Tyrone D Cannon

Publications (142)907.05 Total impact

• Article: Cortisol Levels and Risk for Psychosis: Initial Findings from the North American Prodrome Longitudinal Study.

  Elaine F Walker, Hanan D Trotman, Brad D Pearce, Jean Addington, Kristin S Cadenhead, Barbara A Cornblatt, Robert Heinssen, Daniel H Mathalon, Diana O Perkins, Larry J Seidman, Ming T Tsuang, Tyrone D Cannon, Thomas H McGlashan, Scott W Woods
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  ABSTRACT: BACKGROUND: Studies of biomarkers of hypothalamic-pituitary-adrenal activity indicate that psychotic disorders are associated with elevated cortisol. This study examined cortisol levels in healthy control subjects and individuals who met clinical high-risk (CHR) criteria for psychosis. It was hypothesized that cortisol levels would be 1) elevated in the CHR group relative to control subjects, 2) positively correlated with symptom severity, and 3) most elevated in CHR patients who transition to psychotic level severity. METHODS: Baseline assessments were conducted at eight centers in the North American Prodrome Longitudinal Study. The present CHR sample included 256 individuals meeting the Scale for Prodromal Symptoms criteria and 141 control subjects, all of whom underwent baseline assessment and measurement of salivary cortisol. RESULTS: Consistent with previous reports, there was an effect of age on cortisol, with increases through the adolescent/early adult years. Analysis of covariance showed a main effect of diagnostic group, with the CHR group showing higher cortisol. There were modest, positive correlations of cortisol with baseline symptom severity, and analysis of covariance revealed higher baseline cortisol in those who transitioned to psychotic level symptoms when compared with healthy control subjects and CHR subjects who remitted. CONCLUSIONS: The present findings add to accumulating evidence of heightened cortisol secretion in CHR individuals. The findings also indicate nonspecific associations between cortisol levels and symptom severity, as well as symptom progression. The role of hypothalamic-pituitary-adrenal activity in prediction of conversion to psychosis and its relation with other biomarkers of risk should receive attention in future research.
  Biological psychiatry 04/2013; · 8.93 Impact Factor
• Article: Potential molecular mechanisms for decreased synaptic glutamate release in dysbindin-1 mutant mice.

  Shalini Saggu, Tyrone D Cannon, J David Jentsch, Antonieta Lavin
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  ABSTRACT: Behavioral genetic studies of humans have associated variation in the DTNBP1 gene with schizophrenia and its cognitive deficit phenotypes. The protein encoded by DTNBP1, dysbindin-1, is expressed in forebrain neurons where it interacts with proteins mediating vesicular trafficking and exocytosis. It has been shown that loss of dysbindin-1 results in a decrease in glutamate release in the prefrontal cortex; however the mechanisms underlying this decrease are not fully understood. In order to investigate this question, we evaluated dysbindin-1 null mutant mice, using electrophysiological recordings of prefrontal cortical neurons, imaging studies of vesicles, calcium dynamics and Western blot measures of synaptic proteins and Ca2+ channels. Dysbindin-1 null mice showed a decrease in the ready releasable pool of synaptic vesicles, decreases in quantal size, decreases in the probability of release and deficits in the rate of endo- and exocytosis compared with wild-type controls. Moreover, the dysbindin-1 null mice show decreases in the [Ca2+]i,expression of L- and N-type Ca2+channels and several proteins involved in synaptic vesicle trafficking and priming. Our results provide new insights into the mechanisms of action of dysbindin-1.
  Biological Psychiatry 03/2013; · 8.28 Impact Factor
• Article: Early traumatic experiences in those at clinical high risk for psychosis.

