Early Stages Of Illness Research Articles

Nociplastic pain concept, a mechanistic basis for pragmatic approach to fibromyalgia.

Nociplastic pain (NP), as a mechanistic term, denotes pain arising from altered nociception without clear evidence of tissue or somatosensory damage. Fibromyalgia (FM), a prototypical NP condition, incorporates a broad continuum of phenotypes with a distinct neurobiological signature and shared NP attributes. The nociplastic concept may provide a new opportunity for early diagnosis of FM by identifying the characteristic NP features before a state of pain generalization and symptoms clustering. In this approach, even individual symptoms associated with NP features are worthy of attention to denote FM. It may provide a timely diagnosis of FM before clinical progression to a severe and hard-to-manage condition. Furthermore, collecting all various FM phenotypes under the nociplastic concept and not delimiting FM to the only typical presentation allows investigators to identify FM subgroups reflecting potentially distinct pathophysiologic mechanisms and biomarkers. This viewpoint can be served in future studies to develop individualized management. In this review, we postulate a novel approach to early FM diagnosis and management based on NP conceptualization and phenotype recognition. Key Points • FM as a NP condition represents overlapping clinical phenotypes and incomplete presentations especially in early stage of illness. • The mechanistic approach based on the NP features of FM can be implicated in the timely diagnosis and management of FM. • The NP-based approach to FM provides a broader viewpoint beyond FM delimitation to pain generalization and polysymptomatic complaints.

Detection of SARS-CoV-2 RNA by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) on Self-Collected Nasal Swab Compared With Professionally Collected Nasopharyngeal Swab.

Background: Self-collection of nasal swabs for the detection of SARS-CoV-2 RNA by reverse transcription-polymerase chain reaction (RT-PCR) would considerably increase the testing capability and decrease the risk of transmission among healthcare workers (HCW) and the use of personal protective equipment (PPE).Objectives: This study aimed to evaluate the performance of self-collected nasal swabs compared with professionally collected nasopharyngeal (NP) swabs for detection of SARS-CoV-2 RNA by RT-PCR.Materials and methods: We performed a cross-sectional study where the suspected cases of coronavirus disease 2019 (COVID-19) were instructed about the self-collection of nasal swabs from their mid-turbinate. The results were compared to a nasopharyngeal swab collected by a trained healthcare worker in the same patient at the same sitting.Results: We enrolled 100 participants, of which, 69 (69%) were male and 31 (31%) were female. The median age of the study participant was 36 years. Of the participants, 58 (58%) were symptomatic, and the commonest clinical presentation was cough, which was present in 42 (42%) participants. Out of 100 samples, 31 (31%) professionally collected nasopharyngeal swabs and 28 (28%) self-collected nasal swabs were positive for SARS-CoV-2 by RT-PCR. Out of 31 professionally collected positive samples, three samples were negative in self-collection. Out of 28 self-collected positive samples, no sample was negative in the professional collection. The sensitivity and specificity of self-collected nasal swabs compared to professionally collected nasopharyngeal swabs were 90.32% and 100.00%, respectively. The sensitivity of self-collected nasal was 100% when the cycle threshold (Ct) value of the professionally collected NP swab was less than 30.Conclusion: Our study showed that self-collected nasal swabs' sensitivities were similar to professionally collected NP swabs with a high viral load (low Ct value). Hence, this method could be used when the patient is symptomatic and come to the health providers in the early stage of COVID-19 illness.

White matter integrity and pro-inflammatory cytokines as predictors of antidepressant response in MDD

IntroductionMajor depressive disorder (MDD) often involves immune dysregulation with high peripheral levels of pro-inflammatory cytokines that might have an impact on the clinical course and treatment response. Moreover, MDD patients show brain volume changes and white matter (WM) alterations that are already existing in the early stage of illness.ObjectivesThe aim of the present review is to elucidate the association between inflammation and WM integrity and its impact on the pathophysiology and progression of MDD as well as the role of possible novel biomarkers of treatment response to improve MDD prevention and treatment strategies.MethodsWe conducted an electronic literature search of PubMed on studies that examined the role of inflammation in depression and that focused on WM integrity and pro-inflammatory cytokines as predictors of antidepressant response.ResultsThere is evidence for central effects of peripheral inflammation which could activate microglia which, in turn, might trigger a cascade of inflammatory processes leading to neurotransmitter imbalances. Numerous studies indicated that both altered levels of peripheral inflammatory markers, particularly TNF-α, IL-6, and CRP as well as WM integrity might predict antidepressant treatment outcome.ConclusionsDespite mounting evidence on the impact of the immune system on WM microstructure, no study has yet addressed the interaction between the two factors in influencing antidepressant response. There is a lack of reproducible biomarkers predicting treatment response on an individual basis. The availability of such biomarkers would enable more efficient and personalized treatments with a faster treatment response and better prevention of treatment resistance.DisclosureNo significant relationships.

