Frequency modulation increases the specificity of time-resolved connectivity: A resting-state fMRI study.

Representing data using time-resolved networks is valuable for analyzing functional data of the human brain. One commonly used method for constructing time-resolved networks from data is sliding window Pearson correlation (SWPC). One major limitation of SWPC is that it applies a high-pass filter to the activity time series. Therefore, if we select a short window (desirable to estimate rapid changes in connectivity), we will remove important low-frequency information. Here, we propose an approach based on single sideband modulation (SSB) in communication theory. This allows us to select shorter windows to capture rapid changes in the time-resolved functional network connectivity (trFNC). We use simulation and real resting-state functional magnetic resonance imaging (fMRI) data to demonstrate the superior performance of SSB+SWPC compared to SWPC. We also compare the recurring trFNC patterns between individuals with the first episode of psychosis (FEP) and typical controls (TC) and show that FEPs stay more in states that show weaker connectivity across the whole brain. A result exclusive to SSB+SWPC is that TCs stay more in a state with negative connectivity between subcortical and cortical regions. Based on all the results, we argue that SSB+SWPC is more sensitive for capturing temporal variation in trFNC.

Sex matters: Differences in prodromes, clinical and neuropsychological features in individuals with a first episode mania or psychosis.

OBJECTIVE: This study was aimed at identifying sex differences in patients presenting a first episode mania (FEM) or psychosis (FEP) to help shaping early treatment strategies focused on sex differences. METHODS: Patients with a FEM or FEP underwent a clinical, neuropsychological (neurocognitive functions and emotional intelligence) and functional assessment. Performance on those variables was compared between groups through general linear model, with sex and group (FEM vs FEP) as main effects and group by sex interactions. RESULTS: The total sample included 113 patients: FEM = 72 (45.83 % females) and FEP = 41 (46.34 % females). There were significant main effects for group (not for sex) for most of the clinical features (depressive, negative and positive symptoms) and psychosocial functioning (χ2 = 8.815, p = 0.003). As for neuropsychological performance, there were significant main effects for sex and group. Females performed better than males in verbal memory (χ2 = 9.038, p = 0.003) and obtained a higher emotional intelligence quotient (χ2 = 13.20, p < 0.001). On the contrary, males obtained better results in working memory (χ2 = 7.627, p = 0.006). FEP patients significantly underperformed FEM patients in most cognitive domains. There were significant group by sex interactions for few neuropsychological variables, namely processing speed (χ2 = 4.559, p = 0.033) and verbal fluency (χ2 = 8.913, p = 0.003). LIMITATIONS: Differences between sexes were evaluated, but the influence of gender was not considered. Retrospective evaluation of prodromes and substance use. No healthy control group comparator. CONCLUSION: The main finding is the presence of significant sex effect and group by sex interaction on specific neurocognitive cognition and emotional intelligence measures. Tailored sex-based early treatment strategies might be implemented.

Identification of multimodal brain imaging biomarkers in first-episode drugs-naive major depressive disorder through a multi-site large-scale MRI consortium data.

BACKGROUND: Major depressive disorder (MDD) is a severe and common mental illness. The first-episode drugs-naive MDD (FEDN-MDD) patients, who have not undergone medication intervention, contribute to understanding the biological basis of MDD. Multimodal Magnetic Resonance Imaging can provide a comprehensive understanding of brain functional and structural abnormalities in MDD. However, most MDD studies use single-modal, small-scale MRI data. And several multimodal studies of MDD are limited to simple linear combinations of functional and structural features. METHODS: We screened a large sample of FEDN-MDD patients and healthy controlsmultimodal MRI data. Extracting the fractional amplitude of low-frequency fluctuations (fALFF) feature from functional magnetic resonance imaging and the gray matter volume (GMV) feature from structural magnetic resonance imaging. The mCCA-jICA method was used to integrate these two modal features to investigate the functional-structural co-variation abnormalities in MDD. To validate the stability of the extracted functional-structural covariant abnormalities features, we apply them to identify FEDN-MDD patients. RESULTS: The results show that compared to healthy controls, FEDN-MDD patients exhibit joint group-discriminative independent component and modality-specific group-discriminative independent component, suggesting functional-structural covariant abnormalities in MDD patients. Using lightGBM classifier, we achieve a classification accuracy of 99.84 %. LIMITATION: We use GMV and fALFF for multimodal fusion shows promise, but requires further validation with other datasets and exploration of additional multimodal features. CONCLUSIONS: This may indicate that multimodal fusion features can effectively explore information between different modalities and can accurately identify FEDN-MDD patients, suggesting their potential as multimodal brain imaging biomarkers for MDD.

