PTSD, Immune System, and Inflammation.

Posttraumatic stress disorder (PTSD) is a severe trauma and stress-related disorder associated with different somatic comorbidities, especially cardiovascular and metabolic disorders, and with chronic low-grade inflammation. Altered balance of the hypothalamic-pituitary-adrenal (HPA) axis, cytokines and chemokines, C-reactive protein, oxidative stress markers, kynurenine pathways, and gut microbiota might be involved in the alterations of certain brain regions regulating fear conditioning and memory processes, that are all altered in PTSD. In addition to the HPA axis, the gut microbiota maintains the balance and interaction of the immune, CNS, and endocrine pathways forming the gut-brain axis. Disbalance in the HPA axis, gut-brain axis, oxidative stress pathways and kynurenine pathways, altered immune signaling and disrupted homeostasis, as well as the association of the PTSD with the inflammation and disrupted cognition support the search for novel strategies for treatment of PTSD. Besides potential anti-inflammatory treatment, dietary interventions or the use of beneficial bacteria, such as probiotics, can potentially improve the composition and the function of the bacterial community in the gut. Therefore, bacterial supplements and controlled dietary changes, with exercise, might have beneficial effects on the psychological and cognitive functions in patients with PTSD. These new treatments should be aimed to attenuate inflammatory processes and consequently to reduce PTSD symptoms but also to improve cognition and reduce cardio-metabolic disorders associated so frequently with PTSD.

The Association of the Polymorphisms in the FUT8-Related Locus with the Plasma Glycosylation in Post-Traumatic Stress Disorder.

The molecular underpinnings of post-traumatic stress disorder (PTSD) are still unclear due to the complex interactions of genetic, psychological, and environmental factors. Glycosylation is a common post-translational modification of proteins, and different pathophysiological states, such as inflammation, autoimmune diseases, and mental disorders including PTSD, show altered N-glycome. Fucosyltransferase 8 (FUT8) is the enzyme that catalyzes the addition of core fucose on glycoproteins, and mutations in the FUT8 gene are associated with defects in glycosylation and functional abnormalities. This is the first study that investigated the associations of plasma N-glycan levels with FUT8-related rs6573604, rs11621121, rs10483776, and rs4073416 polymorphisms and their haplotypes in 541 PTSD patients and control participants. The results demonstrated that the rs6573604 T allele was more frequent in the PTSD than in the control participants. Significant associations of plasma N-glycan levels with PTSD and FUT8-related polymorphisms were observed. We also detected associations of rs11621121 and rs10483776 polymorphisms and their haplotypes with plasma levels of specific N-glycan species in both the control and PTSD groups. In carriers of different rs6573604 and rs4073416 genotypes and alleles, differences in plasma N-glycan levels were only found in the control group. These molecular findings suggest a possible regulatory role of FUT8-related polymorphisms in glycosylation, the alternations of which could partially explain the development and clinical manifestation of PTSD.

Heavy Metals and Essential Metals Are Associated with Cerebrospinal Fluid Biomarkers of Alzheimer's Disease.

Various metals have been associated with the pathogenesis of Alzheimer's disease (AD), principally heavy metals that are environmental pollutants (such as As, Cd, Hg, and Pb) and essential metals whose homeostasis is disturbed in AD (such as Cu, Fe, and Zn). Although there is evidence of the involvement of these metals in AD, further research is needed on their mechanisms of toxicity. To further assess the involvement of heavy and essential metals in AD pathogenesis, we compared cerebrospinal fluid (CSF) AD biomarkers to macro- and microelements measured in CSF and plasma. We tested if macro- and microelements' concentrations (heavy metals (As, Cd, Hg, Ni, Pb, and Tl), essential metals (Na, Mg, K, Ca, Fe, Co, Mn, Cu, Zn, and Mo), essential non-metals (B, P, S, and Se), and other non-essential metals (Al, Ba, Li, and Sr)) are associated with CSF AD biomarkers that reflect pathological changes in the AD brain (amyloid ß1-42, total tau, phosphorylated tau isoforms, NFL, S100B, VILIP-1, YKL-40, PAPP-A, and albumin). We used inductively coupled plasma mass spectroscopy (ICP-MS) to determine macro- and microelements in CSF and plasma, and enzyme-linked immunosorbent assays (ELISA) to determine protein biomarkers of AD in CSF. This study included 193 participants (124 with AD, 50 with mild cognitive impairment, and 19 healthy controls). Simple correlation, as well as machine learning algorithms (redescription mining and principal component analysis (PCA)), demonstrated that levels of heavy metals (As, Cd, Hg, Ni, Pb, and Tl), essential metals (Ca, Co, Cu, Fe, Mg, Mn, Mo, Na, K, and Zn), and essential non-metals (P, S, and Se) are positively associated with CSF phosphorylated tau isoforms, VILIP-1, S100B, NFL, and YKL-40 in AD.

