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Biomedical subjects

Cheryl Corcoran

Publications and source records attributed to Cheryl Corcoran.

17 recordsLinked to original sources

Maternal household crowding during pregnancy and the offspring's risk of schizophrenia.

BACKGROUND: Animal models of schizophrenia suggest a link between maternal crowding during pregnancy and increased risk of the offspring to develop physiological, developmental, and behavioral abnormalities that are comparable to those observed in schizophrenia. We tested the hypothesis that a similar link is present in humans. METHOD: We investigated whether prenatal exposure to household crowding was associated with the risk of schizophrenia in a sub-cohort of the Jerusalem Perinatal Study (JPS) consisting 11,015 individuals born between 1964 and 1976. During these years mothers participated in face to face interviews in early pregnancy. The prenatal and birth data, including the number of rooms and individuals living in the mothers' household, was cross-linked with the Israel Psychiatric Registry by ministry personnel. RESULTS: 104 schizophrenia cases were identified in the cohort. Offspring who, while in utero, their mother resided in a household with five or more individuals had RR of 1.47 (95% CI: 0.99-2.16, p=0.05) to develop schizophrenia, compared to those whose mother resided with four or fewer individuals. However, when adjusted for paternal age, the RR was reduced to 1.18 (95% CI: 0.76-1.84, p=0.46). The number of rooms in the household and the household crowding during pregnancy did not significantly impact the offspring's risk to develop schizophrenia. CONCLUSION: The link between maternal household crowding during pregnancy and the offspring's risk of schizophrenia was explained primarily by the impact of paternal age. The authors discuss the results in view of findings from animal and human studies.

Cohort Studies↗

Computerized experience sampling method (ESMc): assessing feasibility and validity among individuals with schizophrenia.

The Experience Sampling Method (ESM) is an ecologically valid, time-sampling of self-reports developed to study the dynamic process of person-environment interactions. ESM with digital wristwatch and booklets (paper-based ESM; ESMp) has been used extensively to study schizophrenia. The present study is designed to test the feasibility and validity of using Computerized ESM (ESMc) among individuals with schizophrenia. ESMc is advantageous in allowing for recording of precise time-stamps of responses. We used PDAs ("Personal Digital Assistant"; Palm handheld computers) to collect data on momentary psychotic symptoms, mood, and thoughts over a one day period among 10 hospitalized schizophrenia patients and 10 healthy controls. ESMc was equally acceptable to both groups, with similar ratings of comfort carrying the PDAs and operating them, interference with daily activities, as well as response rates. The schizophrenia patients reported significantly higher ratings of auditory and visual hallucinations, suspiciousness, sense of unreality, lack of thought control, fear of losing control, difficulty expressing thoughts, as well as depression/sadness, loneliness and less cheerfulness. Significant inverse relationships were found among both groups between ratings of feeling cheerful and being stressed, irritated, and sad/depressed. Among the schizophrenia subjects, the correlation between ratings of suspiciousness on ESMc and Scale for Assessment of Positive Symptoms (SAPS) approached significance, as well as the link between suspiciousness and stress. Our results support the feasibility and validity of using ESMc for assessment of momentary psychotic symptoms, mood, and experiences among individuals with schizophrenia. The authors discuss the potential applications of combining ESMc with ambulatory physiological measures.

Adolescent↗

Delusions in individuals with schizophrenia: factor structure, clinical correlates, and putative neurobiology.

