Difference of Symptoms Networks in Early and Late Phase Schizophrenia; A Cross-Sectional Network Analysis.

OBJECTIVE: The functional remission or recovery of schizophrenia patients is a challenging task which relies on pharmacotherapy but also on the timing of psychotherapy and other therapeutic interventions. The study aimed to assess the difference in strength and structure of symptoms networks between early and late phase schizophrenia. Our secondary objective was to check whether the overall, positive, negative, and general symptoms severity change over the course of treatment and disorder. METHODS: This nested cross-sectional analysis combined the samples from two studies performed during 2014-2016 at University Psychiatric Hospital Vrapce, Zagreb, Croatia on the consecutive sample of men 30-60 years old diagnosed with schizophrenia, 85 of them in the early (≤5 years from diagnosis), and 143 in the late phase of the illness. The study was funded by the project: "Biomarkers in schizophrenia - integration of complementary methods in longitudinal follow up of FEP patients". RESULTS: Median (IQR) age of the participant in the early phase was 36 (32-45) years and in the late phase 44 (38-49) years. Patients in the early phase had significantly higher odds for being in the symptomatic remission compared to the patients in the late-phase schizophrenia (OR=2.11; 95% CI 1.09-4.09) and had 10% less pronounced negative symptoms. The global strength, density, and structure of the symptoms network were not significantly different between the two study groups. CONCLUSIONS: Negative symptoms severity change with the course of illness and differ from the early to the late phase of schizophrenia. However, the overall network of psychotic symptoms is relatively stable, and overall strengths or density and the partial relationship between particular symptoms do not change significantly. The observed worsening of negative symptoms is probably at least partially caused by the lack of clear guidelines and effective treatment options aimed specifically toward negative symptoms.

Neurocognitive Profiles of Patients with the First Episode of Psychosis and Schizophrenia Do not Differ Qualitatively: a Nested Cross-Sectional Study.

BACKGROUND: The aim of study was to analyze neurocognitive profiles in patients with first-episode psychosis (FEP) and patients with schizophrenia (SCH), and their correlations with other clinical features. SUBJECTS AND METHODS: We performed a multicentric cross sectional study including 100 FEP and 100 SCH recruited from three Croatian hospitals during 2015-2017. Assessment included a set of neurocognitive tests, psychiatric scales and self-reporting questionnaires. The main analysis was done by multigroup latent profile analysis. RESULTS: Multigroup latent profile analysis resulted in three structurally equivalent neurocognitive profiles ("Best", "Medium", "Worst"), with differences in the severity of neurocognitive deficits measured with successfulness in solving domain specific tasks. The "Best" profile was statistically significantly more prevalent in FEP and "Worst" profile in the SCH. Negative symptom score was the highest in patients with the "Worst" profile and the lowest among those with the "Best" profiles. CONCLUSIONS: Differences in neurocognitive profiles between FEP and SCH appear to be quantitative rather than qualitative nature, possibly reflecting a specific trait of illness that may progress over time. Defining neurocognitive profiles from the first episode of psychosis could help in tailoring individualized treatment options with focus on neurocognitive and negative symptoms and possible influence on patients' overall clinical outcome.

An Unusual Case of Infertility: Urethral Coitus Due to Cribriform Hymen.

Urethral coitus is a rare type of sexual practice, usually due to vaginal agenesis or hymeneal anomalies. We report a case of urethral coitus in a healthy couple who were evaluated for infertility. The female partner had cribriform hymen and dilated urethral orifice but did not report any problems except infertility and her genital anatomy was normal. The male partner reported concerns over his penile size but was otherwise healthy. After incision of hymen, they were able to have vaginal coitus and successfully conceived. While urethral coitus is rare, it should be suspected in women presenting with infertility and a dilated urethral orifice.

Treatment patterns of schizophrenia based on the data from seven Central and Eastern European Countries.

