Towards a Psychosis Risk Blood Diagnostic for Persons Experiencing High-Risk Symptoms: Preliminary Results From the NAPLS Project
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INTRODUCTION: A barrier to preventative treatments for psychosis is the absence of accurate identification of persons at highest risk. A blood test that could substantially increase diagnostic accuracy would enhance development of psychosis prevention interventions. METHODS: The North American Prodrome Longitudinal Study project is a multisite endeavor that aims to better understand predictors and mechanisms for the development of psychosis. In this study, we measured expression of plasma analytes reflecting inflammation, oxidative stress, hormones, and metabolism. A "greedy algorithm" selected analytes that best distinguished persons with clinical high-risk symptoms who developed psychosis (CHR-P; n = 32) from unaffected comparison (UC) subjects (n = 35) and from those who did not develop psychosis during a 2-year follow-up (CHR-NP; n = 40). RESULTS: The classifier included 15 analytes (selected from 117), with an area under the receiver operating curve for CHR-P vs UC of 0.91 and CHR-P vs CHR-NP of 0.88. Randomly scrambled group membership followed by reconstructions of the entire classifier method yielded consistently weak classifiers, indicating that the true classifier is highly unlikely to be a chance occurrence. Such randomization methods robustly imply the assays contain consistent information distinguishing the groups which was not obscured by the data normalization method and was revealed by classifier construction. These results support the hypothesis that inflammation, oxidative stress, and dysregulation of hypothalamic-pituitary axes may be prominent in the earliest stages of psychosis. CONCLUSION: If confirmed in other groups of persons at elevated risk of psychosis, a multiplex blood assay has the potential for high clinical utility.
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Biochemical, imaging, and electrophysiological measurements may help segregating patients into higher- and lower-risk groups.
“In addition, biochemical 140,141 , imaging 52,142,143 , and electrophysiological measurements 144 may help segregating patients into higher- and lower-risk groups.”
From Developmental timing and critical windows for the treatment of psychiatric disorders (2016) · cites this paper as [141]
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“Early diagnosis and intervention in psychosis and SZ, an important focus of psychiatry [81], is hampered by the lack of valid biomarkers.”
BackgroundCorcoran, C. M., Keilp, J. G., Jürgen Kayser, A., Klim, C. C., Butler, P. D., Bruder, G. E., Gur, R. C., & Javitt, D. C. (2015) · Psychological Medicine · doi:10.1017/s0033291715000902 · Cited by 135 · see citing works
“…patients, 14.3% 2-year conversion rate) was relatively small relative to other recent predictor studies (e.g. Meyer & Kurtz, 2009; Nieman et al. 2014; Perkins et al. 2015), emotion recognition represents a critical construct in schizophrenia research and is relatively understudied in CHR patients.”
ResultInfluentialSchmidt, A., Cappucciati, M., Raduà, J., Rutigliano, G., Rocchetti, M., Dell’Osso, L., Politi, P., Borgwardt, S., Reilly, T. J., Valmaggia, L., et al. (2016) · Schizophrenia Bulletin · doi:10.1093/schbul/sbw098 · Cited by 131 · see citing works
Neuroinflammation in schizophrenia: the role of nuclear factor kappa B
Murphy, C. E., Walker, A. K., & Weickert, C. S. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01607-0 · Cited by 128 · see citing works
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Mongan, D., Ramesar, M., Föcking, M., Cannon, M., & Cotter, D. (2020) · Early Intervention in Psychiatry · doi:10.1111/eip.12859 · Cited by 123 · see citing works
Social Stress and Psychosis Risk: Common Neurochemical Substrates?
Mizrahi, R. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2015.274 · Cited by 115 · see citing works
Jacomb, I., Stanton, C., Vasudevan, R., Powell, H., O׳Donnell, M., Lenroot, R., Bruggemann, J. M., Balzan, R. P., Galletly, C. A., Liu, D., et al. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02230 · Cited by 111 · see citing works
“Increases in inflammatory markers have been shown in subsets of individuals in both the prodromal stage (27, 28) and firstepisode psychosis (29), suggesting that inflammation is not secondary to chronic illness or initiation of antipsychotics.”
