The problems of inattention: methods and interpretations. (Editorial)

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Monoamine activity reflected in urine of young patients with obsessive compulsive disorder, psychosis with and without reality distortion and healthy subjects: an explorative analysis

Introduction: Positive psychotic symptoms are reported to be associated with high dopamine (DA), negative symptoms with low DA activity and serotonin (5-HT) activity may be altered in obsessive-compulsive disorder (OCD). Method: We analysed 24h urine samples in groups of patients with OCD, paranoid and non-paranoid schizophrenia and in healthy controls for supportive evidence. Results: Young unmedicated OCD subjects excreted more adrenaline (AD) and homovanillic acid (HVA) and showed a higher HVA/MHPG metabolite ratio and metabolic rate than healthy controls. Independent of general metabolic rate OCD patients showed higher HVA concentrations which suggests that the relative activity of catecholamine systems in OCD (HVA/MHPG) is due more to high DA than to low noradrenergic (NA) activity. Concentrations of 5-HT were also high in OCD patients. In psychotic patients low levels of DA, HVA, NA and MHPG probably resulted from neuroleptic medication. Conclusions: 1. Patients diagnosed with paranoid psychosis showed higher DA utilization than controls and those with few paranoid symptoms showed high 5-HT utilization. 2. These results support studies suggesting that paranoid psychosis is associated more with increased DA activity (discussed in the context of neuroleptic reactivity), that non-paranoid forms are associated more with increased 5-HT activity and that OCD patients are unusually aroused with high levels of Adrenaline, 5-HT and HVA

Attention deficit disorder with hyperactivity (ADDH): the contribution of catecholaminergic activity

Introduction: An attention deficit disorder with hyperactivity in children (ADDH, later known as ADHD) is now recognized in most countries, although diagnostic practices differ. Evidence is presented to show that the two cardinal symptoms of poor attentional performance and a high degree of motor activity may be functionally and causally separate. Psychobiology: Both attentional and motor-activity alterations are temporarily relieved in a proportion of subjects that respond to psychostimulants. Beneficial treatment decreases noradrenergic (NA) metabolism and normalizes variable levels of dopaminergic (DA) metabolism. Clinical and animal models: Parallels are drawn with other clinical syndromes arising from changed catecholaminergic activity (cf. Phenylketonuria, Tourette's syndrome, Lesch-Nyhan syndrome) and with behavioral interpretations of the result of damage to the dorsal noradrenergic bundle and dopaminergic VTA A10 nucleus (an animal model). Biopsychological research directions: Prognosis of ADDH subjects after treatment remains relatively poor. There may be a further defect of neurotransmitter metabolism in the ADDH syndrome. Research strategies are suggested based on the neurobiological correlates of the cognitive style of ADDH subjects and limbic/septal function in the animal model of the spontaneously hypertensive rat (SHR) Topics: 1 . Psychostimulant response ... Catecholamines / Serotonin, 2 . Electrophysiological and behavioral indices 3 . Responses to monoaminergic agents ... Precursors, L-DOPA, amino acids, monoamine oxidase and others: 4 . Clinical comparisons ... Phenylketonuria, Tourette's syndrome, Lesch-Nyhan syndrome: 5 . Models ... spontaneously hypertensive rat, neurobiology of hypertension Noradrenaline (NA), Glutamate (Glu), Neuropeptide Y (NPY) & Angiotensin, Serotonin (5-HT), Dopamine (DA): 6 . Link between behavior and cognition ... the septum and conditioned blocking measures of selective attention

Conditioned blocking in patients with paranoid, non-paranoid psychosis or obsessive compulsive disorder: associations with symptoms, personality and monoamine metabolism

Introduction: Conditioned blocking (CB) refers to a delay in learning that a new stimulus, added during learning, has the same consequences as the conditioned stimulus already present. In animals such "learned inattention" depends on monoaminergic and limbic function and, thus, CB performance should be informative on selective information processing impairments found in subgroups of psychotic patients. Attenuated CB in acute schizophrenia has been reported to normalize rapidly. Method: This study examines in young patients the specificity of CB performance to illness, and its associations with symptoms, personality traits and monoaminergic metabolic status. Results: Performance: CB was attenuated in psychotic patients with nonparanoid symptoms (NP: n=12, mean age 17 years) with respect to obsessive compulsive (OCD: n=13, mean age 16 years) and healthy subjects (CON; n=29, mean age 18 years), but only a transient attenuation was observed in paranoid hallucinatory patients (PH: n=14, mean age 19 years). The severity of negative symptoms in psychosis and specific negative/positive symptoms in the NP/PH groups were associated with reduced CB. Outgoing personality traits in CON and OCD subjects correlated with CB. In NP patients attenuated CB was associated with increasing neurotic lability. In PH patients CB correlated positively with "manic" but negatively with psychotic or neurotic scores. Monoamines: Increased dopamine activity (24h urine samples) correlated positively with CB, but relative increases of noradrenaline metabolism in NP and serotonin metabolism in OCD patients interfered. Conclusions: Marked psychotic or neurotic traits and some negative symptom states were associated with reduced CB. The particular selective processing problems of NP patients may reflect inappropriate NA activity

