Frontal and temporal cerebral blood flow (CBF) changes are the most common impairments of CBF described in patients with schizophrenia. Those impairments have also been associated with cognitive ...deficits, a hallmark of schizophrenia. In light of that fact, treatment interventions should target cognitive deficits to prevent chronic disability. However, specific therapies targeting cognitive symptoms are very few and far between. One of the treatment possibilities is aripiprazole, because several studies reported its potential procognitive effects. The objective of this study was to investigate whether use of aripiprazole in its long-acting injectable formulation (ALAI), during a 3-month treatment, has beneficial effects on CBF and cognitive functioning in patients with first episode of schizophrenia.
Single-photon emission computed tomography with technetium-99m hexamethylpropylene amine oxime was performed at 2 time points. Cognitive functions were assessed with a standardized test for cognitive functions, 5-KOG test, whereas severity of clinical symptoms was assessed with the Positive and Negative Syndrome Scale, both at the same 2 time points as single-photon emission computed tomography. Three-month treatment with ALAI was associated with improvement of several cognition indices and improvements of right-sided frontal and temporal CBF, as well as of clinical symptoms.
Multivariate tests were used to test for the effects of ALAI treatment on cognitive functions, clinical presentation, and brain perfusion in a 3-month period. Multivariate model revealed statistical significance (F = 11.958, P < 0.001). Of 10 separate 5-KOG parameters, 3-month treatment with ALAI significantly influenced 4: undelayed recall, delayed recall, attention, and working memory-digit span forward. Finally, 3-month ALAI treatment significantly improved regional CBF in 2 of 4 investigated areas, both on the right side of the brain (frontally and temporally).
Results of this research showed that treatment with ALAI in patients with first episode of schizophrenia is associated with improved right-sided frontal and temporal CBF, as well as with improved symptoms, including cognition indices. Although we cannot confirm it directly, it is possible that improved frontotemporal CBF led to the improvement in cognition indices.
Context: Schizophrenia has been associated with disorder of the dopamine system, which is downregulated by projections of the serotonin pathway. Dopamine and serotonin levels are regulated by a ...system of transporters and enzymes. In this research, dopamine transporter polymorphism (DAT-VNTR), serotonin transporter polymorphism (5-HTTLPR), monoamine oxidase A (MAOA-uVNTR), and catechol-o-methyl transferase (COMT Val158Met) polymorphisms have been investigated.
Aims: The aim of this study was to asses frequencies of these polymorphisms in the healthy control group and patients and to asses association with schizophrenia.
Settings and Design: Three hundred and fourteen healthy volunteers and 306 schizophrenia patients were included. Schizophrenia was diagnosed by Diagnostic and Statistical Manual-IV of the American Psychiatric Association, and mini international neuropsychiatric interview questionnaire was used for screening of healthy population.
Materials and Methods: Genotyping was performed using polymerase chain reaction (PCR) reaction followed by gel electrophoresis and PCR-restriction fragment length polymorphism.
Statistical Analysis: Categorical data were analyzed using the Chi-square test, age between subgroups was compared using the Mann-Whitney test, and all polymorphisms were tested for Hardy-Weinberg equilibrium. Logistic regression analysis was used to set the prediction model of schizophrenia.
Results: Difference in genotype distribution was observed for COMT Val158Met in female and DAT-VNTR polymorphism in overall sample P = 0.021 and P = 0.028, respectively. Statistically significant association of MAOA-uVNTR and schizophrenia was observed after adjustment for anamnestic predictors of disease. P = 0.010, 80.45% participants were correctly classified.
Conclusion: Our results suggest an association of MAOA-uVNTR polymorphism with schizophrenia. The difference in the distribution of COMT Val158Met and DAT-VNTR polymorphism support the involvement of dopamine system components in the pathogenesis of schizophrenia.
