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R D Oades

Publications and source records attributed to R D Oades.

At least 19 recordsLinked to original sources
PubMed2006

The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder: association signals in DRD4, DAT1 and 16 other genes.

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, starting in early childhood and persisting into adulthood in the majority of cases. Family and twin studies have demonstrated the importance of genetic factors and candidate gene association studies have identified several loci that exert small but significant effects on ADHD. To provide further clarification of reported associations and identify novel associated genes, we examined 1,038 single-nucleotide polymorphisms (SNPs) spanning 51 candidate genes involved in the regulation of neurotransmitter pathways, particularly dopamine, norepinephrine and serotonin pathways, in addition to circadian rhythm genes. Analysis used within family tests of association in a sample of 776 DSM-IV ADHD combined type cases ascertained for the International Multi-centre ADHD Gene project. We found nominal significance with one or more SNPs in 18 genes, including the two most replicated findings in the literature: DRD4 and DAT1. Gene-wide tests, adjusted for the number of SNPs analysed in each gene, identified associations with TPH2, ARRB2, SYP, DAT1, ADRB2, HES1, MAOA and PNMT. Further studies will be needed to confirm or refute the observed associations and their generalisability to other samples.

Adolescent↗
PubMed2004

Frontal and temporal sources of mismatch negativity in healthy controls, patients at onset of schizophrenia in adolescence and others at 15 years after onset.

Mismatch negativity (MMN) is an event-related potential measure of auditory change detection. It is widely reported to be smaller in patients with schizophrenia and may not improve along with otherwise successful clinical treatment. The main aim of this report is to explore ways of measuring and presenting four features of frequency-deviant MMN dipole sources (dipole moment, peak latency, brain location and orientation) and to relate these to the processes of psychopathology and illness progression. Data from early onset patients (EOS) at the start of the illness in adolescence, and others who had their first break in adolescence 15 years ago (S-15Y) were compared with two groups of age-matched healthy controls (C-EOS, C-15Y). A four-source model fitted the MMN waveform recorded from all four groups, whether MMN amplitude was more (EOS) or less (S-15Y) reduced. The locations were in the left superior temporal and anterior cingulate gyri, right superior temporal and inferior/mid frontal cortices. Dipole latencies confirmed a bottom-up sequence of processing and dipole moments were larger in the temporal lobes and on the left. Patients showed small dipole location changes that were more marked in the S-15Y than the EOS group (more rostral for the left anterior cingulate, more caudal for the right mid-frontal dipole) consistent with illness progression. The modelling of MMN dipole sources on brain atlas and anatomical images suggests that there is a degree of dissociation during illness between small progressive anatomical changes and some functional recovery indexed by scalp recordings from patients with an onset in adolescence 15 years before compared to adolescents in their first episode.

Adolescent↗
PubMed2001

Conditioned blocking and schizophrenia: a replication and study of the role of symptoms, age, onset-age of psychosis and illness-duration.

Measures of selective attention processing like latent inhibition (LI) and conditioned blocking (CB) are disturbed in some patients with schizophrenia. [LI is the delay in learning about the associations of a stimulus that has been associated with no event (versus de novo learning); CB is the delay in learning the associations of a stimulus-component when the other component has already started to acquire these associations.] We proposed: (1) to replicate the reported decreases of CB in patients without paranoid-hallucinatory symptoms; (2) to see if CB depends on the age of illness-onset and its duration, as reported for LI. We studied 101 young and old, acute and chronically ill patients with schizophrenia, of whom 62 learned a modified 'mouse-in-house' CB task, and compared them with 62 healthy controls matched for age, education and socio-economic background. CB was more evident in patients with a diagnosis of paranoid schizophrenia than other subtypes. An unusual persistence of high CB scores through testing was associated with productive symptoms (including positive thought disorder). Reduced CB related to the expression of (a) Schneider's first rank symptoms of ideas-of-reference and (b) to negative symptoms like poor rapport and poor attention. CB was less evident in the older patients and those with an earlier illness-onset. In contrast to the similar LI test of selective attention, CB is found in patients with paranoid schizophrenia and its expression is not related closely to illness duration. This implies that the two tests reflect the activity of different underlying processes. We suggest that reduced CB on initial test-trials in nonparanoid schizophrenia reflects the unusual persistence of controlled information processing strategies that would normally become automatic during conditioning. In contrast, continued CB during testing reflects an unusual persistence of automatic processing strategies.

