SOCIAL COGNITION AND OXIDATIVE STRESS IN SCHIZOPHRENIA PATIENTS AND FIRST-DEGREE RELATIVES OF PATIENTS.

BACKGROUND: Misattribution of motivational salience to non-salient (neutral) stimuli could be viewed as a hallmark of psychosis in schizophrenia. Studies have recently revealed increased subjective experience of emotional arousal (EA) to neutral social stimuli in paranoid schizophrenia psychosis, suggesting a misattribution of emotional salience to them. We examined this phenomenon directly by quantifying the level of EA subjectively attributed to low-arousal, neutral-valenced faces. SUBJECTS AND METHODS: Patients with remitted schizophrenia (PG) (n=26), first-degree relatives of schizophrenic patients (RG) (n=25), and healthy controls (HCG) (n=36) were compared in terms of oxidative stress parameters -serum Superoxide Dismutase, Catalase, Glutathione Peroxidase (GPx), Nitrite, Nitrate, Malondialdehyde, and Total Glutathione levels-, social cognition measured by the Reading the Mind in the Eyes Test and working memory measured by the N-back Task. Groups were compared, assuming that HCG had a genetically lower risk of schizophrenia compared to PG and RG. RESULTS: HCG performed significantly better than PG and RG, who were genetically at high risk, in terms of social cognition (respectively p=0.000, p=0.014), working memory (respectively p=0.001, p=0.003), and had statistically lower Glutathione Peroxidase (GPX) level than the PG and RG (both p:0.000). After controlling for the effect of the general intellectual abilities measured by the Raven Standard Progressive Matrices Test and working memory the differences between groups on the Eyes Test disappeared (p=0.057). However, this value tended to be significant. CONCLUSION: It was concluded that social cognition and working memory and GPx level may be used as endophenotypes and social cognition, working memory, and general intellectual skills are different but strongly related constructs. Endophenotypes guide treatment targets even after the disease has developed. The results of our study showed that in addition to psychopharmacological treatments, interventions to reduce oxidative stress and approaches to improve cognitive skills will have a positive impact on the disease's progression.

The Auditory Consonant Trigram (ACT) Test: A norm updating study for university students.

The Auditory Consonant Trigram (ACT) Test is accepted as a pure measurement of verbal working memory, but its norm study and psychometric properties have not been sufficiently researched. This study aims to update the norm data of the ACT, validity and reliability studies of which have been previously conducted on an adult Turkish sample, on a broader young sample and in a way that would end some methodological limitations. For this purpose, the data is collected from 304 voluntary healthy young adults (aged 18-26, 152 females-152 males). According to the results, a difference is found among all delay intervals. While the test scores decrease in females as delay interval increases, there is no difference in males between the delay intervals of 9 and 18 sec. While there is no difference between the genders for very short delay intervals (0-3 sec), males show a more successful performance than females as the delay interval increases (9-18 sec). Males are also more successful than females in terms of total test scores of the ACT. In this respect, it is concluded that the ACT measurement of working memory with a total score reliability coefficient of 0.75 is reliable.

Impaired auditory and visual time reproduction in adult patients with attention deficit-hyperactivity disorder.

Objective: Although impaired time perception is associated with significant disturbance in the everyday functioning of adult patients with Attention Deficit-Hyperactivity Disorder (ADHD), it is not very well studied. The present study aimed to evaluate both visual and auditory time reproduction (TR) by using eight time intervals in adult ADHD patients compared to healthy controls (HC).Method: Wechsler Adult Intelligence Scale-R (WAIS-R), Adult Attention Deficit-Hyperactivity Disorder Self-Report Scale (ASRS), Wender Utah Rating Scale (WURS), Hyperfocusing Scale (HS), Beck Depression Inventory (BDI) and a 2-back task were administered to participants. In TR tasks, participants reproduced the same duration of the auditory/visual stimulus by pressing a key and absolute discrepancy scores (ADS) were calculated. A 2 (Group) x 2 (Task Modality) x 8 (Time Interval: 500, 1000, 2000, 4000, 6000, 8000, 12000 and 16000 msec) mixed-design ANOVA was performed.Results: All clinical scores of ADHD group were higher than HC (p < .001) while WAIS-R and 2-back performances of the groups were similar. Mixed-design ANOVA yielded significant Group and Time Interval main effects as well as a Group X Time Interval effect (both p < .001). ADHD patients had larger ADS than HC and as time intervals increased, error levels increased. Errors for time intervals >8000 msec were more prominent in patients. For both TR tasks, ASRS-hyperactivity/impulsivity scores were the main predictor of ADS in the linear regression analysis, while ASRS-attention deficit and HS scores were excluded.Conclusion: Results of the present study indicate significant TR impairment in adult ADHD regardless of task modality (visual or auditory), depressive symptoms and working memory performances. Longer time intervals in TR tasks differentiated patients better and TR impairment was associated with hyperactivity/impulsivity. These findings should be replicated in larger samples and underlying neurobiological components of impaired TR need to be examined in future research.

