Whole-genome sequencing of monozygotic twins discordant for schizophrenia indicates multiple genetic risk factors for schizophrenia

Schizophrenia is a common disorder with a high heritability, but its genetic architecture is still elusive.We implemented whole-genome sequencing(WGS) analysis of 8 families with monozygotic(MZ) twin pairs discordant for schizophrenia to assess potential association of de novo mutations(DNMs) or inherited variants with susceptibility to schizophrenia. Eight non-synonymous DNMs(including one splicing site) were identified and shared by twins, which were either located in previously reported schizophrenia risk genes(p.V24689 I mutation in TTN, p.S2506 T mutation in GCN1L1, IVS3+1G > T in DOCK1) or had a benign to damaging effect according to in silico prediction analysis. By searching the inherited rare damaging or loss-of-function(LOF) variants and common susceptible alleles from three classes of schizophrenia candidate genes, we were able to distill genetic alterations in several schizophrenia risk genes, including GAD1, PLXNA2, RELN and FEZ1. Four inherited copy number variations(CNVs; including a large deletion at 16p13.11) implicated for schizophrenia were identified in four families, respectively. Most of families carried both missense DNMs and inherited risk variants, which might suggest that DNMs, inherited rare damaging variants and common risk alleles together conferred to schizophrenia susceptibility. Our results support that schizophrenia is caused by a combination of multiple genetic factors, with each DNM/variant showing a relatively small effect size.

Reduced middle cingulate gyrus volume in late-onset schizophrenia in a Chinese Han population: a voxel-based structural MRI study

Dear Editor：Numerous magnetic resonance imaging（MRI）studies have demonstrated that patients with early-onset schizophrenia（EOS）have widespread structural abnormalities in the cortical gray matter[1],suggesting that neurobiological processes play a central role in the structural abnormalities underlying the pathophysiology of schizophrenia[2].In addition,volumetric abnormalities have been used to identify individuals at risk of mental states of

Neurobiological mechanisms and related clinical treatment of addiction: a review

Drug addiction or substance use disorder(SUD),has been conceptualized as a three-stage(i.e.binge/intoxication,withdrawal/negative affect,and preoccupation/anticipation/craving)recurring cycle that involves complex changes in neuroplasticity,reward,motivation,desire,stress,memory,and cognitive control,and other related brain regions and brain circuits.Neuroimaging approaches,including magnetic resonance imaging,have been key to mapping neurobiological changes correlated to complex brain regions of SUD.In this review,we highlight the neurobiological mechanisms of these three stages of addiction.The abnormal activity of the ventral tegmental,nucleus accumbens,and caudate nucleus in the binge/intoxication stage involve the reward circuit of the midbrain limbic system.The changes in the orbitofrontal cortex,dorsolateral prefrontal cortex,amygdala,and hypothalamus emotional system in the withdrawal/negative affect stage involve increases in negative emotional states,dysphoric-like effects,and stress-like responses.The dysregulation of the insula and prefrontal lobes is associated with craving in the anticipation stage.Then,we review the present treatments of SUD based on these neuroimaging findings.Finally,we conclude that SUD is a chronically relapsing disorder with complex neurobiological mechanisms and multimodal stages,of which the craving stage with high relapse rate may be the key element in treatment efficacy of SUD.Precise interventions targeting different stages of SUD and characteristics of individuals might serve as a potential therapeutic strategy for SUD.