Emotion Processing and Its Relationship to Social Functioning and Symptoms in Psychotic Disorder: A Systematic Review and Meta-analysis.

BACKGROUND: Emotion processing (EP) is impaired in individuals with psychosis and associated with social functioning; however, it is unclear how symptoms fit into this relationship. The aim of this systematic review and meta-analysis was to examine interrelationships between EP, symptoms, and social functioning, test whether different symptom domains mediate the relationship between EP and social functioning, and examine the moderating effects of illness stage and EP task type. STUDY DESIGN: MEDLINE, Embase, and PsycINFO databases were searched for studies that included individuals with psychosis and reported correlations between EP, symptom domains (positive, negative, depressive, and disorganization), and social functioning. Random effects meta-analyses determined the strength of correlations, and subgroup analyses included illness stage and EP task type (lower- vs higher-level processing). Meta-analytic structural equation models tested whether symptom domains mediated the relationship between EP and social functioning. RESULTS: There was a small relationship (r = .18) between EP and social functioning. Positive, negative, and disorganization symptoms mediated this relationship, although indirect effects were small. Higher-level EP tasks were more strongly associated with negative symptoms than lower-level tasks. Relationships between EP and both social functioning and positive symptoms were smaller in the first episode of psychosis than in established illness. CONCLUSIONS: The mediating relationship suggests that EP not only influences social dysfunction directly but contributes to negative and disorganization symptoms, which in turn impair social functioning. This pathway suggests that targeting negative and disorganization symptoms may ultimately improve social outcomes for individuals with psychosis. Future research, particularly in early psychosis, is needed to determine other factors impacting these interrelationships.

Mindfulness-based family psychoeducation intervention for caregivers of young adults with first-episode psychosis: results at 9-month follow-up.

Objectives: To investigate the effects of a mindfulness-based family psychoeducation (MBFPE) intervention on caregivers and the young adults with first-episode psychosis in mental health care. Methods: Sixty-five caregivers were randomly assigned to the MBFPE program (n = 33) or an ordinary family psychoeducation (FPE) program (n = 32). Eighteen young adults in recovery (YAIR) also participated in the study. All of the participants completed the assessments before participating in the intervention (T1), after the intervention (T2), and at 9-month follow-up (T3). Results: Intention-to-treat analyses were conducted. The caregivers reported a significant and large effect size on positive caregiving experiences based on a Time × Group analysis (g = 0.862, p = 0.006). Among the YAIR participants, between-group differences were significant in their perceptions of caregivers' expressed emotions, including large effect sizes of perceived criticism (g = 1.396, p = 0.049) and hostility (g = 1.444, p = 0.043). Caregiver demographics, including age, education level, socioeconomic status, and number of family members, were found to moderate the effect sizes of the variables studied. Conclusion: This study provides evidence of the effects of MBFPE programs on the outcomes of caregivers and the young adults with first-episode psychosis in their care. Specifically, the MBFPE program in this study played a greater role in promoting positive caregiving experiences and changing caregivers' expressed emotions, especially their expressed criticism of YAIR, compared with the regular FPE program. Therefore, the application of mindfulness training to promote family care and YAIR recovery should be encouraged. Clinical trial registration: ClinicalTrials.gov, identifier NCT03688009.

