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ABSTRACT: Distinct gene expression profiles can be detected in peripheral blood mononuclear cells (PBMCs) in patients with schizophrenia; however, little is known about the effects of antipsychotic medication. This study compared gene expression profiles in PMBCs from treatment-naive patients with schizophrenia before and after antipsychotic drug treatment. PBMCs were obtained from 10 treatment-naive schizophrenia patients before and 6 wk after initiating antipsychotic drug treatment and compared to PMBCs collected from 11 healthy community volunteers. Genome-wide expression profiling was conducted using Illumina HumanHT-12 expression bead arrays and analysed using significance analysis of microarrays. This analysis identified 624 genes with altered expression (208 up-regulated, 416 down-regulated) prior to antipsychotic treatment (p < 0.05) including schizophrenia-associated genes AKT1, DISC1 and DGCR6. After 6-8 wk treatment of patients with risperidone or risperidone in combination with haloperidol, only 106 genes were altered, suggesting that the treatment corrected the expression of a large proportion of genes back to control levels. However, 67 genes continued to show the same directional change in expression after treatment. Ingenuity® pathway analysis and gene set enrichment analysis implicated dysregulation of biological functions and pathways related to inflammation and immunity in patients with schizophrenia. A number of the top canonical pathways dysregulated in treatment-naive patients signal through AKT1 that was up-regulated. After treatment, AKT1 returned to control levels and less dysregulation of these canonical pathways was observed. This study supports immune dysfunction and pathways involving AKT1 in the aetiopathophysiology of schizophrenia and their response to antipsychotic medication.
The International Journal of Neuropsychopharmacology 02/2013; · 4.58 Impact Factor
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ABSTRACT: Individuals with developmental disorders frequently report a range of social cognition deficits including difficulties identifying facial displays of emotion. This study examined the specificity of face emotion processing deficits in adolescents with either autism or 22q11DS compared to typically developing (TD) controls. Two tasks (face emotion recognition and weather scene recognition) were used to explore group differences in visual scanpath strategy and concurrent recognition accuracy. For faces, the autism and 22q11DS groups demonstrated lower emotion recognition accuracy and fewer fixations compared to the TD group. Individuals with autism demonstrated fewer fixations to some weather scene stimuli compared to 22q11DS and TD groups, yet achieved a level of recognition accuracy comparable to the TD group. These findings provide evidence for a divergent pattern of social cognition dysfunction in autism and 22q11DS.
Journal of Autism and Childhood Schizophrenia 01/2013; · 3.06 Impact Factor
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ABSTRACT: An important prerequisite for the development of animal models of human auditory evoked potentials (AEP) is the accurate identification of homology. Prior research has revealed some remarkably similar response properties between rat and human AEPs, although there remains little consensus regarding the nature or validity of this correspondence. In the present study we seek to extend this research by examining the response properties of rat AEP as a function of stimulus repetition and interval. The aim being to determine whether rat AEP components show the same paradoxical reversal of repetition suppression observed for the human N100 AEP component at brief stimulus intervals. To achieve this, AEPs were recorded epidurally at the vertex in the freely moving rat in response to acoustic stimuli presented at random stimulus intervals between 50 and 5000ms. Using stimulation and analysis techniques to remove AEP waveform distortion due to overlapping AEP responses, the present results show that rat AEP components can be successfully resolved at intervals as brief as 50ms. The results also demonstrate several fundamental types of correspondence between human and rat AEP components in terms of the sensitivity to stimulus interval and acoustic stimulus type. However the results found no evidence that rat AEP components show the reversal of repetition suppression at brief, relative to long, stimulus intervals as demonstrated for the N100 component in humans. The results are discussed in terms of EEG recording and AEP analysis procedures that provide promising avenues for future research.
