Decision letter for "Sex-specific association between infant caudate volumes and a polygenic risk score for major depressive disorder"

Abstract Psychiatric disease susceptibility partly originates prenatally and is shaped by an interplay of genetic and environmental risk factors. A recent study has provided preliminary evidence that an offspring polygenic risk score for major depressive disorder (PRS-MDD), based on European ancestry, interacts with prenatal maternal depressive symptoms (GxE) on neonatal right amygdalar (US and Asian cohort) and hippocampal volumes (Asian cohort). However, to date, this GxE interplay has only been addressed by one study and is yet unknown for a European ancestry sample. We investigated in 105 Finnish mother–infant dyads (44 female, 11–54 days old) how offspring PRS-MDD interacts with prenatal maternal depressive symptoms (Edinburgh Postnatal Depression Scale, gestational weeks 14, 24, 34) on infant amygdalar and hippocampal volumes. We found a GxE effect on right amygdalar volumes, significant in the main analysis, but nonsignificant after multiple comparison correction and some of the control analyses, whose direction paralleled the US cohort findings. Additional exploratory analyses suggested a sex-specific GxE effect on right hippocampal volumes. Our study is the first to provide support, though statistically weak, for an interplay of offspring PRS-MDD and prenatal maternal depressive symptoms on infant limbic brain volumes in a cohort matched to the PRS-MDD discovery sample.

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Clock gene polygenic risk score and seasonality in major depressive disorder and bipolar disorder

Genes Brain & Behavior ◽

10.1111/gbb.12683 ◽

2020 ◽

Vol 19 (8) ◽

Cited By ~ 1

Author(s):

Alex Ferrer ◽

Javier Costas ◽

Mònica Gratacos ◽

Èrika Martínez‐Amorós ◽

Javier Labad ◽

...

Keyword(s):

Bipolar Disorder ◽

Major Depressive Disorder ◽

Depressive Disorder ◽

Risk Score ◽

Clock Gene ◽

Polygenic Risk Score ◽

Major Depressive ◽

Polygenic Risk

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Stratifying major depressive disorder by polygenic risk for schizophrenia in relation to structural brain measures

Psychological Medicine ◽

10.1017/s003329171900165x ◽

2019 ◽

Vol 50 (10) ◽

pp. 1653-1662 ◽

Cited By ~ 2

Author(s):

Mathew A. Harris ◽

Xueyi Shen ◽

Simon R. Cox ◽

Jude Gibson ◽

Mark J. Adams ◽

...

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Case Control ◽

Anterior Cingulate ◽

Interactive Effects ◽

Polygenic Risk Score ◽

Major Depressive ◽

Polygenic Risk ◽

High Genetic Risk ◽

Effective Diagnosis

AbstractBackgroundSubstantial clinical heterogeneity of major depressive disorder (MDD) suggests it may group together individuals with diverse aetiologies. Identifying distinct subtypes should lead to more effective diagnosis and treatment, while providing more useful targets for further research. Genetic and clinical overlap between MDD and schizophrenia (SCZ) suggests an MDD subtype may share underlying mechanisms with SCZ.MethodsThe present study investigated whether a neurobiologically distinct subtype of MDD could be identified by SCZ polygenic risk score (PRS). We explored interactive effects between SCZ PRS and MDD case/control status on a range of cortical, subcortical and white matter metrics among 2370 male and 2574 female UK Biobank participants.ResultsThere was a significant SCZ PRS by MDD interaction for rostral anterior cingulate cortex (RACC) thickness (β = 0.191, q = 0.043). This was driven by a positive association between SCZ PRS and RACC thickness among MDD cases (β = 0.098, p = 0.026), compared to a negative association among controls (β = −0.087, p = 0.002). MDD cases with low SCZ PRS showed thinner RACC, although the opposite difference for high-SCZ-PRS cases was not significant. There were nominal interactions for other brain metrics, but none remained significant after correcting for multiple comparisons.ConclusionsOur significant results indicate that MDD case-control differences in RACC thickness vary as a function of SCZ PRS. Although this was not the case for most other brain measures assessed, our specific findings still provide some further evidence that MDD in the presence of high genetic risk for SCZ is subtly neurobiologically distinct from MDD in general.