BACKGROUND: Delusions are a central feature of schizophrenia, yet our understanding of their neurobiology is limited. Attempt to link dimensions of psychopathology to putative neurobiological mechanisms depends on careful delineation of symptoms. Previous factor analytic studies of delusions in schizophrenia were limited by several methodological problems, including the use of patients medicated with antipsychotics, inclusion of nondelusion symptoms in the analyses, and/or inclusion of patients with psychotic disorders other than schizophrenia. These problems may have possibly biased the resulting factor structure and contributed to the inconclusive findings regarding the neurobiology of positive symptoms. Our goal is to examine the factor structure of delusions in antipsychotic-free individuals with diagnoses of schizophrenia/schizoaffective disorder. SAMPLING AND METHODS: We assessed 83 antipsychotic-free individuals with DSM-IV diagnoses of schizophrenia/schizoaffective disorder. A principal component analysis was conducted on the delusions symptoms of the SAPS. RESULTS: The principal component analysis resulted in three distinct and interpretable factors explaining 58.3% of the variance. The Delusions of Influence factor was comprised by delusions of being controlled, thought withdrawal, thought broadcasting, thought insertion, and mind reading. The Self-Significance Delusions factor was comprised by delusions of grandeur, reference, religious, and delusions of guilt/sin. The Delusions of Persecution factor was comprised solely by persecutory delusions. The three factors displayed distinct associations with hallucinations, bizarre behavior, attention, positive formal thought disorder, and avolition/apathy. CONCLUSIONS: The results indicate that delusions are best described by three distinct subtypes. The authors propose a novel model linking the three delusion subtypes, attributions to self/other, and putative neurobiological mechanisms. Implications for future research are discussed, as well as links to cognitive-behavioral conceptualizations of delusions.

Adolescent↗

Olfactory deficits, cognition and negative symptoms in early onset psychosis.

BACKGROUND: Smell identification deficits (SID) are common in adult schizophrenia, where they are associated with negative symptoms and lower intelligence. However, smell identification has not been examined in adolescents with early onset psychosis, wherein diagnosis is often obscure, and there are few prognostic predictors. METHOD: We examined smell identification, diagnosis, neuropsychological performance and symptoms in 26 well characterized adolescents with early onset psychosis, age 11-17 years. RESULTS: SID existed in the sample and were more common in patients with schizophrenia and psychotic depression than in patients with psychosis NOS and bipolar disorder. As in adults, SID were significantly associated with greater negative symptoms and lower verbal IQ. However, the associations of verbal IQ (and other verbal tasks) to smell identification in this pediatric sample were explained by the relation of both of these types of variables to negative symptoms. CONCLUSIONS: SID existed across this sample of youths with psychotic disorder, and were specifically related to typical characteristics of schizophrenia, such as negative symptoms and lower intelligence, but not to features of bipolar disorder, such as grandiosity. SID is a characteristic of early onset psychosis that may be useful for prognostic purposes.

Adolescent↗

Prodromal interventions for schizophrenia vulnerability: the risks of being "at risk".

Given the morbidity and difficulty of treating psychotic disorders, including schizophrenia, there has been a move toward identifying and treating adolescents and young adults who appear to be clinically at risk or "prodromal" to psychosis. The field now has greater specificity in identification, with rates of 40-50% conversion to frank psychosis within 1-2 years. There is further evidence that medications and other treatments may have some efficacy for "prodromal" patients, though with variable side effects. However, controversy remains about some of the inherent risks in prodromal research, such as medication exposure and stigma among false-positives. In this paper, we add to this discussion through an analysis of ethics in prodromal research from the more established field of predictive genetic testing. Issues are raised about the effects of information on patients, families, and institutions, as well as future insurability, the limits of confidentiality (as it relies on discretion of patients and families), the autonomy of minors with psychiatric symptoms, and even the risks for the true-positive patient.

Confidentiality↗

Resting neural activity distinguishes subgroups of schizophrenia patients.

BACKGROUND: Schizophrenia is etiologically heterogeneous. It is anticipated, but unproven, that subgroups will differ in neuropathology and that neuroimaging may reveal these differences. The optimal imaging condition may be at rest, where greater variability is observed than during cognitive tasks, which more consistently reveal hypofrontality. We previously demonstrated symptom and physiologic differences between familial and sporadic schizophrenia patients and hypothesized that the groups would show different resting regional cerebral blood flow (rCBF) patterns. METHODS: Ten familial and sixteen sporadic schizophrenia patients and nine comparison subjects had single photon emission computed tomography imaging during passive visual fixation. Images were spatially normalized into Talairach coordinates and analyzed for group rCBF differences using SPM with a Z value threshold of 2.80, p < .001. RESULTS: The subgroups had similar age, gender, illness duration, and medication treatment. Sporadic patients had hypofrontality (anterior cingulate, paracingulate cortices, left dorsolateral and inferior-orbitofrontal), whereas familial patients had left temporoparietal hypoperfusion; all of these regions show resting activity in healthy subjects. Both groups hyperperfused the cerebellum/pons and parahippocampal gyrus; additional hyperperfusion for sporadic patients was observed in the fusiform; familial patients also hyperperfused the hippocampus, dentate, uncus, amygdala, thalamus, and putamen. CONCLUSIONS: Familial and sporadic schizophrenia patients had different resting rCBF profiles, supporting the hypothesis that certain subgroups have distinct neural underpinnings. Different neuropathologic processes among subgroups of schizophrenia patients may account for the prior contradictory results of resting imaging studies.

