Genotypic and Haplotypic Association of Catechol-O-Methyltransferase rs4680 and rs4818 Gene Polymorphisms with Particular Clinical Symptoms in Schizophrenia.

Catechol-O-methyl transferase (COMT) gene variants are involved in different neuropsychiatric disorders and cognitive impairments, associated with altered dopamine function. This study investigated the genotypic and haplotypic association of COMT rs4680 and rs4618 polymorphisms with the severity of cognitive and other clinical symptoms in 544 male and 385 female subjects with schizophrenia. COMT rs4818 G carriers were more frequent in male patients with mild abstract thinking difficulties, compared to CC homozygotes or C allele carriers. Male carriers of COMT rs4680 A allele had worse abstract thinking (N5) scores than GG carriers, whereas AA homozygotes were more frequent in male subjects with lower scores on the intensity of the somatic concern (G1) item, compared to G carriers. Male carriers of COMT rs4818-rs4680 GA haplotype had the highest scores on the G1 item (somatic concern), whereas GG haplotype carriers had the lowest scores on G2 (anxiety) and G6 (depression) items. COMT GG haplotype was less frequent in female patients with severe disturbance of volition (G13 item) compared to the group with mild symptoms, while CG haplotype was more frequent in female patients with severe then mild symptoms. These findings suggest the sex-specific genotypic and haplotypic association of COMT variants with a severity of cognitive and other clinical symptoms of schizophrenia.

The Associations of Neutrophil-Lymphocyte, Platelet-Lymphocyte, Monocyte-Lymphocyte Ratios and Immune-Inflammation Index with Negative Symptoms in Patients with Schizophrenia.

Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR) and systemic immune-inflammation index (SII index) are increasingly used as indicators of inflammation in different conditions, including schizophrenia. However, their relationship with negative symptoms, including anhedonia, is largely unknown. Included were 200 patients with schizophrenia and 134 healthy controls (HC), assessed for physical anhedonia (PA), using the Revised Physical Anhedonia Scale (RPAS), and social anhedonia (SA) by the Revised Social Anhedonia Scale (RSAS). Patients were rated by the Positive and Negative Syndrome Scale (PANSS), the Clinical Assessment Interview for Negative Symptoms (CAINS) and the Brief Negative Symptom Scale (BNSS). Most of the negative symptoms were in a weak to moderate positive correlations with blood cell inflammatory ratios, namely, between NLR and MLR with PANSS negative scale, CAINS, and BNSS, and in male patients, between PLR and PANSS negative scale and CAINS. Fewer correlations were detected in females, but also in a positive direction. An exception was SA, given the negative correlation between its severity and the SII index in females, and its presence and higher PLR in males. While different negative symptoms were associated with subclinical inflammation, the relationship between SA and lower inflammatory markers deserves further exploration.

Changes in substance use and engagement in gaming/gambling in persons with severe mental illness during the COVID-19 pandemic and earthquakes: a community study in two points.

Introduction: External stressors, such as COVID-19 pandemic and earthquake, can cause an increase in substance use and addictive behavior in persons with severe mental illnesses (SMI). We analyzed the changes and predictors of substance use and addictive behavior in SMI during these double disasters in Croatia. Methods: Questionnaires exploring the presence of substance or behavior addiction disorder, mental ill health [Depression Anxiety Stress Scales-21 (DASS-21), Insomnia Severity Index (ISI), Perceived Stress Scale (PSS), Obsessive-Compulsive Inventory-Revised], coping mechanisms, and perceived social support [Multidimensional Scale of Perceived Social Support (MSPSS)] were administered among 90 participants with SMI included in the RECOVER-E study in May/June 2020 (first COVID-19 wave, Zagreb earthquake) and in December 2020/January 2021 (second COVID-19 wave, Petrinja earthquake). Results: In both time points, a major increase was observed in tobacco smoking (25.0%; 28.6%, respectively) predicted by discontinuation of antidepressants and higher DASS-21 score. Increased sedative use was observed (24.4%; 23.8%, respectively) predicted by higher PSS and ISI scores, lower MSPSS scores, antipsychotic discontinuation and not receiving community mental health team (CMHT) service. Discussion: In persons with SMI during a double disaster special attention needs to be given to reducing mental-ill health and stress, providing social support and continuity of psychiatric care, through medications and CMHTs.

The Associations between COMT and MAO-B Genetic Variants with Negative Symptoms in Patients with Schizophrenia.

