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The high symptomatic and biological heterogeneity of major depressive disorder (MDD) makes it very difficult to find broadly efficacious treatments that work against all symptoms. Concentrating on single core symptoms that are biologically well understood might consist of a more viable approach. The Research Domain Criteria (RDoC) framework is a trans-diagnostic dimensional approach that focuses on symptoms and their underlying neurobiology. Evidence is accumulating that psychedelics may possess antidepressant activity, and this can potentially be explained through a multi-level (psychobiological, circuitry, (sub)cellular and molecular) analysis of the cognitive systems RDoC domain. Cognitive deficits, such as negative emotional processing and negativity bias, often lead to depressive rumination. Psychedelics can increase long-term cognitive flexibility, leading to normalization of negativity bias and reduction in rumination. We propose a theoretical model that explains how psychedelics can reduce the negativity bias in depressed patients. At the psychobiological level, we hypothesize that the negativity bias in MDD is due to impaired pattern separation and that psychedelics such as psilocybin help in depression because they enhance pattern separation and hence reduce negativity bias. Pattern separation is a mnemonic process that relies on adult hippocampal neurogenesis, where similar inputs are made more distinct, which is essential for optimal encoding of contextual information. Impairment in this process may underlie the negative cognitive bias in MDD by, for example, increased pattern separation of cues with a negative valence that can lead to excessive deliberation on aversive outcomes. On the (sub) cellular level, psychedelics stimulate hippocampal neurogenesis as well as synaptogenesis, spinogenesis and dendritogenesis in the prefrontal cortex. Together, these effects help restoring resilience to chronic stress and lead to modulation of the major connectivity hubs of the prefrontal cortex, hippocampus, and amygdala. Based on these observations, we propose a new translational framework to guide the development of a novel generation of therapeutics to treat the cognitive symptoms in MDD.

IMPORTANCE The use of autologous fat transfer (AFT) or lipofilling for correcting contour deformities is seen as one of the major breakthroughs in reconstructive plastic surgery. Its applications in facial reconstructive surgery have been of particular interest owing to the prospect of achieving autologous reconstruction by a minimally invasive approach. However, its unpredictability and variable degree of resorption have limited its utility and much skepticism still exists regarding its efficacy. Furthermore, more than 2 decades of clinical research have produced a highly fragmented body of evidence that has not been able to provide definite answers. OBJECTIVE To investigate the safety and efficacy of AFT in facial reconstruction through a systematic review and meta-analysis. DATA SOURCES A literature search was performed in PubMed, Embase, and the Cochrane Library from inception to October 11, 2017. STUDY SELECTION All published studies investigating the efficacy and safety of AFT in facial reconstructive surgery. DATA EXTRACTION AND SYNTHESIS Two independent reviewers performed data extraction systematically, adhering to the PRISMA guidelines. Summary measures were pooled in a random-effects model meta- analysis. MAIN OUTCOMES AND MEASURES The patient and surgeon satisfaction, graft survival, number of AFT sessions, and the incidence of AFT-related complications were the main outcomes of interest in this meta-analysis. RESULTS This systematic review resulted in the inclusion 52 relevant studies consisting of 1568 unique patients. These included 4 randomized clinical trials, 11 cohort studies, and 37 case series. The overall follow-up averaged 1.3 years after AFT. Meta-analysis revealed a very high overall patient satisfaction rate of 91.1% (95% CI, 85.1%-94.8%) and overall surgeon satisfaction rate of 88.6%(95% CI, 83.4%-92.4%). The number of AFT sessions required to achieve the desired result was 1.5 (95% CI, 1.3-1.7) and 50% to 60% of the injected volume was retained at 1 year. Only 4.8%(95% CI, 3.3%-6.9%) of procedures resulted in clinical complications. CONCLUSIONS AND RELEVANCE To our knowledge, this study provides the first overview of the current knowledge about AFT in facial reconstructive surgery. Our results confirm that AFT is an effective technique for treating soft-tissue deformities in the head and neck, with low rate of minor complications.

IMPORTANCE: The use of autologous fat transfer (AFT) or lipofilling for correcting contour deformities is seen as one of the major breakthroughs in reconstructive plastic surgery. Its applications in facial reconstructive surgery have been of particular interest owing to the prospect of achieving autologous reconstruction by a minimally invasive approach. However, its unpredictability and variable degree of resorption have limited its utility and much skepticism still exists regarding its efficacy. Furthermore, more than 2 decades of clinical research have produced a highly fragmented body of evidence that has not been able to provide definite answers. OBJECTIVE: To investigate the safety and efficacy of AFT in facial reconstruction through a systematic review and meta-analysis. DATA SOURCES: A literature search was performed in PubMed, Embase, and the Cochrane Library from inception to October 11, 2017. STUDY SELECTION: All published studies investigating the efficacy and safety of AFT in facial reconstructive surgery. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers performed data extraction systematically, adhering to the PRISMA guidelines. Summary measures were pooled in a random-effects model meta-analysis. MAIN OUTCOMES AND MEASURES: The patient and surgeon satisfaction, graft survival, number of AFT sessions, and the incidence of AFT-related complications were the main outcomes of interest in this meta-analysis. RESULTS: This systematic review resulted in the inclusion 52 relevant studies consisting of 1568 unique patients. These included 4 randomized clinical trials, 11 cohort studies, and 37 case series. The overall follow-up averaged 1.3 years after AFT. Meta-analysis revealed a very high overall patient satisfaction rate of 91.1% (95% CI, 85.1%-94.8%) and overall surgeon satisfaction rate of 88.6% (95% CI, 83.4%-92.4%). The number of AFT sessions required to achieve the desired result was 1.5 (95% CI, 1.3-1.7) and 50% to 60% of the injected volume was retained at 1 year. Only 4.8% (95% CI, 3.3%-6.9%) of procedures resulted in clinical complications. CONCLUSIONS AND RELEVANCE: To our knowledge, this study provides the first overview of the current knowledge about AFT in facial reconstructive surgery. Our results confirm that AFT is an effective technique for treating soft-tissue deformities in the head and neck, with low rate of minor complications. LEVEL OF EVIDENCE: NA.