Adult attention-deficit/hyperactivity disorder and nicotine withdrawal: a qualitative study of patient perceptions

Background: Nicotine use has been reported to ameliorate symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD). Furthermore, adults with ADHD have a relatively high prevalence of cigarette smoking and greater difficulty abstaining from smoking. Overall, though, there is scant literature investigating the beliefs, perceptions and experiences of smokers with ADHD regarding smoking cessation and withdrawal. Methods: Our participants (n = 20) fulfilling criteria for ADHD and a past or current dependence from nicotine were recruited from the in- and outpatient clinic of the Zurich University Psychiatric Hospital and the Psychiatric Services Aargau (Switzerland). We conducted in-depth interviews to explore their motivations to quit, past experiences with and expectations about quitting using a purposeful sampling plan. The sample was selected to provide diversity in relation to level of nicotine dependence, participation in a smoking-cessation program, gender, age, martial status and social class. Mayring’s qualitative content analysis approach was used to evaluate findings. Results: Adult smokers with ADHD had made several attempts to quit, experienced intense withdrawal symptoms, and relapsed early and often. They also often perceived a worsening of ADHD symptoms with nicotine abstinence. We identified three motives to quit smoking: 1) health concerns, 2) the feeling of being addicted, and 3) social factors. Most participants favored a smoking cessation program specifically designed for individuals with ADHD because they thought ADHD complicated their nicotine withdrawal and that an ADHD-specific smoking cessation program should address specific symptoms of this disorder. Conclusions: Since treatment initiation and adherence associate closely with perception, we hope these findings will result in better cessation interventions for the vulnerable subgroup of smokers with ADHD. Keywords: ADHD, Nicotine, Withdrawal, Subjective, Qualitative, Narrative

First clinical trial of tomographic neurofeedback in attention-deficit/hyperactivity disorder: evaluation of voluntary cortical control

Tomographic neurofeedback (tNF) training was evaluated as a treatment for attention-deficit/hyperactivity disorder (ADHD). To investigate the specificity of the treatment, outcomes were related to learning during tNF.

Altered response control and anterior cingulate function in attention-deficit/hyperactivity disorder boys

To investigate mechanisms and structures underlying prefrontal response control and inhibition in boys suffering from attention-deficit/hyperactivity disorder (ADHD).

Complex visual hallucinations and attentional performance in eye disease and dementia: a test of the Perception and Attention Deficit model

OBJECTIVE This study aimed to test the prediction from the Perception and Attention Deficit model of complex visual hallucinations (CVH) that impairments in visual attention and perception are key risk factors for complex hallucinations in eye disease and dementia. METHODS Two studies ran concurrently to investigate the relationship between CVH and impairments in perception (picture naming using the Graded Naming Test) and attention (Stroop task plus a novel Imagery task). The studies were in two populations-older patients with dementia (n = 28) and older people with eye disease (n = 50) with a shared control group (n = 37). The same methodology was used in both studies, and the North East Visual Hallucinations Inventory was used to identify CVH. RESULTS A reliable relationship was found for older patients with dementia between impaired perceptual and attentional performance and CVH. A reliable relationship was not found in the population of people with eye disease. CONCLUSIONS The results add to previous research that object perception and attentional deficits are associated with CVH in dementia, but that risk factors for CVH in eye disease are inconsistent, suggesting that dynamic rather than static impairments in attentional processes may be key in this population.

Psychological therapies for panic disorder with or without agoraphobia in adults: a network meta-analysis.

