Margaret M McClure

Fairfield University, Fairfield, Connecticut, United States

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Publications (18)80.78 Total impact

  • Fiona S. Graff, Margaret M. McClure, Larry J. Siever
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    ABSTRACT: Individuals with schizotypal personality disorder (SPD) often present with cognitive impairment similar, but of a lesser magnitude to, what is seen in schizophrenia. Cognitive dysfunction combined with social and perceptual disturbances, which are the hallmarks of this disorder, are directly related to substantially lower functioning. There is no FDA-approved medication for cognitive deficits in SPD; however, potential agents, including α2a and dopamine agonists, are under investigation. Cognitive remediation therapy (CRT) is a behavioral treatment that has been shown to improve cognitive and psychosocial functioning in individuals with schizophrenia. Application of CRT in this population is novel and more large-scale studies are needed, but this treatment holds promise for the cognitive and social deficits of SPD. There may be a synergy between cognitive remediation and cognitive enhancers such as the α2a agonist guanfacine; research in this area is nascent. Lifestyle modifications such as the use of memory aids, planners, and structured schedules, as well as exercise, may be beneficial for cognitive functioning in this population. Additionally, social skills training in a psychotherapeutic setting can be helpful. Patients frequently present with comorbid mood and anxiety symptoms, and standard SSRI treatment to ameliorate symptoms can have a positive secondary effect on cognitive functioning. For the patient with psychotic-like features, treatment with atypical antipsychotics may also improve overall functioning.
    Current Treatment Options in Psychiatry. 12/2014; 1(4).
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    ABSTRACT: Pharmacological enhancement of prefrontal D1 dopamine receptor function remains a promising therapeutic approach to ameliorate schizophrenia-spectrum working memory deficits, but has yet to be rigorously evaluated clinically. This proof-of-principle study sought to determine whether the active enantiomer of the selective and full D1 receptor agonist dihydrexidine (DAR-0100A) could attenuate working memory impairments in unmedicated patients with schizotypal personality disorder (SPD). We performed a randomized, double-blind, placebo-controlled trial of DAR-0100A (15 mg/150 ml of normal saline administered intravenously over 30 min) in medication-free patients with SPD (n=16) who met criteria for cognitive impairment (i.e., scoring below the 25(th) percentile on tests of working memory). We employed two measures of verbal working memory that are salient to schizophrenia-spectrum cognitive deficits, and clinical data implicate as being associated with prefrontal D1 availability: 1) the Paced Auditory Serial Addition Test (PASAT); and 2) the N-back test (ratio of 2-back:0-back scores). Study procedures occurred over four consecutive days with working memory testing on Days 1 and 4, and DAR-0100A/placebo administration on Days 2-4. Treatment with DAR-0100A was associated with significantly improved PASAT performance relative to placebo, with a very large effect size (Cohen's d=1.14 for both tests). Performance on the N-back ratio was also significantly improved, however, this effect rested on both a non-significant enhancement and diminution of 2-back and 0-back performance, respectively; therefore interpretation of this finding is more complicated. DAR-0100A was generally well tolerated, with no serious medical or psychiatric adverse events; common side-effects were mild-to-moderate and transient, consisting mainly of sedation, lightheadedness, tachycardia, and hypotension; however, we were able to minimize these effects, without altering the dose, with supportive measures, e.g., co-administered normal saline. Although preliminary, these findings lend further clinical support to the potential of D1 receptor agonists to treat schizophrenia-spectrum working memory impairments. These data suggest a need for further studies with larger group sizes, serum DAR-0100A levels, and a more comprehensive neuropsychological battery.Neuropsychopharmacology accepted article preview online, 30 July 2014; doi:10.1038/npp.2014.192.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 07/2014; · 8.68 Impact Factor
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    ABSTRACT: Prior work shows individuals with schizotypal personality disorder (SPD) evince temporal lobe volume abnormalities similar to schizophrenia but sparing of prefrontal cortex, which may mitigate psychosis and the severe neurocognitive impairments observed in schizophrenia. This study examined the extent to which frontal-temporal gray matter volume and neurocognitive performance predict: (1) SPD group membership in a demographically-balanced sample of 51 patients and 37 healthy controls; and (2) symptom severity in SPD. Dimensional gray-matter volume (left frontal-temporal regions (Brodmann area (BA) 10, 21, 22)) and neurocognitive performance on key memory tasks (California Verbal Learning Test (CVLT), Dot Test, Paced Auditory Serial Addition Test (PASAT)), all salient to schizophrenia-spectrum disorders were examined in a multi-variable model. Middle temporal gyrus (BA21) volume and spatial-working memory (Dot Test) performance were significant predictors of SPD group membership likelihood, with poorer working-memory performance indicating increased probability of SPD membership. Combining across regional volumes or cognitive measures resulted in fair-to-good discrimination of group membership, but including neurocognitive and non-collinear regional volume measures together resulted in a receiver-operating-characteristic (ROC) curve with improved diagnostic discrimination. Larger BA10 volume in dorsolateral prefrontal cortex (DLPFC) significantly predicted less symptom severity in SPD. These findings suggest that temporal lobe volume and spatial-working memory performance are promising biological/phenotype markers for likelihood of SPD classification, while greater DLPFC volume may serve as a protective factor.
