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2. Widespread white matter microstructural differences in schizophrenia across 4322 individuals: results from the ENIGMA Schizophrenia DTI Working Group

Author

Kelly, S, Jahanshad, N, Zalesky, A, Kochunov, P, Agartz, I, Alloza, C, Andreassen, OA, Arango, C, Banaj, N, Bouix, S, Bousman, CA, Brouwer, RM, Bruggemann, J, Bustillo, J, Cahn, W, Calhoun, V, Cannon, D, Carr, V, Catts, S, Chen, J, Chen, J-X, Chen, X, Chiapponi, C, Cho, Kl K, Ciullo, V, Corvin, AS, Crespo-Facorro, B, Cropley, V, De Rossi, P, Diaz-Caneja, CM, Dickie, EW, Ehrlich, S, Fan, F-M, Faskowitz, J, Fatouros-Bergman, H, Flyckt, L, Ford, JM, Fouche, J-P, Fukunaga, M, Gill, M, Glahn, DC, Gollub, R, Goudzwaard, ED, Guo, H, Gur, RE, Gur, RC, Gurholt, TP, Hashimoto, R, Hatton, SN, Henskens, FA, Hibar, DP, Hickie, IB, Hong, LE, Horacek, J, Howells, FM, Hulshoff Pol, HE, Hyde, CL, Isaev, D, Jablensky, A, Jansen, PR, Janssen, J, Jönsson, EG, Jung, LA, Kahn, RS, Kikinis, Z, Liu, K, Klauser, P, Knöchel, C, Kubicki, M, Lagopoulos, J, Langen, C, Lawrie, S, Lenroot, RK, Lim, KO, Lopez-Jaramillo, C, Lyall, A, Magnotta, V, Mandl, RCW, Mathalon, DH, McCarley, RW, McCarthy-Jones, S, McDonald, C, McEwen, S, McIntosh, A, Melicher, T, Mesholam-Gately, RI, Michie, PT, Mowry, B, Mueller, BA, Newell, DT, O'Donnell, P, Oertel-Knöchel, V, Oestreich, L, Paciga, SA, Pantelis, C, Pasternak, O, Pearlson, G, Pellicano, GR, Pereira, A, and Pineda Zapata, J

Subjects
Neurosciences, Brain Disorders, Mental Health, Serious Mental Illness, Biomedical Imaging, Schizophrenia, Clinical Research, Mental health, Adult, Aged, Aged, 80 and over, Brain, Cohort Studies, Corpus Callosum, Diffusion Magnetic Resonance Imaging, Diffusion Tensor Imaging, Female, Humans, Image Processing, Computer-Assisted, Male, Middle Aged, White Matter, Young Adult, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

The regional distribution of white matter (WM) abnormalities in schizophrenia remains poorly understood, and reported disease effects on the brain vary widely between studies. In an effort to identify commonalities across studies, we perform what we believe is the first ever large-scale coordinated study of WM microstructural differences in schizophrenia. Our analysis consisted of 2359 healthy controls and 1963 schizophrenia patients from 29 independent international studies; we harmonized the processing and statistical analyses of diffusion tensor imaging (DTI) data across sites and meta-analyzed effects across studies. Significant reductions in fractional anisotropy (FA) in schizophrenia patients were widespread, and detected in 20 of 25 regions of interest within a WM skeleton representing all major WM fasciculi. Effect sizes varied by region, peaking at (d=0.42) for the entire WM skeleton, driven more by peripheral areas as opposed to the core WM where regions of interest were defined. The anterior corona radiata (d=0.40) and corpus callosum (d=0.39), specifically its body (d=0.39) and genu (d=0.37), showed greatest effects. Significant decreases, to lesser degrees, were observed in almost all regions analyzed. Larger effect sizes were observed for FA than diffusivity measures; significantly higher mean and radial diffusivity was observed for schizophrenia patients compared with controls. No significant effects of age at onset of schizophrenia or medication dosage were detected. As the largest coordinated analysis of WM differences in a psychiatric disorder to date, the present study provides a robust profile of widespread WM abnormalities in schizophrenia patients worldwide. Interactive three-dimensional visualization of the results is available at www.enigma-viewer.org.

Published
2018

3. Intimate partner violence perpetration among veterans: Associations with neuropsychiatric symptoms and limbic microstructure

Author

Rojczyk, P., Heller, C., Seitz-Holland, J., Kaufmann, E., Sydnor, V. J., Berger, L., Pankatz, L., Rathi, Y., Bouix, S., Pasternak, O., Salat, D., Hinds, S. R., Esopenko, C., Fortier, C. B., Milberg, W. P., Shenton, M. E., Koerte, I. K., Rojczyk, P., Heller, C., Seitz-Holland, J., Kaufmann, E., Sydnor, V. J., Berger, L., Pankatz, L., Rathi, Y., Bouix, S., Pasternak, O., Salat, D., Hinds, S. R., Esopenko, C., Fortier, C. B., Milberg, W. P., Shenton, M. E., and Koerte, I. K.

Abstract

Background: Intimate partner violence (IPV) perpetration is highly prevalent among veterans. Suggested risk factors of IPV perpetration include combat exposure, post-traumatic stress disorder (PTSD), depression, alcohol use, and mild traumatic brain injury (mTBI). While the underlying brain pathophysiological characteristics associated with IPV perpetration remain largely unknown, previous studies have linked aggression and violence to alterations of the limbic system. Here, we investigate whether IPV perpetration is associated with limbic microstructural abnormalities in military veterans. Further, we test the effect of potential risk factors (i.e., PTSD, depression, substance use disorder, mTBI, and war zone-related stress) on the prevalence of IPV perpetration. Methods: Structural and diffusion-weighted magnetic resonance imaging (dMRI) data were acquired from 49 male veterans of the Iraq and Afghanistan wars (Operation Enduring Freedom/Operation Iraqi Freedom; OEF/OIF) of the Translational Research Center for TBI and Stress Disorders (TRACTS) study. IPV perpetration was assessed using the psychological aggression and physical assault sub-scales of the Revised Conflict Tactics Scales (CTS2). Odds ratios were calculated to assess the likelihood of IPV perpetration in veterans with either of the following diagnoses: PTSD, depression, substance use disorder, or mTBI. Fractional anisotropy tissue (FA) measures were calculated for limbic gray matter structures (amygdala-hippocampus complex, cingulate, parahippocampal gyrus, entorhinal cortex). Partial correlations were calculated between IPV perpetration, neuropsychiatric symptoms, and FA. Results: Veterans with a diagnosis of PTSD, depression, substance use disorder, or mTBI had higher odds of perpetrating IPV. Greater war zone-related stress, and symptom severity of PTSD, depression, and mTBI were significantly associated with IPV perpetration. CTS2 (psychological aggression), a measure of IPV perpetration, was asso

Published
2024

4. Development of the PSYCHS: Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS

Author

Woods, SW, Parker, S, Kerr, MJ, Walsh, BC, Wijtenburg, SA, Prunier, N, Nunez, AR, Buccilli, K, Mourgues-Codern, C, Brummitt, K, Kinney, KS, Trankler, C, Szacilo, J, Colton, B-L, Ali, M, Haidar, A, Billah, T, Huynh, K, Ahmed, U, Adery, LL, Marcy, PJ, Allott, K, Amminger, P, Arango, C, Broome, MR, Cadenhead, KS, Chen, EYH, Choi, J, Conus, P, Cornblatt, BA, Glenthoj, LB, Horton, LE, Kambeitz, J, Kapur, T, Keshavan, MS, Koutsouleris, N, Langbein, K, Lavoie, S, Diaz-Caneja, CM, Mathalon, DH, Mittal, VA, Nordentoft, M, Pasternak, O, Pearlson, GD, Gaspar, PA, Shah, JL, Smesny, S, Stone, WS, Strauss, GP, Wang, J, Corcoran, CM, Perkins, DO, Schiffman, J, Perez, J, Mamah, D, Ellman, LM, Powers, AR, Coleman, MJ, Anticevic, A, Fusar-Poli, P, Kane, JM, Kahn, RS, McGorry, PD, Bearden, CE, Shenton, ME, Nelson, B, Calkins, ME, Hendricks, L, Bouix, S, Addington, J, McGlashan, TH, Yung, AR, Clark, SR, Lewandowski, KE, Torous, J, Woods, SW, Parker, S, Kerr, MJ, Walsh, BC, Wijtenburg, SA, Prunier, N, Nunez, AR, Buccilli, K, Mourgues-Codern, C, Brummitt, K, Kinney, KS, Trankler, C, Szacilo, J, Colton, B-L, Ali, M, Haidar, A, Billah, T, Huynh, K, Ahmed, U, Adery, LL, Marcy, PJ, Allott, K, Amminger, P, Arango, C, Broome, MR, Cadenhead, KS, Chen, EYH, Choi, J, Conus, P, Cornblatt, BA, Glenthoj, LB, Horton, LE, Kambeitz, J, Kapur, T, Keshavan, MS, Koutsouleris, N, Langbein, K, Lavoie, S, Diaz-Caneja, CM, Mathalon, DH, Mittal, VA, Nordentoft, M, Pasternak, O, Pearlson, GD, Gaspar, PA, Shah, JL, Smesny, S, Stone, WS, Strauss, GP, Wang, J, Corcoran, CM, Perkins, DO, Schiffman, J, Perez, J, Mamah, D, Ellman, LM, Powers, AR, Coleman, MJ, Anticevic, A, Fusar-Poli, P, Kane, JM, Kahn, RS, McGorry, PD, Bearden, CE, Shenton, ME, Nelson, B, Calkins, ME, Hendricks, L, Bouix, S, Addington, J, McGlashan, TH, Yung, AR, Clark, SR, Lewandowski, KE, and Torous, J

Abstract

AIM: To harmonize two ascertainment and severity rating instruments commonly used for the clinical high risk syndrome for psychosis (CHR-P): the Structured Interview for Psychosis-risk Syndromes (SIPS) and the Comprehensive Assessment of At-Risk Mental States (CAARMS). METHODS: The initial workshop is described in the companion report from Addington et al. After the workshop, lead experts for each instrument continued harmonizing attenuated positive symptoms and criteria for psychosis and CHR-P through an intensive series of joint videoconferences. RESULTS: Full harmonization was achieved for attenuated positive symptom ratings and psychosis criteria, and modest harmonization for CHR-P criteria. The semi-structured interview, named Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS (PSYCHS), generates CHR-P criteria and severity scores for both CAARMS and SIPS. CONCLUSIONS: Using the PSYCHS for CHR-P ascertainment, conversion determination, and attenuated positive symptom severity rating will help in comparing findings across studies and in meta-analyses.