OBJECTIVE: The aim is to analyze how schizophrenia is pharmacologically treated in seven CEE countries: Croatia, Estonia, Hungary, Poland, Serbia, Slovakia and Slovenia. METHODS: Psychiatrists from selected centers in each of participating countries were asked to complete a pre-defined questionnaire on their current clinical practice. Information on protocols and resource utilization in schizophrenia treatment was included and derived from randomly selected patient medical records. Expert opinions on country-wide treatment patterns were additionally sought. This sub-analysis focuses on pharmacological treatment patterns in the last six months and over the course of the disease. RESULTS: 961 patients' data show that during last six months the most commonly prescribed medications were oral atypical antipsychotics: olanzapine (n=268), clozapine (n=234) and risperidone (n=160). The most frequently prescribed atypical antipsychotics over course of disease were: risperidone (54.5%), olanzapine (52.4%) and clozapine (35.1%), along with haloperidol (39.3%). Experts reported risperidone (four countries) and olanzapine (three countries) as first-line treatment, with the same two medications prescribed as second-line treatment. Clozapine was the most reported medication for refractory patients. Approximately 22% of patients received polypharmacy with antipsychotics in at least one period over the disease course. Mean time since diagnosis was 13.1 years and on average 4.8 treatment courses received during that period. Anxiolytics (70%), antidepressants (42%), mood-stabilizers (27%) were also prescribed, with diazepam (35.4%), sertraline (10.5%), valproic acid (17.5%) the most commonly reported, respectively, in each group. The most frequently reported treatment change was switch from one oral atypical antipsychotic to another (51%). CONCLUSION: Oral atypical antipsychotics, mostly older drugs (risperidone, olanzapine, clozapine), were most commonly prescribed for schizophrenia treatment in participating countries. Given that results are from the first large-scale analysis of RWD, we believe these findings can be a benchmark for future real-world studies, which could contribute to the optimization of treatment for this debilitating disease.

Schizophrenia causes significant burden to patients' and caregivers' lives.

BACKGROUND: Schizophrenia is a serious public health problem and is ranked among the most disabling diseases in the world. The sub-study presented here was part of a larger project to characterize the burden of schizophrenia on healthcare systems and on individuals living with the disease in Central and Eastern Europe (CEE). AIMS: This sub-study aimed to assess and analyze the impact of schizophrenia on many aspects of the lives of patients and caregivers. METHODS: Psychiatrists from selected centers in seven Central and Eastern European countries were asked to complete a questionnaire in order to collect information about the disease history, characteristics, treatment protocols and resources used for each randomly selected patient. All data were statistically analyzed and compared between countries. RESULTS: Data from 961 patients with schizophrenia (mean age 40.7 years, 45.1% female) were included in the analysis. The mean number of days spent in hospital per patient per year across all seven countries was 25.3 days. Hospitalization occurred on average once per year, with psychiatrist visits 9.4 times per year. Of the patients in the study, 61% were single, 12% divorced and 22% married or cohabiting. Almost 84% were living with relatives or a partner; only 17% lived alone and, on average, 25% of patients received support from social workers. Relatives provided care for approximately 60% of patients and 4% of them had to stop working in order to do so. Twenty-nine percent of the patients were unemployed, and 56% received a disability pension or were retired, with only 19% in full-time employment or education. CONCLUSION: Schizophrenia has a significant effect on the lives of patients and caregivers and impacts their social integration.

Testosterone levels and clinical features of schizophrenia with emphasis on negative symptoms and aggression.

BACKGROUND: Aggressive behavior and negative symptoms are two features of schizophrenia that may have a hormonal basis. AIM: The aim of this study was to compare testosterone level with clinical features of schizophrenia, focusing on negative symptoms and aggressive behavior. METHODS: The study population consisted of 120 male schizophrenic patients (ages 18-40) classified into non-aggressive (n = 60) and aggressive (n = 60) groups. Depending on the type of aggression that was manifested prior to admission, the aggressive group was divided into violent (n = 32) and suicidal (n = 28) subgroups. Psychopathological severity, violence and suicidality were assessed using the Positive and Negative Syndrome Scale (PANSS), Overt Aggression Scale and Columbia Suicide Severity Rating Scale, respectively. Total serum testosterone level was determined on the same morning that symptoms were assessed. RESULTS: In the non-aggressive group, testosterone level was negatively correlated with the score on the negative subscale of PANSS (P = 0.04) and depression (P = 0.013), and positively correlated with excitement (P = 0.027), hostility (P = 0.02) and impulsive behavior (P = 0.008). In the aggressive group, testosterone level had non-significant correlation with these parameters, and with violent or suicidal behavior. CONCLUSIONS: The results confirmed that non-aggressive male schizophrenic patients with lower levels of testosterone had a greater severity of negative symptoms. In aggressive patients, there was no correlation between testosterone and clinical features of the disorder or the degree or type of aggression. These findings indicate that therapeutic strategies targeting testosterone could be useful in the treatment of negative symptoms of schizophrenia.

