Serum Levels of Zinc, Albumin, Interleukin-6 and CRP in Patients with Unipolar and Bipolar Depression: Cross Sectional Study.

Unipolar (UD) and bipolar depression (BDD) show a high degree of similarity in clinical presentations, which complicates the differential diagnosis of these disorders. The aim of this study was to investigate the serum levels of interleukin 6 (IL-6), C-reactive protein (CRP), albumin (Alb), and zinc (Zn) in patients with UD, BDD, and healthy controls (HC). A total of 211 samples were collected: 131 patient samples (65 UD and 68 BDD) and 80 HC. The Montgomery-Asberg Depression Rating Scale (MADRS), along with the Hamilton Depression Rating Scale (HAMD-17), were administered to patient groups to evaluate symptoms. A cross-sectional study was performed to analyse the serum levels of IL-6, CRP, albumin, and zinc. The concentration of CRP was determined using the immunoturbidimetry method, zinc using the colorimetric method, and albumin using the colorimetric method with bromocresol green on the Alinity c device. IL-6 cytokine concentration in serum samples was ascertained using a commercial enzyme immunoassay, ELISA. We found no significant differences in serum concentrations of zinc, albumin, CRP, and IL-6 between the groups of patients with unipolar and bipolar depression. There was a significant statistical difference (p < 0.001) between serum levels of all investigated parameters in both groups of depressed patients in comparison with HC. Furthermore, correlations with specific items on HAMD-17; (namely, hypochondrias, work and activities, somatic symptoms-general, and weight loss) and on MADRS (concentration difficulties, lassitude) were observed in both patient groups. These findings confirm the presence of low-grade inflammation in depression, thus adding better insight into the inflammation hypothesis directed to explain the aetiology of depressive disorders. Our results do not indicate potential biomarkers for distinguishing between unipolar and bipolar depression.

The Presence of Minor Physical Anomalies of a Hand in Patients with Mental Disorders.

INTRODUCTION: Minor physical anomalies (MPA) are subtle morphological deviations with little to none clinical significance that are developed prenatally and therefore could be an indicator of structural changes in the brain developing at the same time. Aim of this study was to determine whether the MPA of the hand can distinguish psychotic patients from patients with non-psychotic diagnoses as well as from the healthy individuals. SUBJECTS AND METHODS: 100 consecutive patients from the University Hospital Center Zagreb, Department of psychiatry, were included in this case-control study along with 100 healthy control subjects. Investigators examined the dorsal and palmar side of the hand and were blind to the patient's diagnoses previous to the examination. Examined MPA included thenar crease, proximal transverse crease, proximal interphalangeal joint, eponychium of the middle digit, fingernail size and digital flexibility. RESULTS: Results showed significant differences in the quantity of MPA between the patients and the control group, as well as differences between patients with psychosis and the healthy subjects. CONCLUSIONS: Despite the fact that previous studies demonstrated characteristic distribution of specific MPA in schizophrenia, this study did not prove such results. Moreover, this study showed that all the MPA are equally common in both schizophrenia and other psychoses.

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.

HTR1A, HTR1B, HTR2A, HTR2C and HTR6 Gene Polymorphisms and Extrapyramidal Side Effects in Haloperidol-Treated Patients with Schizophrenia.

Schizophrenia is a serious, chronic psychiatric disorder requiring lifelong treatment. Extrapyramidal side effects (EPS) are common adverse reactions to antipsychotic medications. In addition to the dopaminergic system, serotonergic mechanisms, including serotonin (5-HT) receptors, might be involved in EPS development. This study aimed to examine molecular associations of HTR1A, HTR1B, HTR2A, HTR2C and HTR6 gene polymorphisms with acute EPS in 229 male schizophrenia patients, following two weeks of haloperidol monotherapy. The Simpson-Angus Rating Scale for Extrapyramidal Side Effects (SAS), Barnes Akathisia Rating Scale (BARS) and Extrapyramidal Symptom Rating Scale (ESRS) were used to evaluate EPS severity. Genotyping was performed using real-time PCR, following extraction of blood DNA. Significant acute EPS appeared in 48.03% of schizophrenia patients. For the rs13212041 HTR1B gene polymorphism, affecting microRNA regulation of HTR1B gene expression, a higher frequency of TT carriers was found among haloperidol-treated patients with akathisia when compared to the group without akathisia symptoms. In comparison to C-allele carriers, patients carrying the TT genotype had higher akathisia severity, as determined by the SAS, BARS and ESRS scales. These molecular findings suggest potential involvement of 5-HT1B receptors in akathisia development following haloperidol treatment, as well as possible epigenetic mechanisms of serotonergic modulation associated with antipsychotic-induced EPS.

