Antipsychotic-induced Weight Gain Research Articles

Development of antipsychotic-induced weight gain management guidance: patient experiences and preferences - a qualitative descriptive study

Abstract Introduction It is estimated that 50% of patients with a severe mental illness (SMI) do not adhere to their medication regimen. Antipsychotic-induced weight gain (AIWG) is one of the most common reasons for patient disengagement with treatment.[1] Clinically significant weight gain has been linked to almost all antipsychotics and contributes significantly to the 2-3-fold higher rates of obesity seen in psychiatry.[2] Given the personal, social, and healthcare costs of overweight, obesity and relapse of mental illness, effectively managing AIWG is a priority for patients, clinicians, and policymakers. However, effectively managing AIWG is challenging. Sparse guidance for clinicians invariably contributes to management complexity. An important barrier to the development of high-quality AIWG management guidance is the lack of empirical research assessing patient values and preferences for management and other key guideline decision-making criteria including acceptability, feasibility, and equity considerations. Integration of patient experiences and preferences for management into guidance informing practice is essential to ensure recommendation relevance, applicability, and transferability. Aim To elicit the values and preferences of those with lived experience of AIWG regarding preferred management. Methods Qualitative descriptive methodology was used as it avoids high-level interpretation and theory development in data analysis and results in outputs that can be more readily implementable by policymakers and guideline developers. The study recruited adult outpatients attending a secondary psychiatric care setting with a diagnosis of a SMI and experience of AIWG. Purposive sampling informed recruitment whereby participants who had a diverse range of experiences of AIWG were recruited. Participants took part in online semi-structured interviews. Reflexive thematic analysis informed data analysis. Results Seventeen participants were recruited (24% male; mean age: 51.7 years [range: 26-66]). Participants conceptualised preferred AIWG management as being individualised, proactive, collaborative, and holistic. Participants were asked how the tenets of preferred management could be realised in practice and within clinician management guidance. Results are summarised in Figure 1. Conclusion Use of this research by guideline developers will provide opportunities to maximise the impact of recommendations in practice for those funding, providing, and using services. The opportunity to include a culturally diverse group was unavailable, which may limit transferability of study findings.

Associations between antipsychotics-induced weight gain and brain networks of impulsivity

Given the unpredictable rapid onset and ubiquitous consequences of weight gain induced by antipsychotics, there is a pressing need to get insights into the underlying processes at the brain system level that will allow stratification of “at risk” patients. The pathophysiological hypothesis at hand is focused on brain networks governing impulsivity that are modulated by neuro-inflammatory processes. To this aim, we investigated brain anatomy and functional connectivity in patients with early psychosis (median age: 23 years, IQR = 21–27) using anthropometric data and magnetic resonance imaging acquired one month to one year after initiation of AP medication. Our analyses included 19 patients with high and rapid weight gain (i.e., ≥5% from baseline weight after one month) and 23 patients with low weight gain (i.e., <5% from baseline weight after one month). We replicated our analyses in young (26 years, IQR = 22–33, N = 102) and middle-aged (56 years, IQR = 51–62, N = 875) healthy individuals from the general population. In early psychosis patients, higher weight gain was associated with poor impulse control score (β = 1.35; P = 0.03). Here, the observed brain differences comprised nodes of impulsivity networks - reduced frontal lobe grey matter volume (Pcorrected = 0.007) and higher striatal volume (Pcorrected = 0.048) paralleled by disruption of fronto-striatal functional connectivity (R = −0.32; P = 0.04). Weight gain was associated with the inflammatory biomarker plasminogen activator inhibitor-1 (β = 4.9, P = 0.002). There was no significant association between increased BMI or weight gain and brain anatomy characteristics in both cohorts of young and middle-aged healthy individuals. Our findings support the notion of weight gain in treated psychotic patients associated with poor impulse control, impulsivity-related brain networks and chronic inflammation.

Trajectories and Predictors for the Development of Clinically Significant Weight Gain in Children and Adolescents Prescribed Second-Generation Antipsychotics.