Self-reported emotional and behavioral symptoms, parent-adolescent bonding and family functioning in clinically referred adolescent offspring of Croatian PTSD war veterans.

The presence of posttraumatic stress disorder (PTSD) in male war veterans has been linked with family dysfunction and psychopathology in their children [1, 2]. This study aimed to evaluate self-reported emotional and behavioral symptoms, parent-adolescent bonding and family functioning in clinically referred adolescent offspring of Croatian PTSD war veterans and determine the degree that parent-child bonding and family functioning contributed to adolescent behavior problems. Internalizing and externalizing behavior problems, parent-child bonding and family functioning were assessed in a sample of clinically referred Croatian PTSD veterans adolescent offspring (N = 122) and non-PTSD veteran adolescent offspring (N = 122) matched for age, sex, educational level, family income, parental employment status, ethnicity, and residential area. Youth Self-Report, Parental Bonding Instrument, Family Assessment Device were used. Adolescent offspring of PTSD veterans reported having significantly more internalizing and externalizing problems than non-PTSD veteran offspring, and also more difficulties in their family functioning, lower levels of maternal and paternal care, and more impaired mother-child and father-child bonding than control subjects. Internalizing symptoms were associated with family dysfunction, while externalizing symptoms were associated with paternal overcontrol/overprotection, and low maternal and paternal care. In conclusion, the increase in internalizing and externalizing symptoms as well as family and parental dysfunction among clinically referred adolescent offspring of PTSD veterans compared to their non-PTSD veteran counterparts indicates a need for early detection and interventions targeting both adolescent psychopathology and family relationships.

Association between total serum cholesterol and depression, aggression, and suicidal ideations in war veterans with posttraumatic stress disorder: a cross-sectional study.

AIM: To investigate the relationship between total serum cholesterol and levels of depression, aggression, and suicidal ideations in war veterans with posttraumatic stress disorder (PTSD) without psychiatric comorbidity. METHODS: A total of 203 male PTSD outpatients were assessed for the presence of depression, aggression, and suicidality using the 17-item Hamilton Depression Rating Scale (HAM-D17), Corrigan Agitated Behavior Scale (CABS), and Scale for Suicide Ideation (SSI), respectively, followed by plasma lipid parameters determination (total cholesterol, high density lipoprotein [HDL]-cholesterol, low density lipoprotein [LDL]-cholesterol, and triglycerides). PTSD severity was assessed using the Clinician-Administered PTSD Scale for DSM-IV, Current and Lifetime Diagnostic Version (CAPS-DX) and the Clinical Global Impressions of Severity Scale (CGI-S), before which Mini-International Neuropsychiatric Interview (MINI) was administered to exclude psychiatric comorbidity and premorbidity. RESULTS: After adjustments for PTSD severity, age, body mass index, marital status, educational level, employment status, use of particular antidepressants, and other lipid parameters (LDL- and HDL- cholesterol and triglycerides), higher total cholesterol was significantly associated with lower odds for having higher suicidal ideation (SSI≥20) (odds ratio [OR] 0.09; 95% confidence interval [CI] 0.03-0.23], clinically significant aggression (CABS≥22) (OR 0.28; 95% CI 0.14-0.59), and at least moderate depressive symptoms (HAM-D17≥17) (OR 0.20; 95% CI 0.08-0.48). Association of total cholesterol and HAM-D17 scores was significantly moderated by the severity of PTSD symptoms (P<0.001). CONCLUSION: Our results indicate that higher total serum cholesterol is associated with lower scores on HAM-D17, CABS, and SSI in patients with chronic PTSD.

