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There is a complex relationship between circadian rhythm dysfunctions and various psychiatric disorders. Circadian (~24 h) rhythms indicate the rhythmic change of different physiological activities in relation to the environmental light-dark cycle. Shift work, light exposure at night, and chronic and acute jet lag affect circadian rhythm that have a negative impact on psychological functions, and behaviors. Additionally, professional stress, mental instability, and social disintegration influence psychiatric disorders. PubMed/MEDLINE, Springer Nature, Science Direct (Elsevier), Wiley Online, ResearchGate, and Google Scholar databases were searched to collect relevant articles. Circadian rhythm disruption causes impaired neurotransmitter release, impaired melatonin and cortisol rhythm, metabolic dysfunctions, neuroinflammation, and neural apoptosis; collectively these factors influence the development of psychiatric disorders. Circadian dysfunction also alters the expression of several clock control genes in the mesolimbic areas that are associated with pathologies of psychiatric disorders. Additionally, chronotherapy and applications of anti-psychotic medicine can improve psychiatric diseases. This review focuses on the effects of circadian clock dysfunction on the vulnerability of psychiatric disorders and the implications of chronotherapy.

The specialized literature suggests that the infection with Toxoplasma gondii may be associated with an increased risk of developing psychiatric disorders, particularly those within the schizophrenia spectrum. This article presents a complex case of schizoaffective disorder associated with a recent Toxoplasma gondii infection. Although the infection did not present with obvious clinical symptoms, it was discovered during the seroconversion period, suggesting a recent infectious episode that may be relevant in the context of psychosis. In this infectious background, the biological link raises the possibility of a triggering or exacerbating factor for the current psychotic symptomatology. [ABSTRACT FROM AUTHOR]

Although schizophrenia patients exhibit structural abnormalities in the striatum, it remains largely unknown for the role of the striatum subregions in the treatment response of antipsychotic drugs. The purpose of this study was to investigate the associations between the striatal subregions and improved clinical symptoms in first-episode drug-naïve (FEDN) schizophrenia. Forty-two FEDN schizophrenia patients and 29 healthy controls (HCs) were recruited. At baseline, the Positive and Negative Syndrome Scale (PANSS) was used to assess the clinical symptoms of patients, MRI scanner was used to obtain anatomical images of patients and HCs. After 12-week stable doses of risperidone treatment, clinical symptoms were obtained in 38 patients and anatomical images in 26 patients. After 12 weeks of treatment, the left nucleus accumbens volume decreased, whereas the left pallidum volume increased in schizophrenia patients. The decreased left nucleus accumbens volume was positively correlated with cognitive factor improvement measured by PANSS. Intriguingly, greater left nucleus accumbens volume at baseline predicted greater cognitive improvements. Furthermore, the responders who had >50 % improvement in cognitive symptoms exhibited significantly greater baseline left nucleus accumbens volume compared to non-responders. The left striatum volume at baseline and after treatment predicted the cognitive improvements in FEDN schizophrenia, which could be a potential biomarker for the development of precision medicine approaches targeting cognitive function.

Abstract Antipsychotic drugs are the first line of treatment in schizophrenia; although antipsychotic responses indicate a wide interindividual variety in patients with schizophrenia. This study aimed to investigate the association between four polymorphisms in DRD2, DRD4 and COMT genes and their gene-gene interactions with antipsychotic treatment response in patients with schizophrenia. A total of 101 patients with schizophrenia were recruited and stratified in treatment responder and treatment resistant groups based on the published criteria of resistant to treatment using PANSS. Clinical and demographic factors were analyzed. Genomic DNA was extracted from whole blood and genotyping for the four polymorphisms were done by ARMS-PCR, PCR-RFLP and gap-PCR. Gene-gene interactions were analyzed by logistic regression. In case of DRD2 A-241G, G allele was significantly associated with resistant to treatment. Regarding DRD4 120-bp duplication, 240/240 genotype was significantly associated with resistant to treatment comparing to other genotypes in a dominant model. The genotype combination of DRD4 240/240 and COMT Val/Val was significantly associated with treatment resistant. Among DRD2 AA genotype, COMT met allele carriers which also had a 120 bp allele of DRD4 had a significantly better response to antipsychotics. Moreover, analysis of clinical and demographic factors demonstrated a significantly longer duration of hospitalization and higher chlorpromazine-equivalent daily dose in resistant to treatment patients. Discovering the polymorphisms which effect treatment response to antipsychotics will provide the possibility of genetic screening before starting an antipsychotic treatment which enhances the chance of responding to antipsychotics and decreases drugs side effects and costs.

The article presents a case study of an elderly woman with schizophrenia treated with risperidone and olanzapine. It is reported that despite previous successful treatment with risperidone, her condition worsened, leading to a massive bilateral pulmonary embolism (PE) with cardiac arrest. It further highlights the need for tailored venous thromboembolism (VTE) prevention strategies for elderly psychiatric inpatients due to multiple risk factors.

Antipsychotic drugs are the first line of treatment in schizophrenia; although antipsychotic responses indicate a wide interindividual variety in patients with schizophrenia. This study aimed to investigate the association between four polymorphisms in DRD2, DRD4 and COMT genes and their gene-gene interactions with antipsychotic treatment response in patients with schizophrenia. A total of 101 patients with schizophrenia were recruited and stratified in treatment responder and treatment resistant groups based on the published criteria of resistant to treatment using PANSS. Clinical and demographic factors were analyzed. Genomic DNA was extracted from whole blood and genotyping for the four polymorphisms were done by ARMS-PCR, PCR-RFLP and gap-PCR. Gene-gene interactions were analyzed by logistic regression. In case of DRD2 A-241G, G allele was significantly associated with resistant to treatment. Regarding DRD4 120-bp duplication, 240/240 genotype was significantly associated with resistant to treatment comparing to other genotypes in a dominant model. The genotype combination of DRD4 240/240 and COMT Val/Val was significantly associated with treatment resistant. Among DRD2 AA genotype, COMT met allele carriers which also had a 120 bp allele of DRD4 had a significantly better response to antipsychotics. Moreover, analysis of clinical and demographic factors demonstrated a significantly longer duration of hospitalization and higher chlorpromazine-equivalent daily dose in resistant to treatment patients. Discovering the polymorphisms which effect treatment response to antipsychotics will provide the possibility of genetic screening before starting an antipsychotic treatment which enhances the chance of responding to antipsychotics and decreases drugs side effects and costs. [ABSTRACT FROM AUTHOR]

Background: Resting cerebral blood flow (rCBF) in striatum and thalamus is increased in medicated patients with psychosis, but whether this is caused by treatment or illness pathology is unclear. Specifically, effects of partial dopamine agonism, sex, and clinical correlates on rCBF are sparsely investigated. We therefore assessed rCBF in antipsychotic-naïve psychosis patients before and after aripiprazole monotherapy and related findings to sex and symptom improvement. Methods: We assessed rCBF with the pseudo-Continuous Arterial Spin Labeling (PCASL) sequence in 49 first-episode patients (22.6 ± 5.2 years, 58% females) and 50 healthy controls (HCs) (22.3 ± 4.4 years, 63% females) at baseline and in 29 patients and 49 HCs after six weeks. RCBF in striatum and thalamus was estimated with a region-of-interest (ROI) approach. Psychopathology was assessed with the positive and negative syndrome scale. Results: Baseline rCBF in striatum and thalamus was not altered in the combined patient group compared with HCs, but female patients had lower striatal rCBF compared with male patients (p = 0.009). Treatment with a partial dopamine agonist increased rCBF significantly in striatum (p = 0.006) in the whole patient group, but not significantly in thalamus. Baseline rCBF in nucleus accumbens was negatively associated with improvement in positive symptoms (p = 0.046), but baseline perfusion in whole striatum and thalamus was not related to treatment outcome. Conclusions: The findings suggest that striatal perfusion is increased by partial dopamine agonism and decreased in female patients prior to first treatment. This underlines the importance of treatment effects and sex differences when investigating the neurobiology of psychosis. [ABSTRACT FROM AUTHOR]

Background: Managing mental disorders in the perinatal period is a challenge. The most common mental disorders encountered in this period are major depression, bipolar disorder, anxiety and psychotic disorders. Purpose: This study aimed to investigate the neurodevelopmental effects in children born to mothers who were on antipsychotic medication, during pregnancy. Methodology: Databases MEDLINE, Embase, Cochrane, PsychInfo, Google Scholar and Scopus searched according to inclusion and exclusion criteria. The studies involved mothers with preconception or relapsed mental illness receiving antipsychotic medication during the perinatal period and their children were screened for any neurodevelopmental disorders. From the initial search of the literature, 277 articles emerged and applying the criteria, according to the methodology, we identified 15 articles. Results: Three studies were identified in which children were exposed and developed ADHD with a pooled odds ratio of 2.33 (95% CI = 1.69 - 3.20, p<0.001) indicating that children exposed to antipsychotics are more likely to develop ADHD than unexposed children. Regarding socio-emotional and mental development, it was found that the pooled odds ratio was 2.33 (95% CI = 1.68 - 3.22, p<0.001) indicating that exposed children are more likely to show delay compared to unexposed children. This relationship was statistically significant. Finally, it was found that children who were exposed and showed a delay in motor development had a pooled odds ratio of 2.93 (95% CI = 1.86 - 4.61, p<0.001). Discussion: Fetal exposure to antipsychotic medication can cause short-term developmental delays in motor, social-emotional, and adaptive behavior. However, further investigation is needed since the number of studies. [ABSTRACT FROM AUTHOR]

