Increased burden of rare protein-truncating variants in constrained, brain-specific and synaptic genes in extremely impulsively violent males with antisocial personality disorder.

The genetic correlates of extreme impulsive violence are poorly understood, and there have been few studies that have characterized a large group of affected individuals both clinically and genetically. We performed whole exome sequencing (WES) in 290 males with the life-course-persistent, extremely impulsively violent form of antisocial personality disorder (APD) and analyzed the spectrum of rare protein-truncating variants (rPTVs). Comparisons were made with 314 male controls and publicly available genotype data. Functional annotation tools were used for biological interpretation. Participants were significantly more likely to harbor rPTVs in genes that are intolerant to loss-of-function variants (odds ratio [OR] 2.06; p < 0.001), specifically expressed in brain (OR 2.80; p = 0.036) and enriched for those involved in neurotransmitter transport and synaptic processes. In 60 individuals (20%), we identified rPTVs that we classified as clinically relevant based on their clinical associations, biological function and gene expression patterns. Of these, 37 individuals harbored rPTVs in 23 genes that are associated with a monogenic neurological disorder, and 23 individuals harbored rPTVs in 20 genes reportedly intolerant to loss-of-function variants. The analysis presents evidence in support of a model where presence of either one or several private, functionally relevant mutations contribute significantly to individual risk of life-course-persistent APD and reveals multiple individuals who could be affected by clinically unrecognized neuropsychiatric Mendelian disease. Thus, Mendelian diseases and increased rPTV burden may represent important factors for the development of extremely impulsive violent life-course-persistent forms of APD irrespective of their clinical presentation.

Evaluating and comparing success rates for inpatient treatment of alcohol addiction in the Czech Republic.

OBJECTIVES: This systematic review seeks to present and compare data from studies evaluating the success of medium-term inpatient treatment of alcohol-dependent patients in the Czech Republic. Another aim was to identify the problems that make such comparisons difficult. No previous review comparing the efficiency of various therapeutic programmes has been published in the Czech Republic. METHODS: Bibliographia medica Cechoslovaca and PubMed were used to find studies published in professional medical journals since 1970 evaluating the abstinence of patients who voluntarily completed medium-term inpatient treatment of alcohol dependence. RESULTS: Medium-term inpatient treatment of alcohol addiction leads to one year of abstinence in 34% to 76% of patients. Such variance in value is largely caused by selection bias, differences in the definition of abstinence, and differences in data collection methods. CONCLUSION: The comparison of studies presented many challenges. Further steps should be taken to help compare treatment programmes in the future, as the programmes provide different therapeutic interventions of different intensities and lengths to different patients. Adequate demographic and other pretreatment characteristics data collection, detailed descriptions of therapeutic interventions, and identification of effective components of the therapeutic programme could support further research in this area, optimize existing programmes, and increase the overall treatment efficiency.

COVID-19 vaccine uptake in mental healthcare users: Czech nationwide register study.

BACKGROUND: The excessive covid-related mortality of psychiatric patients was reduced by vaccination. The vaccine uptake in patients diagnosed with different mental health disorders is, however, not fully described. AIMS: A nationwide, record-based retrospective cross-sectional study examines the effect of substance use, psychotic, affective, anxiety, and personality disorders on COVID-19 vaccination rates in August and December 2021. Further, it quantifies the effect of receiving mental healthcare on vaccine uptake. METHODS: The COVID-19 vaccine rates of mental healthcare users in August and December 2021 were examined using logistic regression models adjusted for sex and age on a sample of 7,235,690 adult inhabitants of the Czech Republic. The probability of vaccine uptake in the week following mental healthcare appointment or hospitalization on any day in the fall 2021 was compared to the general probability of getting vaccinated during that week. RESULTS: The vaccination rate in August 2021 was related to history of hospitalization due to substance use (OR = 0.71), personality (OR = 0.87), psychotic (OR = 0.92), and anxiety (OR = 1.15) disorders, while mood disorders had no effect (OR = 1.00). Compared to general population, mental healthcare users were undervaccinated in August but not in December 2021. Vaccine uptake was low in those with history of psychiatric hospitalizations but higher in those utilizing inpatient or outpatient mental healthcare recently, predominantly for affective disorders. Increased vaccine uptake was observed following utilization of mental healthcare as well as in those with repeated psychiatric hospitalizations. CONCLUSIONS: The vaccination rates of mental healthcare users relative to general population largely differ across nosological categories and during the vaccination campaign. Psychiatrists were successful in promoting vaccination against COVID-19.