  Jean Addington, Jacqueline Stowkowy, Kristin S Cadenhead, Barbara A Cornblatt, Thomas H McGlashan, Diana O Perkins, Larry J Seidman, Ming T Tsuang, Elaine F Walker, Scott W Woods, Tyrone D Cannon
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  ABSTRACT: AIM: Several lines of evidence suggest a possible association between a history of trauma in childhood and later psychosis or psychotic-like experiences. The purpose of this study was to determine the extent of childhood trauma and bullying in young people at clinical high risk (CHR) of developing psychosis. METHODS: The sample consisted of 360 individuals who were at CHR of developing psychosis and 180 age- and gender-matched healthy controls. All participants were assessed on past trauma and bullying. The CHR participants were also assessed on a range of psychopathology and functioning. RESULTS: Individuals at CHR reported significantly more trauma and bullying than healthy controls. Those who had experienced past trauma and bullying were more likely to have increased levels of depression and anxiety and a poorer sense of self. CONCLUSIONS: These results offer preliminary support for an association between a history of trauma and later subthreshold symptoms.
  Early Intervention in Psychiatry 01/2013; · 0.92 Impact Factor
• Article: Sexual dimorphisms and prediction of conversion in the NAPLS psychosis prodrome.

  Deborah J Walder, Carrie W Holtzman, Jean Addington, Kristin Cadenhead, Ming Tsuang, Barbara Cornblatt, Tyrone D Cannon, Thomas H McGlashan, Scott W Woods, Diana O Perkins, Larry J Seidman, Robert Heinssen, Elaine F Walker
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  ABSTRACT: Sex differences in age at onset, symptomatology, clinical course (see Walker et al., 2002) and functional impairment (Thorup et al., 2007) are well documented in psychosis. The general pattern of findings is that males manifest an earlier onset, more severe symptoms and poorer prognosis than females. Limited studies examining individuals at clinical high-risk (CHR) suggest a similar pattern of sexual dimorphism (Holtzman et al., in review; Corcoran et al., 2011). As part of the North American Prodrome Longitudinal Study (NAPLS), the current study prospectively examined sexual dimorphisms in relationships among CHR symptoms, childhood (premorbid) academic and social functioning, baseline social and role functioning, and conversion to psychosis. Subjects included 276 (113F/163M) CHR NAPLS participants (ages 12-36.8years). All measures/criteria were assessed at baseline except conversion status, assessed at 6-month intervals up to 30months. Results show sex differences in baseline social and role functioning (though not in early childhood adjustment) that predate psychosis onset, with sexually dimorphic patterns in relation to prodromal symptoms. Among male (but not female) CHRs, baseline social functioning and positive prodromal symptoms predicted conversion. These findings help elucidate early course of vulnerability for, and maximally sensitive and specific etiological and prediction models of, psychosis conversion. Findings highlight the importance of considering sexually differentiated predictors of longitudinal course and outcome, in the context of emerging risk profiles. This may optimize efforts at early identification and individually tailored preventive interventions targeting different neurobiological markers/systems and/or cognitive-behavioral approaches. We speculate a contemporary, multidimensional model of psychosis risk that posits a role of sexually dimorphic, genetically linked influences that converge with a modulating role of gonadal hormones (see Walder et al., 2012) across a temporally sensitive neurodevelopmental trajectory towards conferring risk.
  Biological Psychiatry 01/2013; · 8.28 Impact Factor
• Article: Coping styles of individuals at clinical high risk for developing psychosis.

  Maria Jalbrzikowski, Catherine A Sugar, Jamie Zinberg, Peter Bachman, Tyrone D Cannon, Carrie E Bearden
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  ABSTRACT: AIM: There is a wealth of evidence suggesting that patients with schizophrenia tend to respond to life stressors using less effective coping skills, which are in turn related to poor outcome. However, the contribution of coping strategies to outcome in youth at clinical high risk (CHR) for developing psychosis has not been investigated. METHODS: This longitudinal study followed CHR youth over a 12-month period, using the Brief COPE questionnaire. CHR subjects (n = 88) were compared at baseline with a healthy control sample (n = 53), and then mixed models were used to explore the relationship of coping strategies to clinical and psychosocial outcomes in CHR subjects over time (n = 102). RESULTS: Cross-sectional analyses revealed that, in comparison with healthy controls, CHR youth reported using more maladaptive coping strategies (P < 0.001) and fewer adaptive coping strategies (P < 0.01). Longitudinal analyses within the CHR group showed significant decreases in maladaptive coping and symptom severity over time, with corresponding improvements in social and role functioning. Adaptive coping was associated with better concurrent social functioning and less severe symptomatology (both P < 0.001). Over time, more maladaptive coping was associated with more severe positive and negative symptoms (both P < 0.005). CONCLUSIONS: Youth at risk for psychosis report using fewer adaptive and more maladaptive coping strategies relative to healthy controls. Over 1-year follow-up, more adaptive coping styles are associated with less severe clinical symptomatology and better social functioning. These findings suggest that teaching adaptive coping styles may be an important target for intervention in youth at high risk for psychosis.
  Early Intervention in Psychiatry 11/2012; · 0.92 Impact Factor
• Source