BackgroundCortisol awakening response in patients with psychosis: systematic review and meta-analysis
Berger, M., Kraeuter, A. K., Romanik, D., Malouf, P., Amminger, G. P., & Sarnyai, Z. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.05.027 · Cited by 109 · see citing works
Ethical considerations for precision psychiatry: A roadmap for research and clinical practice
Fusar‐Poli, P., Manchia, M., Koutsouleris, N., Leslie, D., Woopen, C., Calkins, M. E., Dunn, M., Tourneau, C. L., Männikkö, M., Mollema, T., et al. (2022) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2022.08.001 · Cited by 111 · see citing works
Immune-inflammatory markers and psychosis risk: A systematic review and meta-analysis
Misiak, B., Bartoli, F., Carrà, G., Stańczykiewicz, B., Gładka, A., Frydecka, D., Samochowiec, J., Jarosz, K., Hadryś, T., & Miller, B. J. (2021) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2021.105200 · Cited by 107 · see citing works
“The following diagnostic constructs were included in the clinical risk: 1) CHR of psychosis (Delaney et al., 2019; Kelsven et al., 2020; Perkins et al., 2015); 2) UHR of psychosis (Counotte et al.”
InfluentialMongan, D., Föcking, M., Healy, C., Susai, S. R., Heurich, M., Wynne, K. J., Nelson, B., McGorry, P. D., Amminger, G. P., Nordentoft, M., et al. (2020) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2020.2459 · Cited by 102 · see citing works
Potential Roles of Redox Dysregulation in the Development of Schizophrenia
Perkins, D. O., Jeffries, C. D., & Do, K. Q. (2020) · Biological Psychiatry · doi:10.1016/j.biopsych.2020.03.016 · Cited by 103 · see citing works
“(3) A major focus of this paper is the critical role glutathione plays in controlling redox-mediated cell signaling (7).”
BackgroundInfluentialSelf-citationBrain Imaging During the Transition from Psychosis Prodrome to Schizophrenia
Chung, Y., & Cannon, T. D. (2015) · The Journal of Nervous and Mental Disease · doi:10.1097/nmd.0000000000000286 · Cited by 92 · see citing works
“Although neuroinflammatory processes initiated during prenatal stress exposures could play a role (Perkins et al., 2014), activation of such processes in association with the synaptic pruning characteristic of adolescent brain development represents an influence more proximal to psychosis onset (Frick et al.”
BackgroundInfluentialSelf-citationStuderus, E., Ramyead, A., & Riecher‐Rössler, A. (2017) · Psychological Medicine · doi:10.1017/s0033291716003494 · Cited by 91 · see citing works
Bishop, J. R., Zhang, L., & Lizano, P. L. (2022) · Harvard Review of Psychiatry · doi:10.1097/hrp.0000000000000321 · Cited by 90 · see citing works
“stress, hormones, and metabolism distinguished persons who were at high risk for psychosis and eventually converted to a psychosis diagnosis versus those who did not and also controls.(32,33) Using a “greedy algorithm” approach to build analyte profiles distinguishing the three groups, they identified an index of 15 a…”
MethodIs It Possible to Predict the Future in First-Episode Psychosis?
Suvisaari, J., Mantere, O., Keinänen, J., Mäntylä, T. J. S., Rikandi, E., Lindgren, M., Kieseppä, T., & Raij, T. T. (2018) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2018.00580 · Cited by 88 · see citing works
“Of note is that, while the profile of analytes were fairly similar in these two studies, only three individual analytes (interleukin 8, thyroid stimulating hormone, and factor VII) were the same in both panels (138, 139).”
BackgroundMethodProgress and Future Directions in Research on the Psychosis Prodrome
Woodberry, K. A., Shapiro, D. I., Bryant, C., & Seidman, L. J. (2016) · Harvard Review of Psychiatry · doi:10.1097/hrp.0000000000000109 · Cited by 87 · see citing works
“Markers of neuroinflammation, oxidative stress, and dysregulation of the biological stress response system also appear to be promising biological markers of increased risk.(103,142)”
BackgroundSelf-citationFetal programming of schizophrenia: Select mechanisms
Debnath, M., Venkatasubramanian, G., & Berk, M. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.12.003 · Cited by 84 · see citing works
“Several studies have consistently shown altered levels of markers of inflammation, oxidative stress, metabolism and hormonal status in the first onset schizophrenia patients and have suggested the potential implications of such risk biomarkers of schizophrenia (Guest et al., 2011; Perkins et al., 2014) .”