The effect of microbiome composition on impulsive and violent behavior: A systematic review.

The impact of the microbiome on brain function and behavior has recently become an important research topic. We searched for a link between the gut microbiome and impulsive and violent behavior. We focused on critical factors influencing the microbiome establishment that may affect human health later in life, i.e., delivery mode, early-life feeding, and early antibiotic exposure. We searched PubMed, Web of Science, and the Cochrane Library. We included original human studies examining adults and children with impulsive and/or violent behavior that assessed the gut microbiota composition of participants, delivery mode, infant feeding mode, or early antibiotic exposure. Bibliographic searches yielded 429 articles, and 21 met the eligibility criteria. Two studies reported data on patients with schizophrenia with violent behavior, while 19 studies reported data on patients with attention-deficit hyperactivity disorder (ADHD). The results showed several bacterial taxa associated with ADHD symptomatology and with violent behavior in patients with schizophrenia. No association was found between delivery mode and impulsive behavior, nor did any articles relate infant feeding mode to violent human behavior. Those studies investigating early antibiotic exposure yielded ambiguous results. The heterogeneity of the data and the different methodologies of the included studies limited the external validity of the results. We found few studies that addressed the possible microbiome involvement in the pathophysiology of impulsive and violent behavior in humans. Our review revealed a gap in knowledge regarding links between the gut microbiome and these extreme behavioral patterns.

Changes in ambulance departures for assault calls during COVID-19 pandemic restrictions.

Restrictions related to COVID-19 changed the daily behavior of people, including the expression of violence. Although an increased incidence of violent behavior, especially domestic violence, was expected during the pandemic, retrospective analyses have yielded mixed results. Records of ambulance departures to address injuries caused by assaults in the Pilsen region, Czech Republic, during the restrictive measures during the national state of emergency were compared to data from 3 previous years using general linear models. The number and severity of assaults were analyzed for the whole sample and separately for patients of either sex, for residential or nonresidential locations, and for domestic violence. Controlling for the seasonal effects, the number of assaults decreased by 39% during the pandemic restrictions compared to the 3 previous years. No difference was found between the effects of restrictions on assaults resulting in an injury of a male or female patient. The decrease was specifically pronounced in the sample of assaults in nonresidential locations, while no effect of restrictions was observed in assaults in residential locations and domestic assaults. Pandemic restrictions were associated with a decreased incidence of violent assaults that required ambulance services. Although the incidence decreased especially in those assaulted outside of their homes, we found no support for an increase in domestic violence or violence against women. Pandemic restrictions may have served as a protective rather than a risk factor for assaults severe enough to warrant a call for ambulance services.

Violent behavior and the COVID-19 lockdowns: a nationwide register-based study.

OBJECTIVES: The primary aim was to test the hypothesis that physical interpersonal violence is decreased during the lockdown period in comparison with comparable control periods. The secondary aims were to explore the effects of gender and alcohol consumption on the violence during the lockdown. METHODS: Nationwide records of hospitalizations secondary to an assault were analyzed using quasipoisson regression. Assault rates in two lockdown periods, defined as a national emergency state, were compared to baseline data between 2017 and 2020, controlling for seasonal fluctuations and pandemic-related effects other than lockdown. To validate the findings on independent data, differences between lockdown and baseline in Police records of violent criminality between 2017 and 2021 were examined using one-way ANOVA. RESULTS: The rates of hospitalizations secondary to an assault decreased substantially during lockdowns (IRR = .43; P < .001) and the duration of lockdown did not affect assault rates (P = .07). The decrease in assault rates was more pronounced in males than females (IRR = .77; P < .05) and was weakened in patients with history of alcohol abuse (IRR = 1.83; P < .001). Violent crime rate decreased by 19% during the lockdowns compared to prepandemic baseline (P < .001). CONCLUSION: We found that physical interpersonal violence decreased during the COVID-19 lockdown periods. The reduction is significantly greater in males. Emerging evidence suggests an increased risk of alcohol use and intoxication during the lockdowns. Violent crime rate decreased during the lockdown.

Willingness to Vaccinate Against COVID-19: The Role of Health Locus of Control and Conspiracy Theories.

