Biomedical subjects

Bruce I Turetsky

Publications and source records attributed to Bruce I Turetsky.

At least 19 recordsLinked to original sources

PubMed2007

Phenylthiocarbamide (PTC) perception in patients with schizophrenia and first-degree family members: relationship to clinical symptomatology and psychophysical olfactory performance.

The inability to taste phenylthiocarbamide (PTC; "taste-blindness") has been associated with a number of medical and neurological illnesses not typically related to taste. We examined PTC sensitivity in 67 schizophrenia patients, 30 healthy controls, and 30 first-degree relatives to determine whether taster status could represent a simple vulnerability marker. A higher prevalence of non-tasters was seen in patients and family members relative to healthy controls. Among patients, non-tasters exhibited increased levels of negative and first-rank symptoms as well as poorer right nostril odor identification skills relative to PTC tasters. These differences were not explained by age, sex, education, smoking, or intensity differences. Phenotypic variation in PTC sensitivity is thought to be genetic in origin and suggests greater illness risk for those subjects with recessive taster alleles.

Adult↗

PubMed2007

Hemodynamic responses in neural circuitries for detection of visual target and novelty: An event-related fMRI study.

The oddball paradigm examines attentional processes by establishing neural substrates for target detection and novelty. Event-related functional imaging enables characterization of hemodynamic changes associated with these processes. We studied 36 healthy participants (17 men) applying a visual oddball event-related design at 4 Tesla, and performed an unbiased determination of the hemodynamic response function (HRF). Targets were associated with bilateral, albeit leftward predominant changes in frontal-parietal temporal and occipital cortices, and limbic and basal ganglia regions. Activation to novelty was more posteriorly distributed, and frontal activation occurred only on the right, while robust activation was seen in occipital regions bilaterally. Overlapping regions were left thalamus, caudate and cuneus and right parietal precuneus. While robust HRFs characterized most regions, target detection was associated with a negative HRF in the right parietal precuneus and a biphasic HRF in thalamus, basal ganglia, and all occipital regions. Both height of the HRF and longer time to peak in the right cingulate were associated with slower response time. Sex differences were observed, with higher HRF peaks for novelty in men in right occipital regions, and longer time to peak in the left hemisphere. Age was associated with reduced peak HRF in left frontal region. Thus, indices of the HRF can be used to better understand the relationship between hemodynamic changes and performance and can be sensitive to individual differences.

Adolescent↗

PubMed2006

Neurophysiological endophenotypes of schizophrenia: the viability of selected candidate measures.

In an effort to reveal susceptibility genes, schizophrenia research has turned to the endophenotype strategy. Endophenotypes are characteristics that reflect the actions of genes predisposing an individual to a disorder, even in the absence of diagnosable pathology. Individual endophenotypes are presumably determined by fewer genes than the more complex phenotype of schizophrenia and would, therefore, reduce the complexity of genetic analyses. Unfortunately, despite there being rational criteria to define a viable endophenotype, the term is sometimes applied indiscriminately to characteristics that are deviant in affected individuals. Schizophrenia patients exhibit deficits in several neurophysiological measures of information processing that have been proposed as candidate endophenotypes. Successful processing of sensory inputs requires the ability to inhibit intrinsic responses to redundant stimuli and, reciprocally, to facilitate responses to less frequent salient stimuli. There is evidence to suggest that both these processes are "impaired" in schizophrenia. Measures of inhibitory failure include prepulse inhibition of the startle reflex, P50 auditory evoked potential suppression, and antisaccade eye movements. Measures of impaired deviance detection include mismatch negativity and the P300 event-related potential. The purpose of this review is to systematically evaluate the endophenotype candidacy of these key neurophysiological abilities. For each candidate, we describe typical experimental procedures, the current understanding of the underlying neurobiology, the nature of the abnormality in schizophrenia, the reliability, stability and heritability of the measure, and any reported gene associations. We conclude with a discussion of the few studies thus far that have employed a multivariate approach with these candidates.

