Sergi Valero

Association Study of 10 Genes Encoding Neurotrophic Factors and Their Receptors in Adult and Child Attention-Deficit/Hyperactivity Disorder

BACKGROUND Attention-deficit/hyperactivity disorder (ADHD) is a common childhood-onset psychiatric disorder that often persists into adolescence and adulthood and is characterized by inappropriate levels of inattention, hyperactivity, and/or impulsivity. Genetic and environmental factors are believed to be involved in the continuity of the disorder as well as in changes in ADHD symptomatology throughout life. Neurotrophic factors (NTFs), which participate in neuronal survival and synaptic efficiency, are strong candidates to contribute to the neuroplasticity changes that take place in the human central nervous system during childhood, adolescence, and early adulthood and might be involved in the genetic predisposition to ADHD. METHODS We performed a population-based association study in 546 ADHD patients (216 adults and 330 children) and 546 gender-matched unrelated control subjects with 183 single nucleotide polymorphisms covering 10 candidate genes that encode four neurotrophins (NGF, BDNF, NTF3, and NTF4/5), a member of the cytokine family of NTFs (CNTF), and their receptors (NTRK1, NTRK2, NTRK3, NGFR, and CNTFR). RESULTS The single-marker and haplotype-based analyses provided evidence of association between CNTFR and both adulthood (p = .0077, odds ratio [OR] = 1.38) and childhood ADHD (p = 9.1e-04, OR = 1.40) and also suggested a childhood-specific contribution of NTF3 (p = 3.0e-04, OR = 1.48) and NTRK2 (p = .0084, OR = 1.52) to ADHD. CONCLUSIONS Our data suggest that variations in NTFs might be involved in the genetic susceptibility to ADHD, support the contribution of the CNTFR locus as a predisposition factor for the disorder, and suggest that NTF3 and NTRK2 might be involved in the molecular basis of the age-dependent changes in ADHD symptoms throughout life span.

A Longitudinal Follow-Up of 550 Mild Cognitive Impairment Patients: Evidence for Large Conversion to Dementia Rates and Detection of Major Risk Factors Involved

The most recent studies about mild cognitive impairment (MCI) are focused on the search for factors that make patients more vulnerable to conversion to dementia, mainly Alzheimers disease (AD). The aim of this study was to determine which neuropsychological test performances, including episodic memory profiles, and genetic risk factors (APOE ε4) better predict early conversion to dementia among the four MCI subtypes. Data from 550 MCI patients were analyzed for the purpose of this study and were classified according to Petersens criteria (2004), and also taking into account the absence (probable MCI) or presence (possible MCI) of comorbidities that could explain cognitive deficits. MCI cases were divided into Probable amnestic (Pr-aMCI) (n = 115), probable non-amnestic (Pr-naMCI) (n = 37), possible amnestic (Pss-aMCI) (n = 234), and possible non-amnestic (Pss-naMCI) (n = 164), single or multiple domain. In the whole MCI sample, regression analysis showed that low performances on Orientation, Verbal Delayed Recall of the Word List Learning test from WMS-III, and Lurias Clock test were associated with conversion to dementia, independently of APOE ε4 allele. Cox proportional-hazards showed that the Probable MCI subtype, presence of storage memory impairment, multiple domain condition, and presence of at least one ε4 allele increased the risk of conversion to dementia. Multivariate survival and Kapplan-Meier analyses showed that the Pr-aMCI with storage memory impairment had the most and closest risk of conversion to dementia. In conclusion, the Pr-aMCI subset of patients had 8.5 times more risk of converting to dementia than the Pss-naMCI group, who displayed the slowest conversion rate to dementia.

COMORBID ATTENTION-DEFICIT/ HYPERACTIVITY DISORDER IN BORDERLINE PATIENTS DEFINES AN IMPULSIVE SUBTYPE OF BORDERLINE PERSONALITY DISORDER

In order to examine the impulsive profile of a BPD sample with comorbid ADHD, adult patients who met criteria for BPD were assessed for ADHD with the CAADID and the WURS. A high rate of ADHD in the BPD sample was found, with sixty-nine (38.1%) BPD patients diagnosed as having comorbid adult ADHD. BPD-ADHD group had higher rates of general substance use disorder (59.4% vs. 38.4%), antisocial personality disorder (7.2% vs. 0.9%) and obsessive-compulsive personality disorder (21.7% vs. 6.3%). The BPD group without comorbid adult ADHD showed a higher rate of mood disorders (62.5% vs. 37.7%), panic disorders (54.5% vs. 23.1%) and benzodiazepine abuse (18.8% vs. 5.8%). Only in BPD patients without ADHD was comorbid avoidant personality disorder found. BPD patients could be distinguished in two clear subgroups related to the adult ADHD comorbidity. BPD-ADHD patients showed a more homogeneous and impulsive profile while BPD without ADHD comorbidity had more anxiety and depressive disorders.

