I recently started looking in the Slc1a1 gene because of it is highly implicated in OCD. Several other genes are implicated as well, in regards to serotonin and dopamine, but from what I have been reading from Yale's research and pubmed, excess glutamate in the cerebral cortex and in various brain process (especially in the frontal cortex) is seen as being a possibly physiological cause of OCD. I have also read that SSRIs' primary mechanism (in treating OCD) might be in its ability to correct the glutamate balance as increased serotonin modulates glutamate. Slc1a1 is a gene that encodes for the EAAC1 enzyme which is responsible for transport of glutamate from the kidneys and from interneuronal synapses in the brain. People with dysfunction in this gene may have the inability to transport glutamate out of the synapses (and dysfunctional kidneys, the physiology I don't understand exactly), which leads to higher levels sitting around leading to hyperglutamatergic conditions. People who have issues with this gene can have defects that result in high levels of glutamate and aspartate in a amino acid urine analysis, and it's possible that for some individuals with OCD that high levels of both in the test may be an indicator of a bad Slc1a1 gene. People with high urine counts of these substances would be considered to have Dicarboxylic Aciduria (Where I found out about the test: http://phys.org/news/2011-01-obsessive-compulsive-disorder-ocd.htmlI) found a great article that discusses this and the genetic region of Slc1a1 that is implicated. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3007158/ Then on the bottom part of the article, it starts talking about how cysteine is and glutathione are also affected by this defective gene. Here is some of the meat of the aricle: "The increased affinity for l-cysteine resulting from the R445W mutation in SLC1A1 led to a reduction in l-cysteine uptake to levels that were 2% of those of WT, while I395del prevented l-cysteine uptake by SLC1A1. Consequently, the increase in l-glutamate and l-cysteine affinity for R445W not only reduced the size of the transporter currents observed but also substantially reduced the rate of substrate transport."[...] “Our findings on SLC1A1 disruption in humans were in agreement with the DA phenotype reported in Slc1a1 nullizygous mice. Despite this phenotypic similarity between species, the appearance of age-related neurodegeneration, which was observed in outbred Slc1a1 nullizygous mice, has not yet been clearly documented in humans. This neurodegeneration was attributed to decreased neuronal cysteine uptake. Cysteine is the rate-limiting substrate for the synthesis of glutathione, and neurons are dependent on the extracellular uptake of cysteine for normal function. Most cell types transport cysteine in the form of cystine, by heteroexchange with glutamate via the sodium-independent system x, but in vitro studies suggest that neurons lose this capacity as they mature. Neurons use sodium-dependent cysteine uptake as the major route for cysteine uptake (80%–90% of total uptake), most of which is handled by SLC1A1 (75%–85% of total sodium-dependent uptake). Thus, abrogation of cysteine uptake in the neurons of outbredSlc1a1 nullizygous mice led to impaired glutathione metabolism, increased oxidative stress, and neuronal death" This might be an underlying reason for why people with OCD benefit from NAC, if they have some inability to transport the cysteine. If you read the whole article however, there are a whole slew of SNPs that could potentially alter enzyme function, while this article focuses primarily on two specific regions of Slc1A1. Edit** I found out why NAC helps people with ocd and how it modulates glutamate in this article. http://www.ocd.yale.edu/researchers/329_114509_Pittenger et al (2011) Glutamate abnormalities in OCD.pdf "Indeed, excess glutamate has long been known to lead to neuronal death, a phenomenon known as excitotoxicity (Olney, 1969). Glutamate concentration is therefore tightly regulated. The principal mode of regulation is through high-afﬁnity glutamate transporters, which efﬁciently remove glutamate from the perisynaptic and extrasynaptic spaces (Danbolt, 2001). Quantitatively, glutamate transporters on glial cells – principally astrocytes – are responsible for the majority of glutamate removal; these astrocytic glutamate transporters are a target of the glutamate-modulating drug riluzole, which has shown promise in the treatment of refractory OCD (Pittenger et al., 2008a). A smaller fraction of glutamate is removed by the neuronal glutamate transporter, EAAC1/EAAT3; as reviewed below, polymorphisms in the gene encoding this transporter have been repeatedly associated with OCD in recent studies (Arnold et al.,2006; Dickel et al., 2006; Stewart et al., 2007; Shugart et al., 2009). Finally, glutamate is also transported into glial cells in exchange for the oxidized amino acid cystine via the glutamate-cystine antiporter; undersome circumstances the activity of this antiporter, which is inﬂuenced by the drug N-acetylcysteine, may be the principal determinant of baseline levels of extrasynaptic glutamate (Kalivas, 2009)"