An association between PPARα-L162V polymorphism and increased plasma LDL cholesterol levels after risperidone treatment.

Peroxisome proliferator-activated receptor alpha (PPARα) and antipsychotic medications both influence polyunsaturated fatty acids (PUFA) homeostasis, and thus PPARα polymorphism may be linked to antipsychotic treatment response. Here we investigated whether the functional leucine 162 valine (L162V) polymorphism in PPARα influenced antipsychotic treatment in a group of psychosis patients (N = 186), as well as in a patient subgroup with risperidone, paliperidone, or combination treatment (N = 65). Antipsychotic-naïve first-episode patients and nonadherent chronic individuals were genotyped by polymerase chain reaction analysis. At baseline, and after 8 weeks of treatment with various antipsychotic medications, we assessed the patients' Positive and Negative Syndrome Scale (PANSS) scores; PANSS factors; and metabolic syndrome-related parameters, including fasting plasma lipid and glucose levels, and body mass index. In the total patient group, PPARα polymorphism did not affect PANSS psychopathology or metabolic parameters. However, in the subgroup of patients with risperidone, paliperidone, or combination treatment, PPARα polymorphism influenced changes in plasma LDL cholesterol. Specifically, compared to PPARα-L162L homozygous patients, PPARα-L162V heterozygous individuals exhibited significantly higher increases of LDL cholesterol levels after antipsychotic treatment. The PPARα polymorphism had a strong effect size, but a relatively weak contribution to LDL cholesterol level variations (∼12.8 %).

Association between PLA2 gene polymorphisms and treatment response to antipsychotic medications: A study of antipsychotic-naïve first-episode psychosis patients and nonadherent chronic psychosis patients.

Here we investigated whether antipsychotic treatment was influenced by three polymorphisms: rs10798059 (BanI) in the phospholipase A2 (PLA2)G4A gene, rs4375 in PLA2G6, and rs1549637 in PLA2G4C. A total of 186 antipsychotic-naïve first-episode psychosis patients or nonadherent chronic psychosis individuals (99 males and 87 females) were genotyped by polymerase chain reaction analysis/restriction fragment length polymorphism. At baseline, and after 8 weeks of treatment with various antipsychotic medications, we assessed patients' Positive and Negative Syndrome Scale (PANSS) scores, PANSS factors, and metabolic syndrome-related parameters (fasting plasma lipid and glucose levels, and body mass index). We found that PLA2G4A polymorphism influenced changes in PANSS psychopathology, and PLA2G6 polymorphism influenced changes in PANSS psychopathology and metabolic parameters. PLA2G4C polymorphism did not show any impact on PANSS psychopathology or metabolic parameters. The polymorphisms' effect sizes were estimated as moderate to strong, with contributions ranging from around 6.2-15.7%. Furthermore, the polymorphisms' effects manifested in a gender-specific manner.

Clozapine in Treatment-Resistant Schizophrenia and Its Augmentation with Electroconvulsive Therapy in Ultra-Treatment-Resistant Schizophrenia.

Clozapine is considered the gold standard for patients with treatment-resistant schizophrenia (TRS) who have previously tried other antipsychotics at adequate doses (two or more, with at least one being atypical). However, despite optimal treatment, a subgroup of TRS patients with what is known as ultra-treatment-resistant schizophrenia (UTRS) fails to respond to clozapine, which occurs in 40-70% of cases. The most common approach to manage UTRS involves augmenting clozapine with pharmacological or non-pharmacological interventions, with a growing body of evidence that supports the use of electroconvulsive therapy (ECT) as an augmenter. This prospective non-randomized 8-week study, which followed the TRIPP Working Group guidelines and is one of few that separate TRS from UTRS, aimed to evaluate the effectiveness of clozapine in TRS patients and the efficacy of ECT augmentation of clozapine in UTRS patients. Patients with TRS were assigned to receive clozapine alone (clozapine group), whereas UTRS patients received bilateral ECT in addition to their current medication regimen (ECT plus clozapine group). The severity of symptoms was evaluated using the Clinical Global Impression Scale (CGI) and Positive and Negative Syndrome Scale (PANSS) at baseline and at the end of the 8-week trial. Both treatment approaches resulted in improved CGI and PANSS scores. The results suggest that both clozapine and ECT are effective treatment options for patients with TRS and UTRS, respectively, and that adherence to guidelines should provide a better frame for future clinical studies.

