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Anxiety and Low Testosterone</h1><p class="kz la lb lc ld le lf lg lh li" data-test="articleHeaderSubtitle">Male hormone deficiency was known to be associated with anxiety, and now we know how. The discovery suggests a new approach to male angst</p></div><div class="bu a b lj lk ll lm ln lo lp lq lr ls lt lu lv lw lx ly d e "><div class="a fc lz ma mb mc md me mf mg mh mi mj mk ml mm mn mo mp mq mr ms mt mu mv fp"><div class="a fc mw lg mx my al am mp mq ms mt mu fp"><div class="nv nw bu f nx ny nz oa ob oc od oe nt of og oh oi hz dd nu nb nm nn"><img alt="Ruth Schuster" src="https://img.haarets.co.il/bs/0000017f-da24-d249-ab7f-fbe4b5e90000/af/62/e9e9c0569a2e9648f8e37e75f3cf/1018316866.jpg?precrop=1500,1500,x0,y0&height=100&width=100" class="ej em dg dp f oj ok ol om" title="Haaretz's Ruth Schuster., Credit: Tomer Appelbaum" width="1" height="1"/></div><div class="mz na"><address class="on mw lg oo op oq or al am bi"><a data-test="link" href="/ty-WRITER/0000017f-da24-d249-ab7f-fbe4b5f00000" class="os km kp">Ruth Schuster</a></address><div data-display-dates="true" class="ou is aq nk nl"><time dateTime="2024-01-25T15:32:00+02:00" class="do hr nb nc nd ne nf ng nh ni nj ly is 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Possibly checking for signs of anxiety (or lack of) before entering a maze., Credit: Kseniia Vladimirovna/Shutterstock.com" width="15.48" height="9" sizes="(min-width:1280px) 840px, (min-width:1024px) 652px, (min-width:768px) 768px,(min-width:600px) 600px, 100vw" srcSet="https://img.haarets.co.il/bs/0000018d-40b2-d02c-a79f-43bb404b0000/4c/69/df80e6fb45eb93d87383aa0850ad/55318361.JPG?precrop=5616,3265,x0,y479&height=203&width=350 350w,https://img.haarets.co.il/bs/0000018d-40b2-d02c-a79f-43bb404b0000/4c/69/df80e6fb45eb93d87383aa0850ad/55318361.JPG?precrop=5616,3265,x0,y479&height=262&width=450 450w,https://img.haarets.co.il/bs/0000018d-40b2-d02c-a79f-43bb404b0000/4c/69/df80e6fb45eb93d87383aa0850ad/55318361.JPG?precrop=5616,3265,x0,y479&height=349&width=600 600w,https://img.haarets.co.il/bs/0000018d-40b2-d02c-a79f-43bb404b0000/4c/69/df80e6fb45eb93d87383aa0850ad/55318361.JPG?precrop=5616,3265,x0,y479&height=379&width=652 652w,https://img.haarets.co.il/bs/0000018d-40b2-d02c-a79f-43bb404b0000/4c/69/df80e6fb45eb93d87383aa0850ad/55318361.JPG?precrop=5616,3265,x0,y479&height=447&width=768 768w,https://img.haarets.co.il/bs/0000018d-40b2-d02c-a79f-43bb404b0000/4c/69/df80e6fb45eb93d87383aa0850ad/55318361.JPG?precrop=5616,3265,x0,y479&height=488&width=840 840w,https://img.haarets.co.il/bs/0000018d-40b2-d02c-a79f-43bb404b0000/4c/69/df80e6fb45eb93d87383aa0850ad/55318361.JPG?precrop=5616,3265,x0,y479&height=595&width=1024 1024w,https://img.haarets.co.il/bs/0000018d-40b2-d02c-a79f-43bb404b0000/4c/69/df80e6fb45eb93d87383aa0850ad/55318361.JPG?precrop=5616,3265,x0,y479&height=744&width=1280 1280w,https://img.haarets.co.il/bs/0000018d-40b2-d02c-a79f-43bb404b0000/4c/69/df80e6fb45eb93d87383aa0850ad/55318361.JPG?precrop=5616,3265,x0,y479&height=826&width=1420 1420w,https://img.haarets.co.il/bs/0000018d-40b2-d02c-a79f-43bb404b0000/4c/69/df80e6fb45eb93d87383aa0850ad/55318361.JPG?precrop=5616,3265,x0,y479&height=1116&width=1920 1920w" data-test="articleBodyImage"/></div></div></figure><div class="sm sn do fd av so sp sq is aq nk nl sr ss st ar as su sv"><span class="nb">The reflection of a rat in a mirror. Possibly checking for signs of anxiety (or lack of) before entering a maze.