Miguel Casas

Attention deficit hyperactivity disorder in adults

Abstract Objective. To examine available literature regarding attention deficit hyperactivity disorder (ADHD) in adults. Methods. An electronic literature search of peer-reviewed English language articles using MEDLINE (without time limits) was undertaken. Results. Symptoms of ADHD in adults exert a substantial negative impact on daily life, including work, social life and relationships. Co-morbidities are common, further impairing quality of life. Diagnosis of adult ADHD can be difficult, as current criteria require evidence of symptom onset before the age of 7 years and impact on activities typically undertaken by children. Drug therapy is the first-line treatment for adult ADHD, particularly stimulant medication. However, methylphenidate (MPH) immediate-release tablets require three or more times daily dosing, which can impact on compliance, while demonstrating a loss of symptomatic benefit later in the day. Extended-release preparations of MPH, mixed amphetamine salts and dexamphetamine can provide symptom control for 6–12 h and the non-stimulant atomoxetine has demonstrated benefit in reducing ADHD symptoms. These therapies are generally well tolerated, but may be associated with adverse effects on the cardiovascular system, which need to be further assessed in controlled clinical trials. Psychological therapy may be beneficial in adults who continue to experience clinically significant symptoms while receiving pharmacotherapy. Conclusion. Further research in all areas of adult ADHD is urgently needed.

Psychiatric comorbidity in treatment‐seeking substance use disorder patients with and without attention deficit hyperactivity disorder: results of the IASP study

AIMSnTo determine comorbidity patterns in treatment-seeking substance use disorder (SUD) patients with and without adult attention deficit hyperactivity disorder (ADHD), with an emphasis on subgroups defined by ADHD subtype, taking into account differences related to gender and primary substance of abuse.nnnDESIGNnData were obtained from the cross-sectional International ADHD in Substance use disorder Prevalence (IASP) study.nnnSETTINGnForty-seven centres of SUD treatment in 10 countries.nnnPARTICIPANTSnA total of 1205 treatment-seeking SUD patients.nnnMEASUREMENTSnStructured diagnostic assessments were used for all disorders: presence of ADHD was assessed with the Conners Adult ADHD Diagnostic Interview for DSM-IV (CAADID), the presence of antisocial personality disorder (ASPD), major depression (MD) and (hypo)manic episode (HME) was assessed with the Mini International Neuropsychiatric Interview-Plus (MINI Plus), and the presence of borderline personality disorder (BPD) was assessed with the Structured Clinical Interview for DSM-IV Axis II (SCID II).nnnFINDINGSnThe prevalence of DSM-IV adult ADHD in this SUD sample was 13.9%. ASPD [odds ratio (OR)u2009=u20092.8, 95% confidence interval (CI)u2009=u20091.8-4.2], BPD (ORu2009=u20097.0, 95% CIu2009=u20093.1-15.6 for alcohol; ORu2009=u20093.4, 95% CIu2009=u20091.8-6.4 for drugs), MD in patients with alcohol as primary substance of abuse (ORu2009=u20094.1, 95% CIu2009=u20092.1-7.8) and HME (ORu2009=u20094.3, 95% CIu2009=u20092.1-8.7) were all more prevalent in ADHD(+) compared with ADHD(-) patients (Pu2009<u20090.001). These results also indicate increased levels of BPD and MD for alcohol compared with drugs as primary substance of abuse. Comorbidity patterns differed between ADHD subtypes with increased MD in the inattentive and combined subtype (Pu2009<u20090.01), increased HME and ASPD in the hyperactive/impulsive (Pu2009<u20090.01) and combined subtypes (Pu2009<u20090.001) and increased BPD in all subtypes (Pu2009<u20090.001) compared with SUD patients without ADHD. Seventy-five per cent of ADHD patients had at least one additional comorbid disorder compared with 37% of SUD patients without ADHD.nnnCONCLUSIONSnTreatment-seeking substance use disorder patients with attention deficit hyperactivity disorder are at a very high risk for additional externalizing disorders.

