Negative symptoms and cognitive impairment are associated with distinct motivational deficits in treatment resistant schizophrenia.

BACKGROUND: Motivational deficits are a central feature of the negative syndrome in schizophrenia. They have consistently been associated with reduced willingness to expend physical effort in return for monetary rewards on effort based decision making (EBDM) paradigms. Nevertheless, the mechanisms underlying such altered performance are not well characterised, and it remains unclear if they are driven purely by negative symptoms, or also in part by cognitive impairment, antipsychotic treatment or even positive symptoms. Here we investigated the impact of all these factors using a paradigm that has not previously been used to measure EBDM in schizophrenia. METHODS: Forty treatment resistant schizophrenia (TRS) patients on clozapine and matched controls (N = 80) completed a well validated EBDM task which offers monetary rewards in return for physical effort. Choice and reaction time data was analysed using logistic regressions, as well as Bayesian hierarchical drift diffusion modelling (HDDM). Behavioural parameters were compared between groups and their association with negative symptoms, cognitive function and serum clozapine levels were assessed. RESULTS: Overall, TRS patients accepted significantly less offers than controls during effort-based decision making, suggesting they were less motivated. They demonstrated reduced sensitivity to increasing rewards, but surprisingly were also less averse to increasing effort. Despite a positive correlation between negative symptoms and cognitive function in TRS, reward sensitivity was associated only with cognitive performance. In contrast, reduced effort aversion correlated with negative symptom severity. Clozapine levels and positive symptoms were not associated with either behavioural parameter. CONCLUSION: Motivational deficits in TRS are characterised by both diminished reward sensitivity and reduced effort aversion during EBDM. Cognitive dysfunction and negative symptom severity account for distinct aspects of these behavioural changes, despite positive associations between themselves. Overall, these findings demonstrate that negative symptoms and cognitive impairment have significant independent contributions to EBDM in TRS, thereby opening the possibility of individualised treatment targeting these mechanisms to improve motivation.

Cannabis use influence on peripheral brain-derived neurotrophic factor levels in antipsychotic-naïve first-episode psychosis.

The objective of this study is to determine whether cannabis influences BDNF levels in patients with psychosis (FEP) and healthy volunteers (HV) to help understand the role of BDNF in psychosis. We assessed the association between BDNF and cannabis in a cohort of FEP antipsychotic-naïve patients and HV, whilst controlling for other potential confounding factors. 70 FEP drug-naive patients and 57 HV were recruited. A sociodemographic variable collection, structured clinical interview, weight and height measurement, substance use determination, and blood collection to determine BDNF levels by ELISA analysis were done. In FEP patients, cannabis use was associated with BDNF levels (high cannabis use was associated with lower BDNF levels). Moreover, cannabis use was statistically significantly associated with age (high use of cannabis was associated with younger age). In HV, no relationship between cannabis use and BDNF levels was observed. Otherwise, cannabis use was significantly associated with tobacco use, so that high cannabis users were also high tobacco users. This study showed a different association between cannabis use and BDNF levels in FEP patients compared with HV, particularly, with high doses of cannabis. These findings may help understand the deleterious effects of cannabis in some vulnerable individuals, as well as discrepancies in the literature.

Inverse association between negative symptoms and body mass index in chronic schizophrenia.

BACKGROUND: We investigated whether negative symptoms, such as poor motivation or anhedonia, were associated with higher body mass index (BMI) in stable patients with schizophrenia chronically treated with antipsychotic medication. METHODS: 62 olanzapine- or clozapine-treated patients with illness duration of at least four years were selected from an international multicenter study on the characterization of negative symptoms. All participants completed the Brief Negative Symptom Scale (BNSS) and the Positive and Negative Syndrome Scale (PANSS). Bivariate correlations between BMI and negative symptoms (BNSS) were explored, as well as multiple regression analyses. We further explored the association of two principal component factors of the BNSS and BMI. Subsidiary analyses re-modeled the above using the negative symptoms subscale of the PANSS and the EMSLEY factor for negative symptoms for convergent validity. RESULTS: Lower negative symptoms (BNSS score) were associated with higher BMI (r=-0.31; p=0.015). A multiple regression analysis showed that negative symptoms (BNSS score) and age were significant predictors of BMI (p=0.037). This was mostly driven by the motivation/pleasure factor of the BNSS. Within this second factor, BMI was negatively associated with anhedonia (r=-0.254; p=0.046) and asociality (r=-0.253; p=0.048), but not avolition (r=-0.169; p=0.188). EMSLEY score was positively associated with BNSS (r=0.873, p<0.001), but negatively associated with BMI (r=-0.308; p=0.015). The association between PANSS and BMI did not reach significance (r=-224, p=0.080). CONCLUSIONS: We conclude that lower negative symptoms were associated with higher BMI (assessed using both the BNSS and EMSLEY) in chronic stable schizophrenia patients, mostly due to lower anhedonia and asociality levels.