</span><span class="bi cn sw is aq nk nl">Credit: Kseniia Vladimirovna/Shutterstock.com</span></div></div></header><div><section class="br bs bt" data-test="articleLayoutRow"><div class="bu bv bw bx by bz ca"><div class="cq cb cc cd ce cf"><div class="bu a b d e "><div class="a fc lz ma mb mc md me mf mg mh mi mj mk ml mm mn mo mp mq mr ms mt mu mv fp"><div class="a fc mw lg mx my al am mp mq ms mt mu fp"><div class="nv nw bu f nx ny nz oa ob oc od oe nt of og oh oi hz dd nu nb nm nn"><img alt="Ruth Schuster" src="https://img.haarets.co.il/bs/0000017f-da24-d249-ab7f-fbe4b5e90000/af/62/e9e9c0569a2e9648f8e37e75f3cf/1018316866.jpg?precrop=1500,1500,x0,y0&height=100&width=100" class="ej em dg dp f oj ok ol om" title="Haaretz's Ruth Schuster., Credit: Tomer Appelbaum" width="1" height="1"/></div><div class="mz na"><address class="on mw lg oo op oq or al am bi"><a data-test="link" href="/ty-WRITER/0000017f-da24-d249-ab7f-fbe4b5f00000" class="os km kp">Ruth Schuster</a></address><div data-display-dates="true" class="ou is aq nk nl"><time dateTime="2024-01-25T15:32:00+02:00" class="do hr nb nc nd ne nf ng nh ni nj ly is aq nk nl nm nn">Jan 25, 2024</time></div></div></div><div class="no np nq nr ns"><button type="button" class="kc on ov ow ox oy it iu oz pa pb pc do a pd pe pf pg ph" aria-expanded="false" aria-describedby="alerts_btn_description" data-test="writerAlertButton"><span id="alerts_btn_description" class="cz da ii ij db dc dd de dg ik df gz">Get email notification for articles from Ruth Schuster</span><svg width="1em" height="1em" viewBox="0 0 256 256" class="cu hr cv ig pi pj pk pl pm pn po pp pq pr" data-test="IconAlert"> <path fill="currentColor" d="M196.9 169.3c-4-4-6.3-9.2-6.7-14.8L187 94.8c0-25-21.2-45.1-49.1-48.4 0-1.2-.1-2.8-.1-4.3 0-3.3-2-6.4-5.1-7.6-5.4-1.9-10.5 2-10.4 7.1 0 2.1.1 3.7.1 4.8-27.9 3.3-49.6 23.3-49.6 48.3l-3.3 59.6c-.3 5.6-2.7 10.9-6.7 14.9L46 186v7h168v-7l-17.1-16.7zM110.6 202h38c0 10.5-8.3 18.6-18.8 18.6s-19.2-8.1-19.2-18.6z"></path></svg><span> Follow</span></button></div><div data-display-dates="true" class="ou is aq nk nl"><time dateTime="2024-01-25T15:32:00+02:00" class="do hr nb en nd ne nt nf ng nh ni nj nu is aq nk nl nm nn">Jan 25, 2024</time></div></div><div class="dd bu em ey ps pt pu ev pv dv pw px py" aria-expanded="false" aria-hidden="true"><div tabindex="-1" class="pz ds ev pv dv dw dx"></div></div></div></div><div class="ae aw ai aj ay az cg ba ch ci bb bc cj ck cl"><div class="j k" data-test="articleBody"><div data-test="trinity-player"></div><p class="sd tm lb tn to tp">Low testosterone is associated with high anxiety, research has found. Why exactly had never been understood, but now the link has been elucidated in a groundbreaking study recently published in the journal of Molecular Psychiatry.