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Investigating the source of increased bipolar and major depressive disorder polygenic risk in multiplex schizophrenia families

10.1101/2021.11.15.21266368 ◽

2021 ◽

Author(s):

Mohammad Ahangari ◽

Robert Kirkpatrick ◽

Tan-Hoang Nguyen ◽

Nathan Gillespie ◽

Irish Schizophrenia Genomics Consortium ◽

...

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Psychiatric Disorders ◽

Genetic Correlation ◽

Affective Disorders ◽

Genetic Factors ◽

Genetic Correlations ◽

Polygenic Risk Score ◽

Major Depressive ◽

Polygenic Risk

Psychotic and affective disorders often aggregate in the relatives of probands with schizophrenia (SCZ), and genetic studies show substantial genetic correlation among SCZ, bipolar disorder (BIP) and major depressive disorder (MDD). However, the nature of this genetic overlap in polygenic risk score (PRS) analyses of multiplex families has not been fully dissected. In the current study, we investigated the polygenic risk burden of BIP and MDD in a sample of 257 multiplex SCZ families (N=1,005) and population controls (N=2,205). Furthermore, due to the strong genetic correlation among SCZ, BIP, and MDD, we examined whether increased BIP or MDD PRS in members of multiplex SCZ families can be attributed to latent genetic factors unique to BIP or MDD, or latent genetic factors that each of these two disorders share with SCZ. Our results indicate that members of multiplex SCZ families have an increased PRS for BIP and MDD, however, this observation is largely attributable to latent genetic factors that BIP or MDD share with SCZ, rather than latent genetic factors unique to them. These results provide new insight for cross-disorder PRS analyses of psychiatric disorders, by cautioning that for complete interpretation of observed cross-disorder PRS enrichment, we should account for genetic correlations across psychiatric disorders. Our findings further indicates that members of multiplex SCZ families may have an increased genetic vulnerability to both psychotic and affective disorders, and for full assessment of an individual genetic risk, familial backgrounds should be taken into consideration.

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Stratifying major depressive disorder by polygenic risk for schizophrenia in relation to structural brain measures

10.1101/663724 ◽

2019 ◽

Author(s):

Mathew A. Harris ◽

Xueyi Shen ◽

Simon R. Cox ◽

Jude Gibson ◽

Mark J. Adams ◽

...

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Case Control ◽

Anterior Cingulate ◽

Interactive Effects ◽

Polygenic Risk Score ◽

Major Depressive ◽

Polygenic Risk ◽

High Genetic Risk ◽

Effective Diagnosis

AbstractBackgroundSubstantial clinical heterogeneity of major depressive disorder (MDD) suggests it may group together individuals with diverse aetiologies. Identifying distinct subtypes should lead to more effective diagnosis and treatment, while providing more useful targets for further research. Genetic and clinical overlap between MDD and schizophrenia (SCZ) suggests an MDD subtype may share underlying mechanisms with SCZ.MethodsThe present study investigated whether a neurobiologically distinct subtype of MDD could be identified by SCZ polygenic risk score (PRS). We explored interactive effects between SCZ PRS and MDD case/control status on a range of cortical, subcortical and white matter metrics among 2,370 male and 2,574 female UK Biobank participants.ResultsThere was a significant SCZ PRS by MDD interaction for rostral anterior cingulate cortex (RACC) thickness (β=.191, q=.043). This was driven by apositiveassociation between SCZ PRS and RACC thickness among MDD cases (β=.098, p=.026), compared to a negative association among controls (β=–.087, p=.002). MDD cases with low SCZ PRS showed thinner RACC, although the opposite difference for high-SCZ-PRS cases was not significant. There were nominal interactions for other brain metrics, but none remained significant after correcting for multiple comparisons.ConclusionsOur significant results indicate that MDD case-control differences in RACC thickness vary as a function of SCZ PRS. Although this was not the case for most other brain measures assessed, our specific findings still provide some further evidence that MDD in the presence of high genetic risk for SCZ is subtly neurobiologically distinct from MDD in general.

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