SUPPLEMENTAL: Functional connectomics of affective and psychotic pathology

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SUPPLEMENTAL: Functional connectomics of affective and psychotic pathology Justin T. Baker a,b*, Daniel G. Dillon b,c, Lauren M. Patrick d, Joshua L. Roffman b,e,f, Roscoe O. Brady, Jr. a,b,g, Diego A. Pizzagalli b,c, Dost Öngür a,b, Avram J. Holmes c,d,h* a Schizophrenia and Program, McLean Hospital, Belmont, MA 02478 b Department of Psychiatry, Harvard Medical School, Boston, MA 02114 c Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, MA 02478 d Department of Psychology, Yale University, New Haven, CT 06520 e Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital Charlestown, MA 02129 f Department of Psychiatry, Massachusetts General Hospital, Boston, MA 02114 g Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA 02114 h Department of Psychiatry, Yale University, New Haven, CT 06520 *Correspondence and requests for materials should be addressed to A.J.H. (email: avram.holmes@yale.edu) or to J.T.B. (email: jtbaker@partners.org) www.pnas.org/cgi/doi/10.1073/pnas.1820780116

Supplemental Figure 1. Disruptions in frontoparietal network connectivity are evident across scanner and site of acquisition. Bar graphs reflect mean network connectivity for each group. Error bars denote standard error. Functional connectivity difference matrices were obtained by an analysis of variance of z-transformed Pearson correlation values, accounting for the effects of the coil, console software version, age, sex, race, ethnicity, and handedness.

Supplemental Figure 2. Psychotic illness associates with a preferential reduction in default network integrity across scanner and site of acquisition. Bar graphs reflect mean network connectivity for each group within default A, B, C, and D. Error bars denote standard error. Functional connectivity difference matrices were obtained by an analysis of variance of z- transformed Pearson correlation values after linear regression of the effects of coil, console software version, age, sex, race, ethnicity, and handedness.

Supplemental Table 1. Participant demographics Healthy Comparison Non- Treatment Seeking Depression Treatment Seeking Depression (w/o psychosis) (psychosis) Scz Group1 Scz Group 2 Healthy Comparison vs NTSD TSD BD w/o BD w/ Network n=608 n=109 n=57 n=26 n=73 n=97 n=40 F6,1003 /c 2 p-value p-values Age 33.6±13.5 30.1±10.9 35.0±13.7 38.7±15.3 31.3±11.4 33.3±12.0 44.8±10.6 1248.6 <0.001 **** Age range 18-71 18-64 18-68 20-71 18-63 18-65 20-62 Percent female Percent right handed Percent White (not Hispanic or Latino) 44.9 66.1 57.9 53.8 35.6 32.0 22.5 41.5 <0.001 **** * *** 91.4 100.0 89.5 92.3 84.9 84.5 80.0 30.3 <0.005 ** * *** 65.1 65.2 80.4 69.2 75.3 70.1 67.5 4.5 0.62 YMRS N/A N/A PANSS positive PANSS negative PANSS general Average CPZ Equivalent N/A N/A n=54 4.46±3.96 n=53 8.89±2.38 n=24 5.71±3.78 n=24 9.08±2.23 n=73 21.70±11.15 n=73 19.33±7.44 n=92 14.26±8.89 n=92 18.77±6.53 N/A 49.88 <0.001 N/A N/A N/A N/A N/A N/A n=37 18.11±5.99 39.46 <0.001 N/A N/A N/A N/A N/A N/A N/A N/A 14.53±4.66 12.38±3.45 10.64±4.49 15.89±8.03 21.49±5.12 22.44 <0.001 N/A N/A N/A N/A N/A N/A N/A N/A 36.17±6.07 35.21±6.55 29.78±7.43 33.17±9.04 36.84±6.25 8.16 <0.001 N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A n=73 n=92 380.65±277.69 408.22±361.55 N/A 0.29 0.59 N/A N/A N/A N/A N/A N/A Slice SNR 175.3±51.2 196.1±67.3 195.6±53.3 177.6±40.4 140.7±65.4 166.2±66.2 144.3±67.0 10.7 <0.001 ** **** * Number of micromovements 20.3±24.7 15.1±20.4 24.5±23.1 24.8±17.4 35.1±31.8 25.9±26.6 37.9±35.6 8.4 <0.001 **** **** *Note: NTSD: community non-treatment seeking depression; TSD: unipolar treatment seeking depression; BD w/o: bipolar disorder without psychosis; BD w/: bipolar disorder with psychosis; : schizophrenia group 1; : schizophrenia group 2. N/A: Not availablemicro-movements reflect the number of relative translations in 3D space 0.1 mm. P-values for group comparisons * 0.05 ** 0.01 *** 0.005 **** 0.001

