Publications by authors named "Filip Rybakowski"

51 Publications

Decreased leucocyte telomere length in male patients with chronic bipolar disorder: lack of effect of long-term lithium treatment.

Acta Neuropsychiatr 2021 Aug 9:1-8. Epub 2021 Aug 9.

Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.

Objectives: Bipolar disorder (BD) may be connected with accelerated aging, the marker of this can be shorter telomere length (TL). Some data suggest that lithium may exert a protective effect against telomere shortening. The study aimed to compare the TL between patients with BD and control subjects. The effect of long-term lithium treatment was also assessed.

Methods: The study group comprised 41 patients with BD, including 29 patients treated longitudinally with lithium (mean 16.5 years) and 20 healthy people. TL was assessed by the quantitative polymerase chain reaction (qPCR).

Results: In the control group, the TL was significantly longer in males than in females. Male bipolar patients had significantly shorter TL compared with the control male group. In bipolar patients, there was no correlation between TL and duration of treatment. The TL was negatively correlated with age in male bipolar patients.

Conclusions: The study did not confirm the lithium effect on TL in bipolar patients. TL showed gender differences, being shorter in BD males, compared to control males, and longer in healthy males, compared to control females.
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http://dx.doi.org/10.1017/neu.2021.20DOI Listing
August 2021

Evaluation of the Frequency of RETN c.62G>A and RETN c.-180C>G Polymorphisms in the Resistin Coding Gene in Girls with Anorexia Nervosa.

Endokrynol Pol 2021 Jul 22. Epub 2021 Jul 22.

Department of Adult Psychiatry, University of Medical Sciences in Poznań, Poland.

Introduction: Anorexia nervosa (AN) is a serious psychosomatic syndrome, classified as an eating disorder. AN patients strive to lose weight below normal limits defined for a specific age and height, achieving their goal even at the expense of extreme emaciation. AN has a multifactorial etiology. Genetic factors are believed to be significant in the predisposition to the development of AN. In girls suffering from AN significantly lower levels of resistin (RES) in blood serum are observed as compared to healthy girls. These differences may lead to a thesis that functional genetic polymorphisms in RES coding genes can be responsible for this phenomenon. In our pilot study we demonstrated significant differences in the distribution of genotypes in the loci RETN c.-180C>G of the RES gene in 67 girls with AN and 38 healthy girls. It seems reasonable to compare the frequency of polymorphisms of RETN c.62G>A and RETN c.-180C>G in the RES gene in girls with AN and in healthy subjects in a bigger cohort and to analyse correlations between individual variants of the polymorphisms referred to above and the RES levels in blood plasma.

Material And Methods: The study covered 308 girls with the restrictive form of AN (AN) and 164 healthy girls (C) (aged 11-19). The RES levels in blood serum were determined by means of the ELISA method on Bio-Vendor, LLC (Asheville, North Carolina, USA). The DNA isolation was carried out by means of Genomic Mini AX BLOOD (SPIN). The PCR reaction was carried out in the thermocycler ThermoCycle T100. 80-150 ng of the studied DNA and relevant starters F and R were added to the reaction mixture. The reaction products were subjected to digestion by restriction enzymes and separated on agarose gels (RFLP).

Results: The average RES level in blood serum in the AN group was significantly lower (p< 0.0001) than in the C group. The distribution of genotypes in the loci RETN c.62 of the RES gene was similar in both groups. A significant difference was demonstrated in the distribution of genotypes in the polymorphic site RETN c.-180 of the RES gene between AN and C (p=0.0145) and in the distribution of the C and G alleles in the loci RETN c.-180 (p< 0.0001). The C allele occurred significantly more frequently than the G allele in the C group as compared to the AN group. In all the study subjects jointly (AN and C) a significant positive correlation between the blood RES levels on one hand and the body mass (r= 0.42; p< 0.0001) and BMI (r= 0.61; p< 0.0001) on the other hand was observed. There was no correlation between the concentration of RES in blood serum and the distribution of genotypes in the loci of the resistin gene referred to above.

Conclusions: The CG genotype in the loci RETN c.-180 C>G of the RES gene may constitute one of the factors predisposing to the development of AN in girls. The genotype in the loci RETN c.62 G>A and RETN c.-180 C>G of the resistin gene has no influence on the levels of this hormone in blood in AN patients.
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http://dx.doi.org/10.5603/EP.a2021.0065DOI Listing
July 2021

Evaluation of the Frequency of ADIPOQ c.45 T>G and ADIPOQ c.276 G>T Polymorphisms in the Adiponectin Coding Gene in Girls with Anorexia Nervosa.

Endokrynol Pol 2021 Jul 22. Epub 2021 Jul 22.

Department of Adult Psychiatry, University of Medical Sciences in Poznań, Poland.

Introduction: Anorexia nervosa (AN) is a serious chronic psychosomatic disorder, the essence of which are attempts to obtain a slim silhouette by deliberate weight loss (restrictive diet, strenuous physical exercise, provoking vomiting). The etiology of this disorder is multifactorial. Genetic factors which influence the predisposition to AN have been searched for. A broad meta-analysis points to a strong genetic correlation between AN and insulin resistance. Adiponectin (ADIPO) increases insulin sensitivity. In our pilot study we demonstrated that the TT genotype in loci ADIPOQ c.276 G>T of the ADIPO gene and a higher concentration of ADIPO in blood serum occurs significantly more frequently in 68 girls suffering from AN than in 38 healthy girls. The objective of this study is to evaluate the frequency of the occurrence of ADIPOQ c.45 T>G and ADIPOQ c.276 G>T in the ADIPO gene in a bigger cohort of girls with AN and healthy girls, as well as an analysis of correlations between variants of the aforementioned polymorphisms and the levels of ADIPO in blood serum.

