Determination of miR-373 and miR-204 levels in neuronal exosomes in Alzheimer's disease.

BACKGROUND: NLRP3 inflammasome activation has been known to be involved in the etiology and progression of Alzheimer's disease (AD). Furthermore, AD and diabetes mellitus have common pathomechanisms. It has been shown that P2X7R whose expression is increased in brain tissues with AD and plays a role in the activation of NLRP3 inflammasome is suppressed by miR-373 in patients with osteoarthritis. Therefore, the question of whether the suppressive effect of miR-373 on NLRP3 may have a role in the pathophysiology of AD comes to mind. On the other hand, it is known that the miR-204 level increases in response to TXNIP, another NLRP3 inflammasome inducer with high expression in AD. In primary human islets, miR-204 reduces the expression of GLP-1R. It has been discovered that in vivo deletion of miR-204 is protective against diabetes by increasing GLP-1R and insulin secretion. Considering the relationship between miR-204 and TXNIP and the relationship of miR-204 with diabetes suggests investigating the effect of miR-204 on the inflammatory pathway in AD. Based on the common pathophysiological mechanisms between AD and diabetes and the reported changes related to NLRP3 inflammasome, we analyzed miR-373 and miR-204 in neuron-derived serum exosomes in this study. Neuron-derived exosomes in neurodegenerative diseases are considered to be better candidates for developing potential biomarkers. METHODS: The expression levels of miR-204 and miR-373 were investigated in neuron-derived serum exosomes obtained from 15 patients with mild AD, 18 with moderate AD, and 21 cognitively healthy individuals. RESULTS: The miR-204 and miR-373 expressions were significantly decreased in both patient groups compared to the control group. Therefore, we suggest that miR-204 and miR-373 are potential biomarkers for AD. However, due to the preliminary nature of this study, further large-scale studies are needed to support our findings.

[Endogenous and Exogenous Attention in Alzheimer Type of Dementia: Effect of Target Position]. / Alzheimer Tipi Demansta Iç ve Dis Kaynakli Dikkat: Konum Etkisi.

OBJECTIVE: Endogenous attention (EnA) is an ability in goal-driven processes, controlled by top-down mechanisms and exogenous attention (ExA) is an ability in stimulus-driven processes, controlled by bottomup mechanisms. In the present research, it was aimed to investigate in Alzheimer's disease (AD) the EnA and ExA processes in relation to target position (right/left) by using the Spatial Cueing Paradigm (SCP). METHOD: The study was conducted with the participants of 65-90 year age range, consisting of 14 female and 14 male (n=28) participants diagnosed with AD and 12 female and 12 male (n=24) healthy volunteers as controls. The group variable (AD, Control) was tested on the intergroup basis; and the attention type (EnA, ExA), trial type (valid /VT+ and invalid/ VT-) and the target position (left/right) variables were tested on the intra-subject basis (within subject design). Two separate factorial ANOVAs were conducted for mean reaction time and accuracy measures obtained from SCP. RESULTS: In comparison to the control group, the AD group participants gave slow and wrong reactions to stimuli for EnA and ExA. The AD group responses were faster in the VT+s and more accurate in the VT-s to stimuli on the left as compared to those on the right; and the responses of AD patients to the stimuli on the left as compared to those on the right was more accurate in VT-s under ExA condition. CONCLUSION: AD causes impairment of EnA and ExA. Faster reactions by AD participants to the target on the left in VT+s and more accurate reactions to the target on the left in VT-s are in agreement with reports in the literature on the lateralization of visual-spatial attention (VSA) in the right hemisphere. In this study, also in agreement with previous reports, lateralization in AD was noted in favour of the stimuli on the left in ExA.

Genotype and Allele Frequency of CYP3A4 -392A>G in Turkish Patients with Major Depressive Disorder.

