A Novel Relationship for Schizophrenia, Bipolar, and Major Depressive Disorder. Part 8: a Hint from Chromosome 8 High Density Association Screen

Abstract

Familial clustering of schizophrenia (SCZ), bipolar disorder (BPD), and major depressive disorder (MDD) was systematically reported (Aukes, M. F. Genet Med 2012, 14, 338-341) and any two or even three of these disorders could co-exist in some families. In addition, evidence from symptomatology and psychopharmacology also imply that there are intrinsic connections between these three major disorders. A total of 56,569 single nucleotide polymorphism (SNPs) on chromosome 5 were genotyped by Affymetrix Genome-Wide Human SNP array 6.0 on 119 SCZ, 253 BPD (type-I), 177 MDD patients and 1000 controls. Associated SNPs and flanking genes was screen out systematically, and cadherin pathway genes (CDH6, CDH9, CDH10, CDH12, and CDH18) belong to outstanding genes. Unexpectedly, nearly all flanking genes of the associated SNPs distinctive for BPD and MDD were replicated in an enlarged cohort of 986 SCZ patients (P ≤ 9.9E-8). Considering multiple bits of evidence, our chromosome 5 analyses implicated that bipolar and major depressive disorder might be subtypes of schizophrenia rather than two independent disease entities. Also, cadherin pathway genes play important roles in the pathogenesis of the three major mental disorders.

NRG1, PIP4K2A, and HTR2C as Potential Candidate Biomarker Genes for Several Clinical Subphenotypes of Depression and Bipolar Disorder

“…Implication of NRG1 in the pathogenesis of depressive symptoms among patients with bipolar disorder is also supported by previous studies, linking this gene to bipolar disorder and depression (Mei and Nave, 2014;Dang et al, 2016;Wen et al, 2016;Chen et al, 2017).…”

“…NRG1, coding for neuregulin, is implicated in neural development, including myelination, synaptic plasticity, and neurotransmission (Mei and Nave, 2014). It is associated with schizophrenia, bipolar disorder, and depression (Mei and Nave, 2014;Dang et al, 2016;Wen et al, 2016;Chen et al, 2017).…”

Molecular linkage between post-traumatic stress disorder and cognitive impairment: a targeted proteomics study of World Trade Center responders

“… Name Description Up/ down in PTSD–MCI P value in PTSD–MCI AUC in PTSD and MCI Up/ down in PTSD only P value in PTSD only AUC in PTSD only Up/ down in MCI only P value in MCI only AUC in MCI-only Neurocan core protein (NCAN) Modulates neuronal adhesion and neurite growth, implicated BPD, SCZ 47 , and AD 49 Down <0.0001* 0.7745 Down 0.1735 0.6315 Down 0.0842 0.599 Brevican core protein (BCAN) Implicated in central nervous system, neuronal synapse plasticity, and extracellular matrix of the brain, implicated in AD 39 Down 0.0008* 0.7284 Down 0.0718 0.6306 Down 0.0083 0.7055 Cathepsin S (CTSS) Expressed by antigen-presenting cells, play a role in immune responses. Cathepsins are implicated in AD 35 , 36 , SCZ 38 , and PTSD 33 Up 0.0014* 0.6659 Up 0.0200 0.6173 Up 0.0232 0.6351 Macrophage scavenger receptor types I and II (MSR1) Implicated in macrophage-associated physiological and pathological processes, including AD 52 , MDD 53 , SCZ and BPD 54 , and PTSD 42 , 43 Up 0.0023* 0.7073 Up 0.0820 0.6277 Up 0.9440 0.5542 MAM domain-containing glycosylphosphatidylinositol anchor protein 1 (MDGA1) Needed for the radial migration of cortical neurons in the neocortex, and implicated in SCZ ...…”

Aspects of Additional Psychiatric Disorders in Severe Depression/Melancholia: A Comparison between Suicides and Controls and General Pattern

“…A review from 2013 by Domschke [ 34 ] showed several studies that shared potential risk for psychotic depression, schizoaffective disorder, schizophrenia and affective disorder. Chen et al [ 35 ] found a relationship for schizophrenia, bipolar, and MDD. O´Connell et al [ 36 ] identified a genetic association between autism spectrum disorder, schizophrenia, bipolar disorder and OCD.…”