Glutamate drugs and pharmacogenetics of OCD: a pathway-based exploratory approach

Abstract

In the genetically informed network, known genes and identified key connecting components, including DLG4 (a developmental gene), PSD-95 (a synaptic scaffolding protein) and PSEN1 (presenilin, a regulator of secretase), conform a group of potential pharmacological targets. These potential targets can be explored, in the future, to deliver new therapeutic approaches to OCD. There is also the need to develop a better understanding of neuroprotective mechanisms as a foundation for future OCD drug discovery.

Increased orbitofrontal cortex activation associated with “pro-obsessive” antipsychotic treatment in patients with schizophrenia

“…25 Notably, the neurobiological interpretation must not be confined to the serotonergic system; reciprocal interactions of serotonergic, dopaminergic and especially glutamatergic neurotransmission have to be considered. 41,42 Del Casale and colleagues 43 suggested that a striatal dysfunction, mainly of the caudate nucleus, may lead via inefficient thalamic gating to a relative hyperactivity of the OFC and the anterior cingulate cortex (ACC). It is assumed that the OFC activity is linked with intrusive thoughts, whereas the signal in the ACC corresponds with nonspecific anxiety.…”

Evidence-Based Treatments in Treatment-Naïve and Treatment-Resistant Pediatric Obsessive-Compulsive Disorder

“…Augmentation is the procedure off adding drugs with different mechanisms of action compared with the first-line SSRI in order to aid the therapeutic effects. Research indicates that in addition to serotonin, other neurotransmitters may be involved in the pathophysiology of OCD such as glutamate [10] and dopamine [11]. However, the evidence-based literature-at least for pediatric OCD-is lacking.…”

“…Recent evidence from a number of directions (genetic, neuroimaging, animal models, and treatment studies) implies that an abnormal concentration of glutamate, the main neurotransmitter within cortico-striatal-thalamic circuits, may be associated with OCD [10,100]. Thus, researchers have shown increasing interest in the potential efficacy of glutamate-targeting agents for OCD treatment.…”

“…Other glutamatergic drugs are ketamine, memantine, topiramate, and lamotrigine [10]. No studies in the pediatric OCD population exist [6].…”

“…We also filtered in the terms of Brandomized controlled trials^and Bmeta-analysis^. In addition, we read recent reviews and expert guidelines to find any relevant additional publications [1,[4][5][6][7][8][9][10][11].…”