OBJECTIVES: Genetic polymorphisms may help for individualized drug dosing and improved therapeutics. CYP3A4 is responsible for the metabolism of more than 50% of the commonly used drugs and metabolizes typical antipsychotic medications and antidepressant drugs. The objective of the study was to assess the genotype and allele frequencies of CYP3A4 -392A>G in Turkish patients with major depressive disorder receiving any SSRIs and to compare these results with the frequencies of other ethnic groups. MATERIALS AND METHODS: Genotyping analyses of CYP3A4 -392A>G was conducted on 84 Turkish patients using the PCR-RFLP technique. RESULTS: The allele frequencies were found as 0.982 (A) and 0.018 (G) for CYP3A4 -392A>G. The genotype frequencies were determined as 0.976 (AA), 0.012 (AG), and 0.012 (GG). The genotype frequencies were consistent with the Hardy-Weinberg equilibrium. CONCLUSION: The genotype and allele frequencies of CYP3A4 -392A>G were determined to be low in Turkish patients with major depressive disorder receiving SSRIs. Furthermore, the results of the study were compared with those of other ethnic groups and they displayed pronounced differences among other ethnic groups, especially black subjects.

Clinical characteristics of generalized anxiety disorder: older vs. young adults.

BACKGROUND: Generalized anxiety disorder (GAD) is one of the most common anxiety disorders in older people. Although GAD in older adults seems to differ in many aspects like clinical presentation, severity and treatment response, there is a paucity of comparative research. AIMS: The aim of the study is to compare the clinical presentation of GAD between older and young adults. METHODS: One hundred and two non-demented older patients (age ≥65) and 64 young patients (age <45) who were diagnosed with GAD according to the DSM-IV-TR criteria were included to the study. Socio-demographic Data Form, the Structured Clinical Interview for DSM Disorders-1 (SCID-1), the Questionnaire for the Suggested Behavioral Criteria of GAD for DSM-5, the Hamilton Depression Scale (HAM-D), the Generalized Anxiety Disorder Severity Scale (GADSS) and the Sheehan Disability Scale (SDS) were applied to both groups. RESULTS AND CONCLUSIONS: Older GAD patients had more disturbances of sleep, less reassurance seeking behaviors, higher rates of depression and higher depression severity when compared to the young patients. Although older people seemed to have a lower severity of GAD, they had higher disability due to worries. Older patients worried more about their own health and family well-being, whereas young patients worried more about future and other's health.

Frontal activity during a verbal emotional working memory task in patients with Alzheimer's disease: A functional near-infrared spectroscopy study.

Emotional working memory (EWM) is suggested as a working memory (WM) type, distinguished to process emotional stimuli, and may or may not be spared in Alzheimer's disease (AD). The aim was to compare patients with AD and healthy older adults (HC) on verbal EWM performance and accompanying prefrontal cortex activity. Twenty AD patients along with 20 HC individuals are required to complete an emotional one-back task in three conditions (neutral, positive and negative word lists). Prefrontal oxyhemoglobin (oxyHb) concentrations were measured simultaneously by a 24- channel functional near infrared spectroscopy device. Correct response rates were similar in two groups in all conditions. Reaction times were comparable in the EWM positive condition but longer in the AD group in EWMneutral and negative conditions. In the HC group, emotional words had no significant effect on WM. On the other hand, positive compared to neutral words led to greater activation in the left ventral prefrontal cortex (VPFC) in AD group. When compared to HCs, activity in the VPFC was significantly higher in AD patients during the positive condition. Positive words facilitated WM performance in participants with AD. Activity in VPFC may be the functional correlate of this phenomenon.

Hyperfocusing as a dimension of adult attention deficit hyperactivity disorder.

Patients with Attention Deficit Hyperactivity Disorder (ADHD) suffer not only from inability to focus but also from inability to shift attention for events that trigger their interests. This phenomenon is called "hyperfocusing". Previous literature about hyperfocusing is scarce and relies mainly on case reports. The study aimed to investigate and compare the severity of hyperfocusing in adult ADHD with and without psycho-stimulant use. ADHD (DSM-IV-TR) patients either psycho-stimulant naive (n=53) or on psycho-stimulants (n=79) from two ADHD clinics were recruited. The control group (n=65) consisted of healthy university students. A socio-demographic form, the Beck Depression Inventory, the Wender-Utah Rating Scale, the Adult ADHD Self- Report Scale and the Hyperfocusing Scale were applied to the participants. There was no difference between total Hyperfocusing Scale and Adult ADHD Self- Report Scale scores of two patient groups, but both have higher scores than controls (p<0.001). Hyperfocusing is higher in adult ADHD and there was no difference between stimulant-naive patients or patients on stimulants. Hyperfocusing can be defined as a separate dimension of adult ADHD.

