Therapy-relevant factors in adult ADHD from a cognitive behavioural perspective

Adult individuals with attention-deficit hyperactivity disorder (ADHD) have been suffering from this neurobiological and highly heritable disorder chronically since childhood. Resulting from their longstanding neuropsychological impairments, such as attentional problems, emotional instability, and disinhibition, they are familiar to a multiplicity of negative life outcomes and underachievement. Furthermore, a large part of this population suffers from psychiatric comorbidity. This accumulation of negative experiences has an impact on therapy-relevant factors such as the individual's self-esteem, self-efficacy, development of core beliefs/schemas, and coping strategies. Based on negative beliefs about the self, individuals confronted with difficult situations develop maladaptive coping strategies, for instance avoidance and procrastination. These strategies lead to maintenance and reinforcement of maladaptive beliefs, and as such they acquit themselves as schema-confirming. Captured in this vicious cycle, the individual sees her negative view of the self confirmed. The purpose of this paper is to illuminate these interactive factors that influence the aforementioned cycle in order to emphasize the cognitive behavioural interventions tailored to those factors on the basis of latest research. Furthermore, the authors want to attract notice to the resources people with ADHD are said to have, namely creativity and resilience. These postulated resources could be therapy-relevant by creating positive beliefs about the self, hence improving coping skills and breaking the vicious circle of negative appraisal. Taking into account personal resources and their fostering may be an important fundament for the treatment plan of adult ADHD. Information on the current state of research and theoretical approaches concerning the below-mentioned key words was gathered through MEDLINE, PsycINFO, PSYNDEXplus, and PubMed databases.     

Obovatol improves cognitive functions in animal models for Alzheimer's disease

Etiology of Alzheimer's disease (AD) is obscure, but neuroinflammation and accumulation of β-amyloid (Aβ) are implicated in pathogenesis of AD. We have shown anti-inflammatory and neurotrophic properties of obovatol, a biphenolic compound isolated from Magnolia obovata. In this study, we examined the effect of obovatol on cognitive deficits in two separate AD models: (i) mice that received intracerebroventricular (i.c.v.) infusion of Aβ(1-42) (2.0 μg/mouse) and (ii) Tg2576 mice-expressing mutant human amyloid precursor protein (K670N, M671L). Injection of Aβ(1-42) into lateral ventricle caused memory impairments in the Morris water maze and passive avoidance tasks, being associated with neuroinflammation. Aβ(1-42) -induced abnormality was significantly attenuated by administration of obovatol. When we analyzed with Tg2576 mice, long-term treatment of obovatol (1 mg/kg/day for 3 months) significantly improved cognitive function. In parallel with the improvement, treatment suppressed astroglial activation, BACE1 expression and NF-κB activity in the transgenic mice. Furthermore, obovatol potently inhibited fibrillation of Aβin vitro in a dose-dependent manner, as determined by Thioflavin T fluorescence and electron microscopic analysis. In conclusion, our data demonstrated that obovatol prevented memory impairments in experimental AD models, which could be attributable to amelioration of neuroinflammation and amyloidogenesis by inhibition of NF-κB signaling pathway and anti-fibrillogenic activity of obovatol.     

Prevalence of adult ADHD in an all-female prison unit

There is increasing evidence suggesting a link between ADHD and criminality, including a strong association between ADHD symptoms and the likelihood of being on probation or in prison. Most studies investigating the prevalence of ADHD in prison populations have focused on adult male offenders. In the current study, 69 female prisoners were screened for both childhood and adult ADHD symptoms using the Barkley Adult ADHD Rating Scale-IV. The results indicate that 41 % of the prisoners met the diagnostic criteria for ADHD in childhood and continued to meet criteria for ADHD as adults. More importantly, young female prisoners (aged 18–25) were significantly more likely to report symptoms of ADHD than older prisoners. Prisoners who reported symptoms of ADHD also reported high levels of impairment associated with these symptoms. A better understanding of the prevalence of ADHD in female prison units can highlight specific areas for intervention during rehabilitation, as well as the management of serious incidents within prison.     

Astrocytic Piezo1-mediated mechanotransduction determines adult neurogenesis and cognitive functions

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Lithium improves hippocampal neurogenesis, neuropathology and cognitive functions in APP mutant mice

Background

Alzheimer''s disease (AD) is a neurodegenerative disorder characterized by progressive deterioration of cognitive functions, extracellular β-amyloid (Aβ) plaques and intracellular neurofibrillary tangles within neocortex and hippocampus. Adult hippocampal neurogenesis plays an important role in learning and memory processes and its abnormal regulation might account for cognitive impairments associated with AD.