</p><div class="undefined ib"><div class="FI_PH"></div></div><p class="sd tm lb tn to tp">With the help of the radicals in the community – namely, the shrinking violets and members devoid of any anxiety whatsoever – a team at Be'er Sheva's Ben-Gurion University of the Negev led by Prof. Shira Knafo, head of the Molecular Cognition Laboratory, <a class="sy sz ta tb jb kv tc td te tf tg th sg fo jo jp" href="https://www.nature.com/articles/s41380-023-02361-z" target="_blank" referrerpolicy="no-referrer-when-downgrade">discovered the missing link</a> between anxiety and the male hormone. </p><div class="undefined ib"><div class="FI_PH"></div></div><p class="sd tm lb tn to tp">Knafo and the team worked on rats, chiefly males, and chiefly because science frowns on experimentation on and dissection of men. But <a class="sy sz ta tb jb kv tc td te tf tg th sg fo jo jp" href="https://communities.springernature.com/posts/unveiling-the-connection-between-tacr3-testosterone-and-anxiety" target="_blank" referrerpolicy="no-referrer-when-downgrade">their findings</a> apply broadly. </p><div class="undefined ib"><div class="FI_PH"></div></div><p class="sd tm lb tn to tp">In any given population of people/rodents, some will be emotional outliers: some will be prone to high anxiety, while others will feel none at all. In hope of shedding light on the difference and how that connects with male hormone levels, Knafo and the team looked at rats at the extremes of the spectrum, she explained in a phone interview.</p><div class="undefined ib"><div class="FI_PH"></div></div><p class="sd tm lb tn to tp">How does one evaluate anxiety in the rat? By its behavior in a maze. If the rodent skulks in dark corners, it is anxious. If it boldly struts out into the light and solves the maze, it's sanguine. </p><div class="undefined ib"><div class="FI_PH"></div></div><figure class="} bu ib f cn sd"><div class="dd bu rz"><button type="button" class="dg sa sb sc sd hm ic ps hz dd se sf sg dv sh si"><svg width="1em" height="1em" viewBox="0 0 256 256" class="cu sj cv sk ib fx" data-test="IconZoomIn"> <path fill="currentColor" d="M165.9 153.6c7.8-10.8 12.5-24.1 12.5-38.5 0-36.3-29.5-65.8-65.7-65.8S47 78.9 47 115.1c0 36.3 29.5 65.8 65.7 65.8 14.7 0 28.3-4.9 39.3-13.1l51.6 51.6 14.1-14.1-51.8-51.7zM148 120h-28v28h-16v-28H76v-16h28V76h16v28h28v16z"></path></svg><span class="cz da ii ij db dc dd de dg ik df gz">Open gallery view</span></button><div class="nv tq bu f nx"></div></div><div class="sm sn do fd es rl tr is aq nk nl ro rp"><span class="nb">High anxiety on a high wire?</span><span class="bi cn sw is aq nk nl">Credit: Holger Kirk/Shutterstock.com</span></div></figure><p class="sd tm lb tn to tp">The missing link between our mental state and testosterone levels turned out to be a key receptor in the brain called "tachykinin receptor 3" or TACR3, Knafo and the team revealed for the first time.</p><div class="undefined ib"><div class="FI_PH"></div></div><p class="sd tm lb tn to tp"><strong class="fd">When your rat doesn't give a damn</strong></p><div class="undefined ib"><div class="FI_PH"></div></div><p class="sd tm lb tn to tp">The occasional bout of anxiety is rational. It falls into the category of disorder, though, when the anxiety becomes uncontrollable. Low testosterone isn't the cause of all irrational anxiety, but it can be a significant contributor.