Variability in the prevalence of adult ADHD in treatment seeking substance use disorder patients: Results from an international multi-center study exploring DSM-IV and DSM-5 criteria

Background Available studies vary in their estimated prevalence of attention deficit/hyperactivity disorder (ADHD) in substance use disorder (SUD) patients, ranging from 2 to 83%. A better understanding of the possible reasons for this variability and the effect of the change from DSM-IV to DSM-5 is needed. Methods A two stage international multi-center, cross-sectional study in 10 countries, among patients form inpatient and outpatient addiction treatment centers for alcohol and/or drug use disorder patients. A total of 3558 treatment seeking SUD patients were screened for adult ADHD. A subsample of 1276 subjects, both screen positive and screen negative patients, participated in a structured diagnostic interview. Results Prevalence of DSM-IV and DSM-5 adult ADHD varied for DSM-IV from 5.4% (CI 95%: 2.4–8.3) for Hungary to 31.3% (CI 95%:25.2–37.5) for Norway and for DSM-5 from 7.6% (CI 95%: 4.1–11.1) for Hungary to 32.6% (CI 95%: 26.4–38.8) for Norway. Using the same assessment procedures in all countries and centers resulted in substantial reduction of the variability in the prevalence of adult ADHD reported in previous studies among SUD patients (2–83%→ 5.4–31.3%). The remaining variability was partly explained by primary substance of abuse and by country (Nordic versus non-Nordic countries). Prevalence estimates for DSM-5 were slightly higher than for DSM-IV. Conclusions Given the generally high prevalence of adult ADHD, all treatment seeking SUD patients should be screened and, after a confirmed diagnosis, treated for ADHD since the literature indicates poor prognoses of SUD in treatment seeking SUD patients with ADHD.

Genome-wide copy number variation analysis in adult attention-deficit and hyperactivity disorder

Attention-deficit and hyperactivity disorder (ADHD) is a common psychiatric disorder with a worldwide prevalence of 5-6% in children and 4.4% in adults. Recently, copy number variations (CNVs) have been implicated in different neurodevelopmental disorders such as ADHD. Based on these previous reports that focused on pediatric cohorts, we hypothesize that structural variants may also contribute to adult ADHD and that such genomic variation may be enriched for CNVs previously identified in children with ADHD. To address this issue, we performed for the first time a whole-genome CNV study on 400 adults with ADHD and 526 screened controls. In agreement with recent reports in children with ADHD or in other psychiatric disorders, we identified a significant excess of insertions in ADHD patients compared to controls. The overall rate of CNVs >100xa0kb was 1.33 times higher in ADHD subjects than in controls (pxa0=xa02.4e-03), an observation mainly driven by a higher proportion of small events (from 100xa0kb to 500xa0kb; 1.35-fold; pxa0=xa01.3e-03). These differences remained significant when we considered CNVs that overlap genes or when structural variants spanning candidate genes for psychiatric disorders were evaluated, with duplications showing the greatest difference (1.41-fold, pxa0=xa00.024 and 2.85-fold, pxa0=xa08.5e-03, respectively). However, no significant enrichment was detected in our ADHD cohort for childhood ADHD-associated CNVs, CNVs previously identified in at least one ADHD patient or CNVs previously implicated in autism or schizophrenia. In conclusion, our study provides tentative evidence for a higher rate of CNVs in adults with ADHD compared to controls and contributes to the growing list of structural variants potentially involved in the etiology of the disease.