Published
2024

5. Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ): Rationale and Study Design of the Largest Global Prospective Cohort Study of Clinical High Risk for Psychosis

Author

Wannan, CMJ, Nelson, B, Addington, J, Allott, K, Anticevic, A, Arango, C, Baker, JT, Bearden, CE, Billah, T, Bouix, S, Broome, MR, Buccilli, K, Cadenhead, KS, Calkins, ME, Cannon, TD, Cecci, G, Chen, EYH, Cho, KIK, Choi, J, Clark, SR, Coleman, MJ, Conus, P, Corcoran, CM, Cornblatt, BA, Diaz-Caneja, CM, Dwyer, D, Ebdrup, BH, Ellman, LM, Fusar-Poli, P, Galindo, L, Gaspar, PA, Gerber, C, Glenthoj, LB, Glynn, R, Harms, MP, Horton, LE, Kahn, RS, Kambeitz, J, Kambeitz-Ilankovic, L, Kane, JM, Kapur, T, Keshavan, MS, Kim, S-W, Koutsouleris, N, Kubicki, M, Kwon, JS, Langbein, K, Lewandowski, KE, Light, GA, Mamah, D, Marcy, PJ, Mathalon, DH, McGorry, PD, Mittal, VA, Nordentoft, M, Nunez, A, Pasternak, O, Pearlson, GD, Perez, J, Perkins, DO, Powers, AR, Roalf, DR, Sabb, FW, Schiffman, J, Shah, JL, Smesny, S, Spark, J, Stone, WS, Strauss, GP, Tamayo, Z, Torous, J, Upthegrove, R, Vangel, M, Verma, S, Wang, J, Winter-van Rossum, I, Wolf, DH, Wolff, P, Wood, SJ, Yung, AR, Agurto, C, Alvarez-Jimenez, M, Amminger, P, Armando, M, Asgari-Targhi, A, Cahill, J, Carrion, RE, Castro, E, Cetin-Karayumak, S, Chakravarty, MM, Cho, YT, Cotter, D, D'Alfonso, S, Ennis, M, Fadnavis, S, Fonteneau, C, Gao, C, Gupta, T, Gur, RE, Gur, RC, Hamilton, HK, Hoftman, GD, Jacobs, GR, Jarcho, J, Ji, JL, Kohler, CG, Lalousis, PA, Lavoie, S, Lepage, M, Liebenthal, E, Mervis, J, Murty, V, Nicholas, SC, Ning, L, Penzel, N, Poldrack, R, Polosecki, P, Pratt, DN, Rabin, R, Eichi, HR, Rathi, Y, Reichenberg, A, Reinen, J, Rogers, J, Ruiz-Yu, B, Scott, I, Seitz-Holland, J, Srihari, VH, Srivastava, A, Thompson, A, Turetsky, BI, Walsh, BC, Whitford, T, Wigman, JTW, Yao, B, Yuen, HP, Ahmed, U, Byun, AJS, Chung, Y, Do, K, Hendricks, L, Huynh, K, Jeffries, C, Lane, E, Langholm, C, Lin, E, Mantua, V, Santorelli, G, Ruparel, K, Zoupou, E, Adasme, T, Addamo, L, Adery, L, Ali, M, Auther, A, Aversa, S, Baek, S-H, Bates, K, Bathery, A, Bayer, JMM, Beedham, R, Bilgrami, Z, Birch, S, Bonoldi, I, Borders, O, Borgatti, R, Brown, L, Bruna, A, Carrington, H, Castillo-Passi, RI, Chen, J, Cheng, N, Ching, AE, Clifford, C, Colton, B-L, Contreras, P, Corral, S, Damiani, S, Done, M, Estrade, A, Etuka, BA, Formica, M, Furlan, R, Geljic, M, Germano, C, Getachew, R, Goncalves, M, Haidar, A, Hartmann, J, Jo, A, John, O, Kerins, S, Kerr, M, Kesselring, I, Kim, H, Kim, N, Kinney, K, Krcmar, M, Kotler, E, Lafanechere, M, Lee, C, Llerena, J, Markiewicz, C, Matnejl, P, Maturana, A, Mavambu, A, Mayol-Troncoso, R, McDonnell, A, McGowan, A, McLaughlin, D, McIlhenny, R, McQueen, B, Mebrahtu, Y, Mensi, M, Hui, CLM, Suen, YN, Wong, SMY, Morrell, N, Omar, M, Partridge, A, Phassouliotis, C, Pichiecchio, A, Politi, P, Porter, C, Provenzani, U, Prunier, N, Raj, J, Ray, S, Rayner, V, Reyes, M, Reynolds, K, Rush, S, Salinas, C, Shetty, J, Snowball, C, Tod, S, Turra-Farina, G, Valle, D, Veale, S, Whitson, S, Wickham, A, Youn, S, Zamorano, F, Zavaglia, E, Zinberg, J, Woods, SW, Shenton, ME, Wannan, CMJ, Nelson, B, Addington, J, Allott, K, Anticevic, A, Arango, C, Baker, JT, Bearden, CE, Billah, T, Bouix, S, Broome, MR, Buccilli, K, Cadenhead, KS, Calkins, ME, Cannon, TD, Cecci, G, Chen, EYH, Cho, KIK, Choi, J, Clark, SR, Coleman, MJ, Conus, P, Corcoran, CM, Cornblatt, BA, Diaz-Caneja, CM, Dwyer, D, Ebdrup, BH, Ellman, LM, Fusar-Poli, P, Galindo, L, Gaspar, PA, Gerber, C, Glenthoj, LB, Glynn, R, Harms, MP, Horton, LE, Kahn, RS, Kambeitz, J, Kambeitz-Ilankovic, L, Kane, JM, Kapur, T, Keshavan, MS, Kim, S-W, Koutsouleris, N, Kubicki, M, Kwon, JS, Langbein, K, Lewandowski, KE, Light, GA, Mamah, D, Marcy, PJ, Mathalon, DH, McGorry, PD, Mittal, VA, Nordentoft, M, Nunez, A, Pasternak, O, Pearlson, GD, Perez, J, Perkins, DO, Powers, AR, Roalf, DR, Sabb, FW, Schiffman, J, Shah, JL, Smesny, S, Spark, J, Stone, WS, Strauss, GP, Tamayo, Z, Torous, J, Upthegrove, R, Vangel, M, Verma, S, Wang, J, Winter-van Rossum, I, Wolf, DH, Wolff, P, Wood, SJ, Yung, AR, Agurto, C, Alvarez-Jimenez, M, Amminger, P, Armando, M, Asgari-Targhi, A, Cahill, J, Carrion, RE, Castro, E, Cetin-Karayumak, S, Chakravarty, MM, Cho, YT, Cotter, D, D'Alfonso, S, Ennis, M, Fadnavis, S, Fonteneau, C, Gao, C, Gupta, T, Gur, RE, Gur, RC, Hamilton, HK, Hoftman, GD, Jacobs, GR, Jarcho, J, Ji, JL, Kohler, CG, Lalousis, PA, Lavoie, S, Lepage, M, Liebenthal, E, Mervis, J, Murty, V, Nicholas, SC, Ning, L, Penzel, N, Poldrack, R, Polosecki, P, Pratt, DN, Rabin, R, Eichi, HR, Rathi, Y, Reichenberg, A, Reinen, J, Rogers, J, Ruiz-Yu, B, Scott, I, Seitz-Holland, J, Srihari, VH, Srivastava, A, Thompson, A, Turetsky, BI, Walsh, BC, Whitford, T, Wigman, JTW, Yao, B, Yuen, HP, Ahmed, U, Byun, AJS, Chung, Y, Do, K, Hendricks, L, Huynh, K, Jeffries, C, Lane, E, Langholm, C, Lin, E, Mantua, V, Santorelli, G, Ruparel, K, Zoupou, E, Adasme, T, Addamo, L, Adery, L, Ali, M, Auther, A, Aversa, S, Baek, S-H, Bates, K, Bathery, A, Bayer, JMM, Beedham, R, Bilgrami, Z, Birch, S, Bonoldi, I, Borders, O, Borgatti, R, Brown, L, Bruna, A, Carrington, H, Castillo-Passi, RI, Chen, J, Cheng, N, Ching, AE, Clifford, C, Colton, B-L, Contreras, P, Corral, S, Damiani, S, Done, M, Estrade, A, Etuka, BA, Formica, M, Furlan, R, Geljic, M, Germano, C, Getachew, R, Goncalves, M, Haidar, A, Hartmann, J, Jo, A, John, O, Kerins, S, Kerr, M, Kesselring, I, Kim, H, Kim, N, Kinney, K, Krcmar, M, Kotler, E, Lafanechere, M, Lee, C, Llerena, J, Markiewicz, C, Matnejl, P, Maturana, A, Mavambu, A, Mayol-Troncoso, R, McDonnell, A, McGowan, A, McLaughlin, D, McIlhenny, R, McQueen, B, Mebrahtu, Y, Mensi, M, Hui, CLM, Suen, YN, Wong, SMY, Morrell, N, Omar, M, Partridge, A, Phassouliotis, C, Pichiecchio, A, Politi, P, Porter, C, Provenzani, U, Prunier, N, Raj, J, Ray, S, Rayner, V, Reyes, M, Reynolds, K, Rush, S, Salinas, C, Shetty, J, Snowball, C, Tod, S, Turra-Farina, G, Valle, D, Veale, S, Whitson, S, Wickham, A, Youn, S, Zamorano, F, Zavaglia, E, Zinberg, J, Woods, SW, and Shenton, ME

Abstract

This article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of individuals at clinical high risk (CHR) for psychosis and to advance the development and use of novel pharmacological interventions for CHR individuals. We present a description of the participating research networks and the data processing analysis and coordination center, their processes for data harmonization across 43 sites from 13 participating countries (recruitment across North America, Australia, Europe, Asia, and South America), data flow and quality assessment processes, data analyses, and the transfer of data to the National Institute of Mental Health (NIMH) Data Archive (NDA) for use by the research community. In an expected sample of approximately 2000 CHR individuals and 640 matched healthy controls, AMP SCZ will collect clinical, environmental, and cognitive data along with multimodal biomarkers, including neuroimaging, electrophysiology, fluid biospecimens, speech and facial expression samples, novel measures derived from digital health technologies including smartphone-based daily surveys, and passive sensing as well as actigraphy. The study will investigate a range of clinical outcomes over a 2-year period, including transition to psychosis, remission or persistence of CHR status, attenuated positive symptoms, persistent negative symptoms, mood and anxiety symptoms, and psychosocial functioning. The global reach of AMP SCZ and its harmonized innovative methods promise to catalyze the development of new treatments to address critical unmet clinical and public health needs in CHR individuals.

Published
2024

6. Brains of endurance athletes differ in the association areas but not in the primary areas

Author

Geisler, M., de la Cruz, F., Makris, N., Billah, T., Zhang, F., Rathi, Y., O'Donnell, L. J., Bouix, S., Herbsleb, M., Bär, K. J., Kikinis, Z., Weiss, T., Geisler, M., de la Cruz, F., Makris, N., Billah, T., Zhang, F., Rathi, Y., O'Donnell, L. J., Bouix, S., Herbsleb, M., Bär, K. J., Kikinis, Z., and Weiss, T.