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.

Platelet serotonin concentration and trait aggression in veterans with post-traumatic stress disorder: a preliminary study.

Animal and human studies suggest that aggressive behavior may be modulated by brain serotonergic system. Serotonergic (5-HT) dysfunction is associated with post-traumatic stress disorder (PTSD), but also with increased aggression and impulsivity, hallmarks of PTSD. The aim of the study was to investigate the association of platelet 5-HT concentration and various types of aggression and impulsivity in veterans with PTSD. A group of 42 male combat-related PTSD subjects entered the study. Four different aggression facets were measured by the Buss and Perry's Aggression Questionnaire (BPAQ). Verbal and physical types of impulsive aggressive behavior were measured by the subscales of the Zuzul's Aggressiveness Inventory A-87. Impulsivity was determined using Eysenck's IVE questionnaire. PTSD severity was evaluated by Watson's PTSD questionnaire. Platelet serotonin concentration was determined spectrofluorimetrically. Confounding variables were: age, body mass, alcohol use, comorbid depression, and tobacco use. Platelet 5-HT concentration and PTSD severity were independently associated only with impulsive types of aggression, as higher platelet 5-HT concentration and more severe PTSD were related to more impulsive aggression. These results strongly recommend distinguishing between specific types of aggression facets, and advise the importance of theory-based concepts of aggression facets when evaluating the biological correlates of aggression.

A Load to Find Clinically Useful Biomarkers for Depression.

Depression is heterogeneous and complex disease with diverse symptoms. Its neurobiological underpinning is still not completely understood. For now, there are still no validated, easy obtainable, clinically useful noninvasive biomarker(s) or biomarker panel that will be able to confirm a diagnosis of depression, its subtypes and improve diagnostic procedures. Future multimodal preclinical and clinical research that involves (epi)genetic, molecular, cellular, imaging, and other studies is necessary to advance our understanding of the role of monoamines, GABA, HPA axis, neurotrophins, metabolome, and glycome in the pathogenesis of depression and their potential as diagnostic, prognostic, and treatment response biomarkers. These studies should be focused to include the first-episode depression and antidepressant drug-naïve patients with large sample sizes to reduce variability in different biological and clinical parameters. At present, metabolomics study revealed with high precision that a neurometabolite panel consisting of plasma metabolite biomarkers (GABA, dopamine, tyramine, kynurenine) might represent clinically useful biomarkers of MDD.

Biomarkers of Depression Associated with Comorbid Somatic Diseases.

Depression is heterogeneous clinical entity with different clinical symptoms, that imply diverse biological underpinning, different molecular substrates and pathways. Besides different psychiatric comorbidities, depression is frequently interrelated with somatic diseases. Multi-morbidities, i.e. somatic diseases associated with depression, reduce quality of life, worsen clinical picture and increase mortality. The most frequent somatic diseases co-occurring with depression are cardiovascular and metabolic diseases. Vulnerable individuals will develop depression, and the goal in modern research and in precision/personalized medicine is to determine vulnerability factors associated with development of depression and to find easy available biomarkers of depression, especially comorbid with somatic diseases. This mini-review aimed to describe the latest published data (from 2015-20120) considering biomarkers of depression related to somatic diseases. Biomarkers related to inflammatory processes, atherosclerosis, imbalance of the hypothalamic-pituitary-adrenal axis, autonomic nerve system, sympathetic and parasympathetic nervous system, heart rate variability and endothelial dysfunction could improve the understanding of the underlying biological mechanisms of the common pathways of depression comorbid with somatic diseases. These targeted biomarkers might be used to reduce the symptoms, improve the treatment of these interrelated diseases, and decrease the morbidity and mortality.

