TABLE I.
Examples of Conditions With Neuropsychiatric Features Associated With TEs
| Disorder | TE type | Affected gene(s) |
TE feature | Tissue | Sample size | Reference |
|---|---|---|---|---|---|---|
| Schizophrenia | HERV(-W), HERV(-K) | Upregulation of HERV-W and HERV-K transcription in the cortex of post-mortem brains of SCZ and BD vs. HC | Post-mortem brain | 4 SCZ, 4 BD, 6 HC | Yolken et al. [2000] | |
| Schizophrenia | HERVs (-W) | (i) Over-representation of HERV (-W) family in CSF of SCZ vs. HC; (ii) up-regulation of differential expression of HERV(-W) in frontal cortex brain regions in SCZ vs. HC | Cerebrospinal fluid and post-mortem brain | 55 SCZ and 52 HC | Karlsson et al. [2001] | |
| Schizophrenia | HERV(-W) | Presence of particles containing HERV-W RNA in the plasma of patients with recent-onset schizophrenia (subgroup of the sample described in Karlsson et al., 2001) | Blood plasma | 54 SCZ, 46 HC | Karlsson et al. [2004] | |
| Schizophrenia | HERV(-K) | (i) Over-expression of HERV-K in SCZ 8c BD vs. HC | Post-mortem brain | 215 brain tissue samples derived from 39 SCZ, 38 BD, 39 HC | Frank et al. [2005] | |
| Schizophrenia | HERV(-K) | The HERV-K115 insertion appeared to be more frequent in patients with younger onset of schizophrenia than those with later onset. | DNA | 178 SCZ, 181 HC | Lin et al. [2011] | |
| Schizophrenia | HERV(-W) | (i) reduced expression of HERV-W gag in neurons and astroglial cells in SCZ, BP and MDD vs. HC | Post-mortem brain (anterior cingulate cortex, hippocampus) | 15 SCZ, 15 HC | Weis et al. [2007] | |
| Schizophrenia | HERV(-K) | SLAM | Two-polymorphisms haplotype in the envelope region of Herv K-18, located in the CD48 signaling lymphocyte activating [SLAM] gene on chr1, is highly associated with type 2 diabetes in a population of 229 individuals with SCZ vs. 136 HC | DNA | 229 SCZ, 136 HC | Dickerson et al. [2008] |
| Schizophrenia | HERV(-W) | (i) Significantly higher antigenemia of HERV-W ENV and GAG proteins in individuals with SCZ vs. HC; (ii) significant correlation of antigenemia with C-reactive protein (CRP) | Serum | 49 SCZ, ~49 HC | Perron et al. [2008] | |
| Schizophrenia | HERV(-W) | PTD015 (or C11orf67) | (i) Higher prevalence of HERV-W gag transcripts in SCZ vs. HC; (ii) intronic elements on the noncoding strand of PTD015 (11q13.5) appear to be transcribed at a higher rate in the patients during the transition from susceptibility to manifestation of symptoms. | PBMC | 30 SCZ, 26 HC | Yao et al. [2008] |
| Schizophrenia | HERV(-W) | BDNF, NTRK2, DRD3, CREB | (i) Higher prevalence of HERV-W env transcripts in SCZ vs. HC; (ii) over-expression of HERV-W upregulate BDNF, NTRK2, DRD3 and increase CREB protein | Blood plasma | 118 SCZ, 106 HC | Huang et al. [2011] |
| Schizophrenia | HERV(-W) | (i)Significantly higher HERV-W env transcription in BD and in SZ vs. HC (ii)The corresponding DNA copy number was paradoxically lower in the genome of patients with BD or SZ than in HC. |
PBMC | 91 BD, 45 SZ, 73 HC | Perron et al. [2012a,b] | |
| Schizophrenia (& Parkinson–s) | Retrotransposition activity | Effect of somatic retrotransposition on brain metabolism, biosynthesis of 250 metabolites, including dopamine, serotonin and glutamate | in silico | Not Available | Abrusan [2012] | |
| Bipolar disorder | HERV(-W), HERV(-K) | Upregulation of HERV-W and HERV-K transcription in the cortex of post-mortem brains of SCZ and BD vs. HC | Post-mortem brain | 4 SCZ, 4 BD, 6 HC | Yolken et al. [2000] | |
| Bipolar disorder | HERV(-K) | (i) Over-expression of HERV-K in SCZ & BD vs. HC | Post-mortem brain | 215 brain tissue samples derived from 39 SCZ, 38 BD, 39 HC | Frank et al. [2005] | |
| Bipolar disorder | HERV(-W) | (i)Significantly higher HERV-W env transcription in BD and in SZ vs. HC (ii)The corresponding DNA copy number was paradoxically lower in the genome of patients with BD or SZ than in HC. |
PBMC | 91 BD, 45 SZ, 73 HC | Perron et al. [2012b] | |
| Bipolar disorder | HERV(-W) | (i) Reduced expression of HERV-W gag in neurons and astroglial cells in SCZ, BD and MDD vs. HC | Post-mortem brain (anterior cingulate cortex, hippocampus) | 15 SCZ, 15 MDD, 15 HC | Weis et al. [2007] | |
| Major depression | HERV(-W) | (i) Reduced expression of HERV-W gag in neurons and astroglial cells in SCZ, BD and MDD vs. HC | Post-mortem brain (anterior cingulate cortex, hippocampus) | 15 SCZ, 15 MDD, 15 HC | Weis et al. [2007] | |
