Biomedical subjects

D L Braff

Publications and source records attributed to D L Braff.

At least 19 recordsLinked to original sources

PubMed2001

Sensorimotor gating deficits in bipolar disorder patients with acute psychotic mania.

BACKGROUND: Deficits in sensorimotor gating as assessed by prepulse inhibition (PPI) and habituation of the human startle response have been noted in schizophrenia and other patients with known dysfunction in the brain substrates that regulate PPI. During acute mania, bipolar disorder (BD) and schizophrenia patients present with symptoms that are similar. To determine if these clinical similarities extend to neurophysiologic domains, PPI and startle habituation were assessed in BD patients with acute psychotic mania and compared with a sample of acutely psychotic schizophrenia patients and a normal comparison group. METHODS: Fifteen BD patients, 16 schizophrenia patients, and 17 control subjects were assessed on PPI and startle habituation. RESULTS: The BD patients had significantly lower PPI than did the control subjects in two of the three PPI conditions (60- and 120-msec interstimulus intervals) as well as less startle habituation. The BD patients did not statistically differ from the schizophrenia patients in PPI or habituation. CONCLUSIONS: These findings of sensorimotor gating deficits among bipolar disorder patients are consistent with other findings using different measures of information processing and suggest that the neurobiological substrates underlying sensorimotor gating may be dysregulated during acute manic and psychotic states.

Acute Disease↗

PubMed2001

Impact of prepulse characteristics on the detection of sensorimotor gating deficits in schizophrenia.

Schizophrenia patients have prominent deficits in information processing that can be detected by measures of prepulse inhibition (PPI) of the startle response. Deficient PPI in schizophrenia is thought to reflect a failure of brain-based information 'protective' mechanisms that normally inhibit responsivity for 30-500ms after a weak prepulse stimulus. The relationship between specific prepulse stimulus characteristics and PPI deficits in this study was examined in 31 schizophrenia patients and 34 normal comparison subjects. Schizophrenia patients had overall deficits in PPI across four conditions where the prepulse was either discrete (abrupt) or continuous (sustained) and consisted of either white noise or a pure tone. On inspection and analysis of the data, it appears that the white noise conditions, rather than tone conditions, account for the group differences. Thus, the discrete white noise prepulse was most effective in eliciting PPI deficits, resulting in a large effect size between groups (d=0.85; P<0.01). Deficits in information-protective mechanisms in schizophrenia may be differentially sensitive to specific stimulus characteristics; this observation may be relevant both to the neurobiology of information processing deficits in schizophrenia and to the methodologies for studying these deficits experimentally.

Adult↗

PubMed2001

Translating the basic and clinical cognitive neuroscience of schizophrenia to drug development and clinical trials of antipsychotic medications.

Neurocognitive deficits have become increasingly important defining features of schizophrenia and its treatment. Multiple domains of neurocognitive functions are impaired in schizophrenia patients, and these impairments are considered to be core features of the disorder. Many recent reports support the importance of the relationship of these neurocognitive deficits to measures of "functional outcome" such as social skills acquisition, social problem solving, and community outcome. Neurocognitive deficits appear to be improved with newer (atypical) antipsychotic medications across a broad range of domains in schizophrenia patients. Together with clinical neuroscience advances, basic research in cognitive neuroscience ranging from animal models of gating functions to early gene expression induced by antipsychotic medications has illuminated the specific neural basis of neurocognitive deficits in schizophrenia and the neurobiology of antipsychotic actions. These translational basic and clinical studies provide powerful screening tools and strategies for drug development and the subsequent assessment of the clinical efficacy of new antipsychotic medications. These interlocking clinical and basic research findings have substantial implications for improving both drug development and improving clinical trials methodology for antipsychotic medications. Thus, there is an informed translation and cross-fertilization between basic and clinical research focused on the development and assessment of putative new antipsychotic compounds.

Antipsychotic Agents↗

PubMed2001

Trait contributions of complex dysregulated behavioral organization in schizophrenic patients.