Materials And Methods: The study covered 472 girls (age: 11-19): 308 with the restrictive form of AN (AN), and 164 healthy girls (C). The level of ADIPO in blood serum was determined by means of the ELISA method on Bio-Vendor, LLC (Asheville, North Carolina, USA). The DNA isolation was carried out by means of Genomic Mini AX BLOOD (SPIN). The PCR reaction was carried out in the thermocycler ThermoCycle T100. 80-150 ng of the studied DNA and relevant starters F and R were added to the reaction mixture. The reaction products were subjected to digestion by restriction enzymes and separated on agarose gels (RFLP).

Results: The distribution of genotypes in the polymorphic site ADP c.45 of the ADIPO gene and ADP c.276 was similar in both groups. In both groups the T allele was most frequent in loci ADIPOQ c.45 and the G allele in loci ADIPOQ c.276. In all the study subjects collectively (AN and C) a statistically significant negative correlation between the levels of ADIPO in blood serum on one hand and the body weight (r= -0.46; p< 0.0001) and BMI (r= -0.67; p< 0.0001) on the other was demonstrated. Exclusively in the AN group a significant correlation between the level of ADIPO in blood and the distribution of TG, TT, and GG alleles in loci ADIPOQ c.45 and ADIPOQ c.276 was demonstrated (p= 0.0052 and p< 0.0001; respectively).

Conclusions: The genotype in loci ADIPOQ c.45 and ADIPOQ c.276 of the ADIPO gene seems to have no effect on the predisposition to AN. Girls suffering from AN with the TT genotype in loci ADIPOQ c.45 and ADIPOQ c. 276 may demonstrate higher insulin sensitivity as they have significantly higher levels of ADIPO than girls suffering from AN with other genotypes. This may be suggestive of their better adaptation to the state of malnutrition, as well as it can have a potential effect on treatment effects.
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http://dx.doi.org/10.5603/EP.a2021.0064DOI Listing
July 2021

Dysfunctions of the retina and other elements of the visual system in schizophrenia.

Psychiatr Pol 2020 Aug 31;54(4):673-686. Epub 2020 Aug 31.

Uniwersytet Medyczny w Poznaniu, Klinika Psychiatrii Dorosłych.

Schizophrenia is an illness with a large variety of symptoms, significant variability of the individual course, and still not fully explained etiology. It is suggested that genetic, infectious and immunological factors may be involved, and neurodevelopmental, neurodegenerative and neurotransmitter hypotheses have been proposed. Detection of the measurable and reproducible biological indicators of the clinical picture and the course, referred to as biomarkers, may be essential to elucidate the etiopathogenic mechanism of the illness. For schizophrenia, this function may be performed by the retina of the eye and other elements of the visual pathway. The observed abnormalities are of a structural and functional nature. They concern virtually the entire visual system, and, in accordance with the neurodevelopmental theory of schizophrenia, arise at the early stages of brain formation. What is essential - the specific structure of the human eye, its translucency, lack of myelin and low concentration of glial cells provide excellent opportunities for non-invasive assessment of the microstructure and function of the central nervous system. The following paper discusses the most important changes in the visual apparatus observed in patients with schizophrenia. Particular attention was paid to retinal vascular changes, anomalies in the electroretinogram and optical coherence tomography, structural and functional disorders of cortical centers and neurochemical disorders in the cells of the visual pathway.
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http://dx.doi.org/10.12740/PP/114952DOI Listing
August 2020

Psychiatric Symptoms as the First or Solitary Manifestation of Somatic Illnesses: Hyperammonaemia Type II.

Neuropsychobiology 2021 20;80(3):271-275. Epub 2020 Jul 20.

Department of Paediatrics Nutrition and Metabolic Diseases, The Children's Memorial Health Institute, Warsaw, Poland.

Aim: We describe the difficulties encountered in making a diagnosis where a somatic condition manifests itself alongside psychiatric symptoms associated with possible psychiatric comorbidities.

Methods: A case study is presented of a 15-year-old girl who was eventually diagnosed with ornithine transcarbamylase (OTC) deficiency (hyperammonaemia type II), following an initial diagnosis of pervasive developmental disorder, selective mutism, and anorexia nervosa.

Results: The OTC disease is not fully expressed in females and its prevalence is lower than in males. Around 17-20% of female patients found with a defective OTC gene on an X chromosome can suffer from OTC deficiency that may result in elevated levels of ammonia in the blood; this occurs when one of the X chromosomes become inactivated. Patients typically present with nausea, migraines, and a history of dietary protein avoidance. In more severe cases, ataxia, confusion, hallucinations, and cerebral oedema can occur. The OTC deficiency can thus remain undiagnosed in women for many years.

Conclusion: Somatic comorbidity in psychiatric inpatients is commonly found; however, such disorders are rarely diagnosed or even treated adequately.
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http://dx.doi.org/10.1159/000508679DOI Listing
July 2020

Non-pharmacological treatments of inpatients with major depression - The case of Polish (Poznan) and German (Kiel) hospital.

Complement Ther Clin Pract 2020 May 29;39:101129. Epub 2020 Feb 29.

Department of Pharmacoeconomics and Social Pharmacy, Poznan University of Medical Sciences, Rokietnicka 7 St, 60-806, Poznań, Poland.

Background And Purpose: Although the treatment of depression should be comprehensive, there is insufficient information about non-pharmacological interventions used during hospitalization. Hence, the aim was to compare non-pharmacological interventions used in psychiatry clinics in Kiel (Germany) and Poznan (Poland).

Methods And Materials: The retrospective study covered all patients hospitalized in 2016 (F32 or F33). Out of 545 patients hospitalized in 2016 in both centers, the analysis concerns 322 records from Kiel and 168 from Poznan.

