Eveningness chronotype influences social functioning by deteriorating depressive symptoms in remitted patients with schizophrenia.

Sleep and circadian rhythm disruption (SCRD) is common in schizophrenia patients, who also typically experience impaired social functioning. While various factors influence social functioning in schizophrenia, the specific impact of sleep and circadian rhythm disruption remains unclear. This study aimed to investigate the connection between chronotype and social functioning in remitted schizophrenia patients, examining the mediating roles of depression and sleep quality. The study included 185 patients diagnosed with schizophrenia based on DSM-5 criteria. After categorizing the patients into morningness, eveningness, or intermediate chronotypes using the Morningness-Eveningness Questionnaire(MEQ), they were assessed with the Positive and Negative Syndrome Scale(PANSS), Calgary Depression Scale for Schizophrenia(CDSS), Personal and Social Performance Scale(PSPS) and Pittsburgh Sleep Quality Index(PSQI). The eveningness chronotype group showed higher CDSS and PSQI scores and lower PWBS and PSPS-Total scores than the other groups (p < 0.05). A hierarchical linear regression model assessed MEQ, PSQI, and CDSS scores' effects on PSPS total scores. MEQ scores' significance diminished when CDSS scores were included. Eveningness chronotype, particularly with increased depressive symptoms, negatively impacts social functioning in remitted schizophrenia patients.These findings contribute to the understudied area of chronotype in schizophrenia and its impact on social functioning, including its interaction with sleep..

Blood Viscosity and Inflammation in First-Episode and Acute Exacerbations of Schizophrenia: A Case-Control Study with Healthy Controls.

Introduction: Elevated proinflammatory status and alterations in blood flow, both of which are associated with the pathophysiology of schizophrenia, may be linked with an increased risk of cardiovascular diseases. However, such a relationship at different acute stages of schizophrenia has not been evaluated. We aimed to examine whether blood viscosity and systemic inflammatory status varied between first-episode schizophrenia (FES) and acute exacerbations of schizophrenia. Methods: Fifty-two patients with FES, 69 schizophrenia patients with acute exacerbation (S-AE) and 56 healthy controls (HC) were included in the study. Whole blood viscosity (WBV) was calculated according to de Simone's formula at low and high shear rates (LSR and HSR). Systemic immune-inflammation index (SII) and systemic inflammatory response index (SIRI) were calculated from hemogram screening data at admission. Results: When adjusted for age, WBV at both LSR and HSR were significantly decreased in both FES and S-AE groups compared to HCs. Systemic inflammatory response index was significantly higher in FES patients than in the S-AE and HC groups. Total cholesterol (TC) and WBV at HSR were correlated in patients. Total cholesterol predicted WBV at LSR in patients with FES whereas other independent variables including age and SIRI did not. Conclusion: Both first and subsequent episodes of schizophrenia are associated with reduced blood viscosity. Increased inflammatory status may not fully explain such a relationship. Extrapolation of hemorheological characteristics in schizophrenia may help to stratify cardiovascular risk and reflect the pathophysiological process in the early and later stages of schizophrenia.

Can optical coherence tomography findings be related with suicide attempt in bipolar disorder?

BACKGROUND: The aim was to investigate the relationship between OCT findings and suicidal behavior (SB) in patients with Bipolar Disorder type 1 (BPD1) in comparison to healthy controls. METHODS: Forty five euthymic BPD1 patients with previous suicide attempts (BPD1+), 46 euthymic BPD1 patients without previous suicide attempts (BPD1-) and 63 healthy controls were included. The subjects were evaluated with Sociodemographic Data Form, SCID, Suicide Behaviors Questionnaire, Beck Depression Inventory, Young Mania Rating Scale and OCT. RESULTS: All OCT measures were lower in patients with BPD1 than healthy controls (p<0.001). While no significant differences were found between (BPD1+) and (BPD1-) in all GCC levels and inferior RNFL values (p>0.05), the superior RNFL and global RNFL values were found to be lower in the (BPD1+) than in the (BPD1-) (p = 0.037, p = 0.028, respectively). Global RNFL was found to significantly predict suicide risk in a multivariate logistic regression model (p = 0.024 Exp(B):0.930). CONCLUSIONS: Neurodegeneration might occur during the course of BPD1 and SB. Decreased RNFL may be important for neurodegeneration related to SB.

Can the Imbalance between Neurotrophic and Apoptotic Proteins Be the "Beware the Ides of March" for Unaffected Relatives of Schizophrenia Patients?

