Serotonergic underpinnings of obsessive‐compulsive disorder: A systematic review and meta‐analysis of neuroimaging findings
Bibliographic record
Abstract
Obsessive-compulsive disorder (OCD) is a frequent and disabling condition, with many patients being treatment-resistant. Improved understanding of its neurobiology is vital for better therapies. Evidence is still conflicting regarding specific serotonergic-related dysfunctions in OCD. We systematically reviewed the literature to provide a quantitative assessment of the role of serotonin (5-HT) in patients with untreated OCD through imaging. We searched for neuroimaging studies investigating central 5-HT tonus in unmedicated patients with OCD, excluding studies comprising treated patients to prevent bias from antidepressant-induced changes in serotonergic tonus. We also conducted a meta-analysis using a homogeneous group of positron emission tomography and single photon emission computed tomography articles that compared 5-HT transporter (SERT) and 5-HT2A receptor (HT2AR) binding potential in different brain regions of patients with untreated OCD and healthy controls. The systematic review encompassed 18 articles, with 13 included in the subsequent meta-analysis. Risk of bias was assessed by a revised form of the Newcastle-Ottawa Scale. We provided standardized mean difference (SMD) values for SERT and 5-HT2AR binding potential measures across 15 different brain regions. Patients with OCD showed lower SERT binding potential in the brainstem (SMD = -1.13, 95% CI [-1.81 to -0.46]), midbrain (SMD = -0.54, 95% CI [-0.92 to -0.16]), and thalamus/hypothalamus regions (SMD = -0.58, 95% CI [-0.99 to -0.18]) with neglectable to moderate heterogeneity. By combining results from 2 decades of molecular imaging studies, we show that individuals with OCD exhibit lower SERT binding potential in specific brain regions, providing compelling evidence of a 5-HT system dysfunction. However, the exact mechanisms underlying this phenotype remain elusive. The limitations include heterogeneity across studies in populations, imaging techniques, and radiotracer usage.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.011 | 0.004 |
| Bibliometrics | 0.001 | 0.004 |
| Science and technology studies | 0.000 | 0.002 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".