Identification of Distinct Psychosis Biotypes Using Brain-Based Biomarkers
Abstract
Objective:
Method:
Results:
Conclusions:
Method
Subjects
Clinical Characteristic | Biotype 1 (B1) | Biotype 2 (B2) | Biotype 3 (B3) | Analysis | |||||
---|---|---|---|---|---|---|---|---|---|
% | % | % | χ2 | df | p | ||||
Proband’s DSM psychosis diagnosis | |||||||||
Schizophrenia | 58.6 | 46.0 | 31.7 | 34.54 | 2 | <0.001a | |||
Schizoaffective disorder | 21.2 | 26.8 | 24.5 | 1.80 | 2 | 0.41 | |||
Bipolar disorder | 20.2 | 27.2 | 43.9 | 33.02 | 2 | <0.001b | |||
Mean | SD | Mean | SD | Mean | SD | F | df | p | |
Schizo-Bipolar Scale score | 6.0 | 2.8 | 5.3 | 3.2 | 4.2 | 3.2 | 19.16 | 2, 687 | <0.001c |
Proband’s clinical symptom scores | |||||||||
PANSS positive subscale | 16.3 | 5.8 | 16.3 | 6.0 | 15.0 | 5.1 | 4.64 | 2, 692 | 0.01d |
PANSS negative subscale | 16.2 | 5.9 | 15.5 | 5.3 | 13.7 | 5.2 | 13.84 | 2, 692 | <0.001e |
Montgomery-Åsberg Depression Rating Scale | 9.7 | 9.5 | 11.2 | 8.9 | 10.3 | 9.5 | 1.41 | 2, 687 | 0.24 |
Young Mania Rating Scale | 5.5 | 6.1 | 6.6 | 6.7 | 5.7 | 6.0 | 1.99 | 2, 688 | 0.14 |
Birchwood Social Functioning Scale score (healthy group: mean=154.8, SD=17.8) | |||||||||
Probands | 116.8 | 23.4 | 123.0 | 24.1 | 131.3 | 25.0 | 142.41 | 3, 885 | <0.001f |
Relatives | 144.2 | 22.9 | 145.2 | 22.4 | 149.3 | 21.4 | 13.88 | 3, 979 | <0.001g |
% | % | % | χ2 | df | p | ||||
Relative’s diagnosis | |||||||||
Axis I psychosis | 14.0 | 12.3 | 9.2 | 3.53 | 2 | 0.17 | |||
Axis II: clusters A and B personality disorders | 12.3 | 12.3 | 7.8 | 4.54 | 2 | 0.10 | |||
Psychosis-related diagnosis (axis I psychosis + axis II clusters A and B)h | 25.9 | 23.8 | 16.7 | 8.39 | 2 | 0.02i |
Procedures
Laboratory Tasks
Brief Assessment of Cognition in Schizophrenia (BACS).
Pro- and anti-saccade tasks.
Stop signal task.
Auditory paired stimuli and oddball evoked brain responses.
Magnetic resonance imaging acquisition and voxel-based morphometry.
Data Analyses for Biotypes
Data integration within paradigms.
