Manuel Mattheisen

Altered Functional Subnetwork During Emotional Face Processing: A Potential Intermediate Phenotype for Schizophrenia

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Standard

Altered Functional Subnetwork During Emotional Face Processing : A Potential Intermediate Phenotype for Schizophrenia. / Cao, Hengyi; Bertolino, Alessandro; Walter, Henrik; Schneider, Michael; Schäfer, Axel; Taurisano, Paolo; Blasi, Giuseppe; Haddad, Leila; Grimm, Oliver; Otto, Kristina; Dixson, Luanna; Erk, Susanne; Mohnke, Sebastian; Heinz, Andreas; Romanczuk-Seiferth, Nina; Mühleisen, Thomas W; Mattheisen, Manuel; Witt, Stephanie H; Cichon, Sven; Noethen, Markus; Rietschel, Marcella; Tost, Heike; Meyer-Lindenberg, Andreas.

In: JAMA Psychiatry, Vol. 73, No. 6, 01.06.2016, p. 598-605.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Cao, H, Bertolino, A, Walter, H, Schneider, M, Schäfer, A, Taurisano, P, Blasi, G, Haddad, L, Grimm, O, Otto, K, Dixson, L, Erk, S, Mohnke, S, Heinz, A, Romanczuk-Seiferth, N, Mühleisen, TW, Mattheisen, M, Witt, SH, Cichon, S, Noethen, M, Rietschel, M, Tost, H & Meyer-Lindenberg, A 2016, 'Altered Functional Subnetwork During Emotional Face Processing: A Potential Intermediate Phenotype for Schizophrenia', JAMA Psychiatry, vol. 73, no. 6, pp. 598-605. https://doi.org/10.1001/jamapsychiatry.2016.0161

APA

Cao, H., Bertolino, A., Walter, H., Schneider, M., Schäfer, A., Taurisano, P., Blasi, G., Haddad, L., Grimm, O., Otto, K., Dixson, L., Erk, S., Mohnke, S., Heinz, A., Romanczuk-Seiferth, N., Mühleisen, T. W., Mattheisen, M., Witt, S. H., Cichon, S., ... Meyer-Lindenberg, A. (2016). Altered Functional Subnetwork During Emotional Face Processing: A Potential Intermediate Phenotype for Schizophrenia. JAMA Psychiatry, 73(6), 598-605. https://doi.org/10.1001/jamapsychiatry.2016.0161

CBE

Cao H, Bertolino A, Walter H, Schneider M, Schäfer A, Taurisano P, Blasi G, Haddad L, Grimm O, Otto K, Dixson L, Erk S, Mohnke S, Heinz A, Romanczuk-Seiferth N, Mühleisen TW, Mattheisen M, Witt SH, Cichon S, Noethen M, Rietschel M, Tost H, Meyer-Lindenberg A. 2016. Altered Functional Subnetwork During Emotional Face Processing: A Potential Intermediate Phenotype for Schizophrenia. JAMA Psychiatry. 73(6):598-605. https://doi.org/10.1001/jamapsychiatry.2016.0161

MLA

Vancouver

Cao H, Bertolino A, Walter H, Schneider M, Schäfer A, Taurisano P et al. Altered Functional Subnetwork During Emotional Face Processing: A Potential Intermediate Phenotype for Schizophrenia. JAMA Psychiatry. 2016 Jun 1;73(6):598-605. https://doi.org/10.1001/jamapsychiatry.2016.0161

Author

Cao, Hengyi ; Bertolino, Alessandro ; Walter, Henrik ; Schneider, Michael ; Schäfer, Axel ; Taurisano, Paolo ; Blasi, Giuseppe ; Haddad, Leila ; Grimm, Oliver ; Otto, Kristina ; Dixson, Luanna ; Erk, Susanne ; Mohnke, Sebastian ; Heinz, Andreas ; Romanczuk-Seiferth, Nina ; Mühleisen, Thomas W ; Mattheisen, Manuel ; Witt, Stephanie H ; Cichon, Sven ; Noethen, Markus ; Rietschel, Marcella ; Tost, Heike ; Meyer-Lindenberg, Andreas. / Altered Functional Subnetwork During Emotional Face Processing : A Potential Intermediate Phenotype for Schizophrenia. In: JAMA Psychiatry. 2016 ; Vol. 73, No. 6. pp. 598-605.

