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.

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.

Relationship of Anxiety, Depression, Stress, and Post-Traumatic Stress Disorder Symptoms with Disease Severity in Acutely Ill Hospitalized COVID-19 Patients.

We aimed to investigate depression, anxiety, stress, and PTSD symptoms and their relationship with disease severity in acutely ill hospitalized Coronavirus disease 2019 (COVID-19) patients. A single-center cross-sectional observational survey study screening for psychiatric symptoms using the Depression, Anxiety and Stress Scale-21 Items (DASS-21) and the Impact of Events Scale-Revised (IES-R) questionnaires was performed including a total of 169 acutely ill COVID-19 patients. All patients were adults and of white race and developed respiratory insufficiency during hospitalization. Demographic, clinical and laboratory data were evaluated as predictors of psychiatric symptoms. We hypothesized that higher intensity of COVID-19 symptoms and higher oxygen requirement would be associated with occurrence of depression, anxiety, stress, and PTSD symptoms. Depressive symptoms were absent in 29%, mild in 16%, moderate in 27.8%, severe in 10.7% and extremely severe in 16.6% patients. Anxiety symptoms were absent in 43.8%, mild in 6.5%, moderate in 17.2%, severe in 5.3% and extremely severe in 27.2% patients. Stress symptoms were absent in 78.7%, mild in 4.7%, moderate in 7.1%, severe in 7.7%, and extremely severe in 1.8% patients. A total of 60.9% patients had no PTSD symptoms, 16% had undiagnosed symptoms, and 23.1% met the criteria for a PTSD diagnosis. All psychiatric symptoms were more pronounced in female patients, depression and anxiety symptoms were associated with prior chronic obstructive pulmonary disease. Only depressive symptoms were significantly associated with higher intensity of COVID-19 symptoms and higher oxygen requirement. Acutely ill hospitalized COVID-19 patients presented a high prevalence of emergent psychiatric sequelae, especially in females, and more severe COVID-19 influenced mostly the severity of depressive symptoms.

SLC6A3, HTR2C and HTR6 Gene Polymorphisms and the Risk of Haloperidol-Induced Parkinsonism.

Antipsychotic-induced parkinsonism (AIP) is the most common type of extrapyramidal side effect (EPS), caused by the blockage of dopamine receptors. Since dopamine availability might influence the AIP risk, the dopamine transporter (DAT) and serotonin receptors (5-HTRs), which modulate the dopamine release, may be also involved in the AIP development. As some of the individual differences in the susceptibility to AIP might be due to the genetic background, this study aimed to examine the associations of SLC6A3, HTR2C and HTR6 gene polymorphisms with AIP in haloperidol-treated schizophrenia patients. The Extrapyramidal Symptom Rating Scale (ESRS) was used to evaluate AIP as a separate entity. Genotyping was performed using a PCR, following the extraction of blood DNA. The results revealed significant associations between HTR6 rs1805054 polymorphism and haloperidol-induced tremor and rigidity. Additionally, the findings indicated a combined effect of HTR6 T and SLC6A3 9R alleles on AIP, with their combination associated with significantly lower scores of ESRS subscale II for parkinsonism, ESRS-based tremor or hyperkinesia and ESRS subscales VI and VIII. These genetic predictors of AIP could be helpful in better understanding its pathophysiology, recognizing the individuals at risk of developing AIP and offering personalized therapeutic strategies for the patients suffering from this EPS.

Clinical decision-making style preferences of European psychiatrists: Results from the Ambassadors survey in 38 countries.

BACKGROUND: While shared clinical decision-making (SDM) is the preferred approach to decision-making in mental health care, its implementation in everyday clinical practice is still insufficient. The European Psychiatric Association undertook a study aiming to gather data on the clinical decision-making style preferences of psychiatrists working in Europe. METHODS: We conducted a cross-sectional online survey involving a sample of 751 psychiatrists and psychiatry specialist trainees from 38 European countries in 2021, using the Clinical Decision-Making Style - Staff questionnaire and a set of questions regarding clinicians' expertise, training, and practice. RESULTS: SDM was the preferred decision-making style across all European regions ([central and eastern Europe, CEE], northern and western Europe [NWE], and southern Europe [SE]), with an average of 73% of clinical decisions being rated as SDM. However, we found significant differences in non-SDM decision-making styles: participants working in NWE countries more often prefer shared and active decision-making styles rather than passive styles when compared to other European regions, especially to the CEE. Additionally, psychiatry specialist trainees (compared to psychiatrists), those working mainly with outpatients (compared to those working mainly with inpatients) and those working in community mental health services/public services (compared to mixed and private settings) have a significantly lower preference for passive decision-making style. CONCLUSIONS: The preferences for SDM styles among European psychiatrists are generally similar. However, the identified differences in the preferences for non-SDM styles across the regions call for more dialogue and educational efforts to harmonize practice across Europe.

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.

