The P300 waveform has been inconsistently linked to the maladaptive information-processing characterized in panic disorder (PD). The purpose of this study was to synthesize previous event-related potential (ERP) findings and determine whether patients with PD have significant abnormalities in the P300 wave compared to controls. We performed a systematic literature search for studies published between 1980 and 2013 that reported P300 measurements in patients with PD and controls. Effect size estimates were computed using the restricted maximum likelihood model. We identified 14 ERP studies that analyzed P300 amplitude (461 PD and 355 controls), and 11 ERP studies that analyzed latency (320 PD and 282 controls). Patients with PD had reduced P300 amplitudes compared to controls, but this difference was non significant at midline electrodes (n = 14, ES -0.16; z = -1.55, p = 0.122). However, P300 amplitude was significantly reduced when analyzing the Pz electrode independently (n = 7, ES -0.48, z = -3.92, p < 0.001). No significant differences between cases and controls in P300 latency were observed at the midline electrodes (n = 11, ES 0.11, z = 0.64, p = 0.524). This meta-analysis included non-peer reviewed literature and ERP stimuli with varying levels of emotional salience, which may have introduced bias into the analysis. There is no robust evidence that P300 latency alterations are present in patients with PD; however, there are indications of reduced amplitude at Pz relative to controls. Reductions in amplitude may be associated with reduced neural resources allocated to contextual updating, selective attention, and neural inhibition mechanisms.
Dysfunctional mechanisms in the serotonergic system have been implicated in suicidal behavior among patients with schizophrenia. However, previous association analyses of major serotonin genes have provided inconsistent findings regarding their role in suicidal behavior. The goal of the current study was to identify single-nucleotide polymorphisms (SNP) within HTR2A that directly affect CpG methylation sites in schizophrenic patients with suicidal behavior. Furthermore, direct methylation analysis was performed using genomic DNA from peripheral leukocytes employing bisulfite pyrosequencing to assess the contributions of six CpG sites in HTR2A exon I in 67 schizophrenia patients assessed for lifetime suicide attempt. Potential methylation in 25 CpG SNPs across the entire HTR2A gene was analyzed considering their direct contribution to methylation. When we compared direct methylation between attempters and nonattempters, we found that only the polymorphic T102C (rs6313) was significantly different between the two groups (p = 0.02). Furthermore, in the potential methylation analysis, we found a nominal association with suicide attempt for six of the 25 SNPs analyzed, i.e. rs2770293 (p = 0.045), rs6313 (p = 0.033), rs17068986 (p = 0.029), rs4942578 (p = 0.024), rs1728872 (p = 0.014), and rs9534511 (p = 0.003). The results of this investigation provide preliminary evidence that the combined analysis of CpG SNPs and methylation may be useful for investigating the genetic and epigenetic factors involved in suicidal behavior.
Recent studies have shown an association between gene alterations by epigenetic mechanisms and suicidal behavior. These epigenetic mechanisms are mitotically, and in some cases meiotically, heritable changes in the genome through non-DNA sequence coding processes that alter gene expression as a result of variable changes in environmental stimuli. Genome-wide association studies have been inconsistent in elucidating the association between genes and suicidal behavior, thereby making the heritability of suicidal behavior is unclear. However, recent epigenetic studies have provided evidence that epigenetic mechanisms could deliver the missing link between the heritability of suicidal behavior and the interaction between environment and the genome. The present review provides an in-depth discussion of epigenetic mechanisms that may regulate gene expression in suicidal behavior. The findings of current epigenetic studies on suicidal behavior will also be discussed considering future epigenome-wide association studies on elucidating the contributions of environment and genome on suicidal behavior.
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