Acute Disease↗
PubMed2001

Dehydroepiandrosterone sulphate and corticotropin levels are high in young male patients with conduct disorder: comparisons for growth factors, thyroid and gonadal hormones.

Childhood conduct disorder (CD) may originate in a stressful upbringing, and be associated with unusual physical or sexual development and thyroid dysfunction. We therefore explored circulating levels of hormones from adrenal, gonadal and growth hormone axes associated with stress, aggression and development in 28 CD patients and 13 age-matched healthy children (10-18 years old). The CD group had higher levels of dehydroepiandrosterone sulphate (DHEA-S), corticotropin (ACTH) and free tri-iodothyronine (fT(3)) if under 14 years. There were no differences for gonadal hormones or maturity ratings which were not associated with aggression. Smaller physical measures in CD children correlated with DHEA-S and growth factors (e.g. insulin-like growth factor I) increased ACTH and fT(3) correlated with restless-impulsive ratings, and DHEA-S with 'disruptive behaviour'. Imbalances in the adrenal and growth axes may have neurotropic repercussions in development.

Adolescent↗
PubMed2001

Novelty-elicited mismatch negativity in patients with schizophrenia on admission and discharge.

OBJECTIVE: Given recent reports of differences between mismatch negativity (MMN) elicited by always novel sounds (novelty-elicited MMN) and that elicited by repeated rare deviants (conventional MMN), we investigated novelty-elicited MMN and P3a in patients with schizophrenia before and after a nonstandardized inpatient treatment. DESIGN: Electrophysiological and clinical assessment of patients on admission and discharge from hospital. Assessment of control subjects on 2 sessions. SETTING: Inpatient treatment in a psychiatric university hospital. SUBJECTS: 20 patients with schizophrenia and 21 healthy control subjects of similar age and sex. Selection of patients with first- to third-episode schizophrenia. OUTCOME MEASURES: Early and late component MMN amplitudes and latencies, P3a amplitudes and latencies, Positive and Negative Syndrome Scale (PANSS), Global Assessment of Functioning (GAF), Extrapyramidal Symptom Scale (EPS), Abnormal Involuntary Movement Scale (AIMS) and chlorpromazine equivalents. RESULTS: In patients with schizophrenia, novelty-elicited MMN was unimpaired on admission, and there was a statistically significant reduction of the late MMN component with treatment. Improvements in symptom expression were associated with increased latencies of the early MMN component. CONCLUSION: Results indicate differences in information processing between conventional and novelty-elicited MMN. Some components of the novelty-elicited MMN might be more state dependent than those of the conventional MMN.

Adult↗
PubMed2000

Differential measures of 'sustained attention' in children with attention-deficit/hyperactivity or tic disorders: relations to monoamine metabolism.

Controversy exists on whether the constructs tested by paper/pencil and computerized continuous-performance tests (CPT) are similar, and the deficits recorded in children with attention-deficit/hyperactivity symptoms (ADHD) are comparable. Signal-detection measures were recorded on four such tests of 'sustained attention', with increasing working-memory requirements in healthy children (14; mean 10 years), and those with ADHD (14; mean 10 years) or a tic syndrome (TS, 11; mean 11 years). Clinical associations were sought from 24-h urinary measures of monoamine activity. The cancellation paper/pencil test revealed no group differences for errors or signal detection measures. On the CPT, ADHD children made more omission and commission errors than control subjects, but TS children made mostly omissions. This reflected the poor perceptual sensitivity (d-prime, d') for ADHD and conservative response criteria (beta) for TS children. This group difference extended to the CPTax, which was shown on a regression analysis to test for putative working-memory-related abilities as well as concentration. In all children, immediate response-feedback reduced omissions, and modestly improved d'. CPTax performance related negatively to dopamine metabolism in control subjects and to serotonin metabolism in the ADHD group. But comparisons between the metabolites in the ADHD group suggest that increased serotonin and decreased noradrenaline, with respect to dopamine metabolism, may detract from CPT performance in terms of d'. CPT tasks demonstrated a perceptual-based impairment in ADHD and response conservatism in TS patients independent of difficulty. Catecholamine activity was implicated in the promotion of perceptual processing in normal and ADHD children, but serotonin activity may contribute to poor CPTax (working-memory) performance in ADHD patients.