BACKGROUND Panic disorder is characterised by the presence of recurrent unexpected panic attacks, discrete periods of fear or anxiety that have a rapid onset and include symptoms such as racing heart, chest pain, sweating and shaking. Panic disorder is common in the general population, with a lifetime prevalence of 1% to 4%. A previous Cochrane meta-analysis suggested that psychological therapy (either alone or combined with pharmacotherapy) can be chosen as a first-line treatment for panic disorder with or without agoraphobia. However, it is not yet clear whether certain psychological therapies can be considered superior to others. In order to answer this question, in this review we performed a network meta-analysis (NMA), in which we compared eight different forms of psychological therapy and three forms of a control condition. OBJECTIVES To assess the comparative efficacy and acceptability of different psychological therapies and different control conditions for panic disorder, with or without agoraphobia, in adults. SEARCH METHODS We conducted the main searches in the CCDANCTR electronic databases (studies and references registers), all years to 16 March 2015. We conducted complementary searches in PubMed and trials registries. Supplementary searches included reference lists of included studies, citation indexes, personal communication to the authors of all included studies and grey literature searches in OpenSIGLE. We applied no restrictions on date, language or publication status. SELECTION CRITERIA We included all relevant randomised controlled trials (RCTs) focusing on adults with a formal diagnosis of panic disorder with or without agoraphobia. We considered the following psychological therapies: psychoeducation (PE), supportive psychotherapy (SP), physiological therapies (PT), behaviour therapy (BT), cognitive therapy (CT), cognitive behaviour therapy (CBT), third-wave CBT (3W) and psychodynamic therapies (PD). We included both individual and group formats. Therapies had to be administered face-to-face. The comparator interventions considered for this review were: no treatment (NT), wait list (WL) and attention/psychological placebo (APP). For this review we considered four short-term (ST) outcomes (ST-remission, ST-response, ST-dropouts, ST-improvement on a continuous scale) and one long-term (LT) outcome (LT-remission/response). DATA COLLECTION AND ANALYSIS As a first step, we conducted a systematic search of all relevant papers according to the inclusion criteria. For each outcome, we then constructed a treatment network in order to clarify the extent to which each type of therapy and each comparison had been investigated in the available literature. Then, for each available comparison, we conducted a random-effects meta-analysis. Subsequently, we performed a network meta-analysis in order to synthesise the available direct evidence with indirect evidence, and to obtain an overall effect size estimate for each possible pair of therapies in the network. Finally, we calculated a probabilistic ranking of the different psychological therapies and control conditions for each outcome. MAIN RESULTS We identified 1432 references; after screening, we included 60 studies in the final qualitative analyses. Among these, 54 (including 3021 patients) were also included in the quantitative analyses. With respect to the analyses for the first of our primary outcomes, (short-term remission), the most studied of the included psychological therapies was CBT (32 studies), followed by BT (12 studies), PT (10 studies), CT (three studies), SP (three studies) and PD (two studies).The quality of the evidence for the entire network was found to be low for all outcomes. The quality of the evidence for CBT vs NT, CBT vs SP and CBT vs PD was low to very low, depending on the outcome. The majority of the included studies were at unclear risk of bias with regard to the randomisation process. We found almost half of the included studies to be at high risk of attrition bias and detection bias. We also found selective outcome reporting bias to be present and we strongly suspected publication bias. Finally, we found almost half of the included studies to be at high risk of researcher allegiance bias.Overall the networks appeared to be well connected, but were generally underpowered to detect any important disagreement between direct and indirect evidence. The results showed the superiority of psychological therapies over the WL condition, although this finding was amplified by evident small study effects (SSE). The NMAs for ST-remission, ST-response and ST-improvement on a continuous scale showed well-replicated evidence in favour of CBT, as well as some sparse but relevant evidence in favour of PD and SP, over other therapies. In terms of ST-dropouts, PD and 3W showed better tolerability over other psychological therapies in the short term. In the long term, CBT and PD showed the highest level of remission/response, suggesting that the effects of these two treatments may be more stable with respect to other psychological therapies. However, all the mentioned differences among active treatments must be interpreted while taking into account that in most cases the effect sizes were small and/or results were imprecise. AUTHORS' CONCLUSIONS There is no high-quality, unequivocal evidence to support one psychological therapy over the others for the treatment of panic disorder with or without agoraphobia in adults. However, the results show that CBT - the most extensively studied among the included psychological therapies - was often superior to other therapies, although the effect size was small and the level of precision was often insufficient or clinically irrelevant. In the only two studies available that explored PD, this treatment showed promising results, although further research is needed in order to better explore the relative efficacy of PD with respect to CBT. Furthermore, PD appeared to be the best tolerated (in terms of ST-dropouts) among psychological treatments. Unexpectedly, we found some evidence in support of the possible viability of non-specific supportive psychotherapy for the treatment of panic disorder; however, the results concerning SP should be interpreted cautiously because of the sparsity of evidence regarding this treatment and, as in the case of PD, further research is needed to explore this issue. Behaviour therapy did not appear to be a valid alternative to CBT as a first-line treatment for patients with panic disorder with or without agoraphobia.

Novel mutation in the ceruloplasmin gene causing a cognitive and movement disorder with diabetes mellitus

In a Chinese woman who had diabetes mellitus, undetectable ceruloplasmin, hand tremor, neck dystonia, and cognitive disturbances, genetic analyses revealed a novel homozygous mutation (848G > C or W283S) in exon 5 in the ceruloplasmin gene. Another member with a milder phenotype was also affected by this mutation. The healthy sister was heterozygous at the same position. Aceruloplasminemia has not yet been reported in China. This case suggests that increased awareness should be paid to this disorder in the presence of the typical symptoms.