  Available from: Anita Riecher-Rössler

  Article: Whither the attenuated psychosis syndrome?

  Alison R Yung, Scott W Woods, Stephan Ruhrmann, Jean Addington, Frauke Schultze-Lutter, Barbara A Cornblatt, G Paul Amminger, Andreas Bechdolf, Max Birchwood, Stefan Borgwardt, [......], Masafumi Mizuno, Anthony P Morrison, Anita Riecher-Rössler, Raimo K R Salokangas, Larry J Seidman, Michio Suzuki, Lucia Valmaggia, Mark van der Gaag, Stephen J Wood, Thomas H McGlashan
  Schizophrenia Bulletin 11/2012; 38(6):1130-4. · 8.80 Impact Factor
• Article: Social cognition in 22q11.2 microdeletion syndrome: Relevance to psychosis?

  Maria Jalbrzikowski, Chelsea Carter, Damla Senturk, Carolyn Chow, Jessica M Hopkins, Michael F Green, Adriana Galván, Tyrone D Cannon, Carrie E Bearden
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  ABSTRACT: 22q11.2 deletion syndrome (22qDS) represents one of the largest known genetic risk factors for schizophrenia. Approximately 30% of individuals with 22qDS develop psychotic illness in adolescence or young adulthood. Given that deficits in social cognition are increasingly viewed as a central aspect of idiopathic schizophrenia, we sought to investigate abilities in this domain as a predictor of psychotic symptoms in 22qDS participants. We assessed multiple domains of social and non-social cognition in 22qDS youth to: 1) characterize performance across these domains in 22qDS, and identify whether 22qDS participants fail to show expected patterns of age-related improvements on these tasks; and 2) determine whether social cognition better predicts positive and negative symptoms than does non-social cognition. Task domains assessed were: emotion recognition and differentiation, Theory of Mind (ToM), verbal knowledge, visuospatial skills, working memory, and processing speed. Positive and negative symptoms were measured using scores obtained from the Structured Interview for Prodromal Symptoms (SIPS). 22qDS participants (N=31, mean age: 15.9) showed the largest impairment, relative to healthy controls (N=31, mean age: 15.6), on measures of ToM and processing speed. In contrast to controls, 22qDS participants did not show age-related improvements on measures of working memory and verbal knowledge. Notably, ToM performance was the best predictor of positive symptoms in 22qDS, accounting for 39% of the variance in symptom severity. Processing speed emerged as the best predictor of negative symptoms, accounting for 37% of the variance in symptoms. Given that ToM was a robust predictor of positive symptoms in our sample, these findings suggest that social cognition may be a valuable intermediate trait for predicting the development of psychosis.
  Biological Psychiatry 10/2012; · 8.28 Impact Factor
• Article: Childhood neuromotor dysfunction in schizophrenia patients and their unaffected siblings: A prospective cohort study.