Background: As many as 60% of pediatric patients taking second-generation antipsychotics (SGA) experience weight gain (antipsychotic-induced weight gain). However, the subgroup that experienced substantial weight increase was poorly understood. This study aimed to identify the development and predictors of clinically significant weight gain (CSWG) among pediatric SGA recipients. Methods: A retrospective analysis of the 2016 to 2021 IQVIA Ambulatory EMR-US database was conducted. The study cohort comprised SGA-naive patients ages 5 to 19, continuously prescribed SGA for ≥90 days. CSWG was defined as a weight gain in BMI z-score >0.5. The development of CSWG was described using the group-based trajectory model approach, and multinomial logistic regression analysis was conducted to examine the risk factors associated with the CSWG trajectories. Results: Of the 16,262 SGA recipients who met the inclusion criteria, 4 distinctive CSWG trajectories were identified: (1) Rapid (14.6%), (2) Gradual (12.6%), (3) Transit (7%), and (4) no CSWG (65.8%). Factors associated with a higher likelihood of having rapid or gradual CSWG versus nonsignificant weight gain were being younger (OR [95% CI] = 12-17 vs. 5-11, Rapid, 0.727 [0.655-0.806]; Gradual, 0.776 [0.668-0.903]), male (Rapid, 1.131 [1.021-1.253]), non-Hispanic White (Black vs. White: Rapid, 0.833 [0.709-0.98]), with lower baseline BMI z-score (Rapid, 0.376 [0.361-0.392]; Gradual, 0.449 [0.424-0.476]), and receiving olanzapine as the initial SGA (Rapid, 1.38 [1.093-1.74]). The Area under the Receiver operating characteristic (ROC) Curve for the comparison of rapid and gradual CSWG with no CSWG trajectory were 0.83 and 0.80, respectively. Conclusions: SGA recipients experienced four distinctive CSWG trajectories (Rapid, Gradual, Transient, and No CSWG). The risk of CSWG could be predicted using patient characteristics at the SGA initiation. This insight highlights the importance of personalized monitoring and timely intervention strategies for at-risk individuals who experienced persistent CSWG in real practice.

Genome-wide association study implicates lipid pathway dysfunction in antipsychotic-induced weight gain: multi-ancestry validation

Genome-wide association study implicates lipid pathway dysfunction in antipsychotic-induced weight gain: multi-ancestry validation

The effect of continuous theta burst stimulation on antipsychotic-induced weight gain in first-episode drug-naive individuals with schizophrenia: a double-blind, randomized, sham-controlled feasibility trial

Antipsychotic intake may induce weight gain in drug-naive individuals with schizophrenia, leading to poor compliance in clinical management. However, there is still a lack of effective approaches to treat or prevent this side-effect. Therefore, we conducted this pilot study to investigate the effect of continuous theta burst stimulation (cTBS), a non-invasive magnetic stimulation technique, on preventing olanzapine-induced weight gain. Thirty-nine first-episode drug-naive individuals with schizophrenia were randomly assigned to receive either the active or sham cTBS intervention for 25 sessions (5 times per day for 5 consecutive days). The primary outcomes were changes in body weight and body mass index (BMI). Secondary outcomes included psychiatric symptoms, eating behavior scales, behavior tasks, and metabolic measures. For the result, the body weight and BMI increased significantly in the sham group but not in the active group, with a significant group effect. The active group exhibited a selective increase in the cognitive restraint domain in the Three-Factor Eating Questionnaire (TFEQ-CR) and a decrease in stop-signal reaction time compared to the sham group. The effect of cTBS on body weight was mediated by TFEQ-CR. Our findings demonstrated the feasibility that cTBS intervention could be a potential method for preventing olanzapine-induced weight gain in drug-naive first-episode schizophrenia patients through enhancing cognitive restraint to food. Trial registration: clinical trial registered with clinicaltrials.gov (NCT05086133).

Effectiveness of lifestyle intervention on prevention/management of antipsychotic-induced weight gain among persons with severe mental illness: A systematic review and meta-analysis.

Individualized lifestyle interventions using motivational interviewing (MI) approach are recommended for persons with severe mental illness (SMI) for effective weight management. The aim of this meta-analysis was to assess the effectiveness of various lifestyle interventions that addressed obesity among persons with SMI. Twelve RCTs were assessed by individual reviewers using revised cochrane risk-of-bias tool (RoB 2). The standardized mean difference (SMD) was calculated with a 95% CI. The age of participants was between 18 and 70 years. Waist circumference showed an SMD of -0.09 (-0.22, 0.03), weight -0.03 (-0.10, 0.15) and BMI -0.07 (-0.07, 0.22). The findings in this meta-analysis revealed that though lifestyle interventions were statistically insignificant in reducing antipsychotic induced weight gain among persons with SMI, they show changes in intervention group. Psychosocial management along with lifestyle interventions, and MI are effective in the management of antipsychotic induced weight gain.

