2024-02-14
077_ Identifying lipid alterations associated with psychopathological phenotypes
Research Question and Aims
The nervous system is enriched in lipids and maintains a more diverse lipid composition in comparison to other tissues1. Present research has already shown an association of altered lipidomics with psychiatric diseases, such as schizophrenia2,3,4,5. This highlights the significant clinical value to further research and identify lipid alterations associated with psychopathologic phenotypes. Self-assessment scales and external assessment scales are used in the PsyCourse study to record psychopathological data with the aim to understand mental health phenotypes on the affective‐to‐psychotic continuum as well as to make a diagnostic classification using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV).8 We will use available data from clinician- and self-rating assessments for depressive symptoms (IDS-C, BDI-II), manic symptoms (YMRS, ASMR, MSS) and psychotic symptoms (PANS, CAPE-42). In this project, we would like to examine associations of lipid alterations with deep-psychopathological phenotypes as we hypothesize that alterations of plasma lipids play a role in psychopathological phenotypes of individuals with psychiatric disorders in the PsyCourse Study. We will also assess if and if so how lipid alterations associated with psychopathological features are related to outcomes as captured by the CGI and the GAF. This will further aid in elucidating the question whether previously observed lipid alterations in individuals with severe psychiatric disorders are markers of state or trait, or both6. The primary analysis is purely cross-sectional. However, lipidomic profiles were not measured at V1 for all individuals. Accordingly, for the purpose of our analysis, we will consider the visit with the first lipidomic profile available for each individual and the corresponding deep psychopathologic phenotyping dataset from that visit as baseline for a given study participant.
Analytic Plan
We will use the plasma lipidomic data of individuals of the PsyCourse Study as well as the available deep-phenotyping information regarding psychopathology to identify associations between plasma lipids and psychopathological phenotypes. We will adjust the analyses for sex, age, diagnosis, duration of illness, age at onset, body mass index, medication use, PCAs as well as other relevant covariates in the context of repeated measures and linear mixed models. Lipid species known to be altered by fasting status according to Tkachev et al.9 will be discarded from all analyses. Lipidomic profiles from control individuals are necessary to understand which lipid alterations are associated with SCZ and/or BPD diagnosis but simply more pronounced in individuals with particular psychopathologic features and which are uniquely altered by a particular psychopathologic state. All analyses will be performed in R. LipidR7 is an open-source R/Bioconductor package for data mining and is an analysis pipeline designed specifically for lipidomic data. It will be employed, to identify lipid species as well as—through an integrated GSEA-like enrichment algorithm—classes of lipids differentially altered in group comparisons. We will be using an already existing pipeline which has also been used in other PsyCourse studies (Proposal_032 and Proposal_056). We will use the same normalized lipidomics input dataset already available from previous studies. All results will be corrected for multiple testing as appropriate. Since lipidomics data are available from different timepoints, we will select the phenotyping data that corresponds to the timepoint at which the sample was collected (V1 to V4), accordingly all relevant variables are listed below, however, we will not require all variables from all individuals.