Abstract

Regular participation in sports results in a series of physiological adaptations. However, little is known about the brain adaptations to physical activity. Here we aimed to investigate whether young endurance athletes and non-athletes differ in the gray and white matter of the brain and whether cardiorespiratory fitness (CRF) is associated with these differences. We assessed the CRF, volumes of the gray and white matter of the brain using structural magnetic resonance imaging (sMRI), and brain white matter connections using diffusion magnetic resonance imaging (dMRI) in 20 young male endurance athletes and 21 healthy non-athletes. While total brain volume was similar in both groups, the white matter volume was larger and the gray matter volume was smaller in the athletes compared to non-athletes. The reduction of gray matter was located in the association areas of the brain that are specialized in processing of sensory stimuli. In the microstructure analysis, significant group differences were found only in the association tracts, for example, the inferior occipito-frontal fascicle (IOFF) showing higher fractional anisotropy and lower radial diffusivity, indicating stronger myelination in this tract. Additionally, gray and white matter brain volumes, as well as association tracts correlated with CRF. No changes were observed in other brain areas or tracts. In summary, the brain signature of the endurance athlete is characterized by changes in the integration of sensory and motor information in the association areas.

Published
2024

8. Inter-site and inter-scanner diffusion MRI data harmonization

Author

Mirzaalian, H., Ning, L., Savadjiev, P., Pasternak, O., Bouix, S., Michailovich, O., Grant, G., Marx, C.E, Morey, R.A., Flashman, L.A., George, M.S., McAllister, T.W., Andaluz, N., Shutter, L., Coimbra, R., Zafonte, R.D., Coleman, M.J., Kubicki, M., Westin, C.F., Stein, M.B., Shenton, M.E., and Rathi, Y.

Published
2016
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9. Development of the PSYCHS: Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS.

Author

Woods, SW, Parker, S, Kerr, MJ, Walsh, BC, Wijtenburg, SA, Prunier, N, Nunez, AR, Buccilli, K, Mourgues-Codern, C, Brummitt, K, Kinney, KS, Trankler, C, Szacilo, J, Colton, B-L, Ali, M, Haidar, A, Billah, T, Huynh, K, Ahmed, U, Adery, LL, Corcoran, CM, Perkins, DO, Schiffman, J, Perez, J, Mamah, D, Ellman, LM, Powers, AR, Coleman, MJ, Anticevic, A, Fusar-Poli, P, Kane, JM, Kahn, RS, McGorry, PD, Bearden, CE, Shenton, ME, Nelson, B, Calkins, ME, Hendricks, L, Bouix, S, Addington, J, McGlashan, TH, Yung, AR, Accelerating Medicines Partnership Schizophrenia, Woods, SW, Parker, S, Kerr, MJ, Walsh, BC, Wijtenburg, SA, Prunier, N, Nunez, AR, Buccilli, K, Mourgues-Codern, C, Brummitt, K, Kinney, KS, Trankler, C, Szacilo, J, Colton, B-L, Ali, M, Haidar, A, Billah, T, Huynh, K, Ahmed, U, Adery, LL, Corcoran, CM, Perkins, DO, Schiffman, J, Perez, J, Mamah, D, Ellman, LM, Powers, AR, Coleman, MJ, Anticevic, A, Fusar-Poli, P, Kane, JM, Kahn, RS, McGorry, PD, Bearden, CE, Shenton, ME, Nelson, B, Calkins, ME, Hendricks, L, Bouix, S, Addington, J, McGlashan, TH, Yung, AR, and Accelerating Medicines Partnership Schizophrenia

Abstract

AIM: To harmonize two ascertainment and severity rating instruments commonly used for the clinical high risk syndrome for psychosis (CHR-P): the Structured Interview for Psychosis-risk Syndromes (SIPS) and the Comprehensive Assessment of At-Risk Mental States (CAARMS). METHODS: The initial workshop is described in the companion report from Addington et al. After the workshop, lead experts for each instrument continued harmonizing attenuated positive symptoms and criteria for psychosis and CHR-P through an intensive series of joint videoconferences. RESULTS: Full harmonization was achieved for attenuated positive symptom ratings and psychosis criteria, and partial harmonization for CHR-P criteria. The semi-structured interview, named P ositive SY mptoms and Diagnostic Criteria for the C AARMS H armonized with the S IPS (PSYCHS), generates CHR-P criteria and severity scores for both CAARMS and SIPS. CONCLUSION: Using the PSYCHS for CHR-P ascertainment, conversion determination, and attenuated positive symptom severity rating will help in comparing findings across studies and in meta-analyses.

Published
2023

10. Exploring the impact of hippocampal sclerosis on white matter tracts memory in individuals with mesial temporal lobe epilepsy

Author

Zanao, T. A., Seitz-Holland, J., O'Donnell, L. J., Zhang, F., Rathi, Y., Lopes, T. M., Pimentel-Silva, L. R., Yassuda, C. L., Makris, N., Shenton, M. E., Bouix, S., Lyall, A. E., Cendes, F., Zanao, T. A., Seitz-Holland, J., O'Donnell, L. J., Zhang, F., Rathi, Y., Lopes, T. M., Pimentel-Silva, L. R., Yassuda, C. L., Makris, N., Shenton, M. E., Bouix, S., Lyall, A. E., and Cendes, F.

Abstract

Objective To investigate how the presence/side of hippocampal sclerosis (HS) are related to the white matter structure of cingulum bundle (CB), arcuate fasciculus (AF), and inferior longitudinal fasciculus (ILF) in mesial temporal lobe epilepsy (MTLE). Methods We acquired diffusion-weighted magnetic resonance imaging (MRI) from 86 healthy and 71 individuals with MTLE (22 righ-HS; right-HS, 34 left-HS; left-HS, and 15 nonlesional MTLE). We utilized two-tensor tractography and fiber clustering to compare fractional anisotropy (FA) of each side/tract between groups. Additionally, we examined the association between FA and nonverbal (WMS-R) and verbal (WMS-R, RAVLT codification) memory performance for MTLE individuals. Results White matter abnormalities depended on the side and presence of HS. The left-HS demonstrated widespread abnormalities for all tracts, the right-HS showed lower FA for ipsilateral tracts and the nonlesional MTLE group did not differ from healthy individuals. Results indicate no differences in verbal/nonverbal memory performance between the groups, but trend-level associations between higher FA of visual memory and the left CB (r = 0.286, P = 0.018), verbal memory (RAVLT) and -left CB (r = 0.335, P = 0.005), -right CB (r = 0.286, P = 0.016), and -left AF (r = 0.287, P = 0.017). Significance Our results highlight that the presence and side of HS are crucial to understand the pathophysiology of MTLE. Specifically, left-sided HS seems to be related to widespread bilateral white matter abnormalities. Future longitudinal studies should focus on developing diagnostic and treatment strategies dependent on HS's presence/side.

Published
2023

11. Sleep quality disturbances are associated with white matter alterations in veterans with post-traumatic stress disorder and mild traumatic brain injury

Author

Rojczyk, P., Seitz-Holland, J., Kaufmann, E., Sydnor, V. J., Kim, C. L., Umminger, L. F., Wiegand, T. L. T., Guenette, J. P., Zhang, F., Rathi, Y., Bouix, S., Pasternak, O., Fortier, C. B., Salat, D., Hinds, S. R., Heinen, F., O’Donnell, L. J., Milberg, W. P., McGlinchey, R. E., Shenton, M. E., Koerte, I. K., Rojczyk, P., Seitz-Holland, J., Kaufmann, E., Sydnor, V. J., Kim, C. L., Umminger, L. F., Wiegand, T. L. T., Guenette, J. P., Zhang, F., Rathi, Y., Bouix, S., Pasternak, O., Fortier, C. B., Salat, D., Hinds, S. R., Heinen, F., O’Donnell, L. J., Milberg, W. P., McGlinchey, R. E., Shenton, M. E., and Koerte, I. K.

Abstract

Sleep disturbances are strongly associated with mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD). PTSD and mTBI have been linked to alterations in white matter (WM) microstructure, but whether poor sleep quality has a compounding effect on WM remains largely unknown. We evaluated sleep and diffusion magnetic resonance imaging (dMRI) data from 180 male post-9/11 veterans diagnosed with (1) PTSD (n = 38), (2) mTBI (n = 25), (3) comorbid PTSD+mTBI (n = 94), and (4) a control group with neither PTSD nor mTBI (n = 23). We compared sleep quality (Pittsburgh Sleep Quality Index, PSQI) between groups using ANCOVAs and calculated regression and mediation models to assess associations between PTSD, mTBI, sleep quality, and WM. Veterans with PTSD and comorbid PTSD+mTBI reported poorer sleep quality than those with mTBI or no history of PTSD or mTBI (p = 0.012 to <0.001). Poor sleep quality was associated with abnormal WM microstructure in veterans with comorbid PTSD+mTBI (p < 0.001). Most importantly, poor sleep quality fully mediated the association between greater PTSD symptom severity and impaired WM microstructure (p < 0.001). Our findings highlight the significant impact of sleep disturbances on brain health in veterans with PTSD+mTBI, calling for sleep-targeted interventions.

Published
2023

12. Sparse Multi-Shell Diffusion Imaging

Author

Rathi, Yogesh, Michailovich, O., Setsompop, K., Bouix, S., Shenton, M. E., Westin, C. -F., Hutchison, David, Series editor, Kanade, Takeo, Series editor, Kittler, Josef, Series editor, Kleinberg, Jon M., Series editor, Mattern, Friedemann, Series editor, Mitchell, John C., Series editor, Naor, Moni, Series editor, Nierstrasz, Oscar, Series editor, Pandu Rangan, C., Series editor, Steffen, Bernhard, Series editor, Sudan, Madhu, Series editor, Terzopoulos, Demetri, Series editor, Tygar, Doug, Series editor, Vardi, Moshe Y., Series editor, Weikum, Gerhard, Series editor, Fichtinger, Gabor, editor, Martel, Anne, editor, and Peters, Terry, editor

Published
2011
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13. Cell type-specific manifestations of cortical thickness heterogeneity in schizophrenia

Author

Di Biase, MA, Geaghan, MP, Reay, WR, Seidlitz, J, Weickert, CS, Pebay, A, Green, MJ, Quide, Y, Atkins, JR, Coleman, MJ, Bouix, S, Knyazhanskaya, EE, Lyall, AE, Pasternak, O, Kubicki, M, Rathi, Y, Visco, A, Gaunnac, M, Lv, J, Mesholam-Gately, R, Lewandowski, KE, Holt, DJ, Keshavan, MS, Pantelis, C, Ongur, D, Breier, A, Cairns, MJ, Shenton, ME, Zalesky, A, Di Biase, MA, Geaghan, MP, Reay, WR, Seidlitz, J, Weickert, CS, Pebay, A, Green, MJ, Quide, Y, Atkins, JR, Coleman, MJ, Bouix, S, Knyazhanskaya, EE, Lyall, AE, Pasternak, O, Kubicki, M, Rathi, Y, Visco, A, Gaunnac, M, Lv, J, Mesholam-Gately, R, Lewandowski, KE, Holt, DJ, Keshavan, MS, Pantelis, C, Ongur, D, Breier, A, Cairns, MJ, Shenton, ME, and Zalesky, A