Negative symptoms of schizophrenia, including anhedonia, represent a heavy burden on patients and their relatives. These symptoms are associated with cortical hypodopamynergia and impaired striatal dopamine release in response to reward stimuli. Catechol-O-methyltransferase (COMT) and monoamine oxidase type B (MAO-B) degrade dopamine and affect its neurotransmission. The study determined the association between COMT rs4680 and rs4818, MAO-B rs1799836 and rs6651806 polymorphisms, the severity of negative symptoms, and physical and social anhedonia in schizophrenia. Sex-dependent associations were detected in a research sample of 302 patients with schizophrenia. In female patients with schizophrenia, the presence of the G allele or GG genotype of COMT rs4680 and rs4818, as well as GG haplotype rs4818-rs4680, which were all related to higher COMT activity, was associated with an increase in several dimensions of negative symptoms and anhedonia. In male patients with schizophrenia, carriers of the MAO-B rs1799836 A allele, presumably associated with higher MAO-B activity, had a higher severity of alogia, while carriers of the A allele of the MAO-B rs6651806 had a higher severity of negative symptoms. These findings suggest that higher dopamine degradation, associated with COMT and MAO-B genetic variants, is associated with a sex-specific increase in the severity of negative symptoms in schizophrenia patients.

Physical and social anhedonia are associated with suicidality in major depression, but not in schizophrenia.

OBJECTIVE: This cross-sectional study investigated the association of physical and social anhedonia with suicidality in patients with major depressive disorder (MDD), schizophrenia, and in non-psychiatric controls. METHOD: All participants completed the revised Physical Anhedonia Scale (RPAS) and the revised Social Anhedonia Scale (RSAS) and were subdivided according to positive life-time suicide attempt history. MDD patients were evaluated with the Montgomery-Ãsberg Depression Rating Scale (MADRS), healthy respondents with the Patient Health Questionnaire-9 (PHQ-9), and schizophrenia patients with the Calgary Depression Scale for Schizophrenia (CDSS). RESULTS: In 683 study participants, the prevalence of each anhedonia was the highest in MDD, followed by schizophrenia, and lowest in the control group. Among MDD patients, those with physical and social anhedonia had greater rates of recent suicidal ideation, while a higher frequency of individuals with life-time suicide attempts was detected in those with only social anhedonia. In contrast, no association between either anhedonia and life-time suicide attempts or recent suicidal ideation was found in patients with schizophrenia. CONCLUSIONS: Assessing social and physical anhedonia might be important in MDD patients, given its association with both life-time suicide attempts and recent suicidal ideation. Suicidality in schizophrenia, while unrelated to anhedonia, might include other risk factors.

General Functioning in Patients With First-Episode Psychosis After the First 18 Months of Treatment.

BACKGROUND: One of the main goals in the treatment of first-episode psychosis (FEP) is achieving functional remission. This study aims to analyze whether initial neurocognitive status and the use of specific pharmacological and psychosocial treatment options in FEP can predict general functioning after 18 months of treatment. METHODS: We conducted a longitudinal naturalistic study with a sample of 129 patients with FEP treated at 2 Croatian psychiatric clinics from 2016until 2018. Ordinal regression was used to predict the global level of functioning assessed with the Global Assessment of Functioning scale (GAF) at the 18th month of treatment from the baseline symptoms (assessed with a set of neurocognitive tests) and different treatment options. RESULTS: Higher score on GAF at the 18th month was significantly predicted by female sex, better baseline verbal memory and GAF scores, and the type of treatment. Group multimodal psychosocial treatment, antipsychotic polytherapy, and not being treated with sedatives at baseline predicted better GAF scores at follow-up. In the exploratory analysis, taking sedatives in the final assessment and being rehospitalized due to relapse predicted worse GAF scores at the end of follow-up. CONCLUSIONS: Although baseline neurocognitive features and baseline general functioning seem to influence the overall long-term functioning of persons with FEP, addition of a multimodal group psychosocial treatment program and appropriate medication seem to be equally important for improving the patients' level of functioning after the FEP.

Integration of complementary biomarkers in patients with first episode psychosis: research protocol of a prospective follow up study.