Arousal↗

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

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

Olfactory functioning in schizophrenia: relationship to clinical, neuropsychological, and volumetric MRI measures.

Deficits in odor identification and detection threshold sensitivity have been observed in schizophrenia but their relationship to clinical, cognitive, and biologic measures have not been clearly established. Our objectives were to examine the relationship between measures of odor identification and detection threshold sensitivity and clinical, neuropsychological, and anatomic brain measures. Twenty-one patients with schizophrenia and 20 healthy controls were administered psychophysical tests of odor identification and detection threshold sensitivity to phenyl ethyl alcohol. In addition, clinical symptom ratings, neuropsychological measures of frontal and temporal lobe function and whole brain MRIs were concurrently obtained. Patients exhibited significant deficits in odor identification but normal detection threshold sensitivity. Poorer odor identification scores were associated with longer duration of illness, increased negative and disorganized symptoms, and the deficit syndrome, as well as impairments in verbal and nonverbal memory. Better odor detection thresholds were specifically associated with first-rank or productive symptoms. Larger left temporal lobe volumes with MRI were associated with better odor identification in controls but not in patients. Given the relevance of the neural substrate, and the evidence of performance deficits, psychophysical probes of the integrity of the olfactory system hold special promise for illuminating aspects of the neurobiology underlying schizophrenia.

Adult↗

PubMed2006

Apolipoprotein E genotype and odor identification in schizophrenia.

The authors examined Apolipoprotein E (ApoE) genotype frequencies and unirhinal odor identification in 28 schizophrenia patients and 26 healthy comparison subjects. No significant associations between ApoE status and olfaction were observed in either diagnostic group. The authors concluded that olfactory deficits in schizophrenia do not appear to be mediated by the ApoE allele.

Adult↗

PubMed2006

Unirhinal olfactory function in schizophrenia patients and first-degree relatives.

Previous studies report birhinal impairments in odor identification in patients with schizophrenia and their family members. The authors employed unirhinal odor identification and detection threshold sensitivity tests in schizophrenia patients, healthy first-degree family members, and healthy comparison subjects. Patients and family members showed deficits in odor identification performance in both nostrils. Odor detection thresholds differed only between patients and healthy comparison subjects. Comparable odor identification deficits in both patients and healthy family members suggest that odor identification measures may serve as a sensitive endophenotypic vulnerability marker and that unirhinal olfactory measures are as precise, if not more so, than birhinal performance measures.

Adult↗

PubMed2005

Behavioral and physiological findings of gender differences in global-local visual processing.

Hemispheric asymmetries in global-local visual processing are well-established, as are gender differences in cognition. Although hemispheric asymmetry presumably underlies gender differences in cognition, the literature on gender differences in global-local processing is sparse. We employed event related brain potential (ERP) recordings during performance of a global-local reaction time task to compare hemispheric asymmetries and processing biases in adult men (n=15) and women (n=15). Women responded more quickly to local targets while men did not differentially respond to hierarchical stimuli. ERP data indicated that women had P100 responses that were selectively lateralized to the left hemisphere in response to local targets and N150 responses that were smaller for global targets. They also had P300 responses that were greater following local stimuli. The physiological data demonstrate that male-female performance differences arise from biologically based differences in hemispheric asymmetry. Findings are discussed in the context of existing literature regarding gender differences, hemispheric specialization, and the role of stimulus characteristics.

Adult↗

PubMed2005

Global-local visual processing in schizophrenia: evidence for an early visual processing deficit.

