Marcus Willaschek’s new book Kant on the Sources of Metaphysics: The Dialectic of Pure Reason (Cambridge University Press, 2018) is a penetrating analysis of the Transcendental Dialectic of Kant’s Critique of Pure Reason. In his comments, the author first raises some questions concerning the structure of the Transcendental Dialectic (and Willaschek’s reconstruction of it) and then proposes that looking at the second Critique and continuing on into the third Critique will reveal more roles for the idea of God in Kant’s reconstruction of traditional metaphysics than Willaschek’s treatment suggests.

Luigi Caranti seeks to find a foundation for a contemporary theory of human rights in Kant, as well as contemporary relevance for his project of perpetual peace and his teleology of political progress. I agree with much of what he says, but provide a different account of Kant’s foundations for morality in general and human rights in particular, and defend my critique of Kant’s conception of a guarantee of progress from Caranti’s defence of Kant.

Exposure to threat increases the risk for internalizing problems in adolescence. Deficits in integrating bodily cues into representations of emotion are thought to contribute to internalizing problems. Given the role of the medial prefrontal cortex in regulating bodily responses and integrating them into representations of emotional states, coordination between activity in the medial prefrontal cortex and autonomic nervous system responses may be influenced by past threat exposure with consequences for the emergence of internalizing problems. A sample of 179 Mexican-origin adolescents (88 female) reported on neighborhood and school crime, peer victimization, and discrimination when they were 10–16 years old. At age 17, participants underwent a functional neuroimaging scan during which they viewed pictures of emotional faces while respiratory sinus arrhythmia (RSA) and skin conductance responses were measured. Adolescents also reported symptoms of internalizing problems. Greater exposure to threats across adolescence was associated with more internalizing problems. Threat exposure was also associated with stronger negative coupling between the ventromedial prefrontal cortex and RSA. Stronger negative ventromedial prefrontal cortex–RSA coupling was associated with fewer internalizing problems. These results suggest the degree of coordinated activity between the brain and parasympathetic nervous system is both enhanced by threat experiences and decreased in adolescents with more internalizing problems.

OBJECTIVES/SPECIFIC AIMS: Earlier pubertal timing has been associated with risk for depression, particularly in girls (e.g., Keenan etal., 2014). Evidence suggests pubertal timing in girls also relates to alterations in the microstructural properties of brain white matter tracts in late adolescence (Chahal etal., 2018), and structural connectivity of cingulate and frontal regions (Chahal etal., in prep), though differences in pubertal development in both boys and girls have not been examined in the context of brain functional connectivity (FC). Individual differences in the course of puberty may have enduring effects on functional coupling among brain regions that may contribute to the risk for psychopathology. To address this question, we explored the relation between pubertal timing and tempo with depression symptoms (age 16). Then, we examined whether brain network FC (age 16) associates with pubertal indices and predicts concurrent and later depressive symptoms (age 18). METHODS/STUDY POPULATION: Sixty-eight adolescents (37 females) completed the Mini-Mood and Anxiety Symptom Questionnaire (MASQ; Clark & Watson, 1995) at ages 14-18. Gompertz growth curve modelling of pubertal development (age 10-15; Waves 1-6) was used to estimate pubertal timing and tempo per individual, separately for males and females (e.g., Chahal etal., 2018). Resting-state MRI data (age 16) were parcellated into 264 cortical and subcortical regions to create region-to-region FC matrices based on correlations of time-series. Individual matrices were fed to the GraphVar program (Kruschwitz etal., 2015) to assess the interaction of pubertal timing and pubertal tempo with functional network connectivity using Network-based statistic (NBS; Zalesky etal., 2010). Subnetworks showing alterations in relation to pubertal timing and tempo were then examined in association with concurrent (age 16) symptoms and used to predict future depressive symptoms (age 18). RESULTS/ANTICIPATED RESULTS: In all youth, earlier pubertal timing was associated with higher depressive symptoms at age 16 (p<.018). This association was stronger in girls with slower pubertal tempo (p<.039). Interregional connectivity analyses revealed that the interaction of earlier pubertal timing and slower tempo was associated with lower FC between the left cingulate gyrus and right precuneus (p<.0001), regions implicated in emotion processing (i.e., Affective Processing Network) and self-referential thinking (i.e., Default Mode Network). FC of the three other emotion- and self-referential processing network regions (i.g., left insula, superior parietal lobule, and precuneus) was lower in youth with greater age 16 depressive symptoms (p<.0001). Finally, lower FC of of the left and right inferior parietal lobule predicted greater depressive symptoms at age 18 (p<.0001). In summary, FC of overlapping affective and default mode network areas was related to earlier pubertal timing and higher concurrent and future depressive symptoms. DISCUSSION/SIGNIFICANCE OF IMPACT: These findings demonstrate individual differences in pubertal maturation are associated with depressive symptoms and differences in brain connectivity in mid-adolescence. Early pubertal development was associated with greater depression symptoms and lower FC of brain regions involved in emotion regulation and self-referential processing. Further, FC between these regions predicted higher depression symptoms two years later. These neurobiological mechanisms may, in part, underlie the link between off-time pubertal development and the risk for depression. These findings also have important implications for precision psychiatry, as we show that a risk-factor of depression (early pubertal timing) may manifest in developing neurobiology in region-specific ways. Previous network models of depression (e.g., Li etal., 2018) implicated affective network connectivity in sustained negative mood and the default mode/ self-referential network in rumination. Other networks implicated in these past models include the reward network, which may be involved in anhedonia and loss of pleasure. Our study only found associations between affective and self-referential regional connectivity, pubertal maturation, and depression, suggesting that pubertal risk factors may relate more closely with emotion-regulation and self-referential processing deficits.

John Rawls based his theory of justice, in the work of that name, on a ‘Kantian interpretation’ of the status of human beings as ‘free and equal’ persons. In his subsequent, ‘political rather than metaphysical’ expositions of his theory, the conception of citizens of democracies as ‘free and equal’ persons retained its foundational role. But Rawls appealed only to Kant’s moral philosophy, never to Kant’s own political philosophy as expounded in his 1797 Doctrine of Right in the Metaphysics of Morals. I argue here that the structure of Kant’s political philosophy, with its categories of the innate right to freedom, private acquired right and public right, can clarify the relationship between Rawls’s two principles of justice and his scheme of basic liberties and primary goods.