[Discrepancy Between Subjective Memory Complaints and Objective Memory Deficits in Elderly Patients with Depression Compared to Mild Cognitive Impairment]. / Yaslilik Çagi Depresyonu ve Hafif Bilissel Bozuklugu Olan Hastalarda Öznel Bellek Yakinmalari ile Nesnel Bellek Bozukluklarinin Karsilastirilmasi.

OBJECTIVE: Since depression in the elderly usually presents with memory complaints and may impair memory functions, differential diagnosis of cognitive impairment is quite difficult. This study aimed to investigate the discrepancy between subjective memory complaints (SMC) and objective memory deficits in elderly patients with major depressive disorder (MDD) and mild cognitive impairment (MCI). METHOD: The study sample consisted of 30 elderly patients with a diagnosis of MCI (according to Petersen- Mayo criteria) and 29 with a diagnosis of DSM-IV-TR MDD who were admitted to the outpatient geriatric psychiatry clinic. The control group (HC) consisted of 30 healthy elderly volunteers. Turkish versions of the Mini Mental State Examination (MMSE), Clock Drawing Test (CDT), ADAS-Cog, Subjective Memory Complaints Questionnaire (SMCQ) and Geriatric Depression Scale (GDS) were administered to all participants. RESULTS: The SMCQ scores of both MDD and MCI patients were higher than HC. However, there was no difference between HC and MDD groups in terms of the MMSE, the CDT and the ADAS-Cog scores. CONCLUSION: In elderly patients, subjective memory complaints do not seem to differentiate between depression and cognitive impairment. However, the discrepancy between SMC and cognitive performances suggest depression rather than a cognitive impairment. Further longitudinal studies should investigate the role of SMC in future cognitive impairment for elderly patients with depression.

[The Relationship of Verbal Working Memory and Theory of Mind in First Degree Relatives of Patients With Schizophrenia and Bipolar Disorder]. / Sizofreni ve Psikotik Özellikli Bipolar Bozukluk Hastalarinin Birinci Derece Akrabalarinda Zihin Kurami ve Sözel Çalisma Belleginin Iliskisi.

OBJECTIVE: We aimed to compare Theory of Mind (ToM) functions and investigate the relationship between ToM functions and verbal working memory (VWM) in first degree relatives of bipolar disorder and schizophrenia patients. METHOD: The sample consisted of first degree relatives of patients with bipolar disorder (n=22), schizophrenia (n=28), and age, gender, education and total IQ matched healthy volunteers (n=27) without a family history of schizophrenia or bipolar disorder. We administered Auditory Consonants Test (ACT) to evaluate VWM, first and second order false belief tests (ToM-1, ToM-2), Faux Pas Test (FPT), Hinting Test (HT) to evaluate different domains of ToM functions. RESULTS: Both relative groups performed significantly lower in all components of ToM and VWM tests compared to the control group. When VWM scores were employed as covariate in the analyses, the FPT difference between the groups remained significant, HT difference regressed to a marginal level, and the difference between ToM-1 and ToM-2 disappeared. CONCLUSION: To our knowledge, this is the first study indicating the presence of ToM impairment among first degree relatives of bipolar disorder patients similar to relatives of schizophrenia patients. VWM performance seems to affect first and second order ToM functions in relatives of patients with schizophrenia and bipolar disorder. On the other hand, FPT and HT domains seem to be independent of VWM performances in these groups. FPT and HT impairments may be familial vulnerability markers that are independent from neurocognitive impairment.