Adult↗

Trail making and olfaction in schizophrenia: implications for processing speed.

BACKGROUND: Previous research has established a relationship between smell identification deficits (SID) and particular aspects of cognitive function among patients with schizophrenia. OBJECTIVE: To expand the extant literature, we examined the relationship between SID and the Trail Making Test to determine if processing speed is related to SID. METHODS: Our sample included 60 inpatients from the New York State Psychiatric Institute's Schizophrenia Research Unit. We considered age, deficit syndrome, verbal intelligence quotient, and education in our analyses due to their documented relationship to smell identification ability. RESULTS: Trails A errors and Trails A seconds accounted for a significant amount of the variance in University of Pennsylvania Smell Identification Test scores in a regression analysis (R2=.10, P=.008 and R2=.05, P=.04). CONCLUSION: Linking neurocognition to smell identification deficits may prove to be an essential marker for schizophrenia research.

Adult↗

The reliability and clinical correlates of figure-ground perception in schizophrenia.

Schizophrenia subjects are impaired in a number of visual attention paradigms. However, their performance on tests of figure-ground visual perception (FGP), which requires subjects to visually discriminate figures embedded in a rival background, is relatively unstudied. We examined FGP in 63 schizophrenia patients and 27 control subjects and found that the patients performed the FGP test reliably and had significantly lower FGP scores than the control subjects. Figure-ground visual perception was significantly correlated with other neuropsychological test scores and was inversely related to negative symptoms. It was unrelated to antipsychotic medication treatment. Figure-ground visual perception depends on "top down" processing of visual stimuli, and thus this data suggests that dysfunction in the higher-level pathways that modulate visual perceptual processes may also be related to a core defect in schizophrenia.

Adult↗

A brief smell identification test discriminates between deficit and non-deficit schizophrenia.

Evidence is accumulating that smell identification deficits (SID) and social dysfunction in schizophrenia may share a common pathophysiology. While most schizophrenia studies utilize the lengthy 40-item University of Pennsylvania Smell Identification Test (UPSIT) to assess smell identification ability, a brief 12-item smell identification test (B-SIT) has recently been constructed as a culturally neutral substitute for the UPSIT. By selecting the 12 items of the UPSIT from which the B-SIT was originally derived, we constructed a proxy for the B-SIT and compared the performance of 83 patients with schizophrenia to 69 normal subjects. We examined select properties of the B-SIT proxy in relation to the UPSIT to determine its efficacy for use in psychiatric populations. We considered the sensitivity of the B-SIT proxy and evaluated a cutoff score for identifying deficit syndrome schizophrenia (DS). The UPSIT and B-SIT proxy were significantly related in the patients (n=83, r=0.85, P=0.01) and in comparison subjects (n=69, r=0.83, P=0.01), and both measures similarly distinguished DS from non-deficit syndrome (non-DS) patients. The results of this study support the utility of the B-SIT for schizophrenia research and highlight the robustness of the relationship between SID and social dysfunction in schizophrenia.

Adult↗

A qualitative research study of the evolution of symptoms in individuals identified as prodromal to psychosis.

Because schizophrenia is difficult to treat and exacts large personal and societal costs, there is an effort underway to identify adolescents and young adults at high risk for psychosis. Theory-derived criteria of subthreshold positive symptoms identify a "prodromal" or clinically at-risk population who have conversion rates to psychosis of 40 to 50% within one to two years. However, further characterization of the psychosis prodrome by qualitative research methods could increase the predictive value of the "prodromal" designation. We conducted open-ended interviews with 20 parents of prodromal adolescents that focused on changes observed. The narratives fell into two thematically distinct subgroups, identified as "declining" and "never normal." The prodromal adolescents described as "declining" had a higher subsequent rate of conversion to psychosis than did the "never normal" group. Although preliminary, these results suggest that a trajectory of change in personality, relationships, and behavior from an essentially normal baseline may be consistent with increased risk for psychosis among prodromal adolescents.