    Schizophrenia Research 01/2014; · 4.59 Impact Factor
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    ABSTRACT: Impaired vocational functioning is a hallmark of schizophrenia, but limited research has evaluated the relationships between work and schizophrenia-spectrum personality disorders, including schizotypal (SPD) and paranoid personality disorder (PPD). This study compared employment history and job characteristics of 174 individuals drawn from the community or clinic, based on four personality disorder groups: SPD Only, PPD Only, SPD+PPD, and No SPD or PPD. Symptoms and cognitive functioning were also assessed. Both PPD and/or SPD were associated with lower rates of current employment, and a history of having worked at less cognitively complex jobs than people without these disorders. Participants with PPD were less likely to have a history of competitive work for one year, whereas those with SPD tended to have worked at jobs involving lower levels of social contact, compared with those without these disorders. When the effects of symptoms and cognitive functioning were statistically controlled, PPD remained a significant predictor of work history, and SPD remained a significant predictor of social contact on the job. The findings suggest that impaired vocational functioning is an important characteristic of SPD and PPD.
    Psychiatry research. 08/2013;
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    ABSTRACT: BACKGROUND: Individuals with schizotypal personality disorder (SPD) exhibit impaired cognitive functioning in a pattern similar to that found in schizophrenia; less clear is the extent to which these individuals also share schizophrenia patients' impairments in functional capacity and real-world functioning. METHOD: We evaluated 46 SPD patients, as well as 38 individuals with avoidant personality disorder (AvPD) and 55 healthy controls (HC) on: cognitive functioning, real-world functioning (employment and residential status), and functional capacity (indexed by the UPSA, a performance-based skills assessment). RESULTS: We found that individuals with SPD exhibited worse performance on both the cognitive battery and the UPSA than the other groups; they were also less likely to be employed and to be living independently. Additionally, cognitive and UPSA performance in the SPD group was intercorrelated to a degree comparable to what has been found in schizophrenia, and this relationship was not present in the AvPD group. Finally, real-world functioning was related to UPSA performance for both patient groups. CONCLUSIONS: SPD patients exhibit impaired real-world functioning suggesting that these deficits extend across the schizophrenia spectrum. In addition, there is supportive evidence for the validity and importance of performance-based measures such as the UPSA to predict everyday outcomes across the schizophrenia spectrum.
    Schizophrenia Research 01/2013; · 4.59 Impact Factor
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    ABSTRACT: Psychosis has been suggested to represent a clinical manifestation of shared genetic liability between schizophrenia and bipolar disorder. Significant association was found between the CACNA1C risk allele and Paranoid Ideation in two independent cohorts of healthy individuals and risk for schizotypal personality disorder in a third cohort.
