Effects of methylphenidate on attention in Wistar rats treated with the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4).

The aim of this study was to assess the effects of the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) on attention in rats as measured using the 5-choice-serial-reaction-time task (5CSRTT) and to investigate whether methylphenidate has effects on DSP4-treated rats. Methylphenidate is a noradrenaline and dopamine reuptake inhibitor and commonly used in the pharmacological treatment of individuals with attention deficit/hyperactivity disorder (ADHD). Wistar rats were trained in the 5CSRTT and treated with one of three doses of DSP4 or saline. Following the DSP4 treatment rats were injected with three doses of methylphenidate or saline and again tested in the 5CSRTT. The treatment with DSP4 caused a significant decline of performance in the number of correct responses and a decrease in response accuracy. A reduction in activity could also be observed. Whether or not the cognitive impairments are due to attention deficits or changes in explorative behaviour or activity remains to be investigated. The treatment with methylphenidate had no beneficial effect on the rats' performance regardless of the DSP4 treatment. In the group without DSP4 treatment, methylphenidate led to a reduction in response accuracy and bidirectional effects in regard to parameters related to attention. These findings support the role of noradrenaline in modulating attention and call for further investigations concerning the effects of methylphenidate on attentional processes in rats.

The Role of Nutritional Supplements in the Treatment of ADHD: What the Evidence Says.

Attention-deficit hyperactivity disorder (ADHD) is a common behavioral disorder in children and adolescents and may persist into adulthood. Insufficient nutritional supply of long-chain polyunsaturated fatty acids (LC-PUFAs) and other components including various minerals has been suggested to play a role in the development of ADHD symptoms. This review presents the evidence regarding the role of nutritional PUFA, zinc, iron, and magnesium supplements in the treatment of ADHD with a focus on the critical evaluation of the relevant literature published from 2014 to April 2016. The evaluation of therapeutic nutritional LC-PUFA supplementation in ADHD has shown mixed and inconclusive results and at best marginal beneficial effects. The benefits of PUFAs are much smaller than the effect sizes observed for traditional pharmacological treatments of ADHD. The effectiveness of PUFA supplements in reducing medication dosage has been suggested but needs to be confirmed. Zinc, iron, and magnesium supplementation may reduce ADHD symptoms in children with or at high risk of deficiencies in these minerals. However, convincing evidence in this regard is lacking.

Gluten-free and casein-free diets in the therapy of autism.

PURPOSE OF REVIEW: The purpose of this study is to discuss the role of gluten-free and casein-free diets in the treatment of autism. RECENT FINDINGS: In a recent UK survey, more than 80% of parents of children with autism spectrum disorder reported some kind of dietary intervention for their child (gluten-free and casein-free diet in 29%). When asked about the effects of the gluten-free and casein-free diet, 20-29% of the parents reported significant improvements on the autism spectrum disorder core dimensions. The findings of this study suggest additional effects of a gluten-free and casein-free diet on comorbid problems of autism such as gastrointestinal symptoms, concentration, and attention. The findings of another recent investigation suggested that age and certain urine compounds may predict the response of autism symptoms to a gluten-free and casein-free diet. Although these results need to be replicated, they highlight the importance of patient subgroup analysis. Intervention trials evaluating the effects of a gluten-free and casein-free diet on autistic symptoms have so far been contradictory and inconclusive. SUMMARY: Most investigations assessing the efficacy of a gluten-free and casein-free diet in the treatment of autism are seriously flawed. The evidence to support the therapeutic value of this diet is limited and weak. A gluten-free and casein-free diet should only be administered if an allergy or intolerance to nutritional gluten or casein is diagnosed.

Circadian rhythms in obsessive-compulsive disorder.

The etiopathology and neurobiology of obsessive-compulsive disorder (OCD) are not fully understood. As for altered circadian rhythms associated with OCD, hormonal dysregulation and a delayed sleep phase have come into the focus of research. The novel antidepressant agomelatine is able to resynchronize circadian rhythms and the augmentative administration of this compound has been shown to be of benefit in some OCD patients who are refractory to common forms of pharmacotherapy. Adjunctive chronotherapy might also enhance the outcome in treatment-refractory OCD. The present review summarises the findings regarding circadian abnormalities in OCD.

The role of state feelings of loneliness in the situational regulation of social affiliative behavior: Exploring the regulatory relations within a multilevel framework.

