An Exploratory Analysis on the 2D:4D Digit Ratio and Its Relationship with Social Responsiveness in Adults with Prader-Willi Syndrome.

Prader-Willi syndrome (PWS) is a genetic disorder produced by a lack of expression of paternally derived genes in the 15q11-13 region. Research has generally focused on its genetic and behavioral expression, but only a few studies have examined epigenetic influences. Prenatal testosterone or the maternal testosterone-to-estradiol ratio (MaTtEr) has been suggested to play an important role in the development of the 'social brain' during pregnancy. Some studies propose the 2D:4D digit ratio of the hand as an indirect MaTtEr measure. The relationship between social performance and MaTtEr has been studied in other neurodevelopmental conditions such as Autism Spectrum Disorder (ASD), but to our best knowledge, it has never been studied in PWS. Therefore, our study aims to clarify the possible existence of a relationship between social performance-as measured using the Social Responsiveness Scale (SRS)-and MaTtEr levels using the 2D:4D ratio. We found that, as a group, PWS individuals have shorter index and ring fingers than the control group, but no significant difference in the 2D:4D ratios. The 2D:4D ratio showed a correlation only with Restricted Interests and Repetitive Behavior Subscale, where a positive correlation only for male individuals with PWS was found. Considering only PWS with previous GH treatment during childhood/adolescence (PWS-GH), index and ring fingers did not show differences in length with the control group, but the 2D:4D ratio was significantly higher in the right or dominant hand compared to controls.

Social Responsiveness and Psychosocial Functioning in Adults with Prader-Willi Syndrome.

Although various studies have investigated symptoms of autism spectrum disorder (ASD) in Prader−Willi syndrome (PWS), little is known about the consequences of these symptoms, especially in psychosocial function. We aimed to explore ASD symptoms in adults with PWS with special attention to psychosocial functionality. This cross-sectional study included 26 adults (15 women) with PWS who attended a reference unit for rare diseases. Participants' primary caregivers completed the Social Responsiveness Scale (SRS), and clinicians assessed multidimensional functioning with the Personal and Social Performance Scale (PSP). Impaired social responsiveness was identified in 20 (76.9%) participants, and manifest to marked difficulties in social functioning were identified in 13 (50%). Participants with impaired social responsiveness (SRS ≥ 60) had significantly worse scores in functionality measured with the PSP (U = 12.5; p = 0.009) and with three of the four PSP main areas. Moreover, scores for the Social Cognition domain of the SRS correlated positively with the Socially useful activities (p < 0.05) and Personal and social relationships (p < 0.01) main areas of the PSP. These results suggest that difficulties in social skills should be assessed in all psychosocial evaluations of patients with PWS.

An adapted scale to evaluate insight in Prader-Willi Syndrome.

OBJECTIVE: To develop an insight scale for Prader-Willi Syndrome (PWS), a genetically determined neurodevelopmental disorder with different psychopathological and behavioural problems. METHODOLOGY: A sample of 36 PWS patients (58.3% women) attended at the Endocrinological Department of the Corporació Sanitària Parc Taulí (Sabadell, Barcelona) was evaluated. Insight was assessed by means of an adapted version of the Scale of Unawareness of Mental Disorder (SUMD), including three general insight dimensions: awareness of having a PWS, awareness of the effects of psychopharmacological medication and awareness of the social consequences, as well as three items that assess awareness of each particular symptom of the disease (obesity/overweight, excessive appetite and excessive food intake). RESULTS: The final Scale included six items and demonstrated an adequate internal consistency (Cronbach Alfa of 0.857 for Caregivers and 0.798 for Clinicians) but a high inter-rate variability. External validation using an Analytical-Visual Insight Scale was adequate. CONCLUSIONS: The Adapted version for Prader-Willi patients of the Scale of Unawareness of Mental Disorder (APW-SUD) showed adequate psychometric properties and it is an easy to administer means to assess insight in this population.

Multidimensional Evaluation of Awareness in Prader-Willi Syndrome.