Adolescent↗
PubMed2000

Neuropsychological and conditioned blocking performance in patients with schizophrenia: assessment of the contribution of neuroleptic dose, serum levels and dopamine D2-receptor occupancy.

Patients with schizophrenia show impairments of attention and neuropsychological performance, but the extent to which this is attributable to antipsychotic medication remains largely unexplored. We describe here the putative influence of the dose of antipsychotic medication (chlorpromazine equivalents, CPZ), the antipsychotic serum concentration of dopamine (DA) D2-blocking activity and the approximated central dopamine D2-receptor occupancy (DA D2-occupancy), on conditioned blocking (CB) measures of attention and performance on a neuropsychological battery, in 108 patients with schizophrenia (compared with 62 healthy controls). Antipsychotic serum concentration and D2-occupancy were higher in patients with a paranoid versus non-paranoid diagnosis, and in female versus male patients (independent of symptom severity). Controlling for D2-occupancy removed the difference between high CB in paranoid and impaired low CB in non-paranoid patients. Similar partial correlations for antipsychotic drug dose and serum levels of DA D2-blocking activity with performance of the trail-making and picture completion tests (negative) and the block-design task (positive) showed the functional importance of DA-related activity. High estimates of central DA D2-occupancy were related to impaired verbal fluency but were associated with improved recall of stories, especially in paranoid patients. This, the first study of its kind, tentatively imputes a role for DA D2-related activity in left frontal (e.g. CB, verbal fluency) and temporal lobe functions (verbal recall) as well as in some non-verbal abilities mediated more in the right hemisphere in patients with schizophrenia.

Adult↗
PubMed1999

A topographic event-related potential follow-up study on 'prepulse inhibition' in first and second episode patients with schizophrenia.

Dopamine agonists impair and antagonists normalize prepulse inhibition (PPI) of startle and gating of the P50 event-related potential (ERP), but the within-subject effect of treatment on impaired gating in schizophrenia has not been studied. We report the first results of a longitudinal study using PPI of ERPs as a measure of sensory gating in an auditory Go/NoGo discrimination. After admission and approximately 3 months later, at discharge, 15 patients with schizophrenia performed a discrimination between a 1.4 kHz target tone and an 0.8 kHz non-target tone with no prepulse, or with a prepulse at 100 ms or 500 ms before either tone. ERPs were recorded from 19 sites. Healthy subjects were studied twice, with 3 months between sessions. PPI of the P50 peak in the 100-ms condition was reduced in patients on admission. At discharge, decreased negative symptoms correlated with enhanced P50-PPI at frontocentral sites. After treatment increased N100-PPI at centrotemporal sites correlated with fewer positive symptoms. At frontal sites in the 100-ms condition, the initially small difference of non-target minus target P300 amplitudes increased as negative symptoms decreased. It is concluded that weak auditory prepulses interfere with early auditory stimulus processing (P50), channel selection (N100) and selective attention (P300). Gating of these stages of processing is impaired in psychotic patients and treatment tends to normalize gating in tandem with improvements of different types of symptoms.

Acoustic Stimulation↗
PubMed1999

Subclinical polydipsia and polyuria in young patients with schizophrenia or obsessive-compulsive disorder vs normal controls.