Resources needed
v1_id
v1_stat
v1_center
v1_interv_date
v1_sex
v1_age
v1_interv_date
v1_sex
v1_age
v1_age
v1_age_1st_inpat_trm
v1_dur_illness
v1_1st_ep
v1_Antidepressants
v1_Antipsychotics
v1_Mood_stabilizers
v1_Tranquilizers
v1_Other_psychiatric
v1_fam_hist
v1_bmi
v1_scid_dsm_dx
v1_scid_dsm_dx_cat
v1_panss_p1
v1_panss_p2
v1_panss_p3
v1_panss_p4
v1_panss_p5
v1_panss_p6
v1_panss_p7
v1_panss_n1
v1_panss_n2
v1_panss_n3
v1_panss_n4
v1_panss_n5
v1_panss_n6
v1_panss_n7
v1_panss_g1
v1_panss_g2
v1_panss_g3
v1_panss_g4
v1_panss_g5
v1_panss_g6
v1_panss_g7
v1_panss_g8
v1_panss_g9
v1_panss_g10
v1_panss_g11
v1_panss_g12
v1_panss_g13
v1_panss_g14
v1_panss_g15
v1_panss_g16
v1_panss_sum_pos
v1_panss_sum_neg
v1_panss_sum_gen
v1_panss_sum_tot
v1_idsc_itm1
v1_idsc_itm2
v1_idsc_itm3
v1_idsc_itm4
v1_idsc_itm5
v1_idsc_itm6
v1_idsc_itm7
v1_idsc_itm8
v1_idsc_itm9
v1_idsc_itm9a
v1_idsc_itm9b
v1_idsc_itm10
v1_idsc_itm11
v1_idsc_itm12
v1_idsc_itm13
v1_idsc_itm14
v1_idsc_itm15
v1_idsc_itm16
v1_idsc_itm17
v1_idsc_itm18
v1_idsc_itm19
v1_idsc_itm20
v1_idsc_itm21
v1_idsc_itm22
v1_idsc_itm23
v1_idsc_itm24
v1_idsc_itm25
v1_idsc_itm26
v1_idsc_itm27
v1_idsc_itm28
v1_idsc_itm29
v1_idsc_itm30
v1_idsc_sum
v1_ymrs_itm1
v1_ymrs_itm2
v1_ymrs_itm3
v1_ymrs_itm4
v1_ymrs_itm5
v1_ymrs_itm6
v1_ymrs_itm7
v1_ymrs_itm8
v1_ymrs_itm9
v1_ymrs_itm10
v1_ymrs_itm11
v1_ymrs_sum
v1_cgi_s
v1_gaf
v1_cape_itm1A
v1_cape_itm1B
v1_cape_itm2A
v1_cape_itm2B
v1_cape_itm3A
v1_cape_itm3B
v1_cape_itm4A
v1_cape_itm4B
v1_cape_itm5A
v1_cape_itm5B
v1_cape_itm6A
v1_cape_itm6B
v1_cape_itm7A
v1_cape_itm7B
v1_cape_itm8A
v1_cape_itm8B
v1_cape_itm9A
v1_cape_itm9B
v1_cape_itm10A
v1_cape_itm10B
v1_cape_itm11A
v1_cape_itm11B
v1_cape_itm12A
v1_cape_itm12B
v1_cape_itm13A
v1_cape_itm13B
v1_cape_itm14A
v1_cape_itm14B
v1_cape_itm15A
v1_cape_itm15B
v1_cape_itm16A
v1_cape_itm16B
v1_cape_itm17A
v1_cape_itm17B
v1_cape_itm18A
v1_cape_itm18B
v1_cape_itm19A
v1_cape_itm19B
v1_cape_itm20A
v1_cape_itm20B
v1_cape_itm21A
v1_cape_itm21B
v1_cape_itm22A
v1_cape_itm22B
v1_cape_itm23A
v1_cape_itm23B
v1_cape_itm24A
v1_cape_itm24B
v1_cape_itm25A