Results: Non-pharmacological treatments were used in both centers. However, in Kiel there were more therapeutic options. Contrary to Poznan, patients in Kiel used therapies like "Kneippen", Qigong, and light therapy.

Conclusions: Implementing Tai Chi in Kiel would be interesting to develop the scope of used interventions. Investment in non-pharmacological treatment should be a priority for healthcare decision-makers in Poland. The wide range of non-pharmacological interventions should be commonly accessible to provide the most comprehensive treatment.
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http://dx.doi.org/10.1016/j.ctcp.2020.101129DOI Listing
May 2020

Treatment-resistant depression: Neurobiological correlates and the effect of sleep deprivation with sleep phase advance for the augmentation of pharmacotherapy.

World J Biol Psychiatry 2021 01 6;22(1):58-69. Epub 2020 May 6.

Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.

Objectives: To assess the neurobiology of treatment-resistant depression (TRD), and factors connected with improvement after total sleep deprivation (TSD) with sleep phase advance (SPA), for the augmentation of pharmacotherapy.

Methods: The study comprised 43 patients with TRD, (15 male, 28 female), aged 48 ± 13 years, with the illness duration 12 ± 9 years, and the depressive episode 8 ± 7 months. TRD was defined as a lack of significant improvement despite at least two antidepressant treatments and the augmentation with mood-stabilisers. Clinical improvement (response) was a reduction of ≥50% of points in the Hamilton Depression Rating Scale (HDRS), and the remission criterion was ≤7 points in HDRS, lasting until the 14th day after TSD + SPA.

Results: TRD severity was associated with greater activity of the hypothalamic-pituitary-adrenal axis, the pro-inflammatory status of the immune system and lower reactivity of the hypothalamic-pituitary-thyroid axis. The response was achieved by 18 of 42 subjects, and connected with the later onset and shorter duration of the disease. In responders, there was a decrease in cortisol and interferon-gamma. In all subjects, a decrease in thyroid hormones was observed.

Conclusions: TRD can improve after augmentation of pharmacotherapy by TSD + SPA and some biological changes may be compatible with a decrease in allostatic load.
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http://dx.doi.org/10.1080/15622975.2020.1755449DOI Listing
January 2021

Brain-Derived Neurotrophic Factor and Oxytocin Signaling in Association With Clinical Symptoms in Adolescent Inpatients With Anorexia Nervosa-A Longitudinal Study.

Front Psychiatry 2019 28;10:1032. Epub 2020 Feb 28.

Department of Child and Adolescent Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.

Introduction: Brain-derived neurotrophic factor (BDNF), as well as oxytocin (OXY), are centrally secreted neuropeptides regulating a range of physiological processes, including food intake and metabolism. Moreover, numerous reports suggest their role in affective and cognitive symptoms of various psychiatric disorders. Thus, the study aimed to measure the serum level of BDNF and its receptor-tropomyosin-related kinase B (TrkB) and OXY in the malnourished anorexia nervosa patients and following partial weight-recovery. The correlations between levels of these proteins with the primary symptoms of the anorexia nervosa (AN) were also analyzed.

Methodology: Eighty-four adolescent AN patients were recruited into the study, but only forty-two AN patients completed it. The control group comprises of thirty age- and height-matched girls (CG). Serum BDNF, TrkB, and OXY levels were measured in AN group in two time-points-at the beginning of the hospitalization in malnourished patients (AN-T1) and again after partial weight normalization, on the day of discharge (AN-T2). The severity of eating disorders, as well as depressive and obsessive-compulsive symptoms, were assessed at the same two-time points.

Results: Body mass index (BMI) differed significantly between the AN-T1, AN-T2, and CG. BDNF levels for the AN-T2 increased significantly in comparison to the AN-T1, but at two-time points were significantly lower than in the CG. The OXY level did not change with weight gain and in both groups AN-T1 and AN-T2 were statistically significantly higher than in the CG. Statistically significant negative correlations between BDNF and the severity of eating disorders symptoms were found. Depressive and obsessive-compulsive symptoms did not show significant correlations with levels of studied proteins for either malnourished or partially weight recovered AN patients.

Conclusions: BDNF serum levels were decreased in the malnourished AN patients and tended to normalize with partial weight recovery. OXY serum levels were found to be increased in the malnourished AN patients and did not normalize with partial weight recovery, confirming previous reports about its role in the etiopathogenesis of AN. BDNF can be related to aberrant eating behaviors occurring in AN. Our results do not support the role of serum levels of BDNF, TrkB, or OXY in the modulation of depressive or obsessive-compulsive symptoms.
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http://dx.doi.org/10.3389/fpsyt.2019.01032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7058805PMC
February 2020

Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies.

Addict Biol 2021 01 16;26(1):e12880. Epub 2020 Feb 16.

Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, RWTH Aachen University, Aachen, Germany.

Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [r ], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from ~2400 to ~537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (r = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (r = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (r = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (r = -0.19 to -0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors.
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http://dx.doi.org/10.1111/adb.12880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429266PMC
January 2021

Psychiatric disorders in women with polycystic ovary syndrome.

Psychiatr Pol 2019 Aug 31;53(4):955-966. Epub 2019 Aug 31.

Uniwersytet Medyczny w Poznaniu, Klinika Niepłodności i Endokrynologii Rozrodu.