Association study of 37 genes related to serotonin and dopamine neurotransmission and neurotrophic factors in cocaine dependence

Cocaine dependence is a neuropsychiatric disorder in which both environmental and genetic factors are involved. Several processes, that include reward and neuroadaptations, mediate the transition from use to dependence. In this regard, dopamine and serotonin neurotransmission systems are clearly involved in reward and other cocaine‐related effects, whereas neurotrophic factors may be responsible for neuroadaptations associated with cocaine dependence. We examined the contribution to cocaine dependence of 37 genes related to the dopaminergic and serotoninergic systems, neurotrophic factors and their receptors through a case–control association study with 319 single nucleotide polymorphisms selected according to genetic coverage criteria in 432 cocaine‐dependent patients and 482 sex‐matched unrelated controls. Single marker analyses provided evidence for association of the serotonin receptor HTR2A with cocaine dependence [rs6561333; nominal P‐value adjusted for ageu2009=u20091.9e−04, odds ratiou2009=u20091.72 (1.29–2.30)]. When patients were subdivided according to the presence or absence of psychotic symptoms, we confirmed the association between cocaine dependence and HTR2A in both subgroups of patients. Our data show additional evidence for the involvement of the serotoninergic system in the genetic susceptibility to cocaine dependence.

Association of neurexin 3 polymorphisms with smoking behavior.

The Neurexin 3 gene (NRXN3) has been associated with dependence on various addictive substances, as well as with the degree of smoking in schizophrenic patients and impulsivity among tobacco abusers. To further evaluate the role of NRXN3 in nicotine addiction, we analyzed single nucleotide polymorphisms (SNPs) and a copy number variant (CNV) within the NRXN3 genomic region. An initial study was carried out on 157 smokers and 595 controls, all of Spanish Caucasian origin. Nicotine dependence was assessed using the Fagerström index and the number of cigarettes smoked per day. The 45 NRXN3 SNPs genotyped included all the SNPs previously associated with disease, and a previously described deletion within NRXN3. This analysis was replicated in 276 additional independent smokers and 568 controls. Case–control association analyses were performed at the allele, genotype and haplotype levels. Allelic and genotypic association tests showed that three NRXN3 SNPs were associated with a lower risk of being a smoker. The haplotype analysis showed that one block of 16 Kb, consisting of two of the significant SNPs (rs221473 and rs221497), was also associated with lower risk of being a smoker in both the discovery and the replication cohorts, reaching a higher level of significance when the whole sample was considered [odds ratio = 0.57 (0.42–0.77), permuted P = 0.0075]. By contrast, the NRXN3 CNV was not associated with smoking behavior. Taken together, our results confirm a role for NRXN3 in susceptibility to smoking behavior, and strongly implicate this gene in genetic vulnerability to addictive behaviors.

Epidemiology of psychiatric morbidity among migrants compared to native born population in Spain: a controlled study

OBJECTIVEnThe aim of this paper is to explore the prevalence of psychiatric morbidity in different immigrant groups in Spain. In keeping with prior studies carried out in Europe, it is expected that the immigrant population will have elevated levels of psychopathology, with some variation across immigrant groups.nnnMETHODnnnnDESIGNnMulticenter, observational, cross-sectional study.nnnSETTINGnPrimary care settings of two Spanish regions.nnnSAMPLEnN=1.503 immigrants paired with the same number of Spanish controls, adjusted by gender and age.nnnVARIABLESnDemographic variables, MINI International Neuropsychiatric Interview and Standardized Polyvalent Psychiatric Interview, somatic symptoms section. Students t tests, ORs and logistic regressions were used to analyze the data.nnnRESULTSnNo differences in psychiatric morbidity were found (native born 30.9%, population vs. immigrants 29.6%, OR=.942, CI=.806-1.100) when comparing immigrants to native born Spaniards. Relative to Spaniards (30.9%), Latin American immigrants had significantly higher levels of psychopathology (36.8%), Sub-Saharan Africans (24.4%) and Asians (16%) had significantly lower levels, and Eastern Europeans (31.4%) and North Africans (26.8%) showed no significant difference.nnnCONCLUSIONSnThe hypotheses were only partially supported. Although overall immigrants did not differ from the native born population, when analyzed by geographic origin, only Latin Americans had higher levels of psychopathology. It is concluded that multiple factors need to be taken into consideration when studying the mental health of immigrants given that different immigrant groups have different levels of psychopathology.

Relationship between poor decision-making process and fatigue perception in Parkinson's disease patients.