Understanding the predictors of the willingness to get vaccinated against COVID-19 may aid in the resolution of current and future pandemics. We investigate how the readiness to believe conspiracy theories and the three dimensions of health locus of control (HLOC) affect the attitude toward vaccination. A cross-sectional study was conducted based on the data from an online survey of a sample of Czech university students (n = 866) collected in January 2021, using the multivariate linear regression models and moderation analysis. The results found that 60% of Czech students wanted to get vaccinated against COVID-19. In addition, 40% of the variance of willingness to get vaccinated was explained by the belief in the COVID-19-related conspiracy theories and the powerful others dimension of HLOC. One-sixth of the variance of the willingness to get vaccinated was explained by HLOC, cognitive reflection, and digital health literacy [eHealth Literacy Scale (EHEALS)]. HLOC and conspiracy mentality (CM) and its predictors are valid predictors of a hesitancy to get vaccinated against COVID-19. The campaigns promoting vaccination should target the groups specifically vulnerable to the conspiracy theories and lacking HLOC related to powerful others.

Serious physical assault and subsequent risk for rehospitalization in individuals with severe mental illness: a nationwide, register-based retrospective cohort study.

BACKGROUND: Victimization is associated with worse social and clinical outcomes of individuals with severe mental illness (SMI). A relapse of SMI may be one of the clinical consequences of assaultive trauma. As far as we know, there is no published study that analyzes nationwide health registers to assess the risk of SMI rehospitalization following assault. AIM: We aimed to assess whether exposure to assault is associated with an increased risk of psychiatric hospitalization in those with SMI. METHODS: We utilized data from the Czech nationwide registers of all-cause hospitalizations and all-cause deaths. We defined exposed individuals as those discharged from a hospitalization for SMI between 2002 and 2007, and hospitalized for serious injuries sustained in an assault in the subsequent 7 years. For each assaulted individual, we randomly selected five counterparts, matched on SMI diagnosis, age and sex, who were not assaulted in the examined time period. We used mixed effect logistic regression to assess the effect of assault on the risk of SMI rehospitalization within the following 6 months. We fitted unadjusted models and models adjusted for the number of previous SMI hospitalizations and drug use disorders. RESULTS: The sample consisted of 248 exposed and 1 240 unexposed individuals. In the unadjusted model, assaulted individuals were almost four times more likely to be rehospitalized than their non-assaulted counterparts (odds ratio (OR) = 3.96; 95% CI 2.75; 5.71). After adjusting for all covariates, the OR remained threefold higher (OR = 3.07; 95% CI 2.10; 4.49). CONCLUSION: People with a history of SMI hospitalization were approximately three times more likely to be rehospitalized for SMI within 6 months after an assault than their non-assaulted SMI counterparts. Soon after a person with SMI is physically assaulted, there should be a psychiatric evaluation and a close follow-up.

Dissociation, Cognitive Reflection and Health Literacy Have a Modest Effect on Belief in Conspiracy Theories about COVID-19.

Understanding the predictors of belief in COVID-related conspiracy theories and willingness to get vaccinated against COVID-19 may aid the resolution of current and future pandemics. We investigate how psychological and cognitive characteristics influence general conspiracy mentality and COVID-related conspiracy theories. A cross-sectional study was conducted based on data from an online survey of a sample of Czech university students (n = 866) collected in January 2021, using multivariate linear regression and mediation analysis. Sixteen percent of respondents believed that COVID-19 is a hoax, and 17% believed that COVID-19 was intentionally created by humans. Seven percent of the variance of the hoax theory and 10% of the variance of the creation theory was explained by (in descending order of relevance) low cognitive reflection, low digital health literacy, high experience with dissociation and, to some extent, high bullshit receptivity. Belief in COVID-related conspiracy theories depended less on psychological and cognitive variables compared to conspiracy mentality (16% of the variance explained). The effect of digital health literacy on belief in COVID-related theories was moderated by cognitive reflection. Belief in conspiracy theories related to COVID-19 was influenced by experience with dissociation, cognitive reflection, digital health literacy and bullshit receptivity.

Conspiracy theories as a natural part of pandemics.

Effectiveness of the policy measures against the COVID-19 pandemic is reduced by spread of conspiracy theories. Moreover, conspiracy theories induce opposition to vaccines. The text shows that increased occurrence of conspiracy theories is a typical public reaction to a disaster and describes some of the mechanisms contributing to susceptibility to conspiracy explanations on the individual as well as societal level.

Medical Students' Career Choice and Attitudes Toward Psychiatry: Case of the Czech Republic.

