Auditory Sensory Gating Deficits Research Articles

P50 inhibition defects with psychopathology and cognitive impairment in patients with first-episode drug naïve schizophrenia

BackgroundMany studies have announced that P50 inhibition defects represent sensory gating deficits in schizophrenia, but studies seldom have searched the correlation between P50 inhibition defects and the psychopathology or cognitive impairment of patients with first-episode, drug naïve (FEDN) of schizophrenia. In this study, we investigated the auditory sensory gating deficits in a large number of Han patients with FEDN schizophrenia and their correlation with clinical symptoms and cognitive impairment. MethodsA total of 130 patients with FEDN schizophrenia and 189 healthy controls were recruited in this study. Positive and Negative Syndrome Scale (PANSS) and its five-factor model were used to score the psychopathology of the patients, and P50 inhibition was recorded using the 64-channel electroencephalography (EEG) system. ResultsPatients exhibited significantly longer S1 and S2 latency, lower S1 and S2 amplitudes and lower P50 difference than healthy controls (all p < 0.05). Significant correlations existed between S1 latency and PANSS negative symptoms or cognitive factor, P50 ratio and general psychopathology, P50 ratio and PANSS total score, P50 difference and general psychopathology, and P50 difference and PANSS total score (all p < 0.05). Multiple regression analysis revealed that S1 latency, sex, age, and education were contributors to negative symptom score (all p < 0.05). S1 latency, S2 latency, sex, age, and smoking status were contributors to cognitive factor (all p < 0.05). ConclusionsOur results show that patients with FEDN schizophrenia have P50 inhibition defects, which may be related to their psychopathological symptoms and cognitive impairment.

P50, N100, and P200 Auditory Sensory Gating Deficits in Schizophrenia Patients.

BackgroundSensory gating describes neurological processes of filtering out redundant or unnecessary stimuli during information processing, and sensory gating deficits may contribute to the symptoms of schizophrenia. Among the three components of auditory event-related potentials reflecting sensory gating, P50 implies pre-attentional filtering of sensory information and N100/P200 reflects attention triggering and allocation processes. Although diminished P50 gating has been extensively documented in patients with schizophrenia, previous studies on N100 were inconclusive, and P200 has been rarely examined. This study aimed to investigate whether patients with schizophrenia have P50, N100, and P200 gating deficits compared with control subjects.MethodsControl subjects and clinically stable schizophrenia patients were recruited. The mid-latency auditory evoked responses, comprising P50, N100, and P200, were measured using the auditory-paired click paradigm without manipulation of attention. Sensory gating parameters included S1 amplitude, S2 amplitude, amplitude difference (S1-S2), and gating ratio (S2/S1). We also evaluated schizophrenia patients with PANSS to be correlated with sensory gating indices.ResultsOne hundred four patients and 102 control subjects were examined. Compared to the control group, schizophrenia patients had significant sensory gating deficits in P50, N100, and P200, reflected by larger gating ratios and smaller amplitude differences. Further analysis revealed that the S2 amplitude of P50 was larger, while the S1 amplitude of N100/P200 was smaller, in schizophrenia patients than in the controls. We found no correlations between sensory gating indices and schizophrenia positive or negative symptom clusters. However, we found a negative correlation between the P200 S2 amplitude and Bell’s emotional discomfort factor/Wallwork’s depressed factor.ConclusionTill date, this study has the largest sample size to analyze P50, N100, and P200 collectively by adopting the passive auditory paired-click paradigm without distractors. With covariates controlled for possible confounds, such as age, education, smoking amount and retained pairs, we found that schizophrenia patients had significant sensory gating deficits in P50-N100-P200. The schizophrenia patients had demonstrated a unique pattern of sensory gating deficits, including repetition suppression deficits in P50 and stimulus registration deficits in N100/200. These results suggest that sensory gating is a pervasive cognitive abnormality in schizophrenia patients that is not limited to the pre-attentive phase of information processing. Since P200 exhibited a large effect size and did not require additional time during recruitment, future studies of P50-N100-P200 collectively are highly recommended.