BACKGROUND: Abnormalities in early-stage visual processing might contribute to observed higher neurocognitive deficits in schizophrenia, but to date no clear link has been established. Schizophrenia has been associated with deficits in the magnocellular visual pathway, suggesting a relative bias for processing elemental (local) as opposed to configural (global) aspects of a hierarchical stimulus; however, global-local paradigm studies in schizophrenia have yielded mixed results. METHODS: In the current study, global-local and event-related potential (ERP) procedures were concomitantly used to assess temporal and spatial characteristics of hierarchical visual stimulus processing abnormalities. RESULTS: Patients (n = 24) had slower and less accurate responses to global stimuli than a healthy comparison group (n = 29). They exhibited a marked decrement in N150 ERP amplitude, which correlated with speed of response to global stimuli. They also failed to show an augmented P300 response to local stimuli. CONCLUSIONS: Behavioral and physiological data are consistent and support a global visual processing deficit in schizophrenia. This is manifest at a relatively early stage of visual processing and might relate to physiological disturbances in areas V3/V3a of the extrastriate cortex.

Adolescent↗

PubMed2005

Whole-brain morphometric study of schizophrenia revealing a spatially complex set of focal abnormalities.

CONTEXT: Neuroanatomic abnormalities in schizophrenia may underlie behavioral manifestations. Characterization of such abnormalities is required for interpreting functional data. Frontotemporal abnormalities have been documented by using predetermined region-of-interest approaches, but deformation-based morphometry permits examination of the entire brain. OBJECTIVES: To perform whole-brain analyses of structural differences between patients with schizophrenia and controls, to examine sex and medication effects, and to apply a high-dimensional nonlinear pattern classification technique to quantify the degree of separation between patients and controls, thereby testing the potential of this new technique as an aid to diagnostic procedures. DESIGN: Whole-brain morphologic analysis using high-dimensional shape transformations. SETTING: Schizophrenia Research Center, University of Pennsylvania Medical Center. PARTICIPANTS: Neuroleptic-naïve and previously treated patients with DSM-IV schizophrenia (n = 69) and sociodemographically matched controls (n = 79). MAIN OUTCOME MEASURES: Gray matter, white matter, and ventricular cerebrospinal fluid volumes in the brain. RESULTS: Magnetic resonance images showed reduced gray matter and increased ventricular cerebrospinal fluid volumes in patients with schizophrenia in the whole brain and in specific foci: the hippocampus and adjacent white matter, the cingulate and orbitofrontal cortex, the frontotemporal and parietotemporal areas, and the occipital areas near the lingual gyrus. The classifier had a mean classification accuracy of 81.1% for men and women combined (82% for women and 85% for men, when each group was treated separately), determined via cross-validation. CONCLUSIONS: This study confirms previous findings of reduced frontotemporal volumes and suggests new hypotheses, especially involving occipital association and speech production areas. It also suggests finer localization of volume reduction in the hippocampus and other limbic structures and in the frontal lobe. Pattern classification showed high sensitivity and specificity for the diagnosis of schizophrenia, suggesting the potential utility of magnetic resonance imaging as a diagnostic aid.

Adult↗

PubMed2005

Phenylthiocarbamide perception in patients with schizophrenia and first-degree family members.

OBJECTIVE: The inability to taste phenylthiocarbamide (PTC) has been associated with medical and neurological illnesses not typically related to taste. The authors examined PTC sensitivity in schizophrenia patients and their non-ill relatives to determine whether this represented a vulnerability marker. METHOD: PTC sensitivity was assessed in 42 schizophrenia patients, 23 healthy comparison subjects, and 12 first-degree relatives of the patients. RESULTS: More nontasters were found among patients and family members than healthy comparison subjects. Among patients, nontasters had more positive symptoms. Differences were not explained by sex, age, medication, smoking, or cognitive impairment. CONCLUSIONS: The prevalence of PTC nontasters was greater among schizophrenia patients and non-ill first-degree family members. Phenotypic variation in PTC sensitivity is genetic in origin. This suggests a higher risk for illness among subjects with recessive alleles.

Adult↗

PubMed2004

A sexually dimorphic ratio of orbitofrontal to amygdala volume is altered in schizophrenia.