BackgroundThe Link Between the Immune System, Environment, and Psychosis
Radhakrishnan, R., Kaşer, M., & Gülöksüz, S. (2017) · Schizophrenia Bulletin · doi:10.1093/schbul/sbx057 · Cited by 83 · see citing works
Sanfelici, R., Dwyer, D. B., Antonucci, L. A., & Koutsouleris, N. (2020) · Biological Psychiatry · doi:10.1016/j.biopsych.2020.02.009 · Cited by 82 · see citing works
“In 3 cases, for instance, prognostic features were derived from univariate group comparisons or by applying principal component analysis outside the CV scheme (20,43,53), which is a known source of information leakage, because variance from the training sample data is carried into the test sample (25).”
InfluentialLin, C., & Lane, H. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00093 · Cited by 80 · see citing works
Meta-analysis of cytokine and C-reactive protein levels in high-risk psychosis
Park, S., & Miller, B. J. (2019) · Schizophrenia Research · doi:10.1016/j.schres.2019.03.012 · Cited by 75 · see citing works
Goldsmith, D. R., Haroon, E., Miller, A. H., Addington, J., Bearden, C. E., Cadenhead, K., Cannon, T. D., Cornblatt, B. A., Mathalon, D. H., McGlashan, T. H., et al. (2018) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2018.11.315 · Cited by 74 · see citing works
“Details of sample collection and assay have been described previously (Perkins et al., 2015).”
BackgroundMethodInfluentialSelf-citationEnglish, J. A., Lopez, L. M., O’Gorman, A., Föcking, M., Hryniewiecka, M., Scaife, C., Sabherwal, S., Wynne, K. J., Dicker, P., Rutten, B. P. F., et al. (2017) · Schizophrenia Bulletin · doi:10.1093/schbul/sbx075 · Cited by 69 · see citing works
Oliver, D., Raduà, J., Reichenberg, A., Uher, R., & Fusar‐Poli, P. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00174 · Cited by 69 · see citing works
Inflammatory biomarkers in schizophrenia: Implications for heterogeneity and neurobiology
Miller, B. J., & Goldsmith, D. R. (2019) · Biomarkers in Neuropsychiatry · doi:10.1016/j.bionps.2019.100006 · Cited by 66 · see citing works
Labad, J. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.11.028 · Cited by 67 · see citing works
Hamilton, H. K., Boos, A., & Mathalon, D. (2020) · Biological Psychiatry · doi:10.1016/j.biopsych.2020.04.002 · Cited by 59 · see citing works
Self-citationHeurich, M., Föcking, M., Mongan, D., Cagney, G., & Cotter, D. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01197-9 · Cited by 66 · see citing works
Inflammatory biomarkers in individuals at clinical high risk for psychosis (CHR-P): State or trait?
Khoury, R., & Nasrallah, H. A. (2018) · Schizophrenia Research · doi:10.1016/j.schres.2018.04.017 · Cited by 65 · see citing works
“As previously mentioned, MMP-7 was particularly found to be a predictor of psychotic transition in the NAPLS project (Perkins et al., 2015).”
InfluentialUliana, D. L., Lisboa, J. R., Gomes, F. V., & Grace, A. A. (2024) · Biochemical Pharmacology · doi:10.1016/j.bcp.2024.116298 · Cited by 65 · see citing works
Making Sense of Blood-Based Proteomics and Metabolomics in Psychiatric Research
Guest, P. C., Guest, F. L., & Martins‐de‐Souza, D. (2015) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyv138 · Cited by 63 · see citing works
Impaired insulin signaling in unaffected siblings and patients with first-episode psychosis
Chouinard, V., Henderson, D. C., Man, C. D., Valeri, L., Gray, B. E., Ryan, K. P., Cypess, A. M., Cobelli, C., Cohen, B. M., & Öngür, D. (2018) · Molecular Psychiatry · doi:10.1038/s41380-018-0045-1 · Cited by 62 · see citing works
Using neuroimaging to help predict the onset of psychosis
Gifford, G., Crossley, N. A., Fusar‐Poli, P., Schnack, H. G., Kahn, R. S., Koutsouleris, N., Cannon, T. D., & McGuire, P. K. (2016) · NeuroImage · doi:10.1016/j.neuroimage.2016.03.075 · Cited by 58 · see citing works
Self-citationClark, S. R., Baune, B. T., Schubert, K. O., Lavoie, S., Smesny, S., Rice, S., Schäfer, M. R., Benninger, F., Feucht, M., Klier, C. M., et al. (2016) · Translational Psychiatry · doi:10.1038/tp.2016.170 · Cited by 58 · see citing works
Hoang, D. T., Xu, Y., Lutz, O., Bannai, D., Zeng, V., Bishop, J. R., Keshavan, M. S., & Lizano, P. L. (2021) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2021.11.019 · Cited by 58 · see citing works
Lizano, P. L., Keshavan, M. S., Tandon, N., Mathew, I. T., Mothi, S. S., Montrose, D. M., & Yao, J. K. (2015) · Schizophrenia Research · doi:10.1016/j.schres.2015.12.001 · Cited by 57 · see citing works
“Only a few studies have appliedmultiplex biological screens to the plasma and CSF of symptomatic ultra-high risk for psychosis subjects and found changes consistent with the inflammatory hypothesis (Huang et al., 2007; Stojanovic et al., 2014; Hayes et al., 2014; Perkins et al., 2015).”
