Major depressive disorder (MDD) is highly prevalent and has an important impact, with active symptoms present in 4% of the adult population.¹ Although MDD exhibits multiple molecular phenotypes,^2-5 accumulating evidence suggests a role of inflammation in generating the symptoms of a major depressive episode (MDE). For example, induction of inflammation is associated with sad mood in humans,⁶ and direct induction of the central immune system in rodents is associated with the sickness syndrome of anhedonia, weight loss, and anorexia, which overlap with the diagnostic criteria for MDE.⁷ Also in MDD, several markers of peripheral inflammation, including levels of C-reactive protein, interleukin 6 (IL-6), and tumor necrosis factor (TNF), are frequently increased.⁸ Conditions that create neuroinflammation, such as traumatic brain injury, systemic lupus erythematosus, and multiple sclerosis, are associated with prevalence rates of MDE as high as 50%, suggesting a link between brain inflammation and mood symptoms.⁹

Schizophrenia is a psychiatric disorder which has a lifetime prevalence of ~1%. Multiple candidate mechanisms have been proposed in the pathogenesis of schizophrenia. One such mechanism is the involvement of neuroinflammation. Clinical studies, including neuroimaging, peripheral biomarkers and randomized control trials, have suggested the presence of neuroinflammation in schizophrenia. Many studies have also measured markers of neuroinflammation in postmortem brain samples from schizophrenia patients. The objective of this study was to conduct a systematic search of the literature on neuroinflammation in postmortem brains of schizophrenia patients indexed in MEDLINE, Embase and PsycINFO. Databases were searched up until 20th March 2016 for articles published on postmortem brains in schizophrenia evaluating microglia, astrocytes, glia, cytokines, the arachidonic cascade, substance P and other markers of neuroinflammation. Two independent reviewers extracted the data. Out of 5385 articles yielded by the search, 119 articles were identified that measured neuroinflammatory markers in schizophrenic postmortem brains. Glial fibrillary acidic protein expression was elevated, lower or unchanged in 6, 6 and 21 studies, respectively, and similar results were obtained for glial cell densities. On the other hand, microglial markers were increased, lower or unchanged in schizophrenia in 11, 3 and 8 studies, respectively. Results were variable across all other markers, but SERPINA3 and IFITM were consistently increased in 4 and 5 studies, respectively. Despite the variability, some studies evaluating neuroinflammation in postmortem brains in schizophrenia suggest an increase in microglial activity and other markers such as SERPINA3 and IFITM. Variability across studies is partially explained by multiple factors including brain region evaluated, source of the brain, diagnosis, age at time of death, age of onset and the presence of suicide victims in the cohort.

Background: Apathy and depression are the most frequent behavioural and psychiatric disorders in Alzheimer’s disease, and may both have a negative impact on the progression of the illness. Objectives: To examine the clinical correlates of apathy in Alzheimer’s disease (AD), and to determine whether apathy is a significant predictor of more rapid cognitive, functional and emotional decline. Methods: Using a structured psychiatric evaluation, we examined a consecutive series of 354 subjects meeting clinical criteria for AD. Apathy was assessed by the Apathy Scale, and diagnosed using standardised criteria. Additional measurements included scales for depression, functional impairment, and global cognitive functions. A follow up evaluation was carried out in 247 patients (70% of the total sample) between 1 and 4 years after the baseline evaluation. Results: Apathy was significantly associated with older age (p = 0.009), and a higher frequency of minor and major depression (p<0.0001). Apathy at baseline was a significant predictor of depression at follow up (p = 0.01), and was associated with a faster cognitive (p = 0.0007) and functional decline (p = 0.006). Conclusions: Apathy in AD is a behavioural marker of a more aggressive dementia, characterised by a faster progression of cognitive, functional, and emotional impairment.