Alcohol use disorder (AUD) is a psychiatric disorder characterized by excessive and uncontrolled drinking that causes distress and has damaging consequences for men and women of all ages. It is one ...of the four most disabling diseases and it affects approximately 14.6 million persons in Europe.
Objective of this study is to investigate changes in platelet serotonin concentration after four weeks of alcohol abstinence in regards to the genotype of the serotonin transporter.
A total of 154 patients with AUD were included in the study. Platelet serotonin concentrations were assessed by enzyme-linked immunosorbent assay. Genotype of serotonin transporter promoter polymorphism was determined by the polymerase chain reaction-based method.
We did not establish a statistically significant main effect of serotonin transporter polymorphism on platelet serotonin concentration after four weeks of abstinence.
Aforementioned finding is in line with previous research suggesting a complex relationship between serotonin transporter gene and platelet serotonin levels, and congruent with the well-established genotype interaction with numerous other factors, such as sex, ethnicity, education level, and stressful life events.
Depression has been associated with various cardiovascular risk factors such as hypertension, obesity, atherogenic dyslipidemia and hyperglycemia. In depressive disorder, hyperactivity of the ...hypothalamic-pituitary-adrenal (HPA) axis and changes in the immune system have been observed. On the other hand, somatic diseases such as obesity, hyperlipidemia, hypertension and diabetes mellitus type 2 are now perceived as important comorbid conditions in patients with depression. The pathogenesis of the metabolic syndrome and depression is complex and poorly researched; however, it is considered that the interaction of chronic stress, psychotrauma, hypercotisolism and disturbed immune functions contribute to the development of these disorders. The aim of the study was to investigate the relationship between depression and metabolic syndrome regarding the HPA axis dysfunction and altered inflammatory processes. Literature search in Medline and other databases included articles written in English published between 1985 and 2012. Analysis of the literature was conducted using a systematic approach with the search terms such as depression, metabolic syndrome, inflammation, cytokines, glucocorticoids, cortisol, and HPA axis. In conclusion, the relationship between depression and metabolic syndrome is still a subject of controversy. Further prospective studies are required to clarify the possible causal relationship between depression and metabolic syndrome and its components. Furthermore, it is important to explore the possibility of a common biologic mechanism in the pathogenesis of these two disorders, in which special attention should be paid to the immune system function, especially the possible specific mechanisms by which cytokines can induce and maintain depressive symptoms and metabolic disorders. The data presented here emphasize the importance of recognition and treatment of depressive disorders with consequent reduction in the incidence of metabolic syndrome, but also the need of regular search for metabolic disorders and their treatment to avoid all of these adverse effects and maybe reduce the incidence of depressive disorders.
The aim of this study was to validate the Croatian translation of the Toronto Alexithymia Scale (TAS-26). For this purpose, 194 volunteers from the general population, both genders, aged between 18 ...and 60, were tested on this scale after it had undergone a repeated back-translation procedure by an independent bilingual translator. The mean total score on TAS-26 (mean ± SD) was 72.9±8.4. Cronbach's α-coefficient for the entire scale was 0.71, indicating the scale to be sufficiently reliable. When analyzing the α-coefficient of reliability for the entire scale, it was found that upon removal of one of the factors, only 3 factors ('I have physical sensations that even doctors don't understand'; 'When I'm upset, I don't know if I'm sad, frightened, or angry'; and 'I have feelings that I can't quite identify') would determine the α-coefficient of the entire scale amounting to less than 0.67, which would indicate insufficient reliability of the scale. The aforementioned factors belong to the group of F1 facet factors, the facet around which most items are grouped (n=12) and therefore the scale would be reliable enough even without the three factors. The results of factor analysis in our study confirmed the four-factor structure wherein most items are saturated by the first factor (n=12), and it denotes the alexithymia facet F1 (difficulty identifying feelings). Five items are saturated by the second factor and it denotes the alexithymia facet F2 (difficulty describing feelings), and the third factor which denotes facet F3 (reduced daydreaming) also saturated five items, whereas the fourth factor which denotes facet F4 (externally oriented thinking) saturated four items. The four listed facets explain 47.2% of variance wherein the highest percentage (20.1%) is attributed to facet F1, with facet F2 accounting for 12.1%, facet F3 for 7.5%, and facet F4 for 6.6% of variance.