IoT based monitoring system for epileptic patients

The unpredictable nature of epileptic seizures makes it challenging to detect and effectively treat this disorder. The seizures are random, and most epileptic patients experience dangerous physical symptoms during an attack that renders the patient uneasy when conducting their daily tasks. This paper focuses on the generalised type of epilepsy, namely "Grand mal epilepsy Tonic-Clonic (GTC) seizure. The research aims to monitor symptoms of epileptic disease behaviour signals in humans and prevent it at its early stage of illness. To achieve this objective, we used the Electrocardiogram (ECG), Electromyography (EMG), accelerometer 3-axes for fall detection, and Dallas sensor for body temperature signals monitoring for updating the IoT system. The fuzzy logic algorithm that has been used to assess specified data set of diseased patients' parameters allows the classification into diverse types of seizures such as heart rate, body temperature, muscles spasm and falls. These are used as inputs to obtain the seizure type as an output which is then illustrated graphically on the dashboard of an IoT platform (Think-Speak), where abnormal conditions have been used to notify the medical personnel by sending an SMS message through "If This Then That” (IFTTT) technology. A prototype of an epileptic monitoring system has been successfully built and tested. It has an average accuracy of 98.90%, 95.49%, 83.0%, and 87.21% for body temperature, heart rate monitoring, muscle spasm, and fall detection.

Current and Future Molecular Diagnostics of Tick-Borne Diseases in Cattle.

Ticks and tick-borne diseases such as babesiosis, anaplasmosis, ehrlichiosis, Lyme disease, Crimean Congo hemorrhagic fever, and Rocky Mountain spotted fever pose a significant threat to animal and human health. Tick-borne diseases cause billions of dollars of losses to livestock farmers annually. These losses are partially attributed to the lack of sensitive, robust, cost effective and efficient diagnostic approaches that could detect the infectious pathogen at the early stages of illness. The modern nucleic acid-based multiplex diagnostic approaches have been developed in human medicine but are still absent in veterinary medicine. These powerful assays can screen 384 patient samples at one time, simultaneously detect numerous infectious pathogens in each test sample and provide the diagnostic answer in a few hours. Development, commercialization, and wide use of such high throughput multiplex molecular assays in the cattle tick-borne disease surveillance will help in early detection and control of infectious pathogens in the animal reservoir before community spread and spillover to humans. Such approaches in veterinary medicine will save animal life, prevent billions of dollars of economic loss to cattle herders and reduce unwanted stress to both human and animal health care systems. This literature review provides recent updates on molecular diagnostics of tick-borne pathogens and discusses the importance of modern nucleic acid high throughput multiplex diagnostic approaches in the prevention of tick-borne infection to livestock.

Predicting Psychosis: Field Moves From Assessment of Clinical Risk to Search for Biomarkers

Predicting Psychosis: Field Moves From Assessment of Clinical Risk to Search for Biomarkers

Effectiveness of a community health worker-led case management programme to improve outcomes for people with psychotic disorders in Thailand: a one-year prospective cohort study

BackgroundIntensive case management (ICM) programmes for psychotic patients are effective in improving outcomes, but often unfeasible in resource-poor settings, as they typically require extensive human resources and expertise. We developed and evaluated the effectiveness of a less intensive case management program (LICM), led by community health workers, on one-year social functioning and service use.MethodsA prospective cohort study was conducted on patients aged 18 and above residing in a hospital catchment area. Outcomes were compared between LICM (n = 64) and non-LICM participants (n = 485). A counterfactual framework approach was applied to assess causal effects of the LICM on outcomes. The programme effectiveness was analyzed by augmented-inverse probability of treatment weighting (AIPW) to estimate potential outcome mean (POM) and average treatment effect (ATE). Outcomes were employment status and use of emergency, inpatient and outpatient services. Analyses were stratified by the number of previous psychotic relapse (≤ 1, > 1) to assess heterogeneity of treatment effect on those in an early and later stages of psychotic illness.ResultsIn the early-stage cohort, the likelihood of being employed at one year post-baseline was significantly greater in LICM participants than non-LICM participants (ATE 0.10, 95%CI 0.05–0.14, p < 0.001), whereas service use of all types, except outpatient, was not significantly different between the two groups. In the later-stage cohort, the likelihoods of employment between the two groups at post-baseline were similar (ATE -0.02, 95%CI -0.19–0.15, p = 0.826), whereas service use of all types was significantly higher in LICM participants.ConclusionLICM in a setting where community mental services are scarce may benefit those at an early stage of psychotic illness, by leading to better social functioning and no higher use of unscheduled services at the end of the programme, possibly through their better prognosis and medication adherence. A more intensive case management model may be appropriate for those in a later stage of the illness.