A Realist Evaluation of Social Care Practitioners' Experiences With and Understanding of Applied Healthcare Research.

Social care practitioners are often under-represented in research activity and output. Evidence-based practice enables social care practitioners to develop/engage the skills to evaluate evidence and be more actively involved in research. REalist Synthesis Of non-pharmacologicaL interVEntions for antipsychotic-induced weight gain (RESOLVE) is a NIHR-funded study where realist synthesis is used to understand and explain how, why, for whom, and in what contexts non-pharmacological interventions help service users, with severe mental illness, to manage antipsychotic-induced weight gain. Social care practitioners are a key part of the team providing care for people living with severe mental illness and therefore supporting antipsychotic-induced weight gain. The current study, RESOLVE 2, uses realist evaluation and RESOLVE as an illustrative example to help understand why and how social care practitioners engage (or not) with research. Semi-structured, audio-recorded interviews will be undertaken with a purposive sample of approximately 20 social care practitioners working with people who have severe mental illness, are treated with antipsychotics, and have experienced weight gain. Participants will be recruited from NHS Trusts and recruitment avenues such as social media and personal networks. Topics discussed during interviews will include barriers and facilitators to engagement in research, current, and past engagement as well as recommendations for researchers and other practitioners. Interview recordings will be transcribed verbatim and analyzed using realist evaluation which will allow in-depth causal explanations for research engagement. Better understanding of research engagement by social care practitioners will allow for evidence-based practice and better patient outcomes within these settings.

The Effectiveness of Metformin in Managing Second Generation Antipsychotic-Induced Weight Gain in Children and Adolescents.

The Effectiveness of Metformin in Managing Second Generation Antipsychotic-Induced Weight Gain in Children and Adolescents.

Association of clinical parameters and polygenic risk scores for body mass index, schizophrenia, and diabetes with antipsychotic-induced weight gain

Antipsychotic-induced weight gain (AIWG) is a common adverse event in schizophrenia. Genome-wide association studies (GWAS) and polygenic risk scores (PRS) for other diseases or traits are recent approaches to disentangling the genetic architecture of AIWG.200 patients with schizophrenia treated monotherapeutically with antipsychotics were included in this study. A multiple linear regression analysis with ten-fold crossvalidation was performed to predict the percentage weight change after five weeks of treatment. Independent variables were sex, age, body mass index (BMI) at baseline, medication-associated risk, and PRSs (BMI, schizophrenia, diabetes, and metabolic syndrome). An explorative GWAS analysis was performed on the same subjects and traits.PRSs for BMI (β = 3.78; p = 0.0041), schizophrenia (β = 5.38; p = 0.021) and diabetes type 2 (β = 13.4; p = 0.046) were significantly associated with AIWG. Other significant factors were sex, baseline BMI and medication. Compared to the model without genetic factors, the addition of PRSs for BMI, schizophrenia, and diabetes type 2 increased the goodness of fit by 6.5 %. The GWAS identified the association of three variants (rs10668573, rs10249381 and rs1988834) with AIWG at a genome-wide level of p < 1 · 10−6.Using PRS for schizophrenia, BMI, and diabetes type 2 increased the explained variation of predicted weight gain, compared to a model without PRSs. For more precise results, PRSs derived from other traits (ideally AIWG) should be investigated. Potential risk variants identified in our GWAS need to be further investigated and replicated in independent samples.

Antipsychotic-Induced Weight Gain in Severe Mental Illness: Risk Factors and Special Considerations.

Weight gain is a disconcerting issue experienced by patients treated with antipsychotics (APs). This review summarizes current knowledge on the prevalence, etiology, and risk factors for antipsychotic-induced weight gain (AIWG), and evidence for interventions, including special considerations. Predisposing risk factors for AIWG include lack of prior AP exposure, sex, and age. AP dose and duration of exposure are additional treatment-related factors that may contribute to this issue. Among current approaches to target AIWG, metformin has the most evidence to support its use, and this is increasingly reflected in clinical guidelines. While lifestyle approaches are recommended, cost-effectiveness and scalability represent limitations. More research is needed to identify newer treatment options and inform clinical recommendations for AIWG. Concerns around scope of practice in psychiatry to address AIWG and related comorbidities will require enhanced training opportunities and interdisciplinary collaborations, as well as updated position statements/practice guidelines emphasizing prevention.