Abstract Background Schizophrenia (SCZ) is a severe and chronic psychiatric disorder with premature age-related physiological changes. However, numerous previous studies examined the epigenetic age acceleration in SCZ patients and yielded inconclusive results. In this study, we propose to explore the epigenetic age acceleration in drug-naive first-episode SCZ (FSCZ) patients and investigate whether epigenetic age acceleration is associated with antipsychotic treatment, psychotic symptoms, cognition, and subcortical volumes. Methods We assessed the epigenetic age in 38 drug-naive FSCZ patients and 38 healthy controls by using three independent clocks, including Horvath, Hannum and Levine algorithms. The epigenetic age measurements in SCZ patients were repeated after receiving 8 weeks risperidone monotherapy. Results Our findings showed significantly positive correlations between epigenetic ages assessed by three clocks and chronological age in both FSCZ patients and healthy controls. Compared with healthy controls, drug-naive FSCZ patients have a significant epigenetic age deceleration in Horvath clock (p = 0.01), but not in Hannum clock (p = 0.07) and Levine clock (p = 0.43). The epigenetic ages of Hannum clock (p = 0.002) and Levine clock (p = 0.01) were significantly accelerated in SCZ patients after 8-week risperidone treatment. However, no significant associations between epigenetic age acceleration and psychotic symptoms, cognitive function, as well as subcortical volumes were observed in FSCZ patients. Conclusion These results demonstrate that distinct epigenetic clocks are sensitive to different aspects of aging process. Further investigations with comprehensive epigenetic clock analyses and large samples are required to confirm our findings.

Amaç: Son yıllarda sayıları giderek artan toplum ruh sağlığı merkezleri, şizofreni başta olmak üzere ağır psikiyatrik hastalıkların tedavi ve rehabilitasyonunda önemli bir konumda bulunmaktadır. Hasta bireylerin yanında ailelere de destek sunan bu merkezlerde bakımevinde yaşayan hastalar da izlenmektedir. Araştırmamızda, aynı toplum ruh sağlığı merkezinden takipli psikoz hastalarının bakımevi ve evde yaşama durumlarına göre sosyodemografik ve klinik özelliklerinin karşılaştırılması amaçlanmıştır. Gereç ve Yöntem: Çalışmaya Sultanbeyli Toplum Ruh Sağlığı Merkezi’nden takipli 62’si evde 79’u bakımevinde yaşamakta olan 141 psikoz hastası dâhil edilmiştir. Düzenli takibi olan hastaların tıbbi kayıtları geriye dönük olarak incelendi ve bu veriler formlara kaydedilerek gruplar arasındaki farklar istatistiksel yöntemlerle araştırıldı. Bulgular: Çalışmaya 47’si (%33.3) kadın 94’ü erkek (%66.6) olmak üzere 141 psikoz hastası dâhil edilmiştir. Katılımcıların ortalama yaşı 43.76±13.76 olarak saptandı. Klinik Global İzlenim Şiddet Ölçeği puanları bakımevinde yaşayanlarda ortalama 5.07±0.75, evde yaşayanlarda ortalama 4.61±0.79 olarak saptandı (p=0.002). İşlevselliğin Global Değerlendirmesi puanları bakımevi grubunda ortalama 43.60±12.98, evde yaşayanlarda ortalama 54.91±12.42 idi. Hastane yatış (p=0.005) ve EKT sayıları (p=0.013) bakımevinde yaşayanlarda anlamlı derecede yüksek saptandı. Toplam psikotrop ve antipsikotik ilaç sayısı, depo enjeksiyon ve klozapin kullanımı açısından iki grup arasında fark saptanmadı. Sonuç: Bakımevinde kalan hastaların hastalık şiddeti daha yüksek görünmekle birlikte ilaç kullanım özellikleri evde kalan hastalarla benzerdi. Çoklu antipsikotik ilaç kullanımı, sınırlı literatür desteğine rağmen oldukça yüksek görünmektedir. Klozapin kullanım oranlarının düşüklüğü, bu tedaviye geçiş konusundaki zorlukları ortaya koymaktadır. Hastalara daha düzenli takip imkanı sunan toplum ruh sağlığı merkezlerinde ilaç tedavileri konusunda tedavi algoritmalarının önerileri ışığında yeni düzenlemelerin yapılması uygun görünmektedir.

Widespread anatomical alterations and abnormal functional connectivity have shown strong association with symptom severity in first-episode schizophrenia (FES) patients. Second-generation antipsychotic treatment might slow disease progression and possibly modify the cerebral plasticity in FES patients. However, whether a long-acting injectable antipsychotic (paliperidone palmitate [PP]), available in monthly and every-3-months formulations, is more effective than oral antipsychotics (OAP) in improving cerebral organization has been unclear. Therefore, in the current longitudinal study, we evaluated the differences in functional and microstructural changes of 68 FES patients in a randomized clinical trial of PP vs OAP. When compared to OAP treatment, PP treatment was more effective in decreasing abnormally high fronto-temporal and thalamo-temporal connectivity, as well as increasing fronto-sensorimotor and thalamo-insular connectivity. Consistent with previous studies, multiple white matter pathways showed larger changes in fractional anisotropy (FA) and mean diffusivity (MD) in response to PP compared with OAP treatment. These findings suggest that PP treatment might reduce regional abnormalities and improve cerebral connectivity networks compared with OAP treatment, and identified changes that may serve as reliable imaging biomarkers associated with medication treatment efficacy. [ABSTRACT FROM AUTHOR]

Rationale: Weight gain is a frequent side effect of treatment with SGAs (second-generation antipsychotics) and a leading cause for nonadherence. Several candidate genes have been identified that could influence the amount of AIWG (antipsychotic-induced weight gain). The polymorphism rs17782313 near the MC4R (human melanocortin 4 receptor gene) was strongly associated with obesity in a large scale GWAS (genome wide association study), yet previous studies investigating its impact on AIWG did not lead to a definite conclusion regarding its effect. In particular, they were all relatively short and had a naturalistic design. Objective: We therefore examined the influence of the rs17782313 polymorphism on SGA-related weight gain. Methods: Participants of a multicenter randomized, controlled, double-blind study comparing two treatment strategies in individuals with schizophrenia or schizoaffective disorder were genotyped using a rapid-cycle polymerase chain reaction. Up to 252 individuals completed the first 2 weeks (phase I), 212 the entire 8 weeks (hence 'completers'). Patients received either amisulpride or olanzapine or both consecutively. Thirty-seven had their first episode. Weight gain occurring in different genotypes was statistically compared and confounding factors were adjusted by stepwise multiple linear regression. A correction for multiple testing was included. Results: Within 212 'completers', carriers of the C allele had a higher absolute weight gain than those homozygous for the T allele (2.6 kg vs. 1.2 kg), though this observation was not significant (P = 0.063). In the amisulpride subpopulation, this association appeared stronger and reached significance (2.5 kg vs. 0.7 kg, P = 0.043), though failed to remain significant after correction for multiple testing. A stepwise multiple linear regression showed a significant association in both the whole study population (P < 0.001) and the amisulpride subpopulation (P < 0.001). Conclusion: Our results indicate that the rs17782313 polymorphism might influence antipsychotic-induced weight gain and therefore confirm some of the earlier conclusions. [ABSTRACT FROM AUTHOR]

The effect of antipsychotic medications is critical for the long-term outcome of symptoms and functions during first-episode psychosis (FEP). However, how brain functions respond to the antipsychotic treatment in the early stage of psychosis and its underlying neural mechanisms remain unclear. In this study, we explored the cross-sectional and longitudinal changes of regional homogeneity (ReHo), whole-brain functional connectivity, and network topological properties via resting-state functional magnetic resonance images. Thirty-two drug-naïve FEP patients and 30 matched healthy volunteers (HV) were included, where 23 patients were re-visited with effective responses after two months of antipsychotic treatment. Compared to HV, drug-naive patients demonstrated significantly different patterns of functional connectivity involving the right thalamus. These functional alterations mainly involved decreased ReHo, increased nodal efficiency in the right thalamus, and increased thalamic-sensorimotor-frontoparietal connectivity. In the follow-up analysis, patients after treatment showed reduced ReHo and nodal clustering in visual networks, as well as disturbances of visual-somatomotor and hippocampus-superior frontal gyrus connectivity. The longitudinal changes of ReHo in the visual cortex were associated with an improvement in general psychotic symptoms. This study provides new evidence regarding alterations in brain function linked to schizophrenia onset and affected by antipsychotic medications. Moreover, our results demonstrated that the functional alterations at baseline were not fully modulated by antipsychotic medications, suggesting that antipsychotic medications may reduce psychotic symptoms but limit the effects in regions involved in disease pathophysiology. [ABSTRACT FROM AUTHOR]