OBJECTIVE: A survey among medical students of all medical schools in the Czech Republic was conducted to investigate attitudes and views of psychiatry and career choice of psychiatry. METHODS: A Czech version of the Attitudes to Psychiatry Scale (APS) and a questionnaire surveying demographic characteristics and choices of future specialty were distributed to all medical students of eight medical schools in the Czech Republic via the schools' internal communication systems in the form of an anonymous online questionnaire. RESULTS: Out of a total of 10,147 medical students in the Czech Republic (academic year 2019/2020), 2418 students participated in the survey (response rate 23.8%). Psychiatry as a non-exclusive career choice was considered by 31.3% respondents; child and adolescent psychiatry was considered by 15.4% respondents. Psychiatry as the only choice was considered by 1.6%, and child and adolescent psychiatry was not considered at all. The interest in both specialties was declining since the first year of study. The status of psychiatry among other medical specialties was perceived as low; students were rather discouraged from entering psychiatry by their families. They did not feel encouraged by their teachers to pursue career in psychiatry despite the fact that they were interested in psychiatry. They also felt uncomfortable with patients with mental illness. CONCLUSIONS: Despite high enthusiasm for psychiatry in the first year of medical school, only a small proportion of medical students consider to choose psychiatry, and especially child and adolescent psychiatry, as a career at the end of medical school.

Deconstructing violence in acutely exacerbating psychotic patients.

BACKGROUND: This study examined the proximate causes of psychotic patients' aggression upon the admission to the psychiatric wards of a university and two state hospitals. METHODS: The authors used a semistructured interview to elicit proximate causes of assaults from the assailants and victims. The treating psychiatrists and nurses provided additional information. Based on this interview, aggressive episodes were categorized as psychotic, impulsive and planned. RESULTS: A total of 820 assaults committed by 289 newly admitted violent psychotic inpatients were evaluated. The interview ratings indicated that 76.71% of the assaults were directly driven by psychotic symptoms and 22.32% of all attacks were labeled as impulsive. Only 0.98% of assaults were categorized as planned. CONCLUSIONS: These findings indicate that assaultive behavior among recently admitted acute psychiatric inpatients with untreated or undertreated psychosis is primarily driven by psychotic symptoms and disordered impulse control. Because each type of assault requires a different management, identifying the type of assault is crucial in determining treatment interventions.

Rare copy number variation in extremely impulsively violent males.

The genetic correlates of extreme impulsive violence are poorly understood, and there have been no studies that have systematically characterized a large group of affected individuals both clinically and genetically. We performed a genome-wide rare copy number variant (CNV) analysis in 281 males from four Czech prisons who met strict clinical criteria for extreme impulsive violence. Inclusion criteria included age ≥ 18 years, an ICD-10 diagnosis of Dissocial Personality Disorder, and the absence of an organic brain disorder. Participants underwent a structured psychiatric assessment to diagnose extreme impulsive violence and then provided a blood sample for genetic analysis. DNA was genotyped and CNVs were identified using Illumina HumanOmni2.5 single-nucleotide polymorphism array platform. Comparing with 10851 external population controls, we identified 828 rare CNVs (frequency ≤ 0.1% among control samples) in 264 participants. The CNVs impacted 754 genes, with 124 genes impacted more than once (2-25 times). Many of these genes are associated with autosomal dominant or X-linked disorders affecting adult behavior, cognition, learning, intelligence, specifically expressed in the brain and relevant to synapses, neurodevelopment, neurodegeneration, obesity and neuropsychiatric phenotypes. Specifically, we identified 31 CNVs of clinical relevance in 31 individuals, 59 likely clinically relevant CNVs in 49 individuals, and 17 recurrent CNVs in 65 individuals. Thus, 123 of 281 (44%) individuals had one to several rare CNVs that were indirectly or directly relevant to impulsive violence. Extreme impulsive violence is genetically heterogeneous and genomic analysis is likely required to identify, further research and specifically treat the causes in affected individuals.

Violence in persons with and without psychosis in the Czech Republic: risk and protective factors.