Supplemental Table 1 Cont. Participant demographics Non-Treatment Seeking Depression vs Treatment Seeking Depression vs (w/o psychosis) vs (psychosis) vs Scz Group1 vs Scz Group2 TSD BD w/o BD w/ BD w/o BD w/ BD w/ Network p-values p-values p-values p-values p-values Age * **** *** **** **** Age range Percent female **** **** **** * *** **** * ** Percent right handed *** *** **** **** **** Percent White (not Hispanic or Latino) YMRS N/A N/A N/A N/A N/A **** **** N/A **** **** N/A **** N/A N/A PANSS positive N/A N/A N/A N/A N/A **** **** **** **** **** **** PANSS negative N/A N/A N/A N/A N/A **** **** ** **** **** **** **** PANSS general N/A N/A N/A N/A N/A **** * *** *** **** * Average CPZ Equivalent N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A Slice SNR **** *** **** **** * **** * * Number of micro-movements **** * **** *Note: NTSD: community non-treatment seeking depression; TSD: unipolar treatment seeking depression; BD w/o: bipolar disorder without psychosis; BD w/: bipolar disorder with psychosis; : schizophrenia group 1; : schizophrenia group 2. P-values for group comparisons * 0.05 ** 0.01 *** 0.005 **** 0.001 2

Supplemental Table 2. Network interactions affected by psychiatric illnesses with or without psychosis Healthy Comparison Patients without psychosis Patients with psychosis HC vs Pw/o HC vs PP Network n=608 n=192 n=210 F 2,1001 μ 2 p-value p-values PP vs Pw/o Default D 0.38±0.22 0.41±0.24 0.35±0.21 2.66 0.01 0.07 0.06 0.33 0.05 Default C 0.46±0.19 0.46±0.17 0.40±0.16 8.84 0.02 0.001 0.84 0.001 0.005 Default B 0.60±0.23 0.60±0.25 0.45±0.28 23.72 0.05 0.001 0.55 0.001 0.001 Default A 0.46±0.15 0.46±0.16 0.40±0.18 6.41 0.01 0.005 0.93 0.001 0.01 Control C 0.66±0.22 0.64±0.24 0.55±0.19 14.42 0.03 0.001 0.14 0.001 0.005 Control B 0.58±0.16 0.56±0.16 0.42±0.18 63.95 0.11 0.001 0.01 0.001 0.001 Control A 0.33±0.11 0.31±0.11 0.26±0.11 25.65 0.05 0.001 0.06 0.001 0.001 Limbic 0.38±0.26 0.33±0.28 0.31±0.27 6.52 0.01 0.005 0.08 0.001 0.21 Salience 0.45±0.13 0.45±0.13 0.38±0.14 20.39 0.04 0.001 0.18 0.001 0.001 Ventral attention 0.46±0.14 0.46±0.15 0.40±0.16 9.86 0.02 0.001 0.48 0.001 0.005 Dorsal attention B 0.48±0.17 0.50±0.17 0.45±0.19 3.01 0.01 0.05 0.35 0.05 0.05 Dorsal attention A 0.68±0.23 0.71±0.22 0.63±0.27 4.54 0.01 0.05 0.24 0.05 0.005 Somatomotor B 0.67±0.17 0.65±0.18 0.62±0.17 6.88 0.01 0.001 0.09 0.001 0.16 Somatomotor A 0.61±0.25 0.58±0.26 0.44±0.26 26.58 0.05 0.001 0.05 0.001 0.001 Visual peripheral 1.05±0.25 1.08±0.26 0.99±0.24 2.68 0.01 0.07 0.53 0.05 0.05 Visual central 0.72±0.31 0.80±0.32 0.84±0.27 14.83 0.03 0.001 0.01 0.001 0.08 *Note: Values reflect mean of raw z-transformed Pearson correlation values ± standard deviation across all regional interactions for that network; HC: healthy comparison participants; Pw/o: patients without psychosis; PP: patients with psychosis.

