Comment

A recent “umbrella” review examined various biomarkers relating to the serotonin system, and concluded there was no consistent evidence implicating serotonin in the pathophysiology of depression. We present reasons for why this conclusion is overstated, including methodological weaknesses in the review process, selective reporting of data, over-simplification, and errors in the interpretation of neuropsychopharmacological findings. We use the examples of tryptophan depletion and serotonergic molecular imaging, the two research areas most relevant to the investigation of serotonin, to illustrate this.

Behavioural supersensitivity may be a result of increased glutamate sensitivity of D2-MSN and reduced sensitivity to dopamine. We propose that clozapine may address behavioural supersensitivity by modulating glutamate activity which may partially explain its unique effectiveness in the setting of treatment resistant schizophrenia.

ICD and DSM, the standard manuals for psychiatric diagnosis, have each recently been revised. These newest versions have modest updates and retain primarily categorical models. There is growing evidence that these primarily categorical structures of both ICD and DSM do not fit either the clinical presentations of patients, recent discoveries from genetics and neurobiology, nor therapeutic choices well. This commentary reviews the state of current evidence on the structure of psychiatric disorders, focusing on psychotic and mood disorders. That review suggests that future revisions should consider the widely replicated findings that patients present with an individual combination of symptoms or factors, each of specific severity, and that it is these symptoms and factors and their severity that clinicians identify and treat. Moving to such a system loses no details from the current models and adds crucial information on personal aspects of illness and the dimensionality of their conditions. The result would be updated versions of ICD and DSM with improved validity and utility. And such a model would be practical, because clinicians already use it in their work.

The brain remains a key reservoir of latent HIV infection, and people living with HIV (PLWH) face a high risk for cognitive impairment and psychiatric disorders. Although the burden of HIV infection and co-morbidities is greatest in the Global South, a large proportion of HIV mental health research is carried out in the Global North. Large, well-funded observational cohort studies exploring HIV-associated psychopathology generally involve participant groups from WEIRD (Western, educated, industrialised, rich and democratic) settings. The socioeconomic status and institutional access afforded to these participant groups on average does not reflect those of the majority of beneficiaries of HIV mental health research. This misalignment may lead to limitations in generalising findings and developing effective interventions to improve the mental health of PLWH. Here, I offer recommendations to actively cultivate authentic diversity and inclusion in the field, with four focus points: (1) for funding bodies, to actively invest in neuroscientists in the Global South for investigations of HIV-related psychopathology; (2) for scientific publishers, to fund professional support services for researchers in the Global South; (3) for academic institutions, to facilitate meaningful, equitable collaborations with researchers in the Global South and incentivise studies with diverse participant groups; and (4) for individual neuroscientists, to actively cite and converse with colleagues in the Global South, tackle personal biases in those conversations, and avoid overgeneralising findings from primarily WEIRD participant groups.