v1_cape_itm25B
v1_cape_itm26A
v1_cape_itm26B
v1_cape_itm27A
v1_cape_itm27B
v1_cape_itm28A
v1_cape_itm28B
v1_cape_itm29A
v1_cape_itm29B
v1_cape_itm30A
v1_cape_itm30B
v1_cape_itm31A
v1_cape_itm31B
v1_cape_itm32A
v1_cape_itm32B
v1_cape_itm33A
v1_cape_itm33B
v1_cape_itm34A
v1_cape_itm34B
v1_cape_itm35A
v1_cape_itm35B
v1_cape_itm36A
v1_cape_itm36B
v1_cape_itm37A
v1_cape_itm37B
v1_cape_itm38A
v1_cape_itm38B
v1_cape_itm39A
v1_cape_itm39B
v1_cape_itm40A
v1_cape_itm40B
v1_cape_itm41A
v1_cape_itm41B
v1_cape_itm42A
v1_cape_itm42B
v1_med_pst_wk
v1_med_pst_sx_mths
v1_bdi2_itm1
v1_bdi2_itm2
v1_bdi2_itm3
v1_bdi2_itm4
v1_bdi2_itm5
v1_bdi2_itm6
v1_bdi2_itm7
v1_bdi2_itm8
v1_bdi2_itm9
v1_bdi2_itm10
v1_bdi2_itm11
v1_bdi2_itm12
v1_bdi2_itm13
v1_bdi2_itm14
v1_bdi2_itm15
v1_bdi2_itm16
v1_bdi2_itm17
v1_bdi2_itm18
v1_bdi2_itm19
v1_bdi2_itm20
v1_bdi2_itm21
v1_bdi2_sum
v1_asrm_itm1
v1_asrm_itm2
v1_asrm_itm3
v1_asrm_itm4
v1_asrm_itm5
v1_asrm_sum
v1_mss_itm1
v1_mss_itm2
v1_mss_itm3
v1_mss_itm4
v1_mss_itm5
v1_mss_itm6
v1_mss_itm7
v1_mss_itm8
v1_mss_itm9
v1_mss_itm10
v1_mss_itm11
v1_mss_itm12
v1_mss_itm13
v1_mss_itm14
v1_mss_itm15
v1_mss_itm16
v1_mss_itm17
v1_mss_itm18
v1_mss_itm19
v1_mss_itm20
v1_mss_itm21
v1_mss_itm22
v1_mss_itm23
v1_mss_itm24
v1_mss_itm25
v1_mss_itm26
v1_mss_itm27
v1_mss_itm28
v1_mss_itm29
v1_mss_itm30
v1_mss_itm31
v1_mss_itm32
v1_mss_itm33
v1_mss_itm34
v1_mss_itm35
v1_mss_itm36
v1_mss_itm37
v1_mss_itm38
v1_mss_itm39
v1_mss_itm40
v1_mss_itm41
v1_mss_itm42
v1_mss_itm43
v1_mss_itm44
v1_mss_itm45
v1_mss_itm46
v1_mss_itm47
v1_mss_itm48
v1_mss_sum
v2_age
v2_interv_date
v2_cur_psy_trm
v2_bmi
v2_Antidepressants
v2_Antipsychotics
v2_Mood_stabilizers
v2_Tranquilizers
v2_Other_psychiatric
v2_panss_p1
v2_panss_p2
v2_panss_p3
v2_panss_p4
v2_panss_p5
v2_panss_p6
v2_panss_p7
v2_panss_n1
v2_panss_n2
v2_panss_n3
v2_panss_n4
v2_panss_n5
v2_panss_n6
v2_panss_n7
v2_panss_g1
v2_panss_g2
v2_panss_g3
v2_panss_g4
v2_panss_g5
v2_panss_g6
v2_panss_g7
v2_panss_g8
v2_panss_g9
v2_panss_g10
v2_panss_g11
v2_panss_g12
v2_panss_g13
v2_panss_g14
v2_panss_g15
v2_panss_g16
v2_panss_sum_pos
