Table 3.
Summary of evidence for altered lipidation in schizophrenia and/or in association with antipsychotic administration.
| Altered expression of myristoylated substrates in schizophrenia | |
| DLPFC | Decreased protein expression of MARCKS and pMARCKS112 |
| Expression of prenylation-associated enzymes in schizophrenia | |
| DLPFC | Decreased protein expression of FNTA, PGGT1B, and RABGGTB118 |
| Protein S-palmitoylation in schizophrenia | |
| DLPFC | Decreased total levels of palmitoylated protein and reduced levels of palmitoylated protein within specific molecular mass ranges126 |
| Decreased palmitoylation of VGLUT1, Ras, and MBP126 | |
| S-palmitoylation-associated enzyme activity in schizophrenia | |
| Serum | Increased enzyme activity of PPT1130 |
| PPT1 activity is positively correlated with Positive and Negative Syndrome Scale (PANSS) scores for positive, negative, general, and S scales130 | |
| DHHC enzyme (protein acyltransferase) gene expression in schizophrenia | |
| GWAS | ZDHHC18 and ZDHHC5 were among the top 5 genes significantly associated with schizophrenia131 |
| Loss-of-function mutation of ZDHHC5 identified within schizophrenia-associated loci132 | |
| 22q11 deletion syndrome is associated with schizophrenia risk | |
| Reviews | 22q11 deletion syndrome implicated as a genetic subtype of schizophrenia133,135,136 |
| Targeted gene analysis | ~2% of adult caucasians with schizophrenia exhibit 22q11 deletion134 |
| SNP analysis | ZDHHC8 (KIAA1292) gene is located in the 22q11 susceptibility locus and implicated in schizophrenia137 |
| SNP rs175174 in the ZDHHC8 gene is associated with schizophrenia risk | |
| SNP analysis | Increased transmission of the A allele of rs175174 in females with schizophrenia141,143 |
| Meta-analysis | Weakly supports rs175174 as a schizophrenia risk factor in East Asian populations138 |
| SNP analysis | Interaction of the rs175174 and rs5992403 (UFD1L) is associated with schizophrenia age of onset139 |
| Genotype/MRI | GG-genotype at rs175174 is associated with reduced gray matter volume in the frontal lobe, but is not specific to schizophrenia140 |
| Hh family protein lipidation in schizophrenia | |
| GWAS | SNP rs7527939 in the HHAT gene was the strongest indicator of schizophrenia risk in Bulgarian subjects149 |
| Ghrelin octanoylation associated with antipsychotic administration | |
| Plasma | Octanoylated (active) ghrelin levels are unchanged after 4, 8, 12, and 16-weeks olanzapine treatment, despite reductions of total ghrelin at 8, 12, and 16 weeks157 |