[Hoarding Behaviour in Three Different Types of Dementia Cases]. / Farkli Demansi Olan Üç Olguda Biriktirme Davranisi.

INTRODUCTION: Hoarding behaviour, which is generally defined as collecting and keeping unnecessary, cheap objects or things that can not be used, is more common in elderly than young people. The prevelance of hoarding behaviour in dementia was reported as 22%. In this paper, three different types of dementia cases are presented in order to emphasize the clinical awareness for hoarding disorder, which is common in the elderly, especially those with dementia. CASES: The first case is a patient with a diagnosis of frontotemporal dementia who was collecting old things before the appearance of bahavioural changes like verbal and physical agitation. The second one is a patient who was admitted with complaints of forgetting, diagnosed as having Alzheimer's Disease and presented with paper hoarding behavior in his clinical follow-up. The last patient was presented with visual hallucinations, forgetting, collecting old things and depressive symptoms. He received a diagnosis of Lewy body dementia. DISCUSSION: It is prominent that all three different dementia cases hoarding behavior at early stages of dementia. It should be kept in mind that hoarding behavior which begins at late life might be a sign of dementia or it might appear in the dementia process.

Influence of CYP2B6 and CYP2C19 polymorphisms on sertraline metabolism in major depression patients.

BACKGROUND: Genetic polymorphisms in CYP2B6 and CYP2C19 may cause variability in the metabolism of sertraline, a widely used antidepressant in major depressive disorder treatment. OBJECTIVE: This study investigates the impact of CYP2B6*4 (785A > G), CYP2B6*9 (516G > T), CYP2B6*6 (516G > T + 685G > A) CYP2C19*2 (685G > A), CYP2C19*17 (-3402C > T) polymorphisms on plasma concentrations of sertraline and N-desmethyl sertraline in major depression patients treated with sertraline [n = 50]. SETTING: Participants were patients who admitted to an adult psychiatry outpatient unit at a university hospital. These were DSM-IV major depression diagnosed patients with a stable sertraline medication regimen [for at least one month]. METHODS: CYP2B6*4 (rs 2279343; 785A > G), CYP2B6*9 (516G > T; rs 3745274), CYP2B6*6 (516G > T + 685G > A) CYP2C19*2 (rs 4244285; 685G > A), CYP2C19*17 (rs 11188072; -3402C > T), polymorphisms were analyzed by polymerase chain reaction and restriction fragment length polymorphism. Plasma concentrations were measured by high-performance liquid chromatography in patients treated with SERT. MAIN OUTCOME MEASURE: The distribution of CYP2B6*4, *6, *9 and CYP2C19*2, *17 among patient group and the association between genotype and sertraline metabolism. RESULTS: Sertraline, N-desmethyl sertraline, N-desmethyl sertraline/sertraline and dose-adjusted plasma concentrations were statistically compared between individuals with wild-type and variant alleles both for CYP2B6 and CYP2C19 enzymes. The mean N-desmethyl sertraline/sertraline value, was significantly lower in all subgroups with *6 and *9 variant alleles (p < 0.05). Sertraline/C values were significantly higher (p < 0.05) and N-desmethyl sertraline/C values were lower in all subgroups with *6 and *9 variant alleles compared to wild-type subgroup. CONCLUSION: CYP2B6*6 and *9 variant alleles had a significant decreasing effect on sertraline metabolism in major depression patients which might result as variations in sertraline therapy.

[Dimensions of Agitation Based on the Cohen-Mansfield Agitation Inventory in Patients with Dementia]. / Demans Hastalarinda Cohen-Mansfield Ajitasyon Envanteri ile Degerlendirilen Ajitasyon Boyutlarinin Arastirilmasi.