Abstract

Brain morphology differs markedly between individuals with schizophrenia, but the cellular and genetic basis of this heterogeneity is poorly understood. Here, we sought to determine whether cortical thickness (CTh) heterogeneity in schizophrenia relates to interregional variation in distinct neural cell types, as inferred from established gene expression data and person-specific genomic variation. This study comprised 1849 participants in total, including a discovery (140 cases and 1267 controls) and a validation cohort (335 cases and 185 controls). To characterize CTh heterogeneity, normative ranges were established for 34 cortical regions and the extent of deviation from these ranges was measured for each individual with schizophrenia. CTh deviations were explained by interregional gene expression levels of five out of seven neural cell types examined: (1) astrocytes; (2) endothelial cells; (3) oligodendrocyte progenitor cells (OPCs); (4) excitatory neurons; and (5) inhibitory neurons. Regional alignment between CTh alterations with cell type transcriptional maps distinguished broad patient subtypes, which were validated against genomic data drawn from the same individuals. In a predominantly neuronal/endothelial subtype (22% of patients), CTh deviations covaried with polygenic risk for schizophrenia (sczPRS) calculated specifically from genes marking neuronal and endothelial cells (r = -0.40, p = 0.010). Whereas, in a predominantly glia/OPC subtype (43% of patients), CTh deviations covaried with sczPRS calculated from glia and OPC-linked genes (r = -0.30, p = 0.028). This multi-scale analysis of genomic, transcriptomic, and brain phenotypic data may indicate that CTh heterogeneity in schizophrenia relates to inter-individual variation in cell-type specific functions. Decomposing heterogeneity in relation to cortical cell types enables prioritization of schizophrenia subsets for future disease modeling efforts.

Published
2022

21. Exposure to Repetitive Head Impacts Is Associated With Corpus Callosum Microstructure and Plasma Total Tau in Former Professional American Football Players

Author

Kochsiek, J, O'Donnell, LJ, Zhang, F, Bonke, EM, Sollmann, N, Tripodis, Y, Wiegand, TLT, Kaufmann, D, Umminger, L, Di Biase, MA, Kaufmann, E, Schultz, V, Alosco, ML, Martin, BM, Lin, AP, Coleman, MJ, Rathi, Y, Pasternak, O, Bouix, S, Stern, RA, Shenton, ME, Koerte, IK, Kochsiek, J, O'Donnell, LJ, Zhang, F, Bonke, EM, Sollmann, N, Tripodis, Y, Wiegand, TLT, Kaufmann, D, Umminger, L, Di Biase, MA, Kaufmann, E, Schultz, V, Alosco, ML, Martin, BM, Lin, AP, Coleman, MJ, Rathi, Y, Pasternak, O, Bouix, S, Stern, RA, Shenton, ME, and Koerte, IK

Abstract

BACKGROUND: Exposure to repetitive head impacts (RHI) is associated with an increased risk of later-life neurobehavioral dysregulation and neurodegenerative disease. The underlying pathomechanisms are largely unknown. PURPOSE: To investigate whether RHI exposure is associated with later-life corpus callosum (CC) microstructure and whether CC microstructure is associated with plasma total tau and neuropsychological/neuropsychiatric functioning. STUDY TYPE: Retrospective cohort study. POPULATION: Seventy-five former professional American football players (age 55.2 ± 8.0 years) with cognitive, behavioral, and mood symptoms. FIELD STRENGTH/SEQUENCE: Diffusion-weighted echo-planar MRI at 3 T. ASSESSMENT: Subjects underwent diffusion MRI, venous puncture, neuropsychological testing, and completed self-report measures of neurobehavioral dysregulation. RHI exposure was assessed using the Cumulative Head Impact Index (CHII). Diffusion MRI measures of CC microstructure (i.e., free-water corrected fractional anisotropy (FA), trace, radial diffusivity (RD), and axial diffusivity (AD)) were extracted from seven segments of the CC (CC1-7), using a tractography clustering algorithm. Neuropsychological tests were selected: Trail Making Test Part A (TMT-A) and Part B (TMT-B), Controlled Oral Word Association Test (COWAT), Stroop Interference Test, and the Behavioral Regulation Index (BRI) from the Behavior Rating Inventory of Executive Function, Adult version (BRIEF-A). STATISTICAL TESTS: Diffusion MRI metrics were tested for associations with RHI exposure, plasma total tau, neuropsychological performance, and neurobehavioral dysregulation using generalized linear models for repeated measures. RESULTS: RHI exposure was associated with increased AD of CC1 (correlation coefficient (r) = 0.32, P < 0.05) and with increased plasma total tau (r = 0.34, P < 0.05). AD of the anterior CC1 was associated with increased plasma total tau (CC1: r = 0.30, P < 0.05; CC2: r = 0.29, P < 0.05). Highe

Published
2021

24. Advanced Diffusion Imaging in Psychosis Risk: a cross-sectional and longitudinal study of white matter development

Author

Di Biase, M, Karayumak, SC, Zalesky, A, Kubicki, M, Rathi, Y, Lyons, MG, Bouix, S, Billah, T, Higger, M, Anticevic, A, Addington, J, Bearden, CE, Cornblatt, BA, Keshavan, MS, Mathalon, DH, McGlashan, TH, Perkins, DO, Cadenhead, KS, Tsuang, MT, Woods, SW, Seidman, LJ, Stone, WS, Shenton, ME, Cannon, TD, Pasternak, O, Di Biase, M, Karayumak, SC, Zalesky, A, Kubicki, M, Rathi, Y, Lyons, MG, Bouix, S, Billah, T, Higger, M, Anticevic, A, Addington, J, Bearden, CE, Cornblatt, BA, Keshavan, MS, Mathalon, DH, McGlashan, TH, Perkins, DO, Cadenhead, KS, Tsuang, MT, Woods, SW, Seidman, LJ, Stone, WS, Shenton, ME, Cannon, TD, and Pasternak, O

Abstract

Background: Studies in individuals at clinical high risk (CHR) for psychosis provide a powerful means to predict outcomes and inform putative mechanisms underlying conversion to psychosis. In previous work, we applied advanced diffusion imaging methods to reveal that white matter pathology in a CHR population is characterized by cellular-specific changes in white matter, suggesting a preexisting neurodevelopmental anomaly. However, it remains unknown whether these deficits relate to clinical symptoms and/or conversion to frank psychosis. To address this gap, we examined cross-sectional and longitudinal white matter maturation in the largest imaging population of CHR individuals to date, obtained from the North American Prodrome Longitudinal Study (NAPLS-3). Methods: Multi-shell diffusion magnetic resonance imaging (MRI) data were collected across multiple timepoints (1–6 at ~2 month intervals) in 286 subjects (age range=12–32 years). These were 230 unmedicated CHR subjects, including 11% (n=25) who transitioned to psychosis (CHR-converters), as well as 56 age and sex-matched healthy controls. Raw diffusion signals were harmonized to remove scanner/site-induced effects, yielding a unified imaging dataset. Fractional anisotropy of cellular tissue (FAt) and the volume fraction of extracellular free-water (FW) were assessed in 12 major tracts from the IIT Human Brain Atlas (v.5.0). Linear mixed effects (LME) models were fitted to infer developmental trajectories of FAt and FW across age for CHR-converters, CHR-nonconverters and control groups, while accounting for the repeated measurements on each individual. Results: The rate at which FAt changed with age significantly differed between the three groups across commissural and association tracts (5 in total; p<0.05). In these tracts, FAt increased with age in controls (0.002% change per year) and in CHR-nonconverters, albeit at a slower rate (0.00074% per year). In contrast, FAt declined with age in CHR-converters at a r

Published
2020

25. Lifespan Trajectories of White Matter Changes in Rhesus Monkeys

Author

Kubicki, M, primary, Baxi, M, additional, Pasternak, O, additional, Tang, Y, additional, Karmacharya, S, additional, Chunga, N, additional, Lyall, A E, additional, Rathi, Y, additional, Eckbo, R, additional, Bouix, S, additional, Mortazavi, F, additional, Papadimitriou, G, additional, Shenton, M E, additional, Westin, C F, additional, Killiany, R, additional, Makris, N, additional, and Rosene, D L, additional

Published
2018
Full Text
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26. Widespread white matter microstructural differences in schizophrenia across 4322 individuals: results from the ENIGMA Schizophrenia DTI Working Group

Author

Kelly, S., Jahanshad, N., Zalesky, A., Kochunov, P., Agartz, I., Alloza, C., Andreassen, O.A., Arango, C., Banaj, N., Bouix, S., Bousman, C.A., Brouwer, R.M., Bruggemann, J., Bustillo, J., Cahn, W., Calhoun, V., Cannon, D., Carr, V., Catts, S., Chen, J., Chen, J.X., Chen, X, Chiapponi, C., Cho, K.K., Ciullo, V., Corvin, A.S., Crespo-Facorro, B., Cropley, V., Rossi, P., Diaz-Caneja, C.M., Dickie, E.W., Ehrlich, S., Fan, F.M., Faskowitz, J., Fatouros-Bergman, H., Flyckt, L., Ford, J.M., Fouche, J.P., Fukunaga, M., Gill, M., Glahn, D.C., Gollub, R., Goudzwaard, E.D., Guo, H, Gur, R.E., Gur, R.C., Gurholt, T.P., Hashimoto, R., Hatton, S.N., Henskens, F.A., Hibar, D.P., Hickie, I.B., Hong, L.E., Horacek, J., Howells, F.M., Pol, H.E., Hyde, C.L., Isaev, D., Jablensky, A., Jansen, P.R., Janssen, J, Jonsson, E.G., Jung, L.A., Kahn, R.S., Kikinis, Z., Liu, K, Klauser, P., Knochel, C., Kubicki, M., Lagopoulos, J., Langen, C., Lawrie, S., Lenroot, R.K., Lim, K.O., Lopez-Jaramillo, C., Lyall, A., Magnotta, V., Mandl, R.C.W., Mathalon, D.H., McCarley, R.W., McCarthy-Jones, S., McDonald, C., McEwen, S., McIntosh, A., Melicher, T., Mesholam-Gately, R.I., Michie, P.T., Mowry, B., Mueller, B.A., Newell, D.T., O'Donnell, P., Oertel-Knochel, V., Oestreich, L., Paciga, S.A., Pantelis, C., Pasternak, O., Pearlson, G., Pellicano, G.R., Pereira, A., Zapata, J., Sprooten, E., Thompson, P.M., Donohoe, G., Kelly, S., Jahanshad, N., Zalesky, A., Kochunov, P., Agartz, I., Alloza, C., Andreassen, O.A., Arango, C., Banaj, N., Bouix, S., Bousman, C.A., Brouwer, R.M., Bruggemann, J., Bustillo, J., Cahn, W., Calhoun, V., Cannon, D., Carr, V., Catts, S., Chen, J., Chen, J.X., Chen, X, Chiapponi, C., Cho, K.K., Ciullo, V., Corvin, A.S., Crespo-Facorro, B., Cropley, V., Rossi, P., Diaz-Caneja, C.M., Dickie, E.W., Ehrlich, S., Fan, F.M., Faskowitz, J., Fatouros-Bergman, H., Flyckt, L., Ford, J.M., Fouche, J.P., Fukunaga, M., Gill, M., Glahn, D.C., Gollub, R., Goudzwaard, E.D., Guo, H, Gur, R.E., Gur, R.C., Gurholt, T.P., Hashimoto, R., Hatton, S.N., Henskens, F.A., Hibar, D.P., Hickie, I.B., Hong, L.E., Horacek, J., Howells, F.M., Pol, H.E., Hyde, C.L., Isaev, D., Jablensky, A., Jansen, P.R., Janssen, J, Jonsson, E.G., Jung, L.A., Kahn, R.S., Kikinis, Z., Liu, K, Klauser, P., Knochel, C., Kubicki, M., Lagopoulos, J., Langen, C., Lawrie, S., Lenroot, R.K., Lim, K.O., Lopez-Jaramillo, C., Lyall, A., Magnotta, V., Mandl, R.C.W., Mathalon, D.H., McCarley, R.W., McCarthy-Jones, S., McDonald, C., McEwen, S., McIntosh, A., Melicher, T., Mesholam-Gately, R.I., Michie, P.T., Mowry, B., Mueller, B.A., Newell, D.T., O'Donnell, P., Oertel-Knochel, V., Oestreich, L., Paciga, S.A., Pantelis, C., Pasternak, O., Pearlson, G., Pellicano, G.R., Pereira, A., Zapata, J., Sprooten, E., Thompson, P.M., and Donohoe, G.