Remission Is not Associated with DRD2 rs1800497 and DAT1 rs28363170 Genetic Variants in Male Schizophrenic Patients after 6-months Monotherapy with Olanzapine.

BACKGROUND: Symptomatic remission is an achievable goal in the treatment of schizophrenia. The type of antipsychotic medication and particular genetic variants of the dopaminergic system might be associated with remission. Potential pharmacogenetic markers of the treatment response to antipsychotic medication are missing. This study assessed the possible association between dopamine receptor type 2 (DRD2 rs1800497) and dopamine transporter (DAT1 rs28363170) gene variants with symptomatic remission in schizophrenia. SUBJECTS AND METHODS: Olanzapine (5-20 mg/d) monotherapy was administered for 6 months to 150 male Caucasian subjects with schizophrenia. Remission was evaluated according to "Remission in Schizophrenia Working Group" criteria. Genotyping was performed by PCR-RFLP. RESULTS: Symptomatic remission was found in 31% of patients. DRD2 rs1800497 and DAT1 rs28363170 gene variants were not significantly associated with symptomatic remission. The limitations are a relatively small sample size of patients with schizophrenia (N=150), especially of group with symptomatic remission (N=45). However, the study had moderate but adequate sample sizes for most of the comparisons. Only two dopaminergic polymorphisms were analyzed, and plasma concentration of olanzapine was not determined. CONCLUSION: These results revealed a lack of association between DRD2 rs1800497 and DAT1 rs28363170 genetic variants and symptomatic remission in male patients treated with olanzapine, suggesting that these genetic variants could not be used to predict symptomatic remission to olanzapine monotherapy. Negative results should be further confirmed or rejected in the larger samples, including haplotype analyses, to detect clinically useful and easy obtainable pharmacogenetic markers that might predict therapeutic response or remission in schizophrenia.

Religiosity and Severity of Symptoms in Croatian Patients With Major Depressive Disorder or Schizophrenia.

We examined and compared the relationship between religiosity and symptom severity in patients with major depressive disorder (MDD) rated by the Hamilton Depression Rating Scale) and schizophrenia (rated by the Positive and Negative Syndrome Scale). The Duke University Religion Index, the Santa Clara Strength of Religious Faith (SCSORF) questionnaire, and the Brief Religious Coping scale scores were similar between patients with MDD (n = 50) and patients with schizophrenia (n = 50). In patients with MDD, higher organizational religious activity (ORA) (estimate = 2.28, 95% confidence interval [CI] = 0.37-4.19; p = 0.020) and higher negative religious coping (estimate = 0.43, 95% CI = 0.03-0.84; p = 0.037) were independently associated with more severe symptoms. In patients with schizophrenia, higher ORA was associated with lower negative symptoms (estimate = -1.99, 95% CI = -3.94 to -0.03; p = 0.046). Higher SCSORF was associated with lower ORA in both patient subsets, and thus indirectly with milder symptoms in patients with MDD and with more severe negative symptoms in patients with schizophrenia. The relationship between religiosity and symptom severity apparently differs in patients with MDD and those with schizophrenia.

Cognitive deficit in schizophrenia: an overview.