Dynamics of symptom network in patients with first-episode schizophrenia: Insight from the CNFEST project.

BACKGROUND: Schizophrenia is a heterogeneous psychotic disorder. Recent theories have emphasized the importance of interactions among psychiatric symptoms in understanding the pathological mechanisms of schizophrenia. In the current study, we examined the symptom network in patients with first-episode schizophrenia (FES) at four time points during a six-month follow-up period. METHODS: In total, 565 patients with FES were recruited from the Chinese First-Episode Schizophrenia Trial (CNFEST) project. Clinical symptoms were measured using the Positive and Negative Syndrome Scale (PANSS) at baseline and follow-up (514 patients at one month, 429 at three months, and 392 at six months). We used a network analysis approach to estimate symptom networks with individual symptoms as nodes and partial correlation coefficients between symptoms as edges. A cross-lagged panel network (CLPN) model was used to identify predictive pathways for clinical symptoms. RESULTS: We found stable and strongly connected edges in patients across the time points, such as links between delusions and suspiciousness/persecution (P1:P6), and emotional withdrawal and passive/apathetic social withdrawal (N2:N4). Emotional withdrawal (N2), poor rapport (N3), and passive/apathetic social withdrawal (N4) had high centrality estimates across all four time points. CLPN analysis showed that negative symptoms, including emotional withdrawal (N2), poor rapport (N3), and passive/apathetic social withdrawal (N4), and stereotyped thinking (N7) may have predictive effects for negative and general symptoms at follow-ups. CONCLUSIONS: The symptom network of schizophrenia may be dynamic as treatment progresses. Negative symptoms remain the central and stable symptoms of schizophrenia. Negative symptoms may be potential therapeutic targets that predict other symptoms.

Association between exposure to antidepressants and stimulants and age at onset of mania or psychosis: A retrospective population-based cohort study.

This study investigated the impact of prior antidepressant and stimulant exposure on the age at onset (AAO) of first episode mania (FEM) or psychosis (FEP). Patients with FEP and FEM born after 1985 in Olmsted County, Minnesota, were identified using the Rochester Epidemiology Project. Duration and peak dose of antidepressant and stimulant exposure were quantified by review of the electronic health record. Peak doses were converted to defined daily dose (DDD), and cumulative exposure was calculated as DDD multiplied by treatment duration. Linear models were used to assess relationships between AAO with any exposures, and cumulative antidepressant and stimulant exposures. A total of 190 FEM/FEP patients (mean AAO=20.8 ± 3.7 years) were included. There was no significant difference in AAO with vs. without exposure to antidepressants or stimulants. Cumulative antidepressant exposure correlated with a later AAO in overall sample (r = 0.28, p < 0.001), and in FEP (r = 0.33, p < 0.001). No significant correlation emerged between cumulative stimulant exposure and AAO. Multivariable modeling confirmed that cumulative antidepressant exposure (Estimate=2.42, 95 %CI=1.66-3.18, p < 0.001), but not cumulative stimulant exposure (Estimate=-0.04, 95 %CI=-1.10-1.02, p = 0.94), was associated with later AAO. Antidepressant and stimulant exposures were not associated with earlier AAO. However, cumulative antidepressant exposure was associated with later AAO. Limitations include retrospective design and relatively small sample size. Our findings may inform adolescent treatment recommendations when assessing risk for psychotropic-related adverse events. Further risk modeling investigations of antidepressants and stimulants with larger sample sizes are needed to explore the role of antidepressant and stimulant exposure in the trajectory leading to FEM/FEP.

Early Intervention in the Treatment of Psychosis.

This article aims to: (1) describe the evolution of first episode of psychosis (FEP) approaches; (2) define a model of multidisciplinary care; (3) identify challenges and limitations; (4) discuss the unique challenges for those first experiencing psychosis; (5) identify strategies to expand early psychosis interventions. The authors take the medical standpoint and use the differential diagnosis and initial medical work-up as a context for assessment. The remainder of the article will be focused on treatment of FEP in those with schizophrenia-spectrum disorders.