  Isabelle M. Rosso, Carrie E. Bearden, J. Megginson Hollister, Timothy L. Gasperoni, Laura E. Sanchez, Trevor Hadley, Tyrone D. Cannon
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  ABSTRACT: Examined childhood motor predictors of adult psychiatric outcome in a birth cohort sample (72 patients with schizophrenia or schizoaffective disorder, 63 unaffected siblings, and 7,941 nonpsychiatric controls), evaluated prospectively with neurologic examinations at 8 mo, 4 yrs, and 7 yrs of age. Deviance on motor coordination measures at 7 yrs was associated with both adult schizophrenia and unaffected sibling status, suggesting that a cofamilial (and perhaps genetic) factor underlies motor coordination deficits in schizophrenia. Unusual movements at ages 4 and 7 predicted adult schizophrenia but not unaffected sibling status, indicating that these deficits may be specific to those who will develop the clinical phenotype. None of the motor precursors were confined to patients with an early age at 1st treatment contact. Fetal hypoxia predicted unusual movements at 4 but not 7 yrs among the preschizophrenia Ss, suggesting neurodevelopmental dependence of its functional effects. Neither prenatal complications nor birth weight were associated with motor dysfunction in preschizophrenia Ss or their unaffected siblings at any age. Preschizophrenia children did not show the expected developmental decline in unusual movements. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
  Schizophrenia Bulletin 10/2012; 26(2):367-378. · 8.80 Impact Factor
• Source

  Available from: schizophreniabulletin.oxfordjournals.org

  Article: Editors' Introduction: New Frontiers in Prodromal Research.

  Barbara A. Cornblatt, Robert K. Heinssen, Tyrone D. Cannon, Todd Lencz
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  ABSTRACT: This editorial introduces a special issue of the Schizophrenia Bulletin, which examines new frontiers in prodromal research. Just over a decade ago, in the spring of 1992, this journal published a two-part special issue on the study of first episode schizophrenia, which encouraged a major shift in focus to the early phases of schizophrenia. Hundreds of studies later, the field is now much richer in knowledge concerning this critical period. In turn, it has appeared increasingly likely that a push to even earlier phases of illness will benefit the field still further. The initial set of such very early illness studies was first introduced in a 1996 special issue of Schizophrenia Bulletin. Since then, there have been many new developments and many new prodromal studies launched. It is the authors' hope that the articles in the current issue will provide the foundation for the next generation of research concerned with prevention. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
  Schizophrenia Bulletin 10/2012; 29(4):621-623. · 8.80 Impact Factor
• Article: North American Prodrome Longitudinal Study (NAPLS 2): Overview and recruitment.

  Jean Addington, Kristin S Cadenhead, Barbara A Cornblatt, Daniel H Mathalon, Thomas H McGlashan, Diana O Perkins, Larry J Seidman, Ming T Tsuang, Elaine F Walker, Scott W Woods, Jack A Addington, Tyrone D Cannon
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  ABSTRACT: The North American Prodrome Longitudinal Study (NAPLS) is a consortium of eight programs focusing on the psychosis prodrome. Funded by the National Institute of Mental Health (NIMH), the sites are located at Emory University, Harvard University, University of Calgary, UCLA, UCSD, University of North Carolina Chapel Hill, Yale University, and Zucker Hillside Hospital. Although the programs initially developed independently, they previously collaborated to combine their historical datasets and to produce a series of analyses on predictors of psychosis in one of the largest samples of longitudinally followed prodromal subjects worldwide. This led to the development of a five year prospective study "Predictors and Mechanisms of Conversion to Psychosis", (also known as NAPLS-2) with three major aims: (1) to prospectively test the prediction algorithm developed in NAPLS-1, (2) to investigate the neuroanatomical, neurophysiological, neurocognitive, and neurohormonal factors that may contribute to the development of psychosis, and (3) to develop a repository of DNA, RNA, and plasma from participants meeting diagnostic criteria for a clinical high risk (CHR) state and from demographically similar healthy subjects. Funded by NIMH in 2008, NAPLS-2 will generate the largest CHR for psychosis sample with 720 CHR and 240 healthy comparison subjects, and thus will provide statistical power and scientific scope that cannot be duplicated by any single site study. This paper describes the overall methodology of the NAPLS-2 project and reports on the ascertainment and demographics at the midway point of the study with (360 CHR) and 180 controls.
  Biological Psychiatry 10/2012; · 8.28 Impact Factor
• Article: Decreased Birth Weight in Psychosis: Influence of Prenatal Exposure to Serologically Determined Influenza and Hypoxia.

