Biomedical subjects

David L Braff

Publications and source records attributed to David L Braff.

At least 19 recordsLinked to original sources

PubMed2006

Prepulse inhibition and P50 suppression are both deficient but not correlated in schizophrenia patients.

BACKGROUND: Inhibitory measures such as prepulse inhibition of the acoustic startle reflex (PPI) and event related potential P50 suppression have been widely reported to show deficits in schizophrenia patients. The relationship between PPI and P50 suppression in schizophrenia patients has remained unclear. METHODS: One hundred fifty-six schizophrenia patients and 104 normal comparison subjects (NCS) were tested on PPI and P50 suppression. RESULTS: Eighty-one patients and 70 NCS had valid and scorable data on both PPI and P50 suppression paradigms. As in the larger groups, these cohorts had deficits on both PPI (p < .05) and P50 suppression (p < .05). Analyses revealed a weak, but significant correlation between PPI and P50 suppression in the NCS group (r = .33, p < .05) but not in the patient group (r = .03, ns). CONCLUSIONS: Although PPI and P50 suppression were both reduced in the patients, they were not correlated. This divergence suggests that these gating functions are complementary or redundant levels of "protection" against processes that may lead to cognitive fragmentation.

Adult↗

PubMed2006

Social cognition in schizophrenia: relationships with neurocognition and negative symptoms.

Despite the growing importance of social cognition in schizophrenia, fundamental issues concerning the nature of social cognition in schizophrenia remain unanswered. One issue concerns the strength of the relationships between social cognition and key features of the disorder such as neurocognitive deficits and negative symptoms. The current study employed structural equation modeling to examine three key questions regarding the nature of social cognition in schizophrenia: 1) Are social cognition and neurocognition in schizophrenia better modeled as one or two separate constructs? 2) Are social cognition and negative symptoms in schizophrenia better modeled as one or two separate constructs?, and 3) When social cognition, neurocognition, and negative symptoms are included in a single model, is social cognition more closely related to neurocognition or to negative symptoms? In this cross sectional study, one hundred outpatients with schizophrenia or schizoaffective disorder were administered measures of social cognition, neurocognition, and negative symptoms. A two-factor model that represented social cognition and neurocognition as separate constructs fit the data significantly better than a one-factor model, suggesting that social cognition and neurocognition are distinct, yet highly related, constructs. Likewise, a two-factor model that represented social cognition and negative symptoms as separate constructs fit the data significantly better than a one-factor model, suggesting that social cognition and negative symptoms are distinct constructs. A three-factor model revealed that the relationship between social cognition and neurocognition was stronger than the relationship between social cognition and negative symptoms. The current findings start to provide insights into the structure of social cognition, neurocognition, and negative symptoms in schizophrenia.

Adult↗

PubMed2006

Deconstructing schizophrenia: an overview of the use of endophenotypes in order to understand a complex disorder.

The genetics of schizophrenia has been approached utilizing a variety of methods. One emerging strategy is the use of endophenotypes in order to understand and identify the functional importance of genetically transmitted, brain-based deficits across schizophrenia kindreds. The endophenotype strategy is a topic of this issue of Schizophrenia Bulletin. Endophenotypes are quantitative, heritable, trait-related deficits typically assessed by laboratory-based methods rather than clinical observation. Endophenotypes are seen as closer to genetic variation than are clinical symptoms of schizophrenia, and are therefore closely linked to heritable risk factors. There has been a broad expansion of opportunities available to psychiatric neuroscientists who use the endophenotype strategy to understand the genetic basis of schizophrenia. In this context, genetic variation such as single nucleotide polymorphisms (SNPs) induces abnormalities in endophenotypic domains such as neurocognition, neurodevelopment, metabolism, and neurophysiology. This article discusses the challenges that abound in genetic research of schizophrenia, including issues in ascertainment, epistasis, ethnic diversity, and the potentially normalizing effects of second-generation antipsychotic medications on neurocognitive and neurophysiological measures. Robust strategies for meeting these challenges are discussed in this review and the subsequent articles in this issue. This article summarizes conceptual advances and progress in the measurement and use of endophenotypes in schizophrenia that form the basis of the multisite National Institute of Mental Health Consortium on the Genetics of Schizophrenia. The endophenotype strategy offers powerful and exciting opportunities to understand the genetically conferred neurobiological vulnerabilities and possible new strong inference and molecularly based treatments for schizophrenia.