Brain research 12/2012; · 2.46 Impact Factor
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ABSTRACT: With an estimated 80% heritability, molecular genetic research into schizophrenia has remained inconclusive. Recent large-scale, genome-wide association studies only identified a small number of susceptibility genes with individually very small effect sizes. However, the variable expression of the phenotype is not well captured in diagnosis-based research as well as when assuming a 'heterogenic risk model' (as apposed to a monogenic or polygenic model). Hence, the expression of susceptibility genes in response to environmental factors in concert with other disease-promoting or protecting genes has increasingly attracted attention.
The current review summarises findings of microarray gene expression research with relevance to schizophrenia as they emerged over the past decade.
Most findings from post mortem, peripheral tissues and animal models to date have linked altered gene expression in schizophrenia to presynaptic function, signalling, myelination, neural migration, cellular immune mechanisms, and response to oxidative stress consistent with multiple small effects of many individual genes. However, the majority of results are difficult to interpret due to small sample sizes (i.e. potential type-2 errors), confounding factors (i.e. medication effects) or lack of plausible neurobiological theory.
Nevertheless, microarray gene expression research is likely to play an important role in the future when investigating gene/gene and gene/environment interactions by adopting a neurobiologically sound theoretical framework.
Australian and New Zealand Journal of Psychiatry 03/2012; 46(7):598-610. · 2.93 Impact Factor
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ABSTRACT: The model of mismatch negativity (MMN) as a simple index of change detection has been superseded by a richer understanding of how this event-related potential (ERP) reflects the representation of the sound environment in the brain. Our conceptualization of why the MMN is altered in certain groups must also evolve along with a better understanding of the activities reflected by this component. The detection of change incorporates processes enabling an automatic registration of "sameness", a memory for such regularities and the application of this recent acoustic context to interpreting the present and future state of the environment. It also includes "weighting" the importance of this change to an organism's behaviour. In this light, the MMN has been considered a prediction error signal that occurs when the brain detects that the present state of the world violates a context-driven expectation about the environment. In this paper we revisit the consistent observation of reduced MMN amplitude in patients with schizophrenia. We review existing data to address whether the apparent deficit might reflect problems in prediction error generation, estimation or salience. Possible interpretations of MMN studies in schizophrenia are linked to dominant theories about the neurobiology of the illness.
International journal of psychophysiology: official journal of the International Organization of Psychophysiology 02/2012; 83(2):222-31. · 3.05 Impact Factor
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ABSTRACT: Reduction in a pre-attentive measure of auditory change detection, mismatch negativity (MMN), is one of the most consistent findings in schizophrenia. Recently, our group showed a reduction in MMN to changes in the duration and intensity of background sounds in those within 5 years of illness onset, whereas reduced MMNs to changes in sound frequency were only seen in patients with longer illness duration. In this report, we examine whether reduced MMN, as well as P3a, another index of auditory deviance detection, to duration changes is evident even earlier in the illness, that is, in individuals in the first episode of a psychosis (FEP) and individuals identified as being at ultra-high risk of developing schizophrenia (UHR).
Mismatch negativity and P3a were measured in 30 UHR individuals, 10 FEP individuals, and 20 healthy control subjects to both long (100 msec) and short (50 msec) duration deviant sounds.
Mismatch negativity was reduced to both duration deviants not only in the FEP group but also in the UHR group. P3a amplitude was also reduced in the UHR group but at trend level only in FEP. However, MMN and P3a reductions were unrelated in both UHR and FEP groups, suggesting that they reflect distinct deficits.
These results suggest that MMN, as well as P3a, to duration deviants are reduced in very early stages of a psychotic illness including those in an at-risk mental state. Both should be considered as potential markers of the prodrome.
Biological psychiatry 01/2012; 71(2):98-104. · 8.93 Impact Factor
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Stephan Ripke,
Alan R Sanders,
Kenneth S Kendler,
Douglas F Levinson,
Pamela Sklar,
Peter A Holmans,
Dan-Yu Lin,
Jubao Duan,
Roel A Ophoff,
Ole A Andreassen, [......],
Durk Wiersma,
Dieter B Wildenauer,
Hywel J Williams,
Nigel M Williams,
Brandon Wormley,
Stan Zammit,
Patrick F Sullivan,
Michael C O'Donovan,
Mark J Daly,
Pablo V Gejman
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ABSTRACT: We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 × 10(-11)) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 × 10(-9)), ANK3 (rs10994359, P = 2.5 × 10(-8)) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 × 10(-9)).