Methodology/Principal Findings

The double transgenic (Tg) CRND8 mice (overexpressing the Swedish and Indiana mutations in the human amyloid precursor protein), aged 2 and 6 months, were used to examine in vivo the effects of 5 weeks lithium treatment. BrdU labelling showed a decreased neurogenesis in the subgranular zone of Tg mice compared to non-Tg mice. The decrease of hippocampal neurogenesis was accompanied by behavioural deficits and worsened with age and pathology severity. The differentiation into neurons and maturation of the proliferating cells were also markedly impaired in the Tg mice. Lithium treatment to 2-month-old Tg mice significantly stimulated the proliferation and neuron fate specification of newborn cells and fully counteracted the transgene-induced impairments of cognitive functions. The drug, by the inhibition of GSK-3β and subsequent activation of Wnt/ß-catenin signalling promoted hippocampal neurogenesis. Finally, the data show that the lithium''s ability to stimulate neurogenesis and cognitive functions was lost in the aged Tg mice, thus indicating that the lithium-induced facilitation of neurogenesis and cognitive functions declines as brain Aβ deposition and pathology increases.

Conclusions

Lithium, when given on time, stimulates neurogenesis and counteracts AD-like pathology.     

Whole-body arginine dimethylation is associated with all-cause mortality in adult renal transplant recipients

Amino Acids - Arginine residues in proteins can be singly or doubly methylated post-translationally. Proteolysis of arginine-methylated proteins provides monomethyl arginine, asymmetric...     

Childhood and persistent ADHD symptoms associated with educational failure and long-term occupational disability in adult ADHD

Few studies have examined the impact of childhood attention deficit hyperactivity disorder (ADHD) symptoms on adult ADHD functional outcomes. To address this issue dimensionally, ADHD symptoms in childhood and adulthood and their relation to educational deficits and work disability are studied in a clinical sample of adult patients with previously untreated ADHD. About 250 adults diagnosed systematically with ADHD according to DSM-IV were prospectively recruited. Primary outcomes were high school dropout and being out of the work last year. Childhood ADHD symptoms, sex differences, comorbidities of other mental disorders, and adult ADHD symptoms were examined by historical data, clinician interviews, and questionnaires. High levels of ADHD symptom severity in childhood were related to dropping out of high school [odds ratio (OR) = 3.0], as were higher numbers of hyperactive–impulsive symptoms in childhood. Significantly, more women than men were long-term work disabled (OR = 2.0). After adjusting for age and gender, persisting high levels of ADHD inattention symptoms in adulthood (OR = 2.5), number of comorbid disorders, and particularly anxiety disorders were significantly related to long-term work disability. Childhood hyperactive–impulsive symptoms and overall severity of childhood ADHD symptoms were associated with high school dropout rates; however, persisting ADHD inattention symptoms and comorbid mental disorders in adulthood were more correlated to occupational impairment. These findings underline proposals for studies on early recognition and interventions for ADHD and psychiatric comorbidity. They further suggest that inattentive symptoms be a focus of adult ADHD treatment and that workplace interventions be considered to prevent long-term work disability.     

Whole-body vibration increases upper and lower body muscle activity in older adults: potential use of vibration accessories

The current study examined the effects of whole-body vibration (WBV) on upper and lower body muscle activity during static muscle contractions (squat and bicep curls). The use of WBV accessories such as hand straps attached to the platform and a soft surface mat were also evaluated. Surface electromyography (sEMG) was measured for the medial gastrocnemius (MG), vastus lateralis (VL), and biceps brachii (BB) muscles in fourteen healthy older adults (74.8±4.5 years; mean±SD) with a WBV stimulus at an acceleration of 40 m s(-2) (30 Hz High, 2.5 mm or 46 Hz Low, 1.1 mm). WBV increased lower body (VL and MG) sEMG vs baseline (no WBV) though this was decreased with the use of the soft mat. The addition of the bicep curl with hand straps had no effect on lower body sEMG. WBV also increased BB sEMG vs baseline which was further increased when using the hand straps. There was no upper body effect of the soft mat. This study demonstrates WBV increases both lower and upper body muscle activity in healthy older adults. Moreover, WBV accessories such as hand straps attached to the platform or a soft surface mat may be used to alter exercise intensity.     

