Proposed diagnostic criteria for mild cognitive impairment in Down syndrome population.

BACKGROUND: Despite presenting higher risk of dementia, mild cognitive impairment (MCI) is not well defined in Down syndrome population. OBJECTIVE: We aimed to describe cognitive and neuropsychological patterns associated with MCI in Down syndrome individuals. METHOD: Two groups of adults with Down syndrome (control and prodromal) were studied throughout 3 years. Two linear mixed models and a model including the variables that best predicted group membership were built. RESULTS: Behavioural Regulation Index (BRI) (Behaviour Rating Inventory of Executive Function test) and the model composed of BRI, abstraction and delayed verbal memory were the variable and model best predicting group membership, respectively. CONCLUSION: Suggest a diagnosis of MCI when BRI is the earliest change perceived by caregivers and this is combined with low scores in abstract thinking, and when an amnesic pattern in delayed verbal memory is observed, but adaptive skills are preserved.

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.

Compulsions in Prader-Willi syndrome: occurrence and severity as a function of genetic subtype.

INTRODUCTION: Compulsions are among the most typical behaviors in Prader-Willi syndrome (PWS). The most frequent causes of PWS are deletion of the genes located in the segment 15q11-q13 of the paternal allele and maternal uniparental disomy of cromosome 15. The aim of the present work was to study compulsive behavior in a sample of adults with PWS and analyze potential differences as a function of the genetic cause/subtype. MATERIAL AND METHODS: In the 27 study participants, existence of type I deletion (n=7), type II deletion (n=13), and maternal disomy (n=7) was determined by means of genetic tests. The Yale-Brown Obsessive Compulsive Scale, the Compulsive Behavior Checklist, and the Repetitive Behavior Questionnaire were used to assess occurrence and severity of compulsions. RESULTS: Most of the participants showed compulsive behavior, the most frequent compulsions were those of inappropriate grooming (skin picking) and order (hoarding). The occurrence of compulsions was less frequent in the maternal disomy group than in the deletion groups. Severe compulsions were more frequent in those participants with type II deletion than in the other groups. CONCLUSIONS: Differences in occurrence and severity of compulsions exist as a function of PWS genetic subtype. Our results support the idea that individuals with maternal disomy are less affected by compulsive behavior. More research on the severity of compulsions as a function of deletion type should be done, as the studies conducted so far have shown contradictory results.

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.

Neurodevelopmental risk copy number variants in adults with intellectual disabilities and comorbid psychiatric disorders.

BACKGROUND: Copy number variants (CNVs) are established risk factors for neurodevelopmental disorders. To date the study of CNVs in psychiatric illness has focused on single disorder populations. The role of CNVs in individuals with intellectual disabilities and psychiatric comorbidities are less well characterised.AimsTo determine the type and frequency of CNVs in adults with intellectual disabilities and comorbid psychiatric disorders. METHOD: A chromosomal microarray analysis of 599 adults recruited from intellectual disabilities psychiatry services at three European sites. RESULTS: The yield of pathogenic CNVs was high - 13%. Focusing on established neurodevelopmental disorder risk loci we find a significantly higher frequency in individuals with intellectual disabilities and comorbid psychiatric disorder (10%) compared with healthy controls (1.2%, P<0.0001), schizophrenia (3.1%, P<0.0001) and intellectual disability/autism spectrum disorder (6.5%, P < 0.00084) populations. CONCLUSIONS: In the largest sample of adults with intellectual disabilities and comorbid psychiatric disorders to date, we find a high rate of pathogenic CNVs. This has clinical implications for the use of genetic investigations in intellectual disability psychiatry.Declaration of interestNone.

High Incidence of Copy Number Variants in Adults with Intellectual Disability and Co-morbid Psychiatric Disorders.

