Anhedonia is a core symptom of postpartum depression, yet the underlying neurobiological mechanisms remain poorly understood. Emerging evidence suggests that postpartum biological adaptations, including sleep disruption, stress, hormonal fluctuations, and immune remodeling, may influence neural systems involved in motivation. In this review, we examine neuroinflammation as a potential contributor to maternal anhedonia through its effects on dopamine-dependent reward circuitry. We propose two complementary mechanisms by which inflammatory signaling may disrupt motivation: (1) local inflammatory effects within nucleus accumbens microcircuits regulating dopamine release; and (2) dysfunction of corticostriatal networks, whereby inflammation impairs prefrontal regulation and reward valuation processes, leading to downstream anhedonia. We further review neuroimaging evidence supporting reward-system abnormalities in postpartum depression and discuss how multimodal imaging approaches may help distinguish between proposed mechanistic models. Understanding these pathways may facilitate development of biologically informed interventions targeting maternal anhedonia.
Resting-state functional connectivity (rsFC) of the subgenual anterior cingulate cortex (sgACC) may predict response to neuromodulation in major depressive disorder (MDD). We conducted a systematic review of studies examining pre-treatment sgACC rsFC and subsequent neuromodulation outcomes in adults (18–70 years) with MDD. Ovid MEDLINE, Embase, and APA PsycINFO were searched from inception to May 2, 2025 (PROSPERO: CRD420251038212). The primary outcome was the association between pre-treatment sgACC rsFC and change in depressive symptoms. Study quality was assessed using National Institutes of Health tools and established neuroimaging quality checklists. Reported sgACC coordinates were classified descriptively by analytic role; no inferential coordinate-based meta-analysis was performed. Twenty-two studies (N = 1366 participants) met inclusion criteria. Greater baseline sgACC–right dorsolateral prefrontal cortex rsFC was associated with reduced symptom improvement in some studies, whereas stronger sgACC–medial orbitofrontal cortex rsFC was associated with greater improvement. Associations were reported most often in repetitive transcranial magnetic stimulation (rTMS) studies, particularly with individualized targeting, but several studies were null. Reported sgACC coordinates were predominantly investigator-defined seed or region-of-interest locations and were not treated as response-associated peaks. Magnetic resonance imaging (MRI) methodological quality was adequate (mean = 16.1/20, range 13–18). Pre-treatment sgACC–prefrontal rsFC may help predict neuromodulation response in MDD, particularly in rTMS studies using individualized targeting. However, findings were heterogeneous, and the available coordinate evidence did not support inferential spatial-convergence analysis. Larger prospective studies are needed to establish reproducibility and clinical utility.
Functional neurological disorder (FND) sits at the intersection of psychiatry and neurology, producing disabling motor and sensory symptoms despite intact peripheral pathways. FND may reflect altered precision weighting within neural systems, such that the brain generates the dysfunction it predicts. Stress is among the most consistent precipitants, yet how it produces functional symptoms remains mechanistically unspecified. The present account proposes that FND arises from over-precision of maladaptive priors relative to afferent sensory evidence within insula–cingulate–sensorimotor circuits under stress-mediated neuromodulation. Chronic or traumatic stress is proposed to recalibrate precision through hypothalamic–pituitary–adrenal axis dysregulation and noradrenergic modulation. The proposed result is that overly precise expectations about bodily dysfunction dominate proprioceptive and motor inference and override ascending feedback. What may distinguish FND from other stress-linked conditions is the sensorimotor locus of these priors and their implementation in motor control systems. The mechanism is mapped onto circuits including the anterior insula, dorsal anterior cingulate cortex, supplementary motor area, and temporoparietal junction. Falsifiable predictions are derived at algorithmic, neural, and physiological levels, each with an explicit disconfirmation criterion. A discriminative prediction separates this account from competing models. Attenuation of insula prediction-error signalling during voluntary movement should be greater with stress-system dysregulation and may ease under acute reduction of arousal, whereas sensory-gain and attentional-capture models predict no such modulation. The framework offers a possible account of why verbal reassurance alone may be insufficient and provides a computational basis for physiotherapy and, if validated, for pre-treatment precision profiling to help guide treatment planning.
Background Adolescence is a critical period for the emergence of obesity and disordered eating behaviours, yet the biological mechanisms underlying persistent differences in body mass index (BMI) development remain poorly understood. We investigated whether longitudinal BMI profiles are associated with behavioural, neurodevelopmental, and epigenetic variation during adolescence. Methods Participants from the IMAGEN cohort (N = 1,296) were followed from ages 14 to 23 years. Latent profile analysis identified longitudinal BMI profiles. Disordered eating behaviours were repeatedly assessed across adolescence. Structural MRI acquired at ages 14 and 23 characterised longitudinal changes in grey matter volume (GMV), cortical thickness (CT), and sulcal depth (SD). Genome-wide DNA methylation was measured in whole blood at age 14. Epigenome-wide association studies (EWAS), functional enrichment analyses, and a DNA methylation-based BMI risk score (bmiMRS) were conducted. Results Two distinct BMI profiles were identified: a persistently overweight group and a persistently normal-weight group. Adolescents with persistent overweight showed progressively increasing BMI, greater eating-, weight-, and shape-related concerns, and more frequent dieting and binge-eating behaviours. They also exhibited atypical cortical maturation, characterised by attenuated cortical thinning, accelerated reductions in sulcal depth, and reduced grey matter volume loss within frontal and temporal association cortices. EWAS identified 29 BMI-associated CpGs (Bonferroni-corrected P < 1.3×10-7), enriched for genes involved in adipogenesis, immune and inflammatory signalling, type 2 diabetes, and brain-related biological processes. The bmiMRS predicted BMI, cumulative BMI across adolescence, and membership of the persistently overweight group, and remained significantly associated with BMI in an independent cohort. Longitudinal analyses further suggested reciprocal associations between BMI and brain maturation, with higher BMI in early adolescence predicting subsequent regional GMV changes, whereas lower baseline cortical thickness predicted greater BMI increases independently of baseline BMI. Conclusions Persistent adolescent overweight is associated with distinct behavioural, neurodevelopmental, and peripheral epigenetic signatures. Integrating longitudinal neuroimaging and DNA methylation identifies molecular biomarkers and brain developmental features associated with sustained BMI elevation, providing a framework for earlier risk stratification and informing biologically grounded approaches to obesity prevention.
