Elucidating individual aberrance is a critical first step toward precision medicine for heterogeneous disorders such as depression. The neuropathology of depression is related to abnormal inter-regional structural covariance indicating a brain maturational disruption. However, most studies focus on group-level structural covariance aberrance and ignore the interindividual heterogeneity. For that reason, we aimed to identify individualized structural covariance aberrance with the help of individualized differential structural covariance network (IDSCN) analysis.

T1-weighted anatomical images of 195 first-episode untreated patients with depression and matched healthy controls (n = 78) were acquired. We obtained IDSCN for each patient and identified subtypes of depression based on shared differential edges.

As a result, patients with depression demonstrated tremendous heterogeneity in the distribution of differential structural covariance edges. Despite this heterogeneity, altered edges within subcortical-cerebellum network were often shared by most of the patients. Two robust neuroanatomical subtypes were identified. Specifically, patients in subtype 1 often shared decreased motor network-related edges. Patients in subtype 2 often shared decreased subcortical-cerebellum network-related edges. Functional annotation further revealed that differential edges in subtype 2 were mainly implicated in reward/motivation-related functional terms.

In conclusion, we investigated individualized differential structural covariance and identified that decreased edges within subcortical-cerebellum network are often shared by patients with depression. The identified two subtypes provide new insights into taxonomy and facilitate potential clues to precision diagnosis and treatment of depression.

As a neuroprogressive illness, depression is accompanied by brain structural abnormality that extends to many brain regions. However, the progressive structural alteration pattern remains unknown.

To elaborate the progressive structural alteration of depression according to illness duration, we recruited 195 never-treated first-episode patients with depression and 130 healthy controls (HCs) undergoing T1-weighted MRI scans. Voxel-based morphometry method was adopted to measure gray matter volume (GMV) for each participant. Patients were first divided into three stages according to the length of illness duration, then we explored stage-specific GMV alterations and the causal effect relationship between them using causal structural covariance network (CaSCN) analysis.

Overall, patients with depression presented stage-specific GMV alterations compared with HCs. Regions including the hippocampus, the thalamus and the ventral medial prefrontal cortex (vmPFC) presented GMV alteration at onset of illness. Then as the illness advanced, others regions began to present GMV alterations. These results suggested that GMV alteration originated from the hippocampus, the thalamus and vmPFC then expanded to other brain regions. The results of CaSCN analysis revealed that the hippocampus and the vmPFC corporately exerted causal effect on regions such as nucleus accumbens, the precuneus and the cerebellum. In addition, GMV alteration in the hippocampus was also potentially causally related to that in the dorsolateral frontal gyrus.

Consistent with the neuroprogressive hypothesis, our results reveal progressive morphological alteration originating from the vmPFC and the hippocampus and further elucidate possible details about disease progression of depression.

Anticipatory pleasure deficits are closely correlated with negative symptoms in schizophrenia, and may be found in both clinical and subclinical populations along the psychosis continuum. Prospection, which is an important component of anticipatory pleasure, is impaired in individuals with social anhedonia (SocAnh). In this study, we examined the neural correlates of envisioning positive future events in individuals with SocAnh.

Forty-nine individuals with SocAnh and 33 matched controls were recruited to undergo functional MRI scanning, during which they were instructed to simulate positive or neutral future episodes according to cue words. Two stages of prospection were distinguished: construction and elaboration.

Reduced activation at the caudate and the precuneus when prospecting positive (v. neutral) future events was observed in individuals with SocAnh. Furthermore, compared with controls, increased functional connectivity between the caudate and the inferior occipital gyrus during positive (v. neutral) prospection was found in individuals with SocAnh. Both groups exhibited a similar pattern of brain activation for the construction v. elaboration contrast, regardless of the emotional context.

Our results provide further evidence on the neural mechanism of anticipatory pleasure deficits in subclinical individuals with SocAnh and suggest that altered cortico-striatal circuit may play a role in anticipatory pleasure deficits in these individuals.

Schizotypy refers to schizophrenia-like traits below the clinical threshold in the general population. The pathological development of schizophrenia has been postulated to evolve from the initial coexistence of ‘brain disconnection’ and ‘brain connectivity compensation’ to ‘brain connectivity decompensation’.

In this study, we examined the brain connectivity changes associated with schizotypy by combining brain white matter structural connectivity, static and dynamic functional connectivity analysis of diffusion tensor imaging data and resting-state functional magnetic resonance imaging data. A total of 87 participants with a high level of schizotypal traits and 122 control participants completed the experiment. Group differences in whole-brain white matter structural connectivity probability, static mean functional connectivity strength, dynamic functional connectivity variability and stability among 264 brain sub-regions of interests were investigated.

We found that individuals with high schizotypy exhibited increased structural connectivity probability within the task control network and within the default mode network; increased variability and decreased stability of functional connectivity within the default mode network and between the auditory network and the subcortical network; and decreased static mean functional connectivity strength mainly associated with the sensorimotor network, the default mode network and the task control network.

These findings highlight the specific changes in brain connectivity associated with schizotypy and indicate that both decompensatory and compensatory changes in structural connectivity within the default mode network and the task control network in the context of whole-brain functional disconnection may be an important neurobiological correlate in individuals with high schizotypy.

Our study aims to detect different types of response shifts (RS) and true changes of quality of life (QOL) measurement in patients with Alzheimer's disease (AD) using structural equation modeling (SEM) in domain level.

Patients with AD aged over 60 years old were collected from the Department of Neurology and Geriatrics in Taiyuan Central Hospital, China. The 12-item Short Form (SF-12) Health Survey was measured in 238 patients with AD prior to hospitalization and one month following discharge. RS was detected by SEM approach. The statistical process consisted of four steps and fitted four models. We interpreted changes of parameters in models to detect RS and to assess true change.

The results showed reprioritization of social functioning (SF) (χ2 = 4.13, p < 0.05), reconceptualization of role limitations due to emotional problems (RE) (χ2 = 17.03, p < 0.001), uniform recalibration of bodily pain (BP) (χ2 = 12.24, p < 0.001), and non-uniform recalibration of mental health (MH) (χ2 = 4.41, p < 0.05), respectively. The true changes of common factors were deteriorated in general physical health (PHYS) (−0.10, χ2 = 8.30, p < 0.005) and improved in general mental health (MENT) (+0.29, χ2 = 20.95, p < 0.001). The effect-sizes of RS were only small.

This study showed that patients with AD occurred three types of RS and true changes one month following discharge. RS had effects on the QOL of patients. Better understanding of potential changes in QOL in patients with AD is crucial.