Miguel Bajouco,1– 3 David Mota1,2 1Department of Psychiatry, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal; 2Institute of Psychological Medicine, Faculty of Medicine, University of Coimbra, Coimbra, Portugal; 3Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), University of Coimbra, Coimbra, PortugalCorrespondence: Miguel Bajouco, Department of Psychiatry, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal, Tel +351 239 400 454, Email miguel.bajouco@chuc.min-saude.ptAbstract: Cariprazine is an atypical antipsychotic that has D2 and D3 partial agonism properties in addition to the usual 5-HT2A receptor antagonist action of second-generation antipsychotics. It has a distinctly higher affinity for D3 receptors, which is 10-fold higher than for D2 receptors. Cariprazine is also a 5-HT1A partial agonist, with a potential antidepressant effect. Cariprazine has been approved for treatment of both positive and negative symptoms of schizophrenia and for treatment of bipolar disorder. It could potentially be used in depression as an add-on treatment. There are few data reporting effectiveness of cariprazine in the broader spectrum of psychosis. In this paper, the authors report three cases where cariprazine was used in the treatment of psychotic conditions other than schizophrenia, namely a first episode psychosis, a case of delusional disorder, and a case of a patient with borderline personality disorder and psychotic symptoms. The authors suggest that cariprazine may be effective in the treatment of psychosis in a broader sense and should be considered a first-line treatment option.Keywords: antipsychotic treatment, borderline personality disorder, cariprazine, delusional disorder, first-episode psychosis, psychosis, schizophrenia spectrum disorders, tolerability

Background: Schizophrenia (SCZ) is a severe and chronic psychiatric disorder with premature age-related physiological changes. However, numerous previous studies examined the epigenetic age acceleration in SCZ patients and yielded inconclusive results. In this study, we propose to explore the epigenetic age acceleration in drug-naive first-episode SCZ (FSCZ) patients and investigate whether epigenetic age acceleration is associated with antipsychotic treatment, psychotic symptoms, cognition, and subcortical volumes. Methods: We assessed the epigenetic age in 38 drug-naive FSCZ patients and 38 healthy controls by using three independent clocks, including Horvath, Hannum and Levine algorithms. The epigenetic age measurements in SCZ patients were repeated after receiving 8 weeks risperidone monotherapy. Results: Our findings showed significantly positive correlations between epigenetic ages assessed by three clocks and chronological age in both FSCZ patients and healthy controls. Compared with healthy controls, drug-naive FSCZ patients have a significant epigenetic age deceleration in Horvath clock (p = 0.01), but not in Hannum clock (p = 0.07) and Levine clock (p = 0.43). The epigenetic ages of Hannum clock (p = 0.002) and Levine clock (p = 0.01) were significantly accelerated in SCZ patients after 8-week risperidone treatment. However, no significant associations between epigenetic age acceleration and psychotic symptoms, cognitive function, as well as subcortical volumes were observed in FSCZ patients. Conclusion: These results demonstrate that distinct epigenetic clocks are sensitive to different aspects of aging process. Further investigations with comprehensive epigenetic clock analyses and large samples are required to confirm our findings. [ABSTRACT FROM AUTHOR]

Background and aims: Antipsychotic treatment may contribute to low vitamin D levels and have impact on direct anti‐inflammatory activity such as adiponectin activity and indirect proinflammatory activity such as leptin and resistin activity. However, vitamin D levels and adipokines mediated effect on weight gain and increased adiposity are not well evaluated. This study, therefore, assessed vitamin D and adipokines‐mediated obesity among Ghanaian psychiatric patients. Methods: This comparative cross‐sectional study was conducted at psychiatric unit of Komfo Anokye Teaching Hospital, Kumasi, Ghana. Anthropometric measurements, sociodemographic and previous medical history were taken from 300 antipsychotics treatment naïve and active patients. Obesity was classified using World Health Organization (WHO) body mass index (BMI)‐specific cut‐offs. Blood samples were collected for serum vitamin D and adipokines (adiponectin, leptin, and resistin) analysis using enzyme‐linked immunosorbent assay. Statistical analyses were done using SPSS version 26.0 and GraphPad Prism version 8.0. Results: We observed higher prevalence of obesity among treatment active psychiatric patients (40.7%) compared to treatment naïve group (16.8%). Vitamin D insufficiency and deficiency prevalence were significantly higher among the treatment active group (25.3%; 39.5%; p < 0.001) and associated with increased odds of obesity (91.8%; cOR = 91.84, 95% confidence interval [CI]: 24.94–338.13). Moreover, adiponectin (84.2%: cOR = 14.15, 95% CI: 5.52–36.27), leptin (55.6% cOR = 2.20, 95% CI: 1.04–4.67), and resistin (79.4%: cOR = −8.34, 95% CI: 3.39–20.55) were significantly associated with increased odds of obesity among treatment active psychiatric. Furthermore, treatment active psychiatric patients exhibited inverse correlation for adiponectin and leptin with BMI (r = −0.62; −0.24), and WHtR (r = −0.53; −0.24); however, a moderate positive correlation for resistin with BMI (r = 0.80), HC (r = 0.67), and WHtR (r = 0.65). Conclusion: Obesity is more prevalent in psychiatric patients on antipsychotics such as Olanzapine and Clozapine. Obesity among treatment active psychiatric patients is associated with vitamin D insufficiency and deficiency, low adiponectin and leptin levels but higher resistin level. [ABSTRACT FROM AUTHOR]

Background: Carriers of the 22q11.2 deletion syndrome (22q11DS) have an enhanced risk of developing psychotic disorders. Full-blown psychosis is typically diagnosed by late adolescence/adulthood. However, cognitive decline is already apparent as early as childhood. Recent findings in mice show that antipsychotic medication administered during adolescence has a long-lasting neuroprotective effect. These findings offer promising evidence for implementing preventive treatment in humans at risk for psychosis. Methods: We conducted a 12-week double-blind randomized controlled clinical trial with individuals with 22q11DS. Recruitment difficulties resulted in a final sample size of 13 participants (n = 6 treated with antipsychotics and n = 7 receiving placebo). We examined the response to treatment and assessed its short- and long-term effects on psychotic symptomatology using the Structured Interview for Psychosis-Risk Syndromes (SIPS) and cognitive measures. Results: First, two treated participants discontinued treatment after experiencing adverse events. Second, treated participants showed a short-term improvement in 33.3% of the SIPS items, mainly those targeting negative symptoms. Third, reliable improvements in at least one measure of working memory and attention were respectively found in 83.3 and 66.7% of treated participants. Conclusion: This is the first double-blind study to investigate the potential neuroprotective effect of antipsychotics in humans at risk for psychosis. Our preliminary results suggest that antipsychotic treatment may prevent long-term deterioration in clinical symptoms and cognitive skills. Yet, given the limited sample size, our findings need to be replicated in larger samples. To do so, future studies may rather adopt open-label or retrospective designs to ensure sufficient power. [ABSTRACT FROM AUTHOR]