BACKGROUND: The "temporal architecture" of behavior is a construct that can be used to quantify the structure of behavioral sequences in the temporal domain-for example, by using a two-choice prediction task to investigate how past responses, stimuli, and outcomes influence the decision-making process. Using this task, previous investigations of the temporal architecture of the behavior in schizophrenic patients have identified an increased frequency of alternating highly predictable and highly unpredictable response sequences in the same test session in the same patient. Here, the hypothesis is tested that this dysregulation is stable over time and independent of psychosocial factors and symptomatic fluctuations. METHODS: Ninety-one schizophrenic patients were tested on a 128 trial version of the two-choice prediction task; of those, 58 subjects completed a retest session 40 days later. Three sets of measures were obtained: simple response biases, dynamical entropy, and mutual information functions. These measures were subjected to a factor analysis, and the reliability of the resulting factors was examined. RESULTS: First, three factors were obtained, which quantify 1) the level of dysregulation on this task; 2) the extent to which a win-stay/lose-shift strategy was used; and 3) the amount of simple response perseveration. Second, Crohnbach alpha for these factors was .699, .721, and .458, respectively. Third, there were no significant differences in the level of these factors within individual patients at the two time points. Fourth, neither symptom measures (Scale for the Assessment of Positive Symptoms and Scale for the Assessment of Negative Symptoms subscale scores) nor psychosocial or clinical variables (age, gender, illness duration, medication status) were able to predict the level of these factors at test or at retest. CONCLUSIONS: These results support the hypothesis that the fundamental dysregulation of the temporal architecture of behavior in schizophrenic patients is stable across time and independent of symptomatic status. Future studies will examine the heritability of this dysfunction.

Adult↗

PubMed2001

Prefrontal, parietal, and temporal cortex networks underlie decision-making in the presence of uncertainty.

Decision-making in the presence of uncertainty, i.e., selecting a sequence of responses in an uncertain environment according to a self-generated plan of action, is a complex activity that involves both cognitive and noncognitive processes. Using functional magnetic resonance imaging, the neural substrates of decision-making in the presence of uncertainty are examined. Normal control subjects show a significant activation of a frontoparietal and limbic neural system during a two-choice prediction task relative to a two-choice response task. The most prevalent response strategy during the two-choice prediction task was "win-stay/lose-shift," where subjects will repeat the previous response if it successfully predicted the stimulus and switch to the alternative response otherwise. Increased frequency of responses that are consistent with this strategy is associated with activation in the superior temporal gyrus. In comparison, increased frequency of response inconsistent with win-stay/lose-shift is associated with parietal cortex activation. These results support the hypothesis that subjects use a frontoparietal neural system to establish a contingency based decision-making strategy even in the presence of random reinforcement.

Adult↗

PubMed2001

Neural circuit regulation of prepulse inhibition of startle in the rat: current knowledge and future challenges.

RATIONALE: Sensorimotor gating of the startle reflex can be assessed across species, using similar stimuli to elicit similar responses. Prepulse inhibition (PPI), a measure of sensorimotor gating, is reduced in patients with some neuropsychiatric disorders, and in rats after manipulations of limbic cortex, striatum, pallidum or pontine tegmentum ("CSPP" circuitry). OBJECTIVE: To review the current knowledge of the neural circuit regulation of PPI in rats, and to anticipate the future challenges facing this line of inquiry. METHODS: The published literature was reviewed and critically evaluated. RESULTS: Limbic CSPP circuitry has been studied in rats to reveal the neurochemical and neuroanatomical substrates regulating PPI at a high level of resolution. In translational cross-species research, this detailed circuit information is used as a "blueprint" to identify substrates that may lead to PPI deficits in psychiatrically disordered humans. Some human disorders with identifiable, localized lesions in CSPP circuitry may provide direct validation for the contribution of CSPP circuitry to this cross-species model. The rapid collection of experimental data supporting this cross-species PPI circuit "blueprint" has supported continuing advances in the development of theoretical models for understanding how this circuitry normally functions to regulate PPI. Such models are needed for building a conceptual framework for understanding the role of this circuitry in the regulation of sensorimotor gating in normal humans, and in the relative loss of sensorimotor gating, and the resulting clinical consequences, in individuals with particular neuropsychiatric disorders. CONCLUSIONS: Our understanding of the neural regulation of PPI has increased tremendously over the past 15 years. Progress has come in "broad strokes", and a number of important details and complex questions remain to be addressed. It is anticipated that this is a "work in progress", and that the precise models for the neural regulation of PPI will evolve substantially in the coming years.

Animals↗

PubMed2001

Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies.