Alcohol abuse as the strongest risk factor for violent offending in patients with paranoid schizophrenia.

AIM: To determine predictive risk factors for violent offending in patients with paranoid schizophrenia in Croatia. METHOD: The cross-sectional study including male in-patients with paranoid schizophrenia with (N=104) and without (N=102) history of physical violence and violent offending was conducted simultaneously in several hospitals in Croatia during one-year period (2010-2011). Data on their sociodemographic characteristics, duration of untreated illness phase (DUP), alcohol abuse, suicidal behavior, personality features, and insight into illness were collected and compared between groups. Binary logistic regression model was used to determine the predictors of violent offending. RESULTS: Predictors of violent offending were older age, DUP before first contact with psychiatric services, and alcohol abuse. Regression model showed that the strongest positive predictive factor was harmful alcohol use, as determined by AUDIT test (odds ratio 37.01; 95% confidence interval 5.20-263.24). Psychopathy, emotional stability, and conscientiousness were significant positive predictive factors, while extroversion, pleasantness, and intellect were significant negative predictive factors for violent offending. CONCLUSION: This study found an association between alcohol abuse and the risk for violent offending in paranoid schizophrenia. We hope that this finding will help improve public and mental health prevention strategies in this vulnerable patient group.

The relationship between depressive syndrome and suicidal risk in patients with acute schizophrenia.

AIM: To determine the relationship between scores on five factors of the Positive and Negative Syndrome Scale (PANSS) and Calgary Depression scale for Schizophrenia (CDSS) and scores on the InterSePT Scale for Suicidal Thinking (ISST) in patients with acute schizophrenia. METHODS: Data were collected on sociodemographic and clinical characteristics of 180 drug-treated in-patients with acute schizophrenia. Their symptoms were assessed with PANSS, CDSS, and ISST and correlations between the scores were calculated. Statistically significant correlations were included in the logistic regression analysis to identify predictors of suicidal risk. RESULTS: CDSS (P<0.001) score and negative (P<0.001), disorganized (P=0.041), emotional (P<0.001), and total score on PANSS (P<0.001) showed a significant positive correlation with ISST. Stepwise logistic regression analysis revealed that CDSS scores (odds ratio [OR] 5.18; confidence interval [CI] 1.58-16.95), and disorganized (0.90; 0.81-0.99) and emotional (1.15; 1.01-1.30) factors of PANSS were predictors of suicidal risk. CONCLUSION: Our results suggested a considerable association between depressive syndrome as assessed by the PANSS emotional factor and CDSS score and suicidal risk in patients with acute schizophrenia.

Cobalamin deficiency manifested with seizures, mood oscillations, psychotic features and reversible dementia in the absence of typical neurologic and hematologic signs and symptoms: a case report.

Cobalamin deficiency is associated with a wide spectrum of hematologic, neurologic, gastroenterologic and psychiatric disorders or symptoms. We report a case of a 50-year-old man with complex partial seizures with secondary generalization, mood oscillations and psychotic symptoms alternating with confusion and reversible dementia secondary to cobalamin deficiency in the absence of typical neurologic and/or hematologic symptoms and signs. Exclusion of epilepsy, acute, atrophic or expansive lesion of central nervous system and usual etiology associated with reversible dementia (infectious diseases, an endocrine etiology and deficiency of vitamins other than cobalamin); finding of cobalamin deficiency only and complete neuropsychiatric recovery after substitution, confirmed etiology. Typical and atypical psychiatric manifestations due to cobalamin deficiency that precede neurologic and/or hematologic signs and symptoms can recover completely after adequate replacement therapy.

Importance of the newer generations of antipsychotics in reducing schizophrenia hospitalization rates.