Depressive mood, anxiety, delusions, hallucinations and behavioral disturbances have been traditionally recognized as leading symptoms of mental disorders. However, cognitive symptoms went under-recognized or declined. Today there is robust evidence that cognitive dysfunction is present in the majority of mental disorders and is also related to impairments in the functioning of the persons with mental illness. It is proposed that aberrant brain neuronal network connectivity, arising from interplay of genetic, epigenetic, developmental and environmental factors, is responsible for cognitive decline. In schizophrenia, dysfunctions in working memory, attention, processing speed, visual and verbal learning with substantial deficit in reasoning, planning, abstract thinking and problem solving have been extensively documented. Social cognition - the ability to correctly process information and use it to generate appropriate response in situations, is also impaired. The correlation of cognitive impairment with functional outcome and employment, independent living and social functioning has emphasized the need for development of the treatments specific to cognition. It is considered that brain neuroplasticity allows for re-modulating and compensating the impairment process which could give opportunity to improve cognitive functions. Therefore, there is a need for comprehensive clinical assessment and follow-up of cognitive decline in mental illness. Implementation of specific treatment strategies addressing cognitive decline in mental illness, like new drugs, distinct cognitive-behavioural therapy, psychoeducation, social skills training and remediation strategies should be strongly indorsed targeting recovery and reduction of disability due to mental illness.

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.

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.

Nicotine dependence in Croatian male inpatients with schizophrenia.

BACKGROUND: Patients with schizophrenia have the highest known rates of cigarette smoking, but less is known about their smoking behavior and the differences across geographical regions, including Croatia. The aim of this study was to compare patterns of nicotine dependence between patients with schizophrenia and healthy individuals, and to determine the relationship between clinical presentation and the severity of smoking. METHODS: This cross-sectional study included 182 recently hospitalized male inpatients and 280 healthy males, who were daily smokers. All participants have fulfilled the Fagerstrom Test for Nicotine Dependence (FTND). Patients were also evaluated by the Positive and Negative Syndrome Scale (PANSS). RESULTS: Patients had higher FTND total score (p = 0.010), smoked their first cigarette earlier in the morning (p = 0.000), consumed higher number of cigarettes (p = 0.000), while healthy subjects had more difficulties to refrain from smoking in places where it is forbidden (p = 0.000) and smoked more even when they were sick (p = 0.000). While severe dependence was more prevalent in the patient group, light dependence was more frequent in control subjects (p = 0.04). Smoking behavior was not associated with either PANSS total score or any of its subscales and items. CONCLUSIONS: Smokers with schizophrenia differ from healthy smokers in both smoking behavior and level of dependence. Longitudinal studies are needed to shed more light on the complex relationship between smoking and psychopathology in schizophrenia.

Latent Toxoplasma gondii infection is associated with decreased serum triglyceride to high-density lipoprotein cholesterol ratio in male patients with schizophrenia.

BACKGROUND: Previous studies suggested a complex association between Toxoplasma gondii (TG) infection and host lipid metabolism. Both TG infection and metabolic disturbances are very common in patients with schizophrenia, but this relationship is not clear. METHODS: In this cross-sectional study, we evaluated the association between TG seropositivity, serum lipid levels, body mass index (BMI) and metabolic syndrome (MetS) in 210 male inpatients with schizophrenia. RESULTS: In our sample of schizophrenia patients, with the mean age of 43.90 ±â€¯12.70 years, the rate of TG seropositivity was 52.38% and the prevalence of MetS was 17%. Patients with the TG antibodies had lower serum triglyceride levels and body weight compared to TG seronegative patients, despite having more frequently received antipsychotics (clozapine, olanzapine risperidone and quetiapine), which are well known to induce weight gain and metabolic abnormalities. However, the only significant change in metabolic parameters, observed in TG seropositive patients with schizophrenia, was decreased serum triglyceride to high-density lipoprotein cholesterol (HDL-C) ratio. No associations were observed between TG seropositivity and serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and glucose levels, waist circumference, BMI and the rate of MetS. CONCLUSION: This is the first report of the association between TG infection and decreased serum triglyceride to HDL-C ratio in a sample of carefully selected men with chronic schizophrenia.

The relationship among psychopathology, religiosity, and nicotine dependence in Croatian war veterans with posttraumatic stress disorder.