Adolescent↗

The stress cascade and schizophrenia: etiology and onset.

Psychosocial stress is included in most etiologic models of schizophrenia, frequently as a precipitating factor for psychosis in vulnerable individuals. Nonetheless, the stress-diathesis model has not been tested prospectively in prodromal patients as a predictor of psychosis. The biological effects of stress are mediated by the hypothalamic-pituitary-adrenal (HPA) axis, which governs the release of steroids, including cortisol. The past few decades have witnessed an increased understanding of the neural effects of stress and cortisol, including both normal and abnormal diatheses. As few biological markers have been evaluated as risk factors for psychosis in prodromal patients, the HPA axis and its interaction with intervening life events are apt candidates for study. In this article, we review the HPA axis and its neural effects, present a model for how stress might precipitate psychosis in vulnerable individuals, review the empirical evidence of a link between stress and schizophrenia symptoms, and propose a research design and appropriate statistical models to test the stress-diathesis model for psychosis onset in prodromal patients.

Animals↗

Odor identification, eye tracking and deficit syndrome schizophrenia.

BACKGROUND: Deficit syndrome (DS) schizophrenia patients have smooth pursuit eye movement (SPEM) dysfunction. We examined if they also had smell identification deficits, since social affiliation is related to olfaction in other mammals. METHODS: Sixty-seven patients had DS assessments: 31 patients had SPEM and 50 had Smell Identification Test (SIT) assessments, and 14 patients had both measurements. RESULTS: DS patients had worse SPEM and SIT performance than the non-DS patients. Areas under the receiver-operator characteristic (ROC) curves for SIT and SPEM were both fairly accurate in identifying the DS. The odds ratio (OR) for the DS for impaired versus normal SPEM was 6.21 (95% confidence interval [CI]: 1.21, 32.25) and for microsmia versus normosmia was 10.4 (95% CI: 1.23, 88.18). Further analyses showed that the association of SIT with both SPEM and the DS could account for the SPEM-DS association. CONCLUSIONS: We found a strong association between the DS and SIT scores suggesting that the neural substrates of olfaction may be related to social affiliation in humans, as they are in other mammals. These data further support the notion that the DS defines a homogeneous subgroup of schizophrenia patients and further suggest that dysfunction in the neural circuitry of olfaction may contribute to its pathophysiology.

Adult↗

Paternal age and sporadic schizophrenia: evidence for de novo mutations.

Schizophrenia is an etiologically heterogeneous syndrome. It has a strong genetic component and exists in clinically indistinguishable familial and nonfamilial (sporadic) forms. A significant role for de novo genetic mutations in genetic schizophrenia vulnerability is suggested by a strong monotonic increase in schizophrenia risk with advancing paternal age. However, an alternative explanation for the paternal age effect in schizophrenia is that childbearing is delayed in fathers who themselves have genetic schizophrenia vulnerability. In this study, we compared paternal birth ages between patient groups with familial (n = 35) and sporadic (n = 68) patients with DSM-IV schizophrenia from an inpatient schizophrenia research unit. If later age of fathering children is related to having some genetic schizophrenia vulnerability, then paternal birth age should be later in familial schizophrenia cases than in sporadic cases, and any association of father's age and schizophrenia risk in offspring would be a spurious finding, unrelated to etiology. However, if de novo mutations cause sporadic schizophrenia, then patients without a family history of schizophrenia would have older fathers than familial patients. We found that patients without a family history of schizophrenia had significantly older fathers (4.7 years) than familial patients; so later childbirth was not attributable to parental psychiatric illness. These findings support the hypothesis that de novo mutations contribute to the risk for sporadic schizophrenia.

Age Factors↗

Could stress cause psychosis in individuals vulnerable to schizophrenia?