OBJECTIVE: The aim of this study was to investigate the dimensions of agitation in dementia patients using the Turkish version of the Cohen-Mansfield Agitation Inventory (CMAI-T). MATERIALS AND METHODS: The study included 100 patients diagnosed as dementia, according to the DSM-IV-TR. The CMAI-T was administered to the patients' caregivers via face-to-face interviews. The Standardized Mini Mental State Examination (SMMSE) was used to assess cognitive functions. The severity of depression and the functional state of the patients were assessed using the Cornell Scale for Depression in Dementia (CSDD) and the Functional Activities Questionnaire (FAQ). Principal component analysis and varimax rotation were used to determine the factor structure of the CMAI-T. RESULTS: Factor analysis of the CMAI-T indicated a 3-factor structure: physically aggressive agitation, verbal agitation, and physically non-aggressive agitation. In 92% of the patients there was ≥1 agitation behavior during the previous 2 weeks. The CMAI-T total and factor scores were negatively correlated with the SMMSE scores, and positively correlated with the CSDD and the FAQ scores. CONCLUSIONS: The CMAI-T yielded 3 factors (physically aggressive agitation, verbal agitation, and physically non-aggressive agitation), which indicated the scale had construct validity. Agitation behaviors were associated with cognitive dysfunction, symptoms of depression and general level of functioning. Additional research is necessary to identify the predictors of these dimensions in different dementia samples, and to determine the efficacy of therapeutic interventions.

Exploring the Role of Social Anhedonia in the Positive and Negative Dimensions of Schizotypy in a Non-Clinical Sample.

INTRODUCTION: The present study aimed to investigate the role of social anhedonia, defined as the lack of ability to feel pleasure from interpersonal relationship, in a multidimensional model of schizotypy and to determine the psychometric properties of the Turkish version of Chapman's Revised Social Anhedonia Scale (SAS) in a non-clinical sample. METHODS: Second-grade students of Ankara University Medical Faculty were recruited (n=266, Mage=20.28). Confirmatory factor analysis was performed to test schizotypy dimensions. The Cronbach's alpha internal consistency value, test-retest reliability and congruent validity of SAS were calculated. RESULTS: The model in which social anhedonia was allowed to load on both schizotypy dimensions fit the data set better than the model in which social anhedonia was allowed to load on negative dimension alone. The internal consistency assessed with Cronbach's alpha was .84, test-retest reliability was r=.76 and the congruent validity of SAS was r=.55. CONCLUSION: The results of current study were consistent with those of earlier studies showing that social anhedonia was related to both schizotypy dimensions. Furthermore, the psychometric properties of the Turkish Version of SAS revealed that it is a reliable and valid measurement to assess social anhedonia in a non-clinical population.

Prefrontal activity measured by functional near infrared spectroscopy during probabilistic inference in subjects with persecutory delusions.

Jumping to conclusions (JTC) is a probabilistic reasoning bias and is thought to contribute to delusion formation. Neurobiological correlates of the JTC bias are not known. We aimed to examine the rostral prefrontal cortex (rPFC) activity with functional near infrared spectroscopy during a modified version of the Beads in a Jar Task (BIJT) in subjects with persecutory delusions (N=25). In BIJT participants are presented beads either drawn from one of the two jars with opposite probability ratios (PRs) of colored beads and are required to decide from which jar beads are being drawn. We administered the BIJT with 90/10 and 55/45 PRs. Compared to healthy controls (N=20), patients reached a decision earlier in both conditions. While the medial rPFC regions were more active in the 90/10 condition in controls compared to patients, lateral rPFC activation was higher in the 55/45 condition in patients than controls. Only in the control group, there was a marked decline in the lateral rPFC activation in the 55/45 condition compared to the 90/10 condition. The activity in the lateral rPFC was negatively correlated with the amount of beads drawn in healthy controls but not in subjects with persecutory delusions. Our results suggest that during the BIJT, rPFC does not function as a single unit and rather consists of functional subunits that are organized differently in patients and controls. The failure to deactivate the lateral rPFC may be associated with earlier decisions in subjects with persecutory delusions.

[The relationship between right hemi-space visuospatial attention disturbance and anger in antisocial individuals]. / Antisosyal bireylerde sag yari uzaya iliskin görsel dikkat bozukluguyla öfkenin iliskisi.