v2_panss_sum_neg
v2_panss_sum_gen
v2_panss_sum_tot
v2_idsc_itm1
v2_idsc_itm2
v2_idsc_itm3
v2_idsc_itm4
v2_idsc_itm5
v2_idsc_itm6
v2_idsc_itm7
v2_idsc_itm8
v2_idsc_itm9
v2_idsc_itm9a
v2_idsc_itm9b
v2_idsc_itm10
v2_idsc_itm11
v2_idsc_itm12
v2_idsc_itm13
v2_idsc_itm14
v2_idsc_itm15
v2_idsc_itm16
v2_idsc_itm17
v2_idsc_itm18
v2_idsc_itm19
v2_idsc_itm20
v2_idsc_itm21
v2_idsc_itm22
v2_idsc_itm23
v2_idsc_itm24
v2_idsc_itm25
v2_idsc_itm26
v2_idsc_itm27
v2_idsc_itm28
v2_idsc_itm29
v2_idsc_itm30
v2_idsc_sum
v2_ymrs_itm1
v2_ymrs_itm2
v2_ymrs_itm3
v2_ymrs_itm4
v2_ymrs_itm5
v2_ymrs_itm6
v2_ymrs_itm7
v2_ymrs_itm8
v2_ymrs_itm9
v2_ymrs_itm10
v2_ymrs_itm11
v2_ymrs_sum
v2_cgi_s
v2_cgi_c
v2_gaf
v2_med_pst_wk
v2_med_pst_sx_mths
v2_bdi2_itm1
v2_bdi2_itm2
v2_bdi2_itm3
v2_bdi2_itm4
v2_bdi2_itm5
v2_bdi2_itm6
v2_bdi2_itm7
v2_bdi2_itm8
v2_bdi2_itm9
v2_bdi2_itm10
v2_bdi2_itm11
v2_bdi2_itm12
v2_bdi2_itm13
v2_bdi2_itm14
v2_bdi2_itm15
v2_bdi2_itm16
v2_bdi2_itm17
v2_bdi2_itm18
v2_bdi2_itm19
v2_bdi2_itm20
v2_bdi2_itm21
v2_bdi2_sum
v2_asrm_itm1
v2_asrm_itm2
v2_asrm_itm3
v2_asrm_itm4
v2_asrm_itm5
v2_asrm_sum
v2_mss_itm1
v2_mss_itm2
v2_mss_itm3
v2_mss_itm4
v2_mss_itm5
v2_mss_itm6
v2_mss_itm7
v2_mss_itm8
v2_mss_itm9
v2_mss_itm10
v2_mss_itm11
v2_mss_itm12
v2_mss_itm13
v2_mss_itm14
v2_mss_itm15
v2_mss_itm16
v2_mss_itm17
v2_mss_itm18
v2_mss_itm19
v2_mss_itm20
v2_mss_itm21
v2_mss_itm22
v2_mss_itm23
v2_mss_itm24
v2_mss_itm25
v2_mss_itm26
v2_mss_itm27
v2_mss_itm28
v2_mss_itm29
v2_mss_itm30
v2_mss_itm31
v2_mss_itm32
v2_mss_itm33
v2_mss_itm34
v2_mss_itm35
v2_mss_itm36
v2_mss_itm37
v2_mss_itm38
v2_mss_itm39
v2_mss_itm40
v2_mss_itm41
v2_mss_itm42
v2_mss_itm43
v2_mss_itm44
v2_mss_itm45
v2_mss_itm46
v2_mss_itm47
v2_mss_itm48
v2_mss_sum
v3_age
v3_interv_date
v3_cur_psy_trm
v3_bmi
v3_Antidepressants
v3_Antipsychotics
v3_Mood_stabilizers
v3_Tranquilizers
v3_Other_psychiatric
v3_panss_p1
v3_panss_p2
v3_panss_p3
v3_panss_p4
v3_panss_p5
v3_panss_p6
v3_panss_p7
v3_panss_n1
v3_panss_n2
v3_panss_n3
v3_panss_n4
v3_panss_n5
v3_panss_n6
v3_panss_n7
v3_panss_g1
v3_panss_g2
v3_panss_g3
v3_panss_g4
v3_panss_g5