Individuals with first-episode schizophrenia (FES) typically present with acute psychotic symptoms. Though antipsychotic drugs are the mainstay for treatment, the neurobiology underlying successful treatment remains largely elusive. Recent evidence from functional connectivity studies highlights the insula as a key structure in the neural mechanism of response. However, molecular contributions to response across insular regions remain largely unknown. We used 7-Tesla magnetic resonance spectroscopic imaging (MRSI) to measure glutamate (Glu), Glutamine (Gln), and GABA from anterior and posterior regions of the insula across antipsychotic treatment. A total of 36 participants were examined, including 15 individuals with FES and moderate to severe psychosis who were scanned at two time points, while starting and after 6 weeks of antipsychotic treatment. Symptoms were carefully monitored across the study period to characterize treatment response. GABA, Glu, and Gln levels were calculated relative to creatine in anterior and posterior insular regions, bilaterally. In relation to psychotic symptom reduction, we observed a significant increase in Glu across all insular regions with (p < 0.001), but no corresponding changes in Gln or GABA. In group analyses, the FES cohort showed lower levels of Glu (p < 0.001) and GABA (p = 0.02) at baseline. Finally, in exploratory analyses, treatment remitters demonstrated a normalization of lower insular Glu levels across treatment, unlike non-remitters. Overall, these findings contribute to our understating of molecular changes associated with antipsychotic response and demonstrate abnormalities specific to the insula in FES. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate how schizophrenia spectrum disorders and applied long-term (5.1 years) antipsychotic (AP) treatment affect the serum level of acylcarnitines (ACs), cytokines and metabolic biomarkers and to characterize the dynamics of inflammatory and metabolic changes in the early course of the disorder. A total of 112 adults participated in the study (54 patients with first-episode psychosis (FEP) and 58 control subjects). Biomolecule profiles were measured at the onset of first-episode psychosis and 0.6 years and 5.1 years after the initiation of APs. The results of the present study confirmed that specific metabolic–inflammatory imbalance characterizes AP-naïve patients. Short-term (0.6-years) AP treatment has a favourable effect on psychotic symptoms, as well as the recovery of metabolic flexibility and resolution of low-level inflammation. However, 5.1 years of AP treatment resulted in weight gain and increased serum levels of interleukin (IL)-2, IL-4, IL-6, IL-10, interferon-γ, hexoses, acetylcarnitine, short-chain ACs (C3, C4) and long-chain ACs (C16:2, C18:1, C18:2). In conclusion, despite the improvement in psychotic symptoms, 5.1 years of AP treatment was accompanied by a pronounced metabolic–inflammatory imbalance, which was confirmed by the presence of enhanced pro-inflammatory activity and increased obesity with changes in the metabolism of carbohydrates, lipids, and their metabolites. [ABSTRACT FROM AUTHOR]

A 38-year-old army offcer started therapy in 2020 with a four-year history of auditory hallucinations and delusions of reference, persecution and grandeur, symptoms that were resistant to traditional antipsychotic medications. He follows an integrative psychotherapy program that aims to reduce his anxiety, continues his antipsychoticmedications, and has Infra-Low Frequency Neurofeedback. After his initial assessment he had a 40min session of Infra-Low Frequency Neurofeedback before any other kind of intervention. Before and immediately after the session he completed the SCL-90 scale and the Visual Analog Scale covering 20 aspects of his psychological and physical state as well as his schizophrenic symptoms. This first Neurofeedback session had dramatic e [ABSTRACT FROM AUTHOR]

Introduction The variants of the gene for nitric oxide synthase 1 adaptor protein (NOS1AP) are associated with schizophrenia and cardiovascular deficits involving corrected QT (QTc) interval prolongation. Here, we investigated a possible pharmacogenetic effect of antipsychotic treatment on QTc length in interaction with two NOS1AP variants (rs12143842 and rs10494366) whose minor alleles are associated with increased QTc interval length. Methods We conducted a retrospective analysis of electrocardiographic (ECG) and genotype data of 239 patients diagnosed with schizophrenia. We converted antipsychotics dosage to chlorpromazine equivalents and defined daily doses. We analysed the effects of the minor (i. e. rs12143842-CT/TT and rs10494366-GT/GG) and major (i. e. rs12143842-CC and rs10494366-TT) allele genotypes to QTc interval for female and male participants separately. Results As expected, rs12143842 and rs10494366 exhibit strong linkage disequilibrium. Both polymorphisms had no direct effect on antipsychotic use or QTc interval. However, there was a continuous increase in QTc interval with increasing antipsychotic dosage in males. For both variants, positive correlation of QTc length with antipsychotic dosage was found in homozygous male carriers of the major alleles (i. e. rs12143842-CC and rs10494366-TT), but not in minor allele carriers. There was no significant interaction between antipsychotic dosage and QTc interval for either genotype in female patients. Conclusions In this study, a significant interaction was found between both NOS1AP variants, rs12143842 and rs10494366, and antipsychotic treatment on the QTc interval in a sex-dependent manner. Our findings might be relevant for adequate antipsychotic treatment in rs12143842 and rs10494366 major allele carriers. [ABSTRACT FROM AUTHOR]

Abstract Background and aims Antipsychotic treatment may contribute to low vitamin D levels and have impact on direct anti‐inflammatory activity such as adiponectin activity and indirect proinflammatory activity such as leptin and resistin activity. However, vitamin D levels and adipokines mediated effect on weight gain and increased adiposity are not well evaluated. This study, therefore, assessed vitamin D and adipokines‐mediated obesity among Ghanaian psychiatric patients. Methods This comparative cross‐sectional study was conducted at psychiatric unit of Komfo Anokye Teaching Hospital, Kumasi, Ghana. Anthropometric measurements, sociodemographic and previous medical history were taken from 300 antipsychotics treatment naïve and active patients. Obesity was classified using World Health Organization (WHO) body mass index (BMI)‐specific cut‐offs. Blood samples were collected for serum vitamin D and adipokines (adiponectin, leptin, and resistin) analysis using enzyme‐linked immunosorbent assay. Statistical analyses were done using SPSS version 26.0 and GraphPad Prism version 8.0. Results We observed higher prevalence of obesity among treatment active psychiatric patients (40.7%) compared to treatment naïve group (16.8%). Vitamin D insufficiency and deficiency prevalence were significantly higher among the treatment active group (25.3%; 39.5%; p

BackgroundCarriers of the 22q11.2 deletion syndrome (22q11DS) have an enhanced risk of developing psychotic disorders. Full-blown psychosis is typically diagnosed by late adolescence/adulthood. However, cognitive decline is already apparent as early as childhood. Recent findings in mice show that antipsychotic medication administered during adolescence has a long-lasting neuroprotective effect. These findings offer promising evidence for implementing preventive treatment in humans at risk for psychosis.MethodsWe conducted a 12-week double-blind randomized controlled clinical trial with individuals with 22q11DS. Recruitment difficulties resulted in a final sample size of 13 participants (n = 6 treated with antipsychotics and n = 7 receiving placebo). We examined the response to treatment and assessed its short- and long-term effects on psychotic symptomatology using the Structured Interview for Psychosis-Risk Syndromes (SIPS) and cognitive measures.ResultsFirst, two treated participants discontinued treatment after experiencing adverse events. Second, treated participants showed a short-term improvement in 33.3% of the SIPS items, mainly those targeting negative symptoms. Third, reliable improvements in at least one measure of working memory and attention were respectively found in 83.3 and 66.7% of treated participants.ConclusionThis is the first double-blind study to investigate the potential neuroprotective effect of antipsychotics in humans at risk for psychosis. Our preliminary results suggest that antipsychotic treatment may prevent long-term deterioration in clinical symptoms and cognitive skills. Yet, given the limited sample size, our findings need to be replicated in larger samples. To do so, future studies may rather adopt open-label or retrospective designs to ensure sufficient power.Clinical trial registration[www.ClinicalTrials.gov], identifier [NCT04639960].

A 38-year-old army officer started therapy in 2020 with a four-year history of auditory hallucinations and delusions of reference, persecution and grandeur, symptoms that were resistant to traditional antipsychotic medications. He follows an integrative psychotherapy program that aims to reduce his anxiety, continues his antipsychotic medications, and has Infra-Low Frequency Neurofeedback. After his initial assessment he had a 40 min session of Infra-Low Frequency Neurofeedback before any other kind of intervention. Before and immediately after the session he completed the SCL-90 scale and the Visual Analog Scale covering 20 aspects of his psychological and physical state as well as his schizophrenic symptoms. This first Neurofeedback session had dramatic effects on his psychotic symptoms, levels of anxiety and psychosomatic condition, before his first psychotherapy session and/or any changes in his antipsychotic medication. The above results have great importance due to the severity and chronicity of schizophrenia. Informed consent was obtained from the participant for the publication of this case report (including all data and images).