BackgroundResultInfluentialKoutsouleris, N., Worthington, M., Dwyer, D., Kambeitz‐Ilankovic, L., Sanfelici, R., Fusar‐Poli, P., Rosen, M., Ruhrmann, S., Anticevic, A., Addington, J., et al. (2021) · Biological Psychiatry · doi:10.1016/j.biopsych.2021.06.023 · Cited by 58 · see citing works
Self-citationProgression from being at-risk to psychosis: next steps
Addington, J., Farris, M., Devoe, D., & Metzak, P. D. (2020) · npj Schizophrenia · doi:10.1038/s41537-020-00117-0 · Cited by 50 · see citing works
Self-citationPrediction of conversion to psychosis in individuals with an at-risk mental state
Riecher‐Rössler, A., & Studerus, E. (2017) · Current Opinion in Psychiatry · doi:10.1097/yco.0000000000000320 · Cited by 53 · see citing works
Regulation of Reactive Oxygen Species-Mediated Damage in the Pathogenesis of Schizophrenia
Madireddy, S., & Madireddy, S. (2020) · Brain Sciences · doi:10.3390/brainsci10100742 · Cited by 55 · see citing works
Oxidative Stress Biomarkers among Schizophrenia Inpatients
Więdłocha, M., Zborowska, N., Marcinowicz, P., Dębowska, W., Dębowska, M. D., Zalewska, A., Maciejczyk, M., Waszkiewicz, N., & Szulc, A. (2023) · Brain Sciences · doi:10.3390/brainsci13030490 · Cited by 53 · see citing works
“documented the correlation of proinflammatory IL-1, IL-7 and IL-8 levels with the severity of attention deficits [58].”
BackgroundFöcking, M., Sabherwal, S., Cates, H. M., Scaife, C., Dicker, P., Hryniewiecka, M., Wynne, K. J., Rutten, B. P. F., Lewis, G., Cannon, M. D., et al. (2019) · Molecular Psychiatry · doi:10.1038/s41380-018-0306-z · Cited by 54 · see citing works
Hafizi, S., Silva, T. M. S., Gerritsen, C. J., Michael Kiang, A., Bagby, R. M., Prce, I., Wilson, A. A., Houle, S., Rusjan, P., & Mizrahi, R. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2017.111 · Cited by 52 · see citing works
Czepielewski, L. S., Massuda, R., Panizzutti, B., Grün, L. K., Barbé‐Tuana, F. M., Teixeira, A. L., Barch, D. M., & Gama, C. S. (2017) · Schizophrenia Bulletin · doi:10.1093/schbul/sbx015 · Cited by 49 · see citing works
Volk, D. W. (2016) · Neurobiology of Disease · doi:10.1016/j.nbd.2016.12.019 · Cited by 47 · see citing works
Ittig, S., Studerus, E., Heitz, U., Menghini‐Müller, S., Beck, K., Egloff, L., Leanza, L., Andreou, C., & Riecher‐Rössler, A. (2017) · Schizophrenia Research · doi:10.1016/j.schres.2017.02.010 · Cited by 46 · see citing works
Oxidative Stress and Emergence of Psychosis
Rambaud, V., Marzo, A., & Chaumette, B. (2022) · Antioxidants · doi:10.3390/antiox11101870 · Cited by 47 · see citing works
“Indeed, studies have highlighted a dysregulation in redox metabolism during the onset of psychosis and increased oxidative damage is observed in a consistent manner in UHR individuals who subsequently develop psychosis [12,22].”