In this project, we recruited a sample of 150 patients with first episode of psychosis with schizophrenia features (FEP) and 100 healthy controls. We assessed the differences between these two groups, as well as the changes between the acute phase of illness and subsequent remission among patients over 18-month longitudinal follow-up. The assessments were divided into four work packages (WP): WP1- psychopathological status, neurocognitive functioning and emotional recognition; WP2- stress response measured by saliva cortisol during a stress paradigm; cerebral blood perfusion in the resting state (with single photon emission computed tomography (SPECT) and during activation paradigm (with Transcranial Ultrasonography Doppler (TCD); WP3-post mortem analysis in histologically prepared human cortical tissue of post mortem samples of subjects with schizophrenia in the region that synaptic alteration was suggested by WP1 and WP2; WP4- pharmacogenetic analysis (single gene polymorphisms and genome wide association study (GWAS). We expect that the analysis of these data will identify a set of markers that differentiate healthy controls from patients with FEP, and serve as an additional diagnostic tool in the first episode of psychosis, and prediction tool which can be then used to help tailoring individualized treatment options. In this paper, we describe the project protocol including aims and methods and provide a brief description of planned post mortem studies and pharmacogenetic analysis.

Anhedonia in Schizophrenia: Mini-Review.

The perception of reward exerts a powerful influence on human behavior. While anhedonia might occur in healthy individuals, its prevalence and severity are much higher in psychiatric patients, particularly those with depression and schizophrenia. Anhedonia is a negative symptom, and presumably a trait marker in schizophrenia. Recent research confirmed that anhedonia is a complex construct, consisting of anticipatory, consummatory, and reward learning components. In general, schizophrenia patients show anticipation deficits, and a substantial portion of them have physical (PA) and social anhedonia (SA). The relationship between anhedonia and psychopathology appears bidirectional. While gene-environment interactions affect reward circuity, anhedonia modulates clinical features, such as suicidality and nicotine consumption. Future clinical research employing longitudinal designs may shed more light on the dynamics and treatment of anhedonia in schizophrenia.

Effects of Long-Term Multimodal Psychosocial Treatment on Antipsychotic-Induced Metabolic Changes in Patients With First Episode Psychosis.

Background: Antipsychotic-induced weight gain and metabolic abnormalities are one of the major challenges in the treatment of psychosis, contributing to the morbidity, mortality and treatment non-adherence. Different approaches were used to counteract these side effects but showed only limited or short-term effects. This study aims to analyse the effects of a long-term multimodal treatment program for first episode psychosis on antipsychotic-induced metabolic changes. Methods: We enrolled 71 patients with first episode psychosis treated at the Zagreb University Hospital Centre from 2016 until 2018. Participants were assigned to one of the two groups: day hospital program vs. treatment as usual (TAU). Outcomes were: body weight, blood glucose, lipids and cholesterol, psychopathology and global level of functioning during the 18-months follow-up. Results: Although the TAU group gained more weight and had higher increase of blood glucose, while the day hospital group had a higher increase in total cholesterol at 18th month follow-up, after the adjustment for age, gender and baseline measures, the type of treatment was not significantly associated with any of the primary outcome measures. Patients' psychopathology measures significantly decreased and their functional level significantly increased at month 18th in both groups. Conclusion: While both types of treatment were effective in reducing psychopathology and restoring the patients' level of functioning, both were relatively ineffective in counteracting antipsychotic-induced metabolic abnormalities and antipsychotic-induced weight gain.

Peace test: is war sometimes a better solution? Survey of students of Zagreb and Mostar Schools of Medicine.

AIM: To investigate the differences among medical students from two medical schools, one in Zagreb, Croatia, and the other in Mostar, Bosnia and Herzegovina, in their affinity towards peaceful vs violent way of solving conflicts. METHODS: A total of 733 students from the Zagreb and 102 medical students from the Mostar University School of Medicine filled out an anonymous questionnaire during their enrollment into the next academic year. The questionnaire consisted of 10 Likert-type questions with 1-5 answer scale, which were designed to give an illustration of students' attitude towards war. The test score was calculated as the sum of all answers x 2+20. The total score ranged from minimum 40 to maximum 120 points, with a higher score indicating stronger inclination toward peaceful way of solving conflicts. RESULTS: There was no difference between the mean total scores of Zagreb and Mostar students (66-/+17 and 67-/+18, respectively; p=0.744). The mean score of female students was higher than that of male students (71-/+19 vs 63-/+16; p<0.001) for the whole sample as well as for Zagreb and Mostar samples separately (p<0.001 for both). The average score of 2.3-/+0.9 per question indicated that the students' choice was mostly undecided on war-prone activities. Younger students were more war-prone than older ones (p=0.008 for age, and p=0.024 and 0.013 for comparisons between students in earlier and later academic years). Students from cities that were affected by war but not severely damaged seemed less war-prone than students from cities that were either seriously damaged or not directly affected by war (p=0.032). CONCLUSION: Women, older students, and students from cities that were under war threat but not seriously damaged showed to be more morally engaged towards peace.