There are no studies about insight or awareness of illness in patients with Prader-Willi Syndrome (PWS). The objective of this study was to explore the level of awareness of the disorder, of the need for medication, and of the social consequences of the disease, as well as of its main symptoms in PWS. We also aimed to explore relationships between awareness and sociodemographic and clinical characteristics, and to compare all data with a matched sample of patients with psychosis. Insight was assessed by an Adapted version of the Scale of Unawareness of Mental Disorder in a cross-sectional pilot study at a University Hospital. Thirty-six individuals with PWS (58.3% women) were included. Results showed that PWS patients had a good awareness of the illness and of the effects of medication, in contrast to a lack of awareness of illness' social consequences. Awareness of obesity/overweight was excellent, as was the awareness of excessive appetite. Awareness of excessive food intake was only mild. Insight correlated with age and functionality, but not with BMI. PWS patients showed a better insight into the illness but a similar awareness of the effects of the medication and of the social consequences of the disease as compared to schizophrenia-spectrum patients. This profile of insight may have relevant clinical implications.

Altered Gesture Imitation and Brain Anatomy in Adult Prader-Willi Syndrome Patients.

OBJECTIVE: To explore motor praxis in adults with Prader-Willi syndrome (PWS) in comparison with a control group of people with intellectual disability (ID) and to examine the relationship with brain structural measurements. METHOD: Thirty adult participants with PWS and 132 with ID of nongenetic etiology (matched by age, sex, and ID level) were assessed using a comprehensive evaluation of the praxis function, which included pantomime of tool use, imitation of meaningful and meaningless gestures, motor sequencing, and constructional praxis. RESULTS: Results support specific praxis difficulties in PWS, with worse performance in the imitation of motor actions and better performance in constructional praxis than ID peers. Compared with both control groups, PWS showed increased gray matter volume in sensorimotor and subcortical regions. However, we found no obvious association between these alterations and praxis performance. Instead, praxis scores correlated with regional volume measures in distributed apparently normal brain areas. CONCLUSIONS: Our findings are consistent in showing significant impairment in gesture imitation abilities in PWS and, otherwise, further indicate that the visuospatial praxis domain is relatively preserved. Praxis disability in PWS was not associated with a specific, focal alteration of brain anatomy. Altered imitation gestures could, therefore, be a consequence of widespread brain dysfunction. However, the specific contribution of key brain structures (e.g., areas containing mirror neurons) should be more finely tested in future research.

Psychopathological disorders in Prader-Willi syndrome. / Alteraciones psicopatológicas en el síndrome de Prader-Willi.

Prader-Willi syndrome is a genetic disorder caused by chromosomal changes in segment 15q11-q13 including cognitive, mental, and behavioral symptoms, as well as a specific physical phenotype. Both the most common psychopathological changes (intellectual disability, obsessions, impulsivity, autism spectrum disorders, self-injuries) and the main psychiatric comorbidities (affective disorders, psychosis, obsessive-compulsive disorder, autism spectrum disorder) are characterized by a great heterogeneity, which warrants the need for better identification of their frequency and clinical signs. In addition to its effects on body compositionand hypotony, growth hormone has been shown to be useful for regulating patient behavior, and psychoactive drugs are also an option. Other alternatives have shown promising results in experimental trials. Adequate understanding of the psychopathology associated to Prader-Willi syndrome would allow for improving clinical approach, symptom identification, detection of comorbidities, and administration of more effective treatments, leading to better clinical outcomes.

Mapping the sequence of brain events in response to disgusting food.

