ReviewMolecular psychiatry2026
Depression in neurodegenerative disease: neurobiological mechanisms and emerging treatments.
Review in Molecular psychiatry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Depression is one of the most common and disabling neuropsychiatric complications of neurodegenerative diseases. In Alzheimer's disease (AD) and Parkinson's disease (PD), depressive syndromes affect more than one-third of patients and are associated with accelerated cognitive decline, reduced quality of life, and increased healthcare utilisation. Despite this burden, current antidepressant treatments show little or no efficacy in these populations, suggesting that depression arising in the context of neurodegeneration may reflect distinct underlying neurobiological mechanisms. Emerging evidence from molecular imaging, neuropathology, and cognitive neuroscience indicates disease-specific disruption of monoaminergic, glutamatergic, inflammatory, and reward-related circuits in AD and PD. These alterations may undermine the mechanisms of action of standard antidepressants and contribute to treatment resistance. Yet patients with cognitive impairment are routinely excluded from antidepressant trials, and few high-quality studies have evaluated novel therapies in neurodegenerative disease. In this narrative review, we synthesise current evidence on the neurobiological mechanisms underpinning depression in AD and PD and critically evaluate emerging pharmacological and neuromodulatory therapies targeting glutamatergic, serotonergic, dopaminergic, immune, and circuit-level dysfunction. Here, we highlight that depression in neurodegenerative disease offers a unique and underutilised model for mechanistically guided antidepressant development. We identify how interventions including glutamate modulators, dopaminergic agents, kappa opioid antagonists, immune-modulating therapies, and next-generation brain stimulation approaches may offer therapeutic promise. By aligning treatment development with disease-specific circuit and molecular pathology, this framework may improve outcomes for this neglected population while advancing precision psychiatry more broadly.
Identifiers
42410083What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.