  Anna M Fineberg, Lauren M Ellman, Stephen Buka, Robert Yolken, Tyrone D Cannon
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  ABSTRACT: Background:Decreased birth weight (BW) is associated with later psychosis, but the sources of decreased BW for those at risk for psychosis remain unclear. Aim: To determine whether fetal exposure to influenza and/or hypoxia accounts for BW decreases among psychotic cases and controls. Method: Subjects were 111 cases diagnosed with schizophrenia or affective psychosis and 333 matched controls from the Collaborative Perinatal Project. Psychiatric diagnoses were ascertained from medical records. Influenza and hypoxia were determined from maternal and cord sera collected at birth. Results: Cases exposed to severe fetal hypoxia or influenza had significantly lower BW compared with unexposed cases and controls, regardless of exposure status. No significant differences in BW were observed among controls based on exposure status. Conclusions: Decreased BW appears to be a risk factor for psychosis only in the presence of other teratogens. Liability to psychosis likely renders fetuses vulnerable to decreased fetal growth in response to hypoxia and influenza.
  Schizophrenia Bulletin 09/2012; · 8.80 Impact Factor
• Article: Genetic Risk for Schizophrenia, Obstetric Complications, and Adolescent School Outcome: Evidence for Gene-Environment Interaction.

  Jennifer K Forsyth, Lauren M Ellman, Antti Tanskanen, Ulla Mustonen, Matti O Huttunen, Jaana Suvisaari, Tyrone D Cannon
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  ABSTRACT: Low birth weight (LBW) and hypoxia are among the environmental factors most reliably associated with schizophrenia; however, the nature of this relationship is unclear and both gene-environment interaction and gene-environment covariation models have been proposed as explanations. High-risk (HR) designs that explore whether obstetric complications differentially predict outcomes in offspring at low risk (LR) vs HR for schizophrenia, while accounting for differences in rates of maternal risk factors, may shed light on this question. This study used prospectively obtained data to examine relationships between LBW and hypoxia on school outcome at age 15-16 years in a Finnish sample of 1070 offspring at LR for schizophrenia and 373 offspring at HR for schizophrenia, based on parental psychiatric history. Controlling for offspring sex, maternal smoking, social support, parity, age, and number of prenatal care visits, HR offspring performed worse than LR offspring across academic, nonacademic, and physical education domains. LBW predicted poorer academic and physical education performance in HR offspring, but not in LR offspring, and this association was similar for offspring of fathers vs mothers with schizophrenia. Hypoxia predicted poorer physical education score across risk groups. Rates of LBW and hypoxia were similar for LR and HR offspring and for offspring of fathers vs mothers with schizophrenia. Results support the hypothesis that genetic susceptibility to schizophrenia confers augmented vulnerability of the developing brain to the effects of obstetric complications, possibly via epigenetic mechanisms.
  Schizophrenia Bulletin 09/2012; · 8.80 Impact Factor
• Article: Structural and functional neuroimaging phenotypes in dysbindin mutant mice.

  Evan Lutkenhoff, Katherine H Karlsgodt, Boris Gutman, Jason L Stein, Paul M Thompson, Tyrone D Cannon, J David Jentsch
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  ABSTRACT: Schizophrenia is a highly heritable psychiatric disorder that is associated with a number of structural and functional neurophenotypes. DTNBP1, the gene encoding dysbindin-1, is a promising candidate gene for schizophrenia. Use of a mouse model carrying a large genomic deletion exclusively within the dysbindin gene permits a direct investigation of the gene in isolation. Here, we use manganese-enhanced magnetic resonance imaging (MEMRI) to explore the regional alterations in brain structure and function caused by loss of the gene encoding dysbindin-1. We report novel findings that uniquely inform our understanding of the relationship of dysbindin-1 to known schizophrenia phenotypes. First, in mutant mice, analysis of the rate of manganese uptake into the brain over a 24-hour period, putatively indexing basal cellular activity, revealed differences in dopamine rich brain regions, as well as in CA1 and dentate subregions of the hippocampus formation. Finally, novel tensor-based morphometry techniques were applied to the mouse MRI data, providing evidence for structural volume deficits in cortical regions, subiculum and dentate gyrus, and the striatum of dysbindin mutant mice. The affected cortical regions were primarily localized to the sensory cortices in particular the auditory cortex. This work represents the first application of manganese-enhanced small animal imaging to a mouse model of schizophrenia endophenotypes, and a novel combination of functional and structural measures. It revealed both hypothesized and novel structural and functional neural alterations related to dysbindin-1.
  NeuroImage 05/2012; 62(1):120-9. · 5.89 Impact Factor
• Source