Associations between rural/urban status, duration of untreated psychosis and mode of onset of psychosis: a mental health electronic clinical records analysis in the East of England, UK.

PURPOSE: The influence of rurality on the duration of untreated psychosis (DUP) in first-episode psychosis (FEP) is poorly understood. We investigated factors associated with FEP in rural/urban settings and whether there are rural/urban differences in DUP and the mode (speed) of onset of psychosis. METHODS: We used the Cambridgeshire and Peterborough NHS Foundation Trust Research Database (CPFTRD) to identify all persons presenting to an early intervention for psychosis service with FEP between 2013 and 2015. We performed descriptive statistics and multivariable linear and multinomial regression to assess the relationships between the study outcomes and the independent variables. RESULTS: One hundred and fifty-five FEP patients were identified, with a mean age of 23.4 (SD, 5.3) years. The median DUP was 129.0 (IQR: 27.5-524.0) days. In rural areas, FEP patients were more likely to be employed and live with family than those in urban areas. A longer DUP was observed among patients with an insidious onset of psychosis compared with an acute onset (619.5 (IQR: 333.5-945.0)) vs. (17.0 (IQR: 8.0-30.5)) days respectively, p < 0.0001. We found evidence that the mode of onset of psychosis differed by employment status and living circumstances. There was insufficient evidence of rural/urban differences in DUP and mode of onset of psychosis. CONCLUSIONS: Our results suggest that the mode of onset of psychosis is an important indicator of treatment delay and could provide vital information for service planning and delivery. Sociodemographic variations in FEP exist in rural populations, and our findings are similar to those observed in urban settings.

Discussing the concept of substance-induced psychosis (SIP).

Substance-induced psychosis (SIP) is characterized by both substance use and a psychotic state, and it is assumed that the first causes the latter. In ICD-10 the diagnosis is categorized as and grouped together with substance use disorders, and to a large extent also treated as such in the health care system. Though criticism of the diagnostic construct of SIP dates back several decades, numerous large and high-quality studies have been published during the past 5-10 years that substantiate and amplify this critique. The way we understand SIP and even how we name it is of major importance for treatment and it has judicial consequences. It has been demonstrated that substance use alone is not sufficient to cause psychosis, and that other risk factors besides substance use are at play. These are risk factors that are also known to be associated with schizophrenia spectrum disorders. Furthermore, register-based studies from several different countries find that a large proportion, around one in four, of those who are initially diagnosed with an SIP over time are subsequently diagnosed with a schizophrenia spectrum disorder. This scoping review discusses the construct validity of SIP considering recent evidence. We challenge the immanent causal assumption in SIP, and advocate that the condition shares many features with the schizophrenia spectrum disorders. In conclusion, we argue that SIP just as well could be considered a first-episode psychotic disorder in patients with substance use.

Cognitive profiles across the psychosis continuum.

Cognitive impairments are core features in individuals across the psychosis continuum and predict functional outcomes. Nevertheless, substantial variability in cognitive functioning within diagnostic groups, along with considerable overlap with healthy controls, hampers the translation of research findings into personalized treatment planning. Aligned with precision medicine, we employed a data driven machine learning method, self-organizing maps, to conduct transdiagnostic clustering based on cognitive functions in a sample comprising 228 healthy controls, 200 individuals at ultra-high risk for psychosis, and 98 antipsychotic-naïve patients with first-episode psychosis. The self-organizing maps revealed six clinically distinct cognitive profiles that significantly predicted baseline functional level and changes in functional level after one year. Cognitive flexibility in particular, as well as specific executive functions emerged as cardinal in differentiating the profiles. The application of self-organizing maps appears to be a promising approach to inform clinical decision-making based on individualized cognitive profiles, including patient allocation to different interventions. Moreover, this method has the potential to enable cross-diagnostic stratification in research trials, utilizing data-driven subgrouping informed by categories from underlying dimensions of cognition rather than from clinical diagnoses. Finally, the method enables cross-diagnostic profiling across other data modalities, such as brain networks or metabolic subtypes.