Antipsychotic Agents↗

PubMed2006

The Consortium on the Genetics of Endophenotypes in Schizophrenia: model recruitment, assessment, and endophenotyping methods for a multisite collaboration.

BACKGROUND: The Consortium on the Genetics of Schizophrenia (COGS) is an ongoing, National Institute of Mental Health-funded, 7-site collaboration investigating the occurrence and genetic architecture of quantitative endophenotypes related to schizophrenia. The purpose of this article is to provide a description of the COGS structure and methods, including participant recruitment and assessment. METHODS: The hypothesis-driven recruitment strategy ascertains families that include a proband with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of schizophrenia, and at least one unaffected full sibling available for genotyping and endophenotyping, along with parents available for genotyping and (optional depending on age) endophenotyping. The family structure is selected to provide contrast in quantitative endophenotypic traits and thus to maximize the power of the planned genetic analyses. Probands are recruited from many sources including clinician referrals, local National Alliance for the Mentally Ill chapters, and advertising via the media. All participants undergo a standardized protocol that includes clinical characterization, a blood draw for genotyping, and endophenotype assessments (P50 suppression, prepulse inhibition, antisaccade performance, continuous performance tasks, letter-number span, verbal memory, and a computerized neurocognitive battery). Investigators participate in weekly teleconferences to coordinate and evaluate recruitment, clinical assessment, endophenotyping, and continuous quality control of data gathering and analyses. Data integrity is maintained through use of a highly quality-assured, centralized web-based database. RESULTS: As of February 2006, 355 families have been enrolled and 688 participants have been endophenotyped, including schizophrenia probands (n = 154, M:F = 110:44), first-degree biological relatives (n = 343, M:F = 151:192), and community comparison subjects (n = 191, M:F = 81:110). DISCUSSION: Successful multisite genetics collaborations must institute standardized methodological criteria for assessment and recruitment that are clearly defined, well communicated, and uniformly applied. In parallel, studies utilizing endophenotypes require strict adherence to criteria for cross-site data acquisition, equipment calibration and testing and software equivalence, and continuous quality assurance for many measures obtained across sites. This report describes methods and presents the structure of the COGS as a model of multisite endophenotype genetic studies. It also provides demographic information after the first 2 years of data collection on a sample for whom the behavioral data and genetics of endophenotype performance will be fully characterized in future articles. Some issues discussed in the reviews that follow reflect the challenges of evaluating endophenotypes in studies of the genetic architecture of endophenotypes in schizophrenia.

Cooperative Behavior↗

PubMed2006

Statistical genetics concepts and approaches in schizophrenia and related neuropsychiatric research.

Statistical genetics is a research field that focuses on mathematical models and statistical inference methodologies that relate genetic variations (ie, naturally occurring human DNA sequence variations or "polymorphisms") to particular traits or diseases (phenotypes) usually from data collected on large samples of families or individuals. The ultimate goal of such analysis is the identification of genes and genetic variations that influence disease susceptibility. Although of extreme interest and importance, the fact that many genes and environmental factors contribute to neuropsychiatric diseases of public health importance (eg, schizophrenia, bipolar disorder, and depression) complicates relevant studies and suggests that very sophisticated mathematical and statistical modeling may be required. In addition, large-scale contemporary human DNA sequencing and related projects, such as the Human Genome Project and the International HapMap Project, as well as the development of high-throughput DNA sequencing and genotyping technologies have provided statistical geneticists with a great deal of very relevant and appropriate information and resources. Unfortunately, the use of these resources and their interpretation are not straightforward when applied to complex, multifactorial diseases such as schizophrenia. In this brief and largely nonmathematical review of the field of statistical genetics, we describe many of the main concepts, definitions, and issues that motivate contemporary research. We also provide a discussion of the most pressing contemporary problems that demand further research if progress is to be made in the identification of genes and genetic variations that predispose to complex neuropsychiatric diseases.