  Available from: Danijela Piskulic

  Article: Negative symptoms in individuals at clinical high risk of psychosis.

  Danijela Piskulic, Jean Addington, Kristin S Cadenhead, Tyrone D Cannon, Barbara A Cornblatt, Robert Heinssen, Diana O Perkins, Larry J Seidman, Ming T Tsuang, Elaine F Walker, Scott W Woods, Thomas H McGlashan
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  ABSTRACT: Negative symptoms are present in the psychosis prodrome. However, the extent to which these symptoms are present prior to the onset of the first episode of psychosis remains under-researched. The goal of this study is to examine negative symptoms in a sample of individuals at clinical high risk (CHR) for psychosis and to determine if they are predictive of conversion to psychosis. Participants (n=138) were all participants in the North American Prodrome Longitudinal Study (NAPLS 1) project. Negative symptoms were assessed longitudinally using the Scale of Prodromal Symptoms. The mean total negative symptom score at baseline was 11.0, with 82.0% of the sample scoring at moderate severity or above on at least one negative symptom. Over the course of 12 months, the symptoms remained in the above moderate severity range for 54.0% of participants. Associations between individual symptoms were moderate, and a factor analysis confirmed that all negative symptoms loaded heavily on one factor. Negative symptoms were more severe and persistent overtime in those who converted to psychosis, significantly predicting the likelihood of conversion. Thus, early and persistent negative symptoms may represent a vulnerability for risk of developing psychosis.
  Psychiatry Research 03/2012; 196(2-3):220-4. · 2.52 Impact Factor
• Article: Erratum to: Processing Speed and Neurodevelopment in Adolescent-Onset Psychosis: Cognitive Slowing Predicts Social Function.

  Peter Bachman, Tara A Niendam, Maria Jalbrzikowski, Chan Y Park, Melita Daley, Tyrone D Cannon, Carrie E Bearden
  Journal of Abnormal Child Psychology 03/2012; 40(4):655. · 3.09 Impact Factor
• Article: The genetic and environmental determinants of the association between brain abnormalities and schizophrenia: the schizophrenia twins and relatives consortium.

  Neeltje E M van Haren, Fruhling Rijsdijk, Hugo G Schnack, Marco M Picchioni, Timothea Toulopoulou, Matthias Weisbrod, Heinrich Sauer, Theo G van Erp, Tyrone D Cannon, Matti O Huttunen, Dorret I Boomsma, Hilleke E Hulshoff Pol, Robin M Murray, Rene S Kahn
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  ABSTRACT: Structural brain abnormalities are consistently found in schizophrenia (Sz) and have been associated with the familial risk for the disorder. We aim to define the relative contributions of genetic and nongenetic factors to the association between structural brain abnormalities and Sz in a uniquely powered cohort (Schizophrenia Twins and Relatives consortium). An international multicenter magnetic resonance imaging collaboration was set up to pool magnetic resonance imaging scans from twin pairs in Utrecht (The Netherlands), Helsinki (Finland), London (United Kingdom), and Jena (Germany). A sample of 684 subjects took part, consisting of monozygotic twins (n = 410, with 51 patients from concordant and 52 from discordant pairs) and dizygotic twins (n = 274, with 39 patients from discordant pairs). The additive genetic, common, and unique environmental contributions to the association between brain volumes and risk for Sz were estimated by structural equation modeling. The heritabilities of most brain volumes were significant and ranged between 52% (temporal cortical gray matter) and 76% (cerebrum). Heritability of cerebral gray matter did not reach significance (34%). Significant phenotypic correlations were found between Sz and reduced volumes of the cerebrum (-.22 [-.30/-.14]) and white matter (-.17 [-.25/-.09]) and increased volume of the third ventricle (.18 [.08/.28]). These were predominantly due to overlapping genetic effects (77%, 94%, and 83%, respectively). Some of the genes that transmit the risk for Sz also influence cerebral (white matter) volume.
  Biological psychiatry 02/2012; 71(10):915-21. · 8.93 Impact Factor
• Source