Exploring online and offline social experiences and interaction patterns of young adults with psychosis with the social media and internet social engagement questionnaire: Analyses and future directions.

Objective: Social interactions and experiences are increasingly occurring online, including for young adults with psychosis. Healthy social interactions and experiences are widely recognized as a critical component of social recovery, yet research thus far has focused predominantly on offline interactions with limited understanding of these interactions online. We developed the Social Media and Internet sociaL Engagement (SMILE) questionnaire to assess the type, frequency, and nature of online social interactions and experiences among young adults with early psychosis to better assess online social activity and ultimately support personalized interventions. Methods: Participants (N = 49) completed the SMILE questionnaire which asked about online platforms used, frequency of use, and if positive and negative experiences were more likely to happen online or offline. Participants completed additional self-report measures of victimization, positive psychotic symptoms, social functioning, and demographics. Exploratory factor analysis and correlations between identified factors and clinical measures of interest were completed. Results: Exploratory factor analysis revealed three factors: positive engagement, victimization, and internalizing experiences. Most participants (6%-37%) experienced positive engagement offline. Victimization occurred equally online and offline (8%-27% and 4%-24%, respectively). Most participants (37%-51%) endorsed internalizing experiences as occurring equally offline and online, but approximately a third of participants reported internalizing experiences more frequently offline (20%-35%). Victimization was moderately (r = 0.34) correlated with overall online social experiences, suggesting more online time may increase the likelihood of victimization. Age was inversely related to the frequency of overall online social experiences. Conclusion: Young adults with early psychosis experience positive and negative social experiences online and offline. New scales and measures to comprehensively assess the nature and function of online social interactions and experiences are needed.

Evaluation of the Correlation Between Peripheral Inflammatory Markers and Suicide Risk in Drug-Naive First-Episode Schizophrenia.

Introduction: Patients with schizophrenia have a higher lifetime prevalence of suicidal behavior (SB) compared to the general population. Therefore, understanding the possible neurobiology of suicide and predicting the risk of suicide in schizophrenia is a solemnly critical issue. Methods: 31 drug-naïve first episode schizophrenia (FES) patients with current SB (FES-S), 69 drug-naive patients with first episode schizophrenia without SB (FES-NS), and 69 drug-naïve non-psychotic patients with current SB (NPS) who were diagnosed according to The Diagnostic and Statistical Manual of Mental Disorders - 5 (DSM-5) participated the study. The control group (HC) consisted of 127 individuals matched with the patients. Symptoms at the time of evaluation were assessed using The Positive and Negative Syndrome Scale (PANSS) and Columbia Suicide Severity Rating Scale (CSSRS). Blood samples were collected from all participants to determine White blood cell (WBC), neutrophil, monocyte, albumin, C-reactive protein (CRP), Lymphocyte, and Platelet levels and to measure this protein ratio. Results: The blood levels of WBC, neutrophil, monocyte, albumin, CRP, and Neutrophil/Albumin Ratio (NAR) were higher in all patient groups compared to HC. CRP/Albumin Ratio (CAR) value was observed to be highest in the NPS group. Monocyte/Lymphocyte Ratio (MLR) value was significantly higher in patients with FES compared to HC. There were no significant differences between the FES-S group and the FES-NS and NPS groups. Conclusion: It can be suggested that although inflammation is not a predictor for suicide attempts in schizophrenia, it is associated with the degree of suicide risk in schizophrenia. In addition, the strong relationship between suicide and psychiatric disorders can be the main reason for high peripheral inflammation levels in suicidal patients.

Analyzing language ability in first-episode psychosis and their unaffected siblings: A diffusion tensor imaging tract-based spatial statistics analysis study.

