Amphetamines for Attention Deficit Hyperactivity Disorder (ADHD) in adults.

Attention Deficit Hyperactivity Disorder (ADHD) is a childhood onset psychiatric disorder that can persist into adulthood in up to 50% of patients. From a clinical point of view, ADHD is characterized by hyperactivity, mood instability, irritability, difficulties in maintaining attention, lack of organization and impulsive behaviours. The presence of other disorders occurring at the the same time is also common, especially mood disorders and substance abuse. It seems that amphetamines could reverse the underlying neurological problems that feature in ADHD, and so improve ADHD symptoms. We found seven studies, which enrolled 1091 patients. These studies compared amphetamines to placebo and three of them also compared amphetamines with other drugs: guanfacine, modafinil and paroxetine. Three amphetamine derivatives were investigated: dexamphetamine, lisdexamphetamine and mixed amphetamine salts (MAS). Treatment length ranged from two to 20 weeks. All amphetamines improved ADHD symptoms but overall they did not make people more likely to stay in treatment and were associated with a higher risk of treatment ending early due to adverse events. One type of amphetamine, mixed amphetamine salts, did, however, increase retention in treatment. We found no evidence that higher doses worked better than lower ones. We did not find any difference in effectiveness between immediate-release and sustained-release formulations. Therefore, it appears that short-term treatment with amphetamines reduces ADHD symptoms, but studies assessing the effects of amphetamines for longer periods of time are needed.This resource was contributed by The National Documentation Centre on Drug Use.

Neuroanatomical and neuropsychological features of euthymic patients with bipolar disorder.

OBJECTIVE: Previous studies reported that the severity of cognitive deficits in euthymic patients with bipolar disorder (BD) increases with the duration of illness and postulated that progressive neuronal loss or shrinkage and white matter changes may be at the origin of this phenomenon. To explore this issue, the authors performed a case-control study including detailed neuropsychological and magnetic resonance imaging analyses in 17 euthymic elderly patients with BD and 17 healthy individuals. METHODS: Neuropsychological evaluation concerned working memory, episodic memory, processing speed, and executive functions. Volumetric estimates of the amygdala, hippocampus, entorhinal cortex, and anterior cingulate cortex were obtained using both voxel-based and region of interest morphometric methods. Periventricular and deep white matter were assessed semiquantitatively. Differences in cognitive performances and structural data between BD and comparison groups were analyzed using paired t-test or analysis of variance. Wilcoxon test was used in the absence of normal distribution. RESULTS: Compared with healthy individuals, patients with BD obtained significantly lower performances in processing speed, working memory, and episodic memory but not in executive functions. Morphometric analyses did not show significant volumetric or white matter differences between the two groups. CONCLUSIONS: Our results revealed impairment in verbal memory, working memory, and processing speed in euthymic older adults with BD. These cognitive deficits are comparable both in terms of affected functions and size effects to those previously reported in younger cohorts with BD. Both this observation and the absence of structural brain abnormalities in our cohort do not support a progressively evolving neurotoxic effect in BD.

Efficacy of lisdexamfetamine dimesylate throughout the day in children and adolescents with attention-deficit/hyperactivity disorder: results from a randomized, controlled trial.

Lisdexamfetamine dimesylate (LDX) is a long-acting, prodrug stimulant therapy for patients with attention-deficit/hyperactivity disorder (ADHD). This randomized placebo-controlled trial of an optimized daily dose of LDX (30, 50 or 70 mg) was conducted in children and adolescents (aged 6-17 years) with ADHD. To evaluate the efficacy of LDX throughout the day, symptoms and behaviors of ADHD were evaluated using an abbreviated version of the Conners' Parent Rating Scale-Revised (CPRS-R) at 1000, 1400 and 1800 hours following early morning dosing (0700 hours). Osmotic-release oral system methylphenidate (OROS-MPH) was included as a reference treatment, but the study was not designed to support a statistical comparison between LDX and OROS-MPH. The full analysis set comprised 317 patients (LDX, n = 104; placebo, n = 106; OROS-MPH, n = 107). At baseline, CPRS-R total scores were similar across treatment groups. At endpoint, differences (active treatment - placebo) in least squares (LS) mean change from baseline CPRS-R total scores were statistically significant (P < 0.001) throughout the day for LDX (effect sizes: 1000 hours, 1.42; 1400 hours, 1.41; 1800 hours, 1.30) and OROS-MPH (effect sizes: 1000 hours, 1.04; 1400 hours, 0.98; 1800 hours, 0.92). Differences in LS mean change from baseline to endpoint were statistically significant (P < 0.001) for both active treatments in all four subscales of the CPRS-R (ADHD index, oppositional, hyperactivity and cognitive). In conclusion, improvements relative to placebo in ADHD-related symptoms and behaviors in children and adolescents receiving a single morning dose of LDX or OROS-MPH were maintained throughout the day and were ongoing at the last measurement in the evening (1800 hours).