Searching for glycomic biomarkers for predicting resilience and vulnerability in a rat model of posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is triggered by traumatic events in 10-20% of exposed subjects. N-linked glycosylation, by modifying protein functions, may provide an important environmental link predicting vulnerability. Our goals were (1) to find alterations in plasma N-glycome predicting stress-vulnerability; (2) to investigate how trauma affects N-glycome in the plasma (PGP) and in three PTSD-related brain regions (prefrontal cortex, hippocampus and amygdala; BGP), hence, uncover specific targets for PTSD treatment. We examined male (1) controls, (2) traumatized vulnerable and (3) traumatized resilient rats both before and several weeks after electric footshock. Vulnerable and resilient groups were separated by z-score analysis of behavior. Higher freezing behavior and decreased social interest were detected in vulnerable groups compared to control and resilient rats. Innate anxiety did not predict vulnerability, but pretrauma levels of PGP10(FA1G1Ga1), PGP11(FA2G2), and PGP15(FA3G2) correlated positively with it, the last one being the most sensitive. Traumatic stress induced a shift from large, elaborate N-glycans toward simpler neutral structures in the plasma of all traumatized animals and specifically in the prefrontal cortex of vulnerable rats. In plasma trauma increased PGP17(A2G2S) level in vulnerable animals. In all three brain regions, BGP11(F(6)A2B) was more abundant in vulnerable rats, while most behavioral correlations occurred in the prefrontal cortex. In conclusion, we found N-glycans (especially PGP15(FA3G2)) in plasma as possible biomarkers of vulnerability to trauma that warrants further investigation. Posttrauma PGP17(A2G2S1) increase showed overlap with human results highlighting the utility and relevance of this animal model. Prefrontal cortex is a key site of trauma-induced glycosylation changes that could modulate the behavioral outcome.

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.

BDNF Val66Met polymorphism and clinical response to antipsychotic treatment in schizophrenia and schizoaffective disorder patients: a meta-analysis.

Brain-derived neurotrophic factor (BDNF) plays an important role in dopaminergic and serotonergic neurotransmission by modulating dopaminergic neuron differentiation and establishment. Multiple studies have analyzed the functional BDNF Val66Met variant in relation to antipsychotic response in schizophrenia (SCZ) patients, yielding mixed results. A meta-analysis was thus performed to examine the relationship between this variant and symptom improvement during antipsychotic treatment. Searches using PubMed, Web of Science, and PsycInfo until October 2017 yielded 11 studies that met inclusion criteria (total n = 3774). These studies investigated the BDNF Val66Met variant and antipsychotic response in patients with SCZ or schizoaffective disorder. Responders to antipsychotics were defined using the original criteria applied in each study. Effect sizes were computed using odds ratios, which were pooled according to the Mantel-Haenszel method. The BDNF Val66Met variant was not associated with the total number of responders and non-responders (p > 0.05) under dominant, recessive, or allelic models. Secondary analyses stratifying for individuals of each ethnicity and drug type also revealed no significant associations. Our findings suggest that the BDNF Val66Met variant is not associated with response to antipsychotics in individuals with SCZ. However, considering the current sample size, small effects cannot be ruled out. Moreover, recent studies have suggested that Val66Met forms haplotypes with other BDNF variants. Future studies should examine the Val66Met variant in conjunction with these other variants in relation to antipsychotic response. Moreover, since illness duration appears to influence BDNF levels in SCZ patients, future studies should aim to control for this potential confounding factor in response analyses.

Association between reduced brain-derived neurotrophic factor concentration & coronary heart disease.