Polycystic ovary syndrome (PCOS) is the most commonly diagnosed endocrine disorder in women of reproductive age, affecting approximately 5-8% of females in this group. It is characterized by hyperandrogenism, abnormal periods (rare periods or amenorrhea) and polycystic ovaries visualized through ultrasonography. The etiopathogenesis of polycystic ovary syndrome has not been elucidated in detail. There are numerous hypotheses on this subject which tend to complement one another. The most widely recognized hypothesis is that the development of PCOS is due to insulin resistance and hyperinsulinemia, which subsequently lead to hyperandrogenism. On the basis of an as of yet relatively small number of studies, an increased prevalence of various psychiatric disorders can be observed in women with PCOS. These include: depression, generalized anxiety disorder, personality disorders, social phobia, obsessive-compulsive disorder, attention deficit hyperactivity disorder (ADHD), and eating disorders. Bipolar affective disorder, schizophrenia and other psychotic disorders have also been reported in women with PCOS more often than in the general population. The higher prevalence of psychiatric disorders in patients with PCOS, especially depression and anxiety disorders, may be due to both hyperandrogenism and the resulting somatic symptoms. These symptoms can undoubtedly be stigmatizing for women and lower their quality of life. This article is intended to provide an overview of the literature regarding mental disorders associated with polycystic ovary syndrome and to present own research on depression and sexual dysfunction in this group.
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http://dx.doi.org/10.12740/PP/OnlineFirst/93105DOI Listing
August 2019

Interaction between polymorphisms of the oxytocinergic system genes and emotion perception in inpatients with anorexia nervosa.

Eur Eat Disord Rev 2019 09 5;27(5):481-494. Epub 2019 Aug 5.

The Department of Genetics, The Institute of Psychiatry and Neurology, Poland.

Objective: The empirical literature describes the role of the oxytocinergic system in emotion perception (EP). Variants in the oxytocin (OXT) and oxytocin receptor genes have been associated with mental disorders, including anorexia nervosa (AN), that are characterized by difficulties in socioemotional functioning. Our study aimed to examine whether variability within the genes related to OXT pathways may play a role in facial EP in inpatients with AN.

Method: Single nucleotide polymorphisms (SNPs) of the following genes: oxytocin receptor (rs2254298, rs53576), OXT (rs6133010), OXT-arginine-vasopressin (rs2740204), CD38 (rs6449197, rs3796863), and human leucyl/cystinylaminopeptidase (rs4869317) were genotyped in 60 AN female inpatients and 60 healthy control females (HCs). Associations between genetic polymorphisms and EP as well as clinical symptoms were examined.

Results: The AN group showed decreased EP abilities compared with HCs. SNPs of rs2740204, rs6133010, and rs53576 were associated with differences in EP in women with AN and in HCs. The SNP of rs4869317 was associated with the level of eating disorders symptoms in HCs.

Conclusions: The OXT system may be involved in EP difficulties in AN. SNPs within genes related to OXT pathways may influence EP abilities. The leucyl/cystinylaminopeptidase rs4869317 SNP may be involved in the development of eating disorders psychopathology.
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http://dx.doi.org/10.1002/erv.2698DOI Listing
September 2019

Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa.

Nat Genet 2019 08 15;51(8):1207-1214. Epub 2019 Jul 15.

Clinical Genetics Unit, Department of Woman and Child Health, University of Padova, Padova, Italy.

Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness, affecting 0.9-4% of women and 0.3% of men, with twin-based heritability estimates of 50-60%. Mortality rates are higher than those in other psychiatric disorders, and outcomes are unacceptably poor. Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI) and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.
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http://dx.doi.org/10.1038/s41588-019-0439-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6779477PMC
August 2019

Adiponectin and resistin in acutely ill and weight-recovered adolescent anorexia nervosa: Association with psychiatric symptoms.

World J Biol Psychiatry 2019 11 28;20(9):723-731. Epub 2018 Sep 28.

Department of Psychiatry, Poznan University of Medical Sciences, Poznan, Poland.

Anorexia nervosa (AN) is a chronic illness where restriction of food intake results in decreased adipose tissue. The aim of this study was to measure the concentration of adiponectin and resistin in acute and partially weight-recovered anorectic inpatients. The associations of their levels with eating disorder symptoms were also assessed. A longitudinal study was conducted on 76 adolescent patients (ANG) and 30 age-matched healthy girls (CG). Selected adipokines serum levels, as well as the severity of depressive, obsessive-compulsive and disturbed eating behaviours, were analysed in the group of anorectic patients before (accAN) and after weight gain (recAN) and compared with the CG. The concentration of adiponectin in the accAN was higher than in the CG ( = 0.05) and increased in recAN ( = 0.01). Resistin concentrations were lower in accAN and recAN than in the CG ( 0.00). A negative correlation between adiponectin and the scores in Yale-Brown Obsessive Compulsive Scale as well as positive between resistin and Beck Depression Inventory were found. In the acute AN, adiponectin and resistin levels are impaired and partial weight recovery fails to normalise them thus we suggest that they can be involved in the chronicity of certain symptoms. The level of adiponectin is associated with obsessive and compulsive symptoms and resistin with depressive symptoms, which indicates their potential contribution to the regulation of emotions and behaviours in AN.
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http://dx.doi.org/10.1080/15622975.2018.1492735DOI Listing
November 2019

Analysis of shared heritability in common disorders of the brain.

Science 2018 06;360(6395)

Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.
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http://dx.doi.org/10.1126/science.aap8757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6097237PMC
June 2018

The economic burden of inpatient care of depression in Poznan (Poland) and Kiel (Germany) in 2016.

PLoS One 2018 14;13(6):e0198890. Epub 2018 Jun 14.

Department of Pharmacoeconomics and Social Pharmacy, Poznan University of Medical Sciences, Poznan, Poland.