    Psychiatry research. 09/2012;
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    ABSTRACT: Impairment in everyday functioning (also referred to as "disability") is a central feature of schizophrenia (SZ) and bipolar disorder, as well as other neuropsychiatric conditions. There is a genetic contribution to both SZ and bipolar illness (BPI), and the primary putative determinant of impairments in everyday functioning across these 2 conditions, cognitive impairments, also show substantial heritability and in fact have been proposed to be endophenotypes for these disorders. In this article, we review data and make our case that impairments in functional capacity, the functional abilities that result in functional disability, may also be a heritable trait that is common across neuropsychiatric illnesses such BPI and SZ. While there has been little previous research on the heritability of these abilities, it is an area receiving substantial research attention. We consider advances in the measurement of cognitive functioning in SZ that may facilitate the discovery of genetic influences on functional capacity. Functional capacity measures are proximal to real-world impairments, measured with suitable psychometric precision to be used in heritability analyses, and appear to be minimally influenced by environmental factors that may cause disability such as environmental factors, symptoms, and disability compensation. Our conclusion is that these functional capacity measures have potential to be the target of genetic analyses and that these measures should be considered across neuropsychiatric conditions where impairments in everyday functioning are present.
    Schizophrenia Bulletin 05/2011; · 8.80 Impact Factor
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    ABSTRACT: Cognitive deficits observed in schizophrenia are also frequently found in individuals with other schizophrenia spectrum disorders, such as schizotypal personality disorder (SPD). Dopamine appears to be a particularly important modulator of cognitive processes such as those impaired in schizophrenia spectrum disorders. In a double-blind, placebo-controlled clinical trial, we administered pergolide, a dopamine agonist targeting D(1) and D(2) receptors, to 25 participants with SPD and assessed the effect of pergolide treatment, as compared with placebo, on neuropsychological performance. We found that the pergolide group showed improvements in visual-spatial working memory, executive functioning, and verbal learning and memory. These results suggest that dopamine agonists may provide benefit for the cognitive abnormalities of schizophrenia spectrum disorders.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 05/2010; 35(6):1356-62. · 8.68 Impact Factor
  • Journal of clinical psychopharmacology 09/2009; 29(4):396-8. · 5.09 Impact Factor
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    ABSTRACT: Working memory abnormalities, which are particularly pronounced on context processing tasks, appear relatively specific to schizophrenia spectrum illnesses compared with other psychotic disorders. However, the specificity of context processing deficits to schizotypal personality disorder (SPD), a prototype of schizophrenia, has not been studied. The authors administered 3 versions of the modified AX Continuous Performance Test and an N-back working memory test to 63 individuals with SPD and 25 with other personality disorders, as well as 42 healthy controls. For the AX Continuous Performance Test standard and degraded versions, there was a significant Trial Type x Delay x Group interaction, as SPDs made significantly more errors reflecting poor maintenance of context and fewer errors reflecting good maintenance of context. SPDs also demonstrated poor performance on the N-back, especially at the 2-back condition. Context processing errors and N-back accuracy scores were related to disorganization symptoms. These findings, which are quite similar to those previously reported in patients with schizophrenia, suggest that context processing deficits are specific to the schizophrenia spectrum and are not a reflection of overall psychopathology.
    Journal of Abnormal Psychology 06/2008; 117(2):342-54. · 4.86 Impact Factor
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    ABSTRACT: Significant neuropsychological (NP) and functional deficits are found in most schizophrenia patients. Previous studies have left questions as to whether global NP impairment or discrete domains affect functional outcomes, and none have addressed distinctions within and between ability and performance domains. This study examined the different predictive relationships between NP domains, functional competence, social competence, symptoms, and real-world behavior in domains of work skills, interpersonal relationships, and community activities. Two hundred twenty-two schizophrenic outpatients were tested with an NP battery and performance-based measures of functional and social competence and rated for positive, negative, and depressive symptoms. Case managers generated ratings of three functional disability domains. Four cognitive factors were derived from factor analysis. Path analyses revealed both direct and mediated effects of NP on real-world outcomes. All NP domains predicted functional competence, but only processing speed and attention/working memory predicted social competence. Both competence measures mediated the effects of NP on community activities and work skills, but only social competence predicted interpersonal behaviors. The attention/working memory domain was directly related to work skills, executive functions had a direct effect on interpersonal behaviors, and processing speed had direct effects on all three real-world behaviors. Symptoms were directly related to outcomes, with fewer relationships with competence. Differential predictors of functional competence and performance were found from discrete NP domains. Separating competence and performance provides a more precise perspective on correlates of disability. Changes in specific NP or functional skills might improve specific outcomes, rather than promoting global functional improvement.