Nature Genetics 09/2011; 43(10):969-76. · 35.53 Impact Factor
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ABSTRACT: People with 22q11.2 deletion syndrome (22q11DS) have deficits in face emotion recognition. However, it is not known whether this is a deficit specific to faces, or represents maladaptive information processing strategies to complex stimuli in general. This study examined the specificity of face emotion processing deficits in 22q11DS by exploring recognition accuracy and visual scanpath performance to a Faces task compared to a Weather Scene task. Seventeen adolescents with 22q11DS (11=females, age=17.4) and 18 healthy controls (11=females, age=17.7) participated in the study. People with 22q11DS displayed an overall impoverished scanning strategy to face and weather stimuli alike, resulting in poorer accuracy across all stimuli for the 22q11DS participants compared to controls. While the control subjects altered their information processing in response to faces, a similar change was not present in the 22q11DS group indicating different visual scanpath strategies to identify category within each of the tasks, of which faces appear to represent a particularly difficult subcategory. To conclude, while this study indicates that people with 22q11DS have a general visual processing deficit, the lack of strategic change between tasks suggest that the 22q11DS group did not adapt to the change in stimuli content as well as the controls, indicative of cognitive inflexibility rather than a face specific deficit.
Psychiatry Research 08/2011; 189(2):292-8. · 2.52 Impact Factor
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ABSTRACT: Epidemiological data link adolescent cannabis use to psychosis and schizophrenia, but its contribution to schizophrenia neuropathology remains controversial. First-episode schizophrenia (FES) patients show regional cerebral grey- and white-matter changes as well as a distinct pattern of regional grey-matter loss in the vermis of the cerebellum. The cerebellum possesses a high density of cannabinoid type 1 receptors involved in the neuronal diversification of the developing brain. Cannabis abuse may interfere with this process during adolescent brain maturation leading to 'schizophrenia-like' cerebellar pathology. Magnetic resonance imaging and cortical pattern matching techniques were used to investigate cerebellar grey and white matter in FES patients with and without a history of cannabis use and non-psychiatric cannabis users. In the latter group we found lifetime dose-dependent regional reduction of grey matter in the right cerebellar lobules and a tendency for more profound grey-matter reduction in lobule III with younger age at onset of cannabis use. The overall regional grey-matter differences in cannabis users were within the normal variability of grey-matter distribution. By contrast, FES subjects had lower total cerebellar grey-matter:total cerebellar volume ratio and marked grey-matter loss in the vermis, pedunculi, flocculi and lobules compared to pair-wise matched healthy control subjects. This pattern and degree of grey-matter loss did not differ from age-matched FES subjects with comorbid cannabis use. Our findings indicate small dose-dependent effects of juvenile cannabis use on cerebellar neuropathology but no evidence of an additional effect of cannabis use on FES cerebellar grey-matter pathology.
The International Journal of Neuropsychopharmacology 05/2011; · 4.58 Impact Factor
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ABSTRACT: The capacity of the human brain to detect deviance in the acoustic environment pre-attentively is reflected in a brain event-related potential (ERP), mismatch negativity (MMN). MMN is observed in response to the presentation of rare oddball sounds that deviate from an otherwise regular pattern of frequent background standard sounds. While the primate and cat auditory cortex (AC) exhibit MMN-like activity, it is unclear whether the rodent AC produces a deviant response that reflects deviance detection in a background of regularities evident in recent auditory stimulus history or differential adaptation of neuronal responses due to rarity of the deviant sound. We examined whether MMN-like activity occurs in epidural AC potentials in awake and anesthetized rats to high and low frequency and long and short duration deviant sounds. ERPs to deviants were compared with ERPs to common standards and also with ERPs to deviants when interspersed with many different standards to control for background regularity effects. High frequency (HF) and long duration deviant ERPs in the awake rat showed evidence of deviance detection, consisting of negative displacements of the deviant ERP relative to ERPs to both common standards and deviants with many standards. The HF deviant MMN-like response was also sensitive to the extent of regularity in recent acoustic stimulation. Anesthesia in contrast resulted in positive displacements of deviant ERPs. Our results suggest that epidural MMN-like potentials to HF sounds in awake rats encode deviance in an analogous manner to the human MMN, laying the foundation for animal models of disorders characterized by disrupted MMN generation, such as schizophrenia.