Chromosome Mapping↗

PubMed2006

Successful multi-site measurement of antisaccade performance deficits in schizophrenia.

The antisaccade task is a promising schizophrenia endophenotype; it is stable over time and reflects neurophysiological deficits present in both schizophrenia subjects and their first-degree relatives. Meaningful genetic research requires large sample sizes that are best ascertained using multi-site study designs. To establish the criterion validity of the antisaccade task in a multi-site design, the Consortium on the Genetics of Schizophrenia (COGS) examined whether seven sites could detect previously reported antisaccade deficits in schizophrenia subjects. Investigators presented 3 blocks of 20 antisaccade stimuli to 143 schizophrenia subjects and 195 comparison subjects. Frequent collaborator communication, standardized training, and ongoing quality assurance optimized testing uniformity. Data were discarded from only 1.2% of subjects due to poor quality, reflecting the high fidelity of data collection and scoring methods. All sites detected a significant difference in the proportion of correct antisaccades between schizophrenia and comparison subjects (p<.02 at all sites); group differences in gain and latency were less robust. Regression analyses to adjust for the effects of group, site, age, gender, smoking, and parental education on the proportion of correct antisaccades revealed a significant effect of group, site, and age but no effect of gender, smoking, or parental education, and no group-by-site interactions. Intraclass correlations between proportion of correct antisaccades across the blocks of stimuli ranged from 0.87 to 0.93, demonstrating good within-session reliability at sites. These results confirm previous findings of antisaccade deficits in schizophrenia subjects and support the use of the antisaccade task as a potential schizophrenia endophenotype in multi-site genetic studies.

Adolescent↗

PubMed2006

The neural correlates of habituation of response to startling tactile stimuli presented in a functional magnetic resonance imaging environment.

Functional magnetic resonance imaging (fMRI) provides a means of identifying neural circuitry associated with startle and its modulation in humans. Twelve subjects who demonstrated eyeblink startle in the laboratory were recruited for an fMRI study in which they were scanned while presented with two identical runs consisting of alternating blocks of no stimuli and startling tactile stimuli. Together, behavioral and imaging data are consistent with a pattern of general cortical and thalamic activation induced by startling stimuli that shows habituation both across and within runs. From Run 1 to Run 2, both the eyeblink amplitude and the fMRI signal decreased. Within Run 1, there was a graded decrease in eyeblink amplitude and whole-brain fMRI signal across blocks of startling stimuli. A similar graded decrease was observed in the thalamus signal, as well. Thus, startling tactile stimuli initially induce widespread cortical and thalamic activity, perhaps mediated by the reticular activating system. The activity then habituates in a graded fashion with repeated presentations of the stimuli.

Adult↗

PubMed2006

Gamma band oscillations reveal neural network cortical coherence dysfunction in schizophrenia patients.