Add-on Oxytocin in the Treatment of Postpartum Acute Schizophrenia: A Case Report.

An increasing body of research has been published concerning the potential impact of oxytocin (OT) in the pathophysiology of neuropsychiatric disorders that affect social functioning, such as schizophrenia. The possible therapeutic effect of OT in promoting mother-child bonding could be valuable in the management of postpartum psychosis. Studies on the efficacy of OT as an add-on therapy in the treatment of schizophrenia have found reductions in both positive and negative symptoms. The patient in the case reported here developed her second psychotic episode at the age of 22, a month after delivering her first child. Four weeks after treatment with aripiprazole was initiated, the patient's negative symptoms persisted, causing problems in the mother-child interaction. Intranasal OT (40 IU/d) was then added to the aripiprazole. Assessment scales [the Positive and Negative Syndrome Scale (PANSS), the Disability Assessment Schedule (WHODAS 2.0), and the Barkin Index of Maternal Functioning (BIMF)] and qualitative data from her caregiver were obtained at baseline and in the third and eighth weeks after the end of the OT therapy. Improvement was observed on almost all of the domains of the WHODAS 2.0 and the BIMF, as well as on the PANSS negative and general psychopathology scales. Data from the patient's caregiver indicated an overall improvement in mother-child interaction. These results, especially the improvement in results on the PANSS scale, are similar to findings from previous studies in patients with schizophrenia. OT seems to boost the antipsychotic effect on positive symptoms through the OT dopamine pathway, while the effect on negative symptoms probably involves a more general mechanism. Because the postpartum period is of immense significance for child development and mental well-being, future research to investigate the therapeutic efficacy of OT in the management of postpartum psychosis is warranted.

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.

Distinct association of plasma BDNF concentration and cognitive function in depressed patients treated with vortioxetine or escitalopram.

RATIONALE: Cognitive dysfunction is frequent in major depressive disorder (MDD), and brain-derived neurotrophic factor (BDNF) is involved both in regulation of cognition and in therapeutic response in MDD. OBJECTIVES: The aim of this study was to determine if baseline plasma BDNF might predict change in cognitive function in MDD patients treated with vortioxetine or escitalopram, and whether the alterations in BDNF levels correlate with changes in cognitive performance during treatment. METHODS: Drug-naive or drug-free patients with MDD (N=121) were sampled and evaluated at baseline and 4 weeks after treatment initiation with vortioxetine or escitalopram. Cognitive function was evaluated using the F-A-S test, Digit Span test, and Digit Symbol Coding test. Plasma BDNF was determined using ELISA. RESULTS: The results of the study indicate that both vortioxetine (V) and escitalopram (E) improved cognitive functions evaluated with F-A-S test (V: p<0.001; r=-0.427, E: p<0.001; r=-0.370), Digit Symbol Coding test (V: p<0.001; r=-0.706, E: p<0.001; r=-0.435), and Digit Span test-backward span (V: p=0.001; r=-0.311, E: p=0.042; r=-0.185), while only vortioxetine (p<0.001; r=-0.325) improved cognition evaluated with the Digit Span test-forward span. A moderate positive correlation between pretreatment plasma BDNF levels and improvement in cognitive performance was only detected in patients treated with vortioxetine (delta F-A-S test: p=0.011; r=0.325, delta Digit Span test-forward span: p=0.010, r=0.326). CONCLUSIONS: These results suggest that higher baseline plasma BDNF levels might be associated with improvements in verbal fluency and working memory in vortioxetine, but not escitalopram treated patients. Vortioxetine treatment was superior in simple attention efficiency.

Assessment and Treatment of Negative Symptoms in Schizophrenia-A Regional Perspective.

Clinicians and researchers consider that there are a variety of symptoms that constitute negative symptoms in schizophrenia, and they may use different definitions for the same symptoms. These differences are also reflected in a variety of negative symptom rating scales. Both research and clinical work are negatively affected by the lack of consensus regarding the symptoms that constitute negative symptoms in schizophrenia. Leading research groups have investigated ways to reduce heterogeneity in the domain of negative symptoms in schizophrenia; however, little attention has been paid to regional differences in the concepts of negative symptoms in schizophrenia. The objective of this review was to collect and summarize information about the assessment and treatment of negative symptoms of schizophrenia in Central and Eastern Europe (CEE). Nineteen experts from 17 countries in CEE participated in this project. The participants collected information about their countries, including the following: (1) the most important publications about negative symptoms in schizophrenia (irrespective of the time of their publication); (2) the most frequently used negative symptom of schizophrenia in clinical practice; (3) definitions of frequently used negative symptoms; and (4) treatment of negative symptoms in schizophrenia. The participating experts/countries most frequently reported the following five negative symptoms: avolition, blunted affect, alogia, asociality, and anhedonia. Several experts also considered other symptoms as belonging to the negative symptom domain, such as a decrease in energy level and changes in personality. The importance of evaluating the long-term course and the relationship between negative symptoms and other symptom domains was also noted. No noticeable differences were reported in the treatment of negative symptoms compared to currently published guidelines and algorithms. The most frequently reported negative symptoms included those defined by the NIMH-MATRICS consensus statement on negative symptoms and recently endorsed in a guidance paper of the European Psychiatric Association. The main differences in the concepts, names, and definitions of primary negative symptoms, especially those related to personality changes, and to the evaluation of the long-term course and relationship between different symptom domains in CEE compared to the current English language literature deserve the attention of psychiatrists and other professionals in this field.