Warning signals indicating that a food is potentially dangerous may evoke a response that is not limited to the feeling of disgust. We investigated the sequence of brain events in response to visual representations of disgusting food using a dynamic image analysis. Functional MRI was acquired in 30 healthy subjects while they were watching a movie showing disgusting food scenes interspersed with the scenes of appetizing food. Imaging analysis included the identification of the global brain response and the generation of frame-by-frame activation maps at the temporal resolution of 2 s. Robust activations were identified in brain structures conventionally associated with the experience of disgust, but our analysis also captured a variety of other brain elements showing distinct temporal evolutions. The earliest events included transient changes in the orbitofrontal cortex and visual areas, followed by a more durable engagement of the periaqueductal gray, a pivotal element in the mediation of responses to threat. A subsequent core phase was characterized by the activation of subcortical and cortical structures directly concerned not only with the emotional dimension of disgust (e.g., amygdala-hippocampus, insula), but also with the regulation of food intake (e.g., hypothalamus). In a later phase, neural excitement extended to broad cortical areas, the thalamus and cerebellum, and finally to the default mode network that signaled the progressive termination of the evoked response. The response to disgusting food representations is not limited to the emotional domain of disgust, and may sequentially involve a variety of broadly distributed brain networks. Hum Brain Mapp 39:369-380, 2018. © 2017 Wiley Periodicals, Inc.

Lack of Postprandial Peak in Brain-Derived Neurotrophic Factor in Adults with Prader-Willi Syndrome.

CONTEXT: Prader-Willi syndrome (PWS) is characterized by severe hyperphagia. Brain-derived neurotrophic factor (BDNF) and leptin are reciprocally involved in energy homeostasis. OBJECTIVES: To analyze the role of BDNF and leptin in satiety in genetic subtypes of PWS. DESIGN: Experimental study. SETTING: University hospital. SUBJECTS: 90 adults: 30 PWS patients; 30 age-sex-BMI-matched obese controls; and 30 age-sex-matched lean controls. INTERVENTIONS: Subjects ingested a liquid meal after fasting ≥10 hours. MAIN OUTCOME MEASURES: Leptin and BDNF levels in plasma extracted before ingestion and 30', 60', and 120' after ingestion. Hunger, measured on a 100-point visual analogue scale before ingestion and 60' and 120' after ingestion. RESULTS: Fasting BDNF levels were lower in PWS than in controls (p = 0.05). Postprandially, PWS patients showed only a truncated early peak in BDNF, and their BDNF levels at 60' and 120' were lower compared with lean controls (p<0.05). Leptin was higher in PWS patients than in controls at all time points (p<0.001). PWS patients were hungrier than controls before and after eating. The probability of being hungry was associated with baseline BDNF levels: every 50-unit increment in BDNF decreased the odds of being hungry by 22% (OR: 0.78, 95%CI: 0.65-0.94). In uniparental disomy, the odds of being hungry decreased by 66% (OR: 0.34, 90%CI: 0.13-0.9). Postprandial leptin patterns did no differ among genetic subtypes. CONCLUSIONS: Low baseline BDNF levels and lack of postprandial peak may contribute to persistent hunger after meals. Uniparental disomy is the genetic subtype of PWS least affected by these factors.

Safety of cabergoline in the management of pituitary prolactin-induced symptoms with patients treated with atypical neuroleptics.

UNLABELLED: Atypical antipsychotic-induced hyperprolactinemia can cause important clinical symptoms, particularly in young women and also in men, such as impotence, loss of libido, gynecomastia, anovulation and galactorrhea. METHODS: Observational over one-year follow-up of six patients (four women and two men, mean age of 31.1 years, range 26-37), treated with different atypical antipsychotics in an outpatient psychiatric device, who had clinical complications associated to high prolactin serum levels. All of them were treated with standard doses of cabergoline. RESULTS: Most patients experienced significant clinical improvement after treatment with standard doses of cabergoline (mean dosage 1.08 mg/week), maintained for a mean of 18 month. Normal prolactin levels were achieved after the first months of treatment with cabergoline. No side effects or worsening of psychotic or behavioral symptoms were observed. CONCLUSIONS: Long-term treatment with cabergoline seems to be safe in atypical antipsychotic-treated patients.

[Metabolic syndrome in patients with schizophrenia and antipsychotic treatment]. / Síndrome metabólico en pacientes esquizofrénicos con tratamiento antipsicótico.