Background & objectives: Brain-derived neurotrophic factor (BDNF) facilitates neuronal survival, differentiation and synaptic connectivity and affects neurotransmission throughout the brain. However, it has also a modulatory role in energy homeostasis, obesity and cardiovascular function. Obesity, high body mass index (BMI) and dyslipidaemia, among other factors, contribute to coronary heart disease (CHD) development. The exact role of BDNF in development of CHD is not well defined. This study was aimed to evaluate if plasma BDNF concentration was associated with CHD in ethnically homogeneous groups of patients and to correlate plasma BDNF levels with known risk factors for CHD. Methods: Plasma BDNF concentration, BDNF Val66Met polymorphism and other biological and anthropological risk factors for CHD were determined in 208 patients with CHD and 156 healthy controls. Results: Plasma BDNF concentration was significantly (P <0.01) reduced in patients with CHD compared to controls, and it was not influenced by gender, age, smoking or BDNF Val66Met polymorphism. It was considerably correlated with cholesterol (P=0.004), low-density lipoprotein (P=0.006), and diastolic blood pressure (P=0.018) in patients with CHD and with platelet number (P=0.003) in healthy controls. Interpretation & conclusions: The results revealed lower plasma BDNF concentration in patients with CHD, suggesting that decreased plasma BDNF concentration might be associated with CHD pathogenesis. Longitudinal studies with a large sample need to be conducted to confirm these findings.

Genetic Markers of Alzheimer's Disease.

Alzheimer's disease is a complex and heterogeneous, severe neurodegenerative disorder and the predominant form of dementia, characterized by cognitive disturbances, behavioral and psychotic symptoms, progressive cognitive decline, disorientation, behavioral changes, and death. Genetic background of Alzheimer's disease differs between early-onset familial Alzheimer's disease, other cases of early-onset Alzheimer's disease, and late-onset Alzheimer's disease. Rare cases of early-onset familial Alzheimer's diseases are caused by high-penetrant mutations in genes coding for amyloid precursor protein, presenilin 1, and presenilin 2. Late-onset Alzheimer's disease is multifactorial and associated with many different genetic risk loci (>20), with the apolipoprotein E ε4 allele being a major genetic risk factor for late-onset Alzheimer's disease. Genetic and genomic studies offer insight into many additional genetic risk loci involved in the genetically complex nature of late-onset Alzheimer's disease. This review highlights the contributions of individual loci to the pathogenesis of Alzheimer's disease and suggests that their exact contribution is still not clear. Therefore, the use of genetic markers of Alzheimer's disease, for monitoring development, time course, treatment response, and prognosis of Alzheimer's disease, is still far away from the clinical application, because the contribution of genetic variations to the relative risk of developing Alzheimer's disease is limited. In the light of prediction and prevention of Alzheimer's disease, a novel approach could be found in the form of additive genetic risk scores, which combine additive effects of numerous susceptibility loci.

Genetic Markers in Psychiatry.

Psychiatric disorders such as addiction (substance use and addictive disorders), depression, eating disorders, schizophrenia, and post-traumatic stress disorder (PTSD) are severe, complex, multifactorial mental disorders that carry a high social impact, enormous public health costs, and various comorbidities as well as premature morbidity. Their neurobiological foundation is still not clear. Therefore, it is difficult to uncover new set of genes and possible genetic markers of these disorders since the understanding of the molecular imbalance leading to these disorders is not complete. The integrative approach is needed which will combine genomics and epigenomics; evaluate epigenetic influence on genes and their influence on neuropeptides, neurotransmitters, and hormones; examine gene × gene and gene × environment interplay; and identify abnormalities contributing to development of these disorders. Therefore, novel genetic approaches based on systems biology focused on improvement of the identification of the biological underpinnings might offer genetic markers of addiction, depression, eating disorders, schizophrenia, and PTSD. These markers might be used for early prediction, detection of the risk to develop these disorders, novel subtypes of the diseases and tailored, personalized approach to therapy.

The Association between Serotonin Transporter Polymorphism, Platelet Serotonin Concentration and Insomnia in Non-Depressed Veterans with Posttraumatic Stress Disorder.