BACKGROUND: Gamma band activity has been associated with many sensory and cognitive functions, and is important for cortico-cortical transmission and the integration of information across neural networks. The aims of the present study were to determine if schizophrenia patients have deficits in the generation and maintenance of coherent, synchronized oscillations in response to steady-state stimulation, and to examine the clinical and cognitive correlates of the electroencephalography (EEG) oscillatory dynamics. METHODS: Schizophrenia patients (n = 100) and nonpsychiatric subjects (n = 80) underwent auditory steady-state event-related potential testing. Click trains varying in rate of stimulation (20, 30, and 40 Hz) were presented; EEG-evoked power and intertrial phase synchronization were obtained in response to each stimulation frequency. Subjects also underwent clinical and neurocognitive assessments. RESULTS: Patients had reductions in both evoked power and phase synchronization in response to 30- and 40-Hz stimulation but normal responsivity to 20-Hz stimulation. Maximal deficits were detected in response to 40-Hz stimulation. A modest association of reduced working memory performance and 40-Hz intertrial phase synchronization was present in schizophrenia patients (r = .32, p <.01). CONCLUSIONS: Schizophrenia patients have frequency-specific deficits in the generation and maintenance of coherent gamma-range oscillations, reflecting a fundamental degradation of basic integrated neural network activity.

Acoustic Stimulation↗

PubMed2006

Startle gating deficits in a large cohort of patients with schizophrenia: relationship to medications, symptoms, neurocognition, and level of function.

CONTEXT: Patients with schizophrenia exhibit deficits in automatic, preattentive sensorimotor gating (prepulse inhibition [PPI]) of the startle reflex. OBJECTIVE: To assess the relationships between PPI deficits and demographic, clinical, neurocognitive, and functional status in a large cohort of patients with schizophrenia. DESIGN: Cross-sectional comparison of patients with schizophrenia and normal comparison subjects. SETTING: University-based psychophysiology laboratory. PARTICIPANTS: Carefully screened patients with schizophrenia (n = 103) and normal comparison subjects (n = 66). MAIN OUTCOME MEASURES: Participants were assessed in structured clinical interviews and tested in measures of acoustic startle PPI and neurocognition. The level of functioning was assessed in patients using validated scales. Analyses first compared all of the patients vs normal comparison subjects. Patients were then divided based on sex, medications, smoking status, and levels of PPI. The associations of PPI to clinical, neurocognitive, and functional variables were assessed using both continuous and categorical analyses. RESULTS: Compared with normal comparison subjects, patients exhibited PPI deficits at 60-millisecond intervals but not at 30- or 120-millisecond intervals. In addition, patients exhibited deficits in neurocognition. Among patients, PPI levels were associated with sex (higher in men than in women), medication status (highest in patients treated with atypical antipsychotics), and smoking (higher in smokers than in nonsmokers). Compared with patients in the highest quartile of PPI, those in the lowest quartile of PPI were significantly more impaired on specific functional measures but did not differ in neurocognitive measures or symptom severity. The relationship between low PPI and functional impairment was most pronounced and orderly in male patients. CONCLUSIONS: These findings highlight several important factors (sex, medications, and smoking status) that strongly impact the study and interpretation of PPI deficits in patient populations. These results also support the concept that deficient PPI is associated with impaired functional status in schizophrenia.

Acoustic Stimulation↗

PubMed2006

Prepulse-elicited motor reactions do not differ between schizophrenia patients and control subjects.

Electromyographic (EMG) measures were made of the eyeblink response to stimuli 2-16 dB over a 70-dBA noise background as well as the eyeblink response to startling 115-dBA pulses in 15 schizophrenia patients and 10 control subjects. In patients and in control subjects, weak stimuli did not elicit EMG activation. Startling stimuli elicited robust EMG activation in both groups. Compared with control subjects, schizophrenia patients are not more sensitive to motor-activating effects of weak acoustic stimuli that served as prepulses in published reports of prepulse inhibition deficits in schizophrenia. Thus, differential sensitivity to the motor-activating effects of prepulses should not contribute to reduced prepulse inhibition in schizophrenia patients versus control subjects.

Acoustic Stimulation↗

PubMed2006

Convergence and divergence in the neurochemical regulation of prepulse inhibition of startle and N40 suppression in rats.