  Available from: Daqiang Sun

  Article: Phospholipids and insulin resistance in psychosis: a lipidomics study of twin pairs discordant for schizophrenia.

  Matej Orešič, Tuulikki Seppänen-Laakso, Daqiang Sun, Jing Tang, Sebastian Therman, Rachael Viehman, Ulla Mustonen, Theo G van Erp, Tuulia Hyötyläinen, Paul Thompson, Arthur W Toga, Matti O Huttunen, Jaana Suvisaari, Jaakko Kaprio, Jouko Lönnqvist, Tyrone D Cannon
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  ABSTRACT: Several theories have been proposed to conceptualize the pathological processes inherent to schizophrenia. The 'prostaglandin deficiency' hypothesis postulates that defective enzyme systems converting essential fatty acids to prostaglandins lead to diminished levels of prostaglandins, which in turn affect synaptic transmission. Here we sought to determine the lipidomic profiles associated with schizophrenia in twin pairs discordant for schizophrenia as well as unaffected twin pairs. The study included serum samples from 19 twin pairs discordant for schizophrenia (mean age 51 ± 10 years; 7 monozygotic pairs; 13 female pairs) and 34 age and gender matched healthy twins as controls. Neurocognitive assessment data and gray matter density measurements taken from high-resolution magnetic resonance images were also obtained. A lipidomics platform using ultra performance liquid chromatography coupled to time-of-flight mass spectrometry was applied for the analysis of serum samples. In comparison to their healthy co-twins, the patients had elevated triglycerides and were more insulin resistant. They had diminished lysophosphatidylcholine levels, which associated with decreased cognitive speed. Our findings may be of pathophysiological relevance since lysophosphatidylcholines, byproducts of phospholipase A2-catalyzed phospholipid hydrolysis, are preferred carriers of polyunsaturated fatty acids across the blood-brain barrier. Furthermore, diminishment of lysophosphatidylcholines suggests that subjects at risk of schizophrenia may be more susceptible to infections. Their association with cognitive speed supports the view that altered neurotransmission in schizophrenia may be in part mediated by reactive lipids such as prostaglandins.
  Genome Medicine 01/2012; 4(1):1.
• Article: Alterations in white matter microstructure in neurofibromatosis-1.

  Katherine H Karlsgodt, Tena Rosser, Evan S Lutkenhoff, Tyrone D Cannon, Alcino Silva, Carrie E Bearden
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  ABSTRACT: Neurofibromatosis (NF1) represents the most common single gene cause of learning disabilities. NF1 patients have impairments in frontal lobe based cognitive functions such as attention, working memory, and inhibition. Due to its well-characterized genetic etiology, investigations of NF1 may shed light on neural mechanisms underlying such difficulties in the general population or other patient groups. Prior neuroimaging findings indicate global brain volume increases, consistent with neural over-proliferation. However, little is known about alterations in white matter microstructure in NF1. We performed diffusion tensor imaging (DTI) analyses using tract-based spatial statistics (TBSS) in 14 young adult NF1 patients and 12 healthy controls. We also examined brain volumetric measures in the same subjects. Consistent with prior studies, we found significantly increased overall gray and white matter volume in NF1 patients. Relative to healthy controls, NF1 patients showed widespread reductions in white matter integrity across the entire brain as reflected by decreased fractional anisotropy (FA) and significantly increased absolute diffusion (ADC). When radial and axial diffusion were examined we found pronounced differences in radial diffusion in NF1 patients, indicative of either decreased myelination or increased space between axons. Secondary analyses revealed that FA and radial diffusion effects were of greatest magnitude in the frontal lobe. Such alterations of white matter tracts connecting frontal regions could contribute to the observed cognitive deficits. Furthermore, although the cellular basis of these white matter microstructural alterations remains to be determined, our findings of disproportionately increased radial diffusion against a background of increased white matter volume suggest the novel hypothesis that one potential alteration contributing to increased cortical white matter in NF1 may be looser packing of axons, with or without myelination changes. Further, this indicates that axial and radial diffusivity can uniquely contribute as markers of NF1-associated brain pathology in conjunction with the typically investigated measures.
  PLoS ONE 01/2012; 7(10):e47854. · 4.09 Impact Factor
• Source

