Moderating Effects of BDNF Genetic Variants and Smoking on Cognition in PTSD Veterans.

Posttraumatic stress disorder (PTSD) is frequently associated with cognitive disturbances and high prevalence of smoking. This study evaluated cognition in war veterans with PTSD and control subjects, controlled for the effect of smoking and brain derived neurotrophic factor (BDNF) rs6265 and rs56164415 genotypes/alleles. Study included 643 male war veterans with combat related PTSD and 120 healthy controls. Genotyping was done by real time PCR. Cognitive disturbances were evaluated using the Positive and Negative Syndrome Scale (PANSS) cognition subscale and the Rey-Osterrieth Complex Figure (ROCF) test scores. Diagnosis (p < 0.001), BDNF rs56164415 (p = 0.011) and smoking (p = 0.028) were significant predictors of the cognitive decline in subjects with PTSD. BDNF rs56164415 T alleles were more frequently found in subjects with PTSD, smokers and non-smokers, with impaired cognition, i.e., with the higher PANSS cognition subscale scores and with the lower ROCF immediate recall test scores. Presence of one or two BDNF rs56164415 T alleles was related to cognitive decline in PTSD. The T allele carriers with PTSD had advanced cognitive deterioration in smokers and nonsmokers with PTSD, and worse short-term visual memory function. Our findings emphasize the role of the BDNF rs56164415 T allele and smoking in cognitive dysfunction in war veterans with PTSD.

The impact of BDNF Val66Met on cognitive skills in veterans with posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is a trauma-induced disorder characterized with impaired cognitive function. BDNF modulates cognition and is involved in neuroprotection and neurocognitive processing. The BDNF Val66Met polymorphism was found to influence cognitive functions. In PTSD, carriers of the BDNF GG genotype had better spatial processing of navigation performance, and lower hyperarousal and startle reaction than A allele carriers. The hypothesis was that veterans with PTSD, carriers of the BDNF Val66Met A allele, will show reduced cognitive skills. The study included 315 male Caucasian combat veterans, with (N = 199) or without (N = 116) current and chronic PTSD. Cognition was assessed using the Rey-Osterrieth Complex Figure (ROCF) test that determines visual-spatial perception and short and long-term visual memory function. The results revealed that cognitive decline measured with ROCF test was associated with PTSD. Presence of the BDNF Val66Met GG genotype in veterans with PTSD, but not in veterans without PTSD, showed protective association with visual short-term memory and visual object manipulation after few seconds (executive function), assessed with the ROCF immediate recall test, compared to the A carriers with PTSD. In conclusion, this was the first study to confirm the association between BDNF Val66Met and memory and attention performed with ROCF in male veterans with PTSD. The results corroborated that the BDNF Val66Met A allele, compared to GG genotype, is associated with poorer short-term visual memory and attention linked with executive functions, in veterans with PTSD.

RECOVERY OF MEMORY AFTER CEREBRAL ARTERY ANEURYSM SURGERY.

The principal study objective was to define whether memory deficits (numerical, working, verbal-mechanical, verbal-logical and visual memory) occurred in patients submitted to surgery for brain artery aneurysm and whether significant recovery of memory took place with time. The study sample included 92 patients, i.e. 35 (38%) male and 57 (62%) female patients aged 27 to 76 years. Neuropsychological testing was conducted at Zagreb University Hospital Centre, Department of Neurosurgery, from 1998 to 2012, in two time intervals: first within 11 months following surgery, and then 12 to 48 months after surgery. The obtained results showed that verbal-mechanical, verbal-logical, and visual memory deficits were present in the first testing interval. In the second testing, the verbal-logical and visual memory deficits were still present, while the tests of verbal-mechanical memory showed deficits in capacity and learning curve, but the results for short- and long-term memory were within the normal ranges. Neither the first nor the second testing showed deficits of numerical and working memory. Based on our results, we can conclude that long-term verbal-mechanical and visual short- and long-term memory had recovered to a statistically significant level, whereas other types of memory showed no significant recovery.

Significant association between catechol-O-methyltransferase (COMT) Val158/108Met polymorphism and cognitive function in veterans with PTSD.