Abstract

Contains fulltext : 193179.pdf (Publisher’s version ) (Open Access), The regional distribution of white matter (WM) abnormalities in schizophrenia remains poorly understood, and reported disease effects on the brain vary widely between studies. In an effort to identify commonalities across studies, we perform what we believe is the first ever large-scale coordinated study of WM microstructural differences in schizophrenia. Our analysis consisted of 2359 healthy controls and 1963 schizophrenia patients from 29 independent international studies; we harmonized the processing and statistical analyses of diffusion tensor imaging (DTI) data across sites and meta-analyzed effects across studies. Significant reductions in fractional anisotropy (FA) in schizophrenia patients were widespread, and detected in 20 of 25 regions of interest within a WM skeleton representing all major WM fasciculi. Effect sizes varied by region, peaking at (d=0.42) for the entire WM skeleton, driven more by peripheral areas as opposed to the core WM where regions of interest were defined. The anterior corona radiata (d=0.40) and corpus callosum (d=0.39), specifically its body (d=0.39) and genu (d=0.37), showed greatest effects. Significant decreases, to lesser degrees, were observed in almost all regions analyzed. Larger effect sizes were observed for FA than diffusivity measures; significantly higher mean and radial diffusivity was observed for schizophrenia patients compared with controls. No significant effects of age at onset of schizophrenia or medication dosage were detected. As the largest coordinated analysis of WM differences in a psychiatric disorder to date, the present study provides a robust profile of widespread WM abnormalities in schizophrenia patients worldwide. Interactive three-dimensional visualization of the results is available at www.enigma-viewer.org.

Published
2018

27. Widespread white matter microstructural differences in schizophrenia across 4322 individuals: Results from the ENIGMA Schizophrenia DTI Working Group.

Author

Faskowitz J., Jablensky A., Jansen P.R., Janssen J., Jonsson E.G., Jung L.A., Kahn R.S., Kikinis Z., Liu K., Klauser P., Knochel C., Kubicki M., Lagopoulos J., Langen C., Lawrie S., Lenroot R.K., Lim K.O., Lopez-Jaramillo C., Lyall A., Magnotta V., Mandl R.C.W., McIntosh A., Melicher T., Mesholam-Gately R.I., Michie P.T., Mowry B., Mueller B.A., Newell D.T., O'Donnell P., Oertel-Knochel V., Oestreich L., Paciga S.A., Pantelis C., Pasternak O., Pearlson G., Pellicano G.R., Pereira A., Pineda Zapata J., Piras F., Potkin S.G., Preda A., Rasser P.E., Roalf D.R., Roiz R., Roos A., Rotenberg D., Satterthwaite T.D., Savadjiev P., Schall U., Scott R.J., Seal M.L., Seidman L.J., Shannon Weickert C., Whelan C.D., Shenton M.E., Kwon J.S., Spalletta G., Spaniel F., Sprooten E., Stablein M., Stein D.J., Tan Y., Tan S., Tang S., Temmingh H.S., Westlye L.T., Tonnesen S., Tordesillas-Gutierrez D., Doan N.T., Vaidya J., Van Haren N.E.M., Vargas C.D., Vecchio D., Velakoulis D., Voineskos A., Voyvodic J.Q., Wang Z., Wan P., Wei D., Weickert T.W., Whalley H., White T., Whitford T.J., Wojcik J.D., Xiang H., Xie Z., Yamamori H., Yang F., Yao N., Zhang G., Zhao J., Van Erp T.G.M., Turner J., Thompson P.M., Donohoe G., Sundram S., Kelly S., Jahanshad N., Zalesky A., Kochunov P., Agartz I., Alloza C., Andreassen O.A., Arango C., Banaj N., Bouix S., Bousman C.A., Brouwer R.M., Bruggemann J., Bustillo J., Cahn W., Calhoun V., Cannon D., Carr V., Catts S., Chen J., Chen J.-X., Chen X., Chiapponi C., Cho K.K., Ciullo V., Corvin A.S., Crespo-Facorro B., Cropley V., De Rossi P., Diaz-Caneja C.M., Dickie E.W., Ehrlich S., Fan F.-M., Fatouros-Bergman H., Flyckt L., Ford J.M., Fouche J.-P., Fukunaga M., Gill M., Glahn D.C., Gollub R., Goudzwaard E.D., Guo H., Gur R.E., Gur R.C., Gurholt T.P., Hashimoto R., Hatton S.N., Henskens F.A., Hibar D.P., Hickie I.B., Hong L.E., Horacek J., Howells F.M., Hulshoff Pol H.E., Hyde C.L., Isaev D., Mathalon D.H., McCarley R.W., McCarthy-Jones S., McDonald C., McEwen S., Faskowitz J., Jablensky A., Jansen P.R., Janssen J., Jonsson E.G., Jung L.A., Kahn R.S., Kikinis Z., Liu K., Klauser P., Knochel C., Kubicki M., Lagopoulos J., Langen C., Lawrie S., Lenroot R.K., Lim K.O., Lopez-Jaramillo C., Lyall A., Magnotta V., Mandl R.C.W., McIntosh A., Melicher T., Mesholam-Gately R.I., Michie P.T., Mowry B., Mueller B.A., Newell D.T., O'Donnell P., Oertel-Knochel V., Oestreich L., Paciga S.A., Pantelis C., Pasternak O., Pearlson G., Pellicano G.R., Pereira A., Pineda Zapata J., Piras F., Potkin S.G., Preda A., Rasser P.E., Roalf D.R., Roiz R., Roos A., Rotenberg D., Satterthwaite T.D., Savadjiev P., Schall U., Scott R.J., Seal M.L., Seidman L.J., Shannon Weickert C., Whelan C.D., Shenton M.E., Kwon J.S., Spalletta G., Spaniel F., Sprooten E., Stablein M., Stein D.J., Tan Y., Tan S., Tang S., Temmingh H.S., Westlye L.T., Tonnesen S., Tordesillas-Gutierrez D., Doan N.T., Vaidya J., Van Haren N.E.M., Vargas C.D., Vecchio D., Velakoulis D., Voineskos A., Voyvodic J.Q., Wang Z., Wan P., Wei D., Weickert T.W., Whalley H., White T., Whitford T.J., Wojcik J.D., Xiang H., Xie Z., Yamamori H., Yang F., Yao N., Zhang G., Zhao J., Van Erp T.G.M., Turner J., Thompson P.M., Donohoe G., Sundram S., Kelly S., Jahanshad N., Zalesky A., Kochunov P., Agartz I., Alloza C., Andreassen O.A., Arango C., Banaj N., Bouix S., Bousman C.A., Brouwer R.M., Bruggemann J., Bustillo J., Cahn W., Calhoun V., Cannon D., Carr V., Catts S., Chen J., Chen J.-X., Chen X., Chiapponi C., Cho K.K., Ciullo V., Corvin A.S., Crespo-Facorro B., Cropley V., De Rossi P., Diaz-Caneja C.M., Dickie E.W., Ehrlich S., Fan F.-M., Fatouros-Bergman H., Flyckt L., Ford J.M., Fouche J.-P., Fukunaga M., Gill M., Glahn D.C., Gollub R., Goudzwaard E.D., Guo H., Gur R.E., Gur R.C., Gurholt T.P., Hashimoto R., Hatton S.N., Henskens F.A., Hibar D.P., Hickie I.B., Hong L.E., Horacek J., Howells F.M., Hulshoff Pol H.E., Hyde C.L., Isaev D., Mathalon D.H., McCarley R.W., McCarthy-Jones S., McDonald C., and McEwen S.

Abstract

The regional distribution of white matter (WM) abnormalities in schizophrenia remains poorly understood, and reported disease effects on the brain vary widely between studies. In an effort to identify commonalities across studies, we perform what we believe is the first ever large-scale coordinated study of WM microstructural differences in schizophrenia. Our analysis consisted of 2359 healthy controls and 1963 schizophrenia patients from 29 independent international studies; we harmonized the processing and statistical analyses of diffusion tensor imaging (DTI) data across sites and meta-analyzed effects across studies. Significant reductions in fractional anisotropy (FA) in schizophrenia patients were widespread, and detected in 20 of 25 regions of interest within a WM skeleton representing all major WM fasciculi. Effect sizes varied by region, peaking at (d=0.42) for the entire WM skeleton, driven more by peripheral areas as opposed to the core WM where regions of interest were defined. The anterior corona radiata (d=0.40) and corpus callosum (d=0.39), specifically its body (d=0.39) and genu (d=0.37), showed greatest effects. Significant decreases, to lesser degrees, were observed in almost all regions analyzed. Larger effect sizes were observed for FA than diffusivity measures; significantly higher mean and radial diffusivity was observed for schizophrenia patients compared with controls. No significant effects of age at onset of schizophrenia or medication dosage were detected. As the largest coordinated analysis of WM differences in a psychiatric disorder to date, the present study provides a robust profile of widespread WM abnormalities in schizophrenia patients worldwide. Interactive three-dimensional visualization of the results is available at www.enigma-viewer.org.Copyright © The Author(s) 2018.