Depression pharmacotherapy can be described with weak predictability of individual response. Antidepressants are prescribed based on trial and error, as it is not possible to determine which patients ...will respond to antidepressants. It would appear that pharmacogenetics is the most promising path towards achieving the goal of individualized therapy. Today, the most commonly prescribed antidepressants are those from the group of selective serotonin reuptake inhibitors (SSRI). The most investigated genetic variations in the prediction and individualization of antidepressant therapy is the serotonin transporter gene (5-HTTLPR). The objective of this paper is to provide an overview of the research to date on 5-HTTLPR polymorphism in response to SSRI. This paper gives an overview of 35 studies investigating the efficacy of SSRI antidepressants in dependence of 5-HTTLPR polymorphism. The results of three meta-analyses examining this issue are discussed. Briefly, the great majority of studies conducted have shown that L-allele carriers have a faster and better response to SSRI antidepressants, if they are Caucasians. Studies with negative results included ethnically mixed populations, and it is known that there are different allele frequencies among ethnic groups and the consequence of this are the varying results of pharmacogenetic studies. Pharmacogenetic analysis of 5-HTTLPR polymorphism has proven to be economically cost-effective considering the recurrent course of the disease. It would appear that the response to SSRI antidepressants and the development of adverse reactions are associated with 5-HTTLPR polymorphism in Caucasians and this pharmacogenetic analysis could be one of the first in future clinical practice.
Rationale
Beneficial effects of aripiprazole on cognition in schizophrenia have been previously reported, but not in recent onset schizophrenia. Cognitive impairments have also been associated with ...catechol-
O
-methyltransferase (COMT), methylenetetrahydrofolate reductase (MTHFR), and serotonin transporter (SERT) gene polymorphisms which were earlier implicated in the pathophysiology of schizophrenia.
Objectives
This study examined the short-term influence of aripiprazole long-acting injectable (LAI) as well as of COMT, MTHFR, and SERT gene polymorphisms and their interactions on clinical features and cognitive functions in inpatients with recent onset schizophrenia.
Methods
This study included 98 inpatients suffering from recent onset schizophrenia diagnosed according to DSM-5 criteria. Three months after initiating aripiprazole LAI, the severity of symptoms was assessed by the Positive and Negative Syndrome Scale (PANSS), while cognitive functions were measured by 5-KOG test for cognition. Genotypes of SERT, MTHFR, and COMT gene were determined by different polymerase chain reaction (PCR) methods.
Results
Three-month aripiprazole LAI treatment was associated with a statistically significant change of PANSS total (
p
<0.001) and subscale scores as well as cognitive parameters of delayed recall (
p
<0.03), attention (
p
<0.01), and executive functions in the form of less perseverations (
p
<0.03), without influencing other examined cognitive functions. However, it significantly influenced composite cognitive score (
p
<0.02). In regard to the investigated genetic polymorphisms, we established a positive association between the COMT polymorphism (M/M allele carriers) and attention (
p
<0.01). Additionally, we also established a positive association between the COMT – MTHFR interaction and attention (
p
<0.02), as well as perseveration item belonging to executive functions (
p
<0.01). Two other investigated polymorphisms (MTHFR and SERT) were not significantly associated with cognitive indices. Investigated genetic polymorphisms and their interactions were not associated with PANSS scores.
Conclusions
Our findings suggest that aripiprazole LAI improves individual cognitive functions in recent onset schizophrenia. Investigated COMT polymorphism (Met/Met genotype), as well as the COMT-MTHFR interaction, were positively associated with attention and executive functioning (perseveration), potentially implying COMT’s biomarker potential in terms of cognition in schizophrenia.
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