Patients with schizophrenia have a shorter life expectancy and their risk of dying from a cardiovascular disease is higher than the general population. Both facts have been attributed to the raised presence of metabolic syndrome. There is a big amount of scientific publications that deals with the relationship between schizophrenia, antipsychotic treatment, and the development of metabolic syndrome. There is also information about recommendations and clinical guides to achieve an adequate prevention, screening, and treatment of the disease. The aim of this review is to update the current information about this issue and to understand related etiologic factors, differences between antipsychotic drugs, and the current recommendations for patient's care.

Combination of aripiprazole and other psychopharmacological treatments in resistant and multi-resistant patients.

INTRODUCTION: Aripiprazole is a new antipsychotic agent that has proven safe and efficacious in controlled clinical trials. However, few published data on its effectiveness and safety when used in augmentation and combination are available. METHODS: Our study aimed to determine the functional effectiveness and safety of different combinations of aripiprazole with other psychotropics in resistant patients. All acute not selected (15) patients treated with aripiprazole and other psychotropics between February 2005 and May 2007 are included. RESULTS: Mean follow-up 20.4 days. Main diagnosis was schizophrenia (40%) and mean dose of aripiprazole was 25 mg/d. Resistant patients received initially multiple psychotropics (mean 3.3) and their functional status was very low. A significant functional improvement was observed after admission in most (12) of them. Only three patients experienced mild to moderate improvement; another three patients showed extrapyramidal symptoms. No dermatological reactions or adverse effects were observed with lamotrigine association. DISCUSIONS: The combination of aripiprazole with other psychotropics was well tolerated. No significant new adverse reactions were observed. In a short term follow-up, our results show a good tolerability of aripiprazole in combination with other psychotropics of different groups.

Clinical and sociodemographic variables associated with the onset of posttraumatic stress disorder in road traffic accidents.

Our objective was to identify variables related to the onset of acute posttraumatic stress disorder (PTSD) after a road traffic accident. We evaluated 60 victims of a motor vehicle accident (MVA) in 2004 at 2 months postaccident. Thirty of them had developed PTSD; the other 30 had not developed PTSD. Clinical data, physical injuries, and sociodemographic characteristics were determined in 60 victims. The Davidson Trauma Scale (DTS) and a Structured Clinical Interview for DSM-IV (SCID) were used to evaluate PTSD occurrence. PTSD scores assessed by DTS and SCID at 2 months were significantly and positively associated with female sex, severe physical injuries, perceived social deprivation, and loss of job activity due to the accident. Female sex, severe physical injury, perceived social deprivation, and sick leave were related to the diagnosis of PTSD 2 months after the accident.

Remission on thiopurinic immunomodulators normalizes quality of life and psychological status in patients with Crohn's disease.

BACKGROUND: Thiopurinic immunomodulators are effective for maintaining symptom remission in Crohn's disease. Little is known, however, about their effect on patients' quality of life or psychological well-being. The present study aimed to determine whether remission induced by thiopurinic immunomodulators returns levels of quality of life and psychological well-being to normal. MATERIALS AND METHODS: A case-control study was performed. Cases were 33 patients with Crohn's disease treated with azathioprine or 6-mercaptopurine and in stable remission for at least 6 months. Sixty-six healthy individuals matched 2:1 by age and sex and 14 patients with active Crohn's disease were included as control groups. Quality of life was evaluated with the Short Form (SF-36) questionnaire, and the respective Hamilton rating scales were used for anxiety and depression. ANOVA with Bonferroni's correction was used for multiple comparisons. RESULTS: SF-36 global scores were 85 in the study group, 85 in healthy controls (P = 1), and 58.6 in patients with active disease (P < 0.001 for the comparison with the other 2 groups). The differences between values were 0 (95% CI -4-4), 26.4 (95% CI 20-32), and 26.4 (95% CI 19-33), respectively. The respective anxiety and depression scores were 6.5, 5.5, and 16.2 and 3.7, 3.3, and 10.9. No significant differences were observed in any of the SF-36 domains between case and control groups, whereas in patients with active disease, all domains were significantly worse. CONCLUSIONS: Thiopurinic immunomodulator-induced remission restores normal levels of quality of life and psychological well-being in Crohn's disease patients.