Published
2018

28. Widespread white matter microstructural differences in schizophrenia across 4322 individuals: Results from the ENIGMA Schizophrenia DTI Working Group

Author

Kelly, S. (S.), Jahanshad, N. (Neda), Zalesky, A. (A.), Kochunov, P. (P.), Agartz, I. (Ingrid), Alloza, C. (C.), Andreassen, O.A. (O. A.), Arango, C. (C.), Banaj, N. (N.), Bouix, S. (S.), Bousman, C.A. (C. A.), Brouwer, R.M. (Rachel), Bruggemann, J. (J.), Bustillo, J., Cahn, W. (Wiepke), Calhoun, V.D. (Vince), Cannon, D. (D.), Carr, V.J. (Vaughan), Catts, S.V. (Stanley), Chen, J. (J.), Chen, J.-X. (J. X.), Chen, X. (X.), Chiapponi, C. (C.), Cho, K.K. (Kl K), Ciullo, V. (V.), Corvin, A. (Aiden), Crespo-Facorro, B. (Benedicto), Cropley, V. (V.), De Rossi, P. (P.), Diaz-Caneja, C.M. (C. M.), Dickie, E.W. (E. W.), Ehrlich, S.M. (Stefan), Fan, F.-M. (F. M.), Faskowitz, J. (J.), Fatouros-Bergman, H. (H.), Flyckt, L. (L.), Ford, J.M. (J. M.), Fouche, J.-P. (J. P.), Fukunaga, M. (Masaki), Gill, M. (M.), Glahn, D.C. (David), Gollub, R.L. (Randy), Goudzwaard, E.D. (E. D.), Guo, H. (H.), Gur, R.E. (Raquel), Gur, R.C. (R. C.), Gurholt, T.P. (T. P.), Hashimoto, R. (Ryota), Hatton, W., Henskens, F.A. (Frans), Hibar, D.P. (D. P.), Hickie, I.B. (Ian), Hong, L.E. (L. E.), Horacek, J. (J.), Howells, F.M. (F. M.), Hulshoff Pol, H.E. (Hilleke), Hyde, C.L. (C. L.), Isaev, D. (D.), Jablensky, A. (A.), Jansen, P.R. (P. R.), Janssen, J. (J.), Jönsson, E.G. (Erik), Jung, L.A. (L. A.), Kahn, R.S. (R. S.), Kikinis, Z. (Z.), Liu, K. (K.), Klauser, P. (P.), Knöchel, C. (C.), Kubicki, M. (M.), Lagopoulos, J. (Jim), Langen, C.D. (Carolyn), Lawrie, S. (Stephen), Lenroot, R.K. (Rhoshel), Lim, K.O. (Kelvin), Lopez-Jaramillo, C. (C.), Lyall, A. (A.), Magnotta, V., Mandl, R. (René), Mathalon, D.H. (D. H.), McCarley, R.W. (Robert), McCarthy-Jones, S. (S.), McDonald, C. (Colm), McEwen, S. (S.), McIntosh, A.M. (Andrew), Melicher, T. (T.), Mesholam-Gately, R.I. (Raquelle), Michie, P.T. (Patricia), Mowry, B.J. (Bryan J), Mueller, B.A. (Bryon ), Newell, D.T. (D. T.), O'Donnell, P. (P.), Oertel-Knöchel, V. (V.), Oestreich, L. (L.), Paciga, S.A. (S. A.), Pantelis, C. (Christos), Pasternak, O. (O.), Pearlson, G. (G.), Pellicano, G.R. (G. R.), Pereira, A. (A.), Pineda Zapata, J. (J.), Piras, F. (F.), Potkin, S.G. (Steven), Preda, A. (A.), Rasser, P.E. (P. E.), Roalf, D.R. (D. R.), Roiz, R. (R.), Roos, A. (A.), Rotenberg, D. (D.), Satterthwaite, T.D. (Theodore), Savadjiev, P. (P.), Schall, J.D. (Jeffrey), Scott, R.J. (R. J.), Seal, M.L. (M. L.), Seidman, L.J. (Larry), Shannon Weickert, C. (C.), Whelan, C.D. (Christopher), Shenton, M.E. (M. E.), Kwon, J.S. (J. S.), Spalletta, G. (Gianfranco), Spaniel, F. (F.), Sprooten, R. (Roy), Stäblein, M. (M.), Stein, D.J. (Dan), Sundram, S. (S.), Tan, Y. (Y.), Tan, S. (S.), Tang, S. (S.), Temmingh, H.S. (H. S.), Westlye, L.T. (Lars), Tønnesen, S. (S.), Tordesillas-Gutierrez, D. (Diana), Doan, N.T. (N. T.), Vaidya, J. (J.), Van Haren, N.E.M. (N. E.M.), Vargas, C.D. (C. D.), Vecchio, D. (D.), Velakoulis, D. (D.), Voineskos, A. (A.), Voyvodic, J.Q. (J. Q.), Wang, Z. (Z.), Wan, P. (P.), Wei, D. (D.), Weickert, T.W. (T. W.), Whalley, H. (H.), White, T.J.H. (Tonya), Whitford, T.J. (T. J.), Wojcik, J.D. (J. D.), Xiang, H. (H.), Xie, Z. (Z.), Yamamori, H. (H.), Yang, F. (F.), Yao, N. (N.), Zhang, G. (G.), Zhao, J. (J.), Erp, T.G.M. (Theo G.) van, Turner, J. (Jessica), Thompson, P.M. (P. M.), Donohoe, D.J. (Dennis), Kelly, S. (S.), Jahanshad, N. (Neda), Zalesky, A. (A.), Kochunov, P. (P.), Agartz, I. (Ingrid), Alloza, C. (C.), Andreassen, O.A. (O. A.), Arango, C. (C.), Banaj, N. (N.), Bouix, S. (S.), Bousman, C.A. (C. A.), Brouwer, R.M. (Rachel), Bruggemann, J. (J.), Bustillo, J., Cahn, W. (Wiepke), Calhoun, V.D. (Vince), Cannon, D. (D.), Carr, V.J. (Vaughan), Catts, S.V. (Stanley), Chen, J. (J.), Chen, J.-X. (J. X.), Chen, X. (X.), Chiapponi, C. (C.), Cho, K.K. (Kl K), Ciullo, V. (V.), Corvin, A. (Aiden), Crespo-Facorro, B. (Benedicto), Cropley, V. (V.), De Rossi, P. (P.), Diaz-Caneja, C.M. (C. M.), Dickie, E.W. (E. W.), Ehrlich, S.M. (Stefan), Fan, F.-M. (F. M.), Faskowitz, J. (J.), Fatouros-Bergman, H. (H.), Flyckt, L. (L.), Ford, J.M. (J. M.), Fouche, J.-P. (J. P.), Fukunaga, M. (Masaki), Gill, M. (M.), Glahn, D.C. (David), Gollub, R.L. (Randy), Goudzwaard, E.D. (E. D.), Guo, H. (H.), Gur, R.E. (Raquel), Gur, R.C. (R. C.), Gurholt, T.P. (T. P.), Hashimoto, R. (Ryota), Hatton, W., Henskens, F.A. (Frans), Hibar, D.P. (D. P.), Hickie, I.B. (Ian), Hong, L.E. (L. E.), Horacek, J. (J.), Howells, F.M. (F. M.), Hulshoff Pol, H.E. (Hilleke), Hyde, C.L. (C. L.), Isaev, D. (D.), Jablensky, A. (A.), Jansen, P.R. (P. R.), Janssen, J. (J.), Jönsson, E.G. (Erik), Jung, L.A. (L. A.), Kahn, R.S. (R. S.), Kikinis, Z. (Z.), Liu, K. (K.), Klauser, P. (P.), Knöchel, C. (C.), Kubicki, M. (M.), Lagopoulos, J. (Jim), Langen, C.D. (Carolyn), Lawrie, S. (Stephen), Lenroot, R.K. (Rhoshel), Lim, K.O. (Kelvin), Lopez-Jaramillo, C. (C.), Lyall, A. (A.), Magnotta, V., Mandl, R. (René), Mathalon, D.H. (D. H.), McCarley, R.W. (Robert), McCarthy-Jones, S. (S.), McDonald, C. (Colm), McEwen, S. (S.), McIntosh, A.M. (Andrew), Melicher, T. (T.), Mesholam-Gately, R.I. (Raquelle), Michie, P.T. (Patricia), Mowry, B.J. (Bryan J), Mueller, B.A. (Bryon ), Newell, D.T. (D. T.), O'Donnell, P. (P.), Oertel-Knöchel, V. (V.), Oestreich, L. (L.), Paciga, S.A. (S. A.), Pantelis, C. (Christos), Pasternak, O. (O.), Pearlson, G. (G.), Pellicano, G.R. (G. R.), Pereira, A. (A.), Pineda Zapata, J. (J.), Piras, F. (F.), Potkin, S.G. (Steven), Preda, A. (A.), Rasser, P.E. (P. E.), Roalf, D.R. (D. R.), Roiz, R. (R.), Roos, A. (A.), Rotenberg, D. (D.), Satterthwaite, T.D. (Theodore), Savadjiev, P. (P.), Schall, J.D. (Jeffrey), Scott, R.J. (R. J.), Seal, M.L. (M. L.), Seidman, L.J. (Larry), Shannon Weickert, C. (C.), Whelan, C.D. (Christopher), Shenton, M.E. (M. E.), Kwon, J.S. (J. S.), Spalletta, G. (Gianfranco), Spaniel, F. (F.), Sprooten, R. (Roy), Stäblein, M. (M.), Stein, D.J. (Dan), Sundram, S. (S.), Tan, Y. (Y.), Tan, S. (S.), Tang, S. (S.), Temmingh, H.S. (H. S.), Westlye, L.T. (Lars), Tønnesen, S. (S.), Tordesillas-Gutierrez, D. (Diana), Doan, N.T. (N. T.), Vaidya, J. (J.), Van Haren, N.E.M. (N. E.M.), Vargas, C.D. (C. D.), Vecchio, D. (D.), Velakoulis, D. (D.), Voineskos, A. (A.), Voyvodic, J.Q. (J. Q.), Wang, Z. (Z.), Wan, P. (P.), Wei, D. (D.), Weickert, T.W. (T. W.), Whalley, H. (H.), White, T.J.H. (Tonya), Whitford, T.J. (T. J.), Wojcik, J.D. (J. D.), Xiang, H. (H.), Xie, Z. (Z.), Yamamori, H. (H.), Yang, F. (F.), Yao, N. (N.), Zhang, G. (G.), Zhao, J. (J.), Erp, T.G.M. (Theo G.) van, Turner, J. (Jessica), Thompson, P.M. (P. M.), and Donohoe, D.J. (Dennis)

Abstract

The regional distribution of white matter (WM) abnormalities in schizophrenia remains poorly understood, and reported disease effects on the brain vary widely between studies. In an effort to identify commonalities across studies, we perform what we believe is the first ever large-scale coordinated study of WM microstructural differences in schizophrenia. Our analysis consisted of 2359 healthy controls and 1963 schizophrenia patients from 29 independent international studies; we harmonized the processing and statistical analyses of diffusion tensor imaging (DTI) data across sites and meta-analyzed effects across studies. Significant reductions in fractional anisotropy (FA) in schizophrenia patients were widespread, and detected in 20 of 25 regions of interest within a WM skeleton representing all major WM fasciculi. Effect sizes varied by region, peaking at (d=0.42) for the entire WM skeleton, driven more by peripheral areas as opposed to the core WM where regions of interest were defined. The anterior corona radiata (d=0.40) and corpus callosum (d=0.39), specifically its body (d=0.39) and genu (d=0.37), showed greatest effects. Significant decreases, to lesser degrees, were observed in almost all regions analyzed. Larger effect sizes were observed for FA than diffusivity measures; significantly higher mean and radial diffusivity was observed for schizophrenia patients compared with controls. No significant effects of age at onset of schizophrenia or medication dosage were detected. As the largest coordinated analysis of WM differences in a psychiatric disorder to date, the present study provides a robust profile of widespread WM abnormalities in schizophrenia patients worldwide. Interactive three-dimensional visualization of the results is available at www.enigma-viewer.org.