Frontiers in psychology. 01/2011; 2:367.
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ABSTRACT: Cerebellar dysfunction has been proposed to lead to "cognitive dysmetria" in schizophrenia via the cortico-cerebellar-thalamic-cortical circuit, contributing to a range of cognitive and clinical symptoms of the disorder. Here we investigated total cerebellar grey and white matter volumes and cerebellar regional grey matter abnormalities in 13 remitted first-episode schizophrenia patients with less than 2 years' duration of illness. Patient data were compared to 13 pair-wise age, gender, and handedness-matched healthy volunteers using cortical pattern averaging on high-resolution magnetic resonance images. Total cerebellar volume and total grey matter volumes in first-episode schizophrenia patients did not differ from healthy control subjects, but total cerebellar white matter was increased and total grey to white matter ratios were reduced in patients. Four clusters of cerebellar grey matter reduction were identified: (i) in superior vermis; (ii) in the left lobuli VI; (iii) in right-inferior lobule IX, extending into left lobule IX; and (iv) bilaterally in the areas of lobuli III, peduncle and left flocculus. Grey matter deficits were particularly prominent in right lobuli III and IX, left flocculus and bilateral pedunculi. These cerebellar areas have been implicated in attention control, emotional regulation, social functioning, initiation of smooth pursuit eye movements, eye-blink conditioning, language processing, verbal memory, executive function and the processing of spatial and emotional information. Consistent with common clinical, cognitive, and pathophysiological signs of established illness, our findings demonstrate cerebellar pathology as early as in first-episode schizophrenia.
NeuroImage 12/2010; 53(4):1175-80. · 5.89 Impact Factor
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Carmel Loughland,
Daren Draganic,
Kathryn McCabe,
Jacqueline Richards,
Aslam Nasir,
Joanne Allen,
Stanley Catts,
Assen Jablensky,
Frans Henskens,
Patricia Michie,
Bryan Mowry,
Christos Pantelis, Ulrich Schall,
Rodney Scott,
Paul Tooney,
Vaughan Carr
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ABSTRACT: This article describes the establishment of the Australian Schizophrenia Research Bank (ASRB), which operates to collect, store and distribute linked clinical, cognitive, neuroimaging and genetic data from a large sample of people with schizophrenia and healthy controls.
Recruitment sources for the schizophrenia sample include a multi-media national advertising campaign, inpatient and community treatment services and non-government support agencies. Healthy controls have been recruited primarily through multi-media advertisements. All participants undergo an extensive diagnostic and family history assessment, neuropsychological evaluation, and blood sample donation for genetic studies. Selected individuals also complete structural MRI scans.
Preliminary analyses of 493 schizophrenia cases and 293 healthy controls are reported. Mean age was 39.54 years (SD = 11.1) for the schizophrenia participants and 37.38 years (SD = 13.12) for healthy controls. Compared to the controls, features of the schizophrenia sample included a higher proportion of males (cases 65.9%; controls 46.8%), fewer living in married or de facto relationships (cases 16.1%; controls 53.6%) and fewer years of education (cases 13.05, SD = 2.84; controls 15.14, SD = 3.13), as well as lower current IQ (cases 102.68, SD = 15.51; controls 118.28, SD = 10.18). These and other sample characteristics are compared to those reported in another large Australian sample (i.e. the Low Prevalence Disorders Study), revealing some differences that reflect the different sampling methods of these two studies.
