Alina Borkowska

Prefrontal cognition in schizophrenia and bipolar illness in relation to Val66Met polymorphism of the brain-derived neurotrophic factor gene

Abstract  The measures of prefrontal cognition have been used as endophenotype in molecular‐genetic studies. Brain‐derived neurotrophic factor (BDNF) has been implicated in cognitive functions and in the pathogenesis of major psychoses. This study investigates the relationship between Val66Met polymorphisms of the BDNF gene and prefrontal cognitive function in 129 patients with schizophrenia and 111 patients with bipolar mood disorder. Cognitive tests included the Wisconsin Card Sorting Test (WCST), with such domains as number of perseverative errors, non‐perseverative errors, completed corrected categories, conceptual level responses, and set to the first category, and the N‐back test, where mean reaction time and percent of correct reactions were measured. Genotyping for Val66Met BDNF polymorphism was done by polymerase chain reaction method. In schizophrenia, no relationship between Val66Met polymorphism of the BDNF gene and the results of the WCST was observed. Patients with Val/Val genotype had a higher percentage of correct reactions in the N‐back test than those with the remaining genotypes. Bipolar patients with Val/Val genotype obtained significantly better results on three of five domains of the WCST. No relationship between BDNF polymorphism and the results of the N‐back test was found in this group. A limitation to the results could be variable psychopathological state and medication during cognitive testing and lack of Hardy–Weinberg equilibrium in schizophrenia group. Val66Met polymorphism of the BDNF gene may be associated with cognitive performance on the WCST in bipolar mood disorder but not in schizophrenia. An association of this polymorphism with performance on the N‐back test in schizophrenia and not in bipolar illness may suggest that in schizophrenia, the BDNF system may be connected with early phases of information processing.

Eye movement disturbances in schizophrenia and a polymorphism of catechol-O-methyltransferase gene

Previous studies suggested an association between the catechol-O-methyltransferase (COMT) Val/Met polymorphism and the performance on neuropsychological tests, measuring prefrontal function in schizophrenia. The aim of this study was to examine the relationship between this polymorphism and performance on oculomotoric tests in schizophrenic patients. The intensity of eye movement disturbances on fixation and smooth pursuit tests and the Val/Met polymorphism of COMT gene were studied in 117 schizophrenic patients (74 male and 43 female). In male schizophrenic patients, the mean intensity of both kinds of eye movement disturbances was lower in subjects who had the Met/Met genotype, with significant difference compared to other genotypes. Also, a significantly higher frequency of the Met allele and the Met/Met genotype was found in male schizophrenic patients exhibiting a lower intensity of smooth pursuit disturbances, and a trend in this direction was observed for the intensity of fixation disturbances. No such relationship was found in female schizophrenic patients. The results obtained suggest that, in male schizophrenic patients the Met allele of the COMT Val/Met polymorphism may have an alleviating effect on eye movement disturbances. They also point to possible gender differences as to the role of COMT in brain function in schizophrenia.

An association study of dopamine receptors polymorphisms and the Wisconsin Card Sorting Test in schizophrenia

Summary.Dopamine (DA), an important neurotransmitter in prefrontal cortex (PFC), is involved in the pathogenesis of schizophrenia. The aim of the study was to test an association between common polymorphism of genes for DA receptors DRD1, DRD2, DRD3, DRD4, and performance on the Wisconsin Card Sorting Test (WCST), measuring various functions of PFC, in 138 schizophrenic patients. Patients with G/G genotype of DRD1 tended to obtain worse results in all domains of WCST compared to patients with remaining genotypes, particularly for number of completed corrected categories, and trials to set the first category. A relationship was also found in female patients between DRD2 polymorphism and number of perseverative errors, while no association between WCST results and DRD3 or DRD4 polymorphism was observed in patients studied. The results may suggest an association between DRD1 gene polymorphism and performance on PFC test in schizophrenia. Also, the gender-dependent role of DRD2 in this process may be presumed.

