Cell-specific expression of APP and GABA(B)R1 isoforms in wild-type and the APP NL-G-F mouse model of Alzheimer's disease.

Depression and anxiety are prevalent psychiatric disorders characterised by mood dysregulation, psychological distress, and significant impairment. Beyond their neurochemical underpinnings, these disorders have been increasingly associated with alterations in immuneinflammatory activity. Clinical and epidemiological studies over the past two decades have converged on the finding that a subset of individuals with major depressive disorder (MDD) exhibit elevated levels of pro-inflammatory biomarkers in peripheral blood (; ). Concentrations of C-reactive protein (CRP) and interleukin-6 (IL-6) in particular are often higher in patients with depression compared to non-depressed controls (; ). Meta-analyses indicate that other cytokines – including IL-1β, TNF-α, IL-12, and IL-18 – are also upregulated on average in depression, alongside acute-phase reactants like CRP (; ). Collectively, this body of evidence has given rise to the “cytokine hypothesis” of depression, which proposes that excess peripheral inflammation can induce neurobiological changes contributing to depressive symptoms (e.g. cytokine effects on neurotransmitters and the HPA axis). Anxiety disorders have received comparatively less focus in inflammation research, but interest is growing in their immunological aspects. Depression and anxiety frequently co-occur, and some immune findings appear overlapping. For example, generalised anxiety disorder (GAD) has been associated with elevated CRP and certain cytokines in population studies (; ). However, results have been mixed, with some studies showing minimal or no inflammatory differences in pure anxiety states after accounting for depression comorbidity (). PTSD-related symptoms are also relevant to this review because trauma exposure and post-traumatic symptoms share affective and inflammatory features with anxiety-related conditions; however, PTSD is classified in DSM-5/DSM-5-TR as a trauma- and stressor-related disorder rather than an anxiety disorder, and PTSD findings are interpreted separately when relevant (). In parallel with immune research, the past decade has witnessed a surge of interest in the role of the microbiome in psychiatry. While most studies have centred on the gut microbiome, recent work has begun to explore other microbial niches. The oral cavity harbours one of the most diverse microbiomes in the body and is a gateway to both the gastrointestinal and respiratory tracts. Oral bacteria can contribute to systemic inflammation – for instance, through periodontal disease, which has been linked to elevated circulating inflammatory markers and even atherosclerosis. It stands to reason that disturbances in the oral microbiome (“oral dysbiosis”) might have implications for systemic health and possibly neuropsychiatric outcomes. Indeed, oral health has been observed to correlate with mental health; patients with severe mental illness often have poorer dental health, and chronic stress can alter saliva composition and immunity in the mouth. Despite this, the “oral microbiome–brain axis” remains relatively under-studied. Only recently have researchers applied varying sequencing techniques to investigate whether the oral microbial community differs in individuals with depression or anxiety.