Cortical activity during social acceptance and rejection task in social anxiety disorder: A controlled functional near infrared spectroscopy study.

BACKGROUND: The cognitive and emotional vulnerability of individuals with social anxiety disorder (SAD) and their response to repeated experiences of social rejection and social acceptance are important factors for the emergence and maintenance of symptoms of the disorder. Functional neuroimaging studies of SAD reveal hyperactivity in regions involved in the fear circuit such as amygdala, insula, anterior cingulate, and prefrontal cortices (PFC) in response to human faces with negative emotions. Observation of brain activity, however, involving studies of responses to standardized human interaction of social acceptance and social rejection have been lacking. METHODS: We compared a group of index subjects with SAD (N = 22, mean age:26.3 ± 5.4, female/male: 7/15) (SADG) with a group of healthy controls (CG) (N = 21, mean age:28.7 ± 4.5, female/male: 14/7) in measures of cortical activity during standardized experiences of human interaction involving social acceptance (SA) and social rejection (SR) video-simulated handshaking tasks performed by real actors. In a third, control condition (CC), the subjects were expected to press a switch button in an equivalent space. Subjects with a concurrent mood episode were excluded and the severity of subclinical depressive symptoms was controlled. 52-channel functional near-infrared spectroscopy (fNIRS) was used to measure cortical activity. RESULTS: Activity was higher in the SAD subjects compared to healthy controls, in particular in channels that project to middle and superior temporal gyri (STG), frontal eye fields (FEF) and dorsolateral prefrontal cortex (DLPFC) in terms of both SA and SR conditions. Cortical activity during the CC was not different between the groups. Only in the SAD-group, activity in the pre-motor and supplementary motor cortices, inferior and middle temporal gyri and fronto-polar area was higher during the rejection condition than the other two conditions. Anxiety scores were correlated with activity in STG, DLPFC, FEF and premotor cortex, while avoidance scores were correlated with activity in STG and FEF. CONCLUSIONS: SA and SR are represented differently in terms of cortical activity in SAD subjects compared to healthy controls. Higher activity in both social conditions in SAD subjects compared to controls may imply biological sensitivity to these experiences and may underscore the importance of increased cortical activity during social interaction experiences as a putative mediator of vulnerability to SAD. Higher cortical activity in the SADG may possibly indicate stronger need for inhibitory control mechanisms and higher recruitment of theory of mind functions during social stress. Higher activity during the SR compared to the SA condition in the SAD subjects may also suggest distinct processing of social cues, whether they involve acceptance or rejection.

The relationship between plasma levels of clozapine and N-desmethyclozapine as well as M1 receptor polymorphism with cognitive functioning and associated cortical activity in schizophrenia.

Studies that examined the effect of clozapine on cognitive functions in schizophrenia provided contradictory results. N-desmethylclozapine (NDMC) is the major metabolite of clozapine and have procognitive effects via agonistic activity in the M1 cholinergic receptors. The rs2067477 polymorphism in the M1 receptors may play role in cognitive profile in schizophrenia. We investigated the association of plasma clozapine (PClz), NDMC (PNdmc) levels and the rs2067477 polymorphism with cognitive functions and cortical activity measured by functional near infrared spectroscopy during the N-Back task in subjects with schizophrenia (N = 50) who are under antipsychotic monotherapy with clozapine. We found that PClz and PNdmc levels were negatively, PNdmc/PClz ratio was positively correlated with immediate recall score in the Rey Auditory Verbal Learning Test. PNdmc/PClz ratio was positively correlated with cortical activity during the N-back task. M1 wild-type group (CC: wild-type) produced higher cortical activity than M1 non wild-type group (CA: heterozygote / AA: mutant) in cortical regions associated with working memory (WM). These results suggest that individual differences in clozapine's effect on short term episodic memory may be associated with PClz and PNdmc. Higher activity in the M1 wild-type group may indicate inefficient use of cortical resources and/or excessive use of certain cognitive strategies during WM performance.