Flavonols in Action: Targeting Oxidative Stress and Neuroinflammation in Major Depressive Disorder.

Major depressive disorder is one of the most common mental illnesses that highly impairs quality of life. Pharmacological interventions are mainly focused on altered monoamine neurotransmission, which is considered the primary event underlying the disease's etiology. However, many other neuropathological mechanisms that contribute to the disease's progression and clinical symptoms have been identified. These include oxidative stress, neuroinflammation, hippocampal atrophy, reduced synaptic plasticity and neurogenesis, the depletion of neurotrophic factors, and the dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis. Current therapeutic options are often unsatisfactory and associated with adverse effects. This review highlights the most relevant findings concerning the role of flavonols, a ubiquitous class of flavonoids in the human diet, as potential antidepressant agents. In general, flavonols are considered to be both an effective and safe therapeutic option in the management of depression, which is largely based on their prominent antioxidative and anti-inflammatory effects. Moreover, preclinical studies have provided evidence that they are capable of restoring the neuroendocrine control of the HPA axis, promoting neurogenesis, and alleviating depressive-like behavior. Although these findings are promising, they are still far from being implemented in clinical practice. Hence, further studies are needed to more comprehensively evaluate the potential of flavonols with respect to the improvement of clinical signs of depression.

Psychiatric Illness or Immune Dysfunction-Brain Perfusion Imaging Providing the Answer in a Case of Anti-NMDAR Encephalitis.

BACKGROUND: We investigated the potential use of SPECT quantification in addition to qualitative brain perfusion analysis for the detection of anti-NMDAR encephalitis. The question is how to normalize brain activity to be able to quantitatively detect perfusion patterns. Usually, brain activity is normalized to a structure considered unaffected by the disease. METHODS: Brain [99mTc]-HMPAO SPECT was performed as a method to detect brain perfusion patterns. The patterns of abnormal brain perfusion cannot always be reliably and qualitatively assessed when dealing with rare diseases. Recent advances in SPECT quantification using commercial software have enabled more objective and detailed analysis of brain perfusion. The cerebellum and whole brain were used as the normalization structures and were compared with visual analysis. RESULTS: The quantification analysis performed with whole brain normalization confirmed right parietal lobe hypoperfusion while also detecting statistically significant left-to-right perfusion differences between the temporal lobe and thalamus. Whole brain normalization further described bilateral frontal lobe hyperperfusion, predominantly of the left lobe, and was in accordance with visual analysis. CONCLUSION: SPECT quantitative brain perfusion analysis, using the whole brain as the normalization structure rather than the cerebellum, in this case, improved confidence in the visual detection of anti-NMDAR encephalitis and provided unexpected solutions to atypical psychiatric dilemmas.

Association between Insertion-Deletion Polymorphism of the Angiotensin-Converting Enzyme Gene and Treatment Response to Antipsychotic Medications: A Study of Antipsychotic-Naïve First-Episode Psychosis Patients and Nonadherent Chronic Psychosis Patients.

