Quantitatively derived dimensional models of psychopathology enjoy overwhelming empirical support, and a large and active community of psychopathology researchers has been establishing an empirically based dimensional hierarchical taxonomy of psychopathology (or HiTOP) as a strong candidate replacement for the current categorical classification system. The hierarchical nature of this taxonomy implies that different levels of resolution are likely to be optimal for different purposes. Our aim was to identify which level of detail is likely to provide optimal validity and explanatory power with regard to relevant clinical variables.

In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services project, we used data from a sample of 2900 psychiatric outpatients to compare different levels from a bass-ackwards model of psychopathology in relation to psychosocial impairment across different domains (global functioning, inability to work, social functioning, suicidal ideation, history of suicide attempts, history of psychiatric hospitalization).

All functioning indices were significantly associated with general psychopathology, but more complex levels provided significant incremental validity. The optimal level of complexity varied across functioning indices, suggesting that there is no single ‘best’ level for understanding relations between psychopathology and functioning.

Results support the hierarchical organization of psychopathology dimensions with regard to validity considerations and downstream implications for applied assessment. It would be fruitful to develop and implement measurement of these dimensions at the appropriate level for the purpose at hand. These findings can be used to guide HiTOP-consistent assessment in other research and clinical settings.

Cognitive impairment is common in late-life depression, which may increase Alzheimer disease (AD) risk. Therefore, we aimed to investigate whether late-life major depressive disorder (MDD) has worse cognition and increases the characteristic AD neuropathology. Furthermore, we carried out a comparison between treatment-resistant depression (TRD) and non-TRD. We hypothesized that patients with late-life depression and TRD may have increased β-amyloid (Aβ) deposits in brain regions responsible for global cognition.

We recruited 81 subjects, including 54 MDD patients (27 TRD and 27 non-TRD) and 27 matched healthy controls (HCs). Neurocognitive tasks were examined, including Mini-Mental State Examination and Montreal Cognitive Assessment to detect global cognitive functions. PET with Pittsburgh compound-B and fluorodeoxyglucose were used to capture brain Aβ pathology and glucose use, respectively, in some patients.

MDD patients performed worse in Montreal Cognitive Assessment (p = 0.003) and had more Aβ deposits than HCs across the brain (family-wise error-corrected p < 0.001), with the most significant finding in the left middle frontal gyrus. Significant negative correlations between global cognition and prefrontal Aβ deposits existed in MDD patients, whereas positive correlations were noted in HCs. TRD patients had significantly more deposits in the left-sided brain regions (corrected p < 0.001). The findings were not explained by APOE genotypes. No between-group fluorodeoxyglucose difference was detected.

Late-life depression, particularly TRD, had increased brain Aβ deposits and showed vulnerability to Aβ deposits. A detrimental role of Aβ deposits in global cognition in patients with late-onset or non-late-onset MDD supported the theory that late-life MDD could be a risk factor for AD.