Schizophrenia (SZ) is a mental disorder with a strong genetic basis as well as epigenetic aspects. Siblings of patients with SZ can share certain endophenotypes with the patients, suggesting that siblings may be important for distinguishing between trait and state markers. In the current study, we aimed to characterize the balance between pro-BDNF/mature BDNF and its receptors p75NTR/TrkB, which are tPA-BDNF pathways proteins and are thought to play a role in synaptic pruning, as a possible endophenotype of schizophrenia. Forty drug-naïve patients with first-episode psychosis (FEP) matched for age, gender, and level of education, 40 unaffected siblings (UAS) of patients with FEP, and 67 healthy controls (HC) were included in the study. Blood samples were collected from all participants to determine BDNF, pro-BDNF, TrkB and p75NTR, PAI1, tPA, ACTH, and cortisol levels. We showed that levels of proteins of the tPA-BDNF pathway as well as the pro-BDNF/m-BDNF and p75NTR/TrkB ratios could successfully differentiate FEP and their siblings from the HCs by using ROC analysis. Plasma levels of m-BDNF were found to be the lowest in the healthy siblings and highest in the HCs with statistically significant differences between all 3 groups. The plasma level of pro-BDNF in the HC group was similar to the FEP patients, the same in the healthy siblings of the FEP patients. Our data support the hypothesis that imbalance between neurotrophic and apoptotic proteins might occur in SZ and this imbalance could be an endophenotype of the disease.

A novel commentary: Investigation of the role of a balance between neurotrophic and apoptotic proteins in the pathogenesis of psychosis via the tPA-BDNF pathway.

OBJECTIVE: Many hypotheses have put forward to better understand the pathogenesis of schizophrenia (SZ), such as synaptic pruning, stress-diathesis, neurodevelopment, neurodegeneration and neurotransmitter hypothesis; nonetheless, this pathogenesis still remains a mystery. The current study was designed with the hypothesis that impairment of a balance between pro-BDNF/mature BDNF and their receptors p75NTRK/TrkB may cause synaptic pruning in the pathogenesis of psychotic disorders. METHODS: Sixty-five drug-naïve patients with first-episode psychosis (FEP) who applied to outpatient clinics and were diagnosed according to DSM-5 as well as 65 healthy controls (HC) were included in the study. Symptoms at the time of evaluation were assessed with the PANSS scale by an experienced psychiatrist. Blood samples were collected from all participants to determine BDNF, pro-BDNF, TrkB and p75NTR, PAI1, tPA, ACTH and cortisol levels. RESULTS: Mature BDNF, TrkB and PAI-1, tPA levels were significantly lower while the levels of ACTH and cortisol were significantly higher in FEP patients compared to HC. No significant difference was found in pro-BDNF and p75NTR levels between the two independent groups. The pro-BDNF/mature BDNF and the p75NTR/TrkB ratios were significantly higher in FEP patients compared to HC. Moreover, the pro-BDNF/mature BDNF and the p75NTR/TrkB ratios were found to be significantly associated with the pathogenesis of SZ in a hierarchical regression model. DISCUSSION: Imbalance between neurotrophic and apoptotic proteins such as pro-BDNF/mature BDNF and p75NTR/TrkB may be take part pathogenesis of synaptic pruning in psychotic disorders.

Evaluation of IGF-1 as a novel theranostic biomarker for schizophrenia.

OBJECTIVE: In the current study, we aimed to investigate fasting plasma levels of glucose, insulin, growth hormone, IGF-1, and lipid profile in remission schizophrenia patients, treatment resistant schizophrenia patients and healthy controls and to determine whether IGF-1 levels can be used as a theranostic biomarker in schizophrenia. METHODS: Sixty-two patients under remission from schizophrenia, sixty-five treatment-resistant patients with schizophrenia and sixty-two healthy controls were included in the study. All patients were recruited and evaluated over 11 months. Symptoms at the time of evaluation were assessed twice using BPRS, PANSS, CGI, and GAF scales by an experienced psychiatrist in accordance with Andreaseen's remission criteria and TRIPS group resistance criteria. Blood samples were collected from all participants to determine fasting glucose, LDL, HDL, Triglyceride, Total Cholesterol, fasting, insulin, GH and IGF-1 levels. RESULTS: Fasting blood glucose levels were found to be higher in patients with schizophrenia than in healthy controls. Moreover, LDL levels of the treatment sensitive group were higher than that of the treatment resistant group while they were not significantly different from the healthy controls. IGF-1 levels were lower in the treatment sensitive group than in both treatment resistant and healthy control groups. IGF-1, LDL and age of disease onset were found to be significantly associated with treatment resistance in a regression model. DISCUSSION: In the present study, remitted patients with schizophrenia could be distinguished from treatment-resistant patients and healthy controls with serum IGF-1, fasting glucose and LDL levels. In addition, we found that smoking and age of disease onset together with IGF-1 levels could significantly predict resistance to treatment.