We investigated whether a functional insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE) influenced antipsychotic treatment. At baseline, and after 8 weeks of treatment with various antipsychotic medications, we assessed patients' Positive and Negative Syndrome Scale (PANSS) scores, PANSS factors, and metabolic-syndrome-related parameters (fasting plasma lipid and glucose levels, and body mass index). A total of 186 antipsychotic-naïve first-episode psychosis patients or nonadherent chronic psychosis individuals (99 males and 87 females) were genotyped by polymerase chain reaction analysis. The ACE-I/D polymorphism was significantly associated with changes in PANSS psychopathology only (p < 0.05). Compared to ACE-II homozygous males, ACE-DD homozygous and ACE-ID heterozygous males manifested significantly greater decreases in PANSS positive score, PANSS excitement factor, and PANSS cognitive factor. ACE-DD homozygous females manifested higher decreases in PANSS depression factor compared to ACE-II homozygous and ACE-ID heterozygous females. The polymorphism's effect size was estimated as moderate to strong, while its contribution to the PANSS psychopathology ranged from ~5.4 to 8.7%, with the lowest contribution observed for PANSS positive score changes and the highest for PANSS depressive factor changes. Our results indicate that ACE-I/D polymorphism had a statistically significant but weak gender-specific impact on psychopathology data, and showed no association between ACE-I/D polymorphism and metabolic-syndrome-related parameters.

Quetiapine Add-On Therapy May Improve Persistent Sleep Disturbances in Patients with PTSD on Stabile Combined SSRI and Benzodiazepine Combination: A One-Group Pretest-Posttest Study.

BACKGROUND: To assess potential benefits of quetiapine for persistent sleep disturbances in patients with posttraumatic stress disorder (PTSD) on stable combined SSRI and benzodiazepine therapy, who previously failed to respond to various benzodiazepine and non-benzodiazepine hypnotic adjuvant treatment as well as to first-generation antipsychotic add-on treatment. SUBJECTS AND METHODS: Fifty-two male PTSD outpatients on stable combination treatment with SSRI and benzodiazepines, with persistent sleep disturbances not responding to prescription of zolpidem, flurazepam, nitrazepam, promazine, and levopromazine, were assessed for sleep disturbances improvements after prescription of quetiapine in the evening. Each patient met both ICD-10 and DSM-IV criteria for PTSD. Psychiatric comorbidity and premorbidity were excluded using the Mini-International Neuropsychiatric Interview (MINI). Improvement on the CAPS recurrent distressing dream item, reduction in the amount of time needed to fall asleep, prolongation of sleep duration, and reduction in average number of arousals per night in the last 7 days before the assessment period were used as efficacy measures. RESULTS: All sleep-related parameters improved significantly at the end of a five-week follow-up: sleep duration increased by one hour (p<0.001), sleep latency decreased by 52.5 minutes (p<0.001), median number of arousals per night decreased from two to one (p<0.001), CAPS recurrent distressing dream item median decreased from five to four (p<0.001), and the number of patients dissatisfied with their sleep quality and quantity decreased from 45 to two (p<0.001). CONCLUSION: Quetiapine prescribed in the evening may be successful therapy for persistent sleep disturbances in patients with PTSD and generally good response to an SSRI and benzodiazepine combination, who previously failed to respond to some of the usual hypnotic medication or addition of first-generation antipsychotics: zolpidem, flurazepam, nitrazepam, promazine, and levopromazine.

The Impact of Long-acting Paliperidone in Reducing Hospitalizations and Clinical Severity in Recent Onset Schizophrenia: A Mirror-image Study in Real-world Clinical Setting.

OBJECTIVE: Schizophrenia is a debilitating disease that disrupts the lives of many affected individuals and exerts a toll on the health system. Only few studies assessed once-monthly injectable formulation of paliperidone palmitate (PP-1M) and other long-acting antipsychotics in recent onset schizophrenia (ROS). To evaluate whether PP-1M is efficacious in reducing frequency and length of hospitalizations and psychosis symptom severity in patients with ROS. METHODS: This mirror-image study included 112 patients, suffering from ROS admitted in a psychiatric ward and successively treated with PP-1M for 1-year. Other psychotic disorders were excluded. We collected socio-demographic data of all subjects included, number and days of hospitalization, as well as Clinical Global Impression-Severity scale (CGI-S) and Clinician-Rated Dimensions of Psychosis Symptom Severity (CRDPSS) scores at the initiation and after 1-year of PP treatment. RESULTS: After 1-year PP-1M treatment, mean scores of both CGI and CRDPSS significantly decreased (p < 0.001), as well as the mean number of hospitalizations (p = 0.002) and total hospitalization days (p < 0.001) in comparison with those of the previous year. CONCLUSION: Our results suggest that PP-1M can be considered as an important therapeutic option in patients with ROS. Its use led to a meaningful reduction in the patient's use of hospital services, as well as a significant clinical improvement of psychotic symptoms in our sample.