Abnormal beta and gamma frequency neural oscillations mediate auditory sensory gating deficit in schizophrenia

BackgroundSensory gating is a process in which the brain's response to irrelevant and repetitive stimuli is inhibited. The sensory gating deficit in schizophrenia (SZ) is typically measured by the ratio or difference score of the P50 event-related potential (ERP) amplitudes in response to a paired click paradigm. While the P50 gating effect has usually been measured in relation to the peak amplitude of the S1 and S2 P50 ERPs, there is increasing evidence that inhibitory processes may be reflected by evoked or induced oscillatory activity during the inter-click interval in the beta (20–30 Hz) and gamma (30–50 Hz) frequency bands. We therefore examined the relationship between frequency specific activity in the inter-click interval with gating effects in the time and frequency domains. MethodPaired-auditory stimuli were presented to 131 participants with schizophrenia and 196 healthy controls (HC). P50 ERP amplitudes to S1 and S2as well as averaged- and single-trial beta (20–30 Hz) and gamma (30–50 Hz) frequency power during the inter-click interval were measured from the CZ electrode site. ResultsIn the time domain, P50 gating deficits were apparent in both ratio and difference scores. This effect was mainly due to smaller S1 amplitudes in the patient group. SZ patients exhibited less evoked beta and gamma power, particularly at the 0–100 ms time point, in response to S1. Early (0–100 ms) evoked beta and gamma responses were critical in determining the S1 amplitude and extent of P50 gating across the delay interval for both HC and SZ. ConclusionOur findings support a disruption in initial sensory registration in those with SZ, and do not support an active mechanism throughout the delay interval. The degree of response to S1 and early beta and gamma frequency oscillations in the delay interval provides information about the mechanisms supporting auditory sensory gating, and may provide a framework for studying the mechanisms that support sensory inhibition.

Pharmacological Mechanisms Involved in Sensory Gating Disruption Induced by (±)-3,4-Methylene- Dioxymethamphetamine (MDMA): Relevance to Schizophrenia.

Sensory gating deficits have been demonstrated in schizophrenia, but the mechanisms involved remain unclear. In the present study, we used disruption of paired-pulse gating of evoked potentials in rats by the administration of (±)-3,4-methylene-dioxymethamphetamine (MDMA) to study serotonergic and dopaminergic mechanisms involved in auditory sensory gating deficits. Male Sprague-Dawley rats were instrumented with cortical surface electrodes to record evoked potential changes in response to pairs of 85dB tones (S1 and S2), 500msec apart. Administration of MDMA eliminated the normal reduction in the amplitude of S2 compared to S1, representing disruption of auditory sensory gating. Pretreatment of the animals with the dopamine D1 receptor antagonist, SCH23390, the dopamine D2 receptor antagonist, haloperidol, the serotonin (5-HT)1A receptor antagonist, WAY100635, or the 5-HT2A receptor antagonist, ketanserin, all blocked the effect of MDMA, although the drugs differentially affected the individual S1 and S2 amplitudes. These data show involvement of both dopaminergic and serotonergic mechanisms in disruption of auditory sensory gating by MDMA. These and previous results suggest that MDMA targets serotonergic pathways, involving both 5-HT1A and 5-HT2A receptors, leading to dopaminergic activation, involving both D1 and D2 receptors, and ultimately sensory gating deficits. It is speculated that similar interactive mechanisms are affected in schizophrenia.

Impact of childhood trauma on sensory gating in patients with first-episode schizophrenia

BackgroundChildhood trauma (CT) has been found to contribute to the onset of schizophrenia and auditory sensory gating deficit is a leading endophenotype for schizophrenia. However, the association between the CT and sensory gating in first-episode schizophrenia remains elusive.MethodsFifty-six patients and 49 age and sex-matched healthy controls were assessed using the Childhood Trauma Questionnaire-Short Form (CTQ-SF) for CT and Positive and Negative Syndrome Scale (PANSS) for symptoms severity. Sensory gating was tested using the modified paradigm, perceived spatial separation-induced prepulse inhibition (PSS-PPI), and the perceived spatial co-location PPI (PSC-PPI or classical PPI).ResultsComparing with healthy controls, the patients had significantly higher score on sexual abuse (t = 2.729, p < 0.05), lower PSS- PPI, % (ISI = 120 ms and ISI = 60 ms) (t = − 3.089, − 4.196, p < 0.05). Univariate analysis revealed the absence of a significant correlation among CT, PPI paradigms and symptoms. However, multiple linear regression analyses demonstrated the CTQ-SF total was negatively associated with PSS PPI (ISI = 120 ms) (p = 0.018).ConclusionThe current study illustrates that the impact of CT on sensory gating in patients with first-episode schizophrenia, and thus we conclude that CT may be a risk factor to the occurrence of schizophrenia through its impact on sensory gating.