Omega-3 fatty acids prevent inflammation and metabolic disorder through inhibition of NLRP3 inflammasome activation.

Omega-3 fatty acids (ω-3 FAs) have potential anti-inflammatory activity in a variety of inflammatory human diseases, but the mechanisms remain poorly understood. Here we show that stimulation of macrophages with ω-3 FAs, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and other family members, abolished NLRP3 inflammasome activation and inhibited subsequent caspase-1 activation and IL-1β secretion. In addition, G protein-coupled receptor 120 (GPR120) and GPR40 and their downstream scaffold protein β-arrestin-2 were shown to be involved in inflammasome inhibition induced by ω-3 FAs. Importantly, ω-3 FAs also prevented NLRP3 inflammasome-dependent inflammation and metabolic disorder in a high-fat-diet-induced type 2 diabetes model. Our results reveal a mechanism through which ω-3 FAs repress inflammation and prevent inflammation-driven diseases and suggest the potential clinical use of ω-3 FAs in gout, autoinflammatory syndromes, or other NLRP3 inflammasome-driven inflammatory diseases.

Change in biased thinking in a 10-session treatment for borderline personality disorder: Further evidence of the motive-oriented therapeutic relationship.

Abstract Borderline Personality Disorder (BPD) is characterized by both maladaptive thinking and problematic schemas. Kramer and colleagues (2011) showed that using the motive-oriented therapeutic relationship (MOTR), based on the individualized understanding of the patient according to Plan Analysis (Caspar, 2007), can improve treatment outcomes for BPD. The present process-outcome pilot study aimed to examine the effects of the motive-oriented therapeutic relationship on the cognitive biases of patients with BPD. Change in biased cognitions in N=10 patients who were subject to MOTR was compared to that of N=10 patients who received psychiatric-psychodynamic treatment (Gunderson & Links, 2008). Results show a greater decrease in over-generalizations in patients who received MOTR, compared to the patients who received the psychiatric-psychodynamic treatment. These changes were related to outcome in various ways. These findings underline the importance of an individualized case formulation method in bringing about therapeutic change.

Analyses of a novel SCN5A mutation (C1850S): conduction vs. repolarization disorder hypotheses in the Brugada syndrome.

AIMS: Brugada syndrome (BrS) is characterized by arrhythmias leading to sudden cardiac death. BrS is caused, in part, by mutations in the SCN5A gene, which encodes the sodium channel alpha-subunit Na(v)1.5. Here, we aimed to characterize the biophysical properties and consequences of a novel BrS SCN5A mutation. METHODS AND RESULTS: SCN5A was screened for mutations in a male patient with type-1 BrS pattern ECG. Wild-type (WT) and mutant Na(v)1.5 channels were expressed in HEK293 cells. Sodium currents (I(Na)) were analysed using the whole-cell patch-clamp technique at 37 degrees C. The electrophysiological effects of the mutation were simulated using the Luo-Rudy model, into which the transient outward current (I(to)) was incorporated. A new mutation (C1850S) was identified in the Na(v)1.5 C-terminal domain. In HEK293 cells, mutant I(Na) density was decreased by 62% at -20 mV. Inactivation of mutant I(Na) was accelerated in a voltage-dependent manner and the steady-state inactivation curve was shifted by 11.6 mV towards negative potentials. No change was observed regarding activation characteristics. Altogether, these biophysical alterations decreased the availability of I(Na). In the simulations, the I(to) density necessary to precipitate repolarization differed minimally between the two genotypes. In contrast, the mutation greatly affected conduction across a structural heterogeneity and precipitated conduction block. CONCLUSION: Our data confirm that mutations of the C-terminal domain of Na(v)1.5 alter the inactivation of the channel and support the notion that conduction alterations may play a significant role in the pathogenesis of BrS.

Hyperactivity and attention problems in a Swiss sample of school-aged children: effects of school achievement, child gender, and informants.