1. Increased water intake and output is more common among psychiatric patients, especially those with schizophrenia, than in the general population. Animal studies suggest that polydipsia and polyuria derive, in part, from dopamine dysregulation. Stimulated by these observations this study sought to elucidate relationships among water homeostasis, monoamine metabolism, and electrolyte excretion in schizophrenic patients with and without paranoid hallucinatory symptoms (PH vs. NP), thought to reflect hyper- and hypo-dopaminergic states respectively, and to compare these with those shown by patients with obsessive compulsive disorder (OCD). 2. 24 hr-urine samples for electrolyte, monoamine and metabolite measures were taken from 14 schizophrenic patients with PH symptoms, 13 with predominantly nonparanoid (NP) symptoms, 11 OCD patients and 27 healthy controls (matched for age, weight and creatinine production). Water intake and serum electrolytes was sampled during psychological testing. 3. PH patients drank 2-3 times more than the others in a 3-4 hr test, yet 24 hr-urinary volumes were 75% larger in both PH and NP patients than in the two comparison groups. 4. Daily potassium excretion was a bit higher in PH patients, but concentrations of sodium, potassium and phosphate tended to be lower in PH and NP patients than in the others. 5. Positive associations of electrolyte with homovanillic acid excretion were consistent across groups and not directly related to medication. But associations of electrolyte excretion with noradrenergic activity in controls were absent in psychotic patients and associations with serotonin in OCD patients were absent in the other groups. 6. Increased water intake and output in PH patients along with the disturbed association with noradrenergic metabolism are consistent with altered autonomic activity in these patients. 7. The independence of measures of water homeostasis from dopaminergic medication indicates that the associations in clinically responding PH patients of polydipsia with DA function (decreased DA levels) may be pertinent to this subgroup but not to schizophrenia in general.

Adolescent↗
PubMed1998

Plasma neuropeptide-Y levels, monoamine metabolism, electrolyte excretion and drinking behavior in children with attention-deficit hyperactivity disorder.

Against a background of (a) increased drinking behavior in children with attention-deficit hyperactivity disorder (ADHD); (b) the parallel between some behaviors associated with ADHD and hypertension; (c) the use of the spontaneously hypertensive rat as a model for ADHD; and (d) similarities in the changes of neuropeptide Y (NPY) and catecholamine in studies of hypertension and drinking, NPY, catecholamines and electrolyte balance were compared in the plasma and urine of healthy children and those with ADHD. Drinking was monitored during 3 h of neuropsychological tests over 2 days in 14 ADHD and nine healthy children. Patients drank four times as much water and showed twice the levels of NPY found in controls. In controls there were positive and in patients there were negative relationships for NPY with drinking and restless behavior. Patients' plasma levels of norepinephrine (NE) and epinephrine were slightly elevated, but urinary levels of NE and the serotonin metabolite were markedly increased. Urinary excretion rates for sodium (not potassium), phosphate and especially calcium were decreased in patients even after covarying for less urine production in the ADHD group. NPY levels were inversely related to calcium excretion and drinking was inversely related to circulating sodium. Increases of drinking and circulating NPY in ADHD children and decreased electrolyte excretion may reflect a common disturbance in metabolic homeostasis.

Adolescent↗
PubMed1998

Frontal, temporal and lateralized brain function in children with attention-deficit hyperactivity disorder: a psychophysiological and neuropsychological viewpoint on development.

This article considers deficits in the selective aspects of perception underlying symptoms of impaired attention and impulsivity in children with attention-deficit hyperactivity syndrome (ADHD) in terms of frontal and temporal lobe function and cerebral asymmetry. Tomographic studies suggest a disturbed fronto-striatal function, but have neglected limbic contributions under activating conditions and are equivocal on the nature of apparent lateralized differences. Neuropsychological and psychophysiological studies suggest that early and late stages of information processing are affected in both the frontal and temporal lobes and imply impaired intercortical dialog. Given the evidence for a normal specialization in global processing in the right and the processing of details in the left hemisphere, the lateralized impairment may progress from situational ADHD (impaired selective aspects of perception on the right) to pervasive ADHD (additional impairment in decision-making on the left). Accordingly some ADHD children may experience an early negative neurodevelopmental influence that only appears as the brain region matures while others show a delayed development of CNS function.