    Biological psychiatry 04/2008; 63(5):505-11. · 8.93 Impact Factor
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    ABSTRACT: A functional polymorphism of the gene coding for Catechol-O-methyltrasferase (COMT), an enzyme responsible for the degradation of the catecholamine dopamine (DA), epinephrine, and norepinephrine, is associated with cognitive deficits. However, previous studies have not examined the effects of COMT on context processing, as measured by the AX-CPT, a task hypothesized to be maximally relevant to DA function. 32 individuals who were either healthy, with schizotypal personality disorder, or non-cluster A, personality disorder (OPD) were genotyped at the COMT Val158Met locus. Met/Met (n = 6), Val/Met (n = 10), Val/Val (n = 16) individuals were administered a neuropsychological battery, including the AX-CPT and the N-back working memory test. For the AX-CPT, Met/Met demonstrated more AY errors (reflecting good maintenance of context) than the other genotypes, who showed equivalent error rates. Val/Val demonstrated disproportionately greater deterioration with increased task difficulty from 0-back to 1-back working memory demands as compared to Met/Met, while Val/Met did not differ from either genotypes. No differences were found on processing speed or verbal working memory. Both context processing and working memory appear related to COMT genotype and the AX-CPT and N-back may be most sensitive to the effects of COMT variation.
    Neuropsychiatric Disease and Treatment 01/2008; 3(6):925-34. · 2.00 Impact Factor
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    ABSTRACT: Cognitive dysfunction is a common feature of schizophrenia and deficits are present before the onset of psychosis, and are moderate to severe by the time of the first episode. Controversy exists over the course of cognitive dysfunction after the first episode. This study examined age-associated differences in performance on clinical neuropsychological (NP) and information processing tasks in a sample of geriatric community living schizophrenia patients (n=172). Compared to healthy control subjects (n=70), people with schizophrenia did not differ on NP tests across age groups but showed evidence for age-associated cognitive worsening on the more complex components of an information-processing test. Age-related changes in cognitive function in schizophrenia may be a function of both the course of illness and the processing demands of the cognitive measure of interest. Tests with fixed difficulty, such as clinical NP tests, may differ in their sensitivity from tests for which parametric difficulty manipulations can be performed.
    Schizophrenia Research 12/2007; 106(1):50-8. · 4.59 Impact Factor
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    ABSTRACT: The signature of impaired cognition in people with schizotypal personality disorder (SPD) may be centrally related to working memory impairments. Guanfacine, an alpha2A agonist that acts post-synaptically in the prefrontal cortex (PFC), has shown potential for reducing working memory limitations in other populations. This study examined the potential of guanfacine for improving context processing, a feature of working memory, in SPD. 29 individuals with SPD entered into a 4-week, randomized parallel-design, double-blind, placebo-controlled trial of guanfacine treatment, followed by a 4-week open-label extension. A modified version of the AX-Continuous Performance Test (AX-CPT) was administered. On this task, evidence of intact context processing includes few BX errors (false cue, correct probe) and higher levels of AY errors (correct cue, false probe). At the end of double-blind treatment, participants treated with guanfacine demonstrated a significant reduction in BX errors and a small but significant increase in AY errors, a pattern that was not seen in the participants treated with placebo. SPD participants improved in their context processing toward a normal response bias, making fewer BX and more AY errors, after being treated with guanfacine.
    Biological Psychiatry 06/2007; 61(10):1157-60. · 9.25 Impact Factor
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    ABSTRACT: Verbal episodic memory deficits, a well-established feature of the schizophrenia spectrum, have also been found in individuals with schizotypal personality disorder (SPD), although visual-spatial episodic memory has proven harder to examine. To address this, we administered the Visual Object Learning Test (VOLT), a measure of visual-spatial learning and memory, as well as the California Verbal Learning Test (CVLT) and a verbal working memory test, to 50 individuals with SPD, 19 with other personality disorders (OPD), and 17 healthy volunteers. Compared to both other groups, individuals with SPD learned verbal and visual-spatial information at a reduced rate and recalled fewer words and objects after a long delay. Verbal working memory performance eliminated diagnostic differences in these episodic memory domains. These findings suggest that it is possible to detect both auditory and visual processing episodic memory abnormalities in the spectrum and that these deficits are uniformly a function of verbal working memory impairments.