OBJECTIVE: The sensitivity and tolerance regarding ADHD symptoms obviously differ from one culture to another and according to the informants (parents, teachers, or children). This stimulates the comparison of data across informants and countries. METHOD: Parents and teachers of more than 1,000 school-aged Swiss children (5 to 17 years old) fill in Conners's questionnaires on ADHD. Children who are older than 10 years old also fill in a self-report questionnaire. Results are compared to data from a North American sample. RESULTS: Swiss parents and teachers tend to report more ADHD symptoms than American parents and teachers as far as the oldest groups of children are concerned. Interactions are evidenced between school achievement, child gender, and informants. A relatively low rate of agreement between informants is found. CONCLUSION: These results strengthen the importance to take into account all informants in the pediatric and the child psychiatry clinic, as well as in the epidemiological studies.

Assimilation process in a psychotherapy with a client presenting schizoid personality disorder

The assimilation of problematic experiences has been studied as change processes in psychotherapies of different client populations. Several theory-building case studies using the assimilation model have shown how important a meaning bridge is in such change processes. In a client presenting schizoid personality disorder the creation of meaning as an affect-evoking process may be a particularly important stage in the change process. The present case study aims to apply the assimilation model to a psychotherapy process with a highly disturbed client and focuses on the creation of a meaning bridge in the process. Moreover, the assimilation analysis focuses on the effect of an external person, i.e. the partner or the therapist, when responding to the client's unassimilated problematic experiences. Their effects on the client's assimilation processes are discussed.

Emotional processing in a ten-session general psychiatric treatment for borderline personality disorder: a case study.

This study examines the effects of a borderline-specific treatment, called general psychiatric management, on emotional change, outcome and therapeutic alliance of an outpatient presenting with borderline personality disorder. Based on the sequential model of emotional processing, emotional states were assessed in a 10-session setting. The case showed an increase in expressions of distress and no change in therapeutic alliance and tended towards general deterioration. Results suggest emotional processing may play a lesser role in general psychiatric management in early phase treatment than previously hypothezised. Copyright © 2015 John Wiley & Sons, Ltd.

A non-randomized direct comparison of cognitive-behavioral short- and long-term treatment for binge eating disorder

Background: To compare treatment outcomes of a cognitive-behavioral long-term (CBT-L) and short-term (CBT-S) treatment for binge eating disorder (BED) in a non-randomized comparison and to identify moderators of treatment outcome. Methods: 76 female patients with BED participated in the study: 40 in CBT-L and 36 in CBT-S. Outcome values were compared at the end of the active treatment phase (16 sessions for CBT-L, 8 sessions for CBT-S) and at 12-month follow-up. Results: Both treatments produced significant reductions in binge eating. At the end of active treatment, but not at the end of follow-up, effects of primary outcomes (e.g. remission from binge eating, EDE shape concern) were better for CBT-L than for CBT-S. Dropout rates were significantly higher in CBT-L (35%) than in CBT-S (14%). Moderator analyses revealed that treatment efficacy for rapid responders and individuals exhibiting high scores on the mixed dietary negative affect subtype differed between the CBT-L and CBT-S with respect to objective binges, restraint eating and eating concern. Conclusion: Findings suggest that CBT in general represents an effective treatment for BED, but that subgroups of patients might profit more from a prolonged treatment. Short, lessintensive CBT treatments could nevertheless be a viable option in the treatment of BED.

Modification de la composition des cigarettes durant te XXe siècle: rôle de l'industrie du tabac et effet sur la dépendance tabagique [Chemicals added to cigarettes and their effects on tobacco dependence]

This paper summarizes data on the factors involved in addiction and dependence to cigarettes. Nicotine has been intensively studied by the tobacco industry, for instance for its addictive effect at the lowest possible rates. The addition of diammonium phosphate and urea produces an alcalinization of the pH of cigarette smoke, and promotes the absorption and the trans-membrane passage of nicotine. The taste, the smell of smoke, and the visual aspect of the pack of cigarettes are also sensory components that promote addiction. Finally, menthol, sugar, cocoa and liquorice added to cigarettes also play a role in dependence and addiction to cigarettes by, for instance, making an anesthetic effect on the airways.

Mutant huntingtin's effects on striatal gene expression in mice recapitulate changes observed in human Huntington's disease brain and do not differ with mutant huntingtin length or wild-type huntingtin dosage.