PURPOSE: To prevent violence among persons with psychosis, further knowledge of the correlates and risk factors is needed. These risk factors may vary by nation. PATIENTS AND METHODS: This study examined factors associated with violent assaults in 158 patients with psychosis and in a matched control sample of 158 adults without psychosis in the Czech Republic. Participants completed interviews and questionnaires to confirm diagnoses, report on aggressive behavior, current and past victimization, and substance use. Additional information was collected from collateral informants and clinical files. Multiple regression analyses were conducted to identify factors that were independently associated with committing an assault in past 6 months. RESULTS: The presence of a psychotic disorder was associated with an increased risk of assaults (OR =3.80; 95% CI 2.060-7.014). Additional risk factors in persons with and without psychosis included recent physical victimization (OR =7.09; 95% CI 3.922-12.819), childhood maltreatment (OR =3.15; 95% CI 1.877-5.271), the level of drug use (OR =1.13; 95% CI 1.063-1.197), and the level of alcohol use (OR =1.04; 95% CI 1.000-1.084). Increasing age (OR =0.96; 95% CI 0.942-0.978) and employment (OR =0.30; 95% CI 0.166-0.540) were protective factors. Except for drug use, which appeared to have greater effect on violence in the group without psychosis, there were no major differences between patients and controls in these risk and protective factors. To our knowledge, this is the first published comparison of assault predictors between schizophrenia patients and matched controls. CONCLUSION: Recent physical victimization was the strongest predictor of assaults. Our findings are consistent with the emerging empirical evidence pointing to the very important role of victimization in eliciting violent behavior by the victims. Some current prediction instruments may underestimate the risk of violent behavior as they take little account of current victimization. Although psychosis per se elevates the risk of violence, other risk and protective factors for violence in persons with psychosis and comparison group are largely similar.

Very long-term outcome of schizophrenia.

PURPOSE: The principal aim is to review recent data concerning the very long-term outcome of schizophrenia and schizophrenia spectrum disorders. We examine factors that influence outcome, including therapeutic interventions. METHOD: PubMed and Scopus databases were searched for papers published between 2008 and 2017 reporting on prospective studies of schizophrenia or schizophrenia spectrum with a follow-up period ≥5 years with adequate outcome information. Additional publications were found in reference lists and authors' reference libraries. RESULTS: The average proportion of patients with symptomatic remission at follow-up ranged between 16.4% in never-treated patients to 37.5% in patients who were systematically treated with antipsychotics. Good outcomes at follow-up were observed in schizophrenia and schizophrenia spectrum patients on low doses of antipsychotics and in patients with no pharmacological treatment at that time. Early detection and intensive treatment of the first episode as well as the availability of continued psychosocial treatment and support over subsequent years appeared associated with better outcomes. CONCLUSION: The long-term outcome of schizophrenia is highly variable, depending on access to mental healthcare, early detection of psychosis and pharmacological treatment. Recent data support the effectiveness of low-dose antipsychotic treatment for long-term maintenance in some patients. A proportion of first-episode schizophrenia patients, perhaps 20%, do not need long-term maintenance antipsychotic treatment. That proportion may be higher in schizophrenia spectrum patients. The reasons why these patients do not need the long-term treatment are not well understood. Methods to predict the membership in this subgroup are not yet good enough for clinical use in individual patients.

The effect of prolonged simvastatin application on serotonin uptake, membrane microviscosity and behavioral changes in the animal model.

Simvastatin and other statins (HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase inhibitors) are extensively used in clinical practices and are very effective in decreasing serum low-density lipoprotein cholesterol. However, their effect on cholesterol synthesis in central nervous system and its behavioral consequences have not been fully understood yet. We have studied selected biologic traits potentially affected by statin treatment - serotonin (5-HT) uptake in platelets, membrane microviscosity in erythrocytes, cholesterol level in the brain (amygdala; hippocampus and prefrontal cortex), as well as behavioral changes in an elevated plus maze and open field test in male Long-Evans rats, which were treated by simvastatin (30mg/kg per day) for 2 or 4weeks. We demonstrated: 1) a decrease in both serotonin transporter (SERT) activity and membrane microviscosity after treatment with simvastatin, 2) lower cholesterol content in all tested brain regions in animals from the simvastatin treated group, and 3) longer time spent in the open arms and a higher number of entrances to the closed arms in the elevated plus maze by animals from the simvastatin group compared to animals from the control group, but no differences in behavior in the open field test. Taken together, our results confirmed complex alterations, including behavioral changes, after the cholesterol lowering treatment. Furthermore, we discuss the possibility that the behavioral changes, traditionally interpreted as an anxiolytic effect, may be interpreted as increased impulsivity. We also confirmed that such behavioral changes may be attributed to changes in serotonergic neurotransmission.

Recruitment to psychiatry in the Czech Republic: 'waiting for resuscitation'?