Rationale: Though numerous studies demonstrate the superiority of clozapine (CLZ) for treatment of persistent psychotic symptoms that are characteristic of treatment-refractory schizophrenia (TRS), what remains unknown are the neural and molecular mechanisms underlying CLZ's efficacy. Recent work implicates increased corticostriatal functional connectivity as a marker of response to non-CLZ, dopamine (DA) D2-receptor blocking antipsychotic drugs. However, it is undetermined whether this connectivity finding also relates to CLZ's unique efficacy, or if response to CLZ is associated with changes in striatal DA functioning. Objective: In a cohort of 22 individuals with TRS, we examined response to CLZ in relation to the following: (1) change in corticostriatal functional connectivity; and (2) change in a magnetic resonance-based measure of striatal tissue iron (R2'), which demonstrates utility as a proxy measure for elements of DA functioning. Methods: Participants underwent scanning while starting CLZ and after 12 weeks of CLZ treatment. We used both cortical and striatal regions of interest to examine changes in corticostriatal interactions and striatal R2' in relation to CLZ response (% reduction of psychotic symptoms). Results: We first found that response to CLZ was associated with an increase in corticostriatal connectivity between the dorsal caudate and regions of the frontoparietal network (P < 0.05, corrected). Secondly, we observed no significant changes in striatal R2' across CLZ treatment. Conclusion: Overall, these results indicate that changes in corticostriatal networks without gross shifts in striatal DA functioning underlies CLZ response. Our results provide novel mechanistic insight into response to CLZ treatment. [ABSTRACT FROM AUTHOR]

Pedro Such,1 José Manuel Olivares,2 Lizbeth Arias,1 Mette Troels Berg,1 Jessica Madera3 1Medical Strategy and Communication, H. Lundbeck A/S, Valby, 2500, Denmark; 2Department of Psychiatry, Hospital Álvaro Cunqueiro, Health Research Institute Galicia Sur (IISGS), CIBERSAM, Vigo, Spain; 3Global Medical Affairs, Otsuka Pharmaceutical Development & Commercialization, Inc, Princeton, New Jersey, 08540, USACorrespondence: Pedro SuchMedical Strategy and Communication, H. Lundbeck A/S, Ottiliavej 9, Valby, 2500, DenmarkTel +45 3630 1311Email PSU@lundbeck.comBackground: To obtain real-world evidence of functional improvements during atypical long-acting injectable (aLAI) therapy in recent-onset schizophrenia, an online survey was conducted to assess the impact of aripiprazole once-monthly injectable 400 mg (AOM 400; partial D2 receptor agonist) and paliperidone palmitate once-monthly (PP1M; injectable, full D2 receptor antagonist).Methods: Psychiatrists provided data for their 2 most recent AOM 400 patients, 2 most recent PP1M patients. Survey included 2000 patient cases (1000 AOM 400; 1000 PP1M). Eligible patients were aged 18– 35 years, had been diagnosed with schizophrenia within 5 years, received AOM 400 or PP1M continuously for ≥ 6 months according to approved labels (mean durations: 1.6 and 1.7 years with AOM 400 and PP1M, respectively). Assessments included Global Assessment of Functioning (GAF) Scale, Personal and Social Performance Scale, Positive and Negative Syndrome Scale, and Quality of Life Scale. GAF assessments were done retrospectively and also at the time of survey.Results: Baseline mean GAF scores were 43.3 and 43.8 for AOM 400 and PP1M, respectively, indicating serious symptoms/functional impairment in both groups. Mean improvements following AOM 400 and PP1M therapy were 19.7 and 16.3 points, respectively (final scores in mild functional impairment category). Other measures assessing symptoms/functionality/quality of life demonstrated the benefits of long-term aLAI therapy.Conclusion: Schizophrenia patients with serious functional impairment prior to current aLAI treatment showed improvements in functional outcome after AOM 400 or PP1M therapy. These results suggest functional improvements with aLAIs are apparent not only in research but also real-world settings.Keywords: antipsychotic treatment, aripiprazole, aripiprazole once-monthly injectable, AOM, long-acting injectable, paliperidone palmitate once-monthly injectable

Introduction: Second-generation long-acting injectable antipsychotics (SG-LAIAs) may improve outcomes compared to other antipsychotics. Real-world studies using linked administrative databases play an important role in assessing the comparative effectiveness of antipsychotic medications. Methods: We used a prevalent new-user design in a population-based cohort of antipsychotic users with diagnosis of a psychotic disorder to compare the primary outcome of treatment failure, defined as psychiatric hospitalization, completed suicide, incarceration, or treatment discontinuation. Additional outcomes were all-cause mortality. SG-LAIA users were matched on a 1:1 basis with other antipsychotic users based on the time-conditional propensity score, calendar time, and prior antipsychotic exposure. Results: The use of LAIAs was not associated with a lower risk of treatment failure than other antipsychotics (adjusted hazard ratio 1.07 and 95% confidence interval 0.98–1.15) but did reduce all-cause mortality (adjusted hazard ratio 0.69 and 95% confidence interval 0.48–0.99). Monotherapy with LAIAs was superior to other antipsychotic monotherapy (adjusted hazard ratio for treatment failure 0.83 and 95% confidence interval 0.78–0.89), and LAIAs were superior to other antipsychotics in antipsychotic-naïve users (adjusted hazard ratio for treatment failure 0.57 and 95% confidence interval 0.47–0.70). Conclusion: In this population-based cohort, SG-LAIAs reduced the risk of treatment failure in incident new users but not in prevalent new users. [ABSTRACT FROM AUTHOR]

It has remained unclear what factors relate to primary nonadherence to antipsychotic treatment and whether specific agents and routes of administration differ in how patients adhere to them. We collected electronic prescriptions and their dispensings from the Finnish electronic prescription database for 29 956 patients with schizophrenia prescribed antipsychotics via electronic prescription during 2015–2016. We defined primary nonadherence as being prescribed an antipsychotic, which was not dispensed from the pharmacy within one year from prescription. Using logistic regression, we analyzed whether several sociodemographic and clinical factors related to nonadherence. We found that 31.7% (N = 9506) of the patients demonstrated primary nonadherence to any of their prescribed antipsychotics. We found that young age (OR = 1.77, 95%CI = 1.59–1.96), concomitant benzodiazepines (OR = 1.47, 95%CI = 1.40–1.55) and mood stabilizers (OR = 1.29, 95%CI = 1.21–1.36), substance abuse (OR = 1.26 95%CI = 1.19–1.35), previous suicide attempt (OR = 1.21, 95%CI = 1.11–1.31), diabetes (OR = 1.15, 95%CI = 1.06–1.25), asthma/COPD (OR = 1.14, 95%CI = 1.04–1.25), and cardiovascular disease (OR = 1.12, 95%CI = 1.05–1.19), were related to primary nonadherence to antipsychotic treatment. Patients using clozapine showed the lowest nonadherence (4.77%, 95%CI = 4.66–4.89), and patients using long-acting injectables were more adherent to treatment (7.27%, 95%CI = 6.85–7.71) when compared to respective oral agents (10.26%, 95%CI = 10.02–10.49). These results suggest that selection between different pharmacological agents and routes of administration while taking into account patients' concomitant medications (benzodiazepines in particular) and comorbidities play a key role in primary nonadherence to antipsychotic treatment. [ABSTRACT FROM AUTHOR]

Background: Peripheral blood level of brain-derived neurotrophic factor (BDNF) may be used as a diagnostic and/or prognostic marker for schizophrenia. Previous studies were inconsistent. A systematic review was conducted to examine whether BDNF level is different in patients with first episode psychosis (FEP) compared to health controls (HC) and whether it changes after treatment. Methods: Literature search was done in PubMed, Web of Science, and Google Scholar following standard procedures. Hedges' g was used as the measure of effect size (ES), which was pooled with random effects model. Publication bias and moderator effects were examined. Results: Search yielded 29 studies with a total sample size of 2912. First meta-analysis included 27 studies with FEP vs. HC comparison. Pooled ES was −0.63, p < 0.001, indicating that BDNF level was lower in FEP than in HC. Studies were heterogeneous, and moderator analysis showed that studies of younger patient, higher symptom severity, and more drug naïve had larger ES. Second meta-analysis examined change in BDNF levels before and after antipsychotic treatment in eight studies. A pooled ES of −0.003 (p = 0.96) showed no change in peripheral BDNF level after treatment. Conclusion: Peripheral BDNF level was decreased in FEP compared to HC, but it did not change after treatment. [ABSTRACT FROM AUTHOR]

Introduction: Aripiprazole is hypothesized to have an effect on negative and cognitive symptoms in schizophrenia. Likewise, amisulpride is one of the only second-generation antipsychotics with which an effect on negative symptoms is reported. In the present study, we compare the effect of aripiprazole and amisulpride in initially antipsychotic-naïve patients with first-episode psychoses. Methods: Psychopathology and cognitive measures from two consecutive cohorts of antipsychotic-naïve first episode psychotic patients were obtained before and after 6 weeks of antipsychotic monotherapy with either aripiprazole or amisulpride. Matched healthy controls were included to account for retest effects on the cognitive measures. Analyses of variance (repeated-measures ANOVA) were performed to detect effect of time and possible cohort*time interactions. Results: Longitudinal data was obtained from 47 and 48 patients treated for 6 weeks with amisulpride or aripiprazole, respectively. For the Wallwork negative symptom dimension, there was a cohort*time interaction [ F (1, 93) = 4.29, p = 0.041] and a significant effect of time [ F (1, 93) = 6.03, p = 0.016], which was driven by an improvement in patients treated with aripiprazole [ t (47) = 4.1, p < 0.001] and not observed in patients treated with amisulpride (p > 0.5). For the eight cognitive measures, no cohort*time interaction was found and neither was cognitive improvement in any of the cohorts when accounting for retest effect. Conclusion: Patients treated with aripiprazole improved on negative symptoms, which was not the case for patients treated with amisulpride. This may point to a general effect of a partial D2 receptor agonist on negative symptoms in patients with first-episode psychoses. There was, however, no improvement in cognitive functions. [ABSTRACT FROM AUTHOR]