Schizophrenia (SZ) is a highly heritable mental disorder, and language dysfunctions play a crucial role in diagnosing it. Although language-related symptoms such as disorganized speech were predicted by the polygenic risk for SZ which emphasized the common genetic liability for the disease, few studies investigated possible white matter integrity abnormalities in the language-related tracts in those at familial high-risk for SZ. Also, their results are not consistent. In this current study, we examined possible aberrations in language-related white matter tracts in patients with first-episode psychosis (FEP, N = 20), their siblings (SIB, N = 20), and healthy controls (CON, N = 20) by applying whole-brain Tract-Based Spatial Statistics and region-of-interest analyses. We also assessed language ability by Thought and Language Index (TLI) using Thematic Apperception Test (TAT) pictures and verbal fluency to see whether the scores of these language tests would predict the differences in these tracts. We found significant alterations in language-related tracts such as inferior longitudinal fasciculus (ILF) and uncinate fasciculus (UF) among three groups and between SIB and CON. We also proved partly their relationship with the language test as indicated by the significant correlation detected between TLI Impoverished thought/language sub-scale and ILF. We could not find any difference between FEP and CON. These results showed that the abnormalities, especially in the ILF and UF, could be important pathophysiological vulnerability indexes of schizophrenia. Further studies are required to understand better the role of language as a possible endophenotype in schizophrenia with larger samples.

Altered resting-state and dynamic functional connectivity of hypothalamic in first-episode depression: A functional magnetic resonance imaging study.

The hypothalamus is an important component of the hypothalamic-pituitary-adrenal axis and an important brain region of the limbic system. Twenty-four first depressive episode(FDE) patients and 25 healthy controls were recruited for this study. The hypothalamus was used as a seed to observe the characteristics of resting state and dynamic functional connectivity (FC) changes in FDE patients, and further observed the correlation between the different brain regions and clinical symptoms. The results found that compared with the HC group, the FDE group showed sFC was increased of the left hypothalamus with right superior parietal gyrus and right middle temporal gyrus, and dFC was increased of the left hypothalamus with left inferior occipital gyrus. And sFC was increased of the right hypothalamus with right orbital part of inferior frontal gyrus, right supplementary motor area, and right middle temporal gyrus, and the dFC was also increased of right hypothalamus with right superior parietal gyrus and left middle temporal gyrus. In addition,there was a negative correlation between dFC values of the right hypothalamus with the right superior parietal gyrus and clinical symptoms in the FDE group. This study provides new insights into understanding the altered neuropathological mechanisms of the hypothalamic circuit in FDE.

Feuerstein Instrumental Enrichment Program for People With Schizophrenia After the First Episode of Psychosis: Protocol for an Open-Label Intervention Study.

BACKGROUND: Schizophrenia is a disorder associated with neurocognitive deficits that adversely affect daily functioning and impose an economic burden. Cognitive rehabilitation interventions, particularly during the early phases of illness, have been shown to improve cognition, functionality, and quality of life. The Feuerstein Instrumental Enrichment (FIE) program, based on the Mediated Learning Experience and the Structural Cognitive Modifiability theory, has been applied in various disorders, but its applicability in schizophrenia has not yet been clarified. OBJECTIVE: This study aims to investigate the effects of the FIE program on the functionality of patients with first-episode schizophrenia. METHODS: In total, 17 patients will be recruited for an open-label intervention consisting of twice-weekly sessions for 10 weeks. The primary outcome measure will be changes in the Goal Achievement Scale score. Maze task performance from the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) battery will serve as a secondary outcome measure. At the same time, changes in Positive and Negative Syndrome Scale scores and other MATRICS domains will be analyzed as exploratory outcomes. Assessments will be administered before and after the intervention, with a follow-up period of 6 months. RESULTS: This trial was preregistered in The Brazilian Registry of Clinical Trials (RBR-4gzhy4s). By February 2024, 11 participants were enrolled in the training. Recruitment is expected to be completed by May 2024. Data analysis will be conducted between May and September 2024. The results are expected to be published in January 2025. CONCLUSIONS: This study may establish a protocol for the FIE program that uses mediation techniques for individuals in the early stages of schizophrenia. The results will add to the knowledge about strategies to promote cognitive skills and functional impairment in daily life. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/57031.