RATIONALE: Since the mid-1970s, cross-species translational studies of prepulse inhibition (PPI) have increased at an astounding pace as the value of this neurobiologically informative measure has been optimized. PPI occurs when a relatively weak sensory event (the prepulse) is presented 30-500 ms before a strong startle-inducing stimulus, and reduces the magnitude of the startle response. In humans, PPI occurs in a robust, predictable manner when the prepulse and startling stimuli occur in either the same or different modalities (acoustic, visual, or cutaneous). OBJECTIVE: This review covers three areas of interest in human PPI studies. First, we review the normal influences on PPI related to the underlying construct of sensori- (prepulse) motor (startle reflex) gating. Second, we review PPI studies in psychopathological disorders that form a family of gating disorders. Third, we review the relatively limited but interesting and rapidly expanding literature on pharmacological influences on PPI in humans. METHODS: All studies identified by a computerized literature search that addressed the three topics of this review were compiled and evaluated. The principal studies were summarized in appropriate tables. RESULTS: The major influences on PPI as a measure of sensorimotor gating can be grouped into 11 domains. Most of these domains are similar across species, supporting the value of PPI studies in translational comparisons across species. The most prominent literature describing deficits in PPI in psychiatrically defined groups features schizophrenia-spectrum patients and their clinically unaffected relatives. These findings support the use of PPI as an endophenotype in genetic studies. Additional groups of psychopathologically disordered patients with neuropathology involving cortico-striato-pallido-pontine circuits exhibit poor gating of motor, sensory, or cognitive information and corresponding PPI deficits. These groups include patients with obsessive compulsive disorder, Tourette's syndrome, blepharospasm, temporal lobe epilepsy with psychosis, enuresis, and perhaps posttraumatic stress disorder (PTSD). Several pharmacological manipulations have been examined for their effects on PPI in healthy human subjects. In some cases, the alterations in PPI produced by these drugs in animals correspond to similar effects in humans. Specifically, dopamine agonists disrupt and nicotine increases PPI in at least some human studies. With some other compounds, however, the effects seen in humans appear to differ from those reported in animals. For example, the PPI-increasing effects of the glutamate antagonist ketamine and the serotonin releaser MDMA in humans are opposite to the PPI-disruptive effects of these compounds in rodents. CONCLUSIONS: Considerable evidence supports a high degree of homology between measures of PPI in rodents and humans, consistent with the use of PPI as a cross-species measure of sensorimotor gating. Multiple investigations of PPI using a variety of methods and parameters confirm that deficits in PPI are evident in schizophrenia-spectrum patients and in certain other disorders in which gating mechanisms are disturbed. In contrast to the extensive literature on clinical populations, much more work is required to clarify the degree of correspondence between pharmacological effects on PPI in healthy humans and those reported in animals.

Humans↗

PubMed2001

Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: a decade in review.

RATIONALE: Patients with schizophrenia exhibit deficits in an operational measure of sensorimotor gating: prepulse inhibition (PPI) of startle. Similar deficits in PPI are produced in rats by pharmacological or developmental manipulations. These experimentally induced PPI deficits in rats are clearly not animal models of schizophrenia per se, but appear to provide models of sensorimotor gating deficits in schizophrenia patients that have face, predictive, and construct validity. In rodents, disruptions in PPI of startle are produced by: stimulation of D2 dopamine (DA) receptors, produced by amphetamine or apomorphine; activation of serotonergic systems, produced by serotonin (5-HT) releasers or direct agonists at multiple serotonin receptors; and blockade of N-methyl-D-aspartate (NMDA) receptors, produced by drugs such as phencyclidine (PCP). Accordingly, dopaminergic, serotonergic, and glutamatergic models of disrupted PPI have evolved and have been applied to the identification of potential antipsychotic treatments. In addition, some developmental manipulations, such as isolation rearing, have provided non-pharmacological animal models of the PPI deficits seen in schizophrenia. OBJECTIVE: This review summarizes and evaluates studies assessing the effects of systemic drug administrations on PPI in rats. METHODS: Studies examining systemic drug effects on PPI in rats prior to January 15, 2001 were compiled and organized into six annotated appendices. Based on this catalog of studies, the specific advantages and disadvantages of each of the four main PPI models used in the study of antipsychotic drugs were critically evaluated. RESULTS: Despite some notable inconsistencies, the literature provides strong support for significant disruptions in PPI in rats produced by DA agonists, 5-HT2 agonists, NMDA antagonists, and isolation rearing. Each of these models exhibits sensitivity to at least some antipsychotic medications. While the PPI model based on the effects of direct DA agonists is the most well-validated for the identification of known antipsychotics, the isolation rearing model also appears to be sensitive to both typical and atypical antipsychotics. The 5-HT PPI model is less generally sensitive to antipsychotic medications, but can provide insight into the contribution of serotonergic systems to the actions of newer antipsychotics that act upon multiple receptors. The deficits in PPI produced by NMDA antagonists appear to be more sensitive to clozapine-like atypical antipsychotics than to typical antipsychotics. Hence, despite some exceptions to this generalization, the NMDA PPI model might aid in the identification of novel or atypical antipsychotic medications. CONCLUSIONS: Studies of drug effects on PPI in rats have generated four distinctive models that have utility in the identification of antipsychotic medications. Because each of these models has specific advantages and disadvantages, the choice of model to be used depends upon the question being addressed. This review should help to guide such decisions.

