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By choosing the evolutionary development of the forebrain as a starting point, a certain order in the connections can be created. The dorsal diencephalic connection (DDC) system can be applied for the development of biomarkers that can predict treatment response.<\/jats:p><\/jats:sec><jats:sec id=\"S0924270822000151_as2\"><jats:title>Materials and methods:<\/jats:title><jats:p>After providing a brief introduction to the theory, we examined neuroanatomical publications on the connectivity of the DDC system. We then searched for neurochemical components that are specific for the habenula.<\/jats:p><\/jats:sec><jats:sec id=\"S0924270822000151_as3\"><jats:title>Results and discussion:<\/jats:title><jats:p>The best strategy to find biomarkers that reflect the function of the habenular connection is to use genetic variants of receptors, transporters or enzymes specific to this complex. By activating these with probes and measuring the response in people with different functional genotypes, the usefulness of biomarkers can be assessed.<\/jats:p><\/jats:sec><jats:sec id=\"S0924270822000151_as4\"><jats:title>Conclusions:<\/jats:title><jats:p>The most promising biomarkers in this respect are those linked to activation or inhibition of the nicotine receptor, dopamine D4 receptor, \u03bc-opioid receptor and also those of the functioning of habenular glia cells (astrocytes and microglia).<\/jats:p><\/jats:sec>","DOI":"10.1017\/neu.2022.15","type":"journal-article","created":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T09:57:50Z","timestamp":1652954270000},"page":"229-239","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":15,"title":["Circuits regulating pleasure and happiness \u2013 focus on potential biomarkers for circuitry including the habenuloid complex"],"prefix":"10.1017","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4942-6195","authenticated-orcid":false,"given":"Anton J.M.","family":"Loonen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7078-323X","authenticated-orcid":false,"given":"Svetlana A.","family":"Ivanova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2022,5,19]]},"reference":[{"key":"S0924270822000151_ref88","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.12.038"},{"key":"S0924270822000151_ref109","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1119348109"},{"key":"S0924270822000151_ref99","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(92)90046-A"},{"key":"S0924270822000151_ref105","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2018.00414"},{"key":"S0924270822000151_ref108","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2020.108158"},{"key":"S0924270822000151_ref24","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.03.013"},{"key":"S0924270822000151_ref123","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.03.017"},{"key":"S0924270822000151_ref68","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2016.00539"},{"key":"S0924270822000151_ref101","doi-asserted-by":"publisher","DOI":"10.3389\/fnsyn.2018.00039"},{"key":"S0924270822000151_ref113","doi-asserted-by":"publisher","DOI":"10.1517\/03009734000000043"},{"key":"S0924270822000151_ref54","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.201302947"},{"key":"S0924270822000151_ref84","first-page":"1020","article-title":"II. 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