Whole-body vibration induced adaptation in knee extensors; consequences of initial strength, vibration frequency, and joint angle

It was hypothesized that both vibration frequency and muscle length modulate the strengthening of muscles that is assumed to result from whole-body vibration (WBV). Length of knee extensor muscles during vibration is affected by the knee joint angle; the lengths of the knee extensors increase with more flexed knee joint angles. In an intervention study 28 volunteers were randomly assigned to 1 of 4 groups. Each group received 4 weeks of WBV at 1 of 3 different frequencies (20, 27, or 34 Hz) or 1 of 2 different lengths of knee extensors. Voluntary, isometric knee extension moment-angle relationship was determined. Initially, stronger subjects reacted differently to WBV than weaker participants. In stronger subjects knee extension moment did not improve; in the weaker subjects considerable improvements were observed ranging from 10 to 50%. Neither vibration frequency nor muscle length during the intervention affected the improvements. In addition to strength, the knee joint angle at which the maximal joint moment was generated (optimal joint angle) was affected. When trained at short muscle lengths, optimal angle shifted to more extend joint position. WBV training at long muscle lengths tended to induce an opposite shift. The amount of this shift tended to be influenced by vibration frequency; the lower the vibration frequency the larger the shift. Shifts of optimal lengths occurred in both weaker and stronger subjects. This study shows that muscle length during training affects the angle of knee joint at which the maximal extension moment was generated. Moreover, in weaker subjects WBV resulted in higher maximal knee joint extension moments. Vibration frequency and muscle length during vibration did not affect this joint moment gain.     

Dietary deficiencies of single amino acids: Whole-body amino acid composition of adult rats

Abstract

To ascertain whether chronic amino acid deficiency alters the amino acid composition of the body, 44 adult female rats were randomly allocated to one of 11 treatments which included one control group, ingesting an adequate diet with balanced protein, and ten deficient groups in which one group received protein-deficient diets and the other groups consumed diets each deficient in a single essential amino acid. The degree of deficiency was adjusted to achieve a gradual decline in body weight to 85% of the initial weight and was then adjusted so that this weight was maintained until the end of the experiment at 93 days, when the rats were killed. Deficient rats had lower absolute weights of liver, gastrointestinal tract and muscle than animals given the adequate diet but greater relative weights (% of body weight) of heart and kidneys. There were no significant differences amongst groups in percentages of lipid, nitrogen, protein plus lipid or dry matter. Chronic marginal amino acid deficiencies did not selectively alter amino acid composition.     

Glycogen phosphorylase inhibition improves cognitive function of aged mice

Inhibition of glycogen breakdown blocks memory formation in young animals, but it stimulates the maintenance of the long-term potentiation, a cellular mechanism of memory formation, in hippocampal slices of old animals. Here, we report that a 2-week treatment with glycogen phosphorylase inhibitor BAY U6751 alleviated memory deficits and stimulated neuroplasticity in old mice. Using the 2-Novel Object Recognition and Novel Object Location tests, we discovered that the prolonged intraperitoneal administration of BAY U6751 improved memory formation in old mice. This was accompanied by changes in morphology of dendritic spines in hippocampal neurons, and by “rejuvenation” of hippocampal proteome. In contrast, in young animals, inhibition of glycogen degradation impaired memory formation; however, as in old mice, it did not alter significantly the morphology and density of cortical dendritic spines. Our findings provide evidence that prolonged inhibition of glycogen phosphorolysis improves memory formation of old animals. This could lead to the development of new strategies for treatment of age-related memory deficits.     

Supplementation with flax oil and vitamin C improves the outcome of Attention Deficit Hyperactivity Disorder (ADHD)

Considerable clinical and experimental evidence now supports the idea that deficiencies or imbalances in certain highly unsaturated fatty acids may contribute to a range of common developmental disorders including Attention Deficit Hyperactivity Disorder (ADHD). Few intervention studies with LCPUFA supplementation have reported inconsistent and marginal results. This pilot study evaluates the effect of alpha linolenic acid (ALA)-rich nutritional supplementation in the form of flax oil and antioxidant emulsion on blood fatty acids composition and behavior in children with ADHD. Post-supplementation levels of RBC membrane fatty acids were significantly higher than pretreatment levels as well as the levels in control. There was significant improvement in the symptoms of ADHD reflected by reduction in total hyperactivity scores of ADHD children derived from ADHD rating scale.     