Previous empirical evidence suggests that the engagement in social interactions across different everyday contexts occurs in a manner highly responsive to a person's social affiliation needs. As has been shown repeatedly, social engagement (as well as disengagement) can be predicted from earlier situational need states, implying that homeostatic principles underlie a person's social affiliative behaviors. However, little is known about the role of emotion in these regulative processes. For this reason, the present exploratory study investigated the predictive role of state feelings of loneliness in subsequent engagement in social interaction. Since loneliness is conceptually associated with both the need to reaffiliate as well as self-protecting tendencies potentially hindering engagement in social contact, the study investigated the possibility of both increases and decreases in social contacts resulting from state feelings of loneliness. Adopting an experience sampling methodology (ESM), a sample of 65 participants was recruited from a local university and was followed for 14 days. Subjects were prompted several times a day to rate their feeling states and the quantity of social interactions, using a fixed interval assessment schedule. Statistical analyses using multilevel analysis indicated that state feelings of loneliness had complex quadratic effects upon subsequent social interaction, leading to both increases and decreases in subsequent social interaction. Moreover, these effects were contingent upon previous engagement in social interaction, implying spillover effects across social contexts that are conditionally mediated by feelings of loneliness. These findings clearly imply an important, albeit complex role of state feelings of loneliness in the regulation of social affiliation, both as a predictor and a consequence of social interaction. These exploratory findings are discussed against the background of methodological and conceptual limitations, and several recommendations for future studies are made.

Effects of atomoxetine on attention in Wistar rats treated with the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4).

The aim of the present study was to assess the effects of the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4), which allows a depletion of noradrenergic terminals in a dose-dependent manner, on attention in rats as measured using the five-choice serial-reaction time task (5CSRTT). In addition, we investigated whether the effects of DSP4 treatment can be reversed by atomoxetine. Atomoxetine is a selective noradrenaline reuptake inhibitor and has been shown to be effective in the treatment of attention deficit hyperactivity disorder. Wistar rats were trained in the 5CSRTT and treated with one of the three doses of DSP4 (10, 20 or 50 mg/kg) or saline. Following DSP4 treatment, rats were injected with three doses of atomoxetine (0.1, 0.5 or 1 mg/kg) or saline and tested in the 5CSRTT. The treatment with DSP4 caused a reduction in activity and a decline of performance in parameters related to attention in the 5CSRTT. Whether or not these impairments are due to attention deficits or changes in explorative behaviour and activity remains to be investigated. The treatment with atomoxetine had no beneficial effect on the rats' performance regardless of the DSP4 treatment. The present findings support the role of noradrenaline in modulating attentional processes and call for future studies regarding the effects of atomoxetine on attention in rats.

Cognitive impairment in adult ADHD--perspective matters!

OBJECTIVE: The assessment of cognitive functions of adults with attention deficit hyperactivity disorder (ADHD) comprises self-ratings of cognitive functioning (subjective assessment) as well as psychometric testing (objective neuropsychological assessment). The aim of the present study was to explore the utility of these assessment strategies in predicting neuropsychological impairments of adults with ADHD as determined by both approaches. METHOD: Fifty-five adults with ADHD and 66 healthy participants were assessed with regard to cognitive functioning in several domains by employing subjective and objective measurement tools. Significance and effect sizes for differences between groups as well as the proportion of patients with impairments were analyzed. Furthermore, logistic regression analyses were carried out in order to explore the validity of subjective and objective cognitive measures in predicting cognitive impairments. RESULTS: Both subjective and objective assessment tools revealed significant cognitive dysfunctions in adults with ADHD. The majority of patients displayed considerable impairments in all cognitive domains assessed. A comparison of effect sizes, however, showed larger dysfunctions in the subjective assessment than in the objective assessment. Furthermore, logistic regression models indicated that subjective cognitive complaints could not be predicted by objective measures of cognition and vice versa. CONCLUSIONS: Subjective and objective assessment tools were found to be sensitive in revealing cognitive dysfunctions of adults with ADHD. Because of the weak association between subjective and objective measurements, it was concluded that subjective and objective measurements are both important for clinical practice but may provide distinct types of information and capture different aspects of functioning.

The effects of nutritional polyunsaturated fatty acids on locomotor activity in spontaneously hypertensive rats.

The present study investigated the effects of nutritional omega-3 polyunsaturated fatty acids on locomotor activity in spontaneously hypertensive rats (SHRs), which are used as an animal model of attention-deficit/hyperactivity disorder (ADHD). For 6 weeks, two groups of randomly assigned SHRs received food either enriched with or deficient in omega-3 fatty acids (based on the American Institute of Nutrition-93 G/AIN93G). Using an open field, locomotor activity was subsequently assessed for 6 days. A marked difference in locomotor activity as assessed by the distance travelled in the open field was found between the two groups of rats. In comparison with rats fed with omega-3 fatty acid-enriched food, the animals on the omega-3 fatty acid-deficient diet showed a significantly higher locomotor activity. The present findings demonstrated that nutritional enrichment with omega-3 fatty acids was associated with reduced motor activity in an established animal model of ADHD and support the notion that omega-3 polyunsaturated fatty acids may play a role in the pathophysiology of ADHD.

Utility of cognitive neuropsychological assessment in attention-deficit/hyperactivity disorder.

