Search

Background: Despite its advantages over other antipsychotics, for treatment-resistant schizophrenia, clinical use of Clozapine (CLZ) is challenging by its narrow therapeutic index and potentially life-threatening dose-related adverse effects., Research Design and Methods: As the potential role in CLZ metabolism is assigned to CYP1A2 enzyme and consequently Cytochrome P450 oxidoreductase (POR) their genetic variations might help to determine CLZ levels in schizophrenia patients. For this purpose, 112 schizophrenia patients receiving CLZ were included in the current study. Plasma CLZ and N-desmethylclozapine (DCLZ) levels were analyzed by using HPLC and genetic variations were identified with the PCR-RFLP method., Results: The patients' CYP1A2 and POR genotypes seemed to not affect plasma CLZ and DCLZ levels whereas in the subgroup analysis, POR *28 genotype significantly influenced simple and adjusted plasma CLZ and DLCZ levels concerning smoking habit and caffeine consumption., Conclusions: The findings of the present study highlight the importance of both genetic and non-genetic factors (smoking and caffeine consumption) for the individualization of the CLZ treatment. In addition to that, it suggests that the added utility of not only the CLZ metabolizing enzymes but also POR, which is crucial for proper CYP activity, to guide CLZ dosing might be useful for clinical decision-making.

Schizophrenia and bipolar disorder (BD) are psychiatric disorders with economic and social effects that cause disability. Treatment non-compliance is one of the major problems faced by clinicians in both schizophrenia and BD. Treatment non-compliance is associated with recurrence and impaired functionality. Treatment compliance increases with long-acting injectable antipsychotics (LAIAs) and recurrence times are prolonged, hospitalization rates decrease compared to those who use an equivalent oral form of the same drug. The use of LAIAs in the maintenance treatment of schizophrenia has also been associated with a low mortality rate, decrease in caregiver burden, and increase in patient satisfaction. Studies show that LAIAs are cost-effective compared to their oral forms. Data on the use of LAIAs in first-episode schizophrenia and BD are relatively limited. The results of studies on the use of LAIAs in patients with first-episode schizophrenia indicate that LAIAs have advantageous in preventing relapse and re-hospitalization compared to oral antipsychotics. In BD, with the use of LAIAs, the rate of hospitalization due to mood episodes and the frequency of manic episodes have been decreased. LAIAs have not been found to be as effective in preventing depressive episodes in BD as manic episodes. Although there are many studies supporting the use of LAIAs in maintenance treatment of schizophrenia and BD, more studies are needed on this issue. In this article, studies on the use of LAIAs in schizophrenia, first episode schizophrenia and BD are reviewed and the place of LAIAs in treatment was discussed., Competing Interests: Conflict of Interest: We declare that we have no conflicts of interest as the authors of this review., (Copyright: © 2021 Turkish Neuropsychiatric Society.)

Theory of Mind (ToM) deficits interfere in social cognitive functioning in schizophrenia (SCZ) and are increasingly recognized to do so in bipolar disorder (BD), however their clinical and neurobiological correlates remain unclear. This study represents the first direct comparison of subjects with SCZ (N = 26), BD (N = 26) and healthy controls (N = 33) in cortical activity during the Reading the Mind in the Eyes Task (RMET) using functional Near Infrared Spectroscopy (fNIRS) with the control condition (CC) involving gender identification via the same stimuli. The three groups were compared with a comprehensive ToM battery and assessed in terms of the relationship of ToM performance with clinical symptoms, insight and functioning. The controls scored higher than the SCZ and BD groups in ToM assessments, with SCZ group showing the worse performance in terms of meta-representation and empathy. The SCZ group ToM scores inversely correlated with negative symptom severity and positively correlated with insight; BD group ToM scores negatively correlated with subclinical mania symptoms and projected functioning. Cortical activity was higher during the ToM condition compared to the CC in the pre-motor and supplementary-motor cortices, middle and superior temporal gyri, and the primary somatosensory cortex. Group x Condition interaction was detected whereby activity was higher during the ToM condition among controls with no detected difference between SCZ and BD groups. The results suggest that ToM is represented similarly in cortical activity in SCZ and BD compared to healthy controls pointing to possible neurobiological convergence of SCZ and BD in underlying impairments of social cognition., (Copyright © 2020. Published by Elsevier B.V.)

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., Competing Interests: Declaration of Competing Interest We, the authors of this manuscript, declare that we have no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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., Competing Interests: Conflict of Interest We, the authors of this manuscript, declare that we have no conflicts of interest.