The ASRB is a valuable and accessible schizophrenia research facility for use by approved scientific investigators. As recruitment continues, the approach to sampling for both cases and controls will need to be modified to ensure that the ASRB samples are as broadly representative as possible of all cases of schizophrenia and healthy controls.
Australian and New Zealand Journal of Psychiatry 11/2010; 44(11):1029-35. · 2.93 Impact Factor
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ABSTRACT: Early intervention into prodromal schizophrenia has shown promise, but controversy continues regarding the ethical acceptability of identifying a group of 'ultra high risk' individuals of whom only 30 to 50% will develop a psychotic disorder. With well developed early intervention services this group faces the possibility of being labelled as 'pre-psychotic', a condition for which the well known stigma associated with the diagnosis of schizophrenia or bipolar disorder is likely to be associated. In addition, the use of potent antipsychotic and other medications (albeit usually at lower doses than those used for those with manifest psychosis) mandates consideration of the risks associated with their use and neurological and metabolic side effects. The potential for iatrogenic morbidity in the 'false positive' group must be weighed against the need of the 'true positives' identified through screening and assessment. Current evidence for the concept of 'at-risk mental state' was reviewed within a neurodevelopmental framework, including emerging data on the effectiveness of early intervention for the purpose of providing recommendations for community mental health services. The review suggests that different treatment strategies may be appropriate depending on the clinical stage of the condition as long as the benefits of intervention outweigh its risk burden. It further suggests that the severity of psychoses and the evidence of its early onset in utero and its acceleration in adolescence positions 'ultra high risk' intervention as a core model for early intervention for young people by teasing apart the symptomatic components of the 'prepsychotic state' and ensuring the population is reaching targeted mental health services for screening. The model is not restricted to the delivery of intervention for 'pre-psychotic' young people but is applicable for targeted programmes for a number of clinical groups considered at 'ultra high risk'. However, only further research in naturalistic populations embedded in clinical practice and ideally conducted in partnership of mental health services with academic research institutions will help clarify potential risks of early identification and intervention and assist in updating and making more explicit the clinical guidelines services will use in approaching those in the 'ultra high risk' group.
Australian and New Zealand Journal of Psychiatry 10/2010; 44(10):872-82. · 2.93 Impact Factor
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ABSTRACT: Temporal and spectral sound information is processed asymmetrically in the brain with the left-hemisphere showing an advantage for processing the former and the right-hemisphere for the latter. Using monaural sound presentation we demonstrate a context and ability dependent ear-asymmetry in brain measures of temporal change detection. Our measure of temporal processing ability was a gap-detection task quantifying the smallest silent gap in a sound that participants could reliably detect. Our brain measure was the size of the mismatch-negativity (MMN) auditory event-related potential elicited to infrequently presented gap sounds. The MMN indexes discrimination ability and is automatically generated when the brain detects a change in a repeating pattern of sound. MMN was elicited in unattended sequences of infrequent gap-sounds presented among regular no-gap sounds. In Study 1, participants with low gap-detection thresholds (good ability) produced a significantly larger MMN to gap sounds when sequences were presented monaurally to the right-ear than to the left-ear. In Study 2, we not only replicated a right-ear-advantage for MMN in silence in good temporal processors, but also showed that this is reversed to a significant left-ear-advantage for MMN when the same sounds are presented against a background of constant low-level noise. In both studies, poor discriminators showed no ear-advantage, and in Study 2, exhibited no differential sensitivity of the ears to noise. We conclude that these data reveal a context and ability-dependent asymmetry in processing temporal information in non-speech sounds.