Bibtex

@article{1dcfc14405f145c2a3e8ef220ee8247b,
title = "Altered Functional Subnetwork During Emotional Face Processing: A Potential Intermediate Phenotype for Schizophrenia",
abstract = "IMPORTANCE: Although deficits in emotional processing are prominent in schizophrenia, it has been difficult to identify neural mechanisms related to the genetic risk for this highly heritable illness. Prior studies have not found consistent regional activation or connectivity alterations in first-degree relatives compared with healthy controls, suggesting that a more comprehensive search for connectomic biomarkers is warranted.OBJECTIVES: To identify a potential systems-level intermediate phenotype linked to emotion processing in schizophrenia and to examine the psychological association, task specificity, test-retest reliability, and clinical validity of the identified phenotype.DESIGN, SETTING, AND PARTICIPATIONS: The study was performed in university research hospitals from June 1, 2008, through December 31, 2013. We examined 58 unaffected first-degree relatives of patients with schizophrenia and 94 healthy controls with an emotional face-matching functional magnetic resonance imaging paradigm. Test-retest reliability was analyzed with an independent sample of 26 healthy participants. A clinical association study was performed in 31 patients with schizophrenia and 45 healthy controls. Data analysis was performed from January 1 to September 30, 2014.MAIN OUTCOMES AND MEASURES: Conventional amygdala activity and seeded connectivity measures, graph-based global and local network connectivity measures, Spearman rank correlation, intraclass correlation, and gray matter volumes.RESULTS: Among the 152 volunteers included in the relative-control sample, 58 were unaffected first-degree relatives of patients with schizophrenia (mean [SD] age, 33.29 [12.56]; 38 were women), and 94 were healthy controls without a first-degree relative with mental illness (mean [SD] age, 32.69 [10.09] years; 55 were women). A graph-theoretical connectivity approach identified significantly decreased connectivity in a subnetwork that primarily included the limbic cortex, visual cortex, and subcortex during emotional face processing (cluster-level P corrected for familywise error = .006) in relatives compared with controls. The connectivity of the same subnetwork was significantly decreased in patients with schizophrenia (F = 6.29, P = .01). Furthermore, we found that this subnetwork connectivity measure was negatively correlated with trait anxiety scores (P = .04), test-retest reliable (intraclass correlation coefficient = 0.57), specific to emotional face processing (F = 17.97, P < .001), and independent of gray matter volumes of the identified brain areas (F = 1.84, P = .18). Replicating previous results, no significant group differences were found in face-related amygdala activation and amygdala-anterior cingulate cortex connectivity (P corrected for familywise error =.37 and .11, respectively).CONCLUSIONS AND RELEVANCE: Our results indicate that altered connectivity in a visual-limbic subnetwork during emotional face processing may be a functional connectomic intermediate phenotype for schizophrenia. The phenotype is reliable, task specific, related to trait anxiety, and associated with manifest illness. These data encourage the further investigation of this phenotype in clinical and pharmacologic studies.",
keywords = "Journal Article",
author = "Hengyi Cao and Alessandro Bertolino and Henrik Walter and Michael Schneider and Axel Sch{\"a}fer and Paolo Taurisano and Giuseppe Blasi and Leila Haddad and Oliver Grimm and Kristina Otto and Luanna Dixson and Susanne Erk and Sebastian Mohnke and Andreas Heinz and Nina Romanczuk-Seiferth and M{\"u}hleisen, {Thomas W} and Manuel Mattheisen and Witt, {Stephanie H} and Sven Cichon and Markus Noethen and Marcella Rietschel and Heike Tost and Andreas Meyer-Lindenberg",
year = "2016",
month = jun,
day = "1",
doi = "10.1001/jamapsychiatry.2016.0161",
language = "English",
volume = "73",
pages = "598--605",
journal = "J A M A Psychiatry",
issn = "0003-990X",
publisher = "The JAMA Network",
number = "6",