Attention-deficit hyperactivity disorder (ADHD) and glial integrity: an exploration of associations of cytokines and kynurenine metabolites with symptoms and attention

<p>Abstract</p> <p>Background</p> <p>In contrast to studies of depression and psychosis, the first part of this study showed no major differences in serum levels of cytokines and tryptophan metabolites between healthy children and those with attention-deficit/hyperactivity disorder of the combined type (ADHD). Yet, small decreases of potentially toxic kynurenine metabolites and increases of cytokines were evident in subgroups. Therefore we examined predictions of biochemical associations with the major symptom clusters, measures of attention and response variability.</p> <p>Methods</p> <p>We explored systematically associations of 8 cytokines (indicators of pro/anti-inflammatory function) and 5 tryptophan metabolites with symptom ratings (e.g. anxiety, opposition, inattention) and continuous performance test (CPT) measures (e.g. movement, response time (RT), variability) in 35 ADHD (14 on medication) and 21 control children. Predictions from linear regressions (controlled by the false discovery rate) confirmed or disconfirmed partial correlations accounting for age, body mass and socio-economic status.</p> <p>Results</p> <p><b>(1) </b>Total symptom ratings were associated with increases of the interleukins IL-16 and IL-13, where relations of IL-16 (along with decreased S100B) with hyperactivity, and IL-13 with inattention were notable. Opposition ratings were predicted by increased IL-2 in ADHD and IL-6 in control children. <b>(2) </b>In the CPT, IL-16 related to motor measures and errors of commission, while IL-13 was associated with errors of omission. Increased RT variability related to lower TNF-α, but to higher IFN-γ levels. <b>(3) </b>Tryptophan metabolites were not significantly related to symptoms. But increased tryptophan predicted errors of omission, its breakdown predicted errors of commission and kynurenine levels related to faster RTs.</p> <p>Conclusions</p> <p>Many associations were found across diagnostic groups even though they were more marked in one group. This confirms the quantitative trait nature of these features. Conceptually the relationships of the pro- and antiinflammatory cytokines distinguished between behaviours associated more with cognitive or more with motor control respectively. Further study should extend the number of immunological and metabolic markers to confirm or refute the trends reported here and examine their stability from childhood to adolescence in a longitudinal design.</p

Attention-deficit hyperactivity disorder (ADHD) and glial integrity: S100B, cytokines and kynurenine metabolism--effects of medication

Children with attention-deficit/hyperactivity disorder (ADHD) show a marked temporal variability in their display of symptoms and neuropsychological performance. This could be explained in terms of an impaired glial supply of energy to support neuronal activity

Cycles of construing in radicalization and deradicalization: a study of Salafist Muslims.

© Taylor & Francis Group, LLC.This article explores radicalization and deradicalization by considering the experiences of six young Tunisian people who had become Salafist Muslims. Their responses to narrative interviews and repertory grid technique are considered from a personal construct perspective, revealing processes of construing and reconstruing, as well as relevant aspects of the structure and content of their construct systems. In two cases, their journeys involved not only radicalization but self-deradicalization, and their experiences are drawn on to consider implications for deradicalization.Peer reviewedFinal Accepted Versio

Response variability in Attention-Deficit/Hyperactivity Disorder: a neuronal and glial energetics hypothesis