  Available from: Danielle A Schlosser

  Article: A randomized trial of family focused treatment for adolescents and young adults at risk for psychosis: study rationale, design and methods.

  Danielle A Schlosser, David J Miklowitz, Mary P O'Brien, Sandra D De Silva, Jamie L Zinberg, Tyrone D Cannon
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  ABSTRACT: This article outlines the rationale for a family-focused psychoeducational intervention for individuals at risk for psychosis and explains the design of a randomized multisite trial to test its efficacy. Adolescents and young adults that meet criteria for a psychosis risk syndrome at eight participating North American Prodromal Longitudinal Study sites are randomly assigned to a 6-month, 18-session family-focused treatment for prodromal youth or a 3-session psychoeducational enhanced care control intervention and followed over 1 year. The results will determine whether the use of a family intervention is able to significantly improve functional outcomes, decrease the severity of positive symptoms and possibly prevent the onset of full psychosis, compared with enhanced care alone. Levels of familial criticism at baseline are hypothesized to moderate responses to family intervention. Improvements in knowledge about symptoms, family communication and problem solving will be tested as mediators in the pathways between treatment assignment and clinical or psychosocial outcomes in high-risk youth. The ongoing trial evaluates whether a non-invasive psychosocial approach can significantly enhance functional outcomes and prevent the ultra high risk patients from developing psychosis. The results will provide an important stepping stone in the movement of the field from refining early detection strategies to developing efficacious preventative treatments.
  Early Intervention in Psychiatry 12/2011; 6(3):283-91. · 0.92 Impact Factor
• Article: Processing speed and neurodevelopment in adolescent-onset psychosis: cognitive slowing predicts social function.

  Peter Bachman, Tara A Niendam, Maria Jalbrzikowski, Maria Jalbrzikowkski, Chan Y Park, Melita Daley, Tyrone D Cannon, Carrie E Bearden
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  ABSTRACT: Onset of psychosis may be associated with abnormal adolescent neurodevelopment. Here we examined the neurocognitive profile of first-episode, adolescent onset psychosis (AOP) as compared to typically developing adolescents, and asked whether neurocognitive performance varied differentially as a function of age in the cases compared with controls. A comprehensive neuropsychological battery was administered to 35 patients experiencing a first-episode of a DSM-IV psychotic disorder and to 31 matched controls. Clinicians also rated subjects' social and role functioning, both at the time of neuropsychological assessment and 1 year later. Although patients displayed a wide range of impairments relative to controls, their most pronounced deficits included verbal memory, sensorimotor dexterity and cognitive processing speed. Among these, only processing speed showed a significant group-by-age interaction, consistent with an aberrant developmental course among AOP patients. Processing speed also accounted for substantial variance in other areas of deficit, and predicted social functioning 1 year later. AOP patients fail to show normal age-related increases in processing speed, which in turn predicts poorer functional outcomes. This pattern is consistent with the view that adolescent brain developmental processes, such as myelination, may be disrupted in these patients.
  Journal of Abnormal Child Psychology 12/2011; 40(4):645-54. · 3.09 Impact Factor