A genetic analysis of unexplained mild-moderate intellectual disability and co-morbid psychiatric or behavioural disorders is not systematically conducted in adults. A cohort of 100 adult patients affected by both phenotypes were analysed in order to identify the presence of copy number variants (CNVs) responsible for their condition identifying a yield of 12.8% of pathogenic CNVs (19% when including clinically recognizable microdeletion syndromes). Moreover, there is a detailed clinical description of an additional 11% of the patients harbouring possible pathogenic CNVs-including a 7q31 deletion (IMMP2L) in two unrelated patients and duplications in 3q29, 9p24.2p24.1 and 15q14q15.1-providing new evidence of its contribution to the phenotype. This study adds further proof of including chromosomal microarray analysis (CMA) as a mandatory test to improve the diagnosis in the adult patients in psychiatric services.

Anomalous basal ganglia connectivity and obsessive-compulsive behaviour in patients with Prader Willi syndrome.

BACKGROUND: Prader Willi syndrome is a genetic disorder with a behavioural expression characterized by the presence of obsessive-compulsive phenomena ranging from elaborate obsessive eating behaviour to repetitive skin picking. Obsessive-compulsive disorder (OCD) has been recently associated with abnormal functional coupling between the frontal cortex and basal ganglia. We have tested the potential association of functional connectivity anomalies in basal ganglia circuits with obsessive-compulsive behaviour in patients with Prader Willi syndrome. METHODS: We analyzed resting-state functional MRI in adult patients and healthy controls. Whole-brain functional connectivity maps were generated for the dorsal and ventral aspects of the caudate nucleus and putamen. A selected obsessive-compulsive behaviour assessment included typical OCD compulsions, self picking and obsessive eating behaviour. RESULTS: We included 24 adults with Prader Willi syndrome and 29 controls in our study. Patients with Prader Willi syndrome showed abnormal functional connectivity between the prefrontal cortex and basal ganglia and within subcortical structures that correlated with the presence and severity of obsessive-compulsive behaviours. In addition, abnormally heightened functional connectivity was identified in the primary sensorimotor cortex-putamen loop, which was strongly associated with self picking. Finally, obsessive eating behaviour correlated with abnormal functional connectivity both within the basal ganglia loops and between the striatum and the hypothalamus and the amygdala. LIMITATIONS: Limitations of the study include the difficulty in evaluating the nature of content of obsessions in patients with Prader Willi Syndrome and the risk of excessive head motion artifact on brain imaging. CONCLUSION: Patients with Prader Willi syndrome showed broad functional connectivity anomalies combining prefrontal loop alterations characteristic of OCD with 1) enhanced coupling in the primary sensorimotor loop that correlated with the most impulsive aspects of the behaviour and 2) reduced coupling of the ventral striatum with limbic structures for basic internal homeostasis that correlated with the obsession to eat.

Unexpected complexity in the molecular diagnosis of spastic paraplegia 11.

BACKGROUND: Spastic paraplegia 11 (SPG11) is the most prevalent form of autosomal recessive hereditary spastic paraplegia, resulting from biallelic pathogenic variants in the SPG11 gene (MIM *610844). METHODS: The proband is a 36-year-old female referred for genetic evaluation due to cognitive dysfunction, gait impairment, and corpus callosum atrophy (brain MRI was normal at 25-years-old). Diagnostic approaches included CGH array, next-generation sequencing, and whole transcriptome sequencing. RESULTS: CGH array revealed a 180 kb deletion located upstream of SPG11. Sequencing of SPG11 uncovered two rare single nucleotide variants: the novel variant c.3143C>T in exon 17 (in cis with the deletion), and the previously reported pathogenic variant c.6409C>T in exon 34 (in trans). Whole transcriptome sequencing revealed that the variant c.3143C>T caused exon 17 skipping. CONCLUSION: We report a novel sequence variant in the SPG11 gene resulting in exon 17 skipping, which, along with a nonsense variant, causes Spastic Paraplegia 11 in our proband. In addition, a deletion upstream of SPG11 was identified in the patient, whose implication in the phenotype remains uncertain. Nonetheless, the deletion apparently affects cis-regulatory elements of the gene, suggesting a potential new pathogenic mechanism underlying the disease in a subset of undiagnosed patients. Our findings further support the hypothesis that the origin of thin corpus callosum in patients with SPG11 is of progressive nature.

The Global Deterioration Scale for Down Syndrome Population (GDS-DS): A Rating Scale to Assess the Progression of Alzheimer's Disease.