Acculturative stress as a risk factor of depression and anxiety in the Latin American immigrant population

This study explores acculturative stress as a risk factor for depressive and anxiety disorders as well as their symptomatology. It is hypothesized that perceived discrimination and general psychosocial stress will show the greatest association with psychopathology. The sample consists of 414 Latin American immigrant primary care patients in Barcelona. The instruments used are: the Barcelona Immigration Stress Scale (BISS) to evaluate acculturative stress, the Goldberg Anxiety and Depression Scale (GADS) for anxiety and depression symptoms, the Mini International Neurological Interview (MINI), a semi-structured interview, to detect psychiatric pathology, and a questionnaire for sociodemographic and attitudinal characteristics. The most elevated levels of acculturative stress were observed in the factors homesickness and general psychosocial stress. Acculturative stress is associated with depression and anxiety. With the covariants controlled, intercultural contact stress and general psychosocial stress maintain the relationship. Acculturative stress constitutes a risk factor for both depression and anxiety. General psychosocial stress and intercultural contact stress are related to psychopathology. Perceived discrimination and homesickness are not associated with psychopathology in the Spanish context, suggesting that cultural congruity plays a key role in the relationship between immigration and mental health.

Effect of Switching Drug Formulations from Immediate-Release to Extended-Release OROS Methylphenidate

AbstractBackground: The potential advantages of osmotic-release oral system (OROS) methylphenidate (Concerta®) over immediate-release (IR) methylphenidate (Rubifen®) in adults with attention-deficit hyperactivity disorder (ADHD), with respect to medication adherence, effectiveness and tolerability, are yet to be determined. Objective: To compare the adherence, effectiveness and tolerability of OROS methylphenidate versus IR methylphenidate in adults with ADHD. It was hypothesized (after data collection) that adherence and effectiveness would be higher with OROS methylphenidate than with the IR formulation. Study design: A chart review was carried out from April 2004 until April 2005. Setting: Adult ADHD outpatient program in a general hospital in Spain. Patients: Seventy adults with ADHD who met DSM-IV-TR criteria and who did not have any other current major psychiatric disorder. Intervention: Patients were treated with IR methylphenidate three times daily for 3 months and then switched to OROS methylphenidate once daily. Main outcome measure: Effectiveness was assessed by means of the ADHD rating scale-IV (ADHD-RS-IV) and the Clinical Global Impression-Improvement (CGI-I) scale at 3 months (coinciding with treatment switch) and at 6 months. The Simplified Medication Adherence Questionnaire (SMAQ) was used to assess treatment adherence, and was administered at both 3 and 6 months. Results: Seventy adult ADHD patients (mean age ± SD: 30 ± 9.6 years; n = 48 men [68.6%]) were included in this study. The mean baseline ADHD-RS-IV score was 34.6 (SD = 10.9). The mean daily dose of IR methylphenidate was 52.1 mg (SD = 13.8 mg) administered as three divided doses. After the treatment switch, the mean OROS methylphenidate daily dose was 57.9 mg (SD = 16.5 mg) administered once daily.The switch from IR methylphenidate to OROS methylphenidate was associated with a statistically significant improvement in all items of the SMAQ questionnaire. OROS methylphenidate was more effective than IR methylphenidate (p = 0.0005) in reducing symptoms of ADHD. The percentage of responders was 28.6% with IR methylphenidate and 91.4% with the OROS formulation (p = 0.0005). OROS methylphenidate was preferred by 97% of patients. The most common adverse events for each formulation were dry mouth (30% IR methylphenidate) and mood instability (31% OROS methylphenidate). No patients stopped treatment with methylphenidate because of adverse events. Conclusions: The switch from IR to OROS methylphenidate was associated with an improvement in both adherence and effectiveness. There were no differences between IR and OROS methylphenidate in terms of tolerability.

Psychometric Properties of the Zuckerman-Kuhlman Personality Questionnaire in a Spanish Sample

An important question in trait theory is how many major traits are necessary to describe personality and exactly what traits these are. Several investigators have made attempts to answer these questions with solutions of 3, 5, and even 16 primary factors. The Zuckerman-Kuhlman Personality Questionnaire (ZKPQ) is a questionnaire aimed at the evaluation of a five-factor model, which emerged from factor analyses of scales and items. The results were five basic factors, similar in men and women: Neuroticism-Anxiety, Activity, Sociability, Impulsive Sensation-Seeking, and Aggression-Hostility. This study assesses the psychometric properties of the Catalan translation of the ZKPQ. The ZKPQ was administered to a total sample of 933 subjects with an age range from 17 to 25 years. The results obtained show good internal consistency of all the scales and good discriminant validity shown by the lack of correlation among scales. Gender differences are also in the predicted directions. Finally, the replicability of th...

Ecological assessment of executive functions in mild cognitive impairment and mild Alzheimer's disease.