Effect of vortioxetine vs. escitalopram on plasma BDNF and platelet serotonin in depressed patients.

Escitalopram and vortioxetine are efficacious antidepressants. They directly target serotonin (5-HT) system, but vortioxetine mechanism of action is distinct from the one of selective serotonin reuptake inhibitors (SSRIs). Treatment with SSRIs decrease platelet 5-HT concentration and increase peripheral brain-derived neurotrophic factor (BDNF) levels. Since vortioxetine has a multimodal mechanism of action, it is expected to have a greater effect on circulatory BDNF concentration, compared to conventional antidepressants. This longitudinal study aimed to explore and compare the effects of 4-weeks of treatment with vortioxetine and escitalopram on plasma BDNF and platelet 5-HT concentration in patients with major depressive disorder (MDD). The results revealed that vortioxetine significantly increased plasma BDNF concentration (p = .018) and significantly decreased platelet 5-HT concentration (p < .001). Treatment with escitalopram significantly decreased platelet 5-HT concentration (p < .001), but it did not affect plasma BDNF concentration (p = .379). Response to vortioxetine was not predicted by baseline plasma BDNF or platelet 5-HT concentration, but response to escitalopram was predicted by baseline platelet 5-HT concentration. These effects might be due to vortioxetine unique mechanism of action, but the clinical implications are unclear. It remains to be determined whether this finding extends during long-term vortioxetine treatment, and which, if any, clinical effects emerge from BDNF increase.

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

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

Catechol-O-methyltransferase rs4680 and rs4818 haplotype association with treatment response to olanzapine in patients with schizophrenia.

Antipsychotic drugs target primarily dopaminergic system which makes catechol-O-methyltransferase (COMT) an interesting target in studies searching for treatment response predictors in schizophrenia. The study assessed the association of the COMT rs4680 and rs4818 polymorphisms with therapeutic response to olanzapine, risperidone, clozapine or other antipsychotic medication after 8 weeks of monotherapy in patients with schizophrenia. 521 Caucasian patients with schizophrenia received a monotherapy with olanzapine (10-20 mg/day; N = 190), risperidone (3-6 mg/day; N = 99), or clozapine (100-500 mg/day; N = 102). The fourth group (N = 130) consisted of patients receiving haloperidol (3-15 mg/day), fluphenazine (4-25 mg/day) or quetiapine (50-800 mg/day). Treatment response was defined as a 50% reduction from the baseline positive and negative syndrome scale (PANSS) total and subscale scores, but also as an observed percentage reduction from the initial PANSS0-6 total and subscale scores. Carriers of the COMT rs4680 A allele and carriers of the COMT rs4680-rs4818 C-A haplotype block had greater reduction in the PANSS total scores following olanzapine treatment, compared to carriers of the COMT rs4680 GG genotype and other COMT rs4680-rs4818 haplotypes. The COMT rs4680 A allele, and COMT rs4680-rs4818 C-A haplotype, were significantly associated with therapeutic response in patients treated with olanzapine, but not in patients treated with other antipsychotics.

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.

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.

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.

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.

Smoking in schizophrenia: recent findings about an old problem.

PURPOSE OF REVIEW: Recent epidemiology, biological and clinical findings correlate high cigarette consumption in patients with schizophrenia, impeding both treatment strategies and the effectiveness of antipsychotics. RECENT FINDINGS: New data suggests that despite world-wide efforts to curb cigarette consumption, smoking in patients with schizophrenia was still high. Recent reports could not confirm earlier findings regarding smoking's beneficial effects on cognitive dysfunction, however, the association between smoking, positive symptoms and suicidal behavior was revealed. As some patients smoked in an attempt to alleviate extrapyramidal symptoms (EPS) and negative symptoms, the molecular studies shared genetic roots correlating smoking and schizophrenia, revealing that smoking may increase the risk of developing schizophrenia. Preclinical and clinical studies clarified the complex relationship between schizophrenia's pathology and nicotine's effects on the human brain. SUMMARY: Cigarette smoking continues to adversely affect the health of individuals with schizophrenia. Both smoking and heavy nicotine dependence, given the complex biological findings, might influence symptom severity in patients with schizophrenia. Regardless, ceasing smoking activities is strongly advocated to replace 'self-medication by nicotine' with safer and more effective medications.