Motivated behaviors vary widely across individuals and are controlled by a range of environmental and intrinsic factors. However, due to a lack of objective measures, the role of intrinsic v. extrinsic control of motivation in psychiatric disorders remains poorly understood.

We developed a novel multi-factorial behavioral task that separates the distinct contributions of intrinsic v. extrinsic control, and determines their influence on motivation and outcome sensitivity in a range of contextual environments. We deployed this task in two independent cohorts (final in-person N = 181 and final online N = 258), including individuals with and without depression and anxiety disorders.

There was a significant interaction between group (controls, depression, anxiety) and control-condition (extrinsic, intrinsic) on motivation where participants with depression showed lower extrinsic motivation and participants with anxiety showed higher extrinsic motivation compared to controls, while intrinsic motivation was broadly similar across the groups. There was also a significant group-by-valence (rewards, losses) interaction, where participants with major depressive disorder showed lower motivation to avoid losses, but participants with anxiety showed higher motivation to avoid losses. Finally, there was a double-dissociation with anhedonic symptoms whereby anticipatory anhedonia was associated with reduced extrinsic motivation, whereas consummatory anhedonia was associated with lower sensitivity to outcomes that modulated intrinsic behavior. These findings were robustly replicated in the second independent cohort.

Together this work demonstrates the effects of intrinsic and extrinsic control on altering motivation and outcome sensitivity, and shows how depression, anhedonia, and anxiety may influence these biases.

Few studies have examined the concurrent effects of physical disease and systemic inflammation on suicide risk in patients with depression. The authors investigated the independent contributions of chronic physical disease and systemic inflammation as indexed by C-reactive protein (CRP), on risk of suicide attempt.

In this case–control study, 1468 cases of suicide attempters and 14 373 controls, both aged 18–65 years with a diagnosis of depression during 2011–2015, were identified from the hospital-wide database. Regression models were implemented to identify separate effects of physical diseases and systemic inflammation indexed by CRP, on risk of suicide attempt.

Compared with having no physical disease, having one, two, and three or more physical diseases was associated with a 3.6-, 6.4-, and 14.9-fold increase in odds of making a suicide attempt, respectively, after adjusting for age, sex, and race/ethnicity. In a sub-sample of cases and controls with available CRP values, patients with high CRP (>3 mg/L) had 1.9 times the odds of suicide attempt compared with patients with low CRP (<1 mg/L). This association was no longer significant when controlling for the effect of physical disease.

The presence of physical disease is an important risk factor for suicide attempt among patients with depression. Systemic inflammation is likewise associated with increased risk for suicide attempt, however, this association appears to be accounted for by the presence of physical disease among patients receiving care in a medical center setting. Healthcare providers should consider the risk of suicide attempt in depressed patients burdened with multiple comorbidities.