Changes in platelet serotonin concentration after four weeks of alcohol abstinence depending on the genotype of the serotonin transporter.

BACKGROUND: Alcohol use disorder (AUD) is a psychiatric disorder characterized by excessive and uncontrolled drinking that causes distress and has damaging consequences for men and women of all ages. It is one of the four most disabling diseases and it affects approximately 14.6 million persons in Europe. OBJECTIVES: Objective of this study is to investigate changes in platelet serotonin concentration after four weeks of alcohol abstinence in regards to the genotype of the serotonin transporter. METHODS: A total of 154 patients with AUD were included in the study. Platelet serotonin concentrations were assessed by enzyme-linked immunosorbent assay. Genotype of serotonin transporter promoter polymorphism was determined by the polymerase chain reaction-based method. RESULTS: We did not establish a statistically significant main effect of serotonin transporter polymorphism on platelet serotonin concentration after four weeks of abstinence. CONCLUSION: Aforementioned finding is in line with previous research suggesting a complex relationship between serotonin transporter gene and platelet serotonin levels, and congruent with the well-established genotype interaction with numerous other factors, such as sex, ethnicity, education level, and stressful life events.

Major depressive disorder: a possible typisation according to serotonin, inflammation, and metabolic syndrome.

OBJECTIVE: Major depressive disorder (MDD) is closely related to obesity, inflammation, and insulin resistance, all together being etiologically linked to metabolic syndrome (MetS) development. The depressive disorder has a neuroendocrinological component, co-influencing the MetS, while MetS is characterised by increased cytokine levels, which are known to cause a depressed mood. This study aimed to establish biological subtypes of the depressive disorder based on researched clinical, laboratory, and anthropometric variables. METHODS: We performed a cross-sectional study on a sample of 293 subjects (145 suffering from a depressive disorder and 148 healthy controls). Results were analysed with multivariate statistical methods as well as with cluster and discriminant analysis. In order to classify depressive disorder on the grounds of laboratory, anthropometric, and clinical parameters, we performed cluster analysis, which resulted in three clusters. RESULTS: The first cluster is characterised by low platelet serotonin, high cortisol levels, high blood glucose levels, high triglycerides levels, high Hamilton Depression Rating Scale score, high waist circumference, high C-Reactive Protein values, and a high number of previous depressive episodes, was named Combined (Metabolic) depression. The inflammatory depression cluster is defined with average platelet serotonin values, normal cortisol, and all other parameter levels, except for increased IL-6 levels. The serotoninergic depression cluster is characterised by markedly low platelet serotonin, and all other parameters are within the normal range. CONCLUSIONS: From a biological point of view, depressive disorder is not uniform, and as such, these findings suggest potential clinically useful and generalisable biological subtypes of depressive disorder.

Improvements of Frontotemporal Cerebral Blood Flow and Cognitive Functioning in Patients With First Episode of Schizophrenia Treated With Long-Acting Aripiprazole.