The present review addresses the question of whether and how neuropsychological tests assessing cognition in attention-deficit/hyperactivity disorder (ADHD) can contribute to clinical and scientific issues concerning ADHD. Neuropsychological studies have shown various though inconsistent cognitive deficits in patients with ADHD. While patients with ADHD, at group level, may differ from healthy participants in regard to cognitive functioning, there is no distinct psychometric cognitive test or profile allowing an individual diagnosis of ADHD or the identification of subtypes according to DSM. Psychometric neuropsychological tests may provide a precise description of the cognitive problems in individual patients and offer specific information for individualized treatment planning. In addition, neuropsychological assessment may contribute to neuroscientific research by providing endophenotypes or biological markers of ADHD. Cognitive neuropsychological assessment appears to be at present of limited clinical use and confined to individual descriptions.

Stigmatization in teachers towards adults with attention deficit hyperactivity disorder.

OBJECTIVES: Attention deficit hyperactivity disorder (ADHD) is understood as a developmental disorder which shares common characteristics between childhood, adolescence and adulthood. However, ADHD is widely associated with misconceptions and misbeliefs which can lead to stigmatization. Teachers have an important role for the individual development as they accompany students for a long period of time. The aim of the present study was to explore stigmatizing attitudes in teachers towards adults with ADHD, thereby focusing on the developmental trajectory of the condition. Furthermore, it was aimed to identify factors contributing to prevention and intervention of stigmatization in ADHD. METHODS: Stigma responses of 170 teachers and 170 comparison participants were measured and compared with a recently developed tool for the assessment of stigmatization towards adults with ADHD. Furthermore, the contribution of knowledge about ADHD and the frequency of contact with adults with ADHD to stigmatization were explored. RESULTS: Teachers showed significantly less stigmatizing attitudes than comparison participants in various dimensions, including Reliability and Social Functioning, Malingering and Misuse of Medication and the total scale. With regard to teachers, frequency of contact with adults with ADHD was not related to stigma. However, knowledge about the disorder was negatively correlated with stigma in teachers, indicating lower expressed stigma with increasing knowledge about adult ADHD. CONCLUSIONS: Teachers demonstrated more sensitized attitudes towards stigma in adults with ADHD than comparison participants. Since the present results indicate that knowledge about ADHD increase the sensitivity towards the disorder, special education programs for the community may have the potential to reduce stigmatization towards adults with ADHD. Possibilities for intervention strategies of stigmatization in educational settings were discussed.

Spatial memory in spontaneously hypertensive rats (SHR).

The spontaneously hypertensive rat (SHR) is an established animal model of ADHD. It has been suggested that ADHD symptoms arise from deficits in executive functions such as working memory, attentional control and decision making. Both ADHD patients and SHRs show deficits in spatial working memory. However, the data on spatial working memory deficits in SHRs are not consistent. It has been suggested that the reported cognitive deficits of SHRs may be related to the SHRs' locomotor activity. We have used a holeboard (COGITAT) to study both cognition and activity in order to evaluate the influence of the activity on the cognitive performance of SHRs. In comparison to Wistar-Kyoto (WKY) rats, SHRs did not have any impairment in spatial working memory and reference memory. When the rats' locomotor activity was taken into account, the SHRs' working memory and reference memory were significantly better than in WKY rats. The locomotor activity appears to be a confounding factor in spatial memory tasks and should therefore be controlled for in future studies. In the SHR model of ADHD, we were unable to demonstrate an impairment of working memory which has been reported in patients with ADHD.

The effects of the neurotoxin DSP4 on spatial learning and memory in Wistar rats.

The aim of the present study was to investigate the effect of DSP4-induced noradrenaline depletion on learning and memory in a spatial memory paradigm (holeboard). Since Harro et al. Brain Res 976:209-216 (2003) have demonstrated that short-term effects of DSP4 administration include both noradrenaline depletion and changes in dopamine and its metabolites-with the latter vanishing within 4 weeks after the neurotoxic lesion-the behavioural effects observed immediately after DSP4 administration cannot solely be related to noradrenaline. In the present study, spatial learning, reference memory and working memory were therefore assessed 5-10 weeks after DSP4 administration. Our results suggest that the administration of DSP4 did not lead to changes in spatial learning and memory when behavioural assessment was performed after a minimum of 5 weeks following DSP4. This lack of changes in spatial behaviour suggests that the role of noradrenaline regarding these functions may be limited. Future studies will therefore have to take into account the time-course of neurotransmitter alterations and behavioural changes following DSP4 administration.

Effects of DSP4 and methylphenidate on spatial memory performance in rats.

In this experiment, we have investigated the spatial memory performance of rats following a central noradrenaline depletion induced by three different doses of the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) and following administration of three different doses of methylphenidate (MPH). The rats were required to find food pellets hidden on a holeboard. The sole administration of DSP4 induced only minor cognitive deficits. However, the treatment with MPH increased the reference memory error, the impulsivity and the motor activity of the DSP4-treated rats. Since the noradrenergic terminals in a DSP4-treated rat are significantly reduced, the administration of MPH has little effect on the noradrenergic system and increases dopaminergic rather than noradrenergic activity, resulting in an imbalance with relatively high dopaminergic and low noradrenergic activities. It is suggested that a reduction of noradrenaline and an increase of dopamine induce ADHD-related deficits and that the depletion of noradrenaline is not sufficient for an appropriate rat model of ADHD.