BACKGROUND: Neuroanatomic sexual dimorphisms have been correlated with behavioral differences between healthy men and women. We have reported higher orbitofrontal cortex to amygdala ratio (OAR) in women than men. Although gender differences in schizophrenia are evident clinically and correlate with neuroanatomic measures, their relationship to OAR has not been examined. METHODS: Magnetic resonance imaging was performed in 31 neuroleptic-naïve schizophrenic patients (16 men) and 80 healthy volunteers (34 men), aged less than 50 years. An automated tissue segmentation procedure was combined with expert-guided parcellation of orbitofrontal and amygdala volumes. RESULTS: Men with schizophrenia had increased OAR relative to healthy men, whereas women had decreased OAR. Increased OAR in men with schizophrenia reflected abnormally low amygdala volumes, whereas decreased OAR in women reflected abnormally low orbitofrontal volumes. Less severe negative symptoms were associated with increased OAR in men but with decreased OAR in women. In men, increased amygdala volume was associated with greater symptom severity, whereas in women higher volumes of both amygdala and orbitofrontal regions were associated with lesser severity of negative symptoms. CONCLUSIONS: These opposite OAR abnormalities, whereby men show feminization and women masculinization, suggest gender-mediated effects of the underlying neuropathologic processes. The correlations with symptom severity suggest that neuroanatomic abnormalities in OAR reflect compensatory brain changes.

Adult↗

PubMed2004

The effects of ketamine vary among inbred mouse strains and mimic schizophrenia for the P80, but not P20 or N40 auditory ERP components.

N-methyl-D-aspartate (NMDA) antagonists produce behavioral and electrophysiological effects similar to schizophrenia. The mouse P20, N40, and P80 event related potential (ERP) components were analyzed for genetic variance among inbred strains and ketamine-induced differences to model abnormalities in the P50, N100, and P200 in schizophrenia. Ketamine increased P20/N40 amplitude and decreased P80 amplitude. Therefore, the effects of ketamine in mice are inconsistent with alterations in the corresponding P50 and N100 in schizophrenia, suggesting that NMDA receptor dysfunction may not underlie abnormalities of these components in schizophrenia. However, the effects of ketamine on the mouse P80 were consistent with P200 ERP changes in schizophrenia and support the hypothesis that NMDA dysfunction may contribute to some neuronal abnormalities in schizophrenia. The current study lays the groundwork for defining the role of NMDA-mediated transmission for specific aspects of neuronal processing that vary with genetic background. Future studies could use transcription profiling to clarify such interactions between genetic background, specific neuronal circuits, and transmitter systems.

Animals↗

PubMed2004

Effects of chronic olanzapine and haloperidol differ on the mouse N1 auditory evoked potential.

Auditory evoked potentials have been used in a variety of animal models to assess information-processing impairments in schizophrenia. Previous mouse models have primarily employed a paired click paradigm to assess the transient measures of auditory gating. The current study uses stimulus trains at varied interstimulus intervals (ISI) between 0.25 and 8 s in mice to assess the effects of chronic olanzapine and haloperidol on auditory processing. Data indicate that olanzapine increases the amplitude of the N40, P80, and P20/N40 components of the auditory evoked potential, whereas haloperidol had no such effect. The ISI paradigm also allowed for an evaluation of several components of the mouse evoked potential to assess those that display response properties similar to the human P50 and N100. Data suggest that the mouse N40 displays an ISI response relationship that shares characteristics with the human N100, whereas the P20 appears more consistent with the human P50 across the ISI range evaluated in this task. This study suggests that olanzapine may help improve N100 impairments seen in schizophrenia, while haloperidol does not.

Acoustic Stimulation↗

PubMed2004

Patient attitudes towards surgically implantable, long-term delivery of psychiatric medicine.