Supplemental Table 3. Network interactions affected by psychiatric illnesses with or without psychosis Healthy Comparison Non- Treatment Seeking Depression Treatment Seeking Depression (w/o psychosis) (psychosis) Scz Group1 Scz Group 2 Healthy Comparison vs NTSD TSD BD w/o BD w/ Network n=608 n=109 n=57 n=26 n=73 n=97 n=40 F 6,997 μ 2 p- value p-values Default D 0.38±0.22 0.44±0.27 0.37±0.20 0.37±0.20 0.31±0.20 0.41±0.22 0.29±0.17 3.67 0.02 0.001 *** ** Default C 0.46±0.19 0.48±0.18 0.45±0.15 0.38±0.14 0.38±0.14 0.42±0.17 0.36±0.14 4.98 0.03 0.001 * **** * * Default B 0.60±0.23 0.63±0.25 0.59±0.25 0.49±0.22 0.44±0.26 0.51±0.28 0.35±0.30 9.47 0.05 0.001 **** **** **** Default A 0.46±0.15 0.48±0.16 0.46±0.14 0.40±0.16 0.41±0.17 0.43±0.19 0.34±0.16 3.45 0.02 0.005 ** **** Control C 0.66±0.22 0.68±0.25 0.60±0.22 0.55±0.21 0.57±0.20 0.55±0.19 0.54±0.17 5.79 0.03 0.001 **** **** * Control B 0.58±0.16 0.61±0.16 0.51±0.14 0.44±0.16 0.42±0.18 0.46±0.18 0.35±0.16 25.20 0.13 0.001 *** **** **** **** **** Control A 0.33±0.11 0.34±0.11 0.29±0.10 0.25±0.08 0.28±0.11 0.28±0.11 0.20±0.08 12.71 0.07 0.001 * **** **** **** **** Limbic 0.38±0.26 0.36±0.28 0.27±0.28 0.29±0.24 0.30±0.25 0.35±0.27 0.26±0.28 3.63 0.02 0.001 ** *** * Salience 0.45±0.13 0.46±0.12 0.44±0.12 0.39±0.14 0.38±0.14 0.40±0.14 0.34±0.15 7.52 0.04 0.001 **** **** **** Ventral attention 0.46±0.14 0.48±0.16 0.46±0.14 0.41±0.14 0.42±0.15 0.41±0.17 0.33±0.14 4.09 0.02 0.001 * ** **** Dorsal attention B 0.48±0.17 0.52±0.18 0.48±0.15 0.45±0.18 0.45±0.16 0.48±0.21 0.35±0.15 2.81 0.02 0.01 **** Dorsal attention A 0.68±0.23 0.72±0.23 0.73±0.20 0.64±0.17 0.64±0.26 0.68±0.26 0.46±0.23 4.15 0.02 0.001 **** Somatomotor B 0.67±0.17 0.68±0.20 0.64±0.15 0.59±0.17 0.68±0.18 0.59±0.16 0.55±0.14 4.95 0.03 0.001 **** **** Somatomotor A 0.61±0.25 0.64±0.27 0.53±0.21 0.44±0.25 0.50±0.25 0.45±0.25 0.32±0.25 10.94 0.06 0.001 *** **** **** **** Visual peripheral 1.05±0.25 1.10±0.30 1.07±0.20 0.99±0.25 0.99±0.24 1.03±0.24 0.89±0.21 1.77 0.01 0.10 * * Visual central 0.72±0.31 0.76±0.34 0.83±0.29 0.87±0.26 0.85±0.21 0.84±0.32 0.81±0.21 5.65 0.03 0.001 * * **** **** * *Note: Values reflect mean of raw z-transformed Pearson correlation values ± standard deviation across all regional interactions for that network. NTSD: community non-treatment seeking depression; TSD: unipolar treatment seeking depression; BD w/o: bipolar disorder without psychosis; BD w/: bipolar disorder with psychosis; : schizophrenia group 1; : schizophrenia group 2. P-values for group comparisons * 0.05 ** 0.01 *** 0.005 **** 0.001

Supplemental Table 3 Cont. Network interactions affected by psychiatric illnesses with or without psychosis Non-Treatment Seeking Depression vs Treatment Seeking Depression vs (w/o psychosis) vs (psychosis) vs Scz Group1 vs Scz Group2 TSD Bw/o B S1 S2 Bw/o B S1 S2 B S1 S2 S1 S2 Network p-values p-values p-values p-values p-values Default D * **** *** **** * Default C *** **** ** *** * Default B **** * **** *** * **** * * Default A ** **** * * Control C * *** **** * Control B * **** **** **** **** **** * **** * * Control A ** **** **** **** **** **** * *** Limbic * * * Salience **** * * **** * * Ventral attention ** * * * Dorsal attention B * **** ** *** Dorsal attention A **** **** * * **** Somatomotor B * * **** **** Somatomotor A * **** **** * **** *** * Visual peripheral * * * * Visual central * * *Note: CD: community depression; UD: unipolar depression; Bw/o: bipolar depression without psychosis; B: bipolar depression with psychosis; S1: schizophrenia group 1; S2: schizophrenia group 2. P-values for group comparisons * 0.05 ** 0.01 *** 0.005 **** 0.001 2

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