Attachment Style Predicts Cortical Activity in Temporoparietal Junction (TPJ): An fNIRS Study Using a Theory of Mind (ToM) Task in Healthy University Students.

Results of the behavioral studies suggest that attachment styles may have an enduring effect upon theory of mind (ToM). However biological underpinnings of this relationship are unclear. Here, we compared securely and insecurely attached first grade university students (N = 56) in terms of cortical activity measured by 52 channel Functional Near Infrared Spectroscopy (fNIRS) during the Reading the Mind from the Eyes Test (RMET). The control condition involved gender identification via the same stimuli. We found that the ToM condition evoked higher activity than the control condition particularly in the right hemisphere. We observed higher activity during the ToM condition relative to the control condition in the secure group (SG), whereas the overall cortical activity evoked by the two conditions was indistinguishable in the insecure group (ISG). Higher activity was observed in channels corresponding to right superior temporal and adjacent parietal cortices in the SG relative to the ISG during the ToM condition. Dismissive attachment scores were negatively correlated with activity in channels that correspond to right superior temporal cortex. These results suggest that attachment styles do have an effect on representation of ToM in terms of cortical activity in late adolescence. Particularly, dismissive attachment is represented by lower activity in the right superior temporal cortex during ToM, which might be related to weaker social need and habitual unwillingness for closeness among this group of adolescents.

[Prefrontal Cortex Activity During Facial Affect Processing in Schizophrenia: Association with Clinical Symptoms and Social Cognitive Functions]. / Sizofrenide Yüzdeki Duygu Ifadelerini Tanima Sirasindaki Prefrontal Korteks Aktivitesinin Klinik Belirtiler ve Sosyal Bilis Islevleriyle Iliskisi.

OBJECTIVES: In the present study, we aimed to investigate the prefrontal cortex (PFC) activity during facial affect recognition in schizophrenia, as well as the association of this activity with symptom severity and with the higher order social cognitive functions, namely recognition of false beliefs, faux-pas and hinting. METHOD: Functional near infrared spectroscopy (fNIRS) was used to measure frontal cortical activity during a neuroimaging task prepared with a standard set of pictures of facial affect. The data of the Index Group (IG) consisting of 27 subjects with DSM-IV based diagnoses of schizophrenia and schizophreniform disorder and control group (CG) (N=25) were compared. The control condition was to detect nonaffective changes on a neutral face. Associations with frontal activity during affect recognition and clinical symptoms, false belief recognition, hinting and faux-pas were investigated. RESULTS: Prefrontal activity during both affective and non-affective conditions was higher in the IG than the CG. The IG performed worse than the CG in social cognitive tests. Social cognitive test performance was not correlated with cortical activity. There were no correlations between education status, age and PFC activity in both groups. In the IG, right ventral prefrontal cortex (VPFC) and right medial prefrontal cortex (mPFC) activities were associated with hallucination severity. CONCLUSION: These results suggest the presence of hyperfrontality during face processing in schizophrenia. Results also suggest that schizophrenia patients require more frontal resources to achieve a performance comparable to that of healthy controls in order to detect both affective and non-affective changes on a face. There might be a relationship between facial processing and hallucinations.

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.

[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.

[Does Emotional Context Affect Subliminal and Supraliminal Priming?]. / Duygusal Baglam Esikalti ve Esiküstü Hazirlamayi Etkiler mi?

OBJECTIVE: Emotions are complex psychophysiological changes experienced during the interactions of internal and external processes. The stimuli that have emotional value have processing efficiency both in encoding and retrieval processes with respect to the neutral stimuli. Processing advantage is present also for implicit memory. Priming effect does not require conscious recollection and leads to changes in responding due to previous exposure to the stimulus. In this study, it was aimed to investigate the effect of presentation type and different emotional contexts on the priming. METHOD: Sixty-volunteered-university-students were (Female: n=40, X age=19.03±1.23; Male: n=20, X age=19.70±1.92) randomly assigned to the experimental conditions. Presentation type (Subliminal and Supraliminal) was between subject and Emotional Context (pleasant, neutral, and unpleasant pictures) was within subject independent variables. Dependent variables were Word Stem Completion score and completion latencies. RESULTS: Unpleasant emotional context had more capacity to create priming effect than the other emotional contexts. Both Subliminal and Supraliminal conditions favored the priming. Controversially to the transfer appropriate processing approach, the priming effect that was produced by supraliminal condition significantly higher than the priming created by the subliminal condition. CONCLUSION: Unpleasant picture context produced more priming due to reason that evolutionarily important, i.e. thread-related, stimuli have processing priority and they capture the attention, utilize other cognitive resources easily. Even in priming, that is a phenomenon based heavily on data driven processes, concept driven processes are also effectual as indicated by levels-of-processing approach.