OBJECTIVE: Evidence suggests that individuals with antisocial personality disorder (APD) exhibit a less asymmetric pattern than healthy controls during auditory and visuospatial attention tasks characterized by a right hemispheric advantage; however, the association between attention asymmetry and symptomatology is not clear. The present study aimed to examine the relationship between visuospatial attention in the right and left hemi-spaces, and various dimensions of anger in individuals with APD. MATERIALS AND METHODS: We compared visuospatial attention performance in the right and left hemi-spaces during a computerized Line Bisection Test (LBT) in individuals with APD (n = 52) and healthy controls (n = 34). We also administered the Multi-Dimensional Anger Scale (MDAS) to both groups. RESULTS: Subjects in the APD group made larger bisection errors than healthy controls only during the right hemi-space condition and had higher scores than those in the control group on all MDAS dimensions of anger. The severity of anger symptoms and thoughts were predicted by right hemi-space visuospatial attention disturbance in the APD group, whereas no such association was observed in the control group. CONCLUSION: The present findings either suggest a left hemisphere neuropathology or a disturbance in inter-hemispheric transmission in the APD group. Right hemi-space-specific visual attention disturbance may mediate the relationship between neuropathology, and somatic and trait dimensions of anger in APD.

Hemispatial neglect evaluated by visual line bisection task in schizophrenic patients and their unaffected siblings.

Visuospatial attentional asymmetry has been investigated by the line bisection task in patients with schizophrenia, however, those studies are in small number and the results are controversial. The present study aimed to investigate hemispatial neglect in patients with schizophrenia (n=30), their healthy siblings (n=30) and healthy individuals (n=24) by a computerized version of the line bisection task. Deviation from the midline for both hemispaces (mean bisection error-MBE) were calculated and the effects of both hand and line length were controlled. Repeated measures ANOVA yielded a significant hemispace effect for the MBE scores, but no group or group×hemispace interaction effect, i.e., all three groups were inclined to a leftward bias in the left and a rightward bias in the right hemispace. MBEs were significantly different from "zero" only for the right hemispace in siblings and for the left hemispace in controls. Negative symptoms were significantly correlated with the bisection errors in the right hemispace. The results of the present study do not support aberrant hemispheric asymmetry, but bigger bisection errors in schizophrenia.

Social anxiety in patients with Parkinson's disease.

Previous research highlights the presence of social anxiety disorder related to disfiguring diseases, although DSM-IV precludes the diagnosis of social anxiety disorder related to a medical condition. The present study investigated the frequency and severity of social anxiety disorder in patients with Parkinson's disease (n=50) and comparison subjects (n=50). Social anxiety was diagnosed in 16% of patients with Parkinson's disease and 2% of the comparison subjects. Regression analysis revealed younger age and depression as predictive factors of social anxiety. This study supported the likelihood of social anxiety disorder as a comorbid condition in Parkinson's disease. Revision of the criteria for social anxiety disorder in future diagnostic systems is necessary for the detection and management of these patients.

Secondary social anxiety in hyperkinesias.

This is a comparison study that is aimed to investigate and compare the frequency and severity of secondary social anxiety disorder (SAD) in patients with hyperkinesias, which is associated with a significant sense of disfigurement and compromised social interaction. Patients with hemifacial spasm (n = 20), cervical dystonia (n = 20), and essential tremor (n = 20) were evaluated by SCID-I, Liebowitz Social Anxiety Scale, Hamilton Anxiety and Depression Rating Scales, and Sheehan Disability Scale. The DSM-IV H criterion excluding social anxiety related to a medical condition was disregarded for the diagnosis of secondary SAD. The control group (n = 60) consisted of matched healthy subjects. The frequency of the diagnosis and severity of symptoms were compared and associations with sociodemographic and clinical factors were explored. There was no difference between three patient groups in terms of the frequency or the severity of secondary SAD. Younger age and depressive symptoms were associated with the severity of secondary SAD, while severity or duration of the movement disorder or social disability was not. This study revealed a high frequency of secondary SAD in hyperkinesias, emphasizing the need for psychiatric assessment, especially for younger and depressed patients, who seem to be at greater risk.