BackgroundFöcking, M., Dicker, P., Lopez, L. M., Cannon, M. D., Schäfer, M. R., McGorry, P. D., Smesny, S., Cotter, D., & Amminger, G. P. (2016) · BMC Psychiatry · doi:10.1186/s12888-016-1039-7 · Cited by 45 · see citing works
“While inflammatory biomarkers are clearly important in psychosis, few previous studies have examined whether blood markers of inflammation distinguish those who convert to psychotic disorder from those who do not [6, 20].”
BackgroundResultInfluentialLalousis, P. A., Schmaal, L., Wood, S. J., Reniers, R. L. E. P., Cropley, V., Watson, A., Pantelis, C., John Suckling, A., Barnes, N. M., Pariante, C. M., et al. (2023) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2023.06.023 · Cited by 47 · see citing works
“9 significant main effect of group in the following domains: premorbid functioning (F(4,446) = 318 2.”
BackgroundPeripheral complement is increased in schizophrenia and inversely related to cortical thickness
Ji, E., Boerrigter, D., Cai, H. Q., Lloyd, D., Bruggemann, J. M., O׳Donnell, M., Galletly, C. A., Lloyd, A. R., Liu, D., Lenroot, R., et al. (2021) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2021.11.014 · Cited by 44 · see citing works
Serum immune markers and transition to psychosis in individuals at clinical high risk
Mondelli, V., Blackman, G., Kempton, M. J., Pollak, T. A., Iyegbe, C. O., Valmaggia, L., Amminger, G. P., Barrantes‐Vidal, N., Bressan, R. A., van der Gaag, M., et al. (2023) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2023.03.014 · Cited by 43 · see citing works
“Previous studies involved CHR samples of n = 39 (Labad et al., 2015), n = 39 (Föcking et al., 2016), and n = 72 (Perkins et al., 2015).”
BackgroundMethodResultInfluentialMarkers of Psychosis Risk in the General Population
Taylor, J. H., Calkins, M. E., & Gur, R. E. (2020) · Biological Psychiatry · doi:10.1016/j.biopsych.2020.02.002 · Cited by 43 · see citing works
Sabherwal, S., English, J. A., Föcking, M., Cagney, G., & Cotter, D. (2016) · Expert Review of Proteomics · doi:10.1080/14789450.2016.1252262 · Cited by 40 · see citing works
“Furthermore, Perkins and colleagues [90] described the use of clinical high-risk patients who converted to psychosis within 2 years in comparison to those that did not convert (results not included [46]).”
BackgroundWoods, S. W., Bearden, C. E., Sabb, F. W., Stone, W. S., Torous, J. B., Cornblatt, B. A., Perkins, D. O., Cadenhead, K. S., Addington, J., Powers, A. R., et al. (2020) · Schizophrenia Research · doi:10.1016/j.schres.2020.04.020 · Cited by 40 · see citing works
“, 2019), and body fluid (Labad et al., 2015; Perkins et al., 2015; Pruessner et al., 2013; Walker et al., 2013) biomarkers in CHR all map onto psychosis-relevant clinical outcomes, to the point that several biomarkermeta-analyses are available (see recent umbrella review (Fusar-Poli et al.”
BackgroundSelf-citationRedox and Immune Signaling in Schizophrenia: New Therapeutic Potential
Dwir, D., Khadimallah, I., Xin, L., Rahman, M., Du, F., Öngür, D., & Kim, Q. (2023) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyad012 · Cited by 40 · see citing works
“Indeed, increased proinflammatory cytokines were present in ultra-high risk individuals (Zeni-Graiff et al., 2016) and with the risk of conversion to psychosis (Perkins et al., 2015; Khoury and Nasrallah, 2018).”
BackgroundResultBrain Biomarkers of Vulnerability and Progression to Psychosis.