Group Separation From Healthy Subjects (N=278), in Effect Size Units | ||||||
---|---|---|---|---|---|---|
Group and Composite Variablea | Proband DSM Diagnosisb | Proband Biotype Class | ||||
A. Probands | BDP (N=226) | SzAff (N=173) | SZ (N=312) | Biotype 1 (N=198) | Biotype 2 (N=235) | Biotype 3 (N=278) |
Cognitive control | ||||||
BACS | –1.01 | –1.51 | –1.83 | –2.58 | –1.94 | –0.35 |
Stop signal task | –0.41 | –0.61 | –0.55 | –0.99 | –0.78 | –0.05 |
Antisaccade errors | 1.36 | 1.66 | 2.45 | 3.32 | 1.90 | 1.19 |
Sensorimotor reactivity | ||||||
EEG intrinsic activity | 0.07 | 0.09 | –0.01 | –0.55 | 0.68 | –0.05 |
N100 ERP | –0.47 | –0.62 | –0.67 | –1.36 | –0.11 | –0.44 |
Paired S2 ERP | –0.30 | –0.01 | 0.22 | 0.46 | –0.51 | 0.04 |
P300 ERP | –0.35 | –0.49 | –0.73 | –1.27 | –0.15 | –0.34 |
P200 ERP | –0.36 | –0.21 | –0.24 | –0.49 | 0.17 | –0.47 |
Saccade latency | –0.17 | –0.06 | –0.29 | 0.19 | –0.24 | –0.38 |
B. Relatives | BDP (N=289) | SzAff (N=231) | SZ (N=363) | Biotype 1 (N=227) | Biotype 2 (N=286) | Biotype 3 (N=370) |
Cognitive control | ||||||
BACS | –0.25 | –0.42 | –0.46 | –0.86 | –0.45 | –0.03 |
Stop signal task | –0.02 | –0.29 | –0.18 | –0.38 | –0.11 | –0.05 |
Antisaccade errors | 0.82 | 0.93 | 1.09 | 1.72 | 0.68 | 0.70 |
Sensorimotor reactivity | ||||||
EEG intrinsic activity | –0.07 | 0.27 | 0.03 | 0.08 | 0.32 | –0.06 |
N100 ERP | –0.11 | –0.31 | –0.20 | –0.34 | –0.05 | –0.25 |
Paired S2 ERP | –0.08 | –0.02 | 0.13 | 0.19 | –0.11 | 0.02 |
P300 ERP | –0.13 | –0.30 | –0.32 | –0.48 | –0.13 | –0.22 |
P200 ERP | –0.39 | –0.12 | –0.15 | –0.33 | –0.03 | –0.30 |
Saccade latency | –0.17 | –0.17 | –0.10 | –0.04 | –0.14 | –0.17 |
Variable Category | ||||||
C. Familialityc | Biomarker Composites | Discriminant Functions | ||||
Cognitive control | 0.51* | |||||
BACS | 0.40** | |||||
Stop signal task | 0.21† | |||||
Antisaccade errors | 0.32*** | |||||
Sensorimotor reactivity | 0.59* | |||||
EEG intrinsic activity | 0.47*** | |||||
N100 ERP | 0.62** | |||||
Paired S2 ERP | 0.17† | |||||
P300 ERP | 0.52** |
Cluster determination.
Biotype construction.
Results
Distinct Psychosis Biotypes Identified by Multivariate Biomarkers
Clinical Characteristics of Biotypes and Relation to DSM Diagnoses
Structural Neuroanatomical Features of Biotypes
Group Separation From Healthy Subjects, in Effect Size Units | ||||||
---|---|---|---|---|---|---|
Proband DSM Diagnosisb | Proband Biotype Class | |||||
Group and Brain Region | BDP | SzAff | SZ | Biotype 1 | Biotype 2 | Biotype 3 |
Probands | ||||||
Frontal/inferior frontal gyrus | 0.54 | 0.70 | 0.84 | 1.0 | 0.82 | 0.52 |
Cingulate gyrus | 0.43 | 0.73 | 0.68 | 0.97 | 0.66 | 0.52 |
Temporal/superior temporal gyrus | 0.55 | 0.68 | 0.76 | 0.88 | 0.80 | 0.53 |
Occipital/lingual gyrus | 0.16 | 0.64 | 0.60 | 0.73 | 0.65 | 0.38 |
Cerebellum | 0.00 | 0.62 | 0.56 | 0.72 | 0.62 | 0.34 |
Overall | 0.34 | 0.67 | 0.69 | 0.86 | 0.71 | 0.46 |
Relatives | ||||||
Frontal/inferior frontal gyrus | 0.00 | 0.00 | 0.16 | 0.43 | 0.00 | 0.16 |
Cingulate gyrus | 0.00 | 0.21 | 0.35 | 0.41 | 0.00 | 0.00 |
Temporal/superior temporal gyrus | 0.15 | 0.23 | 0.17 | 0.40 | 0.00 | 0.34 |
Occipital/lingual gyrus | 0.00 | 0.36 | 0.40 | 0.41 | 0.42 | 0.00 |
Cerebellum | 0.00 | 0.16 | 0.32 | 0.34 | 0.44 | 0.00 |
Overall | 0.03 | 0.19 | 0.28 | 0.40 | 0.17 | 0.10 |
Neurobiological and Clinical Characteristics of Biological Relatives by Biotype
Discussion
Acknowledgments
Supplementary Material
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