| Post-traumatic stress disorder | LINE-1 and Alu | LINEs were hypermethylated in controls post- versus predeployment, hypomethylated in cases versus controls postdeployment. Alus wer hypermethylated for cases versus controls predeployment | Serum, pre- and post-deployment, DNA methylation assessed via pyrosequencing | 75 post-deployment PTSD and 75 no postdeployment PTSD (controls) | Rusiecki et al. [2012] | |
| Post-traumatic stress disorder | LINE-1 | Identification of a module of stress regulated highly co-expressed transcripts with no annotations mapping to genomic locations corresponding to LINE-1 and up-regulated in the basolateral amygdala of rats | Genome-wide gene expression profile in amygdala | Stress-enhanced fear learning (SEFL) animal model on 56 adult male rats | Ponomarev et al. [2010] | |
| Alcohol dependence | LINE, SINE, LTR | Several module of co-expressed SINE and LTR up-regulated in the central and basolateral amygdala and superior frontal cortex of the alcoholic brain; upregulation of the unique probe corresponding to a currently “active” LINE-1 family, L1HS; regions corresponding to upregulated probes show increased hypomethylation in alcoholics | Post-mortem brain from central (CNA) and basolateral nucleus [BLA] of amygdala, as well as the superior frontal cortex (CTX) | 17 alcoholics and 15 matched control (gene expression); 6 alcoholics and 6 matched control (H3K4 histone methylation); 5 alcoholics and 5 matched controls (Methyl-Histone H3K4 ChIP) | Muotri et al. [2009] | |
| Autism | HERV(-H, -W,- E, -K) | (i) HERV-H over-expression in ASD vs. HC; (ii) HERV-W down-expression in ASD vs. HC | PBMC | 28 ASD, 28 HC | Balestrieri et al. [2012] | |
| Attention deficit hyperactivity disorder (ADHD) | HERV(-H, -K, -W) | HERV-H over-expression in patients with ADHD vs. HC; no differences in the expression levels of HERV-K and W. | PBMC | 30 ADHD, 30 HC | Balestrieri et al. [2013] | |
| Rett syndrome | LINE-1 | MECP2 | MeCP2 mutations increase susceptibility for L1 retrotransposition in RTT patients | In vitro cell culture of neuronal progenitor cells derived from human induced pluripotent cells | Not available | Muotri et al. [2010] |
| Ataxia telangiectasia (neurodegenerative disorders) | LINE-1 | ATM | (i) Increase in retrotransposition activity in L1s cells with lack of ATM; (ii) increased copy number of L1HS in ataxia telangiectasia patients vs. HC | L1RP-EGFP transgenic mouse, human brain post-mortem tissue, in vitro cell culture | Not available | Coufal et al. [2011] |
| Infantile encephalopathy (neurodegenerative disorder) | LINE-1 | lincRNA SLC7A2 | Point mutation in intron of SLC7A2 in a primate-specific retrotransposon sequence and related increase of neuronal apoptosis in in vitro KO for this transcript | DNA, post-mortem brain tissue, in vitro cell culture | 9 families, 15 patients and 17 unaffected siblings | Cartault et al. [2012] |
| Frontotemporal lobar degeneration (FTLD) (neurodegenerative disorder) | LINE, SINE and LTR | TDP-43 (RNA-binding protein) | (i) TDP-43 broadly targets TE-derived transcripts, including many SINE, LINE and LTR classes as well as some DNA elements; (ii) the association between TDP-43 and TE-derived RNA targets is reduced in FTLD patients relative to healthy subjects; (iii) over-expression of TE derived transcripts in each of two different mouse models with TDP-43 dysfunction. | In vivo crosslinking-immunoprecipitation sequencing (CLIP-seq) datasets of human healthy and FTLD post-mortem brain, RNA immunoprecipitation sequencing (RIP-seq) data of rat cortical neuron cells, mouse CLIP-seq and mRNA-seq datasets | Not available | Li et al. [2012] |
| Neurodevelopment | LINE-1, Alus, SVAs | CAMTA1, DRD3, SLCBA5, SLC6A6 SLCBA9 | High-throughput de novo insertions of LINEs, Alus and SVA wit over-representation in protein-coding genes implicated in neurogenesis and synaptic function pathways, in introns (LINEs), exons (Alus) | Post-mortem brain | 3 HC | Baillie et al. [2011] |
| DiGeorge syndrome (mental retardation) | Alu | Alu-mediated chromosomal rearrangements leading to microdeletions on 22q11 | DNA | Not available | Babcock et al. [2003] |
For each psychiatric disorders (Schizophrenia, Bipolar Disorder, Major Depression, etc.) results are shown from published investigations, presenting the specific TE element involved and its features, the genes that are affected by the TE when this information is known, the tissue that has been investigated and a summary description of the sample that made it possible to detect a putative role of a given TE.