Effect of a social defeat experience on prefrontal activity in schizophrenia.

The social defeat (SD) hypothesis of schizophrenia posits that repeated experiences of SD may lead to sensitization of the mesolimbic dopaminergic system and to precipitation of psychosis. Based on previous definitions adapted to a human experimental paradigm, we prepared a computer simulation of SD to mimic this subjective experience. We measured prefrontal cortex (PFC) activity in subjects with schizophrenia and healthy controls during exposure to a single SD experience with functional near infrared spectroscopy. PFC activity declined in both groups. Compared with the control condition, SD exposure was associated with a broader decline in left ventromedial, right medial and right lateral PFC activity in healthy controls (n=25), and a sharper decline in right ventrolateral PFC activity in subjects with schizophrenia (n=25). The activity in the right ventrolateral PFC, was significantly lower in patients compared with controls. This may be due to a deficiency in emotion regulation or self-control, or it may be related to impaired empathy in schizophrenia. Different patterns of brain activity during the SD experience in subjects with schizophrenia versus healthy controls may provide indirect evidence regarding the SD hypothesis of schizophrenia.

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 impact of aging and Alzheimer's disease on emotional enhancement of memory.

Emotional enhancement of memory (EEM) has been a well-known phenomenon which corresponds to the advantage of emotional stimuli to be better recalled than neutral ones. Previous studies suggest that aging favours recollection of positive items and this pattern is disrupted in Alzheimer's disease (AD). Emotional valence of different stimulus modalities, i.e. pictures and words, may also have an effect on each other's memory performances. However, none of these were clearly studied in AD. This study aimed to evaluate how emotional valences of simultaneously presented stimuli affected recall in healthy young (YG, n = 30), healthy elderly (HE, n = 30) participants and in patients with AD (n = 30). A battery consisting of emotional words presented on emotional pictures was developed. An analysis of a 3 (Groups) × 3 (Emotional Valence of Picture) × 3 (Emotional Valence of Word) mixed ANOVA design was carried out. Patients with AD could process emotional information similarly to healthy participants; however, they had EEM only for picture recalling. Emotional valence of the co-presented stimulus had a boosting effect both in the YG and HE, but not in AD group, especially if both of the stimuli had the same emotional valence. This study highlights the impaired EEM for verbal and preserved EEM for non-verbal declarative memory in patients with AD, the neurobiological underpinnings of which should be addressed by future studies.

A comprehensive neuropsychological mapping battery for functional magnetic resonance imaging.

Existing batteries for FMRI do not precisely meet the criteria for comprehensive mapping of cognitive functions within minimum data acquisition times using standard scanners and head coils. The goal was to develop a battery of neuropsychological paradigms for FMRI that can also be used in other brain imaging techniques and behavioural research. Participants were 61 healthy, young adult volunteers (48 females and 13 males, mean age: 22.25 ± 3.39 years) from the university community. The battery included 8 paradigms for basic (visual, auditory, sensory-motor, emotional arousal) and complex (language, working memory, inhibition/interference control, learning) cognitive functions. Imaging was performed using standard functional imaging capabilities (1.5-T MR scanner, standard head coil). Structural and functional data series were analysed using Brain Voyager QX2.9 and Statistical Parametric Mapping-8. For basic processes, activation centres for individuals were within a distance of 3-11 mm of the group centres of the target regions and for complex cognitive processes, between 7 mm and 15 mm. Based on fixed-effect and random-effects analyses, the distance between the activation centres was 0-4 mm. There was spatial variability between individual cases; however, as shown by the distances between the centres found with fixed-effect and random-effects analyses, the coordinates for individual cases can be used to represent those of the group. The findings show that the neuropsychological brain mapping battery described here can be used in basic science studies that investigate the relationship of the brain to the mind and also as functional localiser in clinical studies for diagnosis, follow-up and pre-surgical mapping.