Prepulse inhibition of startle ('PPI'), a cross-species measure of sensorimotor gating, is impaired in schizophrenia patients. Suppression of P50 event-related potentials (ERPs) in response to the second of two clicks ('P50 gating') is also impaired in schizophrenia. Suppression of N40 ERPs to the second of two clicks ('N40 gating') is thought by some to be a rat homolog of human P50 gating. Emerging evidence suggests differences in the neurobiology of deficits detected by PPI vs P50 (or N40) gating. We recorded PPI and N40 gating contemporaneously in rats, to assess convergence and divergence in the neurochemical regulation of these measures. Dose-response studies examined the effects of apomorphine (APO), phencyclidine (PCP) or the 5HT2A agonist DOI on PPI, and on motor responses to stimuli (S1 and S2) that elicit N40 gating. Effects of optimal drug doses on PPI and N40 gating were then assessed in other rats with implanted cortical surface electrodes. APO, PCP and DOI caused dose-dependent disruptions of both PPI and gating of motor responses to N40 stimuli. Reduced PPI reflected diminished prepulse effectiveness, demonstrated by increased startle levels on prepulse+pulse trials. In contrast, reduced gating of motor responses to N40 stimuli reflected a reduced motor response to S1. In separate rats, robust PPI, N40 potentials and N40 gating could be detected within one test. PPI and N40 gating were disrupted by APO, PCP, and DOI. Again, drug effects on PPI reflected increased startle on prepulse+pulse trials, while those on N40 gating reflected reduced ERP responses to S1. In conclusion, when PPI and N40 gating were studied concurrently in rats, drug effects on PPI reflected reduced inhibition of startle by the prepulse, while diminished N40 gating reflected S1 response suppression. Despite similarities in drug sensitivity, these results suggest that distinct neurobiological mechanisms underlie drug-induced deficits in PPI and N40 gating.

Acoustic Stimulation↗

PubMed2005

Effects of background and prepulse characteristics on prepulse inhibition and facilitation: implications for neuropsychiatric research.

BACKGROUND: Both prepulse inhibition (PPI) and prepulse facilitation (PPF) deficits have been reported in schizophrenia patients, but the use of different experimental parameters across laboratories makes direct comparisons of results difficult. We assessed the effects of different parameters on PPI and PPF in normal subjects. METHODS: Eyeblink startle was measured in 14 healthy male subjects, using 115 dB[A] white noise startle pulses and 86 dB[A] prepulses. Analyses compared the effects of: 1) background noise level (ambient 54 vs. 70 dB[A]) on PPI and PPF, 2) prepulse duration (discrete 20 msec vs. continuous) on PPF, 3) prepulse frequency (1000 Hz vs. white noise) on PPI and PPF, and 4) prepulse interval (2000 vs. 4500 msec) on PPF. RESULTS: Compared to an experimentally delivered 70 dB[A] background, ambient 54 dB[A] background led to significantly more PPI (with discrete white noise prepulses), and more PPF (with continuous prepulses). Continuous and longer (4500 msec) prepulses induced more PPF than did discrete and shorter (2000 msec) prepulses. CONCLUSIONS: Paradigmatic differences appear likely to be responsible for divergent findings in studies of PPI and PPF in normal and schizophrenia subjects. The present study should guide investigators in the selection of parameters for assessing PPI and PPF in studies of normal subjects and schizophrenia patients. Attention to the 4 factors of 1) background noise, 2) prepulse duration, 3) frequency, and 4) interval will facilitate comparability of results across different laboratories, especially when using PPI/PPF in schizophrenia research as neural substrate probes, as biomarkers, and as endophenotypes.

Acoustic Stimulation↗

PubMed2005

P50 suppression in individuals at risk for schizophrenia: the convergence of clinical, familial, and vulnerability marker risk assessment.