The potential effect of metformin on cognitive and other symptom dimensions in patients with schizophrenia and antipsychotic-induced weight gain: a systematic review, meta-analysis, and meta-regression.

Metformin has shown good efficacy in the management of antipsychotic-induced metabolic syndrome (MetS) in patients with schizophrenia or schizoaffective disorders. Its ability to induce antidepressant behavioural effects and improve cognitive functions has also been investigated: yet information has not been systematized. The aim of this study was therefore to investigate the effects of metformin on cognitive and other symptom dimension in schizophrenic patients treated with antipsychotics through a systematic review and meta-analysis. We searched PubMed, ClinicalTrials.Gov, Embase, PsycINFO, and WHO ICTRP database up to February 2022, Randomised Controlled Trials (RCT) evaluating patients diagnosed with schizophrenia and related disorders, who were treated with metformin as add-on therapy to antipsychotics for the treatment of weight gain and in which changes in psychiatric symptoms and cognitive functions were evaluated. A total of 19 RCTs met the inclusion criteria. Meta-analysis was performed on 12 eligible studies. We found a positive trend after 24 weeks of treatment in schizophrenic patients with stable conditions [SMD (95%CI) = -0.40 (-0.82;0.01), OR (95%CI) = 0.5 (-2.4;3.4)]. Better performance was detected in the Brief Assessment of Cognition in Schizophrenia and Positive and Negative Syndrome Scale (PANSS) with low heterogeneity among studies. One study reported changes in BACS-verbal memory subdomain in favour of placebo [MD (95%CI) = -16.03 (-23.65;8.42)]. Gastrointestinal disorders, xerostomia, and extrapyramidal syndrome were the most reported adverse effects. Psychiatric adverse events were also described: in particular, symptoms attributable to a relapse of schizophrenia. Some degree of efficacy was found for Metformin in improving cognitive and other symptom dimensions in patients with Schizophrenia. Given the clinical relevance of this potential pharmacological effect, longer specific studies using adequate psychometric scales are strongly recommended. Likewise, how metformin acts in this context needs to be evaluated in order to enhance its efficacy or find more efficacious drugs.

Pharmacological Interventions for the Prevention of Antipsychotic-Induced Weight Gain in People With Schizophrenia: A Cochrane Systematic Review and Meta-Analysis.

Patients with schizophrenia are burdened by higher rates of obesity, cardiovascular disease and reduced life expectancy than the general population. In addition to illness, genetic and lifestyle factors, the associated weight gain and metabolic adverse effects of antipsychotic (AP) medications are known to exacerbate and accelerate these cardiometabolic problems significantly. Given the detrimental consequences of weight gain and other metabolic disturbances, there is an urgent need for safe and effective strategies to manage these issues as early on as possible. This review summarizes the literature of adjunctive pharmacological interventions aimed at preventing AP-induced weight gain.

Effects of semaglutide on body weight in clozapine-treated people with schizophrenia and obesity: study protocol for a placebo-controlled, randomised multicentre trial (COaST)

Background People with schizophrenia die almost 20 years earlier than the general population, most commonly from avertable cardiometabolic disease. Existing pharmacological weight-loss agents including metformin have limited efficacy. Recently available glucagon-like peptide (GLP-1) receptor agonists such as semaglutide have shown promise for weight loss but have yet to be trialled in this population. Aims To examine the efficacy of semaglutide to ameliorate antipsychotic-induced obesity in people with schizophrenia who have been treated with clozapine for more than 18 weeks. Method This is a 36-week, double-blinded, randomised placebo-controlled trial. We will recruit 80 clozapine-treated patients with schizophrenia or schizoaffective disorder, aged 18–64 years, with a baseline body mass index ≥26 kg/m2, who will be randomised to subcutaneous semaglutide of 2.0 mg once a week or placebo for 36 weeks. The primary endpoint will be percentage change in body weight from baseline. Results This trial will assess the efficacy and side-effects of the GLP-1 receptor agonist semaglutide on body weight and provide evidence on the possible clinical utility of semaglutide in patients with inadequate response to metformin. The study is registered with the Australian New Zealand Clinical Trials Registry (www.anzctr.org.au) with clinical trial registration number ACTRN12621001539820. Conclusion This research could benefit individuals with schizophrenia who experience significant health issues, leading to premature mortality, owing to antipsychotic-induced weight gain. Study findings will be disseminated through peer-reviewed publications and conference presentations.

