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BACKGROUND Depression is the leading cause of diseases globally and is often characterized by a lack of social connection. With the rise of social media, it is seen that Twitter users are seeking Web-based connections for depression. OBJECTIVE This study aimed to identify communities where Twitter users tweeted using the hashtag #MyDepressionLooksLike to connect about depression. Once identified, we wanted to understand which community characteristics correlated to Twitter users turning to a Web-based community to connect about depression. METHODS Tweets were collected using NCapture software from May 25 to June 1, 2016 during the Mental Health Month (n=104) in the northeastern United States and Washington DC. After mapping tweets, we used a Poisson multilevel regression model to predict tweets per community (county) offset by the population and adjusted for percent female, percent population aged 15-44 years, percent white, percent below poverty, and percent single-person households. We then compared predicted versus observed counts and calculated tweeting index values (TIVs) to represent undertweeting and overtweeting. Last, we examined trends in community characteristics by TIV using Pearson correlation. RESULTS We found significant associations between tweet counts and area-level proportions of females, single-person households, and population aged 15-44 years. TIVs were lower than expected (TIV 1) in eastern, seaboard areas of the study region. There were communities tweeting as expected in the western, inland areas (TIV 2). Counties tweeting more than expected were generally scattered throughout the study region with a small cluster at the base of Maine. When examining community characteristics and overtweeting and undertweeting by county, we observed a clear upward gradient in several types of nonprofits and TIV values. However, we also observed U-shaped relationships for many community factors, suggesting that the same characteristics were correlated with both overtweeting and undertweeting. CONCLUSIONS Our findings suggest that Web-based communities, rather than replacing physical connection, may complement or serve as proxies for offline social communities, as seen through the consistent correlations between higher levels of tweeting and abundant nonprofits. Future research could expand the spatiotemporal scope to confirm these findings.