There are significant differences between men and women in the efficacy and tolerability of antipsychotic drugs. Here, we provide a comprehensive overview of what is currently known about the pharmacokinetics and pharmacodynamics of antipsychotics in women with schizophrenia spectrum disorders (SSDs) and translate these insights into considerations for clinical practice. Slower drug absorption, metabolism and excretion in women all lead to higher plasma levels, which increase the risk for side-effects. Moreover, women reach higher dopamine receptor occupancy compared to men at similar serum levels, since oestrogens increase dopamine sensitivity. As current treatment guidelines are based on studies predominantly conducted in men, women are likely to be overmedicated by default. The risk of overmedicating generally increases when sex hormone levels are high (e.g. during ovulation and gestation), whereas higher doses may be required during low-hormonal phases (e.g. during menstruation and menopause). For premenopausal women, with the exceptions of quetiapine and lurasidone, doses of antipsychotics should be lower with largest adjustments required for olanzapine. Clinicians should be wary of side-effects that are particularly harmful in women, such as hyperprolactinaemia which can cause oestrogen deficiency and metabolic symptoms that may cause cardiovascular diseases. Given the protective effects of oestrogens on the course of SSD, oestrogen replacement therapy should be considered for postmenopausal patients, who are more vulnerable to side-effects and yet require higher dosages of most antipsychotics to reach similar efficacy. In conclusion, there is a need for tailored, female-specific prescription guidelines, which take into account adjustments required across different phases of life. [ABSTRACT FROM AUTHOR]

Chengcheng Pu,1,* Bingjie Huang,1,* Tianhang Zhou,1 Zhang Cheng,1 Yi Wang,2 Chuan Shi,1 Xin Yu1 1Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, People’s Republic of China; 2Neuropsychology and Applied Cognitive Neuroscience Laboratory, CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Department of Psychology, University of Chinese Academy of Sciences, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xin Yu; Chuan ShiPeking University Sixth Hospital, 51 Huayuan North Road, Beijing 100089, People’s Republic of ChinaEmail yuxin@bjmu.edu.cn; shichuan@bjmu.edu.cnObjective: To investigate the gender differences in the efficacy and side effects of three frequently used antipsychotic medicines (risperidone, olanzapine, aripiprazole) for patients with first-episode schizophrenia during the first year of treatment.Methods: A total of 569 patients with first-episode schizophrenia were randomly assigned to risperidone, olanzapine, and aripiprazole groups. All patients were treated according to their actual clinical needs. Clinical efficacies were assessed by the Positive and Negative Symptom Scale (PANSS) and side effects were assessed by the Udvalg for Kliniske Undersogelser Side-Effect scale (UKU). All assessments were completed at baseline and at 1, 2, 3, 6, 9, and 12 months.Results: Males had higher baseline PANSS total scores and PANSS negative and general pathological scores. No significant interactions were found between treatment time and gender in psychopathology improvements in all three groups. In the end of the first year, female patients receiving risperidone reported more dermatological symptoms (rashes) than males, female patients receiving olanzapine reported more autonomic side effects and dermatological symptoms than males, and female patients receiving aripiprazole reported more psychotic side effects than males.Conclusion: Gender differences exhibited in response to antipsychotic treatments for Chinese patients with first-episode schizophrenia. After the first year of antipsychotic treatment, drug-related side effects were more likely presented in female patients than male patients.Keywords: first-episode schizophrenia, gender difference, antipsychotic treatment, treatment response, side effects

Systemic Lupus Erythematosus (SLE) affects various systems in human including central and peripheral nervous systems. The Neuropsychiatric Systemic Lupus Erythematosus (NPSLE) is a severe complication of SLE which causes a formidable challenge in term of diagnosis and its management. Acute confusional state (delirium) is a rare entity of numerous symptoms of NPSLE which is being overlooked even though it is associated with increased mortality. The present case report describe about the presentation of SLE consisting of hyperpigmentation maculopapular rashes over face, neck regions, lower back and extremities in a 36-year-old female with abrupt onset and fluctuating course of psychotic symptoms, acute confusional state and oddities in behaviours. Treatment with low dose of antipsychotic (aripiprazole) resolve the symptom with due consideration taken to rule out steroid induced manifestation of above symptoms.

Introduction: Second-generation long-acting injectable antipsychotics (SG-LAIAs) may improve outcomes compared to other antipsychotics. Real-world studies using linked administrative databases play an important role in assessing the comparative effectiveness of antipsychotic medications.Methods: We used a prevalent new-user design in a population-based cohort of antipsychotic users with diagnosis of a psychotic disorder to compare the primary outcome of treatment failure, defined as psychiatric hospitalization, completed suicide, incarceration, or treatment discontinuation. Additional outcomes were all-cause mortality. SG-LAIA users were matched on a 1:1 basis with other antipsychotic users based on the time-conditional propensity score, calendar time, and prior antipsychotic exposure.Results: The use of LAIAs was not associated with a lower risk of treatment failure than other antipsychotics (adjusted hazard ratio 1.07 and 95% confidence interval 0.98–1.15) but did reduce all-cause mortality (adjusted hazard ratio 0.69 and 95% confidence interval 0.48–0.99). Monotherapy with LAIAs was superior to other antipsychotic monotherapy (adjusted hazard ratio for treatment failure 0.83 and 95% confidence interval 0.78–0.89), and LAIAs were superior to other antipsychotics in antipsychotic-naïve users (adjusted hazard ratio for treatment failure 0.57 and 95% confidence interval 0.47–0.70).Conclusion: In this population-based cohort, SG-LAIAs reduced the risk of treatment failure in incident new users but not in prevalent new users.

Cognitive symptoms of schizophrenia are reported to be minimally responsive to treatment with antipsychotic medications, though variability exists and many prior studies have significant confounds. Here, we examined the response of cognitive symptoms to antipsychotic medications in 71 inpatients with schizophrenia on and off antipsychotic medications in a blinded, placebo-controlled, cross-over study design. Patients received either antipsychotic medication monotherapy or placebo for 4–6 weeks before switching conditions. Neuropsychological testing, including working memory, intelligence, episodic memory, and verbal fluency tests, was administered during each condition. Additionally, we assessed whether polygenic scores for cognitive ability (PGScog) related to variability in antipsychotic medication-induced changes in cognitive performance. Overall, significant changes in cognition were not observed in response to medications (p's > 0.05) except for in episodic memory (p = 0.01), which showed a medication-related improvement. Some antipsychotic medication-related cognitive changes were associated with genetic predisposition to cognitive ability: PGScog showed positive correlations with medication-induced improvements in verbal list learning (p = 0.02) and category fluency (p = 0.03). Our primary results reinforce the notion that in general, cognitive measures are minimally responsive to antipsychotic medication. However, PGScog results suggest that genetic variation may influence the ability of current treatments to affect cognitive change within this patient population. This study underscores the need for development of novel treatment options specifically targeting cognitive symptoms as well as the importance of genetic variability in treatment response for patients with schizophrenia.

IntroductionAripiprazole is hypothesized to have an effect on negative and cognitive symptoms in schizophrenia. Likewise, amisulpride is one of the only second-generation antipsychotics with which an effect on negative symptoms is reported. In the present study, we compare the effect of aripiprazole and amisulpride in initially antipsychotic-naïve patients with first-episode psychoses.MethodsPsychopathology and cognitive measures from two consecutive cohorts of antipsychotic-naïve first episode psychotic patients were obtained before and after 6 weeks of antipsychotic monotherapy with either aripiprazole or amisulpride. Matched healthy controls were included to account for retest effects on the cognitive measures. Analyses of variance (repeated-measures ANOVA) were performed to detect effect of time and possible cohort*time interactions.ResultsLongitudinal data was obtained from 47 and 48 patients treated for 6 weeks with amisulpride or aripiprazole, respectively. For the Wallwork negative symptom dimension, there was a cohort*time interaction [F(1, 93) = 4.29, p = 0.041] and a significant effect of time [F(1, 93) = 6.03, p = 0.016], which was driven by an improvement in patients treated with aripiprazole [t(47) = 4.1, p < 0.001] and not observed in patients treated with amisulpride (p > 0.5). For the eight cognitive measures, no cohort*time interaction was found and neither was cognitive improvement in any of the cohorts when accounting for retest effect.ConclusionPatients treated with aripiprazole improved on negative symptoms, which was not the case for patients treated with amisulpride. This may point to a general effect of a partial D2 receptor agonist on negative symptoms in patients with first-episode psychoses. There was, however, no improvement in cognitive functions.