Histaminergic regulation of food intake.

Histamine is a biogenic amine that acts as a neuromodulator within the brain. In the hypothalamus, histaminergic signaling contributes to the regulation of numerous physiological and homeostatic processes, including the regulation of energy balance. Histaminergic neurons project extensively throughout the hypothalamus and two histamine receptors (H1R, H3R) are strongly expressed in key hypothalamic nuclei known to regulate energy homeostasis, including the paraventricular (PVH), ventromedial (VMH), dorsomedial (DMH), and arcuate (ARC) nuclei. The activation of different histamine receptors is associated with differential effects on neuronal activity, mediated by their different G protein-coupling. Consequently, activation of H1R has opposing effects on food intake to that of H3R: H1R activation suppresses food intake, while H3R activation mediates an orexigenic response. The central histaminergic system has been implicated in atypical antipsychotic-induced weight gain and has been proposed as a potential therapeutic target for the treatment of obesity. It has also been demonstrated to interact with other major regulators of energy homeostasis, including the central melanocortin system and the adipose-derived hormone leptin. However, the exact mechanisms by which the histaminergic system contributes to the modification of these satiety signals remain underexplored. The present review focuses on recent advances in our understanding of the central histaminergic system's role in regulating feeding and highlights unanswered questions remaining in our knowledge of the functionality of this system.

EPH137 Group-Based Trajectory Modeling to Identify Patterns of Antipsychotic-Induced Weight Gain Among Children and Adolescents

Antipsychotic-induced weight gain (AIWG) is the most common side effect associated the use of second-generation antipsychotic (SGA) medications among children and adolescents. Group-based trajectory model (GBTM) can graphically display the longitudinal weight change overtime. The objective of this study was to model the development of AIWG among children and adolescents taking SGAs.

Mice lacking Ptprd exhibit deficits in goal-directed behavior and female-specific impairments in sensorimotor gating.

Protein Tyrosine Phosphatase receptor type D (PTPRD) is a member of the protein tyrosine phosphatase family that mediates cell adhesion and synaptic specification. Genetic studies have linked Ptprd to several neuropsychiatric phenotypes, including Restless Leg Syndrome (RLS), opioid abuse disorder, and antipsychotic-induced weight gain. Genome-wide association studies (GWAS) of either pediatric obsessive-compulsive traits, or Obsessive-Compulsive Disorder (OCD), have identified loci near PTPRD as genome-wide significant, or strongly suggestive for this trait. We assessed Ptprd wild-type (WT), heterozygous (HT), and knockout (KO) mice for behavioral dimensions that are altered in OCD, including anxiety and exploration (open field test, dig test), perseverative behavior (splash-induced grooming, spatial d), sensorimotor gating (prepulse inhibition), and home cage goal-directed behavior (nest building). No effect of genotype was observed in any measure of the open field test, dig test, or splash test. However, Ptprd KO mice of both sexes showed impairments in nest building behavior. Finally, female, but not male, Ptprd KO mice showed deficits in prepulse inhibition, an operational measure of sensorimotor gating that is reduced in female, but not male, OCD patients. Our results indicate that constitutive lack of Ptprd may contribute to the development of certain domains that are altered OCD, including goal-directed behavior, and reduced sensorimotor gating specifically in females.

Identification of four novel loci associated with psychotropic drug-induced weight gain in a Swiss psychiatric longitudinal study: A GWAS analysis