Depression is a global health problem associated with a significant public health burden and costs. Although studies on costs of diseases are being considered as an increasingly important factor for health policies, information concerning costs of inpatient care of depression is still insufficient. Thus, the main aim of this study was to evaluate costs of hospitalization of patients treated in 2016 in psychiatric clinics in Poznan (Poland) and in Kiel (Germany) and to analyze treatment used in these centers. The study was conducted from September 2017 to February 2018. 545 hospital records were considered (187 in Poznan and 358 in Kiel). Eventually, 490 hospital records were included, 168 in Poland and 322 in Germany. In general, the costs were calculated based on the patients' sex and diagnosis (F32 and F33) separately and, subsequently, the outcomes were added and multiplied by the length of hospital stay, giving the cost of hospitalization. The annual cost of inpatient care of depression in 2016 was EUR 491,067.19 ([Formula: see text]) in Poznan and EUR 2,847,991.00 [Formula: see text] in Kiel. In Poznan, hospitalization was underfunded reaching EUR 183,042.55 (37.27% of total costs in Poznan). In Poznan, the most frequently prescribed medicine was quetiapine, followed by olanzapine and venlafaxine, whereas in Kiel it was venlafaxine, followed by mirtazapine and promethazine. Although non-pharmacological therapies were commonly used in both centers, in Kiel this type of treatment was better structured. The study confirms the degree of the economic burden of inpatient care of depression. The underfunding of mental health revealed, emphasizes the need for urgent amendment of organization and funding of mental health care in Poland. Patients in Poznan were hospitalized on average 10 days longer than in Kiel, thus a reduction of length of hospitalization in Poznan seems possible. Although pharmacotherapy seemed to be comprehensive in both centers, there were some differences between Poznan and Kiel. Access to non-pharmacological therapies during outpatient care was limited in Poznan, however, compared to Kiel.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0198890PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6001949PMC
December 2018

Inpatient psychiatric treatment is not always effective in adolescent sample.

Int J Psychiatry Clin Pract 2018 Mar 21;22(1):70-76. Epub 2017 Aug 21.

c Insitute of Psychology , University of Social Sciences and Humanities , Poznan , Poland.

Objective: Numerous studies confirm efficacy of psychiatric treatment as well as psychiatric placebo. The aim of the current study was the assessment of improvement rate and factors associated with treatment response in naturalistic group of adolescent inpatients.

Methods: Eighty two consecutive adolescent inpatients were recruited. Each patient at the admission and discharge was assessed with brief psychiatric rating scale (BPRS), eating attitude test (EAT-26), clinical global impression scale (CGI-S) and children global assessment scale (CGAS). Individual and family history was assessed by semi-structured interview. Patients, who improved in at least two interviewer-based scales (IMP, n = 67) were compared to the rest (N-IMP, n = 15). For statistical analysis STATISTICA package was used.

Results: The main difference between groups was ICD-10 diagnosis distribution: in the IMP group more anxiety-related disorders (F4), in the N-IMP group more personality disorders (F6). Other differences include history of paediatric hospitalisations and surgery (more in the N-IMP group). Most of the analysed factors did not differ between groups.

Conclusions: The inpatient treatment seems to be most effective in severe mental states and in anxiety-related disorders and least effective in personality disorders. Due to limited inpatient treatment efficacy we believe outpatients services are crucial in adolescent psychiatry.
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http://dx.doi.org/10.1080/13651501.2017.1364771DOI Listing
March 2018

Genetic polymorphisms and serum concentrations of adiponectin and resistin in anorexia nervosa and healthy controls - pilot study.

Neuro Endocrinol Lett 2017 Jul;38(3):215-223

Department of Adult Psychiatry, Poznan University of Medical Sciences, ul.Szpitalna 27/33, 60-572 Poznan, Poland.

Background: A possible role of adipokines in the regulation of body weight in patients with anorexia nervosa (AN) has been proposed. Polymorphisms in genes encoding adiponectin and resistin in AN have not been widely assessed, yet.

Objectives: 1) Assessment the frequency of ADIPOQ c.45T>G, ADIPOQ c.276G>T polymorphisms in adiponectin and RETN c.62G>A, RETN c.-180C>G in resistin genes in AN patients and control group (C) 2) Analysis of correlation between these polymorphisms and serum ADP or RETN.

Methods: We examined 67 AN girls and 38 C aged 11-18. Analyses of polymorphisms in ADIPOQ and RETN genes were performed using RFLP method and adiponectin and resistin serum levels - with commercially available ELISA kits.

Results: In AN subjects, TT genotype in ADIPOQ c.276 polymorphism as well as GG genotype of RETN c.-180 were significantly more frequent than in CG. In ADIPOQ c.45 polymorphic site, TT alleles were the most frequent in both examined groups. In RETN c.62 GA and GG alleles distribution did not differ between the groups and the most frequently observed genotype was GG. The mean serum adiponectin level in AN was significantly higher and resistin - lower than in controls. There were no statistically significant relationships between serum adiponectin and resistin levels and allele frequency in polymorphisms ADIPOQ c.276 as well as RETN c.-180 in the examined groups.

Conclusion: Differences in genotype frequencies of ADIPOQ c.276 and RETN c.-180 suggest a need for studies on a larger cohort of patients with AN.
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July 2017

Overweight in Boys With ADHD Is Related to Candidate Genes and Not to Deficits in Cognitive Functions.

J Atten Disord 2018 10 3;22(12):1158-1172. Epub 2016 Nov 3.

2 Poznan University of Medical Sciences, Poland.

Objective: The aim of the study was to assess the relationship of overweight, the polymorphisms of selected candidate genes, and deficits in the executive functions among children with ADHD.

Method: We examined 109 boys with ADHD aged between 7 and 17 years. The study indicated variants of 14 polymorphisms in eight candidate genes. We applied seven neuropsychological tests to evaluate the executive functions. Overweight was diagnosed on the basis of the guidelines of the International Obesity Task Force.

Results: Analyses revealed significant association between DRD4 rs1800955, SNAP25 rs363039 and rs363043, 5HTR2A rs17288723, and overweight in boys with ADHD. There were no significant differences in the level of neuropsychological test results between patients with overweight and without overweight.