Background: Although remission is a priority target in psychosis, reported rates show a marked variation across studies and instability over time. Such variability, partly due to methodology, emphasizes the need to define the optimal assessment procedure, as well as to identify reliable predictors. This study aims to: 1. longitudinally compare remission status according to different criteria; 2. identify predictors of duration and stability.Methods: 112 patients with schizophrenia or schizoaffective disorder underwent comprehensive clinical evaluations, with 24-month follow-up. Remission was assessed using three criteria: Remission in Schizophrenia Working Group (RSWG) vs Positive and Negative Syndrome Scale (PANSS) positive and negative scales (PANSS-PN) vs total score (PANSS-T). Kaplan-Meier survival analysis was used for longitudinal comparison, regression models to identify predictors of duration and stability.Results: At enrolment 50% of patients were in remission according to RSWG, while only 23.2% reached the other criteria. PANSS-T cumulative remission rates showed the greatest stability. Stable remission according to RSWG criteria was predicted by negative symptoms, while no significant predictors emerged for PANSS-T. Remission duration was predicted by negative, positive and cognitive symptoms and treatment dosage for RSWG criteria, while for PANSS-T the predictors were cognitive symptoms and duration of illness.Conclusion: Results are in line with previous literature on remission rates and further support the role of basal clinical predictors. In addition, this study shows that more stringent criteria are more stable over time, suggesting their predictive value and the relevance of their use to optimize evaluations also in clinical settings. [ABSTRACT FROM AUTHOR]

Aims: Non‐compliance is still an important problem in psychotic patients. Although antipsychotic (AP) treatment leads to a decrease in psychotic relapses, there are no clear recommendations about how long treatment should be maintained after first‐episode psychosis (FEP) and no indication of the rates and causes of treatment withdrawal in this group. Methods: We evaluated a large sample of patients with FEP for 2 years to compare the time to all‐cause treatment discontinuation of AP drugs and the time to the first relapse. We collected the sociodemographic and psychopathological characteristics of the sample. The number of relapses was also recorded. Results: A total of 310 FEP patients were assessed across seven early intervention teams (mean age = 30.2 years; SD = 11.2). The most prevalent diagnosis at baseline was psychotic disorder not otherwise specified (36.1%), and the most commonly used APs were risperidone (26.5%) and olanzapine (18.7%). A lack of efficacy was the most frequent reason for the withdrawal of the first AP prescribed, followed by non‐compliance. There were no differences in the relapse rates between different APs. Patients treated with long‐acting injectable (LAI) APs presented less disengagement from services than patients treated with oral APs. Conclusions: Although there were no differences between the different APs in terms of relapse rates, LAIs had higher retention rates than oral APs in early intervention services. Compliance is still an important issue in Psychiatry, so clinicians should use different strategies to encourage it, such as the use of LAI treatments. [ABSTRACT FROM AUTHOR]

Abstract Background The Reelin (RELN) gene encodes the protein reelin, which is a large extracellular matrix glycoprotein that plays a key role in brain development. Additionally, this protein may be involved in memory formation, neurotransmission, and synaptic plasticity, which have been shown to be disrupted in schizophrenia (SCZ). A decreasing trend in the expression of RELN mRNA in the brain and peripheral blood of SCZ patients has been observed. There is a need to determine whether changes in RELN mRNA expression in SCZ patients are the result of long-term antipsychotic treatment rather than the etiological characteristics of schizophrenia. The expression levels of RELN mRNA in the peripheral blood of 48 healthy controls and 30 SCZ patients before and after 12-weeks of treatment were measured using quantitative real-time PCR. Results The expression levels of RELN mRNA in the SCZ group were significantly lower than that of healthy controls; however, after 12-weeks of antipsychotic treatment, RELN mRNA levels were significantly increased in the SCZ group. Conclusion The up-regulation of RELN mRNA expression was current in SCZ patients after antipsychotic treatment, suggesting that the changes in RELN mRNA expression were related to the effect of the antipsychotic treatment.

Musical hallucinations (MH) represent a rare and complex auditory phenomenon where individuals perceive music without external stimuli. This case study explores auditory Charles Bonnet syndrome (ACBS) in a 51-year-old male with a history of bilateral sensorineural hearing loss. The patient reported hearing recognizable prayer chants, initially perceived as external sounds from a nearby temple. Over time, these hallucinations persisted and interfered with his daily activities, prompting medical consultation. Despite the absence of psychiatric illness, the patient was diagnosed with ACBS and treated with risperidone, an atypical antipsychotic. The intervention led to a significant reduction in the frequency and intensity of the hallucinations, alongside improved sleep and concentration. The patient also experienced a recurrence of symptoms upon discontinuation of the medication, highlighting the importance of adherence to treatment. This case underscores the need for awareness and understanding of non-psychotic auditory hallucinations in individuals with hearing impairments. The pathophysiology of MH is not fully understood but is believed to involve abnormal activity in the auditory associative cortices due to sensory deprivation. Treatment approaches often include both pharmacological and non-pharmacological strategies, such as optimizing hearing with aids and providing psychoeducation. This study contributes to the limited literature on ACBS and emphasizes the efficacy of antipsychotics in managing MH. Further research is essential to explore the underlying mechanisms and to develop comprehensive management plans for patients experiencing these distressing auditory phenomena. The findings advocate for a multidisciplinary approach to treatment, integrating audiological and psychiatric care to improve patient outcomes., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, D et al.)

• α 2A - and α 2C -adrenoceptor protein expression was determined by Western Blot in the postmortem prefrontal cortex of 24 subjects with schizophrenia and 24 matched controls. • Experiments were performed in synaptosomal membranes (SPM) and in presynaptic (Pre) and postsynaptic density fractions (PSD). • Functional coupling of α 2 -AR to G α proteins induced by the agonist UK14304 was also tested. • In antipsychotic-treated schizophrenia subjects, increased α 2A -AR expression was found in SPM and PSD fractions. • G αi2 and G αi3 proteins mediated stimulation was lower in antipsychotic-treated schizophrenia subjects, whereas in antipsychotic-free schizophrenia subjects remained unchanged. G αo protein stimulation was significantly decreased in both antipsychotic-free and antipsychotic-treated schizophrenia subjects compared to controls. Previous evidence suggests that α 2 -adrenoceptors (α 2 -AR) may be involved in the pathophysiology of schizophrenia. However, postmortem brain studies on α 2 -AR expression and functionality in schizophrenia are scarce. The aim of our work was to evaluate α 2A -AR and α 2C -AR expression in different subcellular fractions of prefrontal cortex postmortem tissue from antipsychotic-free (absence of antipsychotics in blood at the time of death) (n = 12) and antipsychotic-treated (n = 12) subjects with schizophrenia, and matched controls (n = 24). Functional coupling of α 2 -AR to G α proteins induced by the agonist UK14304 was also tested. Additionally, G α protein expression was also evaluated. In antipsychotic-free schizophrenia subjects, α 2A -AR and α 2C -AR protein expression was similar to controls in all the subcellular fractions. Conversely, in antipsychotic-treated schizophrenia subjects, increased α 2A -AR expression was found in synaptosomal plasma membrane and postsynaptic density (PSD) fractions (+60% and +79% vs controls, respectively) with no significant changes in α 2C -AR. [35S]GTPγS SPA experiments showed a significant lower stimulation of G αi2 and G αi3 proteins by UK14304 in antipsychotic-treated schizophrenia subjects, whereas stimulation in antipsychotic-free schizophrenia subjects remained unchanged. G αo protein stimulation was significantly decreased in both antipsychotic-free and antipsychotic-treated schizophrenia subjects compared to controls. Expression of G αi3 protein did not differ between groups, whereas G αi2 levels were increased in PSD of schizophrenia subjects, both antipsychotic-free and antipsychotic-treated. G αo protein expression was increased in PSD of antipsychotic-treated subjects and in the presynaptic fraction of antipsychotic-free schizophrenia subjects. The present results suggest that antipsychotic treatment is able to modify in opposite directions both the protein expression and the functionality of α 2A -AR in the cortex of schizophrenia patients. [ABSTRACT FROM AUTHOR]