Psychiatric Symptoms, Posttraumatic Growth, and Life Satisfaction Among Parents of Seriously Ill Infants: A Prospective Case-Controlled Study

We evaluated psychiatric symptoms, posttraumatic growth, and life satisfaction among the parents (n = 34) of newborns (n = 17) requiring therapeutic hypothermia or urgent surgery (interest group). Our control group included 60 parents of healthy newborns (n = 30). The first surveys were completed soon after diagnosis or delivery and the follow-up surveys 1 year later (participation rate 88% in the interest group and 70% in the control group). General stress was common in both groups but was more prevalent in the interest group as were depressive symptoms, too. Anxiety was more common in the interest group, although it showed a decrease from the baseline in both groups. Life satisfaction had an inverse correlation with all measures of psychiatric symptoms, and it was lower in the interest group in the early stage, but similar at 12 months due to the slight decline in the control group. Mothers in the interest group had more anxiety and depressive symptoms than fathers in the early stage. Mothers had more traumatic distress than fathers at both time points. Half of the parents experienced substantial posttraumatic growth at 12 months. In conclusion, the serious illness of an infant substantially affects the well-being of the parents in the early stages of illness and one year after the illness.

Central Oxidative Stress and Early Vocational Outcomes in First Episode Psychosis: A 7-Tesla Magnetic Resonance Spectroscopy Study of Glutathione.

Following the first episode of psychosis, some patients develop poor social and occupational outcomes, while others display a pattern of preserved functioning. Evidence from preclinical, genetic, and biochemical studies suggest a role for high oxidative stress in poor functional outcomes among patients. The measurement of intracortical glutathione (GSH) using magnetic resonance spectroscopy (MRS) enables investigating the relationship between central antioxidant tone and functional outcomes at the time of first-episode psychosis (FEP). We hypothesized that patients with higher central antioxidant tone at first presentation will have better functional outcomes in early stages of illness. We scanned 57 patients with FEP and 30 matched healthy controls and estimated GSH resonance using 7-Tesla MRS. We minimized the confounding effects of illness chronicity, long-term treatment exposure, and metabolic complications by recruiting patients with <2 weeks of lifetime antipsychotic exposure on average and followed up this cohort for the next 1 year to determine functional outcomes. Patients who achieved employment/education or training status (EET) in the first year, had higher GSH at the baseline than healthy controls. Social and occupational functioning assessment scale (SOFAS) scores were also significantly higher in patients with higher GSH levels at the outset, after adjusting for various confounds including baseline SOFAS. Patients who were not in EET did not differ from healthy subjects in their GSH levels. Our observations support a key role for the central antioxidant tone in the functional outcomes of early psychosis.

Analytically sensitive Rickettsia species detection for laboratory diagnosis.

ABSTRACT.Clinical and laboratory diagnosis of rickettsial diseases is challenging because of the undifferentiated symptoms (commonly fever, headache, and malaise) and low bacteremia (< 100 genomic copies [gc]/mL) during the early acute stage of illness. Early treatment with doxycycline is critical for a positive outcome, especially in Rickettsia rickettsii (Rocky Mountain spotted fever) infections where cases may be fatal within 5 to 10 days from symptom onset, emphasizing the need for more sensitive diagnostics. A real-time reverse transcriptase polymerase chain reaction (PCR) assay, RCKr, was developed and validated for Rickettsia spp. nucleic acid detection in human clinical samples. The limit of detection for RCKr was determined to be 20 gc/mL, compared with our 2013 (Kato et al.) laboratory developed test, PanR8 at 1,800 to 2,000 gc/mL. Inclusivity, exclusivity, accuracy, and precision results correlated as expected. From an evaluation of 49 banked clinical samples, RCKr detected 35 previously positive samples, as well as two specimens that were PanR8 real-time PCR negative yet clinically diagnosed as possible rickettsiosis. Ct values from RCKr clinical sample testing show a 100-fold increase relative to PanR8. Additional testing is needed to understand the clinical sensitivity of RCKr; however, this study demonstrates RCKr to have high analytical specificity and sensitivity for Rickettsia detection.