AIM: To examine relationships among combat exposure, posttraumatic stress disorder (PTSD) symptoms, depression, suicidality, nicotine dependence, and religiosity in Croatian veterans. METHODS: This cross-sectional study used Combat Exposure Scale (CES) to quantify the stressor severity, PTSD Checklist 5 (PCL) to quantify PTSD severity, Duke University Religion Index to quantify religiosity, Montgomery Asberg (MADRS) and Hamilton Depression (HAM-D) rating scales to measure depression/suicidality, and Fagerstrom Test for Nicotine Dependence to assess nicotine dependence. Zero-order correlations, cluster analysis, multivariate regression, and mediation models were used for data analysis. RESULTS: Of 69 patients included, 71% met "high religiosity" criteria and 29% had moderate/high nicotine dependence. PTSD was severe (median PCL 71), depression was mild/moderate (median MADRS 19, HAM-D 14), while suicidality was mild. A subset of patients was identified with more severe PTSD/depression/suicidality and nicotine dependence (all P<0.001). Two "chains" of direct and indirect independent associations were detected. Higher CES was associated with higher level of re-experiencing and, through re-experiencing, with higher negativity and hyperarousal. It also showed "downstream" division into two arms, one including a direct and indirect association with higher depression and lower probability of high religiosity, and the other including associations with higher suicidality and lower probability of high nicotine dependence. CONCLUSIONS: Psychopathology, religiosity, and nicotine dependence are intertwined in a complex way not detectable by simple direct associations. Heavy smoking might be a marker of severe PTSD psychopathology, while spirituality might be targeted in attempts of its alleviation. Oxford Centre for Evidence-based Medicine level of evidence: 3.

Electroconvulsive therapy - general considerations and experience in Croatia.

Despite controversy, ECT has been recognized as significantly effective for the treatment of mental disorders since 1938, when Cerletti and Bini introduced ECT in clinical psychiatric practice for treatment of schizophrenia. In the next period, indication for ECT switched more toward depression and catatonia. ECT was even banned from psychiatric training in 1960's, due to the anti-psychiatric movement, which were fortified by Oscar winning movie "One Flew over the Cuckoo's Nest". Due to its robust effectiveness, ECT revived in the early 1980's and today holds its position in clinical psychiatric practices around the world. Mechanism of ECT on brain and psychopathology is still not fully understood. Main theories have been neurotransmitter, post-receptor, neurophysiological and neuroendocrine theory. Regarding best clinical practices and evidence reported in the literature, ECT today is considered a treatment option for, traditionally, depression, suicidality and catatonia, and also schizophrenia, schizoaffective disorder, bipolar disorder, malignant neuroleptic syndrome, postpartal depression and psychosis, obsessive compulsive disorder, post-traumatic stress disorder, dementia, etc. Recent evidence of ECT efficacy is growing stronger also in the treatment resistant cases, for depression and psychosis. Great advantage of ECT is lack of absolute contraindications. ECT in Croatia was introduced in clinical psychiatric practice in 1960's in four institutions. Mainly due to stigma, but also a tendency for shifting toward hypothesized action mechanism, ECT in Croatia has been re-named to electrostimulative therapy or electroneuromodulatory treatment. In recent decades, the Department of psychiatry in the University Hospital Centre Zagreb (KBC Zagreb), has continuously been practicing ECT. Our department is considered a regional leader, regarding number of patient cases and overall experience in homeland and neighbouring countries. In the 2016, Croatian expert group, selected by the Croatian Psychiatric Association, proposed national guidelines for the ECT. Research in ECT at our department has shown predominance of the treatment for therapy resistance in depression and psychosis. The other research at our department also showed improvement in several cognitive functions of patients after ECT application.

Smoking in Schizophrenia: an Updated Review.