Animals↗

PubMed2001

Self-monitoring enhances Wisconsin Card Sorting Test performance in patients with schizophrenia: performance is improved by simply asking patients to verbalize their sorting strategy.

Patients with schizophrenia have Wisconsin Card Sorting Test (WCST) deficits, which are commonly interpreted as reflecting frontal cortex-based executive dysfunction. One means of assessing the refractoriness of frontal-executive impairment is to utilize a training or modification strategy to improve WCST performance. In this study, 73 patients with schizophrenia were assigned to 1 of 2 groups. Group 1 received the standard WCST instructions for 64 cards (Condition 1). For the second 64-card deck, the patients were asked to verbalize the reason that they placed the card where they did after each sort (Condition 2). Group 2 received this modified instruction 1st (Condition 1) and then the standard instructions for the second deck (Condition 2). A group of normal comparison participants was also tested using standard instructions alone. Group 2 committed significantly fewer perseverative responses than did Group 1. Furthermore, there was no significant difference between Group 2 (Condition 1) and the normal participants. Group 1's performance improved when patients were exposed to the modified instructions (Condition 2). Additionally, poor premorbid factors and disorganized symptoms were associated with decreased benefit from the modified instructions across both groups. Cumulatively, these data suggest that a simple instruction may enhance executive function and impact WCST performance in patients with schizophrenia.

Adult↗

PubMed2001

Working memory in schizophrenia: transient "online" storage versus executive functioning.

Working memory has been described as the temporary "online" storage and the subsequent manipulation and retrieval of information. It has been suggested that the prefrontal cortex is a primary site of working memory. Schizophrenia patients, who are thought to have prefrontal cortical dysfunction, have demonstrated inconsistent deficits on a variety of verbal and spatial working memory tests. This has led to questions about how to define and measure working memory, whether these deficits are distinct to one cognitive domain, and what role factors such as intelligence and symptoms play in working memory performance. We compared schizophrenia patients to normal comparison subjects in four separate studies. Based upon the results we recommend that working memory tests be characterized as either transient "online" storage and retrieval tasks (where short-term storage and retrieval of information is required) or executive-functioning working memory tasks (where storage, manipulation, and retrieval of information is required). The importance of clearly identifying which distinct aspects of working memory are assessed is discussed.

Adolescent↗

PubMed2001

Measuring P50 suppression and prepulse inhibition in a single recording session.

OBJECTIVE: Two distinct measures have been used to assess inhibitory gating deficits in schizophrenia patients: P50 suppression and prepulse inhibition of the startle response. It remains unclear whether both measures can be assessed in a single testing session. METHOD: Twelve normal subjects underwent testing in a carefully designed combined P50/prepulse inhibition session using stimulus characteristics similar to those described in the existing literature. RESULTS: The levels of both P50 suppression and prepulse inhibition obtained in the combined session were highly similar to those obtained in independent testing of previous cohorts of normal subjects. As in previous experiments, P50 suppression and prepulse inhibition were not significantly correlated. CONCLUSIONS: Measuring P50 suppression and prepulse inhibition in a single session is feasible and offers a unique opportunity to assess these two distinct gating measures contemporaneously in cohorts of normal comparison subjects and schizophrenia patients, so that temporal shifts in one or both measures are minimized.

Acoustic Stimulation↗

PubMed2000

Schizophrenia patients demonstrate a dissociation on declarative and non-declarative memory tests.