The aim of this study is to adapt and validate the global deterioration scale (GDS) for the systematic tracking of Alzheimer's disease (AD) progression in a population with Down syndrome (DS). A retrospective dual-center cohort study was conducted with 83 participants with DS (46.65 ± 5.08 years) who formed the primary diagnosis (PD) group: cognitive stability (n = 48), mild cognitive impairment (n = 24), and Alzheimer's disease (n = 11). The proposed scale for adults with DS (GDS-DS) comprises six stages, from cognitive and/or behavioral stability to advanced AD. Two neuropsychologists placed the participants of the PD group in each stage of the GDS-DS according to cognitive, behavioral and daily living skills data. Inter-rater reliability in staging with the GDS-DS was excellent (ICC = 0.86; CI: 0.80-0.93), and the agreement with the diagnosis categories of the PD group ranged from substantial to excellent with κ values of 0.82 (95% CI: 0.73-0.92) and 0.85 (95% CI: 0.72, 0.99). Performance with regard to the CAMCOG-DS total score and orientation subtest of the Barcelona test for intellectual disability showed a slight progressive decline across all the GDS-DS stages. The GDS-DS scale is a sensitive tool for staging the progression of AD in the DS population, with special relevance in daily clinical practice.

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.

Brain signal complexity in adults with Down syndrome: Potential application in the detection of mild cognitive impairment.

Background: Down syndrome (DS) is considered the most frequent cause of early-onset Alzheimer's disease (AD), and the typical pathophysiological signs are present in almost all individuals with DS by the age of 40. Despite of this evidence, the investigation on the pre-dementia stages in DS is scarce. In the present study we analyzed the complexity of brain oscillatory patterns and neuropsychological performance for the characterization of mild cognitive impairment (MCI) in DS. Materials and methods: Lempel-Ziv complexity (LZC) values from resting-state magnetoencephalography recordings and the neuropsychological performance in 28 patients with DS [control DS group (CN-DS) (n = 14), MCI group (MCI-DS) (n = 14)] and 14 individuals with typical neurodevelopment (CN-no-DS) were analyzed. Results: Lempel-Ziv complexity was lowest in the frontal region within the MCI-DS group, while the CN-DS group showed reduced values in parietal areas when compared with the CN-no-DS group. Also, the CN-no-DS group exhibited the expected pattern of significant increase of LZC as a function of age, while MCI-DS cases showed a decrease. The combination of reduced LZC values and a divergent trajectory of complexity evolution with age, allowed the discrimination of CN-DS vs. MCI-DS patients with a 92.9% of sensitivity and 85.7% of specificity. Finally, a pattern of mnestic and praxic impairment was significantly associated in MCI-DS cases with the significant reduction of LZC values in frontal and parietal regions (p = 0.01). Conclusion: Brain signal complexity measured with LZC is reduced in DS and its development with age is also disrupted. The combination of both features might assist in the detection of MCI within this population.

Cognitive training in adults with intellectual disability: pilot study applying a cognitive tele-rehabilitation program.

Introduction: This pilot study analyzes the effect of a cognitive training program in adults with intellectual disability (ID). Method: Twenty subjects (mean age 52.7 ± 9.77 years) with mild and moderate ID were divided in control and experimental group. Only the experimental group received the training program. This program was applied through the GNPT® (Guttmann, NeuroPersonalTrainer®) platform for people with ID. Results: The results revealed a significant improvement in the Kaufman Brief Intelligence Test-2 scores (Matrices subtest) in the experimental group [Z = 2.12; p = .03] after the intervention, indicating an enhancement in fluid ability due to effect of cognitive training program. Conclusion: Findings provide evidence of the importance of applying these programs in a systematized way in adults with ID.

One Year of Recombinant Human Growth Hormone Treatment in Adults with Prader-Willi Syndrome Improves Body Composition, Motor Skills and Brain Functional Activity in the Cerebellum.