To test the hypotheses that mutant huntingtin protein length and wild-type huntingtin dosage have important effects on disease-related transcriptional dysfunction, we compared the changes in mRNA in seven genetic mouse models of Huntington's disease (HD) and postmortem human HD caudate. Transgenic models expressing short N-terminal fragments of mutant huntingtin (R6/1 and R6/2 mice) exhibited the most rapid effects on gene expression, consistent with previous studies. Although changes in the brains of knock-in and full-length transgenic models of HD took longer to appear, 15- and 22-month CHL2(Q150/Q150), 18-month Hdh(Q92/Q92) and 2-year-old YAC128 animals also exhibited significant HD-like mRNA signatures. Whereas it was expected that the expression of full-length huntingtin transprotein might result in unique gene expression changes compared with those caused by the expression of an N-terminal huntingtin fragment, no discernable differences between full-length and fragment models were detected. In addition, very high correlations between the signatures of mice expressing normal levels of wild-type huntingtin and mice in which the wild-type protein is absent suggest a limited effect of the wild-type protein to change basal gene expression or to influence the qualitative disease-related effect of mutant huntingtin. The combined analysis of mouse and human HD transcriptomes provides important temporal and mechanistic insights into the process by which mutant huntingtin kills striatal neurons. In addition, the discovery that several available lines of HD mice faithfully recapitulate the gene expression signature of the human disorder provides a novel aspect of validation with respect to their use in preclinical therapeutic trials.

Effects of perinatal stress and maternal traumatic stress on the cortisol regulation of preterm infants.

Preterm infants experience intense stress during the perinatal period because they endure painful and intense medical procedures. Repeated activation of the hypothalamic-pituitary-adrenal (HPA) axis during this period may have long-term effects on subsequent cortisol regulation. A premature delivery may also be intensely stressful for the parents, and they may develop symptoms of posttraumatic stress disorder (PTSD). Usable saliva samples were collected (4 times per day over 2 days, in the morning at awakening, at midday, in the afternoon, and in the evening before going to bed) to assess the diurnal cortisol regulation from 46 preterm infants when the infants were 12 months of corrected age (∼ 14 months after birth). Mothers reported their level of PTSD symptoms. The results showed an interaction between perinatal stress and maternal traumatic stress on the diurnal cortisol slope of preterm infants (R(2) = .32). This suggests that the HPA axis of preterm infants exposed to high perinatal stress may be more sensitive to subsequent environmental stress.

Brain volumetric correlates of autism spectrum disorder symptoms in attention deficit/hyperactivity disorder.

Autism spectrum disorder (ASD) symptoms frequently occur in subjects with attention deficit/hyperactivity disorder (ADHD). While there is evidence that both ADHD and ASD have differential structural correlates, no study to date has investigated these structural correlates within a framework that robustly accounts for the phenotypic overlap between the two disorders. The presence of ASD symptoms was measured by the parent-reported Children's Social and Behavioural Questionnaire (CSBQ) in ADHD subjects (n = 180), their unaffected siblings (n = 118) and healthy controls (n = 146). ADHD symptoms were assessed by a structured interview (K-SADS-PL) and the Conners' ADHD questionnaires. Whole brain T1-weighted MPRAGE images were acquired and the structural MRI correlates of ASD symptom scores were analysed by modelling ASD symptom scores against white matter (WM) and grey matter (GM) volumes using mixed effects models which controlled for ADHD symptom levels. ASD symptoms were significantly elevated in ADHD subjects relative to both controls and unaffected siblings. ASD scores were predicted by the interaction between WM and GM volumes. Increasing ASD score was associated with greater GM volume. Equivocal results from previous structural studies in ADHD and ASD may be due to the fact that comorbidity has not been taken into account in studies to date. The current findings stress the need to account for issues of ASD comorbidity in ADHD.

Effects of prior hydrogenation on the structure and properties of thermally nanocrystallized silicon layers

Nanocrystalline silicon layers have been obtained by thermal annealing of films sputtered in various hydrogen partial pressures. The as-deposited and crystallized films were investigated by infrared, Raman, x-ray diffraction, electron microscopy, and optical absorption techniques. The obtained data show evidence of a close correlation between the microstructure and properties of the processed material, and the hydrogen content in the as-grown deposit. The minimum stress deduced from Raman was found to correspond to the widest band gap and to a maximum hydrogen content in the basic unannealed sample. Such a structure relaxation seems to originate from the so-called "chemical annealing" thought to be due to Si-H2 species, as identified by infrared spectroscopy. The variation of the band gap has been interpreted in terms of the changes in the band tails associated with the disorder which would be induced by stress. Finally, the layers originally deposited with the highest hydrogen pressure show a lowest stress-which does not correlate with the hydrogen content and the optical band gap¿and some texturing. These features are likely related to the presence in these layers of a significant crystalline fraction already before annealing.