BACKGROUNDnFatigue is a common non-motor symptom in Parkinsons disease patients. The reasons for its perception are not completely understood. One suggested possibility might be that perceived fatigue is related with abnormal interpretation of somatic symptoms. It has been described that somatic markers misinterpretation leads to poor decision-making. We hypothesized that fatigued Parkinsons disease patients would show poorer performance than non-fatigued in a decision-making task.nnnMETHODSnTo test our hypothesis, 89 Parkinsons disease patients were assessed for the presence of fatigue using the Parkinson Fatigue Scale. All patients were also administered scales evaluating psychopathology and neuropsychological tests, including the Iowa Gambling Task.nnnRESULTSn33 (37.1%) patients fulfilled the established criteria for fatigue. In the univariate analysis, fatigued patients showed higher levels of anxiety (state: p = 0.001, trait: p < 0.001), impulsivity (p = 0.051), and depression (p < 0.001) than non-fatigued patients. No statistically significant differences in other neuropsychological test results (Stroop, Trail Making Test, Tower of London) were found between fatigued and non-fatigued patients except for the Iowa Gambling Task, in which fatigued patients showed poorer performance (p = 0.001) after controlling for confounding factors.nnnCONCLUSIONSnThese results suggest that fatigued Parkinsons disease patients may present abnormal decision-making process, which may reflect abnormal processing of somatic markers when faced with an activity that requires effort.

Serum Brain-Derived Neurotrophic Factor Levels and Cocaine-Induced Transient Psychotic Symptoms

Background: Cocaine-induced psychosis (CIP) is among the most serious adverse effects of cocaine. Reduced serum brain-derived neurotrophic factor (BDNF) levels have been reported in schizophrenia and psychosis; however, studies assessing the involvement of BDNF in CIP are lacking. Methods: A total of 22 cocaine-dependent patients (aged 33.65 ± 6.85) who had never experienced psychotic symptoms under the influence of cocaine (non-CIP) and 18 patients (aged 34.18 ± 8.54) with a history of CIP completed a 2-week detoxification program in an inpatient facility. Two serum samples were collected from each patient at baseline and at the end of the protocol. Demographic, consumption and clinical data were recorded for all patients. A paired group of healthy controls was also included. Results: At the beginning of the detoxification treatment, serum BDNF levels were similar in both the non-CIP and the CIP groups. During early abstinence, the non-CIP group exhibited a significant increase in serum BDNF levels (p = 0.030), whereas the CIP group exhibited a decrease. Improvements in depression (Beck Depression Inventory, BDI, p = 0.003) and withdrawal symptoms (Cocaine Selective Severity Assessment, CSSA, p = 0.013) show a significant positive correlation with serum BDNF levels in the non-CIP group, whereas no correlation between the same variables was found in the CIP group. Conclusions: This study suggests that BDNF plays a role in the transient psychotic symptoms associated with cocaine consumption. In the non-CIP group, the increase in serum BDNF appears to be driven by the effects of chronic cocaine consumption and withdrawal. In contrast, patients with CIP share some of the neurotrophic deficiencies that characterize schizophrenia and psychosis.

Effectiveness of combined individual and group dialectical behavior therapy compared to only individual dialectical behavior therapy: a preliminary study.

Dialectical behavior therapy (DBT) is an effective therapy. However, treating borderline personality disorder (BPD) patients with standard DBT can be problematic in some institutions due to logistical or cost limitations. The aim of this preliminary study is to examine the efficacy of Individual DBT in 37 BPD patients, compared with Combined individual/Group DBT in 14 BPD patients. Outcome measures included suicide attempts, self-harm behaviors, and visits to emergency departments. These variables were examined at pretreatment, 12 months/end of treatment, and at an 18-month follow-up. In addition, dropout rates were examined. Significant improvements on the outcome measures were observed across both versions of DBT treatment, particularly at the 18-month follow-up assessment. No significant differences were observed between Individual DBT and Combined individual/Group DBT on any of the posttreatment evaluations. An individual version of DBT may be an effective and less costly option for BPD treatment. Larger controlled trials are needed to confirm the results.