Metabolic syndrome or glucose challenge in first episode of psychosis?

Patients with schizophrenia exhibit a reduced life expectancy. Although unhealthy lifestyle or suicide risk plays a role, the main causes are diverse medical conditions such as cardiovascular diseases, type 2 diabetes mellitus and metabolic syndrome. Albeit pharmacological secondary side effects might also trigger previous conditions, studies in naïve patients reflect diverse anomalies at the onset. Patients with a first episode of psychosis, display a wide scope of metabolic abnormalities, ranging from normality till pathological values depending on the parameters studied. We attempted to evaluate the metabolic syndrome and glycemic homeostasis in a subset of antipsychotic-naïve patients with a first episode of non-affective psychosis. Patients (n=84) showed a similar prevalence of metabolic syndrome compared with a matched control sample (n=98) (6% vs 4%, P=0.562), while glucose homeostasis values differed significantly (14% vs. 5%, P=0.034). Our results suggest that metabolic syndrome is not a useful clinical condition to be evaluated in patients before pharmacological treatment. Abnormal glycemic homeostasis at the onset of the disease requires specific diagnostic tools and preventive measures in order to avoid future cardiovascular events. New strategies must be implemented in order to evaluate the cardiovascular risk and subsequent morbidity in patients at the onset of the disease.

Association of the brain-derived neurotrophic factor Val66Met polymorphism with negative symptoms severity, but not cognitive function, in first-episode schizophrenia spectrum disorders.

OBJECTIVE: A functional polymorphism of the brain-derived neurotrophic factor gene (BDNF) Val66Met has been associated with cognitive function and symptom severity in patients with schizophrenia. It has been suggested that the Val66Met polymorphism has a role as a modulator in a range of clinical features of the illness, including symptoms severity, therapeutic responsiveness, age of onset, brain morphology and cognitive function. However, little work has been done in first-episode schizophrenia (FES) spectrum disorders. The objective of this study is to investigate the association of the BDNF Val66Met polymorphism on cognitive function and clinical symptomatology in FES patients. METHODS: Using a cross-sectional design in a cohort of 204 patients with FES or a schizophrenia spectrum disorder and 204 healthy matched controls, we performed BDNF Val66Met genotyping and tested its relationship with cognitive testing (attention, working memory, learning/verbal memory and reasoning/problem-solving) and assessment of clinical symptom severity. RESULTS: There was no significant influence of the BDNF allele frequency on cognitive factor scores in either patients or controls. An augmented severity of negative symptoms was found in FES patients that carried the Met allele. CONCLUSIONS: The results of this study suggest that in patients with a first-episode of schizophrenia or a schizophrenia spectrum disorder, the BDNF Val66Met polymorphism does not exert an influence on cognitive functioning, but is associated with negative symptoms severity. BDNF may serve as suitable marker of negative symptomatology severity in FES patients within the schizophrenia spectrum.

Valence-dependent influence of serotonin depletion on model-based choice strategy.

Human decision-making arises from both reflective and reflexive mechanisms, which underpin goal-directed and habitual behavioural control. Computationally, these two systems of behavioural control have been described by different learning algorithms, model-based and model-free learning, respectively. Here, we investigated the effect of diminished serotonin (5-hydroxytryptamine) neurotransmission using dietary tryptophan depletion (TD) in healthy volunteers on the performance of a two-stage decision-making task, which allows discrimination between model-free and model-based behavioural strategies. A novel version of the task was used, which not only examined choice balance for monetary reward but also for punishment (monetary loss). TD impaired goal-directed (model-based) behaviour in the reward condition, but promoted it under punishment. This effect on appetitive and aversive goal-directed behaviour is likely mediated by alteration of the average reward representation produced by TD, which is consistent with previous studies. Overall, the major implication of this study is that serotonin differentially affects goal-directed learning as a function of affective valence. These findings are relevant for a further understanding of psychiatric disorders associated with breakdown of goal-directed behavioural control such as obsessive-compulsive disorders or addictions.