Published
2018
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29. Widespread white matter microstructural differences in schizophrenia across 4322 individuals: Results from the ENIGMA Schizophrenia DTI Working Group

Author

Onderzoeksgroep 1, Brain, Affectieve & Psychotische Med., Research Office, Onderzoek Bob Oranje, Onderzoeksgroep 11, Onderzoeksgroep 8, Onderzoeksgroep 4, Kelly, S., Jahanshad, N., Zalesky, A., Kochunov, P., Agartz, I., Alloza, C., Andreassen, O. A., Arango, C., Banaj, N., Bouix, S., Bousman, C. A., Brouwer, R. M., Bruggemann, J., Bustillo, J., Cahn, W., Calhoun, V., Cannon, D., Carr, V., Catts, S., Chen, J., Chen, J. X., Chen, X., Chiapponi, C., Cho, Kl K., Ciullo, V., Corvin, A. S., Crespo-Facorro, B., Cropley, V., De Rossi, P., Diaz-Caneja, C. M., Dickie, E. W., Ehrlich, S., Fan, F. M., Faskowitz, J., Fatouros-Bergman, H., Flyckt, L., Ford, J. M., Fouche, J. P., Fukunaga, M., Gill, M., Glahn, D. C., Gollub, R., Goudzwaard, E. D., Guo, H., Gur, R. E., Gur, R. C., Gurholt, T. P., Hashimoto, R., Hatton, S. N., Henskens, F. A., Hibar, D. P., Hickie, I. B., Hong, L. E., Horacek, J., Howells, F. M., Hulshoff Pol, H. E., Hyde, C. L., Isaev, D., Jablensky, A., Jansen, P. R., Janssen, J., Jönsson, E. G., Jung, L. A., Kahn, R. S., Kikinis, Z., Liu, K., Klauser, P., Knöchel, C., Kubicki, M., Lagopoulos, J., Langen, C., Lawrie, S., Lenroot, R. K., Lim, K. O., Lopez-Jaramillo, C., Lyall, A., Magnotta, V., Mandl, R. C.W., Mathalon, D. H., McCarley, R. W., McCarthy-Jones, S., McDonald, C., McEwen, S., McIntosh, A., Melicher, T., Mesholam-Gately, R. I., Michie, P. T., Mowry, B., Mueller, B. A., Newell, D. T., O'Donnell, P., Oertel-Knöchel, V., Oestreich, L., Paciga, S. A., Pantelis, C., Pasternak, O., Pearlson, G., Pellicano, G. R., Pereira, A., Pineda Zapata, J., Piras, F., Potkin, S. G., Preda, A., Rasser, P. E., Roalf, D. R., Roiz, R., Roos, A., Rotenberg, D., Satterthwaite, T. D., Savadjiev, P., Schall, U., Scott, R. J., Seal, M. L., Seidman, L. J., Shannon Weickert, C., Whelan, C. D., Shenton, M. E., Kwon, J. S., Spalletta, G., Spaniel, F., Sprooten, E., Stäblein, M., Stein, D. J., Sundram, S., Tan, Y., Tan, S., Tang, S., Temmingh, H. S., Westlye, L. T., Tønnesen, S., Tordesillas-Gutierrez, D., Doan, N. T., Vaidya, J., Van Haren, N. E.M., Vargas, C. D., Vecchio, D., Velakoulis, D., Voineskos, A., Voyvodic, J. Q., Wang, Z., Wan, P., Wei, D., Weickert, T. W., Whalley, H., White, T., Whitford, T. J., Wojcik, J. D., Xiang, H., Xie, Z., Yamamori, H., Yang, F., Yao, N., Zhang, G., Zhao, J., Van Erp, T. G.M., Turner, J., Thompson, P. M., Donohoe, G., Onderzoeksgroep 1, Brain, Affectieve & Psychotische Med., Research Office, Onderzoek Bob Oranje, Onderzoeksgroep 11, Onderzoeksgroep 8, Onderzoeksgroep 4, Kelly, S., Jahanshad, N., Zalesky, A., Kochunov, P., Agartz, I., Alloza, C., Andreassen, O. A., Arango, C., Banaj, N., Bouix, S., Bousman, C. A., Brouwer, R. M., Bruggemann, J., Bustillo, J., Cahn, W., Calhoun, V., Cannon, D., Carr, V., Catts, S., Chen, J., Chen, J. X., Chen, X., Chiapponi, C., Cho, Kl K., Ciullo, V., Corvin, A. S., Crespo-Facorro, B., Cropley, V., De Rossi, P., Diaz-Caneja, C. M., Dickie, E. W., Ehrlich, S., Fan, F. M., Faskowitz, J., Fatouros-Bergman, H., Flyckt, L., Ford, J. M., Fouche, J. P., Fukunaga, M., Gill, M., Glahn, D. C., Gollub, R., Goudzwaard, E. D., Guo, H., Gur, R. E., Gur, R. C., Gurholt, T. P., Hashimoto, R., Hatton, S. N., Henskens, F. A., Hibar, D. P., Hickie, I. B., Hong, L. E., Horacek, J., Howells, F. M., Hulshoff Pol, H. E., Hyde, C. L., Isaev, D., Jablensky, A., Jansen, P. R., Janssen, J., Jönsson, E. G., Jung, L. A., Kahn, R. S., Kikinis, Z., Liu, K., Klauser, P., Knöchel, C., Kubicki, M., Lagopoulos, J., Langen, C., Lawrie, S., Lenroot, R. K., Lim, K. O., Lopez-Jaramillo, C., Lyall, A., Magnotta, V., Mandl, R. C.W., Mathalon, D. H., McCarley, R. W., McCarthy-Jones, S., McDonald, C., McEwen, S., McIntosh, A., Melicher, T., Mesholam-Gately, R. I., Michie, P. T., Mowry, B., Mueller, B. A., Newell, D. T., O'Donnell, P., Oertel-Knöchel, V., Oestreich, L., Paciga, S. A., Pantelis, C., Pasternak, O., Pearlson, G., Pellicano, G. R., Pereira, A., Pineda Zapata, J., Piras, F., Potkin, S. G., Preda, A., Rasser, P. E., Roalf, D. R., Roiz, R., Roos, A., Rotenberg, D., Satterthwaite, T. D., Savadjiev, P., Schall, U., Scott, R. J., Seal, M. L., Seidman, L. J., Shannon Weickert, C., Whelan, C. D., Shenton, M. E., Kwon, J. S., Spalletta, G., Spaniel, F., Sprooten, E., Stäblein, M., Stein, D. J., Sundram, S., Tan, Y., Tan, S., Tang, S., Temmingh, H. S., Westlye, L. T., Tønnesen, S., Tordesillas-Gutierrez, D., Doan, N. T., Vaidya, J., Van Haren, N. E.M., Vargas, C. D., Vecchio, D., Velakoulis, D., Voineskos, A., Voyvodic, J. Q., Wang, Z., Wan, P., Wei, D., Weickert, T. W., Whalley, H., White, T., Whitford, T. J., Wojcik, J. D., Xiang, H., Xie, Z., Yamamori, H., Yang, F., Yao, N., Zhang, G., Zhao, J., Van Erp, T. G.M., Turner, J., Thompson, P. M., and Donohoe, G.

Published
2018

30. Brain microglia in psychiatric disorders

Author

Mondelli, Valeria, Vernon, Anthony C, Turkheimer, Federico, Dazzan, Paola, Pariante, Carmine M, Frost, JL, Schafer, DP, Banati, RB, Newcombe, J, Gunn, RN, al., et, Tang, Y, Le, W, Estes, ML, McAllister, AK, Ransohoff, RM, Davalos, D, Grutzendler, J, Yang, G, Peferoen, LA, Vogel, DY, Ummenthum, K, Norden, DM, Trojanowski, PJ, Villanueva, E, Navarro, E, Godbout, JP, Kreisel, T, Frank, MG, Licht, T, Wachholz, S, Eßlinger, M, Plümper, J, Manitz, MP, Juckel, G, Friebe, A, Trépanier, MO, Hopperton, KE, Mizrahi, R, Mechawar, N, Bazinet, RP, Torres-Platas, SG, Cruceanu, C, Chen, GG, Turecki, G, Steiner, J, Bielau, H, Brisch, R, Schnieder, TP, Trencevska, I, Rosoklija, G, Fillman, SG, Cloonan, N, Catts, VS, Rupprecht, R, Papadopoulos, V, Rammes, G, Qiu, ZK, Li, MS, He, JL, Hannestad, J, Gallezot, JD, Schafbauer, T, Israel, I, Ohsiek, A, Al-Momani, E, Mirzaei, N, Tang, SP, Ashworth, S, Gulyás, B, Makkai, B, Kása, P, Turkheimer, FE, Rizzo, G, Bloomfield, PS, Owen, DR, Yeo, AJ, DellaGioia, N, Setiawan, E, Wilson, AA, Su, L, Faluyi, YO, Hong, YT, Haarman, BC, Lek, RF Riemersma-Van der, Groot, JC de, Berckel, BN van, Bossong, MG, Boellaard, R, Doorduin, J, Vries, EF de, Willemsen, AT, Dierckx, RA, Klein, HC, Takano, A, Arakawa, R, Ito, H, Kenk, M, Selvanathan, T, Rao, N, Selvaraj, S, Veronese, M, Coughlin, JM, Wang, Y, Ambinder, EB, Doef, TF van der, Witte, LD de, Sutterland, AL, Hafizi, S, Tseng, HH, Holmes, SE, Hinz, R, Drake, RJ, Yaqub, M, Schuitemaker, A, Edison, P, Pavese, N, Lockhart, A, Davis, B, Matthews, JC, Quarantelli, M, Laule, C, Vavasour, IM, Kolind, SH, Pasternak, O, Sochen, N, Gur, Y, Intrator, N, Assaf, Y, Andreasen, NC, Ehrhardt, JC, Swayze, VW, Supprian, T, Hofmann, E, Warmuth-Metz, M, Franzek, E, Becker, T, Pfefferbaum, A, Sullivan, EV, Hedehus, M, Moseley, M, Lim, KO, Mandl, RC, Schnack, HG, Luigjes, J, Cahn, W, Bagary, MS, Symms, MR, Barker, GJ, Mutsatsa, SH, Joyce, EM, Ron, MA, Foong, J, Maier, M, Brocklehurst, S, Miller, DH, Kubicki, M, Park, H, Westin, CF, Bouix, S, Dahlben, B, Oestreich, LK, Shenton, ME, Amato, D, Beasley, CL, Hahn, MK, Vernon, AC, Natesan, S, Modo, M, Kapur, S, Mondelli, V, Reininghaus, U, Kempton, MJ, Valmaggia, L, Baumeister, D, Lightman, SL, Pariante, CM, Danese, A, Moffitt, TE, Ambler, A, Poulton, R, Caspi, A, Akhtar, R, Ciufolini, S, Meyer, U, So, PW, Lythgoe, DJ, Cotel, MC, Lenartowicz, EM, Anacker, C, Calcia, MA, Bonsall, DR, Barichello, T, Howes, OD, Burke, NN, Fan, CY, Trang, T, McMahon, SB, Russa, F La, Bennett, DL, Püntener, U, Booth, SG, Perry, VH, Teeling, JL, Hahn, YK, Podhaizer, EM, Farris, SP, Miles, MF, Hauser, KF, Knapp, PE, Notter, T, Gschwind, T, Varga, B, Markó, K, Hádinger, N, Cattaneo, A, Ferrari, C, Uher, R, Belvederi, Murri M, Sandiego, CM, Pittman, B, Weber, MD, Sheridan, JF, Raison, CL, Rutherford, RE, Woolwine, BJ, Möller, T, Boddeke, HW, O'Connor, JC, Lawson, MA, André, C, Hinwood, M, Morandini, J, Day, TA, Walker, FR, Bard, F, Bhattacharya, A, Pae, CU, Marks, DM, Han, C, Patkar, AA, Oya, K, Kishi, T, Iwata, N, Pathology, NCA - Neuroinflamation, Molecular cell biology and Immunology, Gastroenterology and hepatology, CCA - Disease profiling, ICaR - Heartfailure and pulmonary arterial hypertension, ICaR - Ischemia and repair, NCA - Brain imaging technology, Radiology and nuclear medicine, Amsterdam Neuroscience - Brain Imaging, Otolaryngology / Head & Neck Surgery, EMGO - Quality of care, AII - Infectious diseases, CCA - Imaging, and Neurology