Neuropsychologia 10/2010; 49(1):69-82. · 3.64 Impact Factor
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ABSTRACT: This study examined whether post-infective fatigue syndrome (PIFS) is associated with a disturbance in bidirectional autonomic signalling resulting in heightened perception of symptoms and sensations from the body in conjunction with autonomic hyper-reactivity to perceived challenges. We studied 23 patients with PIFS and 25 healthy matched control subjects. A heartbeat discrimination task and a pressure pain threshold test were used to assess interoceptive sensitivity. Cardiac response was assessed over a 4-min Stroop task. PIFS was associated with higher accuracy in heartbeat discrimination and a lower pressure pain threshold. Increased interoceptive sensitivity correlated strongly with current symptoms and potentiated differences in the cardiac response to the Stroop task, which in PIFS was characterized by insensitivity to task difficulty and lack of habituation. Our results provide the first evidence of heightened interoceptive sensitivity in PIFS. Together with the distinct pattern in cardiac responsivity these findings present a picture of physiological hyper-vigilance and response inflexibility.
Biological psychology 09/2010; 85(1):97-103. · 4.36 Impact Factor
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ABSTRACT: Previous research demonstrates that people with 22q11.2 deletion syndrome (22q11DS) have social and interpersonal skill deficits. However, the basis of this deficit is unknown. This study examined, for the first time, how people with 22q11DS process emotional face stimuli using visual scanpath technology. The visual scanpaths of 17 adolescents and age/gender matched healthy controls were recorded while they viewed face images depicting one of seven basic emotions (happy, sad, surprised, angry, fear, disgust and neutral). Recognition accuracy was measured concurrently. People with 22q11DS differed significantly from controls, displaying visual scanpath patterns that were characterised by fewer fixations and a shorter scanpath length. The 22q11DS group also spent significantly more time gazing at the mouth region and significantly less time looking at eye regions of the faces. Recognition accuracy was correspondingly impaired, with 22q11DS subjects displaying particular deficits for fear and disgust. These findings suggest that 22q11DS is associated with a maladaptive visual information processing strategy that may underlie affect recognition accuracy and social functioning deficits in this group.
Psychiatry Research 04/2010; 177(1-2):211-5. · 2.52 Impact Factor
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Renate Thienel,
Bianca Voss,
Thilo Kellermann,
Martina Reske,
Sarah Halfter,
Abigail J Sheldrick,
Katrin Radenbach,
Ute Habel,
Nadim Jon Shah, Ulrich Schall,
Tilo Kircher
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ABSTRACT: Cholinergic neurotransmission has been implicated in memory and attention. We investigated the effect of the non-competitive nicotinic antagonist mecamylamine on three components of attention processes (i.e. alerting, orienting and executive control) in 12 healthy male subjects whilst performing the Attention Network Task (ANT) in a magnetic resonance imaging (MRI) scanner. Participants received 15 mg mecamylamine in a single blind and placebo- controlled randomized procedure 90 min prior to obtaining functional MRI data. Our results confirm previous reports of beneficial effects of cueing (alerting and orienting) and detrimental effects of conflict (executive control) on reaction times when performing the ANT. The functional MRI data confirmed distinct neural networks associated with each of the three attention components. Alerting was associated with increased left temporal lobe activation while orienting increased bilateral prefrontal, right precuneus and left caudate activation. Executive control activated anterior cingulate and precuneus. Mecamylamine slowed overall response time and down-regulated brain activation associated with orienting and to some extent brain activation associated with executive control when compared to placebo. These findings are consistent with nicotinic modulation of orienting attention by cueing and executive control when responding to conflicting information. The latter nicotine antagonist effect may be mediated via cholinergic modulation of dopamine neurotransmission in mesolimbic pathways.