BACKGROUND: The role of serotonin transporter and its functional gene polymorphism (5-HTTLPR, serotonin transporter linked polymorphic region) was investigated in sleep disturbances in various mental disorders, with conflicting findings. Here, the association of particular sleep disturbances with 5-HTTLPR genotypes and platelet serotonin (5-HT) concentration was determined simultaneously in veterans with posttraumatic stress disorder (PTSD), who were subdivided into those with or without comorbid depression. SUBJECTS AND METHODS: Croatian male, medication-free war veterans with PTSD (N=325), subdivided into those with or without comorbid depression, and subdivided further according to the various sleep disturbances, were evaluated using the Structured Clinical Interview, the Hamilton Rating Scale for Depression and the Clinician Administered PTSD Scale. Genotyping and platelet 5-HT concentration measurements were conducted using PCR and spectrofluorimetric methods, respectively. RESULTS: Nominally higher frequency of the 5-HTTLPR LL genotype compared to S carriers (p=0.026; χ2 test) and significantly higher platelet 5-HT concentration (p=0.001; one-way ANOVA) were detected in non-depressed veterans with PTSD with early insomnia, compared to matched veterans without early insomnia. CONCLUSIONS: Over-representation of the LL genotype of the 5-HTTLPR and higher platelet 5-HT concentrations were detected in veterans with PTSD who did not develop comorbid depression but had severe early insomnia. These results suggest that 5-HTTLPR genotypes and platelet 5-HT concentration are associated with early insomnia in non-depressed veterans with PTSD. Limitations of the study were the cross-sectional nature of the study, biallelic assessment of the 5-HTTLPR, and a lack of use of the specific sleep measurement scales. These results should be replicated in larger samples, validated on different populations, using specific sleep measurement scales and triallelic 5-HTTLPR assessment.

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.

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.

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.

Theranostic Biomarkers for Schizophrenia.

Schizophrenia is a highly heritable, chronic, severe, disabling neurodevelopmental brain disorder with a heterogeneous genetic and neurobiological background, which is still poorly understood. To allow better diagnostic procedures and therapeutic strategies in schizophrenia patients, use of easy accessible biomarkers is suggested. The most frequently used biomarkers in schizophrenia are those associated with the neuroimmune and neuroendocrine system, metabolism, different neurotransmitter systems and neurotrophic factors. However, there are still no validated and reliable biomarkers in clinical use for schizophrenia. This review will address potential biomarkers in schizophrenia. It will discuss biomarkers in schizophrenia and propose the use of specific blood-based panels that will include a set of markers associated with immune processes, metabolic disorders, and neuroendocrine/neurotrophin/neurotransmitter alterations. The combination of different markers, or complex multi-marker panels, might help in the discrimination of patients with different underlying pathologies and in the better classification of the more homogenous groups. Therefore, the development of the diagnostic, prognostic and theranostic biomarkers is an urgent and an unmet need in psychiatry, with the aim of improving diagnosis, therapy monitoring, prediction of treatment outcome and focus on the personal medicine approach in order to improve the quality of life in patients with schizophrenia and decrease health costs worldwide.

Occurrence of post-injection delirium/sedation syndrome after application of olanzapine long-acting injection during one year period.

INTRODUCTION: The aim was to report the occurrence of after application of olanzapine long-acting injection (OLAI) in patients with schizophrenia during one year period. SUBJECTS AND METHODS: During one year period, OLAI was applied to 30 patients with schizophrenia (18 men, 12 women) who were non-adherent to previous treatment with oral olanzapine. Patients were 20-58 years of age (39 years old on average), diagnosed with SCID based on DSM-IV-TR criteria. Patients received OLAI in dosage between 210-405 mg (287±62 (mean ± SD)) every 2-4 weeks. RESULTS: Out of 30 patients that received OLAI, 29 patients improved significantly without side-effects, and one patient developed post-injection delirium/sedation syndrome (PDSS). The patient's somatic condition stabilized and treatment with OLAI was discontinued due to the PDSS. CONCLUSION: The occurrence of PDSS is not common and when it occurs, in our experience, it was reversible.