Ameliorative patterns of grey matter in patients with first-episode and treatment-naïve schizophrenia.

Grey matter (GM) reduction is a consistent observation in established late stages of schizophrenia, but patients in the untreated early stages of illness display an increase as well as a decrease in GM distribution relative to healthy controls (HC). The relative excess of GM may indicate putative compensatory responses, though to date its relevance is unclear. 343 first-episode treatment-naïve patients with schizophrenia (FES) and 342 HC were recruited. Multivariate source-based morphometry was performed to identify covarying 'networks' of grey matter concentration (GMC). Neurocognitive scores using the Cambridge Neuropsychological Test Automated Battery (CANTAB) and symptom burden using the Positive and Negative Symptoms Scale (PANSS) were obtained. Bivariate linear relationships between GMC and cognition/symptoms were studied. Compared to healthy subjects, FES had prominently lower GMC in two components; the first consists of the anterior insula, inferior frontal gyrus, anterior cingulate and the second component with the superior temporal gyrus, precuneus, inferior/superior parietal lobule, cuneus, and lingual gyrus. Higher GMC was seen in adjacent areas of the middle and superior temporal gyrus, middle frontal gyrus, inferior parietal cortex and putamen. Greater GMC of this component was associated with lower duration of untreated psychosis, less severe positive symptoms and better performance on cognitive tests. In untreated stages of schizophrenia, both a distributed lower and higher GMC is observable. While the higher GMC is relatively modest, it occurs across frontoparietal, temporal and subcortical regions in association with reduced illness burden suggesting a compensatory role for higher GMC in the early stages of schizophrenia.

Dengue virus: A review

Dengue fever is a mosquito-borne viral illness that is quickly spreading over the globe, with significant death and morbidity rates. Dengue fever is an acute viral infection transmitted by Aedes mosquitos and caused by an RNA virus from the Flaviviridae family. The symptoms might vary from asymptomatic fever to life-threatening complications including hemorrhagic fever and shock. Although dengue virus infections are normally self-limiting, the disease has become a public health concern in tropical and subtropical countries. Dengue fever is a major public health concern owing to its rapid worldwide spread, and its burdens are now unmet due to a lack of accurate therapy and a simple diagnostic approach for the early stages of illness.

Follow-up of subjects labelled with putative pre-psychotic states: Viewed from a transdiagnostic clinical high-at-risk mental state (CHARMS) paradigm

Follow-up of subjects with putative pre-psychotic states is essential to clarify the transition process to psychosis, while "non-converters" also deserve clinical attention as many may evolve into other psychiatric disorders with diverse outcomes. This study aimed to examine help-seeking individuals who have been labelled at clinical high-risk state but not converting to full-blown psychosis during first two years of follow-up. A retrospective observational cohort study of help-seeking subjects was conducted by reviewing medical records of participants in a previous early psychosis study at the study hospital between 2006 and 2020. We portrayed those who developed first episode psychosis after first 2-year follow-up in detail, and provided sketches of clinical macrophenotypes other than psychosis emerging from subjects among different risk groups. Among 132 eligible subjects, data of 98 (74.2%) were available for detailed evaluation. Of these, 15 transitioned to first-episode psychosis (11.4%) with time to psychosis from 2 to 11 years, 11 had anxiety spectrum (8.3%), 11 had depressive spectrum (8.3%), 10 had obsessive compulsive (7.6%), 5 had bipolar spectrum disorders (3.8%), 13 had predominantly schizotypal (9.8%) and 4 had other personality traits (3%), and 13 had problems attributable to adjustment or developmental issues (9.8%). Various diagnoses, either full- or sub-threshold, appropriately describe the diverse clinical phenomenology of a cohort presenting with non-specific and/or subthreshold psychotic symptoms. The clinical high-at-risk mental state (CHARMS) paradigm provides a reasonable transdiagnostic approach for orienting clinicians' attention toward young subjects seeking mental health help at an early stage of illness to potentially pluripotent trajectories.

Dynamic and progressive changes in thalamic functional connectivity over the first five years of psychosis.