Subjects
0301 basic medicine, medicine.medical_specialty, 03 medical and health sciences, 0302 clinical medicine, medicine, Animals, Humans, Psychology, In patient, Psychiatry, Biological Psychiatry, Neuroinflammation, Inflammation, Microglia, business.industry, Macrophages, Mental Disorders, Brain, Magnetic Resonance Imaging, Psychiatry and Mental health, 030104 developmental biology, medicine.anatomical_structure, Psychosocial stress, Treatment strategy, Autopsy, business, Neuroscience, 030217 neurology & neurosurgery, Stress, Psychological, Immune activation
Abstract

SummaryThe role of immune activation in psychiatric disorders has attracted considerable attention over the past two decades, contributing to the rise of a new era for psychiatry. Microglia, the macrophages of the brain, are progressively becoming the main focus of the research in this field. In this Review, we assess the literature on microglia activation across different psychiatric disorders, including post-mortem and in-vivo studies in humans and experimental studies in animals. Although microglia activation has been noted in all types of psychiatric disorder, no association was seen with specific diagnostic categories. Furthermore, the findings from these studies highlight that not all psychiatric patients have microglial activation. Therefore, the cause of the neuroinflammation in these cohorts and its implications are unclear. We discuss psychosocial stress as one of the main factors determining microglial activation in patients with psychiatric disorders, and explore the relevance of these findings for future treatment strategies.

Published
2016
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31. Widespread white matter microstructural differences in schizophrenia across 4322 individuals: results from the ENIGMA Schizophrenia DTI Working Group

Author

Kelly, S, primary, Jahanshad, N, additional, Zalesky, A, additional, Kochunov, P, additional, Agartz, I, additional, Alloza, C, additional, Andreassen, O A, additional, Arango, C, additional, Banaj, N, additional, Bouix, S, additional, Bousman, C A, additional, Brouwer, R M, additional, Bruggemann, J, additional, Bustillo, J, additional, Cahn, W, additional, Calhoun, V, additional, Cannon, D, additional, Carr, V, additional, Catts, S, additional, Chen, J, additional, Chen, J-x, additional, Chen, X, additional, Chiapponi, C, additional, Cho, Kl K, additional, Ciullo, V, additional, Corvin, A S, additional, Crespo-Facorro, B, additional, Cropley, V, additional, De Rossi, P, additional, Diaz-Caneja, C M, additional, Dickie, E W, additional, Ehrlich, S, additional, Fan, F-m, additional, Faskowitz, J, additional, Fatouros-Bergman, H, additional, Flyckt, L, additional, Ford, J M, additional, Fouche, J-P, additional, Fukunaga, M, additional, Gill, M, additional, Glahn, D C, additional, Gollub, R, additional, Goudzwaard, E D, additional, Guo, H, additional, Gur, R E, additional, Gur, R C, additional, Gurholt, T P, additional, Hashimoto, R, additional, Hatton, S N, additional, Henskens, F A, additional, Hibar, D P, additional, Hickie, I B, additional, Hong, L E, additional, Horacek, J, additional, Howells, F M, additional, Hulshoff Pol, H E, additional, Hyde, C L, additional, Isaev, D, additional, Jablensky, A, additional, Jansen, P R, additional, Janssen, J, additional, Jönsson, E G, additional, Jung, L A, additional, Kahn, R S, additional, Kikinis, Z, additional, Liu, K, additional, Klauser, P, additional, Knöchel, C, additional, Kubicki, M, additional, Lagopoulos, J, additional, Langen, C, additional, Lawrie, S, additional, Lenroot, R K, additional, Lim, K O, additional, Lopez-Jaramillo, C, additional, Lyall, A, additional, Magnotta, V, additional, Mandl, R C W, additional, Mathalon, D H, additional, McCarley, R W, additional, McCarthy-Jones, S, additional, McDonald, C, additional, McEwen, S, additional, McIntosh, A, additional, Melicher, T, additional, Mesholam-Gately, R I, additional, Michie, P T, additional, Mowry, B, additional, Mueller, B A, additional, Newell, D T, additional, O'Donnell, P, additional, Oertel-Knöchel, V, additional, Oestreich, L, additional, Paciga, S A, additional, Pantelis, C, additional, Pasternak, O, additional, Pearlson, G, additional, Pellicano, G R, additional, Pereira, A, additional, Pineda Zapata, J, additional, Piras, F, additional, Potkin, S G, additional, Preda, A, additional, Rasser, P E, additional, Roalf, D R, additional, Roiz, R, additional, Roos, A, additional, Rotenberg, D, additional, Satterthwaite, T D, additional, Savadjiev, P, additional, Schall, U, additional, Scott, R J, additional, Seal, M L, additional, Seidman, L J, additional, Shannon Weickert, C, additional, Whelan, C D, additional, Shenton, M E, additional, Kwon, J S, additional, Spalletta, G, additional, Spaniel, F, additional, Sprooten, E, additional, Stäblein, M, additional, Stein, D J, additional, Sundram, S, additional, Tan, Y, additional, Tan, S, additional, Tang, S, additional, Temmingh, H S, additional, Westlye, L T, additional, Tønnesen, S, additional, Tordesillas-Gutierrez, D, additional, Doan, N T, additional, Vaidya, J, additional, van Haren, N E M, additional, Vargas, C D, additional, Vecchio, D, additional, Velakoulis, D, additional, Voineskos, A, additional, Voyvodic, J Q, additional, Wang, Z, additional, Wan, P, additional, Wei, D, additional, Weickert, T W, additional, Whalley, H, additional, White, T, additional, Whitford, T J, additional, Wojcik, J D, additional, Xiang, H, additional, Xie, Z, additional, Yamamori, H, additional, Yang, F, additional, Yao, N, additional, Zhang, G, additional, Zhao, J, additional, van Erp, T G M, additional, Turner, J, additional, Thompson, P M, additional, and Donohoe, G, additional

Published
2017
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35. Reduced interhemispheric connectivity in schizophrenia-tractography based segmentation of the corpus callosum

Author

STYNER, M, KUBICKI, M, GERIG, G, MARKANT, D, SMITH, K, MCCARLEY, R, SHENTON, M, BOUIX, S, and KIKINIS, R

Subjects
nervous system, mental disorders, behavioral disciplines and activities
Abstract

A reduction in interhemispheric connectivity is thought to contribute to the etiology of schizophrenia. Diffusion Tensor Imaging (DTI) measures the diffusion of water and can be used to describe the integrity of the corpus callosum white matter tracts, thereby providing information concerning possible interhemispheric connectivity abnormalities. Previous DTI studies in schizophrenia are inconsistent in reporting decreased Fractional Anisotropy (FA), a measure of anisotropic diffusion, within different portions of the corpus callosum. Moreover, none of these studies has investigated corpus callosum systematically, using anatomical subdivisions.

Published
2008
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38. Affine Registration of label maps in Label Space

Author

Rathi, Yogesh, Malcolm, James, Bouix, Sylvain, Tannenbaum, Allen, and Shenton, Martha E

Subjects
Computer Science: Machine Vision, Machine Vision
Abstract

Two key aspects of coupled multi-object shape analysis and atlas generation are the choice of representation and subsequent registration methods used to align the sample set. For example, a typical brain image can be labeled into three structures: grey matter, white matter and cerebrospinal fluid. Many manipulations such as interpolation, transformation, smoothing, or registration need to be performed on these images before they can be used in further analysis. Current techniques for such analysis tend to trade off performance between the two tasks, performing well for one task but developing problems when used for the other. This article proposes to use a representation that is both flexible and well suited for both tasks. We propose to map object labels to vertices of a regular simplex, e.g. the unit interval for two labels, a triangle for three labels, a tetrahedron for four labels, etc. This representation, which is routinely used in fuzzy classification, is ideally suited for representing and registering multiple shapes. On closer examination, this representation reveals several desirable properties: algebraic operations may be done directly, label uncertainty is expressed as a weighted mixture of labels (probabilistic interpretation), interpolation is unbiased toward any label or the background, and registration may be performed directly. We demonstrate these properties by using label space in a gradient descent based registration scheme to obtain a probabilistic atlas. While straightforward, this iterative method is very slow, could get stuck in local minima, and depends heavily on the initial conditions. To address these issues, two fast methods are proposed which serve as coarse registration schemes following which the iterative descent method can be used to refine the results. Further, we derive an analytical formulation for direct computation of the "group mean" from the parameters of pairwise registration of all the images in the sample set. We show results on richly labeled 2D and 3D data sets.

Published
2010

40. Electrophysiological and diffusion tensor imaging evidence of delayed corollary discharges in patients with schizophrenia

Author

Whitford, T. J., primary, Mathalon, D. H., additional, Shenton, M. E., additional, Roach, B. J., additional, Bammer, R., additional, Adcock, R. A., additional, Bouix, S., additional, Kubicki, M., additional, De Siebenthal, J., additional, Rausch, A. C., additional, Schneiderman, J. S., additional, and Ford, J. M., additional

Published
2010
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