PURPOSE/BACKGROUND: Frontal and temporal cerebral blood flow (CBF) changes are the most common impairments of CBF described in patients with schizophrenia. Those impairments have also been associated with cognitive deficits, a hallmark of schizophrenia. In light of that fact, treatment interventions should target cognitive deficits to prevent chronic disability. However, specific therapies targeting cognitive symptoms are very few and far between. One of the treatment possibilities is aripiprazole, because several studies reported its potential procognitive effects. The objective of this study was to investigate whether use of aripiprazole in its long-acting injectable formulation (ALAI), during a 3-month treatment, has beneficial effects on CBF and cognitive functioning in patients with first episode of schizophrenia. METHODS/PROCEDURES: Single-photon emission computed tomography with technetium-99m hexamethylpropylene amine oxime was performed at 2 time points. Cognitive functions were assessed with a standardized test for cognitive functions, 5-KOG test, whereas severity of clinical symptoms was assessed with the Positive and Negative Syndrome Scale, both at the same 2 time points as single-photon emission computed tomography. Three-month treatment with ALAI was associated with improvement of several cognition indices and improvements of right-sided frontal and temporal CBF, as well as of clinical symptoms. FINDINGS/RESULTS: Multivariate tests were used to test for the effects of ALAI treatment on cognitive functions, clinical presentation, and brain perfusion in a 3-month period. Multivariate model revealed statistical significance (F = 11.958, P < 0.001). Of 10 separate 5-KOG parameters, 3-month treatment with ALAI significantly influenced 4: undelayed recall, delayed recall, attention, and working memory-digit span forward. Finally, 3-month ALAI treatment significantly improved regional CBF in 2 of 4 investigated areas, both on the right side of the brain (frontally and temporally). IMPLICATIONS/CONCLUSIONS: Results of this research showed that treatment with ALAI in patients with first episode of schizophrenia is associated with improved right-sided frontal and temporal CBF, as well as with improved symptoms, including cognition indices. Although we cannot confirm it directly, it is possible that improved frontotemporal CBF led to the improvement in cognition indices.

Dysregulated inflammation may predispose patients with serious mental illnesses to severe COVID­19 (Review).

Genetic and nongenetic factors associated with an increased inflammatory response may mediate a link between severe coronavirus disease 2019 (COVID­19) and serious mental illness (SMI). However, systematic assessment of inflammatory response­related factors associated with SMI that could influence COVID­19 outcomes is lacking. In the present review, dietary patterns, smoking and the use of psychotropic medications are discussed as potential extrinsic risk factors and angiotensin­converting enzyme (ACE) insertion/deletion (I/D) gene polymorphisms are considered as potential intrinsic risk factors. A genetics­based prediction model for SMI using ACE­I/D genotyping is also proposed for use in patients experiencing severe COVID­19. Furthermore, the literature suggests that ACE inhibitors may have protective effects against SMI or severe COVID­19, which is often linked to hypertension and other cardiovascular comorbidities. For this reason, we hypothesize that using these medications to treat patients with severe COVID­19 might yield improved outcomes, including in the context of SMI associated with COVID­19.

Long acting aripiprazole influences cognitive functions in recent onset schizophrenia.

RATIONALE: Beneficial effects of aripiprazole on cognition in schizophrenia have been previously reported, but not in recent onset schizophrenia. Cognitive impairments have also been associated with catechol-O-methyltransferase (COMT), methylenetetrahydrofolate reductase (MTHFR), and serotonin transporter (SERT) gene polymorphisms which were earlier implicated in the pathophysiology of schizophrenia. OBJECTIVES: This study examined the short-term influence of aripiprazole long-acting injectable (LAI) as well as of COMT, MTHFR, and SERT gene polymorphisms and their interactions on clinical features and cognitive functions in inpatients with recent onset schizophrenia. METHODS: This study included 98 inpatients suffering from recent onset schizophrenia diagnosed according to DSM-5 criteria. Three months after initiating aripiprazole LAI, the severity of symptoms was assessed by the Positive and Negative Syndrome Scale (PANSS), while cognitive functions were measured by 5-KOG test for cognition. Genotypes of SERT, MTHFR, and COMT gene were determined by different polymerase chain reaction (PCR) methods. RESULTS: Three-month aripiprazole LAI treatment was associated with a statistically significant change of PANSS total (p<0.001) and subscale scores as well as cognitive parameters of delayed recall (p<0.03), attention (p<0.01), and executive functions in the form of less perseverations (p<0.03), without influencing other examined cognitive functions. However, it significantly influenced composite cognitive score (p<0.02). In regard to the investigated genetic polymorphisms, we established a positive association between the COMT polymorphism (M/M allele carriers) and attention (p<0.01). Additionally, we also established a positive association between the COMT - MTHFR interaction and attention (p<0.02), as well as perseveration item belonging to executive functions (p<0.01). Two other investigated polymorphisms (MTHFR and SERT) were not significantly associated with cognitive indices. Investigated genetic polymorphisms and their interactions were not associated with PANSS scores. CONCLUSIONS: Our findings suggest that aripiprazole LAI improves individual cognitive functions in recent onset schizophrenia. Investigated COMT polymorphism (Met/Met genotype), as well as the COMT-MTHFR interaction, were positively associated with attention and executive functioning (perseveration), potentially implying COMT's biomarker potential in terms of cognition in schizophrenia.

