Genetic overlap between schizophrenia and bipolar disorder: A study with AKT1 gene variants and clinical phenotypes

Karege, Félicien; Méary, Alexandre; Perroud, Nader; Jamain, Stéphane; Leboyer, Marion; Ballmann, Eladia; Fernandez, Raphael; Malafosse, Alain; Schürhoff, Franck

doi:10.1016/j.schres.2011.12.015

Cited by 36 publications

(26 citation statements)

References 40 publications

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“…Moreover, a positive correlation between AKT1 gene expression after lithium treatment and an improvement of depressive symptoms has been reported in BD patients (Machado-Vieira et al, 2015). Of note, previous findings have also linked BD with genetic variants of the AKT1 gene (Karege et al, 2012), and AKT1 expression levels have been shown to be increased in BD patients compared to controls (Gouvea et al, 2016). Interesting, our results show that lithium decreased AKT1 expression in cells from patients, suggesting the possible effect of lithium on this gene expression.…”

Section: Discussionmentioning

confidence: 86%

Distinct lithium-induced gene expression effects in lymphoblastoid cell lines from patients with bipolar disorder

Fries

Colpo

Monroy-Jaramillo

et al. 2017

European Neuropsychopharmacology

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Lithium is the most commonly prescribed medication for the treatment of bipolar disorder (BD), yet the mechanisms underlying its beneficial effects are still unclear. We aimed to compare the effects of lithium treatment in lymphoblastoid cell lines (LCLs) from BD patients and controls. LCLs were generated from sixty-two BD patients (based on DSM-IV) and seventeen healthy controls matched for age, sex, and ethnicity. Patients were recruited from outpatient clinics from February 2012 to October 2014. LCLs were treated with 1 mM lithium for 7 days followed by microarray gene expression assay and validation by real-time quantitative PCR. Baseline differences between groups, as well as differences between vehicle- and lithium-treated cells within each group were analyzed. The biological significance of differentially expressed genes was examined by pathway enrichment analysis. No significant differences in baseline gene expression (adjusted p-value < 0.05) were detected between groups. Lithium treatment of LCLs from controls did not lead to any significant differences. However, lithium altered the expression of 236 genes in LCLs from patients; those genes were enriched for signaling pathways related to apoptosis. Among those genes, the alterations in the expression of PIK3CG, SERP1 and UPP1 were validated by real-time PCR. A significant correlation was also found between circadian functioning and CEBPG and FGF2 expression levels. In summary, our results suggest that lithium treatment induces expression changes in genes associated with the apoptosis pathway in BD LCLs. The more pronounced effects of lithium in patients compared to controls suggest a disease-specific effect of this drug.

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Section: Discussionmentioning

confidence: 86%

Distinct lithium-induced gene expression effects in lymphoblastoid cell lines from patients with bipolar disorder

Fries

Colpo

Monroy-Jaramillo

et al. 2017

European Neuropsychopharmacology

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“…Dysregulation in Akt signaling and altered Akt protein levels were found in the frontal cortex and hippocampus of post-mortem brain samples from individuals affected by schizophrenia [218]. Since the first report by Emamian et al (2004) [218], numerous subsequent studies further confirmed the genetic association of AKT1 gene variants with schizophrenia, supporting the key role of impaired Akt–mTOR signaling in the pathogenesis of this psychiatric disorder [219,220,221,222,223,224]. In line with this, increased AKT1 gene expression, due to increased hypomethylation of AKT1 gene promoter, was detected in human METH abusers [225].…”

Section: Mtor Modulation Of Dopamine Transmission In Methamphetamimentioning

confidence: 99%

mTOR-Related Brain Dysfunctions in Neuropsychiatric Disorders

Ryskalin

Limanaqi

Frati

et al. 2018

IJMS

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The mammalian target of rapamycin (mTOR) is an ubiquitously expressed serine-threonine kinase, which senses and integrates several intracellular and environmental cues to orchestrate major processes such as cell growth and metabolism. Altered mTOR signalling is associated with brain malformation and neurological disorders. Emerging evidence indicates that even subtle defects in the mTOR pathway may produce severe effects, which are evident as neurological and psychiatric disorders. On the other hand, administration of mTOR inhibitors may be beneficial for a variety of neuropsychiatric alterations encompassing neurodegeneration, brain tumors, brain ischemia, epilepsy, autism, mood disorders, drugs of abuse, and schizophrenia. mTOR has been widely implicated in synaptic plasticity and autophagy activation. This review addresses the role of mTOR-dependent autophagy dysfunction in a variety of neuropsychiatric disorders, to focus mainly on psychiatric syndromes including schizophrenia and drug addiction. For instance, amphetamines-induced addiction fairly overlaps with some neuropsychiatric disorders including neurodegeneration and schizophrenia. For this reason, in the present review, a special emphasis is placed on the role of mTOR on methamphetamine-induced brain alterations.

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“…a Data on genetics show only some common genes as examples of genetic overlapping between schizophrenia and bipolar disorder. [79][80][81][82] and childhood-and adolescent-onset schizophrenia. 35,40 Early-onset cases of schizophrenia seem to have a worse premorbid adjustment compared with adult-onset cases.…”

mentioning

confidence: 99%

Differential Neurodevelopmental Trajectories in Patients With Early-Onset Bipolar and Schizophrenia Disorders

Arango¹,

Fraguas

Parellada

2013

Schizophrenia Bulletin

103

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Schizophrenia and bipolar disorders share not only clinical features but also some risk factors such as genetic markers and childhood adversity, while other risk factors such as urbanicity and obstetric complications seem to be specific to schizophrenia. An intriguing question is whether the wellestablished abnormal neurodevelopment present in many children and adolescents who eventually develop schizophrenia is also present in bipolar patients. The literature on adult bipolar patients is controversial. We report data on a subgroup of patients with pediatric-onset psychotic bipolar disorder who seem to share some developmental trajectories with patients with early-onset schizophrenia. These earlyonset psychotic bipolar patients have low intelligence quotient, more neurological signs, reduced frontal gray matter at the time of their first psychotic episode, and greater brain changes than healthy controls in a pattern similar to earlyonset schizophrenia cases. However, patients with earlyonset schizophrenia seem to have more social impairment, developmental abnormalities (eg, language problems), and lower academic achievement in childhood than early-onset bipolar patients. We suggest that some of these abnormal developmental trajectories are more related to the phenotypic features (eg, early-onset psychotic symptoms) of these 2 syndromes than to categorically defined Diagnostic and Statistical Manual of Mental Disorders disorders.

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Genetic overlap between schizophrenia and bipolar disorder: A study with AKT1 gene variants and clinical phenotypes

Cited by 36 publications

References 40 publications

Distinct lithium-induced gene expression effects in lymphoblastoid cell lines from patients with bipolar disorder

Distinct lithium-induced gene expression effects in lymphoblastoid cell lines from patients with bipolar disorder

mTOR-Related Brain Dysfunctions in Neuropsychiatric Disorders

Differential Neurodevelopmental Trajectories in Patients With Early-Onset Bipolar and Schizophrenia Disorders

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