Declarative memory refers to the recall and recognition of factual information. In contrast, non-declarative memory entails a facilitation of memory based on prior exposure and is typically assessed with priming and perceptual-motor sequencing tasks. In this study, schizophrenia patients were compared to normal comparison subjects on two computerized memory tasks: the Word-stem Priming Test (n=30) and the Pattern Sequence Learning Test (n=20). Word-stem Priming includes recall, recognition (declarative) and priming (non-declarative) components of memory. The schizophrenia patients demonstrated an impaired performance on recall of words with relative improvement during the recognition portion of the test. Furthermore, they performed normally on the priming portion of the test. Thus, on tests of declarative memory, the patients had retrieval deficits with intact performance on the non-declarative memory component. The Pattern Sequence Learning Test utilizes a serial reaction time paradigm to assess non-declarative memory. The schizophrenia patients' serial reaction time was significantly slower than that of comparison subjects. However, the patients' rate of acquisition was not different from the normal comparison group. The data suggest that patients with schizophrenia process more slowly than normal, but have an intact non-declarative memory. The schizophrenia patients' dissociation on declarative vs. non-declarative memory tests is discussed in terms of possible underlying structural impairment.

Adult↗

PubMed2000

Toward understanding the biology of a complex phenotype: rat strain and substrain differences in the sensorimotor gating-disruptive effects of dopamine agonists.

Sensorimotor gating, measured by prepulse inhibition (PPI) of the startle reflex, is reduced in schizophrenia patients and in rats treated with dopamine agonists. Strain differences in the sensitivity to the PPI-disruptive effects of dopamine agonists may provide insight into the genetic basis for human population differences in sensorimotor gating. We reported strain differences in the sensitivity to the PPI-disruptive effects of the D1/D2 agonist apomorphine in adult rats, with greater sensitivity in Harlan Sprague Dawley (SDH) versus Wistar (WH) rats. However, Kinney et al. (1999) recently reported opposite findings, using Bantin-Kingman Sprague Dawley (SDBK) and Wistar (WBK) rats; in fact, SDBK rats did not exhibit clear apomorphine-induced reductions in sensorimotor gating. These new findings of Kinney et al. (1999) directly conflict with over 15 years of results from our laboratories and challenge interpretations from a large body of literature. The present studies carefully assessed drug effects on sensorimotor gating in SD versus W strains, across rat suppliers (H vs BK). Significantly greater SDH than WH apomorphine sensitivity in PPI measures was observed in both adult and 18 d pups, confirming that these strain differences are both robust and innate. These strain differences in apomorphine sensitivity were not found in adult BK rats. Supplier differences in sensitivity (SDH > SDBK) were also evident in the PPI-disruptive effects of D1 but not D2-family agonists; PPI was clearly disrupted by quinpirole in both SDH and SDBK rats. These findings demonstrate robust, innate, neurochemically specific, and apparently heritable phenotypic differences in an animal model of sensorimotor gating deficits in human neuropsychiatric disorders.

Acoustic Stimulation↗

PubMed2000

Environmental enrichment and isolation rearing in the rat: effects on locomotor behavior and startle response plasticity.

BACKGROUND: Laboratory rats exhibit behavioral changes that reflect a continuum of early life experience, from isolation-reared to socially reared to enrichment-reared conditions. In this study, we further characterize the behavioral effects of isolation, social, and enriched rearing on locomotor activity, patterns of movement and exploration, startle reactivity, prepulse inhibition (PPI), and habituation in adult rats. METHODS: Male Sprague-Dawley rat pups (21 days old) were housed under enrichment (three per cage with toys and exposure to enriched environments), normal social (three per cage), or isolation (one per cage) conditions. Eight weeks later, locomotor and exploratory behaviors, acoustic startle reactivity, PPI, and habituation were measured in the three groups. RESULTS: Enrichment-reared rats exhibited reduced exploration and rapid habituation of locomotor activity, increased startle reactivity, and normal PPI and startle habituation compared with socially reared controls. Isolation-reared rats exhibited increased exploration and normal habituation of locomotor activity, increased startle reactivity, reduced PPI, and normal startle habituation. CONCLUSIONS: Isolation- and enrichment-reared rats exhibited opposite changes in some behaviors and similar changes in other behaviors. Specifically, rats raised in enriched conditions appear more efficient at assimilating stimuli from their environment than do rats reared in isolation. Nevertheless, both enrichment- and isolation-rearing conditions increased startle reactivity, whereas only isolation rearing led to disruptions of PPI in adulthood. These results suggest that isolation- and enrichment-rearing conditions produce some common and some differential effects on how rats process environmental stimuli. For studies of isolation-rearing effects on PPI, however, the complex and resource-intensive enrichment condition seems to offer few advantages over the normal social condition.

Animals↗

PubMed2000

Do self-reports of perceptual anomalies reflect gating deficits in schizophrenia patients?