No evidence for an association of posttraumatic stress disorder with circulating levels of CRP and IL-18 in a population-based study.

Several studies have shown associations of posttraumatic stress disorder (PTSD) with the development of cardiometabolic diseases. The underlying psychopathological mechanisms, including potential links to inflammatory processes, have been discussed but remain elusive. Therefore, the aim of the present study was to evaluate the association of PTSD symptoms with the inflammatory biomarkers C-reactive protein (CRP) and interleukin-18 (IL-18). The study population consisted of 3012 participants aged 32-81years drawn from the population-based KORA F4 study conducted in 2006-08 in the Augsburg region (Southern Germany). PTSD symptoms were measured by the Impact of Event Scale, the Posttraumatic Diagnostic Scale and interview data and classified as no, partial or full PTSD. The associations of PTSD with CRP and IL-18 concentrations were estimated by multiple regression analyses with adjustments for age, sex and cardiometabolic risk factors. Linear regression analyses showed no significant association between PTSD and CRP or IL-18 concentration: adjusted for age and sex, the geometric mean concentrations in participants with full PTSD was for CRP 9% lower and for IL-18 1% higher than in participants with no PTSD (p values 0.53 and 0.89). However, further analyses indicated that individuals with partial PTSD had an increased chance of belonging to the highest quartile of the IL-18 concentration. No significant association was observed for any of the three subscales intrusion, avoidance or hyperarousal with CRP or IL-18 concentration. This large, population-based study could not find an association of full PTSD with CRP and IL-18 concentrations. Further research is needed to analyse these relationships.

The association of childhood trauma and personality disorder with adult chronic depression. A cross-sectional study in depressed outpatients

Objective: Chronic depression has often been associated with childhood trauma. There may, however, be an interaction between personality pathology, childhood trauma, and chronic depression. This interaction has not yet been studied. Method: This retrospective analysis is based on 279 patients contacted for a randomized trial in an outpatient psychotherapy center over a period of 18 months from 2010 to 2012. Current diagnoses of a personality disorder and presence of chronic depression were systematically assessed using the Structured Clinical Interview for DSM-IV. Retrospective reports of childhood trauma were collected using the short form of the Childhood Trauma Questionnaire (CTQ-SF). DSM-IV–defined chronic depression was the primary outcome. The association between chronic depression, childhood trauma, and personality disorders was analyzed using correlations. Variables that had at least a small effect on correlation analysis were entered into a series of logistic regression analyses to determine the predictors of chronic depression and the moderating effect of childhood trauma. Results: The presence of avoidant personality disorder, but no CTQ-SF scale, was associated with the chronicity of depression (odds ratio [OR] = 2.20, P = .015). The emotional abuse subscale of the CTQ-SF did, however, correlate with avoidant personality disorder (OR = 1.15, P = .000). The level of emotional abuse had a moderating effect on the effect of avoidant personality disorder on the presence of chronic depression (OR = 1.08, P = .004). Patients who did not suffer from avoidant personality disorder had a decreased rate of chronic depression if they retrospectively reported more severe levels of emotional abuse (18.9% vs 39.7%, respectively). Conclusions: The presence of avoidant personality pathology may interact with the effect of childhood trauma in the development of chronic depression. This has to be confirmed in a prospective study.

Bipolar disorder risk alleles in children with ADHD

Bipolar disorder (BD) and attention deficit/hyperactivity disorder (ADHD) may share common genetic risk factors as indicated by the high co-morbidity of BD and ADHD, their phenotypic overlap especially in pediatric populations, the high heritability of both disorders, and the co-occurrence in families. We therefore examined whether known polygenic BD risk alleles are associated with ADHD. We chose the eight best SNPs of the recent genome-wide association study (GWAS) of BD patients of German ancestry and the nine SNPs from international GWAS meeting a 'genome-wide significance' level of α = 5 × 10(-8). A GWAS was performed in 495 ADHD children and 1,300 population-based controls using HumanHap550v3 and Human660 W-Quadv1 BeadArrays. We found no significant association of childhood ADHD with single BD risk alleles surviving adjustment for multiple testing. Yet, risk alleles for BD and ADHD were directionally consistent at eight of nine loci with the strongest support for three SNPs in or near NCAN, BRE, and LMAN2L. The polygene analysis for the BP risk alleles at all 14 loci indicated a higher probability of being a BD risk allele carrier in the ADHD cases as compared to the controls. At a moderate power to detect association with ADHD, if true effects were close to estimates from GWAS for BD, our results suggest that the possible contribution of BD risk variants to childhood ADHD risk is considerably lower than for BD. Yet, our findings should encourage researchers to search for common genetic risk factors in BD and childhood ADHD in future studies.