Conclusion: Overweight in boys with ADHD is associated with polymorphisms in three candidate genes: DRD4, SNAP25, and 5HTR2A, but not through conditioning deficits in cognitive functions.
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http://dx.doi.org/10.1177/1087054716676364DOI Listing
October 2018

The role of genetic factors and pre- and perinatal influences in the etiology of autism spectrum disorders - indications for genetic referral.

Psychiatr Pol 2016 ;50(3):543-54

Poradnia Zaburzeń Komunikowania Kliniki Audiologii i Foniatrii, Instytut Fizjologii i Patologii Słuchu w Kajetanach.

Autism spectrum disorders (ASD) are caused by disruptions in early stages of central nervous system development and are usually diagnosed in first years of life. Despite common features such as impairment of socio-communicative development and stereotypical behaviours, ASD are characterised by heterogeneous course and clinical picture. The most important aetiological factors comprise genetic and environmental influences acting at prenatal, perinatal and neonatal period. The role of rare variants with large effect i.e. copy number variants in genes regulating synapse formation and intrasynaptic connections is emphasised. Common variants with small effect may also be involved, i.e. polymorphisms in genes encoding prosocial peptides system - oxytocin and vasopressin. The environmental factors may include harmful effects acting during pregnancy and labour, however their specificity until now is not confirmed, and in some of them a primary genetic origin cannot be excluded. In several instances, especially with comorbid disorders - intellectual disability, epilepsy and dysmorphias - a detailed molecular diagnostics is warranted, which currently may elucidate the genetic background of disorder in about 20% of cases.
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http://dx.doi.org/10.12740/PP/43234DOI Listing
April 2017

Impaired social cognition processes in Asperger syndrome and anorexia nervosa. In search for endophenotypes of social cognition.

Psychiatr Pol 2016 ;50(3):533-42

Klinika Psychiatrii Dzieci i Młodzieży IPiN w Warszawie.

A growing number of publications indicates presence of significant deficits in social cognition in patients with anorexia nervosa (AN). These deficits appear to be comparable in qualitative and quantitative dimension with impairment of the same functions among people with Asperger syndrome (AS). The aim of this study is to identify subject areas in the field of impairment of social cognition processes among people with Asperger syndrome and anorexia nervosa taking into consideration the potential contribution of genetic pathways of oxytocin and vasopressin in the pathogenesis of these diseases. In the first part of the paper a systematic analysis of studies aimed at the evaluation of the processes of social cognition among patients with AN and AS has been carried out. The results of a significant number of studies confirm the presence of deficits in social cognition in AN and AS. In addition, among patients with AN and AS there exists a similar structure and distribution of the brain functions in regions responsible for social cognition. The second part of the paper describes the role of the oxytocin-vasopressin system (OT-AVP) in the processes of social cognition in AN and AS. Its genetic basis and the possible importance of single nucleotide polymorphisms within the genes: OXT, AVP, CD38, OXTR, AVPR1A and LNPEP have also been presented.
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http://dx.doi.org/10.12740/PP/OnlineFirst/33485DOI Listing
April 2017

Executive functioning improves after remission of psychosis and may not deteriorate at short follow-up in early-onset schizophrenia.

Neuro Endocrinol Lett 2015 ;36(2):153-60

Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Neurology, Warsaw, Poland.

Objective: Cognitive functions are important determinants of outcome in schizophrenia. Psychiatric hospitalization and intensive treatment in the early-onset psychosis may reduce the severity of psychotic symptoms and improve cognitive functions. It is not clear if after discharge improvement or further deterioration of cognition is observed. The aim of the current study is the evaluation of executive functioning in early onset schizophrenia (EOS) across stages of illness.

Methods: Two groups of EOS patients: hospitalized subjects with first episode (FES, n=16) at the introduction of pharmacotherapy (T1) and after mean 7 weeks (T2) and stable outpatients group (SO, n=24) were assessed with the Wisconsin Card Sorting Test (WCST) the Positive and Negative Syndrome Scale. Matched healthy (n=32) controls were assessed with WCST.

Results: All patients performed significantly worse in WCST than healthy controls. Subjects in acute psychotic episode (FES T1) presented more pronounced executive impairment and psychopathological symptoms than after the resolution of psychotic symptoms (FES T2). No differences in executive function between FES T2 and SO group were observed. In all assessments perseverative errors correlated with negative symptoms.

Conclusion: Cognitive impairment is present at the onset of EOS and persists in attenuated but stable form after the resolution of psychotic symptoms.
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September 2015

Which aspects of long-term outcome are predicted by positive and negative symptoms in early-onset psychosis? An exploratory eight-year follow-up study.

Psychopathology 2015 2;48(1):47-55. Epub 2014 Dec 2.

Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Neurology, Warsaw, Poland.

Background: Early-onset psychoses show substantial variability of diagnostic and functional outcome. Finding reliable prognostic factors may allow to allocate resources to those with the worst prognosis. The aim of the study was to gain new insights regarding the potential value of baseline negative and positive symptoms as predictors of outcome in psychoses of early onset.

Method: Sixty-three patients with early-onset schizophrenia spectrum psychosis hospitalized in an adolescent psychiatry unit were assessed with the Positive and Negative Syndrome Scale during the index admission. Associations with diagnosis, illness course and functional outcome were analysed in mean 8 years of follow-up (range 3.4-13.5 years).

Results: The mean age at the index admission and the follow-up was 16.6 ± 1.2 and 24.5 ± 3.0 years, respectively. A significant majority of subjects continued psychiatric treatment (95%) and had been readmitted (71%). The mortality rate was 3% (suicide and accident). Negative symptoms were related to mental health service utilization during the follow-up. General severity of symptoms, specifically positive and cognitive factors were associated with the diagnosis of schizophrenia and inversely with diagnostic shift outside the schizophrenia spectrum at the catamnesis. Poor impulse control at baseline was associated with worse functional outcome. The drug-free subgroup with no occupational/educational activity compared with the drug-treated subjects showed lower levels of baseline negative symptomatology.