Jin and colleagues presented an innovative study examining P50 suppression and patients' self-reported perceptual anomalies as two related operational measures of sensory gating deficits in schizophrenia patients. They found that those schizophrenia patients who endorsed experiences of sensory inundation had normal levels of P50 suppression, whereas patients who tended to endorse fewer complaints of perceptual anomalies had P50 suppression deficits. Jin et al's finding challenges the common belief that P50 suppression deficits are associated with cognitive and sensory anomalies reflecting poor gating in schizophrenia patients. This article comments on how the dissociation between phenomenological experiences of gating disturbances and P50 suppression might be explained by the limits of self-report in schizophrenia patients who have deficient insight and self-awareness. We hypothesize that the self-reported inability to screen out irrelevant stimuli reflects a voluntary, controlled process that is different from the involuntary, automatic process measured by P50 suppression.

Attention↗

PubMed2000

Neurocognitive deficits and functional outcome in schizophrenia: are we measuring the "right stuff"?

There has been a surge of interest in the functional consequences of neurocognitive deficits in schizophrenia. The published literature in this area has doubled in the last few years. In this paper, we will attempt to confirm the conclusions from a previous review that certain neurocognitive domains (secondary verbal memory, immediate memory, executive functioning as measured by card sorting, and vigilance) are associated with functional outcome. In addition to surveying the number of replicated findings and tallying box scores of results, we will approach the review of the studies in a more thorough and empirical manner by applying a meta-analysis. Lastly, we will discuss what we see as a key limitation of this literature, specifically, the relatively narrow selection of predictor measures. This limitation has constrained identification of mediating variables that may explain the mechanisms for these relationships.

Cognition Disorders↗

PubMed2000

Animal models of deficient sensorimotor gating: what we know, what we think we know, and what we hope to know soon.

Sensorimotor gating of the startle reflex can be studied in humans and laboratory animals using measures of prepulse inhibition (PPI) of the startle reflex. PPI is reduced in patients with specific neuropsychiatric disorders and in rats after manipulation of the limbic cortex, striatum, pallidum or pontine tegmentum. Studies are rapidly identifying the neurochemical and neuroanatomical substrates regulating PPI in laboratory animals; this detailed circuit information has been used as a 'blueprint' to identify possible candidate substrates responsible for PPI deficits in psychiatrically disordered humans. In parallel, studies have also begun to assess the homology of pharmacological effects on PPI across species, as an initial step towards translating detailed neural circuit information from rats to humans. Despite this rapid progress, there is an increasing danger of overlooking important methodological and interpretative issues that could impact either positively or negatively on the ultimate utility of models based on measures of PPI. Some of these issues--ranging from the cross-species methods for quantifying specific variables to the relevance of genetic drift to animal and human studies of PPI--and their implications for future studies are the focus of this review.

Animals↗

PubMed2000

Sensory gating deficits assessed by the P50 event-related potential in subjects with schizotypal personality disorder.

OBJECTIVE: The schizophrenia spectrum includes individuals with schizophrenia, their relatives, and individuals with schizotypal personality disorder. Subjects in the schizophrenia spectrum have disorders of attention, cognition, and information processing. Attention and information processing can be assessed by testing suppression of the P50 event-related potential; the amplitude of the P50 wave is measured in response to each of two auditory clicks. In normal subjects, the P50 wave following the second click is suppressed, or "gated." Schizophrenic patients and their relatives show less suppression of the second P50 wave. Deficits in P50 suppression have high heritability and show linkage to the alpha-7 subunit of the nicotinic cholinergic receptor gene in families with schizophrenia, suggesting that deficits in P50 suppression are trait markers for gating abnormalities in schizophrenia spectrum subjects. Although schizotypal subjects have been shown to have deficits in sensorimotor gating as measured by prepulse inhibition, to the authors' knowledge P50 sensory gating in schizotypal personality disorder has yet to be reported. METHOD: P50 suppression in 26 subjects with schizotypal personality disorder and 23 normal subjects was assessed through auditory conditioning and testing. RESULTS: The subjects with schizotypal personality had significantly less P50 suppression than did the normal subjects. CONCLUSIONS: Subjects with schizotypal personality disorder may have trait-linked sensory gating deficits similar to those in patients with schizophrenia and their relatives. Because these subjects may manifest sensory gating deficits without overt psychotic symptoms, it is likely that these deficits represent a core cognitive dysfunction of the schizophrenia spectrum.

Acoustic Stimulation↗