Genetic variables of the glutamatergic system associated with treatment-resistant depression: A review of the literature.

Depression is a common, recurrent mental disorder and one of the leading causes of disability and global burden of disease worldwide. Up to 15%-40% of cases do not respond to diverse pharmacological treatments and, thus, can be defined as treatment-resistant depression (TRD). The development of biomarkers predictive of drug response could guide us towards personalized and earlier treatment. Growing evidence points to the involvement of the glutamatergic system in the pathogenesis of TRD. Specifically, the N-methyl-D-aspartic acid receptor (NMDAR) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), which are targeted by ketamine and esketamine, are proposed as promising pathways. A literature search was performed to identify studies on the genetics of the glutamatergic system in depression, focused on variables related to NMDARs and AMPARs. Our review highlights GRIN2B, which encodes the NR2B subunit of NMDAR, as a candidate gene in the pathogenesis of TRD. In addition, several studies have associated genes encoding AMPAR subunits with symptomatic severity and suicidal ideation. These genes encoding glutamatergic receptors could, therefore, be candidate genes for understanding the etiopathogenesis of TRD, as well as for understanding the pharmacodynamic mechanisms and response to ketamine and esketamine treatment.

Genetics of adult attachment: An updated review of the literature.

Attachment style, which has been theorized to be rooted in childhood bonding experiences, influences adult cognitive, emotional and interpersonal functioning. Despite its relationship with early experiences, research indicates that the continuity of attachment style across childhood and adulthood is only partial, being a malleable tendency that is shaped throughout development, with an increasing influence of genetics, as it occurs in other cognitive and behavioral phenotypes. Genetic research indicates that up to 45% of the variability in anxious and 39% in avoidant adult attachment style could be explained by genetic causes, but the precise mechanisms remain unclear. A narrative review is conducted analyzing the existing literature regarding the implication of candidate genes related to oxytocin, dopaminergic pathways, serotonergic pathways and brain-derived neurotrophic factor in adult attachment, with both vulnerability and differential susceptibility approaches, yielding mixed results. We highlight the lack of genome-wide studies and the scarcity of epigenetic investigation. Based on the existing data, we conclude that the genetics of adult attachment is an area that requires further research to clarify its etiological role and that it should be preferably approached as an interaction between nature and nurture.

Cannabis use and cognitive functioning in first-episode schizophrenia patients.

Cannabis is one of the most widely used illicit drugs in the world. In healthy individuals cannabis is associated with cognitive impairments. Research into the effect of cannabis use in schizophrenia has yielded contradictory findings. Our aim has been to explore the correlates of cannabis use in cognitive and psychopathological features, both cross-sectional and longitudinally, in early phases of schizophrenia. 104 patients with a first episode of non-affective psychosis and 37 healthy controls were studied. Patients were classified according to their use of cannabis prior to the onset of the illness (47 users vs. 57 non-users). They were cross-sectionally and longitudinally studied and compared on clinical and cognitive variables and also on their level of premorbid adjustment. Cannabis user patients had better attention and executive functions than non-cannabis user patients at baseline and after 1 year of treatment. Both groups showed similar improvement in their cognitive functioning during the 1-year follow-up period. We also found that users had a better social premorbid adjustment, particularly during the early periods of life. The amount of cannabis consumed and the length of time of consumption did not significantly relate to cognitive performance. The use of cannabis does not seem to be associated with a negative effect on cognition in a representative sample of first-episode schizophrenia patients. Cannabis user patients appear to comprise a subgroup of patients with a better premorbid adjustment and premorbid frontal cognitive functions.