Attention Deficit Disorder with Hyperactivity↗
PubMed1997

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

A measure of auditory prepulse inhibition (PPI) 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. ERPs were recorded at right and left, frontal and temporal sites in groups of patients with schizophrenia (SCH) or obsessive compulsive disorder (OCD) and healthy controls (CON). A prepulse 100 ms but not 500 ms before either tone reduced the P1 ERP amplitude in healthy and OCD subjects but not SCH patients. At frontal and temporal recording sites the P1 amplitude was similar bilaterally in controls but showed a right temporal shift in the SCH patients. If the tone was the 'no-go' tone, the prepulse reduced the N1 amplitude in both the CON and SCH groups. The N1 was similar, bilaterally in controls but again showed a right temporal shift in the SCH group. These results show a reduction of a PPI-like effect on early processing (P1) that is more marked in the left hemisphere of SCH patients and may affect channel selection for processing information (N1) about task-relevant sounds.

Acoustic Stimulation↗
PubMed1997

Impaired attention-dependent augmentation of MMN in nonparanoid vs paranoid schizophrenic patients: a comparison with obsessive-compulsive disorder and healthy subjects.

Mismatch negativity (MMN), in the deviant-minus-standard event-related potential (ERP) difference-waveform, may represent a working memory trace of the tone difference. Most but not all studies find MMN reduced in schizophrenic patients. This report investigates if differences may be attributable to experimental condition (diffuse vs focused attention), component identification (N1-like vs N2-like), topographic distribution, and clinical condition (with/without paranoid-hallucinatory symptoms, PH/NP). Comparisons were made for 12 PH, 12 NP schizophrenic patients with 13 obsessive compulsive and 25 normal control subjects. Frontal MMN reduction in schizophrenics largely resulted from an absence of an increase in focused attention conditions as in comparison groups. But there was a marked temporal activity locus in NP patients. These features were not reflected in other components except for a visible but nonsignificant N1-like temporal locus in NP patients. Further, schizophrenic patients did not show an increase in late positivity with focused attention like the comparison groups. The results show that so-called automatic processing deficits (amount and locus of MMN) are best seen in situations requiring the activation of controlled attentional processes. It is suggested that impaired processing of irrelevant stimuli and reduced frontal MMN in NP patients may reflect reduced dopaminergic responsivity.

Adolescent↗
PubMed1997

Stimulus dimension shifts in patients with schizophrenia, with and without paranoid hallucinatory symptoms, or obsessive compulsive disorder: strategies, blocking and monoamine status.

Reversal, and intra-dimensional (ID) and extra-dimensional (ED) nonreversal discrimination shifts were studied to see if learned inattention to the irrelevant dimension differentially influenced the efficacy of learning and stimulus choice strategy. Performance was compared with conditioned blocking (CB) and monoamine metabolic status between healthy controls, patients with obsessive compulsive disorder (OCD) or schizophrenia with (PH) or without (NP) active paranoid hallucinatory symptoms. PH and NP patients improved learning with practice, but showed an impaired shift on each task. OCD patients were impaired only on the ED-shift. The NP patient's impairment was nonspecific and, unlike PH and controls, it related to reversal performance. All subjects acquired an attentional set for colour reflected in the length of stimulus-response sequences. Analysis of paired-stimulus choice-strategies showed that while all patients showed fewer correct win-stay choices, only PH patients perseverated with lose-stay choices. Learning about the added stimulus in the CB task related to ID-shift efficiency in NP patients. Increases of dopamine activity related to delayed learning but more switches of stimulus choice in the shift-tasks. Increases of serotonin activity correlated with faster learning in controls, OCD and PH patients. In NP patients the opposite held for dopamine and serotonin activity. Thus the two learned inattention tasks have different if related requirements and correlates: the data are consistent with the use of automatic exogenous attention strategies by NP patients, of inefficient controlled attention by PH patients and the automatization of endogenous processes in controls.

Adolescent↗
PubMed1997

The development of conditioned blocking and monoamine metabolism in children with attention-deficit-hyperactivity disorder or complex tics and healthy controls: an exploratory analysis.