Throughout history, given the lack of understanding of schizophrenia and lack of effective treatment options, patients were often committed to asylums and later psychiatric institutions, often for prolonged periods of time. First antipsychotic medications helped to bring about changes in approach to these patients and facilitated deinstitutionalization, and discovery of new drugs with differing side-effects profiles introduced new options in treating schizophrenia patients. Data on hospitalization of patients in University Psychiatric Hospital Vrapce from the mid-1990s, as well as data on national level, suggests a trend of drop in hospitalization of schizophrenia patients. At the same time, that period saw significant increase in a number of available newer-generations antipsychotics and the rise in their use compared to first-generation one. Although far from being the only contributing factor, seem to play an important role in continuing the trend of reducing hospitalization rates for schizophrenia patients that started with first antipsychotics. Newer antipsychotics with a more tolerable side-effects profile promote better compliance and further reduce rate of relapse and hospitalizations. No less important is the contribution of newer antipsychotics with new receptor profiles to the personalized psychopharmacotherapy approach that is in tune with emerging conceptualizations of schizophrenia as a complex syndrome with a number of separate symptom domains, whose specific combinations produce specific individual clinical presentation and in turn ask for a specific individual approach to the patient.

Familial risk factors favoring drug addiction onset.

This study, primarily aimed at identification of familial risk factors favoring drug addiction onset, was carried out throughout 2008 and 2009. The study comprised a total of 146 addicts and 134 control subjects. Based on the study outcome, it can be concluded that in the families the addicts were born into, familial risk factors capable of influencing their psychosocial development and favoring drug addiction onset had been statistically more frequently encountered during childhood and adolescence as compared to the controls. The results also indicated the need for further research into familial interrelations and the structure of the families addicts were born into, as well as the need for the implementation of family-based approaches to both drug addiction prevention and therapy.

Impact of destruction of classic moral principles on ethical questions in psychiatry.

Society's treatment of psychiatric patients was always a reflection of social development and social awareness, as well as of ethical principles dominating a certain time period in that society. Over the last two and a half millennia, during which principles of Hippocratic ethics applied, attitudes towards psychiatric patients, from an ethical and practical standpoint, were and still are controversial to say the least. During this period thousands of people with mental disorders were abused, tortured, or killed, all of this in accordance to the existing ethical and legislative norms (Malleus Maleficarum, eugenic laws of totalitarian regimes...). In the last forty years many international organizations and associations brought forth a number of resolutions and declarations warning of the position and of the rights of psychiatric patients and giving instructions on the humane, that is to say ethical, treatment of this category of patients. In almost all the western countries laws are passed to protect the rights of people with mental disorders. Thanks to this and maybe even more to the development of psychiatry as a medical and scientific profession, the position of those with mental disorders is improving. However, at the same time over the last 40 years we are witnesses to the destruction of the classic moral principles and the establishment of certain "new" ethics which put psychiatric patients at a disadvantage, only in a more subtle way then before. This is why it is important to reexamine many of the ethical questions in psychiatry in the context of present ethical controversy.

Minor physical anomalies in women with recurrent unipolar depression.

According to earlier observations, minor physical anomalies (MPAs) are more prevalent in psychotic disorders, especially in schizophrenia, and represent an indicator of abnormal fetal development. Limited research has been conducted on these structural abnormalities among patients with unipolar depression, with and without psychotic features. We hypothesized that the mean total MPA score would be greater in patients with psychotic depression than depressive patients without psychosis and control subjects. An extended scale of MPAs was used to detect the presence or absence of 51 MPAs in women with recurrent unipolar depression with psychotic symptoms (n=50), women with recurrent unipolar depression without psychotic symptoms (n=50) and healthy female controls (n=50). Women with recurrent depression had significantly more MPAs than controls. With regard to MPAs of specific body regions, depressive patients had significantly higher rates of MPAs in the mouth area than control subjects. Higher rates of MPAs were not significantly related to psychotic features of depression. The study results are indicative of possible early neurodevelopmental disturbance in recurrent unipolar depression.

Diagnoses of personality disorders between 1879 and 1929 in the largest Croatian psychiatric hospital.

