Treatment resistant late-life depression: A narrative review of psychosocial risk factors, non-pharmacological interventions, and the role of clinical phenotyping.

BACKGROUND: Treatment resistant depression (TRD) is a subset of major depressive disorder (MDD) in which symptoms do not respond to front line therapies. In older adults, the assessment and treatment of TRD is complicated by psychosocial risk factors unique to this population, as well as a relative paucity of research. METHODS: Narrative review aimed at (1) defining TRLLD for clinical practice and research; (2) describing psychosocial risk factors; (3) reviewing psychological and non-pharmacological treatments; (4) discussing the role of clinical phenotyping for personalized treatment; and (5) outlining research priorities. RESULTS: Our definition of TRLLD centers on response to medication and neuromodulation in primary depressive disorders. Psychosocial risk factors include trauma and early life adversity, chronic physical illness, social isolation, personality, and barriers to care. Promising non-pharmacological treatments include cognitive training, psychotherapy, and lifestyle interventions. The utility of clinical phenotyping is highlighted by studies examining the impact of comorbidities, symptom dimensions (e.g., apathy), and structural/functional brain changes. LIMITATIONS: There is a relative paucity of TRLLD research. This limits the scope of empirical data from which to derive reliable patterns and complicates efforts to evaluate the literature quantitatively. CONCLUSIONS: TRLLD is a complex disorder that demands further investigation given our aging population. While this review highlights the promising breadth of TRLLD research to date, more research is needed to help elucidate, for example, the optimal timing for implementing risk mitigation strategies, the value of collaborative care approaches, specific treatment components associated with more robust response, and phenotyping to help inform treatment decisions.

Digital Collateral Information Through Electronic and Social Media in Psychotherapy: Comparing Clinician-reported Trends Before and During the COVID-19 Pandemic.

BACKGROUND: Patient clinical collateral information is critical for providing psychiatric and psychotherapeutic care. With the shift to primarily virtual care triggered by the COVID-19 pandemic, psychotherapists may have received less clinical information than they did when they were providing in-person care. This study assesses whether the shift to virtual care had an impact on therapists' use of patients' electronic and social media to augment clinical information that may inform psychotherapy. METHODS: In 2018, we conducted a survey of a cohort of psychotherapists affiliated with McLean Hospital. We then reapproached the same cohort of providers for the current study, gathering survey responses from August 10, 2020, to September 1, 2020, for this analysis. We asked clinicians whether they viewed patients' electronic and social media in the context of their psychotherapeutic relationship, what they viewed, how much they viewed it, and their attitudes about doing so. RESULTS: Of the 99 respondents, 64 (64.6%) had viewed at least 1 patient's social media and 8 (8.1%) had viewed a patient's electronic media. Of those who reported viewing patients' media, 70 (97.2%) indicated they believed this information helped them provide more effective treatment. Compared with the 2018 prepandemic data, there were significantly more clinicians with>10 years of experience reporting media use in therapy. There was also a significant increase during the pandemic in the viewing of media of adult patients and a trend toward an increase in viewing of media of older adult patients. CONCLUSIONS: Review of patients' electronic and social media in therapy became more common among clinicians at a large psychiatric teaching hospital during the COVID-19 pandemic. These findings support continuing research about how reviewing patients' media can inform and improve clinical care.

The Stress-Active Cell Division Protein ZapE Alters FtsZ Filament Architecture to Facilitate Division in Escherichia coli.

During pathogenic infections, bacterial cells experience environmental stress conditions, including low oxygen and thermal stress. Bacterial cells proliferate during infection and divide by a mechanism characterized by the assembly of a large cytoskeletal structure at the division site called the Z-ring. The major protein constituting the Z-ring is FtsZ, a tubulin homolog and GTPase that utilizes the nucleotide to assemble into dynamic polymers. In Escherichia coli, many cell division proteins interact with FtsZ and modulate Z-ring assembly, while others direct cell wall insertion and peptidoglycan remodeling. Here, we show that ZapE, an ATPase that accumulates during late constriction, directly interacts with FtsZ and phospholipids in vitro. In the presence of adenosine triphosphate (ATP), ZapE induces bundling of GTP-induced FtsZ polymers; however, ZapE also binds FtsZ in the absence of GTP. The ZapE mutant protein ZapE(K84A), which is defective for ATP hydrolysis, also interacts with FtsZ and induces FtsZ filament bundling. In vivo, cultures of zapE deletion cells contain a low percentage of filamentous cells, suggesting that they have a modest division defect; however, they are able to grow when exposed to stress, such as high temperature and limited oxygen. When combined with the chromosomal deletion of minC, which encodes an FtsZ disassembly factor, ΔzapE ΔminC cells experience growth delays that slow proliferation at high temperature and prevent recovery. This synthetic slow growth phenotype after exposure to stress suggests that ZapE may function to ensure proliferation during and after stress, and this is exacerbated when cells are also deleted for minC. Expression of either ZapE or ZapE(K84A) complements the aberrant growth phenotypes in vivo suggesting that the division-associated role of ZapE does not require ZapE ATP hydrolysis. These results support that ZapE is a stress-regulated cell division protein that interacts directly with FtsZ and phospholipids, promoting growth and division after exposure to environmental stress.