Cannon, T. D. (2016) · Schizophrenia bulletin · doi:10.1093/schbul/sbv173 · Cited by 36 · see citing works
Self-citationZhu, Y., Webster, M. J., Murphy, C. E., Middleton, F. A., Massa, P. T., Liu, C., Dai, R., & Weickert, C. S. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.858989 · Cited by 36 · see citing works
Psychotic disorders as a framework for precision psychiatry
Coutts, F., Koutsouleris, N., & McGuire, P. K. (2023) · Nature Reviews Neurology · doi:10.1038/s41582-023-00779-1 · Cited by 35 · see citing works
Antibodies in the Diagnosis, Prognosis, and Prediction of Psychotic Disorders
Pollak, T. A., Rogers, J. P., Nagele, R. G., Peakman, M., Stone, J. M., David, A. S., & McGuire, P. K. (2018) · Schizophrenia Bulletin · doi:10.1093/schbul/sby021 · Cited by 35 · see citing works
The critical need for help-seeking controls in clinical high-risk research
Millman, Z. B., Gold, J. M., Mittal, V. A., & Schiffman, J. (2019) · Clinical Psychological Science · doi:10.1177/2167702619855660 · Cited by 33 · see citing works
“, 2016) and inflammatory cytokines (Perkins et al., 2014), hippocampal atrophy (Fusar-Poli et al.”
BackgroundSawa, A., & Seidman, L. J. (2014) · Neuron · doi:10.1016/j.neuron.2014.08.028 · Cited by 31 · see citing works
Self-citationSchiavone, S., & Trabace, L. (2017) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2017.00203 · Cited by 31 · see citing works
Exploring schizophrenia spectrum psychopathology in borderline personality disorder
Zandersen, M., & Parnas, J. (2019) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-019-01039-4 · Cited by 31 · see citing works
An Update on Promising Biomarkers in Schizophrenia
Goldsmith, D. R., Crooks, C. L., Walker, E. F., & Cotes, R. O. (2018) · FOCUS The Journal of Lifelong Learning in Psychiatry · doi:10.1176/appi.focus.20170046 · Cited by 30 · see citing works
Self-citationKelsven, S., de la Fuente‐Sandoval, C., Achim, C. L., Reyes-Madrigal, F., Mirzakhanian, H., Domingues, I., & Cadenhead, K. S. (2020) · Schizophrenia Research · doi:10.1016/j.schres.2020.01.003 · Cited by 29 · see citing works
Self-citationHuang, J., Park, H., Iaconelli, J., Berkovitch, S. S., Watmuff, B., McPhie, D. L., Öngür, D., Cohen, B. M., Clish, C. B., & Karmacharya, R. (2016) · Journal of Proteome Research · doi:10.1021/acs.jproteome.6b00628 · Cited by 28 · see citing works
Models Predicting Psychosis in Patients With High Clinical Risk: A Systematic Review
Montemagni, C., Bellino, S., Bracale, N., Bozzatello, P., & Rocca, P. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.00223 · Cited by 28 · see citing works
Insights into psychosis risk from leukocyte microRNA expression
Jeffries, C. D., Perkins, D. O., Chandler, S. D., Stark, T., Yeo, E., Addington, J., Bearden, C. E., Cadenhead, K. S., Cannon, T. D., Cornblatt, B. A., et al. (2016) · Translational Psychiatry · doi:10.1038/tp.2016.148 · Cited by 28 · see citing works
“24,25 Thus, peripheral immune cells may be of value for schizophrenia biomarker discovery because their dysregulation may be directly linked to emerging psychosis.”
BackgroundSelf-citationGalantamine-Memantine Combination as an Antioxidant Treatment for Schizophrenia
Koola, M. M., Praharaj, S. K., & Pillai, A. (2019) · Current Behavioral Neuroscience Reports · doi:10.1007/s40473-019-00174-5 · Cited by 27 · see citing works
Ellis, J. K., Walker, E. F., & Goldsmith, D. R. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.567534 · Cited by 27 · see citing works
“Increased peripheral cytokines have been associated with both symptom severity and degree of grey matter loss in CHR subjects (24), as well as predicting conversion to psychosis (78), and peripheral TNF-alpha levels have been shown to predict negative symptom severity (79).”
BackgroundSelf-citationSmesny, S., Milleit, B., Schaefer, M. R., Hesse, J., Schlögelhofer, M., Langbein, K., Hipler, U., Berger, M., Cotter, D., Sauer, H., et al. (2017) · Schizophrenia Research · doi:10.1016/j.schres.2017.01.026 · Cited by 26 · see citing works
“, 2016), and were identified in the search for a particular pattern of biomarkers in UHR individuals that might be predictive in terms of outcome (Perkins et al., 2015).”