Spanish adaptation and validation of the Brief Negative Symptoms Scale.

Negative symptoms prevalent in schizophrenia are associated with poor outcome. Developing new instruments to identify new treatments was highlighted at the NIMH-MATRICS Consensus Development Conference on Negative Symptoms. The new Brief Negative Symptoms scale (BNSS) demonstrated strong psychometric properties, but there is a need for validating it in non-English languages. A multi-center study was conducted to validate the Spanish version of the BNSS (BNSS-Sp) in 20 schizophrenia patients, following the original BNSS validation methodology. We found strong inter-rater, test-retest and internal consistency properties (for the total BNSS-Sp, intraclass correlation coefficient=0.97, Pearson's correlation coefficient r=0.95 (p<0.001), Cronbach's alpha=0.98).

[Velo-cardio-facial syndrome at the psychiatry consulting-liaison service in a general hospital]. / El síndrome velocardiofacial en la interconsulta psiquiátrica en un hospital general.

Psychotic syndromes secondary to genomic disorders have low prevalence and may easily go unnoticed in the daily clinical practice. The velo-cardio-facial syndrome or DiGeorge syndrome (VCFS/DGS) is the genomic disorder most frequently associated to an interstitial deletion of the 22q11 region, with an incidence of one per every 4,000 newborns. Clinical manifestations constitute a constellation of cardiac, facial, urogenital and psychiatric disorders, among which schizophrenia or schizophreniform disorder stand out with an incidence of about 30% over the lifetime. In the following, we present the case of a 21 year old female patient who was admitted to the hematology service of our hospital due to pancytopenia secondary to metimazole, who had non-specified psychiatric background and who received antipsychotic treatment.

[Psychiatric disease in patients with psychogenic non-epileptic seizures referred from an epilepsy unit in a general hospital]. / Patología psiquiátrica en pacientes con crisis no epilépticas psicógenas derivados a una unidad de epilepsia en un hospital general.

INTRODUCTION: We evaluate psychiatric disease associated with psychogenic non-epileptic seizures (PNES) and study the role played by previous traumatic experiences, dissociative episodes and personality disorders. METHOD: After diagnosing PNES in our epilepsy unit, we obtained a sample of 46 patients and carried out a structured psychiatric interview (SCID) following DSM-III-R criteria. We looked for previous dissociative episodes and prepared a questionnaire for traumatic experiences and basic clinical data. RESULTS: The most frequent psychiatric disorders were depression, anxiety and somatoform disorders. Personality disorders were found in 16 patients (34.78%), dissociative episodes in 17 (36.95%), and previous traumatic experiences in 14 (30.43%). No statistically significant differences were found in regards to PNES, with respect to presence or absence of previous traumatic experiences, dissociative episodes, and personality disorders. CONCLUSIONS: As in previous studies, our research project confirms the co-existence of PNES with other mental disorders, and although we do find a higher frequency of seizures, the role played by traumatic experiences and dissociative disorders in CNEP remains unclear.

Patología psiquiátrica en pacientes con crisis no epilépticas psicógenas derivados a una unidad de epilepsia en un hospital general / Psychiatric disease in patients with psychogenic non-epileptic seizures referred from an epilepsy unit in a general hospital