Combination of scoring functions improves discrimination in protein-protein docking

Two structure-based potentials are used for both filtering (i.e., selecting a subset of conformations generated by rigid-body docking), and rescoring and ranking the selected conformations. ACP (atomic contact potential) is an atom-level extension of the Miyazawa-Jernigan potential parameterized on protein structures, whereas RPScore (residue pair potential score) is a residue-level potential, based on interactions in protein-protein complexes. These potentials are combined with other energy terms and applied to 13 sets of protein decoys, as well as to the results of docking 10 pairs of unbound proteins. For both potentials, the ability to discriminate between near-native and non-native docked structures is substantially improved by refining the structures and by adding a van der Waals energy term. It is observed that ACP and RPScore complement each other in a number of ways (e.g., although RPScore yields more hits than ACP, mainly as a result of its better performance for charged complexes, ACP usually ranks the near-native complexes better). As a general solution to the protein-docking problem, we have found that the best discrimination strategies combine either an RPScore filter with an ACP-based scoring function, or an ACP-based filter with an RPScore-based scoring function. Thus, ACP and RPScore capture complementary structural information, and combining them in a multistage postprocessing protocol provides substantially better discrimination than the use of the same potential for both filtering and ranking the docked conformations.     

Neuroimaging of cognitive functions in human parietal cortex

Functional neuroimaging has proven highly valuable in mapping human sensory regions, particularly visual areas in occipital cortex. Recent evidence suggests that human parietal cortex may also consist of numerous specialized subregions similar to those reported in neurophysiological studies of non-human primates. However, parietal activation generalizes across a wide variety of cognitive tasks and the extension of human brain mapping into higher-order "association cortex" may prove to be a challenge.     

Methylphenidate improves the behavioral and cognitive deficits of neurogranin knockout mice

Neurogranin (Ng), a brain‐specific calmodulin‐binding protein, is expressed highly in hippocampus, and is important for cognitive function. Deletion of the Ng gene from mice caused attenuation of signal reaction cascade in hippocampus, impairments in learning and memory and high frequency stimulation‐induced long‐term potentiation (LTP). Environmental enrichment alone failed to improve cognitive function. In this study, behavioral testing revealed that Ng knockout (NgKO) mice were both hyperactive and socially withdrawn. Methylphenidate (MPH) was given to mice while they were also kept under an enrichment condition. MPH treatment reduced the hyperactivity of NgKO mice tested in both the open field and forced swim chamber. MPH improved their social abilities such that mice recognized and interacted better with novel subjects. The cognitive memories of MPH‐treated mutants were improved in both water maze and contextual fear conditioning tests. High frequency stimulation‐induced LTP of NgKO mice was also improved by MPH. The present treatment regimen, however, did not fully reverse the deficits of the mutant mice. In contrast, MPH exerted only a minimal effect on the wild type mice. At the cellular level, MPH increased the number of glial fibrillary acidic protein‐positive cells in hippocampus, particularly within the dentate gyrus of NgKO mice. Therefore it will be of interest to determine the nature of MPH‐mediated astrocyte activation and how it may modulate behavior in future studies. Taken together these NgKO mice may be useful for the development of better drug treatment to improve cognitive and behavioral impairments.     

Motor and cognitive functions of the ventral premotor cortex

Recent data show that the ventral premotor cortex in both humans and monkeys has motor and cognitive functions. The cognitive functions include space perception, action understanding and imitation. The data also show a clear functional homology between monkey area F5 and human area 44. Preliminary evidence suggests that the ventral part of the lateral premotor cortex in humans may correspond to monkey area F4. A tentative map of the human lateral premotor areas founded on the reviewed evidence is presented.     

Erythropoietin improves operant conditioning and stability of cognitive performance in mice

Background  

Executive functions, learning and attention are imperative facets of cognitive performance, affected in many neuropsychiatric disorders. Recently, we have shown that recombinant human erythropoietin improves cognitive functions in patients with chronic schizophrenia, and that it leads in healthy mice to enhanced hippocampal long-term potentiation, an electrophysiological correlate of learning and memory. To create an experimental basis for further mechanistic insight into erythropoietin-modulated cognitive processes, we employed the Five Choice Serial Reaction Time Task. This procedure allows the study of the effects of erythropoietin on discrete processes of learning and attention in a sequential fashion.