Clinical, environmental, and molecular factors associated to the occurrence and persistence of posttraumatic stress disorder after an earthquake.

Post-traumatic stress disorder (PTSD) is a common and disabling condition with high incidence after an earthquake. The objective of the present study was to identify risk factors associated with the occurrence and persistence of PTSD. Individuals (18-65 years old) who experienced the earthquake of September 19th, 2017, attended the National Institute of Psychiatry (INPRFM) between October and November 2017 (baseline n = 68). Participants were followed 4-6 (first follow-up, n = 40) and 7-9 (second follow-up n = 41) months after the earthquake. Delay returning to normal activities, a negative emotional valence to a previous earthquake, comorbidity with depression, history of childhood maltreatment, and low expression of Glucocorticoid Receptor (GR) were associated with PTSD in the basal assessment. The earthquake-related variable associated with the persistence of PTSD at the second follow-up was that the earthquake had directly affected the participants, either because they were evicted, had damage to their homes, or suffered some injury. Comorbidity with dysthymia, history of childhood maltreatment, and higher severity of PTSD in the basal assessment were associated with persistent PTSD in the second follow-up. The lower expression of the FK506 binding protein 5 (FKBP5) in participants with persistent PTSD in the second follow-up was better explained by childhood physical abuse than with PTSD severity. These findings suggest that acute exposure to earthquake-related stressful situations is relevant for the initial risk of PTSD, while potential long-term stressful conditions are associated with its persistence. Likewise, molecular markers associated with hypothalamus-pituitary-adrenal-axis dysregulation were differentially associated with PTSD diagnosis at the different assessment times.

Increased Expression of Brain-Derived Neurotrophic Factor Transcripts I and VI, cAMP Response Element Binding, and Glucocorticoid Receptor in the Cortex of Patients with Temporal Lobe Epilepsy.

A body of evidence supports a relevant role of brain-derived neurotrophic factor (BDNF) in temporal lobe epilepsy (TLE). Magnetic resonance data reveal that the cerebral atrophy extends to regions that are functionally and anatomically connected with the hippocampus, especially the temporal cortex. We previously reported an increased expression of BDNF messenger for the exon VI in the hippocampus of temporal lobe epilepsy patients compared to an autopsy control group. Altered levels of this particular transcript were also associated with pre-surgical use of certain psychotropic. We extended here our analysis of transcripts I, II, IV, and VI to the temporal cortex since this cerebral region holds intrinsic communication with the hippocampus and is structurally affected in patients with TLE. We also assayed the cyclic adenosine monophosphate response element-binding (CREB) and glucocorticoid receptor (GR) genes as there is experimental evidence of changes in their expression associated with BDNF and epilepsy. TLE and pre-surgical pharmacological treatment were considered as the primary clinical independent variables. Transcripts BDNF I and BDNF VI increased in the temporal cortex of patients with pharmacoresistant TLE. The expression of CREB and GR expression follow the same direction. Pre-surgical use of selective serotonin reuptake inhibitors, carbamazepine (CBZ) and valproate (VPA), was associated with the differential expression of specific BDNF transcripts and CREB and GR genes. These changes could have functional implication in the plasticity mechanisms related to temporal lobe epilepsy.

Increased expression of BDNF transcript with exon VI in hippocampi of patients with pharmaco-resistant temporal lobe epilepsy.

A putative role of the brain-derived neurotrophic factor (BDNF) in epilepsy has emerged from in vitro and animal models, but few studies have analyzed human samples. We assessed the BDNF expression of transcripts with exons I (BDNFI), II (BDNFII), IV (BDNFIV) and VI (BDNFVI) and methylation levels of promoters 4 and 6 in the hippocampi of patients with pharmaco-resistant temporal lobe epilepsy (TLE) (n=24). Hippocampal sclerosis (HS) and pre-surgical pharmacological treatment were considered as clinical independent variables. A statistical significant increase for the BDNFVI (p<0.05) was observed in TLE patients compared to the autopsy control group (n=8). BDNFVI was also increased in anxiety/depression TLE (N=4) when compared to autopsies or to the remaining group of patients (p<0.05). In contrast, the use of the antiepileptic drug Topiramate (TPM) (N=3) was associated to a decrease in BDNFVI expression (p<0.05) when compared to the remaining group of patients. Methylation levels at the BDNF promoters 4 and 6 were similar between TLE and autopsies and in relation to the use of either Sertraline (SRT) or TPM. These results suggest an up-regulated expression of a specific BDNF transcript in patients with TLE, an effect that seems to be dependent on the use of specific drugs.