}

RIS

TY - JOUR

T1 - Altered Functional Subnetwork During Emotional Face Processing

T2 - A Potential Intermediate Phenotype for Schizophrenia

AU - Cao, Hengyi

AU - Bertolino, Alessandro

AU - Walter, Henrik

AU - Schneider, Michael

AU - Schäfer, Axel

AU - Taurisano, Paolo

AU - Blasi, Giuseppe

AU - Haddad, Leila

AU - Grimm, Oliver

AU - Otto, Kristina

AU - Dixson, Luanna

AU - Erk, Susanne

AU - Mohnke, Sebastian

AU - Heinz, Andreas

AU - Romanczuk-Seiferth, Nina

AU - Mühleisen, Thomas W

AU - Mattheisen, Manuel

AU - Witt, Stephanie H

AU - Cichon, Sven

AU - Noethen, Markus

AU - Rietschel, Marcella

AU - Tost, Heike

AU - Meyer-Lindenberg, Andreas

PY - 2016/6/1

Y1 - 2016/6/1

N2 - IMPORTANCE: Although deficits in emotional processing are prominent in schizophrenia, it has been difficult to identify neural mechanisms related to the genetic risk for this highly heritable illness. Prior studies have not found consistent regional activation or connectivity alterations in first-degree relatives compared with healthy controls, suggesting that a more comprehensive search for connectomic biomarkers is warranted.OBJECTIVES: To identify a potential systems-level intermediate phenotype linked to emotion processing in schizophrenia and to examine the psychological association, task specificity, test-retest reliability, and clinical validity of the identified phenotype.DESIGN, SETTING, AND PARTICIPATIONS: The study was performed in university research hospitals from June 1, 2008, through December 31, 2013. We examined 58 unaffected first-degree relatives of patients with schizophrenia and 94 healthy controls with an emotional face-matching functional magnetic resonance imaging paradigm. Test-retest reliability was analyzed with an independent sample of 26 healthy participants. A clinical association study was performed in 31 patients with schizophrenia and 45 healthy controls. Data analysis was performed from January 1 to September 30, 2014.MAIN OUTCOMES AND MEASURES: Conventional amygdala activity and seeded connectivity measures, graph-based global and local network connectivity measures, Spearman rank correlation, intraclass correlation, and gray matter volumes.RESULTS: Among the 152 volunteers included in the relative-control sample, 58 were unaffected first-degree relatives of patients with schizophrenia (mean [SD] age, 33.29 [12.56]; 38 were women), and 94 were healthy controls without a first-degree relative with mental illness (mean [SD] age, 32.69 [10.09] years; 55 were women). A graph-theoretical connectivity approach identified significantly decreased connectivity in a subnetwork that primarily included the limbic cortex, visual cortex, and subcortex during emotional face processing (cluster-level P corrected for familywise error = .006) in relatives compared with controls. The connectivity of the same subnetwork was significantly decreased in patients with schizophrenia (F = 6.29, P = .01). Furthermore, we found that this subnetwork connectivity measure was negatively correlated with trait anxiety scores (P = .04), test-retest reliable (intraclass correlation coefficient = 0.57), specific to emotional face processing (F = 17.97, P < .001), and independent of gray matter volumes of the identified brain areas (F = 1.84, P = .18). Replicating previous results, no significant group differences were found in face-related amygdala activation and amygdala-anterior cingulate cortex connectivity (P corrected for familywise error =.37 and .11, respectively).CONCLUSIONS AND RELEVANCE: Our results indicate that altered connectivity in a visual-limbic subnetwork during emotional face processing may be a functional connectomic intermediate phenotype for schizophrenia. The phenotype is reliable, task specific, related to trait anxiety, and associated with manifest illness. These data encourage the further investigation of this phenotype in clinical and pharmacologic studies.

AB - IMPORTANCE: Although deficits in emotional processing are prominent in schizophrenia, it has been difficult to identify neural mechanisms related to the genetic risk for this highly heritable illness. Prior studies have not found consistent regional activation or connectivity alterations in first-degree relatives compared with healthy controls, suggesting that a more comprehensive search for connectomic biomarkers is warranted.OBJECTIVES: To identify a potential systems-level intermediate phenotype linked to emotion processing in schizophrenia and to examine the psychological association, task specificity, test-retest reliability, and clinical validity of the identified phenotype.DESIGN, SETTING, AND PARTICIPATIONS: The study was performed in university research hospitals from June 1, 2008, through December 31, 2013. We examined 58 unaffected first-degree relatives of patients with schizophrenia and 94 healthy controls with an emotional face-matching functional magnetic resonance imaging paradigm. Test-retest reliability was analyzed with an independent sample of 26 healthy participants. A clinical association study was performed in 31 patients with schizophrenia and 45 healthy controls. Data analysis was performed from January 1 to September 30, 2014.MAIN OUTCOMES AND MEASURES: Conventional amygdala activity and seeded connectivity measures, graph-based global and local network connectivity measures, Spearman rank correlation, intraclass correlation, and gray matter volumes.RESULTS: Among the 152 volunteers included in the relative-control sample, 58 were unaffected first-degree relatives of patients with schizophrenia (mean [SD] age, 33.29 [12.56]; 38 were women), and 94 were healthy controls without a first-degree relative with mental illness (mean [SD] age, 32.69 [10.09] years; 55 were women). A graph-theoretical connectivity approach identified significantly decreased connectivity in a subnetwork that primarily included the limbic cortex, visual cortex, and subcortex during emotional face processing (cluster-level P corrected for familywise error = .006) in relatives compared with controls. The connectivity of the same subnetwork was significantly decreased in patients with schizophrenia (F = 6.29, P = .01). Furthermore, we found that this subnetwork connectivity measure was negatively correlated with trait anxiety scores (P = .04), test-retest reliable (intraclass correlation coefficient = 0.57), specific to emotional face processing (F = 17.97, P < .001), and independent of gray matter volumes of the identified brain areas (F = 1.84, P = .18). Replicating previous results, no significant group differences were found in face-related amygdala activation and amygdala-anterior cingulate cortex connectivity (P corrected for familywise error =.37 and .11, respectively).CONCLUSIONS AND RELEVANCE: Our results indicate that altered connectivity in a visual-limbic subnetwork during emotional face processing may be a functional connectomic intermediate phenotype for schizophrenia. The phenotype is reliable, task specific, related to trait anxiety, and associated with manifest illness. These data encourage the further investigation of this phenotype in clinical and pharmacologic studies.

KW - Journal Article

U2 - 10.1001/jamapsychiatry.2016.0161

DO - 10.1001/jamapsychiatry.2016.0161

M3 - Journal article

C2 - 27145286

VL - 73

SP - 598

EP - 605

JO - J A M A Psychiatry

JF - J A M A Psychiatry

SN - 0003-990X

IS - 6

ER -