The early stage of psychosis (ESP) is a critical period where effective intervention has the most favorable impact on outcomes. Thalamic connectivity abnormalities have been consistently found in psychosis, and are associated with clinical symptoms and cognitive deficits. However, most studies consider ESP patients as a homogeneous population and fail to take the duration of illness into account. In this study, we aimed to capture the progression of thalamic connectivity changes over the first five years of psychosis. Resting-state functional MRI scans were collected from 156 ESP patients (44 with longitudinal data) and 82 healthy controls (24 with longitudinal data). We first performed a case-control analysis comparing thalamic connectivity with 13 networks in the cortex and cerebellum. Next, we modelled the shape (flat, linear, curvilinear) of thalamic connectivity trajectories by comparing flexible non-linear versus linear models. We then tested the significance of the duration of illness and diagnosis in trajectories that changed over time. Connectivity changed over the ESP period between the thalamus and default mode network (DMN) and fronto-parietal network (FPN) nodes in both the cortex and cerebellum. Three models followed a curvilinear trajectory (early increase followed by a subsequent decrease), while thalamo-cerebellar FPN connectivity followed a linear trajectory of steady reductions over time, indicating different rates of change. Finally, diagnosis significantly predicted thalamic connectivity. Thalamo-cortical and thalamo-cerebellar connectivity change in a dynamic fashion during the ESP period. A better understanding of these changes may provide insights into the compensatory and progressive changes in functional connectivity in the early stages of illness.

Dynamics of Salivary Adenosine Deaminase, Haptoglobin, and Cortisol in Lipopolysaccharide-Challenged Growing Pigs.

Infectious and inflammatory conditions are common especially in growing pigs. Lipopolysaccharide (LPS) is an important antigenic structure of Gram-negative bacteria and can be used to induce inflammation experimentally. As pigs are usually group-housed in commercial conditions, it is difficult to detect sick individuals, particularly at an early stage of illness. Acute phase proteins such as haptoglobin (Hp) are known indicators of an activated innate immune system whereas adenosine deaminase (ADA) is a relatively novel inflammatory biomarker in pigs. Both parameters can be measured in saliva and could be used as indicators of inflammation. Compared with blood sampling, saliva sampling is a less stressful procedure that is rapid, non-invasive and easy to perform both at group and at individual level. In this blinded randomized clinical trial, 32 female pigs at their post-weaning phase were allocated to one of four treatments comprising two injections of the following substance combinations: saline-saline (SS), ketoprofen-saline (KS), saline-LPS (SL), and ketoprofen-LPS (KL). First, ketoprofen or saline was administered intramuscularly on average 1 h before either LPS or saline was given through an ear vein catheter. In all groups, saliva was collected prior to injections (baseline) and at 4, 24, 48, and 72 h post-injection for determination of ADA, Hp, and cortisol concentrations. A multivariate model was applied to describe the dynamics of each biomarker. Pairwise relationships between ADA, Hp, and cortisol responses from baseline to 4 h post-injection within the SL group were studied with Spearman correlations. A significant increase in the SL group was seen in all biomarkers 4 h post-injection compared to baseline and other time points (pairwise comparisons, p < 0.01 for all) and ketoprofen alleviated the LPS effect. We found a significant positive correlation between ADA and Hp within the SL group (r = 0.86, p < 0.05). The primary and novel findings of the present study are the response of ADA to LPS, its time course and alleviation by ketoprofen. Our results support the evidence that ADA and Hp can be used as inflammatory biomarkers in pigs. We suggest further studies to be conducted in commercial settings with larger sample sizes.

Exercise interventions in child and adolescent mental health care: An overview of the evidence and recommendations for implementation.

The use of physical activity interventions in mental health care for adults has a large academic evidence base and numerous examples of real-world implementation. However, the use of physical activity within mental health care for children and young people (CYP) has received less attention to date. A narrative review was conducted to summarize the relevant literature in the area. Online databases were searched using terms synonymous with CYP, exercise, physical health, and mental health. Findings from existing systematic reviews, meta-analyses, meta-syntheses, and consensus statements were reviewed, and used alongside the authors' experience to inform clinical recommendations. We first discuss the importance of applying physical health interventions in early stages of mental illness for CYP to prevent physical comorbidities and premature mortality in the long term. We then provide a brief summary of the current evidence of the benefits of exercise interventions in CYP with mental illness. We then present our top five recommendations on the implementation of exercise interventions within CYP mental health care. The key conclusions from this suggest there is an increasingly strong evidence base for the benefits of using physical activity interventions to improve, prevent, and manage physical and mental health outcomes in CYP with mental illness. However, more work needs to be done to improve the evidence base, refine its implementation into standard mental health care, and develop strategies for large-scale dissemination of such interventions across various care and cultural contexts.