Risk factors for borderline personality disorder in treatment seeking patients with a substance use disorder: an international multicenter study

Borderline personality disorder (BPD) and substance use disorders (SUDs) often co-occur, partly because they share risk factors. In this international multicenter study, risk factors for BPD were examined for SUD patients. In total, 1,205 patients were comprehensively examined by standardized interviews and questionnaires on psychiatric diagnosis and risk factors, and it was found that 1,033 (85.7%) had SUDs without BPD (SUD) and 172 (14.3%) had SUD with BPD (SUD + BPD). SUD + BPD patients were significantly younger, more often females and more often diagnosed with comorbid adult attention deficit/hyperactivity disorder. SUD + BPD patients did not differ from SUD patients on most risk factors typical for SUD such as maternal use of drugs during pregnancy or parents having any SUD. However, SUD + BPD patients did have a higher risk of having experienced emotional and physical abuse, neglect, or family violence in childhood compared to SUD patients, suggesting that child abuse and family violence are BPD-specific risk factors in patients with SUDs. © 2015 S. Karger AG, Basel.

Neurophysiological correlates of delinquent behaviour in adult subjects with ADHD

The attention deficit/hyperactivity disorder (ADHD) shows an increased prevalence in arrested offenders compared to the normal population. The aim of the present study was to investigate whether ADHD symptoms are a major risk factor for criminal behaviour, or whether further deficits, mainly abnormalities in emotion-processing, have to be considered as important additional factors that promote delinquency in the presence of ADHD symptomatology. Event related potentials (ERPs) of 13 non-delinquent and 13 delinquent subjects with ADHD and 13 controls were compared using a modified visual Go/Nogo continuous performance task (VCPT) and a newly developed version of the visual CPT that additionally requires emotional evaluation (ECPT). ERPs were analyzed regarding their topographies and Global Field Power (GFP). Offenders with ADHD differed from non-delinquent subjects with ADHD in the ERPs representing higher-order visual processing of objects and faces (N170) and facial affect (P200), and in late monitoring and evaluative functions (LPC) of behavioural response inhibition. Concerning neural activity thought to reflect the allocation of neural resources and cognitive processing capability (P300 Go), response inhibition (P300 Nogo), and attention/expectancy (CNV), deviances were observable in both ADHD groups and may thus be attributed to ADHD rather than to delinquency. In conclusion, ADHD symptomatology may be a risk factor for delinquency, since some neural information processing deficits found in ADHD seemed to be even more pronounced in offenders with ADHD. However, our results suggest additional risk factors consisting of deviant higher-order visual processing, especially of facial affect, as well as abnormalities in monitoring and evaluative functions of response inhibition.

Randomised controlled trials of homeopathy in hyperactive children: treatment procedure leads to an unconventional study design. Experience with open-label homeopathic treatment preceding the Swiss ADHD placebo controlled, randomised, double-blind, cross-over trial

BACKGROUND: Treatment of patients with attention deficit hyperactivity disorder (ADHD) with homeopathy is difficult. The Swiss randomised, placebo controlled, cross-over trial in ADHD patients (Swiss ADHD trial) was designed with an open-label screening phase prior to the randomised controlled phase. During the screening phase, the response of each child to successive homeopathic medications was observed until the optimal medication was identified. Only children who reached a predefined level of improvement participated in the randomised, cross-over phase. Although the randomised phase revealed a significant beneficial effect of homeopathy, the cross-over caused a strong carryover effect diminishing the apparent difference between placebo and verum treatment. METHODS: This retrospective analysis explores the screening phase data with respect to the risk of failure to demonstrate a specific effect of a randomised controlled trial (RCT) with randomisation at the start of the treatment. RESULTS: During the screening phase, 84% (70/83) of the children responded to treatment and reached eligibility for the randomised trial after a median time of 5 months (range 1-18), with a median of 3 different medications (range 1-9). Thirteen children (16%) did not reach eligibility. Five months after treatment start, the difference in Conners Global Index (CGI) rating between responders and non-responders became highly significant (p = 0.0006). Improvement in CGI was much greater following the identification of the optimal medication than in the preceding suboptimal treatment period (p < 0.0001). CONCLUSIONS: Because of the necessity of identifying an optimal medication before response to treatment can be expected, randomisation at the start of treatment in an RCT of homeopathy in ADHD children has a high risk of failure to demonstrate a specific treatment effect, if the observation time is shorter than 12 months.