Patients suffering from mental disorders are at high risk of developing cardiovascular diseases, leading to a reduction in life expectancy. Genetic variants can display greater influence on cardiometabolic features in psychiatric cohorts compared to the general population. The difference is possibly due to an intricate interaction between the mental disorder or the medications used to treat it and metabolic regulations. Previous genome wide association studies (GWAS) on antipsychotic-induced weight gain included a low number of participants and/or were restricted to patients taking one specific antipsychotic. We conducted a GWAS of the evolution of body mass index (BMI) during early (i.e., ≤ 6) months of treatment with psychotropic medications inducing metabolic disturbances (i.e., antipsychotics, mood stabilizers and some antidepressants) in 1135 patients from the PsyMetab cohort. Six highly correlated BMI phenotypes (i.e., BMI change and BMI slope after distinct durations of psychotropic treatment) were considered in the analyses. Our results showed that four novel loci were associated with altered BMI upon treatment at genome-wide significance (p < 5 × 10−8): rs7736552 (near MAN2A1), rs11074029 (in SLCO3A1), rs117496040 (near DEFB1) and rs7647863 (in IQSEC1). Associations between the four loci and alternative BMI-change phenotypes showed consistent effects. Replication analyses in 1622 UK Biobank participants under psychotropic treatment showed a consistent association between rs7736552 and BMI slope (p = 0.017). These findings provide new insights into metabolic side effects induced by psychotropic drugs and underline the need for future studies to replicate these associations in larger cohorts.

Antipsychotic-induced weight gain: exploring the role of psychiatrists in managing patients' physical health - challenges, current options and direction for future care.

Antipsychotics and severe mental illness (SMI) are associated with weight gain, and obesity increases the risks of cardiometabolic disease and premature death. These present management and liability issues for psychiatrists. Physical healthcare for people with SMI is poor, and this may partly be owing to training limitations and lack of proactiveness by psychiatrists. Ethically and legally, psychiatrists have a duty to avoid unnecessary harm and to maintain an acceptable standard of care. This would apply particularly to patients receiving compulsory treatment for their SMI owing to their vulnerability. Discrepancy between psychiatric and non-psychiatric approaches to pharmacological treatment creates ambiguity, and weight gain could demotivate antipsychotic adherence. This article explores how the Mental Health Act could be used to address these issues, and the ethical considerations, and proposes how long-acting glucagon-like peptide-1 receptor agonists could be introduced into existing psychiatric practice as a treatment option for antipsychotic-induced weight gain and obesity in SMI.

Polygenic risk scores analyses of psychiatric and metabolic traits with antipsychotic-induced weight gain in schizophrenia: an exploratory study.

Given the polygenic nature of antipsychotic-induced weight gain (AIWG), we investigated whether polygenic risk scores (PRS) for various psychiatric and metabolic traits were associated with AIWG. We included individuals with schizophrenia (SCZ) of European ancestry from two cohorts (N = 151, age = 40.3 ± 11.8 and N = 138, age = 36.5 ± 10.8). We investigated associations of AIWG defined as binary and continuous variables with PRS calculated from genome-wide association studies of body mass index (BMI), coronary artery disease (CAD), fasting glucose, fasting insulin, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides, type 1 and 2 diabetes mellitus, and SCZ, using regression models. We observed nominal associations (uncorrected p < 0.05) between PRSs for BMI, CAD, and LDL-C, type 1 diabetes, and SCZ with AIWG. While results became non-significant after correction for multiple testing, these preliminary results suggest that PRS analyses might contribute to identifying risk factors of AIWG and might help to elucidate mechanisms at play in AIWG.

The positive association between antipsychotic-induced weight gain and therapeutic response: New biotypes of schizophrenia

Co-occurrence of antipsychotic-induced weight gain (AIWG) and therapeutic response (TR) did exist in clinic but was rarely studied. This study aims to identify potential TR/ AIWG biotypes and explore the clinical, genetic and neuroimaging features. This study enrolled 3030 patients to identify potential TR/AIWG biotypes and explore the clinical, genetic and neuroimaging features. We found three biotypes: TR+nonAIWG (46.91%), TR+AIWG (18.82%), and nonTR+nonAIWG (34.27%). TR+AIWG showed lower weight and lipid level at baseline, but higher changing rate, and higher genetic risk of obesity than TR+nonAIWG and nonTR+nonAIWG. GWAS identified ADIPOQ gene related to TR+AIWG biotypes and top-ranked loci enriched in one-carbon metabolic process, which related to both schizophrenia and metabolic dysfunction. Genetically predicted TR+AIWG was associated with higher odds of diabetes (OR=1.05). The left supplementary motor area was significantly negatively correlated with PRS of obesity. The distinguishing ability with multi-omics data to identify TR+AIWG reached 0.787. In a word, the “thin” patients with a higher risk of obesity are the target population of early intervention.