AIM: To study demographic characteristics, comorbidities, and diagnoses of patients admitted for personality disorders to Psychiatric Hospital Vrapce between 1879 and 1929. METHODS: Data were collected from the archives of Vrapce Psychiatric Hospital for a 50-year period from November 1879 to December 1929. The ratio between the number of patients with personality disorder and the number of all admitted patients was determined. We used 3 systems of definitions of personality disorder: for cases before 1923, we used Prichard's concept of moral insanity and unpublished definitions of one of the hospital managers at that time; for cases after 1923, we used Schneider's classification of psychopathic personalities and unpublished definitions of one of the hospital managers at that time. RESULTS: The total number of admissions during the study period was 18 960, 141 (0.74%) of which were for a personality disorder. Of the admitted patients, 85.8% were men and 59.7% were single. The average age was 29.7 } 9.5 years. Most of them (61.7%) were sent to the hospital by courts or police, and the median length of stay was 92 days (interquartile range, 92.0 - 127.5 days). The first patient with a personality disorder was admitted in 1889 with a diagnosis of moral insanity. Until 1920, only 3 terms were used for personality disorder: moral insanity, psychopathic inferiority, and psychopathy. The term was subdivided only after that year. Of the 141 patients admitted for personality disorder, 34 (24.1%) were discharged with comorbid disorders, mainly substance abuse. The most common single comorbid diagnosis was Ganser syndrome (prison psychosis). CONCLUSION: Archives of the Vrapce Psychiatric Hospital contain reliable data about the earliest nomenclature of personality disorders, the increase in the prevalence of personality disorders, and further subdivision of the term personality disorder. Nomenclature for these disorders used at the Vrapce Psychiatric Hospital was consistent with that used in clinical practice in other parts of the world at the time.

Can we prevent blood dyscrasia (leucopenia, thrombocytopenia) and epileptic seizures induced by clozapine.

Clozapine is associated with various haematological adverse effects, including leukopenia, neutropenia, agarnulocytosis, leukocytosis, anaemia, eosinophilia, thrombocytopenia and thrombocythaemia. Recognition and treatment of clozapine-related seizures also will become increasingly important as clozapine use grows in the 1990s. The decision to stop clozapine as a result of haematological adverse effects or seizures is a frustrating one for the clinician, and frequently disastrous for the patient. Cessation of treatment results in relapse. In case that patient is unresponsive to other antipsychotic, restarting clozapine should be consider, despite the risk involved. As the risk of a second agranulocytosis is much higher in those patients, various methods of militating against repeat blood dyscrasias have been treated, including granulocyte colony-stimulating factor and lithium. The decision to restart clozapine should be taken on case-by-case basis and should take into account the likely risks and benefits of restarting. Prior response to clozapine and magnitude of patient deterioration on stopping treatment are important factors to take into this consideration. Clozapine-related seizures did not preclude successful treatment with clozapine. A strategy that has been proposed to reduce the occurrence of seizures is the addition of an anticonvulsant agent. However, clozapine does induce a variety of adverse effects, most of which are of limited duration and either preventable or manageable if a number of simple clinical procedures are followed. With careful haematologyc control, the risk of agranulocytosis can be minimized and in case of clozapine related seizures recommendations include dose reduction, electroencephalogram (EEG), plasma-level monitoring and prophylactic antiepileptic treatment. Re-exposure to clozapine may rarely be attempted where there are facilities for very close and frequent monitoring.

Movies in education of psychiatry residents.

Movies are a complex entity representing simultaneously an art form, a powerful industry, and a social phenomenon. The movie industry has always shown keen interest in physicians and medicine in general, and psychiatry in particular has often been in the spotlight. While there can be positive aspects of interaction of the movies and the psychiatry, stigmatization and negative public perception are also the results we often have to consider. Movies exploit psychiatric topics, at the same time portrayal of mental conditions, psychiatrists, and psychiatry on big screen could be used in different kinds of education in psychiatry. We present our initial experience with introducing movies in education of psychiatry residents in Psychiatric Hospital Vrapce.

[The organization of mental health care in community]. / Organizacija zastite mentalnog zdravlja u zajednici.

Integration of the psychiatry in primary care is beneficial for the early detection of mental disorder, better outcome of mental disorder and reduction of stigma. Psychiatry is a leading profession in organisation of mental health services. General practitioners (GPs) in Europe deal with mental disorders in their everyday practice, so the same is expected in Croatia. Graduate and postgraduate education of our GPs is insufficient for this new role. The paper compares actual situation in Croatia with forthcoming needs. The paper suggests that community psychiatry, anti-stigma program, continuing medical education of GPs and network of consultant psychiatrists give the best results in the early detection and treatment of mental disorder.