Sensory Gating Deficits and their Clinical Correlates in Drug-Free/Drug-Naive Patients with Schizophrenia.

Background:Sensory gating refers to “filtering” of irrelevant sensory input in the brain. Auditory sensory gating deficit has been considered as a marker of schizophrenia (SCZ) and assessed using P50 paired-click paradigm. We explore sensory gating deficits and their clinical correlates in SCZ.Materials and Methods:Twenty-five drug-free/drug-naïve patients with SCZ, whose psychopathology was assessed using Positive and Negative Syndrome Scale (PANSS), and 25 age-matched normal controls (NC) were recruited. ERP recordings were done using 40-channel event-related potential measuring system.Results:S2-S1 P50 amplitude difference, an index of sensory gating, was significantly lower in SCZ at F3 and F4 sites when compared to NC, indicating impaired gating. SCZ had significantly lower S1 amplitude compared to NC at these sites; S2 amplitudes were comparable. The sensory gating index also showed significant correlations with PANSS scores.Conclusions:Our study reiterates sensory gating abnormalities in SCZ and confers a frontal specificity, implying specific deficits in early preattentive processes to them. Further, we suggest that gating deficits in SCZ are driven predominantly by abnormally small S1 rather than an inability to suppress S2. A correlation between sensory gating parameters and measures of psychopathology strengthens the hypothesis that abnormal response to sensory input may contribute to the psychopathology in SCZ.

Nicotinic modulation of auditory evoked potential electroencephalography in a rodent neurodevelopmental model of schizophrenia

Schizophrenia is a chronic disease that has been hypothesized to be linked to neurodevelopmental abnormalities. Schizophrenia patients exhibit impairments in basic sensory processing including sensory gating deficits in P50 and mismatch negativity (MMN). Neuronal nicotinic acetylcholine receptor (nAChR) agonists have been reported to attenuate these deficits. Gestational exposure of rats to methylazoxymethanol acetate (MAM) at embryonic day 17 leads to developmental disruption of the limbic-cortical system. MAM exposed offspring show neuropathological and behavioral changes that have similarities with those seen in schizophrenia. In this study, we aimed to assess whether N40 auditory sensory gating (the rodent form of P50 gating) and MMN deficits as measures of auditory evoked potential (AEP) electroencephalography (EEG) are present in MAM rats and whether nAChR agonists could attend the deficit. E17 male MAM and sham rats were implanted with cortical electrodes at 2 months of age. EEG recordings evaluating N40 gating and MMN paradigms were done comparing effects of vehicle (saline), nicotine and the α7 agonist ABT-107. Deficits were seen for MAM rats compared to sham animals in both N40 auditory sensory gating and MMN AEP recordings. There was a strong trend for N40 deficits to be attenuated by both nicotine (0.16mg/kg i.p. base) and ABT-107 (1.0mg/kg i.p. base). MMN deficits were significantly attenuated by ABT-107 but not by nicotine. These data support the MAM model as a useful tool for translating pharmacodynamic effects in clinical medicine studies of novel therapeutic treatments for schizophrenia.