It has long been considered that psychosocial stress plays a role in the expression of symptoms in schizophrenia (SZ), as it interacts with latent neural vulnerability that stems from genetic liability and early environmental insult. Advances in the understanding of the neurobiology of the stress cascade in both animal and human studies lead to a plausible model by which this interaction may occur: through neurotoxic effects on the hippocampus that may involve synaptic remodeling. Of late, the neurodevelopmental model of SZ etiology has been favored. But an elaboration of this schema that credits the impact of postnatal events and considers a role for neurodegenerative changes may be more plausible, given the evidence for gene-environment interaction in SZ expression and progressive structural changes observed with magnetic resonance imaging. Furthermore, new insights into nongliotic neurotoxic effects such as apoptosis, failure of neurogenesis, and changes in circuitry lead to an expansion of the time frame in which environmental effects may mediate expression of SZ symptoms.

Journal Article↗

Low heart rate variability is not caused by typical neuroleptics in schizophrenia patients.

Both elevated cardiovascular mortality and low cardio-vagal (parasympathetic) heart rate variability (HRV)--a risk factor for postmyocardial infarction--are reported in schizophrenia (SZ). Since a number of medications have strong effects of cardiac conductivity, we thought it important to examine if typical neuroleptic medications might also affect HRV. We examined cardiac vagal activity during both neuroleptic treatment and a drug-free condition in seven SZ patients who were participating in a pilot double-blind, crossover study of placebo and haloperidol treatment. Twenty-four-hour Holter electrocardiograms were analyzed for high frequency HRV, quantitated as the percent of successive normal interbeat intervals greater than 50 milliseconds (PNN50), which is a good index of parasympathetic cardiac modulation. The patients showed unchanged PNN50 (8.4+/-9.5 versus 8.3+/-10.5; t=.22, df=6, P=.5) between the haloperidol treatment and drug-free conditions. Despite the elapsed time, change in medication, and altered clinical state, the PNN50s were highly correlated (Spearman r=.98, P=.000). SAPS positive symptom scores declined with treatment from 12.8+/-6.5 to 8.5+/-3.5; paired t=3.26: df=6; P=.01. PNN50s were significantly associated with positive (r=-.86, df=6, P=.012) and negative symptom scores (r=-.87, df=6, P=.01). We found low cardiovagal modulation in medication-free SZ patients that was associated with core SZ symptoms and was unchanged by haloperidol and benztropine treatment. The reduced HRV in SZ patients at baseline may render them at greater cardiovascular risk than healthy subjects when treated with medications having strong cardiovascular effects.

Journal Article↗

Are cognitive symptoms of schizophrenia mediated by abnormalities in emotional arousal?

We tested 28 individuals with schizophrenia (SZ) and 16 healthy individuals on a test of logical reasoning and "cognitive gating," defined as the ability to discriminate between relevant and irrelevant information in confirming or disconfirming a given belief. The Logical Reasoning and Cognitive Gating Task tests both processes under neutral and affect-laden conditions. This is done by presenting formally identical constructs using benign and emotionally arousing language. When separated by symptom profiles, we found statistically significant differences for performance and arousal response between patients with delusions, patients with formal thought disorder, and patients with neither delusions nor formal thought disorder, as well as between patients and healthy controls. When analyzed by error type, we found that nearly all errors by delusional patients were caused by overly restrictive information choice, a pattern that may be related to a delusional patient's tendency to "jump to conclusions" on Bayesian probabilistic tasks. This is in contrast to patients with formal thought disorder, whose low performance resulted also from overly extensive information choice. The tendencies towards restriction were exacerbated by arousal, which is consistent with studies on cognition and arousal in healthy individuals. After briefly examining research on emotional arousal and SZ, and the interaction between emotional arousal and restriction of perceptual cues in healthy individuals, we conclude by suggesting a model which accounts for the distinctive cognitive characteristics of delusional patients by their possessing distinct vulnerabilities to emotional arousal. Specifically, these results suggest the possibility that delusional patients process information in a manner that is essentially intact. However, delusional patients may possess an acute vulnerability to emotional arousal that might cause delusional individuals to behave cognitively as if they were healthy individuals under significantly more severe forms of stress.

Journal Article↗