Eye movement and neuropsychological studies in first-degree relatives of schizophrenic patients

The aim of the study was to compare the results of oculomotor and neuropsychological tests in first-episode schizophrenic patients, in both their parents and matched healthy controls. Eye movement tests included fixation and a smooth pursuit task and neuropsychological tests which comprised the Trail Making Test (TMT) A and B, the Stroop Test A and B, and the Wisconsin Card Sorting Test (WCST). There was a significant difference between the 21 patients and their 33 healthy parents in the results of both the eye movement tests and the TMT and WCST but not in the Stroop test. On the other hand, a significant difference between parents and their matched control subjects was found in both oculomotor tests, in the Stroop B, and in two indices of the WCST (completed categories, CC and percentage of conceptual level responses, %CONC). A correlation was obtained between patients and their fathers in the intensity of smooth pursuit disturbances and two indices of the WCST (CC and %CONC), but not between patients and their mothers. The results obtained confirm those of other studies pointing to the presence of a significant impairment on oculomotor and neuropsychological tests in first-degree nonpsychotic relatives (parents) of schizophrenic patients, which may be used as an endophenotypic markers of genetic predisposition to schizophrenia.

Polish validation of the TEMPS-A: the profile of affective temperaments in a college student population.

BACKGROUND AND AIMS The TEMPS-A scale is a self-evaluation measure to assess five affective temperaments: depressive, cyclothymic, hyperthymic, irritable and anxious. The scale has already been validated in over 10 languages. In this paper, the first report on the validation of the Polish version of TEMPS-A is presented. METHODS The TEMPS-A questionnaire version that includes 110 questions has been adapted following the translation-back translation methodology from English to Polish, checked by the originators of the five scales (H.S.A., K.K.A.). In the next step, the Polish version of TEMPS-A was administered to 521 Polish undergraduate students. Internal consistency of temperamental scales was measured with Cronbach-alpha coefficients. Correlation among the temperaments was examined using Pearsons bivariate correlation. Differences between sexes were tested with ANOVA. RESULTS The Cronbach-alpha and the Kuder-Richardson 20 reliability coefficients for the depressive, cyclothymic, hyperthymic, irritable and anxious temperaments were between 0.69 and 0.83. The percentage of subjects whose Z-scores were above 2 SD, was the highest among depressive (4%) and anxious (3.5%) temperaments, followed by the cyclothymic (2.9%), hyperthymic (1%), and irritable (0.6%). The strongest positive correlations between the temperamental scales were found between depressive and anxious, as well as between cyclothymic and irritable ones (correlation coefficients 0.63 and 0.57, respectively). Male subjects attained significantly higher scores for hyperthymic temperament, compared to females, while females scored significantly higher than males on cyclothymic and anxious temperaments. LIMITATIONS Our healthy young subjects are not representative of the Polish population. As external validation has been achieved in other language versions, it was not repeated in the present Polish version. CONCLUSIONS The Polish version of TEMPS-A has a good internal consistency. The findings generally cohere with those from previously validated versions in other languages.

The study of cytosolic phospholipase A2 gene polymorphism in schizophrenia using eye movement disturbances as an endophenotypic marker.

Phospholipase A2 (PLA2) is a key enzyme of the phospholipid metabolism which shows alteration in schizophrenia. Eye movement disturbances occur in a majority of patients with schizophrenia and in a proportion of their first-degree relatives, and they have been suggested as an endophenotypic marker in genetic studies of this illness. Here we report an association between the Ban I polymorphism of the cytosolic PLA2 gene (single nucleotide polymorphism in the first intron of the gene) and the intensity of eye movement disturbances (fixation and smooth pursuit) observed in 126 schizophrenic patients. The mean intensity of both kinds of eye movement disturbances was significantly higher in individuals homozygous for the A2 genotype compared with the remaining phenotypes. There was also a trend for greater A2 allele frequency in schizophrenic patients with a higher degree of eye movement disturbances. The relative frequency of the A2/A2 genotype was higher in patients with a greater degree of eye movement disturbances occurring during both fixation and smooth pursuit tests. Our results correspond to the other studies showing an association between the cPLA2 polymorphism and schizophrenia (predominance of the A2 allele in schizophrenic subjects).

Response to prophylactic lithium in bipolar disorder may be associated with a preservation of executive cognitive functions

We assessed performance on the Wisconsin Card Sorting Test (WCST), measuring executive functions, in 30 patients showing different prophylactic effect of lithium (excellent lithium responders-ER, partial responders-PR and non-responders-NR), and in fifty persons of their offspring (12 of ER, 26 of PR, and 12 of NR). Age- and gender head-to-head matched population consisted of 30 subjects for lithium group and 50 subjects for the offspring of lithium patients. In lithium patients, NR had significantly worse results compared to the remaining groups and to control subjects on perseverative errors (WCST-P) and conceptual responses (WCST-%conc). No differences were observed in the offspring of patients with different effect of lithium, however, they showed an impairment on WCST-P and WCST-%conc compared to matched healthy controls. Therefore, the favorable effect of lithium prophylaxis may be associated with a preservation of executive cognitive functions and the offspring of bipolar patients shows an impairment of such functions.

