Major depressive disorder (MDD) is a clinically and biologically heterogeneous syndrome. Identifying discrete subtypes of illness with distinguishing neurobiological substrates and clinical features is a promising strategy for guiding personalised therapeutics.

This study aimed to identify depression subtypes with correlated patterns of functional network connectivity and clinical symptoms by clustering patients according to a weighted linear combination of both features in a relatively large, medication-naïve depression sample.

We recruited 115 medication-naïve adults with MDD and 129 matched healthy controls, and evaluated all participants with magnetic resonance imaging. We used regularised canonical correlation analysis to identify component mapping relationships between functional network connectivity and symptom profiles, and K-means clustering was used to define distinct subtypes of patients.

Two subtypes of MDD were identified: insomnia-dominated subtype 1 and anhedonia-dominated subtype 2. Subtype 1 was characterised by abnormal hyperconnectivity within the ventral attention network and sleep maintenance insomnia. Subtype 2 was characterised by abnormal hypoconnectivity in the subcortical and dorsal attention networks, and prominent anhedonia symptoms.

Our study identified two distinct subtypes of patients with specific neurobiological and clinical symptom profiles. These findings advance understanding of the biological and clinical heterogeneity of MDD, offering a pathway for defining categorical subtypes of illness via consideration of both biological and clinical features.

Although numerous studies have used functional neuroimaging to identify executive dysfunction in patients with bipolar disorder (BD), the findings are not consistent. The aim of this meta-analysis is to identify the most reliable functional anomalies in BD patients during performance of Executive Function (EF) tasks.

A web-based search was performed on publication databases to identify functional magnetic resonance imaging studies of BD patients performing EF tasks and a voxel-based meta-analytic method known as anisotropic Effect Size Signed Differential Mapping (ES-SDM) was used to identify brain regions which showed anomalous activity in BD patients compared with healthy controls (HC).

Twenty datasets consisting of 463 BD patients and 484 HC were included. Compared with HC, BD patients showed significant hypo-activation or failure of activation in the left striatum (p = 0.00007), supplementary motor area (BA 6, p = 0.00037), precentral gyrus (BA 6, p = 0.0014) and cerebellum (BA 37, p = 0.0019), and hyper-activation in the left gyrus rectus (BA 11, p ≈ 0) and right middle temporal gyrus (BA 22, p = 0.00031) during performance of EF tasks. Sensitivity and subgroup analyses showed that the anomaly of left striatum is consistent across studies and present in both euthymic and BD I patients.

Patients with BD consistently showed abnormal activation in the cortico-striatal system during performance of EF tasks compared with HC. Failure of activation of the striatum may be a reliable marker for impairment in performance of especially inhibition tasks by patients with BD.