Effects of aripiprazole long-acting injectable antipsychotic on hospitalization in recent-onset schizophrenia.

OBJECTIVE: Recent-onset schizophrenia (ROS) represents a critical period that can greatly influence the clinical course of schizophrenia. The use of long-acting injectable antipsychotics (LAIs) in this period is increasingly being considered as a first-line treatment option. Aripiprazole LAI (ALAI) is the newest of all LAI's available on the market, with limited data on its effects on hospitalization rates after first episode of schizophrenia. It was our goal to evaluate whether ALAI has an effect on hospitalization rates, number of bed days and clinical improvement in patients with ROS. METHODS: This mirror-image study included 138 inpatients suffering from schizophrenia. We collected sociodemographic data on all individuals, number of hospitalization days, hospitalization rates as well as Clinical Global Impression Scale-severity of illness (CGI-S) and Clinician-Rated Dimensions of Psychosis Symptom Severity (CRDPSS) scores at the initiation of ALAI and at the end of a 1 year follow up. RESULTS: Mean number of hospitalizations and hospitalization days in the year after starting ALAI significantly decreased compared to the year before (p = 0.005 and p < 0.001). Mean scores on both CGI and CRDPSS also significantly decreased after initiating ALAI (p < 0.001). CONCLUSION: Results suggest that ALAI is an important therapeutic option in patients with ROS. It leads to reduced usage of hospital services, potentially reducing the socio-economic healthcare burden.

Platelet Serotonin Concentration Is Associated with Illness Duration in Schizophrenia and Chronological Age in Depression.

OBJECTIVE: Impaired serotonergic neurotransmission has been implicated in the pathogenesis of depression and schizophrenia. Blood platelets have been used for years as a peripheral model of neuronal serotonin dynamics. The objective was to investigate platelet count and serotonin concentration in patients with depression and schizophrenia, in an attempt to ascertain their clinical usefulness. METHODS: 953 participants were included in the study, 329 patients with depression, 339 patients with schizophrenia and 285 healthy controls. ELISA was used to assess platelet serotonin concentrations. RESULTS: There were no statistically significant differences among groups regarding age, total platelet count and serotonin concentration. Linear regression analyses revealed inverse correlations between platelet serotonin concentration and age of patients with depression and healthy individuals, as well as between platelet serotonin concentration and illness duration in patients with schizophrenia. In other words, longer illness duration in patients with schizophrenia, and higher age in patients with depression and healthy individuals was associated with lower platelet serotonin concentrations. CONCLUSION: Platelet count and serotonin concentration did not prove to be of diagnostic value in differentiating patients and healthy individuals. However, illness duration in patients with schizophrenia may be associated with reduced concentrations of platelet serotonin.

EIGHTY YEARS OF ELECTROCONVULSIVE THERAPY IN CROATIA AND IN SESTRE MILOSRDNICE UNIVERSITY HOSPITAL CENTRE.