Gentamicin-collagen sponge reduces the risk of sternal wound infections after heart surgery: Meta-analysis.

OBJECTIVES Sternal wound infections are serious postoperative complications that increase the length of hospital stay and healthcare costs. The benefit of implantable gentamicin-collagen sponges in reducing sternal wound infections has been questioned in a recent multicenter trial. We aimed to perform a comprehensive meta-analysis of studies assessing the efficacy of implantable gentamicin-collagen sponges in sternal wound infection prevention. METHODS Multiple databases were screened for studies assessing the efficacy of implantable gentamicin-collagen sponges after heart surgery. The primary end point was sternal wound infection, and secondary end points were the occurrence of deep sternal wound infection, superficial sternal wound infection, mediastinitis, and mortality. Randomized controlled trials and observational studies were analyzed separately. By means of meta-regression, we examined the correlation between sternal wound infection and extent to which the bilateral internal thoracic artery was harvested. RESULTS A total of 14 studies (N = 22,135, among them 4 randomized controlled trials [N = 4672]) were included in the analysis. Implantable gentamicin-collagen sponges significantly reduced the risk of sternal wound infection by approximately 40% when compared with control (risk ratio [RR], 0.61; 95% confidence interval [CI], 0.39-0.98; P = .04 for randomized controlled trials and RR, 0.61; 95% CI, 0.42-0.89; P = .01 for observational studies). A similar, significant benefit was demonstrated for deep sternal wound infection (RR, 0.60; 95% CI, 0.42-0.88; P = .008) and superficial sternal wound infection (RR, 0.60; 95% CI, 0.43-0.83; P = .002). The overall analysis revealed a reduced risk of mediastinitis (RR, 0.64; 95% CI, 0.45-0.91; P = .01). The risk of death was unchanged. A significant positive linear correlation (P = .05) was found between the log RR of sternal wound infection and the percentage of patients receiving bilateral internal thoracic artery grafts. CONCLUSIONS Implantable gentamicin-collagen sponges significantly reduce the risk of sternal wound infection after cardiac surgery, with evidence consistent in randomized and observational-level data. However, the extent of this benefit might be attenuated in patients receiving bilateral internal thoracic artery grafts.

The Wisconsin Card Sorting Test and the N-back test in mild cognitive impairment and elderly depression

The aim of this study was to assess cognitive functions in 30 non-depressed patients with mild cognitive impairment (MCI), compared with 30 age-, gender- and education-matched patients with acute depressive episode, and with 30 healthy subjects. Neuropsychological assessment included the Mini Mental State Examination (MMSE), memory tests as well as the Wisconsin Card Sorting Test (WCST) and the N-back test. Patients with MCI obtained significantly worse results on all domains of the WCST and the N-back test compared to both depressed and healthy subjects. Depressed patients showed significantly worse performance than controls on most scores. In the MCI group, no association with MMSE was found with any of WCST domains, or with reaction time in the N-back test. Three tests, WCST-P, N-back %CORR and WCST 1st CAT obtained highest ranks (>90) as predictors for differentiating between groups. The results suggest a usefulness of employing WCST and N-back tests for a neuropsychological evaluation of patients with MCI.

Polymorphisms of the Fyn kinase gene and a performance on the Wisconsin Card Sorting Test in schizophrenia.

The glutamatergic system has been implicated in the pathogenesis and prefrontal cortex dysfunctions in schizophrenia. The Src-family tyrosine kinase Fyn plays a key role in the interaction between brain-derived neurotrophic factor and glutamatergic receptor N-methyl-D-aspartate, in prefrontal cortex. We estimated an association between three polymorphisms of Fyn gene and performance on the Wisconsin Card Sorting Test, measuring prefrontal cortex functions, in 188 schizophrenic patients. Patients with T/T genotype of IVS10+T/C polymorphism and T/T genotype of Ex12+894T/G polymorphism made significantly less perseverative errors in the Wisconsin Card Sorting Test compared with patients with remaining genotypes, and obtained numerically better results in other Wisconsin Card Sorting Test domains. No significant differences in Wisconsin Card Sorting Test performance were found as to −93 A/G polymorphism. The main finding of the study is showing a relationship between polymorphisms of the Fyn gene, related to the function of glutamatergic system, and a performance on neuropsychological test of prefrontal cortex activity in schizophrenic patients.