    Archives of Clinical Neuropsychology 02/2007; 22(1):109-16. · 2.00 Impact Factor
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    ABSTRACT: Neuropsychological (NP) performance is a consistent correlate of everyday functioning in schizophrenia, but it is unclear whether relationships between individual NP ability areas and domains of everyday functioning are general or specific. Assessments of real-world everyday functioning may be influenced by environmental and social factors (e.g., social security, disability status, opportunities and restrictions in living situations). This study examined the specificity of the relationships between different NP abilities and performance-based measures of social and living skills. 181 ambulatory older (age>50) patients with schizophrenia were examined with NP tests measuring episodic and working memory, executive functioning, verbal fluency, and processing speed. All subjects performed tasks examining social (Social Skills Performance Assessment: SSPA) and everyday living (UCSD Performance Based Skills Assessment: UPSA) skills. Using canonical analysis, the NP variables were used to predict the functional capacity measures. The analysis found that 37% of the variance in the functional capacity and NP measures was shared, X(2) (54)=106.29, p<.001. Two canonical roots described the cognitive variables and the roots were differentially associated with everyday living and social skills. The root loading on processing speed, episodic memory, and executive functions were associated with UPSA scores, while the root loading on working and episodic memory and verbal fluency were associated most strongly with social competence. Social and everyday living skills deficits in patients with schizophrenia may reflect generally independent domains of functional outcome, linked through cognitive performance. The data suggest that somewhat different cognitive processes are associated with these two domains of functional capacity, although there appears to be some overlap, which may be due to the nature of the NP tests employed.
    Schizophrenia Research 02/2007; 89(1-3):330-8. · 4.59 Impact Factor
  • Philip D Harvey, Margaret M McClure
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    ABSTRACT: Cognitive dysfunction is a core feature of schizophrenia as deficits that are present in the majority of patients with schizophrenia frequently precede the onset of other symptoms and persist even after other symptoms have been effectively treated. The use of atypical antipsychotics has produced some small improvements, although the need for adjunctive treatment specifically targeting cognitive dysfunction is gaining widespread acceptance. Animal models and some small clinical trials have yielded results that are promising but not definitive. Psychosocial interventions have also met with some success in ameliorating some cognitive limitations. The mixed results of pharmacological interventions are most likely to be as a result of a combination of methodological flaws of many studies, poor outcome measures, dose administration effects and problems with the agents themselves.
    Drugs 02/2006; 66(11):1465-73. · 4.13 Impact Factor
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    ABSTRACT: Cognitive dysfunction is a core component of schizophrenia and is strongly related to functional outcome. Schizotypal personality disorder (SPD) appears closely linked to schizophrenia in terms of biology, phenomenology, outcome, and treatment response. Individuals with SPD demonstrate a similar pattern of cognitive deficits, albeit with less severity in most areas, to individuals with schizophrenia, with core impairments in working memory, context processing, and processing capacity. The validity of the SPD cognitive profile is thus discussed in terms of these areas of impairment that are as great as those in schizophrenia, which lends support to the relationship between schizophrenia and SPD.
    Current Psychosis and Therapeutics Reports 4(3).

Publication Stats

365 Citations
80.78 Total Impact Points


  • 2013–2014
    • Fairfield University
      Fairfield, Connecticut, United States
    • Boston University
      • Center for Psychiatric Rehabilitation
      Boston, MA, United States
  • 2006–2014
    • Mount Sinai School of Medicine
      • Department of Psychiatry
      Manhattan, New York, United States
  • 2011
    • University of Miami Miller School of Medicine
      • Department of Psychiatry and Behavioral Sciences
      Miami, FL, United States