Subthalamic deep brain stimulation improves auditory sensory gating deficit in Parkinson’s disease

ObjectiveWhile motor effects of dopaminergic medication and subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson’s disease (PD) patients are well explored, their effects on sensory processing are less well understood. Here, we studied the impact of levodopa and STN-DBS on auditory processing. MethodsRhythmic auditory stimulation (RAS) was presented at frequencies between 1 and 6Hz in a passive listening paradigm. High-density EEG-recordings were obtained before (levodopa ON/OFF) and 5months following STN-surgery (ON/OFF STN-DBS). We compared auditory evoked potentials (AEPs) elicited by RAS in 12 PD patients to those in age-matched controls. Tempo-dependent amplitude suppression of the auditory P1/N1-complex was used as an indicator of auditory gating. ResultsParkinsonian patients showed significantly larger AEP-amplitudes (P1, N1) and longer AEP-latencies (N1) compared to controls. Neither interruption of dopaminergic medication nor of STN-DBS had an immediate effect on these AEPs. However, chronic STN-DBS had a significant effect on abnormal auditory gating characteristics of parkinsonian patients and restored a physiological P1/N1-amplitude attenuation profile in response to RAS with increasing stimulus rates. ConclusionsThis differential treatment effect suggests a divergent mode of action of levodopa and STN-DBS on auditory processing. SignificanceSTN-DBS may improve early attentive filtering processes of redundant auditory stimuli, possibly at the level of the frontal cortex.

Auditory M50 and M100 sensory gating deficits in bipolar disorder: A MEG study

ObjectivesAuditory sensory gating deficits have been reported in subjects with bipolar disorder, but the hemispheric and neuronal origins of this deficit are not well understood. Moreover, gating of the auditory evoked components reflecting early attentive stage of information processing has not been investigated in bipolar disorder. The objectives of this study were to investigate the right and left hemispheric auditory sensory gating of the M50 (preattentive processing) and M100 (early attentive processing) in patients diagnosed with bipolar I disorder by utilizing magnetoencephalography (MEG). MethodsWhole-head MEG data were acquired during the standard paired-click paradigm in 20 bipolar I disorder patients and 20 healthy controls. The M50 and the M100 responses were investigated, and dipole source localizations were also investigated. Sensory gating were determined by measuring the strength of the M50 and the M100 response to the second click divided by that of the first click (S2/S1). ResultsIn every subject, M50 and M100 dipolar sources localized to the left and right posterior portion of superior temporal gyrus (STG). Bipolar I disorder patients showed bilateral gating deficits in M50 and M100. The bilateral M50 S2 source strengths were significantly higher in the bipolar I disorder group compared to the control group. LimitationsThe sample size was relatively small. More studies with larger sample sizes are warranted. Bipolar subjects were taking a wide range of medications that could not be readily controlled for. ConclusionsThese findings suggest that bipolar I disorder patients have auditory gating deficits at both pre-attentive and early attentive levels, which might be related to STG structural abnormality.

Sensory gating deficit is associated with catechol-O-methyltransferase polymorphisms in bipolar disorder

Objectives. Recent studies have evidenced that bipolar patients show a sensory gating deficit (P50). Among the neural systems that could be influencing this electrophysiological phenotype, dopamine seems to play an important role. We hypothesize that catechol-O-methyltransferase (COMT), the main metabolizer of dopamine in prefrontal cortex, is related to this deficit. Methods. We selected three polymorphisms in COMT gene: rs2075507 (Promoter 2 region), Val158Met (rs4680) and rs165599 (3’ region). A case–control study was performed in 784 controls and 238 bipolar patients. Besides, 122 euthymic bipolar subjects and 95 healthy subjects carried out a sensory gating task (P50). Results. Polymorphism rs165599 in the COMT gene was associated with susceptibility to bipolar disorder (BD), mainly in women (AG: OR = 1.46; GG: OR = 1.84; P = 0.03). In the female group, haplotype AAG was associated with an OR = 7.6. Subjects who carried Val158 allele evidenced a deficit in suppression (P = 0.046) and rs165599 allele G carriers (mainly in homozygosis) had a bigger S2 amplitude and a higher S2/S1 ratio (1.6e-5 < P < 0.01). Not a single association was proven in the control group. Conclusions. Our results support the association of the COMT gene with BD and with one of its potential endophenotypes, auditory sensory gating deficit, measured by the P50 paradigm.