In 1937, Ugo Cerletti and Lucio Bini performed electroconvulsive treatment (ECT) in Rome for the first time. That was the time when different types of 'shock therapy' were performed; beside ECT, insulin therapies, cardiazol shock therapy, etc. were also performed. In 1938, Cerletti and Bini reported the results of ECT. Since then, this method has spread rapidly to a large number of countries. As early as 1940, just two years after the results of the ECT had been published, it was also introduced in Croatia, at Sestre milosrdnice Hospital, for the first time in our hospital and in the then state of Yugoslavia. Since 1960, again the first in Croatia and the state, we performed ECT in general anesthesia and continued it down to the present, with a single time brake.

THE USE OF ELECTRORETINOGRAPHY AND OPTICAL COHERENCE TOMOGRAPHY IN PATIENTS WITH SCHIZOPHRENIA.

The use of electroretinography (ERG) and optical coherence tomography (OCT) has currently expanded beyond ophthalmology alone. The aim of this review is to present the results and knowledge acquired by these two methods in patients suffering from schizophrenia. Reviewing the studies applying ERG and OCT methods in the field of psychiatry, one can conclude that results of the research imply morphological and functional changes of retina in patients with schizophrenia that are not consistent. However, in most studies there was reduction of the amplitude and changes in the implicit time related parameters on ERG and thinning of the retinal nerve fiber layer on OCT. Neurons in the eye use the same neurotransmitters as neurons in the basal brain structures that are most affected in schizophrenia, according to the dopamine hypothesis of schizophrenia. Unlike neurons in the basal brain structures, the neurons in the eye are in vivo available to ERG. Using the aforementioned tests together with clinical diagnostic criteria of schizophrenia, the subgroups with different prognostic and therapeutic specificities within schizophrenia as a group of diseases might be identified more precisely.

THE ENIGMA OF LEWY BODY DEMENTIA: A CASE REPORT.

Lewy body dementia is a progressive neurodegenerative disease and is considered to be the second most common cause of dementia in the elderly. Because of the complexity of clinical presentation, it is often misdiagnosed and mistaken for other dementias, which may result in administering inappropriate therapy, and thus worsening of the patient condition. We reviewed a case of a 71-year-old patient whose clinical presentation gradually occurred with complex visual hallucinations, atypical extrapyramidal motor symptoms, fluctuating cognitive impairments with delirious episodes, and oscillating syncope. Depressive mood, impaired daily functioning and sensitivity to antipsychotics were also noted. Extensive diagnostic workup was performed with neuropsychological testing and use of single-photon emission computerized tomography. Considering the clinical presentation and diagnostic procedures performed, the diagnosis of Lewy body dementia was set and pharmacotherapy was revised. We discuss the importance of taking overall clinical presentation and diagnostic treatment in consideration and applying appropriate therapy to slow down the progression of the disease and exacerbation of the patient's psychological functions.

Vitamin D and Neurotrophin Levels and Their Impact on the Symptoms of Schizophrenia.

INTRODUCTION: Vitamin D is involved in brain development and functioning, as well as in regulation of neurotrophic factors. Changes in the expression of those factors are possibly responsible for morphologic abnormalities and symptoms in patients suffering from schizophrenia. OBJECTIVE: The main goal of this research was to investigate the interrelationship between vitamin D, nerve growth factors (NGF, brain-derived neurotrophic factor [BDNF], and neuregulin-1 [NRG1]), and schizophrenia symptom domains. METHODS: This research included 97 inpatients diagnosed with schizophrenia. Schizophrenia symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). Blood samples were taken in order to analyze concentrations of vitamin D, BDNF, NRG1, and NGF growth factors. The obtained results were used in a multiple regression analysis. RESULTS: The vitamin D concentration positively affected the concentration of NRG1 (F = 8.583, p = 0.005) but not the concentration of other investigated growth factors (BDNF and NGF). The clinical characteristics and symptom domains of schizophrenia seemed to be unaffected by the concentrations of vitamin D, BDNF, and NGF, while the NRG1 concentration significantly affected positive symptom domains of schizophrenia (F = 4.927, p = 0.030). CONCLUSION: The vitamin D concentration positively affected NRG1 levels but not schizophrenia symptomatology as measured by PANSS. The as-sociation between the two could be intermediated via NRG1.