BACKGROUND: Current concepts of Attention-Deficit/Hyperactivity Disorder (ADHD) emphasize the role of higher-order cognitive functions and reinforcement processes attributed to structural and biochemical anomalies in cortical and limbic neural networks innervated by the monoamines, dopamine, noradrenaline and serotonin. However, these explanations do not account for the ubiquitous findings in ADHD of intra-individual performance variability, particularly on tasks that require continual responses to rapid, externally-paced stimuli. Nor do they consider attention as a temporal process dependent upon a continuous energy supply for efficient and consistent function. A consideration of this feature of intra-individual response variability, which is not unique to ADHD but is also found in other disorders, leads to a new perspective on the causes and potential remedies of specific aspects of ADHD. THE HYPOTHESIS: We propose that in ADHD, astrocyte function is insufficient, particularly in terms of its formation and supply of lactate. This insufficiency has implications both for performance and development: H1) In rapidly firing neurons there is deficient ATP production, slow restoration of ionic gradients across neuronal membranes and delayed neuronal firing; H2) In oligodendrocytes insufficient lactate supply impairs fatty acid synthesis and myelination of axons during development. These effects occur over vastly different time scales: those due to deficient ATP (H1) occur over milliseconds, whereas those due to deficient myelination (H2) occur over months and years. Collectively the neural outcomes of impaired astrocytic release of lactate manifest behaviourally as inefficient and inconsistent performance (variable response times across the lifespan, especially during activities that require sustained speeded responses and complex information processing). TESTING THE HYPOTHESIS: Multi-level and multi-method approaches are required. These include: 1) Use of dynamic strategies to evaluate cognitive performance under conditions that vary in duration, complexity, speed, and reinforcement; 2) Use of sensitive neuroimaging techniques such as diffusion tensor imaging, magnetic resonance spectroscopy, electroencephalography or magnetoencephalopathy to quantify developmental changes in myelination in ADHD as a potential basis for the delayed maturation of brain function and coordination, and 3) Investigation of the prevalence of genetic markers for factors that regulate energy metabolism (lactate, glutamate, glucose transporters, glycogen synthase, glycogen phosphorylase, glycolytic enzymes), release of glutamate from synaptic terminals and glutamate-stimulated lactate production (SNAP25, glutamate receptors, adenosine receptors, neurexins, intracellular Ca(2+)), as well as astrocyte function (α(1), α(2 )and β-adrenoceptors, dopamine D1 receptors) and myelin synthesis (lactate transporter, Lingo-1, Quaking homolog, leukemia inhibitory factor, and Transferrin). IMPLICATIONS OF THE HYPOTHESIS: The hypothesis extends existing theories of ADHD by proposing a physiological basis for specific aspects of the ADHD phenotype – namely frequent, transient and impairing fluctuations in functioning, particularly during performance of speeded, effortful tasks. The immediate effects of deficient ATP production and slow restoration of ionic gradients across membranes of rapidly firing neurons have implications for daily functioning: For individuals with ADHD, performance efficacy would be enhanced if repetitive and lengthy effortful tasks were segmented to reduce concurrent demands for speed and accuracy of response (introduction of breaks into lengthy/effortful activities such as examinations, motorway driving, assembly-line production). Also, variations in task or modality and the use of self- rather than system-paced schedules would be helpful. This would enable energetic demands to be distributed to alternate neural resources, and energy reserves to be re-established. Longer-term effects may manifest as reduction in regional brain volumes since brain areas with the highest energy demand will be most affected by a restricted energy supply and may be reduced in size. Novel forms of therapeutic agent and delivery system could be based on factors that regulate energy production and myelin synthesis. Since the phenomena and our proposed basis for it are not unique to ADHD but also manifests in other disorders, the implications of our hypotheses may be relevant to understanding and remediating these other conditions as well

A left temporal lobe impairment of auditory information processing in schizophrenia: an event-related potential study

Introduction: A measure of auditory prepulse inhibition (PPI) or sensory gating is the reduction of the scalp-recorded P1 event-related potential (ERP) after a sound that is preceded by 100-300 ms by a click as prepulse. This measure of sensory gating was adapted to study the effect of a prepulse on processing tones that were part of a "Go/no-go" discrimination. Methods: ERPs were recorded at right and left frontal and temporal sites on the scalp of groups of patients with schizophrenia (SCH, 8), obsessive compulsive disorder (OCD, 10) and healthy controls (CON, 19). Results: a) Both patient groups responded slower and showed more errors of omission than controls. b) A prepulse presented 100 ms (but not at 500 ms) before either tone reduced the P1 or P50 ERP amplitude on healthy controls, but showed a right temporal shift in the SCH patients. c) If the tone was the 'no-go' stimulus in the tone discrimination the prepulse reduced the N1 amplitude in both normal controls and SCH patients. This N100 amplitude was similar in records from over the left and right hemisphere of controls but was shifted to right temporal sites in the SCH group. d) OCD patients showed a relative predominance of the left hemisphere in the gating of frontal P1, N100 and P300 components, but early gating was not significantly impaired in this group. Conclusions: These results show a reduction of a PPI-like effect on early processing (e.g. P50/P1) that is more marked in the left hemisphere of SCH patients, and may affect channel selection for processing information about task-relevant sounds (e.g. N100