Activity-dependent neuroprotective protein (ADNP) expression level is correlated with the expression of the sister protein ADNP2: deregulation in schizophrenia

Eur Neuropsychopharmacol. 2011 May;21(5):355-61. doi: 10.1016/j.euroneuro.2010.06.004. Epub 2010 Jul 3.


Activity-dependent neuroprotective protein (ADNP) and the homologous protein ADNP2 provide cell protection. ADNP is essential for brain formation, proper brain development and neuronal plasticity, all reported to be impaired in the schizophrenia patient brains. Furthermore, reduction in ADNP expression affects social interactions, a major hallmark of schizophrenia. To evaluate a possible involvement of ADNP and ADNP2 in the pathophysiology of schizophrenia in humans, we measured relative brain mRNA transcripts of both proteins compared with control subjects. Quantitative real time polymerase chain reaction in postmortem hippocampal specimens from normal control subjects exhibited a significant ADNP to ADNP2 transcript level correlation (r=0.931, p<0.001), also apparent in a neuroglial model system. In contrast, in the hippocampus of matched schizophrenia patients, this correlation (r=0.637, p=0.014) was drastically decreased in a statistically significant manner (p=0.03), mirroring disease-associated increased ADNP2 transcripts. In the prefrontal cortex of schizophrenia patients the correlation between ADNP and ADNP2 mRNA levels was apparently higher than in the hippocampus (r=0.854, p<0.001), but did not reach a significant difference (p=0.25). Thus, imbalance in ADNP/ADNP2 expression in the brain may impact disease progression in schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analysis of Variance
  • Animals
  • Brain / metabolism*
  • Cell Line, Tumor
  • Disease Progression
  • Female
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Humans
  • Male
  • Mice
  • Middle Aged
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Postmortem Changes
  • RNA, Messenger / metabolism
  • Schizophrenia* / metabolism
  • Schizophrenia* / pathology
  • Schizophrenia* / physiopathology
  • Statistics as Topic
  • Teratocarcinoma / pathology
  • Tretinoin / pharmacology


  • ADNP protein, human
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • RNA, Messenger
  • Tretinoin