Showing papers by "Stephan F. Taylor published in 2012"

Resting-State Functional Connectivity between Fronto-Parietal and Default Mode Networks in Obsessive-Compulsive Disorder

Abstract: Background: Obsessive-compulsive disorder (OCD) is characterized by an excessive focus on upsetting or disturbing thoughts, feelings, and images that are internally-generated. Internally-focused thought processes are subserved by the ‘‘default mode network’’ (DMN), which has been found to be hyperactive in OCD during cognitive tasks. In healthy individuals, disengagement from internally-focused thought processes may rely on interactions between DMN and a frontoparietal network (FPN) associated with external attention and task execution. Altered connectivity between FPN and DMN may contribute to the dysfunctional behavior and brain activity found in OCD. Methods: The current study examined interactions between FPN and DMN during rest in 30 patients with OCD (17 unmedicated) and 32 control subjects (17 unmedicated). Timecourses from seven fronto-parietal seeds were correlated across the whole brain and compared between groups. Results: OCD patients exhibited altered connectivity between FPN seeds (primarily anterior insula) and several regions of DMN including posterior cingulate cortex, medial frontal cortex, posterior inferior parietal lobule, and parahippocampus. These differences were driven largely by a reduction of negative correlations among patients compared to controls. Patients also showed greater positive connectivity between FPN and regions outside DMN, including thalamus, lateral frontal cortex, and somatosensory/motor regions. Conclusions: OCD is associated with abnormal intrinsic functional connectivity between large-scale brain networks. Alteration of interactions between FPN and DMN at rest may contribute to aspects of the OCD phenotype, such as patients’ inability to disengage from internally-generated scenarios and thoughts when performing everyday tasks requiring external attention.

Risk Factors Associated With Metabolic Syndrome in Bipolar and Schizophrenia Subjects Treated With Antipsychotics: The Role of Folate Pharmacogenetics

Abstract: Folate has been implicated in cardiovascular disease with atypical antipsychotic (AAPs) use, and individuals with methylenete- trahydrofolate reductase (MTHFR) and catechol-O-methyl transferase (COMT) variants are at greater risk. This study examined the relationship between the MTHFR 677C/T, MTHFR 1298A/C, and COMT Val158Met variants; metabolic syndrome; and lifestyle measures in schizophrenia and bipolar subjects. A total of 237 subjects with bipolar or schizophrenia receiving an antipsychotic for at least 6 months were included in this cross- sectional analysis. Subjects were screened for the metabolic syndrome (National Cholesterol Education Program Adult Treatment Panel III criteria) and MTHFR 677C/T, MTHFR 1298A/C, and Val158Met ge- notypes. In addition, serum folate and homocysteine were measured along with lifestyle factors. The subject's mean age was 44.7 (SD, 11.7) years; 72% were white, and 51% male; 61% were receiving an AAP; the mean body mass index was 32.6 (SD, 8.2) kg/m 2 , and 48% were current smokers. Overall, 41% met metabolic syndrome criteria (n = 98). There were no differences in age, sex, AAP exposure, or body mass index be- tween genotype groups. Metabolic syndrome was related to age, smoking, and the MTHFR 677T and COMT 158Val alleles (W 2 =3 4.4,P G 0.0001). In addition, AAP use showed a trend association with metabolic syn- drome (W 2 =3 .21,P = 0.07). These data support our previous reports and add more data pointing to folate's role in mediating a link between mental illness and cardiovascular disease. Use of this information clini- cally may help to reduce the risk for AAP metabolic complications in those whose clinical care necessitates the use of AAPs.

Eye-contact perception in schizophrenia: relationship with symptoms and socioemotional functioning.

