Ketamine reduces the neural distinction between self- and other-produced affective touch: a randomized double-blind placebo-controlled study.

A coherent sense of self is crucial for social functioning and mental health. The N-methyl-D-aspartate antagonist ketamine induces short-term dissociative experiences and has therefore been used to model an altered state of self-perception. This randomized double-blind placebo-controlled cross-over study investigated the mechanisms for ketamine's effects on the bodily sense of self in the context of affective touch. Thirty healthy participants (15 females/15 males, age 19-39) received intravenous ketamine or placebo while performing self-touch and receiving touch by someone else during functional MRI - a previously established neural measure of tactile self-other-differentiation. Afterwards, tactile detection thresholds during self- and other-touch were assessed, as well as dissociative states, interoceptive awareness, and social touch attitudes. Compared to placebo, ketamine administration elicited dissociation and reduced neural activity associated with self-other-differentiation in the right temporoparietal cortex, which was most pronounced during other-touch. This reduction correlated with ketamine-induced reductions in interoceptive awareness. The temporoparietal cortex showed higher connectivity to somatosensory cortex and insula during other- compared to self-touch. This difference was augmented by ketamine, and correlated with dissociation strength for somatosensory cortex. These results demonstrate that disrupting the self-experience through ketamine administration affects neural activity associated with self-other-differentiation in a region involved in touch perception and social cognition, especially with regard to social touch by someone else. This process may be driven by ketamine-induced effects on top-down signaling, rendering the processing of predictable self-generated and unpredictable other-generated touch more similar. These findings provide further evidence for the intricate relationship of the bodily self with the tactile sense.

Contributions of Polygenic Risk and Disease Status to Gray Matter Abnormalities in Major Depression.

BACKGROUND: Gray matter (GM) abnormalities in depression are potentially attributable to some combination of trait, state, and illness history factors. Here, we sought to determine the contributions of polygenic risk for depression, depressive disease status, and the interaction of these factors to these GM abnormalities. METHODS: We conducted a cross-sectional comparison using a 2 × 3 factorial design examining effects of polygenic risk for depression (lower vs. upper quartile) and depression status (never depressed, currently depressed, or remitted depression) on regional GM concentration and GM volume. Participants were a subset of magnetic resonance imaging-scanned UK Biobank participants comprising 2682 people (876 men, 1806 women) algorithmically matched on 16 potential confounders. RESULTS: In women but not men, we observed that elevated polygenic risk for depression was associated with reduced cerebellar GM volume. This deficit occurred in salience and dorsal attention network regions of the cerebellum and was associated with poorer performance on tests of attention and executive function but not fluid intelligence. Moreover, in women with current depression compared to both women with remitted depression and women who never had depression, we observed GM reductions in ventral and medial prefrontal, insular, and medial temporal regions. These state-related abnormalities remained when accounting for antidepressant medication status. CONCLUSIONS: Neuroanatomical deficits attributed broadly to major depression are more likely due to an aggregation of independent factors. Polygenic risk for depression accounted for cerebellar structural abnormalities that themselves accounted for cognitive deficits observed in this disorder. Medial and ventral prefrontal, insular, and temporal cortex deficits constituted a much larger proportion of the aggregate deficit and were attributable to the depressed state.

Towards a multilevel model of major depression: genes, immuno-metabolic function, and cortico-striatal signaling.

Biological assay and imaging techniques have made visible a great deal of the machinery of mental illness. Over fifty years of investigation of mood disorders using these technologies has identified several biological regularities in these disorders. Here we present a narrative connecting genetic, cytokine, neurotransmitter, and neural-systems-level findings in major depressive disorder (MDD). Specifically, we connect recent genome-wide findings in MDD to metabolic and immunological disturbance in this disorder and then detail links between immunological abnormalities and dopaminergic signaling within cortico-striatal circuitry. Following this, we discuss implications of reduced dopaminergic tone for cortico-striatal signal conduction in MDD. Finally, we specify some of the flaws in the current model and propose ways forward for advancing multilevel formulations of MDD most efficiently.

Cryopreserved platelets in bleeding management in remote hospitals: A clinical feasibility study in Sweden.

Background: Balanced transfusions, including platelets, are critical for bleeding patients to maintain hemostasis. Many rural hospitals have no or limited platelet inventory, with several hours of transport time from larger hospitals. This study aimed to evaluate the feasibility of using cryopreserved platelets that can be stored for years, in remote hospitals with no or limited platelet inventory. Material and methods: Three remote hospitals participated in a prospective study including adult bleeding patients where platelet transfusions were indicated. Cryopreserved platelets were prepared in a university hospital, concentrated in 10 ml, transported on dry ice, and stored at -80°C at the receiving hospital. At request, the concentrated platelet units were thawed and diluted in fresh frozen plasma. The indications, blood transfusion needs, and laboratory parameters pre- and post-transfusion, as well as logistics, such as time from request to transfusion and work efforts in preparing cryopreserved platelets, were evaluated. Results: Twenty-three bleeding patients were included. Nine patients (39%) were treated for gastrointestinal bleeding, five (22%) for perioperative bleeding, and four (17%) for trauma bleeding. The transfusion needs were 4.9 ± 3.3 red blood cell units, 3.2 ± 2.3 plasma units, and 1.9 ± 2.2 platelet units, whereof cryopreserved were 1.5 ± 1.1 (mean ± SD). One patient had a mild allergic reaction. We could not show the difference in laboratory results between pre- and post-transfusion of the cryopreserved units in the bleeding patients. The mean time from the order of cryopreserved platelets to transfusion was 64 min, with a range from 25 to 180 min. Conclusion: Cryopreserved platelets in remote hospitals are logistically feasible in the treatment of bleeding. The ability to have platelets in stock reduces the time to platelet transfusion in bleeding patients where the alternative often is many hours delay. Clinical effectiveness and safety previously shown in other studies are supported in this small feasibility study.