BACKGROUND: Identification of individuals at risk for the development of schizophrenia is important because it can lead to a greater understanding of the early stages of the illness. The aim of the present study was to determine whether individuals "at risk" for schizophrenia have deficits in P50 suppression, a preattentive measure of sensory gating. METHODS: Thirty-one at-risk and 21 normal comparison subjects were referred to the CARE (Cognitive Assessment and Risk Evaluation) Program at University of California San Diego. The primary aim of the CARE Program is to identify individuals who are at the greatest risk for conversion to psychosis, with a combination of clinical, familial, and vulnerability markers, including P50 suppression. RESULTS: As a group, the at-risk subjects had modestly lower levels (effect size=.43) of P50 suppression (55.1%, SD=39.8) relative to comparison subjects (71.5%, SD=34.7). At-risk subjects with a first-degree relative with schizophrenia had profoundly deficient P50 suppression (16.4%, SD=33.8) compared with other at-risk (p<.05) and comparison subjects (p<.005). CONCLUSIONS: Ongoing longitudinal follow-up studies will determine whether it is possible to improve the predictive validity of the clinical and familial variables by using P50 suppression alone or in combination with other measures in determining which individuals are at greatest risk for schizophrenia.

Acoustic Stimulation↗

PubMed2005

On the waveform of the acoustic startle blink in the paradigm of prepulse inhibition - methodological and physiological aspects.

Recent studies suggest that the eye blink response to intense acoustic stimuli consists of two components that may occasionally result in waveforms with two peaks. In the present study, the prevalence, peak latencies, and peak magnitudes in responses exhibiting one or two peaks were investigated in healthy subjects in 25 pulse-alone and 25 prepulse-pulse trials using an interstimulus interval of 60 ms. Electromyographic activity was recorded simultaneously from the orbicularis oculi muscle (OOM) and from the sternocleidomastoid muscle (SCM) to explore the temporal relationship of the peaks to the generalized startle reaction. Responses in the OOM occurred with shorter onset and peak latencies than the responses in the SCM. In about 30% of pulse-alone trials, OOM responses exhibited two peaks that showed similar prepulse inhibition. These findings support the view that both components of the acoustically evoked OOM response exhibit similar plasticity in the paradigm of prepulse inhibition.

Acoustic Stimulation↗

PubMed2005

Female schizophrenia patients have prepulse inhibition deficits.

BACKGROUND: Prepulse inhibition (PPI) of startle shows sexual dimorphism: women have lower levels of PPI than do men, and have menstrual cycle shifts in PPI. Many studies report PPI deficits in male schizophrenia patients; one recent report identified PPI deficits in male but not female patients. This study was designed to determine whether female schizophrenia patients have lower levels of PPI than normal females. METHODS: Twenty-five female schizophrenia patients, and 26 normal females were tested in a startle paradigm using 115 dB startle pulses and prepulses of 8 and 16 dB above a 70 dB background, with 30 and 120 msec prepulse intervals. RESULTS: Female patients had significantly less PPI compared with normal females, particularly when 16 dB prepulses were utilized. Patients also exhibited a nonsignificant trend towards lower levels of habituation compared to normal subjects. CONCLUSIONS: Under the present paradigmatic and subject acquisition conditions, female schizophrenia patients had PPI deficits compared to normal females.

Acoustic Stimulation↗

PubMed2005

Mismatch negativity deficits are associated with poor functioning in schizophrenia patients.