v3_panss_g6
v3_panss_g7
v3_panss_g8
v3_panss_g9
v3_panss_g10
v3_panss_g11
v3_panss_g12
v3_panss_g13
v3_panss_g14
v3_panss_g15
v3_panss_g16
v3_panss_sum_pos
v3_panss_sum_neg
v3_panss_sum_gen
v3_panss_sum_tot
v3_idsc_itm1
v3_idsc_itm2
v3_idsc_itm3
v3_idsc_itm4
v3_idsc_itm5
v3_idsc_itm6
v3_idsc_itm7
v3_idsc_itm8
v3_idsc_itm9
v3_idsc_itm9a
v3_idsc_itm9b
v3_idsc_itm10
v3_idsc_itm11
v3_idsc_itm12
v3_idsc_itm13
v3_idsc_itm14
v3_idsc_itm15
v3_idsc_itm16
v3_idsc_itm17
v3_idsc_itm18
v3_idsc_itm19
v3_idsc_itm20
v3_idsc_itm21
v3_idsc_itm22
v3_idsc_itm23
v3_idsc_itm24
v3_idsc_itm25
v3_idsc_itm26
v3_idsc_itm27
v3_idsc_itm28
v3_idsc_itm29
v3_idsc_itm30
v3_idsc_sum
v3_ymrs_itm1
v3_ymrs_itm2
v3_ymrs_itm3
v3_ymrs_itm4
v3_ymrs_itm5
v3_ymrs_itm6
v3_ymrs_itm7
v3_ymrs_itm8
v3_ymrs_itm9
v3_ymrs_itm10
v3_ymrs_itm11
v3_ymrs_sum
v3_cgi_s
v3_cgi_c
v3_gaf
v3_med_pst_wk
v3_med_pst_sx_mths
v3_bdi2_itm1
v3_bdi2_itm2
v3_bdi2_itm3
v3_bdi2_itm4
v3_bdi2_itm5
v3_bdi2_itm6
v3_bdi2_itm7
v3_bdi2_itm8
v3_bdi2_itm9
v3_bdi2_itm10
v3_bdi2_itm11
v3_bdi2_itm12
v3_bdi2_itm13
v3_bdi2_itm14
v3_bdi2_itm15
v3_bdi2_itm16
v3_bdi2_itm17
v3_bdi2_itm18
v3_bdi2_itm19
v3_bdi2_itm20
v3_bdi2_itm21
v3_bdi2_sum
v3_asrm_itm1
v3_asrm_itm2
v3_asrm_itm3
v3_asrm_itm4
v3_asrm_itm5
v3_asrm_sum
v3_mss_itm1
v3_mss_itm2
v3_mss_itm3
v3_mss_itm4
v3_mss_itm5
v3_mss_itm6
v3_mss_itm7
v3_mss_itm8
v3_mss_itm9
v3_mss_itm10
v3_mss_itm11
v3_mss_itm12
v3_mss_itm13
v3_mss_itm14
v3_mss_itm15
v3_mss_itm16
v3_mss_itm17
v3_mss_itm18
v3_mss_itm19
v3_mss_itm20
v3_mss_itm21
v3_mss_itm22
v3_mss_itm23
v3_mss_itm24
v3_mss_itm25
v3_mss_itm26
v3_mss_itm27
v3_mss_itm28
v3_mss_itm29
v3_mss_itm30
v3_mss_itm31
v3_mss_itm32
v3_mss_itm33
v3_mss_itm34
v3_mss_itm35
v3_mss_itm36
v3_mss_itm37
v3_mss_itm38
v3_mss_itm39
v3_mss_itm40
v3_mss_itm41
v3_mss_itm42
v3_mss_itm43
v3_mss_itm44
v3_mss_itm45
v3_mss_itm46
v3_mss_itm47
v3_mss_itm48
v3_mss_sum
v4_age
v4_interv_date
v4_cur_psy_trm
v4_bmi
v4_Antidepressants
v4_Antipsychotics
v4_Mood_stabilizers
v4_Tranquilizers
v4_Other_psychiatric
v4_panss_p1
v4_panss_p2
v4_panss_p3
v4_panss_p4
v4_panss_p5