Effect of high gastric residual volume on the critically ill patients' outcomes

Abstract Background: Gastrointestinal (GI) dysfunction is a danger for critically sick patients who receive mechanical breathing. During the course of enteral feeding in the early stages of critical illness, gastric residual volume (GRV) is used as a surrogate metric for GI dysfunction. This study aimed to investigate the effect of high gastric residual volume on critically ill patient outcomes. Design: A prospective, observational research design. Methods: A purposive sample of 60 adult critically ill patients of both sex from the intensive care units (ICUs) at Assiut University Hospital, Egypt were included in the study from August 2020 to April 2021. According to the measurement of gastric residual volume, those patients were not randomly allocated in group 1[the normal limit of gastric residual volume (NGRV) 500]. Five tools were used to collect data included patient's assessment tool, APACHE 11 score, nutritional intervention assessment tool, gastric residual volume assessment tool, and Patient outcomes assessment tools. Results: there was a significant decrease in the Length of ICU stay, duration of mechanical ventilation, and mortality rate in NGRV group than the HGRV group (11.04±4.12 versus 13.91±5.88, 8.43± 4.5 versus 13.02 ±5.04, 30.4% versus 70.3%) respectively. Conclusion: HGRV had an adverse effect on critically ill patients' outcomes such as high ICU mortality, long duration of mechanical ventilation and long ICU stay. Recommendation: Frequent monitoring of gastric residual volume and gastric residual volume protocol and guidelines should be applied in ICU.

Future Role of the Clinical Lab in Population Health.

Future Role of the Clinical Lab in Population Health.

Clinical Staging for Youth Mental Disorders: Progress in Reforming Diagnosis and Clinical Care

Current silo-based diagnostic systems for mental disorders lack utility and fail to fulfil a fundamental purpose of diagnosis: to guide treatment planning and predict outcomes. Diagnostic reform has gained momentum, and clinical staging has emerged as a promising framework to improve the precision of diagnosis, particularly in early illness stages, and fill current gaps in linking diagnosis to more personalized and effective intervention, prognosis, and neurobiological markers. Transdiagnostic clinical staging recognizes that the early development of mental ill-health is marked by substantial fluidity and that symptoms may, although not inevitably, evolve into more stable diagnosable syndromes. Staging facilitates the selection of interventions that are proportionate to the current need and risk of illness progression and provides an efficient framework to organize biomarker data and guide service delivery. Here, we provide an overview of transdiagnostic clinical staging and summarize key evidence supporting its ability to integrate biomarkers and guide mental health care.

Relationship of subjective quality of life with symptomatology, neurocognition and psychosocial functioning in first-episode psychosis: a structural equation modelling approach.

Subjective quality of life (SQoL) represents an important outcome of psychotic disorders. However, determinants of SQoL and their complex inter-relationships in the early course of illness remain to be clarified. Association between neurocognitive impairment and SQoL in first-episode psychosis (FEP) is understudied. This study employed structural equation modeling (SEM) to examine relationships among SQoL, depressive, positive and negative symptoms, neurocognition, and psychosocial functioning in FEP patients. Three hundred and forty-seven patients aged 25-55years presenting with FEP to early intervention program in Hong Kong were recruited. Assessment encompassing symptom profiles, psychosocial functioning and a battery of neurocognitive tests were conducted. SF-12 mental component summary scores were computed as the primary measure of SQoL. Our correlation analyses revealed differential relationships between negative symptom subdomains and SQoL, with amotivation, but not diminished expression, being related to SQoL. Final SEM model yielded a good model fit (comparative fix index = 0.94; root mean square error of approximation = 0.05; standardized root mean square residuals = 0.07) and demonstrated that depression, positive symptoms and psychosocial functioning were directly associated with SQoL, with depression showing the strongest effect. Amotivation, neurocognition and positive symptoms had an indirect effect on SQoL via the mediation of psychosocial functioning. This study affirms depression as a critical determinant of subjective mental wellbeing, and underscores an intermediary role of psychosocial functioning in linking amotivation, neurocognitive impairment and positive symptoms to SQoL in FEP patients. Depression and functional impairment thus constitute as crucial therapeutic targets for improvement of SQoL in the early illness stage.