The introduction of surgically implantable medication delivery systems provides psychiatric patients with reversible, uninterrupted access to medication for up to 14 months. This study designed and administered a survey to assess patients' attitudes and beliefs towards illness, medication, and this potential new treatment method. The survey included questions about demographics, insight and attitudes towards illness, current and past medication adherence, attitudes towards psychiatric and nonpsychiatric medications, and understanding and attitudes towards surgical implants. The sample of 206 psychiatric patients was almost equally split between favorably and unfavorably considering implants. Patients favorable towards implants ascribed forgetting and failure to refill medication on time as the reasons for missing doses, recognized the benefits of medication in general, and understood that the implant would be inserted under the skin. Favorable consideration of implants was positively correlated with the desire to avoid adverse consequences of missing medicine, stay well, avoid the need for daily oral medications, and decrease family burden. Unfavorable consideration of implants was related to a preference to take medication orally, concern about feeling controlled, unwillingness to try something new, and not understanding that the implant would be placed under the skin. Demographic variables, past/current medications, specific diagnosis, and illness severity did not influence the decision. This survey elucidates patients' attitudes and beliefs towards illness, medication, and surgical implants. The results indicate that a significant proportion of patients recognize the difficulties of medication adherence and the need for better methods to attain therapeutic response. Thus, the study provides impetus for future work in this area.

Adult↗

PubMed2004

Smaller nasal volumes as stigmata of aberrant neurodevelopment in schizophrenia.

OBJECTIVE: Anatomical and functional deficits of the olfactory neural system have been identified in patients with schizophrenia. Since olfactory structures develop in conjunction with both the palate and ventral forebrain, the authors hypothesized that schizophrenia patients might have structural abnormalities of the nasal cavity, which could represent specific markers of embryological dysmorphogenesis underlying schizophrenia. METHOD: A measurement of nasal volume was acquired by acoustic rhinometry for 40 male schizophrenia patients and 24 healthy male comparison subjects. RESULTS: The patients had smaller posterior nasal volumes than the comparison subjects but did not differ in anterior nasal volumes. This difference persisted after covarying for height and smoking history. CONCLUSIONS: The lower observed posterior nasal volume likely reflects a specific developmental craniofacial abnormality. This finding confirms an early disruption in embryological development in males with schizophrenia and may represent a genetic or environmental "first hit" that leaves the individual vulnerable to subsequent pathology.

Adult↗

PubMed2004

Event-related fMRI of frontotemporal activity during word encoding and recognition in schizophrenia.

OBJECTIVE: Neuropsychological studies have demonstrated verbal episodic memory deficits in schizophrenia during word encoding and retrieval. This study examined neural substrates of memory in an analysis that controlled for successful retrieval. METHOD: Event-related blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) was used to measure brain activation during word encoding and recognition in 14 patients with schizophrenia and 15 healthy comparison subjects. An unbiased multiple linear regression procedure was used to model the BOLD response, and task effects were detected by contrasting the signal before and after stimulus onset. RESULTS: Patients attended during encoding and had unimpaired reaction times and normal response biases during recognition, but they had lower recognition discriminability scores, compared with the healthy subjects. Analysis of contrasts was restricted to correct items. Previous findings of a deficit in bilateral prefrontal cortex activation during encoding in patients were reproduced, but patients showed greater parahippocampal activation rather than deficits in temporal lobe activation. During recognition, left dorsolateral prefrontal cortex activation was lower in the patients and right anterior prefrontal cortex activation was preserved, as in the authors' previous study using positron emission tomography. Successful retrieval was associated with greater right dorsolateral prefrontal cortex activation in the comparison subjects, whereas orbitofrontal, superior frontal, mesial temporal, middle temporal, and inferior parietal regions were more active in the patients during successful retrieval. CONCLUSIONS: The pattern of prefrontal cortex underactivation and parahippocampal overactivation in the patients suggests that functional connectivity of dorsolateral prefrontal and temporal-limbic structures is disrupted by schizophrenia. This disruption may be reflected in the memory strategies of patients with schizophrenia, which include reliance on rote rehearsal rather than associative semantic processing.

Adult↗