Conclusion: The study findings suggest that in patients with early-onset psychosis negative and positive symptoms show a differential prognostic value. Pharmacotherapy may attenuate the effect of symptoms on functional outcome. These hypotheses need to be tested in future studies using confirmatory approaches.
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http://dx.doi.org/10.1159/000366489DOI Listing
July 2015

Executive impairment predicts schizophrenia diagnosis and treatment status in mid-term follow-up of early-onset psychosis.

Neuropsychobiology 2014 1;70(3):181-8. Epub 2014 Nov 1.

Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Neurology, Warsaw, Poland.

Objectives: Early-onset psychoses (EOP) vary considerably with regard to diagnostic stability and functional outcome. The aim of this study was the assessment of executive dysfunction as a predictor of outcome in EOP.

Method: This was a retrospective cohort study. Twenty-five hospitalized patients with non-affective EOP were assessed with the Wisconsin Card Sorting Test (WCST) during the index admission. Associations with current diagnosis, further admissions, current treatment status and occupational and relationship outcome were analyzed in 6 years of follow-up.

Results: The mean age at the index admission and the follow-up was 16.1 ± 1.35 and 22.0 ± 2.1 years, respectively. After discharge, almost all subjects (96%) at least briefly continued psychiatric treatment, and the majority of them (76%) were readmitted. Worse baseline WCST results were associated with a follow-up schizophrenia diagnosis, being a psychiatric in- or outpatient at the moment of follow-up assessment and receiving psychotropic medication. A low number of completed categories correlated with receiving a disability pension at the follow-up.

Conclusion: In patients with EOP, baseline executive function impairment was associated with schizophrenia diagnosis and psychiatric treatment at the follow-up. The association between baseline results and psychiatric treatment may explain the limited effect of baseline impairment on follow-up occupational and relationship status.
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http://dx.doi.org/10.1159/000366486DOI Listing
July 2015

[Autism spectrum disorders - epidemiology, symptoms, comorbidity and diagnosis].

Psychiatr Pol 2014 Jul-Aug;48(4):653-65

In the new classification of American Psychiatric Association - DSM-5 - a category of autistic spectrum disorders (ASD) was introduced, which replaced autistic disorder, Asperger syndrome, childhood disintegrative disorder and pervasive developmental disorder not otherwise specified. ASD are defined by two basic psychopathological dimensions: communication disturbances and stereotyped behaviors, and the diagnosis is complemented with the assessment of language development and intellectual level. In successive epidemiological studies conducted in 21 century the prevalence of ASD has been rising, and currently is estimated at 1% in general population. The lifetime psychiatric comorbidity is observed in majority of patients. The most common coexisting diagnoses comprise disorders ofanxiety-affective spectrum, and in about 1/3 of patients attention deficit/ hyperactivity disorders could be diagnosed. Prodromal symptoms of ASD may emerge before 12 months of life, however reliability of diagnosis at such an early age is poor. Several screening instruments, based on the parental and/or healthcare professional assessments may be helpful in ASD detection. However, structured interviews and observation schedules remain the gold standard of diagnosis.
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November 2014

[Neurocognitive and social cognition deficits in patients with anorexia nervosa].

Psychiatr Pol 2014 May-Jun;48(3):465-75

In the first part of the article the authors present a set of the actual concepts explaining problems of cognitive functions and social cognition currently observed in patients with anorexia nervosa (AN). It is possible; through the neuroimaging research, to get better understanding of the brain specifics in these individuals. Even though, the AN remains a disease with very complex and multifactorial etiology which remains a huge medical challenge. Currently, popular is the view that takes into consideration the integrating role of the insula and subcortical structures (such as hippocampus, amygdala, thalamus) in the regulation of cognitive and emotional processes in people suffering from AN. There is still an open problem, however, of the selection of therapeutic interventions targeting these deficits. The second part of the article presents the attempt to describe deficits in neurocognitive and social cognition in people with AN occurring prior to illness, during and after the recovery. Particular attention has been paid to the most frequently described in the literature--neurocognitive deficits such as rigidity of thinking, weak central coherence, and deficits in social cognition, including mental processes of perception and expression of emotions, disorders of the theory of mind (ToM) and empathy. The results of previous studies, their scarcity in Poland, do not give a satisfactory answer to the question whether the above mentioned disorders are a feature of endophenotype or condition in an episode of the disease. Research point to the more permanent nature, which may be more resistant to therapeutic modifications.
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October 2014

Adolescent insanity revisited: course and outcome in early-onset schizophrenia spectrum psychoses in an 8-year follow-up study.

Compr Psychiatry 2014 Jul 31;55(5):1174-81. Epub 2014 Mar 31.

Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Neurology, ul. Sobieskiego 9, 02-957 Warsaw, Poland; University of Social Sciences and Humanities, ul. Kutrzeby 10, Poznan, Poland. Electronic address:

Objectives: Despite inclusion of adolescent insanity-a concept proposed by Thomas Clouston in late XIX century-into the broader nosological entity of dementia praecox, the uniqueness of early psychosis is still discussed. The aim of the current study is the assessment of course and outcome in the large sample of early-onset psychosis subjects.

Method: Of 299 patients hospitalized in the period 1998-2008 in an adolescent psychiatry ward with schizophrenia spectrum diagnosis 158 completed a follow-up interview. Data concerning current diagnosis, further admissions, current treatment status and occupational and relationship outcome were analyzed after a mean of 8 years of follow-up.

