomes are scarce. This study aimed to examine the long-term course of OCD in patients treated with different approaches (drugs, psychotherapy, and psychosurgery) and to identify predictors of clinical outcome by machine learning. METHOD: We included outpatients with OCD treated at our referral unit. Demographic and neuropsychological data were collected at baseline using standardized instruments. Clinical data were collected at baseline, 12 weeks after starting pharmacological treatment prescribed at study inclusion, and after follow-up. RESULTS: Of the 60 outpatients included, with follow-up data available for 5-17 years (mean = 10.6 years), 40 (67.7 %) were considered non-responders to adequate treatment at the end of the study. The best machine learning model achieved a correlation of 0.63 for predicting the long-term Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score by adding clinical response (to the first pharmacological treatment) to the baseline clinical and neuropsychological characteristics. LIMITATIONS: Our main limitations were the sample size, modest in the context of traditional ML studies, and the sample composition, more representative of rather severe OCD cases than of patients from the general community. CONCLUSIONS: Many patients with OCD showed persistent and disabling symptoms at the end of follow-up despite comprehensive treatment that could include medication, psychotherapy, and psychosurgery. Machine learning algorithms can predict the long-term course of OCD using clinical and cognitive information to optimize treatment options.

The genomics of visuospatial neurocognition in obsessive-compulsive disorder: A preliminary GWAS.

BACKGROUND: The study of Obsessive-Compulsive Disorder (OCD) genomics has primarily been tackled by Genome-wide association studies (GWAS), which have encountered troubles in identifying replicable single nucleotide polymorphisms (SNPs). Endophenotypes have emerged as a promising avenue of study in trying to elucidate the genomic bases of complex traits such as OCD. METHODS: We analyzed the association of SNPs across the whole genome with the construction of visuospatial information and executive performance through four neurocognitive variables assessed by the Rey-Osterrieth Complex Figure Test (ROCFT) in a sample of 133 OCD probands. Analyses were performed at SNP- and gene-level. RESULTS: No SNP reached genome-wide significance, although there was one SNP almost reaching significant association with copy organization (rs60360940; P = 9.98E-08). Suggestive signals were found for the four variables at both SNP- (P < 1E-05) and gene-levels (P < 1E-04). Most of the suggestive signals pointed to genes and genomic regions previously associated with neurological function and neuropsychological traits. LIMITATIONS: Our main limitations were the sample size, which was limited to identify associated signals at a genome-wide level, and the composition of the sample, more representative of rather severe OCD cases than a population-based OCD sample with a broad severity spectrum. CONCLUSIONS: Our results suggest that studying neurocognitive variables in GWAS would be more informative on the genetic basis of OCD than the classical case/control GWAS, facilitating the genetic characterization of OCD and its different clinical profiles, the development of individualized treatment approaches, and the improvement of prognosis and treatment response.

Neuropsychological performance and predictors of pharmacological treatment response in obsessive compulsive disorder.

BACKGROUND: Obsessive Compulsive Disorder (OCD) is characterized by the presence of executive dysfunctions. As organizational strategies may play an important role as a possible endophenotype of the disorder, we decided to investigate non-verbal memory and organizational abilities in OCD. We also investigated how organization and non-verbal memory differ between responder and non-responder patients to pharmacological treatment, to test whether cognitive functions can predict the response to pharmacological treatment. METHODS: In Study 1, executive and clinical functioning measures were applied to 162 OCD and 95 controls. In Study 2, clinical, intelligence and executive functioning measures were applied to 72 OCD responders and 63 OCD non-responder patients. RESULTS: OCD patients and controls from Study 1 differed in copy organization (p < 0.01) and delayed recall (p = 0.048). In Study 2, the OCD responders displayed better copy organization (p = 0.013) and lower depressive, anxious and OCD symptoms (p < 0.01 in the three cases). Scores in the following instruments were found to predict the response to pharmacological treatment: HDRS, Y-BOCS, Raven progressive matrices, and Direct digit subtest from the Wechsler's scale (p < 0.01 in all four cases). LIMITATIONS: In Study 1, the imbalance of the sample can be considered a limitation, whilst in Study 2, some of the levels of pharmacological resistance were not represented. CONCLUSIONS: In this study, non-verbal memory and organization was affected in OCD. Responder patients also displayed better executive functioning and fluid intelligence. Organizational ability is a predictor of pharmacological response to SSRI monotherapy in a predictive model controlling for anxious symptoms.

Exploring the biological role of postzygotic and germinal de novo mutations in ASD.

De novo mutations (DNMs), including germinal and postzygotic mutations (PZMs), are a strong source of causality for Autism Spectrum Disorder (ASD). However, the biological processes involved behind them remain unexplored. Our aim was to detect DNMs (germinal and PZMs) in a Spanish ASD cohort (360 trios) and to explore their role across different biological hierarchies (gene, biological pathway, cell and brain areas) using bioinformatic approaches. For the majority of the analysis, a combined ASD cohort (N = 2171 trios) was created using previously published data by the Autism Sequencing Consortium (ASC). New plausible candidate genes for ASD such as FMR1 and NFIA were found. In addition, genes harboring PZMs were significantly enriched for miR-137 targets in comparison with germinal DNMs that were enriched in GO terms related to synaptic transmission. The expression pattern of genes with PZMs was restricted to early mid-fetal cortex. In contrast, the analysis of genes with germinal DNMs revealed a spatio-temporal window from early to mid-fetal development stages, with expression in the amygdala, cerebellum, cortex and striatum. These results provide evidence of the pathogenic role of PZMs and suggest the existence of distinct mechanisms between PZMs and germinal DNMs that are influencing ASD risk.