BACKGROUND: Schizophrenia patients exhibit widespread deficits in many domains, ranging from abnormalities in preattentional sensory processing to gross impairments in everyday functioning. Mismatch negativity (MMN) is an event-related potential measure that occurs in the absence of directed attention. While many studies have reported MMN deficits in schizophrenia patients, little is known about the functional significance of MMN deficits in schizophrenia patients. OBJECTIVE: To determine if a schizophrenia-linked deficit in MMN, an "automatic" preattentional measure, is associated with impairments in everyday functional status, level of independence in living situation, and the ability to perform tasks routinely encountered in everyday situations. SETTING AND PARTICIPANTS: Twenty-five patients with a DSM-IV diagnosis of schizophrenia recruited from inpatient and outpatient community facilities affiliated with the University of California, San Diego, and 25 healthy, nonpsychiatric, comparison subjects. MAIN OUTCOME MEASURES: Mismatch negativity, clinical symptoms, performance on a multidimensional laboratory-based functional skills assessment battery, clinician ratings on the Global Assessment of Functioning Scale, and level of independence in community living situation. RESULTS: Schizophrenia patients had significantly reduced MMN (P<.001). Greater levels of MMN impairment were associated with lower Global Assessment of Functioning Scale ratings. Consistent with clinical ratings, patients with greater MMN impairments were more likely to live in highly structured vs independent settings. A regional analysis of MMN revealed that the largest correlations of MMN to everyday functioning were present at frontocentral recording sites (eg, r(s) = -0.65). In contrast, MMN deficits were not associated with symptom severity or performance on laboratory-based tasks measuring skills that are often considered necessary for independent living. CONCLUSIONS: This pattern of results suggests that MMN deficits represent a core neurophysiological dysfunction that is linked to global impairments in everyday functioning in schizophrenia patients. These deficits in automatic preattentive information processing account for up to 42% of the variance in global functional status in schizophrenia patients. Thus, basic preattentional cognitive deficits may be excellent measures for predicting functional outcome. Longitudinal studies are needed to better understand the relationships between deficits in automatic sensory information processing, associated neural substrate dysfunctions, and deficits in everyday functioning across the course of the illness.

Activities of Daily Living↗

PubMed2005

Prepulse inhibition of perceived stimulus intensity: paradigm assessment.

In 1939, Helen Peak reported that the presentation of paired acoustic stimuli, separated by 177ms, resulted in a 25% reduction in the perceived intensity of the second stimulus. After 65 years, this form of prepulse inhibition of perceived stimulus intensity (PPIPSI) remains relatively less developed, compared to technically and analytically complex "gating" measures, e.g. PPI of startle and P50 event related potential (ERP) suppression. We report that unlike PPI, which can be observed at very brief inter-stimulus intervals (ISI's), PPIPSI requires ISI's >or=60ms. It exhibits significant test-retest stability over a 2-week period, does not exhibit sex differences or menstrual cyclicity, and is not significantly associated with personality dimensions of novelty seeking, harm avoidance, reward dependence or sensation seeking. PPIPSI is a robust, stable, parametrically sensitive and "low tech" measure of sensory gating that is relatively unaffected by a number of biological variables in normal individuals.

Acoustics↗

PubMed2005

Startle modulation in Caucasian-Americans and Asian-Americans: a prelude to genetic/endophenotypic studies across the 'Pacific Rim'.

OBJECTIVES: Deficient prepulse inhibition (PPI) of startle in schizophrenia patients and unaffected family members may be a useful endophenotype in studies seeking to identify vulnerability genes for schizophrenia. Before expanding such studies to include Pacific Rim populations with distinct genetic origins compared with North American Caucasian populations, we examined PPI and related startle measures in normal North American Caucasian and Asian men. METHODS: One hundred and seventy-four consecutive carefully screened right-handed male 18-35 year olds completed tests of startle and PPI using bilateral electromyography measures of orbicularis oculi. Subjects identified their racial background. RESULTS: Startle in Caucasian subjects was of significantly larger magnitude and shorter latency compared with Asian subjects; the percent PPI was significantly greater in Asian versus Caucasian subjects at 60 and 120 ms prepulse intervals. Group differences in PPI but not reflex latency were eliminated when groups were matched for startle magnitude on pulse alone trials. Caucasian-American and Asian-American groups did not differ significantly in resting blink rate, resting electromyography activity, or startle reflex habituation. CONCLUSIONS: Robust phenotypic differences in acoustic startle magnitude and latency between Caucasian-American and Asian-American populations must be considered in studies using startle and PPI as endophenotypes across these populations.

Adolescent↗