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To investigate this poorly understood clinical question, we examined the involvement of frontolimbic post-synaptic 5-HT<jats:sub>2A<\/jats:sub> receptors in 20 medication-resistant depressed (MRD) patients with half of them diagnosed with comorbid GAD with <jats:sup>123<\/jats:sup>I-5-I-R91150 SPECT. To explore whether 5-HT<jats:sub>2A<\/jats:sub> receptor-binding indices (BI) associated with comorbid GAD could be related to distinct psychopathological symptoms, all were assessed with the symptom Checklist-90-Revised (SCL-90-R). MRD patients with comorbid GAD displayed significantly higher 5-HT<jats:sub>2A<\/jats:sub> receptor BI in the hippocampal\u2013amygdala complex, compared to MRD patients without GAD. Correlation analyses revealed that the 5-HT<jats:sub>2A<\/jats:sub> receptor BI in these areas were significantly related to the SCL-90-R subscale hostility (HOS), especially for those MRD patients with comorbid GAD. Comorbid MRD-GAD may be characterized with increased hippocampal\u2013amygdala 5-HT<jats:sub>2A<\/jats:sub> receptor BI which could represent enhanced levels in hostility in such kinds of patients. Adapted psychotherapeutic interventions may be warranted.<\/jats:p>","DOI":"10.1007\/s00406-021-01243-1","type":"journal-article","created":{"date-parts":[[2021,4,27]],"date-time":"2021-04-27T08:02:17Z","timestamp":1619510537000},"page":"1369-1378","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Hostility in medication-resistant major depression and comorbid generalized anxiety disorder is related to increased hippocampal\u2013amygdala 5-HT2A receptor density"],"prefix":"10.1007","volume":"271","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9885-3041","authenticated-orcid":false,"given":"Chris","family":"Baeken","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanfeng","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo-Rong","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robrecht","family":"Dockx","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathelijne","family":"Peremans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudi","family":"De Raedt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,4,27]]},"reference":[{"key":"1243_CR1","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1017\/S0033291712001511","volume":"43","author":"AJ Ferrari","year":"2013","unstructured":"Ferrari AJ, Somerville AJ, Baxter AJ, Norman R, Patten SB, Vos T, Whiteford HA (2013) Global variation in the prevalence and incidence of major depressive disorder: a systematic review of the epidemiological literature. 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