Core features of posttraumatic stress disorder (PTSD) are cognitive disturbances. Enzyme catechol-O-methyltransferase (COMT) degrades dopamine primarily in prefrontal cortex. Its functional polymorphism, COMT Val158/108Met, affects COMT activity and dopamine availability and is associated with disturbances in cognition. The hypothesis was that PTSD subjects will have worse working memory than healthy controls and that the carriers of the COMT Met allele will show better cognitive performance compared to Val/Val carriers in PTSD and controls subjects. The aim of this study was to assess the differences in cognitive functioning between PTSD and control subjects and to evaluate the association between COMT Val158/108Met polymorphism and cognitive function determined using the Rey-Osterrieth complex figure (ROCF) copy, immediate and delayed test. The study included 323 male Caucasian participants of Croatian origin: 205 male combat veterans with PTSD and 118 control subjects. A significant association between the COMT Val158/108Met and the ROCF immediate and delayed scores in veterans with PTSD was found. We confirmed, on ethnically homogenous groups of veterans with matched combat experience, that controls had higher ROCF immediate and delayed test scores than veterans with PTSD. In PTSD subjects, the Met carriers of the COMT Val158/108Met performed better (i.e. had higher ROCF scores) than Val/Val homozygotes on both ROCF immediate recall and delayed recall test. Our results provide the first evidence that the presence of one or two Met alleles of the COMT Val158/108Met might act as a protective variant in working memory tasks in combat exposed veterans with PTSD.

Personality Changes Following Brain Artery Aneurysm Surgery

Neuropsychological testing of patients in the course of their recovery from brain injuries enables analysis of cognitive deficiencies and/or emotional changes. The principle study objective was to define organic and/or reactive personality changes and the course of these changes in the function of the time span following brain artery aneurysm surgery in both female and male patients. The study was carried out at the Clinical Department of Neurosurgery, Zagreb University Hospital Center in Zagreb. The data refer to the period from 1989 to 2012 collected in two time intervals, i.e. 11 months and 12-48 months following brain artery aneurysm surgery. Of 72 patients included in the study, there were 28 male and 44 female patients. Neuropsychological testing consisted of clinical interview, clinical assessment of frontal lobe syndrome, Cornell personality questionnaire and Emotional Profile Index. Study results showed evidence of frontal lobe syndrome in 32% of patients on first testing and significant recovery on retesting, when only 17% of patients presented with frontal lobe syndrome. The reactive personality changes found in both testing intervals indicated increased neuroticism. In the first testing period, asthenic syndrome occurred most often, followed by conversion and aggressive-antisocial syndromes, while in the second testing interval asthenic syndrome was most pronounced and conversion and antisocial syndromes showed the same level of expression. The results also showed higher depressive and disorganizing states, which were even more pronounced in the second testing interval. As regards sex differences, the inclination toward cardiovascular somatization and destructiveness was more expressed in females than in males, showing a tendency of aggravation with increasing the time span following surgery. It may be concluded that the study has contributed to better understanding of organic and/or reactive personality changes in patients undergoing brain artery aneurysm surgery.

Prevalence of the metabolic syndrome in the old institutionalized people in Zagreb, Croatia.

Metabolic syndrome (MeS) is defined by a cluster of abnormalities comprising obesity, hypertension, carbohydrate intolerance and dyslipidemia. MeS increases the risk of developing various diseases, including coronary heart disease, stroke, peripheral angiopathy and type 2 diabetes. In our study, the subjects were 561 persons, residents of 11 homes for the elderly in Zagreb, Croatia. There were 160 men (28.5%) and 401 women (71.5%), aged from 56 to 96 years (the average being 79 years). Physical examination was conducted, which included blood pressure measurement, and body height and weight. Blood samples were taken for biochemical analysis. Along with other biochemical parameters, the levels of glucose, triglycerides and cholesterol (LDL, HDL-C) were also measured. The results have shown the prevalence of MeS in the elderly instutionalised people to be in the range of 20.8%, according to WHO criteria. The most common MeS component was hypertension, and it was significantly more frequent in women than in men; also, the elevated triglyceride levels were more often found in women; the difference between men and women was also statistically significant. MeS is a serious and growing health problem not only in Croatia but worldwide as well. Further studies are needed to verify the prevalence of MeS in Croatia, as it is a major risk for CVD and many other severe diseases.