Laurikainen, H., Vuorela, A., Toivonen, A., Reinert‐Hartwall, L., Trontti, K., Lindgren, M., Keinänen, J., Mäntylä, T. J. S., Paju, J., Ilonen, T., et al. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-0776-z · Cited by 27 · see citing works
Consolidation of metabolomic, proteomic, and GWAS data in connective model of schizophrenia
Kopylov, A. T., Stepanov, A. A., Butkova, T. V., Malsagova, K. A., Zakharova, N. V., Kostyuk, G. P., Elmuratov, A. U., & Kaysheva, A. L. (2023) · Scientific Reports · doi:10.1038/s41598-023-29117-7 · Cited by 25 · see citing works
Taylor, J. H., Bermúdez-Gómez, J., Zhou, M., Gómez, Ó., Ganz-Leary, C., Palacios, C., Huque, Z. M., Barzilay, R., Goldsmith, D. R., & Gur, R. E. (2023) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2023.12.019 · Cited by 24 · see citing works
“An additional limitation of the current meta -analysis is the requirement of mean age less than or equal to 18 for inclusion, which excluded the large biomarker study NAPLS, which found that baseline markers of inflammation and oxidative stress were associated with transition from CHR-P to TPD (Perkins et al., 2015).”
BackgroundInfluentialPrediction and prevention of psychosis: current progress and future tasks
Ruhrmann, S., Schultze‐Lutter, F., Schmidt, S. J., Kaiser, N., & Klosterkötter, J. (2014) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-014-0541-5 · Cited by 23 · see citing works
Sonnenschein, S. F., & Grace, A. A. (2020) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2021.1849144 · Cited by 23 · see citing works
Preventing discrimination based on psychiatric risk biomarkers
Brannan, C., Foulkes, A. L., & Lázaro‐Muñoz, G. (2019) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32629 · Cited by 22 · see citing works
“Nongenomic biomarkers (e.g., blood analytes, gray matter volume) can be as predictive and, in some cases, even more predictive of disease than genomic biomarkers (Koutsouleris et al., 2015; Lu et al., 2017; Perkins et al., 2015; Sullivan et al., 2017).”
BackgroundInfluentialNetworks of blood proteins in the neuroimmunology of schizophrenia
Jeffries, C. D., Perkins, D. O., Fournier, M., Kim, Q., Cuénod, M., Khadimallah, I., Domenici, E., Addington, J., Bearden, C. E., Cadenhead, K. S., et al. (2018) · Translational Psychiatry · doi:10.1038/s41398-018-0158-y · Cited by 22 · see citing works
Self-citation
- Authors
- Perkins, D. O., Jeffries, C. D., Addington, J., Bearden, C. E., Cadenhead, K. S., Cannon, T. D., Cornblatt, B. A., Mathalon, D. H., McGlashan, T. H., Seidman, L. J., Tsuang, M. T., Walker, E. F., Woods, S. W., & Heinssen, R.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- University of Calgary (CA)
- University of California, Los Angeles (US)
- University of California San Diego (US)
- Yale University (US)
- Zucker Hillside Hospital (US)
- University of California, San Francisco (US)
- Beth Israel Deaconess Medical Center (US)
- Emory University (US)
- National Institute of Mental Health (US)
- Corresponding author
- Perkins, Diana O.
- Jeffries, Clark D.
- ORCID
- Venue
- Schizophrenia Bulletin
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-08-06
- Volume
- 41
- Issue
- 2
- Pages
- 419-428
- ISSN
- 0586-7614 (ISSN-L)
- 1745-1701
- PMC
- PMC4332942
- OpenAlex
- W2144107861
- Cited by
- 238
- References
- 60
- Citations by year
- 2026: 8 · 2025: 15 · 2024: 16 · 2023: 28 · 2022: 14 · 2021: 15 · 2020: 25 · 2019: 22 · 2018: 17 · 2017: 20 · 2016: 32 · 2015: 19 · 2014: 7
- FWCI
- 19.85
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Schizophrenia Bulletin (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc)
- UNC Libraries
- Funders
- National Institute of Mental Health (U01MH081928, U01MH066160, U01MH082022, U01MH076989, U01MH081984, U01MH0818902, U01MH081857, U01MH082004, U01MH081944, P50MH066286, U01MH081988)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Social Sciences › Psychology › Clinical Psychology › Psychopathy, Forensic Psychiatry, Sexual Offending
- Keywords
- psychosis risk, clinical high risk for psychosis
- MeSH terms
- Adult, Female, Follow-Up Studies, Humans, Hypothalamo-Hypophyseal System, Inflammation, Male, Pituitary-Adrenal System, Psychotic Disorders, Oxidative Stress, Risk Assessment, Young Adult, Prodromal Symptoms
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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