How is COVID-19 affecting patients with obsessive-compulsive disorder? A longitudinal study on the initial phase of the pandemic in a Spanish cohort.

BACKGROUND: Although the consequences of the COVID-19 pandemic on emotional health are evident, little is known about its impact on patients with obsessive-compulsive disorder (OCD). METHODS: One hundred and twenty-seven patients with OCD who attended a specialist OCD Clinic in Barcelona, Spain, were assessed by phone from April 27 to May 25, 2020, during the early phase of the pandemic, using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and a structured interview that collected clinical and sociodemographic information. Results were compared with those for 237 healthy controls from the same geographic area who completed an online survey. RESULTS: Although 65.3% of the patients with OCD described a worsening of their symptoms, only 31.4% had Y-BOCS scores that increased >25%. The risk of getting infected by SARS-CoV2 was reported as a new obsession by 44.8%, but this only became the main obsessive concern in approximately 10% of the patients. Suicide-related thoughts were more frequent among the OCD cohort than among healthy controls. The presence of prepandemic depression, higher Y-BOCS scores, contamination/washing symptoms, and lower perceived social support all predicted a significantly increased risk of OCD worsening. CONCLUSIONS: Most patients with OCD appear to be capable of coping with the emotional stress of the COVID-19 outbreak and its consequences during the initial phase of the pandemic. Nevertheless, the current crisis constitutes a risk factor for a significant worsening of symptoms and suicidal ideation. Action is needed to ensure effective and individualized follow-up care for patients with OCD in the COVID-19 era.

[Potential validity of thermolabile drugs outside the preservation conditions recommended by the manufacturer]. / Posible validez de medicamentos termolábiles fuera de las condiciones de conservación recomendadas por el fabricante.

Hospital pharmacists, according to the Ley del Medicamento 25/1990 of 20th December, should ensure appropriate drug preservation within the Pharmacy Department and in hospital stocks. The storage and preservation of thermolabile drugs according to manufacturer recommendations guarantees stability and optimal use conditions until the expiration date. Cold chain disruption may significantly affect the activity and toxicity of these drugs. Pharmacists should make quick decisions in case of cold chain-related events, hence the relevance of up-to-date information on stability under temperatures differing from those recommended. A review of the information available on the stability of drugs commonly used in the hospital setting that require a fridge for storage has been carried out.

[Disorders affecting the emotional sphere and impulse control in Parkinson's disease]. / Alteraciones de la esfera emocional y el control de los impulsos en la enfermedad de Parkinson.

INTRODUCTION: Parkinson's disease (PD) is associated with mood and behavioral symptoms contributing to morbidity and reduced quality of life of the patients. Most characteristic are depression, anxiety and impulse control disorder. DEVELOPMENT: Identification and treatment of neuropsychiatric symptoms is necessary for an appropriate management of PD. Affective symptoms may be the initial manifestation of PD, are highly prevalent and pathogenically complex. Impulse control disorders are usually not a spontaneous complaint, so asking about these symptoms may be the only way to detect and treat a serious socio-familial problem. Pharmacological treatment of these manifestations is difficult to balance with an adequate control of motor symptoms. Psychological support from early stages and throughout the evolution of PD is fundamental. CONCLUSIONS: Neurologist and other healthcare professionals treating PD patients need to be aware of behavioral and emotional manifestations of the disease. This will lead to an appropriate patient management and better adaptation of the familial and social situation.

[Comparative analysis of attributional style and self-esteem in a sample of depressed patients and normal control subjects]. / Análisis comparativo del estilo atribucional y de la autoestima en una muestra de pacientes depresivos y sujetos control normales.

INTRODUCTION: The present study assesses the role of attributions and self-esteem in depressive states. In depression, attributions can become central biased coping mechanisms that guide individual behavior. METHODS: Self-esteem and attribution bias was assessed in 40 depressed and 80 normal controls. RESULTS: Results of this investigation show that depressed patients made more internal attributions to negative events, and more external attributions for positive events than their normal counterparts, confirming an exaggerated attributional bias. CONCLUSIONS: The results suggest that depressed patients tend to blame themselves for their mistakes. Depressed patients made more stable and global attributions for negative events than for positive events, as opposed to what happens with the normal controls, making us believe that this bias will be maintained in time, and will eventually generalize to other life areas. This kind of study seems useful to develop efficient treatment programs and evaluation tools of depression.

[Eating disorders among Spanish university students]. / Los trastornos de la conducta alimentaria en estudiantes universitarios espanoles.

OBJECTIVE: This present work assesses the prevalence of anorexia nervosa, its partial syndromes, bulimia nervosa and binge eating in a university sample of Galician students (Spain). METHOD: The sample is made up of 298 women and 157 men. The scales used were: Eating Disorders Inventory (EDI) and a Questionnaire on eating behavior. RESULTS: Women had higher scores in drive for thinness, bulimia, interoceptive awareness, body dissatisfaction and ineffectiveness than men; furthermore the women had lower scores in BMI. We find a very high prevalence, a total of 6.4% of cases of eating disorders. CONCLUSIONS: The high values of probable eating disorders make it especially necessary to carry out primary and secondary prevention programs in university students populations.