Patients with schizophrenia continue to have the highest rate of both smoking and heavy nicotine dependence. The interaction between smoking and schizophrenia is complex. There is evidence of the shared genetic background. Recent preclinical and clinical research has further investigated self-medication hypothesis, given that nicotine might alleviate cortical dysfunction. While prior research indicated some favorable effects of smoking on cognitive performance, particulatly on attention/vigilance, recent studies did not confirm those findings. Lower severity of negative symptoms in smokers was not confirmed across studies. Cigarette smoking decreases clozapine and olanzapine concentrations. There is no consistent evidence of favorable effects of nicotine on symptoms in schizophrenia, but the evidence of detrimental effects of smoking on general health is highly consistent. Smoking cessation should be a priority in patients with schizophrenia.

Brain-derived neurotrophic factor serum and plasma levels in the treatment of acute schizophrenia with olanzapine or risperidone: 6-week prospective study.

Antipsychotics have been the mainstay of the treatment of schizophrenia, and their potential role in neuroprotection could be related to brain-derived neurotrophic factor (BDNF). So far different effects on both serum and plasma levels of BDNF were reported related to the various antipsychotic treatments. Aim of this study was to investigate the influence of olanzapine or risperidone on both plasma and serum levels of BDNF in patients with acute schizophrenia. For 50 participants with acute episode of schizophrenia both plasma and serum BDNF, along with the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression scale, were assessed pretreatment and post treatment - after 6 weeks of either risperidone or olanzapine. Results show that a weak correlation between pretreatment plasma and serum levels of BNDF was found no longer significant after 6 weeks of treatment. Antipsychotics, olanzapine and risperidone showed no significant effect on post treatment plasma and serum levels of BDNF. Pretreatment plasma level of BDNF and PANSS positive subscale were positively correlated. Post treatment serum level of BDNF and Clinical Global Impression were negatively correlated. In conclusion, plasma and serum BDNF levels could be different markers to some extent with regard to clinical symptoms, response to therapy and outcome. The interrelation between serum and plasma BDNF should be established in further studies.

Remission and employment status in schizophrenia and other psychoses: One-year prospective study in Croatian patients treated with risperidone long acting injection.

BACKGROUND: While numerous studies have confirmed the efficacy of risperidone long-acting injectable (RLAI) on many clinical outcomes in patients with schizophrenia, there is no data regarding its influence on employment status. SUBJECT AND METHODS: This was a 12-month observational study with flexible doses of RLAI on a Croatian population of patients with schizophrenia and other psychoses. Visits were at baseline and after 1, 3, 6 and 12 months of treatment. Treatment response was evaluated using Clinical Global Impression of Illness Severity (CGI-S) and Improvement (CGI-I) scales, while remission was defined by 8 items of Positive and Negative Syndrome Scale (PANSS). Employment status was determined at baseline and at study endpoint. RESULTS: A total of 362 patients were included, with a median age of 37 (interquartile range 29-47) years, 63.5 % were males and 67.4% were hospitalised at baseline. Overall 258 (71.3%) patients completed the study. Improvements in CGI-S scores from baseline were significant (p<0.001) at all visits. Remission criteria were met in 9 (2.5%) patients at baseline, and in 199 (54.9%) at endpoint, while 144 patients (52.7%) achieved symptomatic remission. Female patients were five times more likely to achieve symptomatic remission (OR=5.2; 95%CI=2.64-10.19). At baseline, 74/362 (20.4%) patients were employed, compared to 77/257 (30.0%) at endpoint (p<0.001). Adverse events were spontaneously reported in 55 (15.2%) patients. Three patients died (judged not to be related to RLAI) and one patient committed homicide. CONCLUSIONS: Patients treated with RLAI had significant improvements in CGI-S scale scores, hospitalization status, rates of remission and employment status, indicating the benefits of continuous treatment over time. Further studies on the comparative impact of different treatment strategies on functional recovery are needed.

Metabolic syndrome and cortisol/DHEAS ratio in patients with bipolar disorder and schizophrenia.

The cortisol/DHEAS ratio has been found to predict different health outcomes. We examined the association between cortisol/DHEAS ratio and metabolic syndrome (MetS) in patients suffering from bipolar disorder and schizophrenia. The only subcomponent of MetS positively associated with the cortisol/DHEAS ratio was diastolic blood pressure. Possible reasons for this finding, as well as study limitations, are discussed.