Introducción. Se evalúa la patología psiquiátrica que acompaña a las crisis no epilépticas psicógenas (CNEP) y se estudia el papel que desempeñan en ellas las experiencias traumáticas previas, los episodios disociativos y los trastornos de la personalidad. Método. Después del diagnóstico de CNEP en la Unidad de Epilepsia de nuestro centro se realizó en una muestra de 46 pacientes una entrevista psiquiátrica estructurada siguiendo criterios DSM-III-R (SCID). Se evaluó la existencia de episodios disociativos siguiendo criterios DSM-IV, y para las experiencias traumáticas y los datos clínicos de interés se confeccionó un cuestionario ad hoc. Resultados. Los trastornos psiquiátricos más frecuentes fueron los estados depresivos, los de ansiedad y los somatomorfos. Presentaban trastornos de la personalidad 16 pacientes (34,78 por ciento), fenómenos disociativos 17 pacientes (3695 9ó) y 14 pacientes (30,43 por ciento) antecedentes de experiencias traumáticas. No se observaron diferencias estadísticamente significativas en relación con las CNEP, respecto a la presencia o ausencia de experiencias traumáticas previas, trastornos disociativos o trastornos de la personalidad. Conclusiones. Como en trabajos previos, en nuestro estudio se confirma la existencia de una gran comorbilidad psiquiátrica en relación con las CNEP, y aunque asociadas a la presencia de un mayor número de crisis, el papel que tienen las experiencias traumáticas y los trastornos disociativos en relación con las CNEP permanece poco claro (AU)

[Relationship between patient's subjective stress perception and the course of inflammatory bowel disease]. / Relación entre los acontecimientos estresantes y el curso de la enfermedad inflamatoria intestinal según la percepción subjetiva del paciente.

INTRODUCTION: Studies examining the relationship between stress secondary to adverse life events (ALE) and inflammatory bowel disease (IBD) have produced controversial data. The aim of this study was to explore the subjective perception of this relationship in IBD patients. PATIENTS AND METHODS: Seventy consecutive patients suffering from IBD (40 Crohn's disease, 30 ulcerative colitis) were assessed using a self-rating questionnaire related to demographic variables, clinical characteristics, subjective perception of the influence of ALE on the course of IBD, psychiatric background, and the HAD scale. The results of this scale were compared with a group of 25 relatives. RESULTS: Forty-two patients (60%) perceived that there was relationship between ALE and the onset of their disease, forty-nine (70%) between ALE and the increasing IBD symptoms severity, and fifty-one patients (72.9%) with disease activity. Sixteen of the patients (22.9%) had been visited by a psychiatrist during relapses of IBD. Twenty-five patients (42.4%) reached a score of 11 or higher on the depression or anxiety subscales of the HAD, indicating a probable psychological disorder. CONCLUSIONS: IBD patients perceive a strong relationship between ALE and the course of IBD. We have found a high prevalence of anxiety and depression symptoms in these patients. If this observation is confirmed with objective measurements, it will be important to consider psychiatric intervention for these patients.

[Functional neuroimaging of auditory hallucinations in schizophrenia]. / Neuroimagen funcional de las alucinaciones auditivas en la esquizofrenia.

The neurobiological bases underlying the generation of auditory hallucinations, a distressing and paradigmatic symptom of schizophrenia, are still unknown in spite of in-depth phenomenological descriptions. This work aims to make a critical review of the latest published literature in recent years, focusing on functional neuroimaging studies (PET, SPECT, fMRI) of auditory hallucinations. Thus, the studies are classified according to whether they are sensory activation, trait and state. The two main hypotheses proposed to explain the phenomenon, external speech vs. subvocal or inner speech, are also explained. Finally, the latest unitary theory as well as the limitations the studies published are commented on. The need to continue investigating in this field, that is still underdeveloped, is posed in order to understand better the etiopathogenesis of auditory hallucinations in schizophrenia.

Neuroimagen funcional de las alucinaciones auditivas en la esquizofrenia / Functional neuroimaging of auditory hallucinations in schizophrenia

Las bases neurobiológicas subyacentes a la generación de las alucinaciones auditivas, síntoma paradigmático y angustiante de la esquizofrenia son aún desconocidas a pesar de estar descritas fenomenológicamente con profundidad. El propósito de este trabajo es realizar una revisión crítica de la literatura publicada en los últimos años, centrándose en los estudios de neuroimagen funcional (PET, SPECT, RMf) del fenómeno alucinatorio. Para ello se clasifican los estudios según sean de rasgo, de estado y de activación sensorial. También se exponen las dos principales hipótesis propuestas para la explicación del fenómeno: lenguaje exterior frente a lenguaje interior o subvocal (inner speech). Finalmente se presenta una hipótesis unitaria, así como las limitaciones de los estudios publicados. Se plantea la necesidad de seguir la investigación en este campo, todavía en estado incipiente, con el objetivo de comprender mejor la etiopatogenia de las alucinaciones auditivas en la esquizofrenia. (AU)