Results: Mean age at the index admission and the follow-up was 16.6 ± 1.2 and 24.5 ± 3.0 years respectively. After the subsequent discharge almost all subjects (97%) at least briefly continued psychiatric treatment and 75% of patients had been readmitted. Overall diagnostic stability was 42%. For schizophrenia spectrum disorders and schizophrenia diagnostic stability was 72% and 78%, respectively. At the follow-up assessment 119 (77.3%) of the traced subjects declared current psychiatric treatment and 110 (73.3%) were receiving pharmacotherapy. Almost half of the subjects (48%) were employed or studying and more than a third (35.8%) remained in a stable relationship. Different distributions of baseline diagnoses were observed in males and females, and the latter showed a better outcome.

Conclusion: Early-onset psychoses were characterized by limited diagnostic stability, a necessity for further treatment and hospitalizations and significant percentage of unfavorable functional outcomes. Baseline diagnosis of acute and transient psychotic disorders and female gender were associated with an overall better outcome.
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http://dx.doi.org/10.1016/j.comppsych.2014.03.013DOI Listing
July 2014

Inverse relationship between leptin increase and improvement in depressive symptoms in anorexia nervosa.

Neuro Endocrinol Lett 2014 ;35(1):64-7

Department of Child and Adolescent Psychiatry, Poznan University of Medical Sciences, Poland.

Objectives: Anorexia nervosa (AN) often presents with comorbid depressive symptoms and is characterized by low levels of neuroimmunomodulatory hormone - leptin. Treatment-induced weight gain tends to normalize those variables. The aim of the study was the longitudinal assessment of the relationship between leptin levels and depressive symptoms in patients with AN, since previous cross-sectional studies in different populations brought conflicting results.

Methods: Thirty AN inpatients were assessed twice - at admission and after mean body mass index (BMI) increase of 3.2 kg/m(2). Physical parameters were measured, blood samples for leptin levels drawn and depression evaluated with both clinician - (Hamilton Depression Rating Scale - HDRS) and self - (Beck Depression Inventory - BDI) rated scales at the same morning. Correlation coefficients between changes in assessed variables, and linear regression for changes in depression scores were calculated.

Results: BMI and leptin levels showed significant increase after treatment, respectively 14.45±0.90 vs. 17.61±0.87 and 1.87±1.14 vs. 7.47±4.65, whereas severity of depressive symptoms measured with BDI and HDRS was significantly reduced: 18.69±12.65 vs. 11.62±11.59; 12.76±6.90 vs. 5.66±4.91, respectively. In linear regression analysis decrease of the clinician-rated depression score (HDRS) was directly associated with decrease in the self-assessed depressive symptoms (BDI) (standardized Beta=0.45; t=2.60; p<0.05) and inversely related to the increase in leptin level (standardized Beta=-0.33; t=-2.08; p<0.05).

Conclusions: These results may suggest, that increase in leptin levels during weight recovery in patients with AN is associated with objectively measured depressive symptoms. Longitudinal studies in other populations are warranted to establish whether this relationship is valid across the weight spectrum.
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June 2014

Cognition and communication dysfunctions in early-onset schizophrenia: effect of risperidone.

Prog Neuropsychopharmacol Biol Psychiatry 2012 Dec 17;39(2):348-54. Epub 2012 Jul 17.

Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Neurology, Sobieskiego 9, 02-957 Warsaw, Poland.

Background: Cognitive impairment and formal thought disorder, also referred to as communication disturbances, are considered the core symptoms of schizophrenia, strongly affecting social functioning and long-term outcome. Several studies in adult patients suggest improvement of both functions after the treatment with atypical antipsychotic drugs. Such medications are also used as first line treatment in early-onset schizophrenia, however their efficacy in cognitive and communication domains in this population have not been systematically assessed.

Aim Of The Study: Evaluation of risperidone efficacy at psychopathological symptoms, cognitive impairment and formal thought disorder in adolescents with schizophrenia spectrum diagnosis.

Material And Method: Psychopathological symptoms, cognitive functioning and formal thought disorder were evaluated in 32 hospitalized adolescent patients with schizophrenia spectrum diagnosis at the beginning of risperidone treatment and after clinical improvement and compared to the results of matched healthy control group.

Results: Risperidone treatment was associated with reduction of symptom severity and moderate improvement of formal thought disorder and some aspects of executive functions. Working memory and verbal fluency were not improved. There were few correlations between psychopathological symptoms and results of cognitive tests, mainly between negative symptoms and executive functions.

Discussion: In early-onset schizophrenia spectrum disorders atypical antipsychotic treatment is associated with alleviation of symptoms and only selective and moderate cognitive and communication improvement.
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http://dx.doi.org/10.1016/j.pnpbp.2012.07.007DOI Listing
December 2012

Cognitive impairment and formal thought disorders in parents of early-onset schizophrenia patients.

Neuropsychobiology 2012 Jun 25;65(4):206-15. Epub 2012 May 25.

Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Neurology, Warsaw, Poland.

Background: Both cognitive impairment and formal thought disorder (communication disturbances) found in patients with schizophrenia are also commonly observed in their relatives. Recently, the role of such deficits as putative endophenotypes of schizophrenia has been proposed. However, in a majority of studies, the families of adult patients were assessed whereas the relatives of early-onset psychotic subjects were rarely studied. The aim of our study was to evaluate the presence of cognitive impairment and formal thought disorders in parents of adolescents with a diagnosis of schizophrenia spectrum disorder (SSD) and in matched healthy controls.

Method: Thirty-eight parents of 29 SSD adolescents and 38 healthy controls were assessed with a battery of neurocognitive tests and the Thought, Language and Communication Scale.

Results: Parents of schizophrenia patients showed an increased tendency for perseverative thinking when compared to matched healthy controls. No statistically significant differences in cognitive functioning were observed between the groups.

Conclusion: These results may suggest the need for further exploration of communication disturbances as a potential endophenotypic marker of early-onset schizophrenia.
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http://dx.doi.org/10.1159/000337001DOI Listing
June 2012
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