Conditioned blocking (CB) measures the transient suppression of learning that a new stimulus, added during learning, has the same consequences as the conditioned stimulus already present. Normal CB increases between the age of 8 and 20 years (Oades, R.D., Roepcke, B. and Schepker, R., A. test of conditioned blocking and its development in childhood and adolescence: relationship to personality and monoamine metabolism, Dev. Neuropsychol., 12 (1996) 207-230). In the present study CB development is compared between healthy children (CN), children with attention deficit (ADHD) and those with complex tics or Tourette's syndrome (TS) with mean ages of 10-11 years. All children needed fewer learning trials with increasing age: the ADHD group showed a slight impairment. Only controls improved CB with increasing age. A trend for worse CB in the TS than the other groups was significant for those over 11 years. While ADHD children over 11 years showed less CB than controls, younger ADHD children showed more. A correlational analysis of the status of monoamine metabolism in 24 h urine samples showed a positive relationship for CB with dopamine metabolism in controls and TS children, but a negative relationship in ADHD children. In contrast, increases of serotonin metabolism were negatively related to CB in TS but positively in ADHD patients. In conclusion, when selective information processing abilities reflected by CB start to develop at puberty-onset, there is a relative worsening in ADHD patients. But TS patients show an impairment independent of age. Changes in the balance between dopamine and serotonin systems may contribute to normal and abnormal cognitive development.

Adolescent↗
PubMed1997

Development and topography of auditory event-related potentials (ERPs): mismatch and processing negativity in individuals 8-22 years of age.

How do event-related potentials (ERPs) reflecting auditory processing develop across adolescence? Such development was described for five ERP components in four groups of 11 healthy participants with mean ages of 10, 14, 17, and 21 years. Data from 19 sites during diffuse (passive) and focused (discrimination) attention in a three-tone oddball were analyzed to see how ERP loci varied with age for tone type, attention condition, and for four types of difference waves reflecting nontarget and target comparisons. Age interacted with site for most components. P1 loci sensitive to rare tones moved posteriorly and N1 loci lost their right bias in early puberty. The P2 loci did not move anterior to Cz until adulthood. N2 amplitude, sensitive to attention condition, developed a frontal focus by 17 years. Right-biased P3 loci moved to the midline with focused attention similarly in all age groups. Difference waves developed in three stages: In 10-year-old participants, early deflections (< 150 ms) were diffusely distributed; in midadolescent participants, the main frontal negative component (150-300 ms) became well formed and lost an earlier right bias; and for participants 17 years old and older, the late positive complex developed a right bias in target-derived waves. Latency decreases for early frontal components were marked in participants 10-14 years old and for later posterior components in participants 14-17 years old. Major developments appeared at the onset of adolescence in early stimulus selection processes and during adolescence in the differential use of this information (N2- and P3-like latencies).

Acoustic Stimulation↗
PubMed1996

Auditory event-related potentials (ERPs) and mismatch negativity (MMN) in healthy children and those with attention-deficit or tourette/tic symptoms.

The study compares 5 auditory event-related potential (ERP) components (P1 to P3) after 3 tones differing in pitch and rarity, and contrasts the mismatch negativity (MMN) between them in 12 children with attention-deficit hyperactivity disorder (ADHD; mean 10.2 years of age), 12 healthy controls pairwise matched for age (controls), and 10 with Chronic Tic or Tourette Syndrome (TS). Topographic recordings were derived from 19 scalp electrodes. Four major effects are reported. (a) Shorter latencies in ADHD patients were evident as early as 100 ms. (b) Both ADHD and TS groups showed very large P2 components where the maxima were shifted anteriorly. The differences in the later potentials were of a topographical nature. (c) Frontal MMN was non-significantly larger in the ADHD group but normalized data showed a left rather than a right frontal bias as in control subjects. Maxima for TS were usually posterior. (d) ADHD patients did not show the usual right-biased P3 asymmetry nor the frontal versus parietal P3 latency difference. From these results it is suggested that ADHD patients process perceptual information faster from an early stage (N1). Further, along with the TS group, ADHD patients showed an unusually marked inhibitory phase in processing (P2), interpreted as a reduction of the normal controls on further processing. Later indices of stimulus processing (N2-P3) showed a frontal impairment in TS and a right hemisphere impairment in ADHD patients. These are interpreted in terms of the difficulties in sustaining attention experienced by both ADHD and TS patients.

Adolescent↗