Psychological interventions for early-phase schizophrenia: protocol for a systematic review and network meta-analysis.

Introduction: Treating the early phase of schizophrenia is crucial for preventing further episodes and improving quality of life, functioning, and social inclusion. Pharmacotherapies are first-line treatments, but have limitations. There is consensus on the need for non-pharmacological interventions for individuals in the early phase of schizophrenia. Several psychological interventions have shown promising effects; however, their comparative effectiveness remains largely unknown. To address this issue, a network meta-analysis will be performed. We aim to develop a hierarchy of existing psychological treatments concerning their efficacy and tolerability, which will inform treatment guidelines. Protocol: Randomized controlled trials (RCTs) investigating psychological interventions for first-episode psychosis, first-episode schizophrenia, or early phase schizophrenia will be included. The primary outcome will be overall schizophrenia symptoms (measured up to 6 and 12 months, and at the longest follow-up) and relapse as a co-primary outcome. Secondary outcomes are premature discontinuation; change in positive, negative, and depressive symptoms of schizophrenia; response; quality of life; overall functioning; satisfaction with care; adherence; adverse events; and mortality. The study selection and data extraction are performed by two independent reviewers. We will assess the risk of bias of each study using the Cochrane Risk of Bias tool 2 and evaluate the confidence in the results using Confidence in Network Meta-Analysis (CINeMA). Subgroup and sensitivity analyses will be conducted to explore heterogeneity and assess the robustness of our findings. Discussion: This systematic review and network meta-analysis aims to compare multiple existing psychological interventions, establishing which are best for symptom reduction, relapse prevention, and other important outcomes in early phase schizophrenia. Our results may provide practical guidance concerning the most effective psychological intervention to reduce symptom severity and the societal burden associated with the disorder.

Olanzapine-Induced Weight Gain and Glycolipid Metabolism Aberrations in First-Episode and Antipsychotic-Naïve Schizophrenia Patients: A Longitudinal Study.

OBJECTIVE: Limited research has delved into the comprehensive impact of monotherapy on weight and glycolipid metabolism in schizophrenia (SCZ) patients. Our study aims to longitudinally investigate the multidimensional effects of olanzapine (OLA) monotherapy on weight and glycolipid metabolism in first-episode and antipsychotic-naïve (FEAN) SCZ patients. METHODS: A total of 74 FEAN-SCZ patients were recruited, as well as 58 sex- and age-matched healthy controls. Eligible patients underwent a 4-week OLA treatment regimen, with weight assessments conducted at baseline and week 4. Moreover, lipid profiles and fasting plasma glucose (FPG) were measured at baseline and week 4. Insulin, leptin (LEP), and adiponectin (APN) levels were determined using enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: At baseline, FEAN-SCZ patients showed elevated levels of insulin, low-density lipoprotein (LDL), impaired insulin sensitivity, and reduced levels of APN compared to the healthy controls. Following 4-week OLA treatment, patients showed an increase in body mass index (BMI) of 0.96 kg/m2. Additionally, FPG, quantitative insulin sensitivity check index (QUICKI), HOMA-insulin sensitivity index (HOMA-ISI), and fasting plasma glucose to insulin ratio (G/I) displayed significant decreases, while insulin, HOMA-IR, and LEP levels showed significant increases. Stepwise regression analysis revealed that baseline FPG independently predicted the change in BMI after 4 weeks of OLA treatment. CONCLUSION: FEAN-SCZ patients exhibited pre-existing alterations in glucose homeostasis. After 4 weeks of OLA treatment, SCZ patients experienced significant weight gain, deteriorating insulin resistance, and increased LEP levels. In addition, baseline FPG emerged as a predictor of BMI changes after 4 weeks of OLA treatment.