The International Journal of Neuropsychopharmacology 10/2009; 12(10):1295-305. · 4.58 Impact Factor
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Renate Thienel,
Thilo Kellermann, Ulrich Schall,
Bianca Voss,
Martina Reske,
Sarah Halfter,
Abigail J Sheldrick,
Katrin Radenbach,
Ute Habel,
Nadim Jon Shah,
Tilo Kircher
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ABSTRACT: Acetylcholine plays a major role in mediating attention processes. We investigated the muscarinic antagonist effect of scopolamine on functional neuro-anatomy of attention and cognition. We assessed 12 healthy volunteers while performing the Attention Network Task on 0.4 mg scopolamine and placebo in a single-blind randomized trial in a 1.5 T magnetic resonance scanner. Neurocognitive measures included verbal learning, verbal memory, verbal fluency, trail making, digit span, a continuous performance task and a planning task (Tower of London). When compared to placebo, scopolamine increased reaction times for conflicting stimulus processing, together with decreasing brain activation in the anterior cingulate cortex (a brain region involved in conflict processing) suggestive of a muscarinic antagonist effect on executive control of attention. Contrary to the notion of a predominantly right-hemispheric lateralization of cognitive processes associated with orienting attention, scopolamine reduced brain activity in left superior and left middle frontal brain areas. Our neuropsychological test data revealed a selective effect of scopolamine on verbal learning and memory while other cognitive domains, such as planning and working memory, were unaffected. These findings are consistent with muscarinic modulation of dopaminergic neurotransmission in frontal attention networks when processing conflicting information.
The International Journal of Neuropsychopharmacology 10/2009; 12(10):1307-17. · 4.58 Impact Factor
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ABSTRACT: Disrupted sensorimotor gating has been found in various neuropsychiatric conditions which are characterized by impaired attention, poor impulse control, dysfunctional dopamine neurotransmission, and neurodevelopmental deficits. We investigated sensorimotor gating by prepulse inhibition (PPI) of the acoustic startle eyeblink reflex in 23 young adults diagnosed with attention deficit hyperactivity disorder (ADHD) as children and still symptomatic at the time of testing and 29 age-matched healthy control subjects. Sensorimotor gating was assessed in a passive listening task at prepulse-to-startle probe intervals of 30, 60, 120, 240, and 480 ms, and subsequently at prepulse-to-startle probe intervals of 60, 120, 240, and 480 ms whilst participants were performing a two-tone auditory discrimination task on the prepulse. Consistent with increased neural maturity and partially remitted symptomatology, our results indicate intact sensorimotor gating for both tasks in adult ADHD with no comorbidity, independent of the subjects' gender and whether ADHD subjects were receiving ongoing stimulant treatment or not. Reduced PPI at 120-ms lead intervals, on the other hand, was recorded in a subset of 10 ADHD subjects who were taken off their prescribed regular stimulants for 24 h and tested in a randomized counterbalanced order for on vs. off medication. However, our data remained inconclusive as to whether this observation constitutes beneficial treatment or acute stimulant withdrawal effects on sensorimotor gating.
The International Journal of Neuropsychopharmacology 01/2009; 12(5):701-7. · 4.58 Impact Factor
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ABSTRACT: A reduction in the size of the auditory event-related potential component known as mismatch negativity (MMN) is a consistent finding in schizophrenia. This study was designed to test the hypothesis that sound intensity and duration might be more sensitive to MMN reduction early in the development of schizophrenia because of the computational complexity in extracting these two sound dimensions.
The MMN elicited to sounds deviating in duration, frequency, or intensity was measured in participants with a short (n = 14, mean 2.6 years) and longer length of illness (n = 29, mean 18.9 years) relative to healthy age-matched control subjects.
For participants early in the illness, a clear reduction was evident in MMN to duration and intensity but not frequency deviants. A different pattern was observed in patients with a longer length of illness--that is, a reduction in frequency and in duration to a lesser degree but not intensity MMN.
The results indicate a pronounced age-related decline in duration and intensity MMN in control subjects that might reduce the sensitivity of these indices in schizophrenia when measured later in the course of the illness. The MMN elicited to changes in different sound properties provides potentially complementary information on the onset and progression of neuropathological changes that underlie the reduction in MMN in schizophrenia.
Biological psychiatry 02/2008; 63(1):58-64. · 8.93 Impact Factor