Recruitment to psychiatry is becoming a serious obstacle in providing first-class mental health treatment in many countries worldwide. We attempt to address this burning issue by examining medical student's attitudes towards psychiatry and factors influencing their career choice in the Czech Republic. In 2010, 71 students in their last year of medical school at the First Faculty of Medicine, Charles University, Prague were recruited in this quantitative cross-sectional online study. From the sample, 16% (n = 11) of students were considering psychiatry as a career path. An important factor in choosing psychiatry as a career path was personal/family presence of mental illness. Longer experience with psychiatry placement also contributed to the choice of psychiatry, as well as participation in elective courses or psychiatric research projects. Students considering psychiatry were less systematic compared to the group not considering psychiatry. Low reported levels of recruitment to psychiatry present a problematic issue in the Czech Republic. To make psychiatry more appealing to medical students, proactive steps by the relevant stakeholders need to be implemented. These strategies should include steps such as allocating more time for psychiatry in the medical curriculum, better quality of lectures, and the inclusion of additional elective courses.

Depression, traumatic stress and interleukin-6.

BACKGROUND: Recent evidence indicates that various types of interactions between nervous and immune system are important in pathogenesis of depression. These findings show that a significant role in developing depression play pro-inflammatory cytokines that may mediate its psychological, and neurobiological manifestations. Great importance among these cytokine molecules plays interleukin-6 (IL-6). There is growing evidence that this inflammatory process related to depression may be influenced by psychological stress as well as organic inflammatory conditions. These findings suggest that specific influences related to traumatic stress and dissociation could be found in close relationship to increased level of cytokine IL-6. METHODS: In the present study we have performed psychometric measurement of depression (BDI-II), traumatic stress symptoms (TSC-40) and dissociation (DES, SDQ-20), and immunochemical measure of serum IL-6 in 40 inpatients with unipolar depression (mean age 42.3+/-6.8). RESULTS: The results show that IL-6 is significantly correlated to BDI-II (Spearman R=0.47, p<0.01), TSC-40 (Spearman R=0.32, p<0.05), SDQ-20 (Spearman R=0.34, p<0.05) but not to DES (Spearman R=0.25, p=0.11). CONCLUSION: The findings of the present study indicate that increased level of IL-6 in depression could be directly related to symptoms of traumatic stress and somatoform dissociation.

COMT polymorphisms in impulsively violent offenders with antisocial personality disorder.

OBJECTIVE: The relationship between catechol-O-methyltransferase (COMT) polymorphisms and violent behaviour was tested in highly selected group of non-psychotic violent offenders. METHODS: We conducted an association study comparing 47 male repeatedly sentenced for impulsive violent attacks diagnosed with Antisocial Personality Disorder (APD) with 43 healthy male controls matched on education. Three COMT polymorphisms were analysed: COMT Val158Met and COMT Ala146Val on exon 4, and untranslated polymorphism on the 6th exon, at the regulatory region of the COMT gene with deletion-insertion character del/C. RESULTS: Logistic regression analysis revealed that while Val158Met is not associated with violence in APD, another COMT polymorphism - COMT Ala146Val is more frequent among violent offenders with APD (p=0.017). CONCLUSIONS: To conclude, our findings provide further support that COMT is a modifying gene that plays a role in determining interindividual variability in the proclivity for violent behaviour in subjects without major mental disorder.

Platelet serotonin uptake in drug-naïve depressive patients before and after treatment with citalopram.

We investigated the kinetic parameters of serotonin (5-HT) uptake into platelets in a group of 26 drug-naïve patients suffering from major depression before and after 3-7 weeks of treatment with citalopram. The degree of depression was rated using the Hamilton Depression Rating Scale (HDRS). The 5-HT uptake characteristics in untreated depressive patients were not significantly different from those of normal subjects. The apparent Michaelis constant (K(M)) was significantly increased, the apparent maximal velocity (V(max)) was not different from baseline, and the uptake efficiency (V(max)/K(M)) was significantly decreased after citalopram treatment. A significantly positive correlation between K(M) and V(max) was found in all groups. There was a significantly lower V(max) and V(max)/K(M) in the female compared with the male depressed patients before citalopram treatment; a hypothesis was supported that lowered 5-HT uptake may reflect a gender-linked vulnerability to a serotonin-related depression. A significant negative correlation between 5-HT uptake efficiency and the initial HDRS score suggests that platelet 5-HT uptake can be used as a marker of effective depressive disorder pharmacotherapy. The initial severity of depression was significantly negatively correlated with V(max), which supported a hypothesis that the initial severity of depressive disorder could be related to the lower V(max).