v4_panss_p6
v4_panss_p7
v4_panss_n1
v4_panss_n2
v4_panss_n3
v4_panss_n4
v4_panss_n5
v4_panss_n6
v4_panss_n7
v4_panss_g1
v4_panss_g2
v4_panss_g3
v4_panss_g4
v4_panss_g5
v4_panss_g6
v4_panss_g7
v4_panss_g8
v4_panss_g9
v4_panss_g10
v4_panss_g11
v4_panss_g12
v4_panss_g13
v4_panss_g14
v4_panss_g15
v4_panss_g16
v4_panss_sum_pos
v4_panss_sum_neg
v4_panss_sum_gen
v4_panss_sum_tot
v4_idsc_itm1
v4_idsc_itm2
v4_idsc_itm3
v4_idsc_itm4
v4_idsc_itm5
v4_idsc_itm6
v4_idsc_itm7
v4_idsc_itm8
v4_idsc_itm9
v4_idsc_itm9a
v4_idsc_itm9b
v4_idsc_itm10
v4_idsc_itm11
v4_idsc_itm12
v4_idsc_itm13
v4_idsc_itm14
v4_idsc_itm15
v4_idsc_itm16
v4_idsc_itm17
v4_idsc_itm18
v4_idsc_itm19
v4_idsc_itm20
v4_idsc_itm21
v4_idsc_itm22
v4_idsc_itm23
v4_idsc_itm24
v4_idsc_itm25
v4_idsc_itm26
v4_idsc_itm27
v4_idsc_itm28
v4_idsc_itm29
v4_idsc_itm30
v4_idsc_sum
v4_ymrs_itm1
v4_ymrs_itm2
v4_ymrs_itm3
v4_ymrs_itm4
v4_ymrs_itm5
v4_ymrs_itm6
v4_ymrs_itm7
v4_ymrs_itm8
v4_ymrs_itm9
v4_ymrs_itm10
v4_ymrs_itm11
v4_ymrs_sum
v4_cgi_s
v4_cgi_c
v4_gaf
v4_med_pst_wk
v4_med_pst_sx_mths
v4_bdi2_itm1
v4_bdi2_itm2
v4_bdi2_itm3
v4_bdi2_itm4
v4_bdi2_itm5
v4_bdi2_itm6
v4_bdi2_itm7
v4_bdi2_itm8
v4_bdi2_itm9
v4_bdi2_itm10
v4_bdi2_itm11
v4_bdi2_itm12
v4_bdi2_itm13
v4_bdi2_itm14
v4_bdi2_itm15
v4_bdi2_itm16
v4_bdi2_itm17
v4_bdi2_itm18
v4_bdi2_itm19
v4_bdi2_itm20
v4_bdi2_itm21
v4_bdi2_sum
v4_asrm_itm1
v4_asrm_itm2
v4_asrm_itm3
v4_asrm_itm4
v4_asrm_itm5
v4_asrm_sum
v4_mss_itm1
v4_mss_itm2
v4_mss_itm3
v4_mss_itm4
v4_mss_itm5
v4_mss_itm6
v4_mss_itm7
v4_mss_itm8
v4_mss_itm9
v4_mss_itm10
v4_mss_itm11
v4_mss_itm12
v4_mss_itm13
v4_mss_itm14
v4_mss_itm15
v4_mss_itm16
v4_mss_itm17
v4_mss_itm18
v4_mss_itm19
v4_mss_itm20
v4_mss_itm21
v4_mss_itm22
v4_mss_itm23
v4_mss_itm24
v4_mss_itm25
v4_mss_itm26
v4_mss_itm27
v4_mss_itm28
v4_mss_itm29
v4_mss_itm30
v4_mss_itm31
v4_mss_itm32
v4_mss_itm33
v4_mss_itm34
v4_mss_itm35
v4_mss_itm36
v4_mss_itm37
v4_mss_itm38
v4_mss_itm39
v4_mss_itm40
v4_mss_itm41
v4_mss_itm42
v4_mss_itm43
v4_mss_itm44
v4_mss_itm45
v4_mss_itm46
v4_mss_itm47
v4_mss_itm48
v4_mss_sum
v1_lip_id
v2_lip_id
v3_lip_id
v4_lip_id