Abstract: Accurately perceiving self-referential social signals, particularly eye contact, is critical to social adaptation. Schizophrenia is often accompanied by deficits in social cognition, but it is unclear whether this includes gaze discrimination deficits. This study investigated whether eye-contact perception is preserved or impaired and if it is related to symptoms and broader socioemotional functioning in schizophrenia. Twenty-six participants with schizophrenia (SCZ) and 23 healthy controls (HC) made eye-contact judgments for faces in varying gaze direction (from averted to direct in ten 10% increments), head orientation (forward, 30° averted), and emotion (neutral, fearful). Psychophysical analyses for forward faces showed that SCZ began endorsing eye contact with weaker eye-contact signal and their eye-contact perception was less of a dichotomous function, as compared with HC. SCZ were more likely than HC to endorse eye contact when gaze was ambiguous, and this overperception of eye contact was modulated by head orientation and emotion. Overperception of eye contact was associated with more severe negative symptoms. Decreased categorical gaze perception explained variance of socioemotional deficits in schizophrenia after taking basic neurocognition into consideration, suggesting the relationship was not solely due to a general deficit problem. These results were discussed in relation to the nature of categorical gaze perception and its significance to clinical and functional presentations of schizophrenia.

The effects of maternal separation on adult Methamphetamine self-administration

Abstract: The maternal separation (MS) paradigm is an animal model used to investigate long-term effects of early life stress. Animals that undergo daily maternal separation during a critical period of neurological development display altered behavioral and neuroendocrinological responses to psychological stressors as adults. MS also leads to altered drug-induced behaviors and drugseeking behaviors in adulthood. Previous work has investigated drugs such as cocaine, ethanol, and amphetamine in paradigms such as conditioned place preference, locomotor activity, and intravenous/oral self-administration. However, to our knowledge no studies have examined the effects of MS on methamphetamine self-administration. We examined the effects of MS on adult methamphetamine self-administration, extinction, and cue-induced reinstatement of methamphetamine-seeking behavior. Long-Evans rat pups and dams were separated on postnatal days (PND) 2-14 for either 180 minutes (MS180), 15 minutes (MS15), or were left undisturbed other than for general husbandry (animal facility reared (AFR) condition). Male offspring were allowed to acquire methamphetamine self-administration (0.05 mg/kg/infusion) in 2hr daily sessions starting at PND67 for 15 days, followed by extinction training and cue-induced reinstatement of methamphetamine-seeking behavior. The MS180 group selfadministered significantly more methamphetamine and acquired methamphetamine self-administration earlier than the MS15 group but not the AFR group. No significant group differences in extinction or cue-induced reinstatement were observed. These findings suggest that MS may cause lasting effects in the brain that lead to an increased propensity for methamphetamine use. Additional studies are needed to determine if intervention efforts such as environmental enrichment can reverse this stressinduced increase in susceptibility to methamphetamine intake. Supported by DA025606.

Brain Mapping Biomarkers of Socio-Emotional Processing in Schizophrenia

Abstract: The Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative has formed with the expressed intent of identifying constructs and paradigms that would identify biomarkers of psychosis. The manipulation of these biomarkers would serve as targets for treatment interventions. The second phase of CNTRICS consisted of critical discussions evaluating brain mapping (functional neuroimaging and brain electrical activity) paradigms as biomarkers to measure specific constructs. Among the constructs identified in, CNTRICS I was socio-emotional processing, specifically focused on affect recognition. Here, we provide a critical appraisal of the ability of candidate socio-emotional tasks to identify putative biomarkers and recommendations for future directions in this rapidly moving research domain.

Self-assessment of psychological stress in schizophrenia: Preliminary evidence of reliability and validity

Abstract: Heightened stress sensitivity is a common characteristic of schizophrenia and may be predictive of clinical and functional outcomes. However, systematic assessment is not part of routine clinical practice. This study investigated the reliability and predictive values of two versions of a new scale for the assessment of psychological stress in psychosis (Psychological Stress Index; PSI). Thirty-seven patients with schizophrenia/schizoaffective disorder and 30 healthy controls completed a battery of self-report measures at baseline and 4–8 weeks for test–retest. Thirty-four patients were followed up at 12 months. Both of the 18-item and 9-item PSI demonstrated good levels of reliability and could significantly discriminate patients from healthy controls. Both versions showed moderate convergence with self-report and clinician ratings of depression and anxiety, and superior predictive validity of 12-month follow-up clinical and functional outcomes compared to an existing measure of stress (Perceived Stress Scale). The clinical usefulness of the PSI is supported by its predictive power on cross-sectional and longitudinal outcome. The PSI-9 performed as well as, if not better than, the PSI-18 in this study, but further evaluation is warranted for more conclusive comparison.

Trial-by-Trial Adjustments of Cognitive Control Following Errors and Response Conflict are Altered in Pediatric Obsessive Compulsive Disorder.