The single-injection start regimen for aripiprazole once-monthly 400 mg (AOM 400) in patients with schizophrenia requires a single intramuscular injection in the gluteal or deltoid site and 14 days of concurrent oral therapy. A simplified, single-day regimen of two injections at separate gluteal and/or deltoid injection sites, together with a single 20-mg dose of oral aripiprazole on the 1st day, was assessed. A previously developed population-pharmacokinetic (popPK) model for characterizing aripiprazole PK following oral administration and gluteal intramuscular depot injection was expanded to include deltoid injection. Simulations were conducted to assess PK profiles following various (including two-injection) start regimens. Postmarketing data on patients who received higher-than-recommended AOM doses were used to assess overall safety/tolerability. The two-injection start regimen with a single concurrent oral dose displayed a comparable PK profile to the single-injection start regimen with concurrent 14-day oral administration in simulations. The safety assessment indicated the two-injection start regimen was unlikely to be associated with safety concerns beyond those expected with a single-injection start regimen. These data support use of the two-injection start regimen in clinical practice to reduce reliance on daily oral administration and optimize the therapeutic benefits of AOM 400 in patients with schizophrenia. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate how schizophrenia spectrum disorders and applied long-term (5.1 years) antipsychotic (AP) treatment affect the serum level of acylcarnitines (ACs), cytokines and metabolic biomarkers and to characterize the dynamics of inflammatory and metabolic changes in the early course of the disorder. A total of 112 adults participated in the study (54 patients with first-episode psychosis (FEP) and 58 control subjects). Biomolecule profiles were measured at the onset of first-episode psychosis and 0.6 years and 5.1 years after the initiation of APs. The results of the present study confirmed that specific metabolic–inflammatory imbalance characterizes AP-naïve patients. Short-term (0.6-years) AP treatment has a favourable effect on psychotic symptoms, as well as the recovery of metabolic flexibility and resolution of low-level inflammation. However, 5.1 years of AP treatment resulted in weight gain and increased serum levels of interleukin (IL)-2, IL-4, IL-6, IL-10, interferon-γ, hexoses, acetylcarnitine, short-chain ACs (C3, C4) and long-chain ACs (C16:2, C18:1, C18:2). In conclusion, despite the improvement in psychotic symptoms, 5.1 years of AP treatment was accompanied by a pronounced metabolic–inflammatory imbalance, which was confirmed by the presence of enhanced pro-inflammatory activity and increased obesity with changes in the metabolism of carbohydrates, lipids, and their metabolites.

Background: Studies have mentioned that mixed-lineage leukemia 1 (MLL1) and histone 3 lysine 4 trimethylation (H3K4me3) of brain-derived neurotrophic factor (BDNF) exon IV from the postmortem brain tissue of patients with schizophrenia are related to the psychopathology of schizophrenia. We intended to investigate the levels of MLL1 messenger RNA (mRNA) and BDNF exon IV histone H3K9me2 and K27me3 in peripheral blood of patients with schizophrenia and healthy controls and to evaluate the relationships between aforementioned biomarkers and patients with/without clozapine treatment. Methods: During a one-year period, we recruited 36 patients with schizophrenia and 32 healthy controls. Symptom severity was assessed using the Positive and Negative Syndrome Scale (PANSS). We sampled 10 mL of peripheral blood from each participant to analyze the MLL1 mRNA and BDNF exon IV H3K9me2 and K27me3 levels. Results: Significantly higher blood H3K9me2 (p < 0.01) levels were observed in patients with schizophrenia than those in healthy controls. However, no significant difference was found in H3K27me3 levels between patients with schizophrenia and controls. PANSS scores had significant correlations with H3K9me2 levels (p < 0.01). No significant differences were found in MLL1 mRNA levels, H3K9me2 levels, and H3K27me3 levels between patients with clozapine treatment and nonclozapine treatment. Conclusion: Blood BDNF exon IV H3K9me2 levels may be involved in the psychopathology of schizophrenia. More knowledge is needed before we can develop it to be a biomarker for schizophrenia.

Background: Schizophrenia (SCZ) and bipolar disorder (BD) are severe mental illnesses (SMI) associated with elevated cardiovascular disease (CVD) risk, including obesity. Leptin and adiponectin are secreted by adipose tissue, with pro- and anti-inflammatory properties, respectively. The second generation antipsychotics (AP) olanzapine, clozapine, and quetiapine have been associated with high leptin levels in SMI. However, the link between inflammatory dysregulation of leptin and adiponectin and CVD risk in SMI, and how this risk is influenced by body mass and AP medication, is still not completely understood. We investigated herein if leptin, adiponectin or their ratio (L/A ratio) could predict increased CVD risk in SCZ, BD, and in subgroups according to use of antipsychotic (AP) treatment, independent of other cardio-metabolic risk factors.Methods: We measured fasting plasma levels of leptin and adiponectin, and calculated the L/A ratio in n = 1,092 patients with SCZ and BD, in subgroups according to AP treatment, and in n = 176 healthy controls (HC). Differences in the levels of adipokines and L/A between groups were examined in multivariate analysis of covariance, and the correlations between adipokines and body mass index (BMI) with linear regression. CVD risk was defined by total cholesterol/high-density lipoprotein (TC/HDL) and triglyceride/HDL (TG/HDL) ratios. The adipokines and L/A ratios ability to discriminate individuals with TG/HDL and TC/HDL ratios above threshold levels was explored by ROC analysis, and we investigated the possible influence of other cardio-metabolic risk factors on the association in logistic regression analyses.Results: We observed higher leptin levels and L/A ratios in SMI compared with HC but found no differences in adiponectin. Both adipokines were highly correlated with BMI. The low adiponectin levels showed a fair discrimination in ROC analysis of individuals with CVD risk, with AUC between 0.7 and 0.8 for both TC/HDL and TG/HDL, in all groups examined regardless of diagnosis or AP treatment. Adiponectin remained significantly associated with an elevated TC/HDL and TG/HDL ratio in SMI, also after further adjustment with other cardio-metabolic risk factors.Conclusions: Adiponectin is not dysregulated in SMI but is associated with CVD risk regardless of AP treatment regime.

Introduction In spite of the long history of antipsychotic treatment there are still no clear criteria, which can be robust support for drug decision-making. Objectives To determine the important hallmarks of patient’s current state, life span and history of illness defining the doctor’s decision about the type of antipsychotic to be chosen. Methods The data from the case charts of 275 patients with episodic schizophrenia and rather benign course of the disease were analyzed. Results The group included: male 62%, mean age 33 (SD 11), education 10 years 23%, 13 years 27%, 16 years 29%, disability - 51%, number of hospitalizations due to psychotic episodes in the past 7 (SD 6). The symptoms of the current episode varied from patient to patient: delusions and hallucinations, symptoms of disorganization, negative symptoms of different severity were registered Atypical antipsychotics were more often than typical prescribed to the patients with developmental problems: traumatic obstetric complications (p=0,009), poor somatic health in the childhood (p= 0,02), cognitive dysfunction during school years (p=0,04), and quality of first remission – presence of residual symptoms in the first remission (p=0.005). Good compliance in the past was one more important factor for choosing a atypical antipsychotic for a patient (p=0.05). It appeared that the most important for the decision-making was the specific features of the patient’s development and early period of the disease, but not the specific signs of current psychotic state. Conclusions Doctor’s decision upon the type of antipsychotics in this category of patients is most probably based on other than current clinical symptoms signs.

Background: Schizophrenia (SCZ) and bipolar disorder (BD) are severe mental illnesses (SMI) associated with elevated cardiovascular disease (CVD) risk, including obesity. Leptin and adiponectin are secreted by adipose tissue, with pro- and anti-inflammatory properties, respectively. The second generation antipsychotics (AP) olanzapine, clozapine, and quetiapine have been associated with high leptin levels in SMI. However, the link between inflammatory dysregulation of leptin and adiponectin and CVD risk in SMI, and how this risk is influenced by body mass and AP medication, is still not completely understood. We investigated herein if leptin, adiponectin or their ratio (L/A ratio) could predict increased CVD risk in SCZ, BD, and in subgroups according to use of antipsychotic (AP) treatment, independent of other cardio-metabolic risk factors. Methods: We measured fasting plasma levels of leptin and adiponectin, and calculated the L/A ratio in n = 1,092 patients with SCZ and BD, in subgroups according to AP treatment, and in n = 176 healthy controls (HC). Differences in the levels of adipokines and L/A between groups were examined in multivariate analysis of covariance, and the correlations between adipokines and body mass index (BMI) with linear regression. CVD risk was defined by total cholesterol/high-density lipoprotein (TC/HDL) and triglyceride/HDL (TG/HDL) ratios. The adipokines and L/A ratios ability to discriminate individuals with TG/HDL and TC/HDL ratios above threshold levels was explored by ROC analysis, and we investigated the possible influence of other cardio-metabolic risk factors on the association in logistic regression analyses. Results: We observed higher leptin levels and L/A ratios in SMI compared with HC but found no differences in adiponectin. Both adipokines were highly correlated with BMI. The low adiponectin levels showed a fair discrimination in ROC analysis of individuals with CVD risk, with AUC between 0.7 and 0.8 for both TC/HDL and TG/HDL, in all groups examined regardless of diagnosis or AP treatment. Adiponectin remained significantly associated with an elevated TC/HDL and TG/HDL ratio in SMI, also after further adjustment with other cardio-metabolic risk factors. Conclusions: Adiponectin is not dysregulated in SMI but is associated with CVD risk regardless of AP treatment regime. [ABSTRACT FROM AUTHOR]