The moderating role of the dopamine transporter 1 gene on P50 sensory gating and its modulation by nicotine

Although schizophrenia has been considered primarily a disease of dopaminergic neurotransmission, the role of dopamine in auditory sensory gating deficits in this disorder and their amelioration by smoking/nicotine is unclear. Hypothesizing that individual differences in striatal dopamine levels may moderate auditory gating and its modulation by nicotine, this preliminary study used the mid-latency (P50) auditory event-related potential (ERP) to examine the single dose (6 mg) effects of nicotine (vs. placebo) gum on sensory gating in 24 healthy nonsmokers varying in the genetic expression of the dopamine transporter (DAT). Consistent with an inverted-U relationship between dopamine level and the drug effects, individuals carrying the 9R (lower gene expression) allele, which is related to greater striatal dopamine levels, tended to evidence increased baseline gating compared to 10R (higher gene expression) allele carriers and showed a reduction in gating with acute nicotine. The present results may help to understand the link between excessive smoking and sensory gating deficits in schizophrenia and to explain the potential functional implications of genetic disposition on nicotinic treatment in schizophrenia.

Lateralized abnormalities in auditory M50 sensory gating and cortical thickness of the superior temporal gyrus in post-traumatic stress disorder: Preliminary results

Auditory sensory gating deficits have been reported in subjects with post-traumatic stress disorder (PTSD), but the hemispheric and neuronal origins of this deficit are not well understood. The objectives of this study were to: (1) investigate auditory sensory gating of the 50-ms response (M50) in patients diagnosed with PTSD by utilizing magnetoencephalography (MEG); (2) explore the relationship between M50 sensory gating and cortical thickness of the superior temporal gyrus (STG) measured with structural magnetic resonance imaging (MRI); and (3) examine the association between PTSD symptomatology and bilateral sensory gating. Seven participants with combat-related PTSD and eleven controls underwent the paired-click sensory gating paradigm. MEG localized M50 neuronal generators to the STG in both groups. The PTSD group displayed impaired M50 gating in the right hemisphere. Thinner right STG cortical thickness was associated with worse right sensory gating in the PTSD group. The right S1 M50 source strength and gating ratio were correlated with PTSD symptomatology. These findings suggest that the structural integrity of right hemisphere STG cortices play an important role in auditory sensory gating deficits in PTSD.

P27-4 Auditory sensory gating deficit to voices in psychotic bipolar disorder: an MEG study

P27-4 Auditory sensory gating deficit to voices in psychotic bipolar disorder: an MEG study

Contributions of spectral frequency analyses to the study of P50 ERP amplitude and suppression in bipolar disorder with or without a history of psychosis

The present study investigated event-related brain potential (ERP) indices of auditory processing and sensory gating in bipolar disorder and subgroups of bipolar patients with or without a history of psychosis using the P50 dual-click procedure. Auditory-evoked activity in two discrete frequency bands also was explored to distinguish between sensory registration and selective attention deficits. Thirty-one individuals with bipolar disorder and 28 non-psychiatric controls were compared on ERP indices of auditory processing using a dual-click procedure. In addition to conventional P50 ERP peak-picking techniques, quantitative frequency analyses were applied to the ERP data to isolate stages of information processing associated with sensory registration (20-50 Hz; gamma band) and selective attention (0-20 Hz; low-frequency band). Compared to the non-psychiatric control group, patients with bipolar disorder exhibited reduced S1 response magnitudes for the conventional P50 peak-picking and low-frequency response analyses. A bipolar subgroup effect suggested that the attenuated S1 magnitudes from the P50 peak-picking and low-frequency analyses were largely attributable to patients without a history of psychosis. The analysis of distinct frequency bands of the auditory-evoked response elicited during the dual-click procedure allowed further specification of the nature of auditory sensory processing and gating deficits in bipolar disorder with or without a history of psychosis. The observed S1 effects in the low-frequency band suggest selective attention deficits in bipolar patients, especially those patients without a history of psychosis, which may reflect a diminished capacity to selectively attend to salient stimuli as opposed to impairments of inhibitory sensory processes.