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 disor-der (ADHD) in substance use disorder (SUD) patients, ranging from 2 to 83%. A better understanding ofthe 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 patientsform inpatient and outpatient addiction treatment centers for alcohol and/or drug use disorder patients. Atotal 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. 5AdultsResults: Prevalence of DSM-IV and DSM-5 adult ADHD varied for DSM-IV from 5.4% (CI 95%: 2.4–8.3) forHungary 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 to32.6% (CI 95%: 26.4–38.8) for Norway. Using the same assessment procedures in all countries and centersresulted in substantial reduction of the variability in the prevalence of adult ADHD reported in previousstudies among SUD patients (2–83% → 5.4–31.3%). The remaining variability was partly explained byprimary substance of abuse and by country (Nordic versus non-Nordic countries). Prevalence estimatesfor DSM-5 were slightly higher than for DSM-IV.Conclusions: Given the generally high prevalence of adult ADHD, all treatment seeking SUD patientsshould be screened and, after a confirmed diagnosis, treated for ADHD since the literature indicates poorprognoses of SUD in treatment seeking SUD patients with ADHD.

Validity of the Adult ADHD Self-Report Scale (ASRS) as a screener for adult ADHD in treatment seeking substance use disorder patients

Background: To detect attention deficit hyperactivity disorder (ADHD) in treatment seeking substance use disorders (SUD) patients, a valid screening instrument is needed. Objectives: To test the performance of the Adult ADHD Self-Report Scale V 1.1(ASRS) for adult ADHD in an international sample of treatment seeking SUD patients for DSM-IV-TR; for the proposed DSM-5 criteria; in different subpopulations, at intake and 1–2 weeks after intake; using different scoring algorithms; and different externalizing disorders as external criterion (including adult ADHD, bipolar disorder, antisocial and borderline personality disorder). Methods: In 1138 treatment seeking SUD subjects, ASRS performance was determined using diagnoses based on Conner's Adult ADHD Diagnostic Interview for DSM-IV (CAADID) as gold standard. Results: The prevalence of adult ADHD was 13.0% (95% CI: 11.0–15.0%). The overall positive predictive value (PPV) of the ASRS was 0.26 (95% CI: 0.22–0.30), the negative predictive value (NPV) was 0.97 (95% CI: 0.96–0.98). The sensitivity (0.84, 95% CI: 0.76–0.88) and specificity (0.66, 95% CI: 0.63–0.69) measured at admission were similar to the sensitivity (0.88, 95% CI: 0.83–0.93) and specificity (0.67, 95% CI: 0.64–0.70) measured 2 weeks after admission. Sensitivity was similar, but specificity was significantly better in patients with alcohol compared to (illicit) drugs as the primary substance of abuse (0.76 vs. 0.56). ASRS was not a good screener for externalizing disorders other than ADHD. Conclusions: The ASRS is a sensitive screener for identifying possible ADHD cases with very few missed cases among those screening negative in this population.

Monitoring of threo-methylphenidate enantiomers in oral fluid by capillary electrophoresis with head-column field-amplified sample injection

Threo-methylphenidate is a chiral psychostimulant drug widely prescribed to treat attention-deficit hyperactivity disorder in children and adolescents. An enantioselective CE-based assay with head-column field-amplified sample stacking for analysis of threo-methylphenidate enantiomers in liquid/liquid extracts of oral fluid is described. Analytes are electrokinetically injected across a short water plug placed at the capillary inlet and become stacked at the interface between plug and buffer. Enantiomeric separation occurs within a few minutes in a pH 3.0 phosphate/triethanolamine buffer containing 20 mg/mL (2-hydroxypropyl)-β-CD as chiral selector. The assay with six point multilevel internal calibration provides a linear response for each enantiomer in the 10-200 ng/mL concentration range, is simple, inexpensive, and reproducible, and has an LOQ of 5 ng/mL. It was applied to oral fluid patient samples that were collected up to 12 h after intake of an immediate release tablet and two different extended release formulations with racemic methylphenidate. Drug profiles could thereby be assessed in a stereoselective way. Almost no levorotary threo-methylphenidate enantiomer was detected after intake of the two extended release formulations, whereas this enantiomer was detected during the first 2.5 h after intake of the immediate release preparation. The noninvasive collection of oral fluid is an attractive alternative to plasma for the monitoring of methylphenidate exposure in the pediatric community.