We compared body composition, biochemical parameters, motor function, and brain neural activation in 27 adults with Prader-Willi syndrome and growth-hormone deficiency versus age-and sex-matched controls and baseline versus posttreatment values of these parameters after one year of recombinant human growth hormone (rhGH) treatment. To study body composition, we analyzed percentage of fat mass, percentage of lean mass, and muscle-mass surrogate variables from dual X-ray absorptiometry. Biochemical parameters analyzed included IGF-I, glucose metabolism, and myokines (myostatin, irisin, and IL6). To explore muscle function, we used dynamometer-measured handgrip strength, the Timed Up and Go (TUG) test, and the Berg Balance Scale (BBS). To study brain activation, we acquired functional magnetic resonance images during three motor tasks of varying complexity. After one year of treatment, we observed an increase in lean mass and its surrogates, a decrease in fat mass, improvements in TUG test and BBS scores, and increased neural activation in certain cerebellar areas. The treatment did not significantly worsen glucose metabolism, and no side-effects were reported. Our findings support the benefits of rhGH treatment in adults with Prader-Willi syndrome and growth-hormone deficiency on body composition and suggest that it may also improve balance and brain neural activation.

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.

Hypersynchronized Magnetoencephalography Brain Networks in Patients with Mild Cognitive Impairment and Alzheimer's Disease in Down Syndrome.

Introduction: The majority of individuals with Down syndrome (DS) show signs of Alzheimer's disease (AD) neuropathology in their fourth decade. However, there is a lack of specific markers for characterizing the disease stages while considering this population's differential features. Methods: Forty-one DS individuals participated in the study, and were classified into three groups according to their clinical status: Alzheimer's disease (AD-DS), mild cognitive impairment (MCI-DS), and controls (CN-DS). We performed an exhaustive neuropsychological evaluation and assessed brain functional connectivity (FC) from magnetoencephalographic recordings. Results: Compared with CN-DS, both MCI-DS and AD-DS showed a pattern of increased FC within the high alpha band. The neuropsychological assessment showed a generalized cognitive impairment, especially affecting mnestic functions, in MCI-DS and, more pronouncedly, in AD-DS. Discussion: These findings might help to characterize the AD-continuum in DS. In addition, they support the role of the excitatory/inhibitory imbalance as a key pathophysiological factor in AD. Impact statement The pattern of functional connectivity (FC) hypersynchronization found in this study resembles the largely reported Alzheimer's disease (AD) FC evolution pattern in population with typical development. This study supports the hypothesis of the excitatory/inhibitory imbalance as a key pathophysiological factor in AD, and its conclusions could help in the characterization and prediction of Down syndrome individuals with a greater likelihood of converting to dementia.

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.

Growth Hormone (GH) Treatment Decreases Plasma Kisspeptin Levels in GH-Deficient Adults with Prader-Willi Syndrome.

Obesity and growth hormone (GH)-deficiency are consistent features of Prader-Willi syndrome (PWS). Centrally, kisspeptin is involved in regulating reproductive function and can stimulate hypothalamic hormones such as GH. Peripherally, kisspeptin signaling influences energy and metabolic status. We evaluated the effect of 12-month GH treatment on plasma kisspeptin levels in 27 GH-deficient adult PWS patients and analyzed its relationship with metabolic and anthropometric changes. Twenty-seven matched obese subjects and 22 healthy subjects were also studied. Before treatment, plasma kisspeptin concentrations in PWS and obese subjects were similar (140.20 (23.5-156.8) pg/mL vs. 141.96 (113.9-165.6) pg/mL, respectively, p = 0.979)) and higher (p = 0.019) than in healthy subjects (124.58 (107.3-139.0) pg/mL); plasma leptin concentrations were similar in PWS and obese subjects (48.15 (28.80-67.10) ng/mL vs. 33.10 (20.50-67.30) ng/mL, respectively, p = 0.152) and higher (p < 0.001) than in healthy subjects (14.80 (11.37-67.30) ng/mL). After GH therapy, lean body mass increased 2.1% (p = 0.03), total fat mass decreased 1.6% (p = 0.005), and plasma kisspeptin decreased to levels observed in normal-weight subjects (125.1(106.2-153.4) pg/mL, p = 0.027). BMI and leptin levels remained unchanged. In conclusion, 12-month GH therapy improved body composition and decreased plasma kisspeptin in GH deficient adults with PWS. All data are expressed in median (interquartile range).