Sensory Gating Endophenotype Based on Its Neural Oscillatory Pattern and Heritability Estimate

The auditory sensory gating deficit has been considered a leading endophenotype in schizophrenia. However, the commonly used index of sensory gating, P50, has low heritability in families of people with schizophrenia, raising questions about its utility in genetic studies. We hypothesized that the sensory gating deficit may occur in a specific neuronal oscillatory frequency that reflects the underlying biological process of sensory gating. Frequency-specific sensory gating may be less complex than the P50 response, and therefore closer to the direct genetic effects, and thus a more valid endophenotype. To compare the gating of frequency-specific oscillatory responses with the gating of P50 and to compare their heritabilities. We explored single trial-based oscillatory gating responses in people with schizophrenia, their relatives, and control participants from the community. Outpatient clinics. Persons with schizophrenia (n = 102), their first-degree relatives (n = 74), and control participants from the community (n = 70). Gating of frequency-specific oscillatory responses, gating of the P50 wave, and their heritability estimates. Gating of the theta-alpha-band responses of the control participants were significantly different from those with schizophrenia (P < .001) and their first-degree relatives (P = .04 to .009). The heritability of theta-alpha-band gating was estimated to be between 0.49 and 0.83 and was at least 4-fold higher than the P50 heritability estimate. Gating of the theta-alpha-frequency oscillatory signal in the paired-click paradigm is more strongly associated with schizophrenia and has significantly higher heritability compared with the traditional P50 gating. This measure may be better suited for genetic studies of the gating deficit in schizophrenia.

Irradiation in Adulthood as a New Model of Schizophrenia

BackgroundEpidemiological studies suggest that radiation exposure may be a potential risk factor for schizophrenia in adult humans. Here, we investigated whether adult irradiation in rats caused behavioral abnormalities relevant to schizophrenia.Methodology/Principal FindingsA total dose of 15-Gy irradiation in six fractionations during 3 weeks was exposed to the forebrain including the subventricular zone (SVZ) and subgranular zone (SGZ) with male rats in the prone position. Behavioral, immunohistochemical, and neurochemical studies were performed three months after fractionated ionizing irradiation. Three months after fractionated ionizing irradiation, the total numbers of BrdU-positive cells in both the SVZ and SGZ zones of irradiated rats were significantly lower than those of control (sham-irradiated) rats. Hyperactivity after administration of the dopaminergic agonist methamphetamine, but not the N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine, was significantly enhanced in the irradiated rats although spontaneous locomotion in the irradiated rats was significantly lower than that of controls. Behavioral abnormalities including auditory sensory gating deficits, social interaction deficits, and working memory deficits were observed in the irradiated rats.Conclusion/SignificanceThe present study suggests that irradiation in adulthood caused behavioral abnormalities relevant to schizophrenia, and that reduction of adult neurogenesis by irradiation may be associated with schizophrenia-like behaviors in rats.

Sensory gating deficits, pattern completion, and disturbed fronto-limbic balance, a model for description of hallucinations and delusions in schizophrenia

Schizophrenia, if not the most difficult, is one of the most difficult mysterious puzzles for psychiatrists, psychologists, and neuroscientists to solve. In this paper, based on the previously known pathologies of schizophrenia, a new model is proposed for explanation of the formation of positive psychotic symptoms of hallucinations and delusions. This model can be used for understanding psychotic or psychotic-like positive symptoms of bipolar mood disorder, posttraumatic stress disorder, obsessive compulsive, and amphetamine and drug-induced psychotic disorders. Based on the postulated model, a spectral view on these disorders with psychotic features is also proposed. These pathologies include auditory sensory gating deficits in hippocampus, abnormal emotional coding in amygdala, pattern completion in thalamic and cortical areas, and disturbed fronto-limbic balance. This model includes anatomical and neurotransmitter defects of hippocampus, amygdala, thalamus, cingula, and prefrontal cortex and their interconnections. A role for hippocampal sensory gating deficits in the pathogenesis of positive psychotic symptoms and interrelation between amygdala and its dopamine level with hippocampus is speculated. This model also hires the interesting function of pattern completion in thalamus and cortical areas for a better explanation of the pathogenesis of hallucinations and delusional psychotic symptoms. Furthermore, there is also explanation for the polygenic etiology of the schizophrenic and psychotic disorders and relation between schizophrenia and bipolar mood disorder in anatomy and neural systems involved. A spectral view is proposed that explains the absence of clear cut border between different psychotic or psychotic-like disorders in their form and severity based on the involved genes and brain functional systems. Including excessive prefrontal pruning, there is also explanation for the appearance of positive psychotic symptoms in early adulthood. An explanation for the high dopamine level of amygdala despite its decreased size and abnormal anatomy is also suggested as a compensatory function which might explain the decline in positive psychotic symptoms when schizophrenics age according to amygdala burn out. Based on this model, speculations are provided for: late onset of the effects of antipsychotics on positive psychotic symptoms, mechanism for the therapeutic effect of serotonin type 2A receptor blockers and GABAergic medications in psychosis, role of smoking in diminution of psychotic symptoms, and relationship between biological and psychological issues in the formation of psychotic symptoms. Finally, based on this model, a new role for nicotinic cholinergic drugs (such as galantamine) for treatment of schizophrenia and other psychotic or psychotic-like disorders is proposed.