Abstract: Background: Impairments of cognitive control have been theorized to drive the repetitive thoughts and behaviors of obsessive compulsive disorder (OCD) from early in the course of illness. However, it remains unclear whether altered trial-by-trial adjustment of cognitive control characterizes young patients. To test this hypothesis, we determined whether trial-by-trial adjustments of cognitive control are altered in children with OCD, relative to healthy controls. Methods: Forty-eight patients with pediatric OCD and forty-eight healthy youth performed the Multi-Source Interference Task. Two types of trial-by-trial adjustments of cognitive control were examined: post-error slowing (i.e., slower responses after errors than after correct trials) and post-conflict adaptation (i.e., faster responses in high-conflict incongruent trials that are preceded by other high-conflict incongruent trials, relative to low-conflict congruent trials). Results: While healthy youth exhibited both post-error slowing and post-conflict adaptation, patients with pediatric OCD failed to exhibit either of these effects. Further analyses revealed that patients with low symptom severity showed a reversal of the post-conflict adaptation effect, whereas patients with high symptom severity did not show any post-conflict adaptation. Conclusion: Two types of trial-by-trial adjustments of cognitive control are altered in pediatric OCD. These abnormalities may serve as early markers of the illness.

Influence of threat and serotonin transporter genotype on interference effects

Abstract: Emotion-cognition interactions are critical in goal-directed behavior and may be disrupted in psychopathology Growing evidence also suggests that emotion-cognition interactions are modulated by genetic variation, including genetic variation in the serotonin system The goal of the current study was to examine the impact of threat-related distracters and serotonin transporter promoter polymorphism (5-HTTLPR/rs25531) on cognitive task performance in healthy females Using a novel threat-distracter version of the Multiple-Source Interference Task specifically designed to probe emotion-cognition interactions, we demonstrate a robust and temporally dynamic modulation of cognitive interference effects by threat-related distracters relative to other distracter types and relative to no-distracter condition We further show that threat-related distracters have dissociable and opposite effects on cognitive task performance in easy and difficult task conditions, operationalized as the level of response interference that has to be surmounted to produce a correct response Finally, we present evidence that the 5-HTTLPR/rs25531 genotype in females modulates susceptibility to cognitive interference in a global fashion, across all distracter conditions and irrespective of the emotional salience of distracters, rather than specifically in the presence of threat-related distracters Taken together, these results add to our understanding of the processes through which threat-related distracters affect cognitive processing, and may have implications for our understanding of disorders in which threat signals may have a particularly detrimental effect on cognition, including depression and anxiety disorders

The Influence of the Brain‐Derived Neurotropic Factor Val66Met ‐Genotype and HMG‐CoA Reductase Inhibitors on Insulin Resistance in the Schizophrenia and Bipolar Populations

Abstract: Introduction: The brain-derived neurotrophic factor (BDNF) Val66Met variant and HMG-COA reductase inhibitors (statins) have been implicated in insulin resistance with a possible increased risk of diabetes. We sought to determine the effect of the BDNF Met variant and statin medication use on insulin resistance in schizophrenia and bipolar disorder using the homeostasis model assessment of insulin resistance (HOMA-IR). Methods: A cross-sectional design was used and patients with diabetes or on any medications affecting glucose regulation were -excluded. Associations between insulin resistance and genotype were then analyzed by ANOVA and regression analysis. Subjects were grouped by BDNF genotype as well as presence of statin. Results: Two hundred fifty-two subjects with a mean age of 44 years were included. The group was 53% male and 41% had a diagnosis of bipolar disorder; 78% and 19% were receiving atypical antipsychotics (AAPs) and statin medications, respectively. Analysis showed schizophrenia subjects with the BDNF met allele as well as schizophrenia subjects with both the BDNF met allele and were receiving a statin had significantly higher HOMA-IR values compared to the other groups (p= 0.046 and p= 0.016, respectively). Conclusions: Our results suggest that in the metabolically high-risk population of schizophrenia the BDNF met allele alone and in combination with statin medications is associated with higher insulin resistance values. This was not seen in the bipolar population. Further validation of these associations remains necessary. Clin Trans Sci 2012; Volume 5: 486–490