Diagnostic psychiatric and somatic comorbidity in patients with depression in the Western Balkan countries.

INTRODUCTION: This paper aims to examine the frequency and significance of diagnostic comorbidity of psychiatric disorders and somatic diseases in a sample of patients with depression as well as present current psychopharmacological treatment of the patients in the sample. METHODS: The subjects in this study sample were 489 patients from the four Western Balkan countries with current primary diagnosis of major depression according to ICD 10. Comorbid psychiatric disorders and non-psychiatric illnesses were noted according to ICD 10 criteria during the diagnostic interview and analysed later. Additionally, the pharmacological treatment (existing and newly introduced) for each patient was noted and analysed later. RESULTS: At least one comorbid psychiatric disorder was present in 72.5% of patients. The most frequent were anxiety disorders (53.6%), specifically generalized anxiety disorder (20.2%); non-organic sleep disorders (50.7%), specifically insomnia (48.4%); and sexual dysfunctions (21.4%), specifically lack of sexual desire (20.2%). Comorbidity with any non-psychiatric illness was present in 80.3% of patients. The most frequent were circulatory system diseases (55.9%), specifically hypertension (45.9%); endocrine, nutritional and metabolic disorders (51.3%), specifically hyperlipidaemia (24.0%); and other non-psychiatric disorders (60.7%), specifically low back pain (22.7%). All patients received pharmacological treatment with different medications. Most patients received monotherapy or combination therapy of antidepressants, anxiolytics, antipsychotics and antiepileptics. The most frequently used antidepressants were escitalopram, sertraline, and duloxetine. The most frequently used anxiolytics were alprazolam and diazepam, the most used antiepileptic was pregabalin, and the most used antipsychotics were olanzapine, quetiapine, and aripiprazole. CONCLUSION: The results of the study confirm the results of previous research studies about the high prevalence of psychiatric and non-psychiatric comorbidities in patients with depression that were conducted in the past. It would be important if future studies could prove the importance of those comorbidities on clinical severity, choice of treatment, and its outcome in patients with depression.

The association study of polymorphisms in DAT, DRD2, and COMT genes and acute extrapyramidal adverse effects in male schizophrenic patients treated with haloperidol.

Extrapyramidal symptoms (EPSs) are common adverse effects of antipsychotics. The development of acute EPSs could depend on the activity of dopaminergic system and its gene variants. The aim of this study was to determine the association between dopaminergic type 2 receptor (DRD2) dopamine transporter (SLC6A3) and catechol-O-methyltransferase (COMT) gene polymorphisms and acute EPSs in 240 male schizophrenic patients treated with haloperidol (15-mg/d) over a period of 2 weeks. Acute EPSs were assessed with Simpson-Angus Scale. Three dopaminergic gene polymorphisms, the DRD2 Taq1A, the SLC6A3 VNTR, and the COMT Val158Met, were determined. Extrapyramidal symptoms occurred in 116 (48.3%) of patients. Statistically significant associations were found for SLC6A3 VNTR and COMT Val158Met polymorphisms and EPS susceptibility. Patients with SLC6A3 9/10 genotype had almost twice the odds to develop EPSs compared with those with all other SLC6A3 genotypes (odds ratio, 1.9; 95% confidence interval, 1.13-3.30), and patients with COMT Val/Met genotype had 1.7 times greater odds to develop EPSs than those with all other COMT genotypes (odds ratio, 1.7; 95% confidence interval, 1.01-2.88). There was no statistically significant association between genotype and allele frequencies of DRD2, SLC6A3, or COMT polymorphisms and the development of particular EPSs.In conclusion, the results of the present study showed for the first time the association between acute haloperidol-induced EPSs and SLC6A3 VNTR and COMT Val158Met polymorphisms. Although the precise biological mechanisms underlying these findings are not yet understood, the results suggest that the dopaminergic gene variations could predict the vulnerability to the development of the acute EPSs in haloperidol-treated schizophrenic patients.