Auditory sensory gating deficit in abstinent chronic alcoholics

P50 event-related potential was studied in abstinent chronic alcoholics to determine whether they had normal sensory gating. Repeated tones were presented to 17 recently detoxified chronic alcoholic patients and 17 healthy subjects while EEG was recorded. Low-resolution tomography (LORETA) was performed to obtain cerebral sources of P50. Abstinent chronic alcoholics showed reduced P50 sensory gating. Present results suggest an inhibitory deficit in early pre-attentive auditory sensory processing in chronic alcoholism.

Auditory sensory gating deficit and negative symptoms in schizophrenia

Although several investigations have shown that the local GABAergic circuit in the rat hippocampus is functional very early in development, this result has not been yet completed by the investigation of the full dendritic and axonal arborization of the neonatal interneurones. In the present study, intracellular injection of biocytin was used to assess the branching pattern of interneurones in the hippocampal CA3 region of rat between 2 and 6 days of age. Based on their dendritic morphology, the biocytin-filled interneurones were divided into four classes: bipolar, stellate, pyramidal-like and fusiform interneurones. About half of the biocytin-filled neonatal interneurones exhibited dendritic or somatic filopodial processes. The axonal arbors of the filled-interneurones were widely spread into the CA3 region, and in four out of nine cases extended beyond the CA3 region to branch into the CA1 region. These results show that, despite immature features, the filopodial processes, the hippocampal interneurones are well developed early in development at a time when their target cells, the pyramidal neurones, are still developing. These observations are consistent with a trophic role that GABA may play early in development.

Evidence for linkage disequilibrium between the alpha 7-nicotinic receptor gene (CHRNA7) locus and schizophrenia in Azorean families.

Recent studies have suggested that the alpha 7-nicotinic receptor gene (CHRNA7) may play a role in the pathogenesis of schizophrenia. The alpha 7-nicotinic receptor gene (CHRNA7) is involved in P50 auditory sensory gating deficits, and the genomic locus for this gene lies in the chromosome 15q13-14 regions. The human gene is partially duplicated (exons 5-10) with four novel upstream exons. The marker D15S1360 has been shown to be significantly linked with the phenotype of abnormal P50 suppression in schizophrenia families. The marker L76630 is 3 kb in the 3' direction from the last exon of the CHRNA7 gene and is located in the duplicated region. The function of the two L76630 copies is unknown. We genotyped three polymorphic markers D15S1360, D15S165, and L76630 that are localized in a genomic fragment containing the CHRNA7 in 31 Azorean schizophrenia families/trios (including 41 schizophrenia individuals and 97 unaffected families members). An overall analysis utilizing the family-based association test revealed significant linkage disequilibrium between L76630 and schizophrenia (P = 0.0004). Using the extended transmission disequilibrium test and limiting the analysis to one triad per family, transmission disequilibrium of D15S1360 was near significance (P = 0.078). The 15q13 region overlaps with the location of two well-known genomically imprinted disorders: Angelman syndrome and Prader-Willi syndrome. Therefore, we investigated maternal and paternal meioses. We found significant transmission disequilibrium for D15S1360 through paternal transmission (P = 0.0006) in our schizophrenia families. The L76630 marker showed a significant disequilibrium in maternal transmissions (P = 0.028). No parent-of-origin effect was found in D15S165. Overall, our results suggest that the CHRNA7 may play a role in schizophrenia in these families. A parent of origin effect may be present and requires further study.