COVID-19-related cognitive dysfunction may be associated with transient disruption in the DLPFC glutamatergic pathway.

Cognitive impairment has recently attracted researchers as one of the possible neuropsychiatric manifestations of COVID-19, although how the infection perpetuates impairment of cognitive functions is still obscure. We presented a 29-year-old male patient with COVID-19 who developed new-onset transient attention deficit and memory problems following a SARS-CoV-2 infection. Structural neuroimaging was normal. MR-spectroscopy (MRS) of the bilateral DLPFC revealed significant for decreased levels of N-acetylaspartate (NAA), glutamate, and glutamate/glutamine ratio. After a follow-up without any medical treatment but with suggestions of memory exercises for three months a control MRS screening of DLPFC showed improved levels of NAA, glutamate, and glutamate/glutamine ratio. This report may suggest that cognitive deficits in SARS-CoV-2 infection can result from glutamatergic dysfunction with decreased NAA and glutamate levels in bilateral DLPFC.

SARS-CoV-2-associated first episode of acute mania with psychotic features.

Despite neuropsychiatric outcomes of SARS-CoV-2 infection are now under close scrutiny, psychoneuroimmunological characteristics of COVID-19 and precise pathophysiology of neuropsychiatric manifestations of the infection are still obscure. Moreover, there still exists a shortfall in demonstrating specific clinical manifestations of the brain involvement of the virus. Here, we presented a 33-year-old female patient with COVID-19, reporting acute-onset paranoid delusions symptoms, insomnia and irritability. Cranial MRI showed an hyperintense signal in the splenium of the corpus callosum with decreased apparent diffusion coefficient, which might possibly indicate the presence of cytotoxic edema related to the brain involvement of the infection. Following the completion of SARS-CoV-2 treatment, both cytotoxic edema and psychiatric symptoms resolved. In light of this report, we suggest that either heightened immune response and direct viral infection that SARS-CoV-2 may lead to such psychiatric manifestations and neuropsychiatric monitoring should be performed in patients with COVID-19. Prompt recognition of psychiatric consequences of COVID-19 may help clinicians provide guidance for differential diagnosis and manage them accordingly.

Psychotic Agitation in a Patient with COVID-19: Pathogenesis or Iatrogenesis?

The pathophysiological underpinnings of central nervous system (CNS) involvement in SARS-CoV-2 infection, as well as the profile of adverse neuropsychiatric effects of pharmacological agents employed in the management of COVID-19, are yet to be elucidated. Here, we report a 43-year-old female patient who suffered from COVID-19 and who developed new-onset psychotic agitated behavior which may be related to either the COVID-19 infection itself or to the drugs that were used in the treatment. On her third day of treatment with oseltamivir, hydroxychloroquine, and azithromycin, the patient, who had no previous background of neurological or psychiatric diagnosis, presented with a new-onset psychomotor agitation with auditory hallucinations and insomnia. Her psychiatric symptoms have improved with oral olanzapine 5 mg/d. This report underscores the importance of neuropsychiatric monitoring in patients with COVID-19. Clinicians should be aware of the limited knowledge on the neuropsychiatric safety profile of the medication used for COVID-19 treatment, while they have focused on the neuropsychiatric outcomes of COVID-19 itself.

One Plus One Sometimes Equals More Than Two: Long-acting Injectable Aripiprazole Adjunction in Clozapine-Resistant Schizophrenia.

In this report, we present a patient whose positive symptoms did not improve despite being treated with clozapine monotherapy at a therapeutic dose for 4 months, and whose symptoms began to resolve after aripiprazole long-acting injection adjunction to clozapine. A 22-year-old man was diagnosed as having schizophrenia last year in his first admission, with symptoms of auditory hallucinations, persecutory delusions, and associated social withdrawal. His positive symptoms did not improve despite being treated with risperidone, olanzapine, and paliperidone. Oral clozapine monotherapy was planned, and the daily dose was increased to provide a therapeutic plasma clozapine concentration and measured as effective (545 mg/dL). Aripiprazole long-acting injection 400 mg monthly was combined with the ongoing clozapine treatment for augmentation. One week after the third injection, a psychiatric examination revealed a significant improvement in the positive symptoms, and his caregivers confirmed an increase in the social interaction of the patient. Although we cannot postulate on a single exact mechanism for the increased efficacy of clozapine and aripiprazole combination, we may suggest that, at least for a subgroup of patients with schizophrenia who respond clinically to clozapine at a suboptimal level, combination with aripiprazole may be an effective therapeutic strategy.