Cerebellar Dysfunction in Adults with Prader Willi Syndrome.

Severe hypotonia during infancy is a hallmark feature of Prader Willi syndrome (PWS). Despite its transient expression, moto development is delayed and deficiencies in motor coordination are present at older ages, with no clear pathophysiological mechanism yet identified. The diverse motor coordination symptoms present in adult PWS patients could be, in part, the result of a common alteration(s) in basic motor control systems. We aimed to examine the motor system in PWS using functional MRI (fMRI) during motor challenge. Twenty-three adults with PWS and 22 matched healthy subjects participated in the study. fMRI testing involved three hand motor tasks of different complexity. Additional behavioral measurements of motor function were obtained by evaluating hand grip strength, functional mobility, and balance. Whole brain activation maps were compared between groups and correlated with behavioral measurements. Performance of the motor tasks in PWS engaged the neural elements typically involved in motor processing. While our data showed no group differences in the simplest task, increasing task demands evoked significantly weaker activation in patients in the cerebellum. Significant interaction between group and correlation pattern with measures of motor function were also observed. Our study provides novel insights into the neural substrates of motor control in PWS by demonstrating reduced cerebellar activation during movement coordination.

Hunger and Satiety Peptides: Is There a Pattern to Classify Patients with Prader-Willi Syndrome?

Hyperphagia is one of the main problems of patients with Prader-Willi syndrome (PWS) to cope with everyday life. The underlying mechanisms are not yet well understood. Gut-brain hormones are an interrelated network that may be at least partially involved. We aimed to study the hormonal profile of PWS patients in comparison with obese and healthy controls. Thirty adult PWS patients (15 men; age 27.5 ± 8.02 years; BMI 32.4 ± 8.14 kg/m2), 30 obese and 30 healthy controls were studied before and after eating a hypercaloric liquid diet. Plasma brain-derived neurotrophic factor (BDNF), leptin, total and active ghrelin, peptide YY (PYY), pancreatic polypeptide (PP), Glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and amylin were determined at times 0', 30', 60' and 120'. Cluster analysis was used. When considering all peptides together, two clusters were established according to fasting hormonal standardized concentrations. Cluster 1 encompassed most of obese (25/30) and healthy controls (28/30). By contrast, the majority of patients with PWS were located in Cluster 2 (23/27) and presented a similar fasting profile with hyperghrelinemia, high levels of leptin, PYY, GIP and GLP-1, compared to Cluster 1; that may reflect a dysfunction of these hunger/satiety hormones. When peptide behavior over the time was considered, PP concentrations were not sustained postprandially from 60 min onwards in Cluster 2. BDNF and amylin did not help to differentiate the two clusters. Thus, cluster analysis could be a good tool to distinguish and characterize the differences in hormone responses between PWS and obese or healthy controls.

Efficacy and safety of a GABAergic drug (Gamalate® B6): effects on behavior and cognition in young adults with borderline-to-mild intellectual developmental disabilities and ADHD.

BACKGROUND: We evaluated Gamalate® B6 (GB6) in patients with borderline intellectual functioning (BIF) or mild intellectual development disability (IDD). PATIENTS AND METHODS: This was a prospective phase IV observational pilot study in 30 patients who underwent neuropsychological evaluation during treatment with GB6 for 12 weeks. RESULTS: In comparison with baseline, the responses were positive, with a significant improvement in hyperactivity (51.7%), irritability (35.5%), and logorrhea (50%), and no sedative effect. The Clinical Global Impressions - Severity (CGI-S) score was much improved or very much improved in 73% of cases. Reaction time was better with fewer errors, thus indicating an improvement in attentional processes. A statistically significant result was obtained for the number of movements used to solve the problem and for the total number of correctly solved problems. CONCLUSION: In this pilot study, GB6 was effective and well tolerated in cases of ADHD and challenging behavior in young adults with borderline-to-mild BIF/IDD. However, given the small number of patients involved and the uncontrolled nature of the study, these results should be viewed cautiously.