Although memory deficits are typically the earliest and most profound symptoms of Alzheimers disease (AD) and mild cognitive impairment (MCI), there is increasing recognition of subtle executive dysfunctions in these patients. The purpose of the present study was to determine the sensitivity of the Behavioral Assessment of the Dysexecutive Syndrome (BADS), and to detect early specific signs of the dysexecutive syndrome in the transition from normal cognition to dementia. The BADS was administered to 50 MCI subjects, 50 mild AD patients, and 50 normal controls. Statistically significant differences were found among the three groups with the AD patients performing most poorly, and the MCI subjects performing between controls and AD patients. The Rule Shift Cards and the Action Program subtests were the most highly discriminative between MCI and controls; the Zoo Map and Modified Six Elements between MCI and AD; and the Action Program, Zoo Map, and Modified Six Elements between AD and controls. These results demonstrate that the BADS is clinically useful in discriminating between normal cognition and progressive neurodegenerative conditions. Furthermore, these data confirm the presence of a dysexecutive syndrome even in mildly impaired elderly subjects.

Risk factors for cocaine-induced psychosis in cocaine-dependent patients.

Cocaine consumption can induce transient psychotic symptoms, expressed as paranoia or hallucinations. Cocaine induced psychosis (CIP) is common but not developed in all cases. This is the first European study on the relationship between CIP, consumption pattern variables and personality disorders. We evaluated 173 cocaine-dependent patients over 18 years; mostly males, whose average age was 33.6 years (SD=7.8). Patients attending an outpatient addictions department were enrolled in the study and subsequently systematically evaluated using SCID I and SCID II interviews for comorbid disorders, a clinical interview for psychotic symptoms and EuropASI for severity of addiction. A high proportion of cocaine dependent patients reported psychotic symptoms under the influence of cocaine (53.8%), the most frequently reported being paranoid beliefs and suspiciousness (43.9%). A logistic regression analysis was performed, finding that a model consisting of amount of cocaine consumption, presence of an antisocial personality disorder and cannabis dependence history had 66.2% sensitivity 75.8% specificity predicting the presence of CIP. In our conclusions, we discuss the relevance of evaluating CIP in all cocaine dependent-patients, and particularly in those fulfilling the clinical profile derived from our results. These findings could be useful for a clinical approach to the risks of psychotic states in cocaine-dependent patients.

Detection of visuoperceptual deficits in preclinical and mild Alzheimer’s disease

Exhaustive neuropsychological assessment of mild cognitive impairment (MCI) subjects frequently identifies cognitive deficits other than memory. However, visuoperception has rarely been investigated in MCI. The 15-Objects Test (15-OT), a visual discrimination task based on the Poppelreuter Test, consists of 15 overlapping objects. Poppelreuter-type tests are frequently used to detect visual agnosia. However, more complex tests, such as the 15-OT, are required to detect visuoperceptual signs in those patients who perform correctly on simple tests. The aim of the present study was to investigate visuoperceptual deficits in MCI patients and to assess the usefulness of the 15-OT to discriminate Alzheimers disease (AD) and MCI patients from controls. The 15-OT, and a neuropsychological battery included in the diagnostic assessment, was administered to 44 healthy controls, 44 MCI patients, and 44 mild AD patients. Performance on the 15-OT was significantly different between groups. MCI scored between AD and controls. When MCI and AD patients had relatively normal performance on simple tests (Poppelreuter), increased significant abnormalities were found by a more difficult visuoperceptual test (15-OT). Regression analyses showed that the 15-OT was a significant predictor of group membership, but the Poppelreuter Test did not significantly contribute to the models. Visuoperceptual processing is impaired early in the clinical course of AD. The 15-OT allows detection of visuoperceptual deficits in the preclinical and mild AD stages, when classical tests are still unable to detect subtle deficits. So, its inclusion in neuropsychological batteries that are nowadays used in the clinical practice would allow increasing their diagnostic potential.

Development and psychometric properties of the Verona Service Satisfaction Scale for methadone-treated opioid-dependent patients (VSSS-MT).

We adapted the 32-item Verona Service Satisfaction Scale (VSSS-32) to assess opioid-dependent patient satisfaction with services received from methadone treatment centres. The preliminary version of the VSSS for methadone treatment (VSSS-MT) was filled out anonymously and completed by 516 randomly recruited patients. After exploratory factor analysis and item refinement, the definitive 27-item VSSS-MT accounted for 58.8% of the total variance, comprising four factors: Basic Interventions, Specific Interventions, Social Worker Skills, and Psychologist Skills. These factors showed good to excellent internal reliabilities (Chronbachs alpha: 0.91, 0.85, 0.87, and 0.92, respectively). At test-retest, intraclass correlation coefficients of VSSS-MT overall and factor scores were fair to good. The results of this study suggest that the VSSS-MT measures, briefly but also multidimensionally, opioid-dependent patient satisfaction with methadone treatment centres.