</p><div class="undefined ib"><div class="FI_PH"></div></div><ul class="sd ts" data-test="relatedArticles"><li class="tt bu a tu tv tw tx ty tz ua gg ub uc ud ue uf ug uh ui uj uk ul um"><a data-test="articleLink" href="/science-and-health/2023-09-24/ty-article/can-intermittent-fasting-help-you-live-longer-ask-these-rats/0000018a-88ef-db38-a18b-ffff71e20000"><span class="tw fd bu ps un uo up uq ur us ut uu uv uw ux uy lb lc to uz du je va vb vc">Can intermittent fasting help you live longer? Ask these rats</span></a></li><li class="tt bu a tu tv tw tx ty tz ua gg ub uc ud ue uf ug uh ui uj uk ul um"><a data-test="articleLink" href="/israel-news/science/2024-01-08/ty-article-magazine/science-discovers-secret-of-dieting-in-pigs/0000018c-e9d8-d249-a1ce-efdd11220000"><span class="tw fd bu ps un uo up uq ur us ut uu uv uw ux uy lb lc to uz du je va vb vc">Science discovers secret of dieting, in pigs</span></a></li><li class="tt bu a tu tv tw tx ty tz ua gg ub uc ud ue uf ug uh ui uj uk ul um"><a data-test="articleLink" href="/science-and-health/2023-10-26/ty-article/granny-knows-best-menopause-identified-in-the-chimpanzee/0000018b-6af5-df4c-a78b-7efd43c50000"><span class="tw fd bu ps un uo up uq ur us ut uu uv uw ux uy lb lc to uz du je va vb vc">Granny knows best? Menopause identified in the chimpanzee</span></a></li></ul><p class="sd tm lb tn to tp">Knafo and the team knew that rats can suffer from anxiety disorder as well. That is sad. Among related rats, within the family, some siblings are bold and some are nervous wrecks. </p><div class="undefined ib"><div class="FI_PH"></div></div><p class="sd tm lb tn to tp">"Most rats show a normal distribution of anxiety, but from time to time you see a really anxious rat and sometimes see a rat who isn't anxious at all," the professor elaborates. About 5 to 10 percent of rats are emotional outliers, she estimates.</p><div class="undefined ib"><div class="FI_PH"></div></div><p class="sd tm lb tn to tp">Knafo wondered what made the brash rats and anxious rats different. So the team chose the most radical cases based on their behavior in the maze, subsequently led these radicals to their Maker and analyzed gene expression in their hippocampi – because the hippocampus is thought to be related to anxiety. </p><div class="undefined ib"><div class="FI_PH"></div></div><p class="sd tm lb tn to tp">There were differences in the expression of several genes, but the tachykinin receptor TACR3 stood out, Knafo says. </p><div class="undefined ib"><div class="FI_PH"></div></div><p class="sd tm lb tn to tp">Anxious boy rats turned out consistently to have low expression of TACR3 in the hippocampus. Brash rats consistently had high expression (lots of testosterone receptor in their hippocampi). </p><div class="undefined ib"><div class="FI_PH"></div></div><p class="sd tm lb tn to tp">Tachykinins are a nervous system protein that <a class="sy sz ta tb jb kv tc td te tf tg th sg fo jo jp" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6880623" target="_blank" referrerpolicy="no-referrer-when-downgrade">exists in all bilateral animals</a> – you, fish, dogs, worms. They are involved in a vast array of roles. A 2019 study describing tachykinins in the fruit fly, for instance, said they are involved in "early olfactory processing, neuromodulation in circuits controlling locomotion and food search, nociception, aggression, metabolic stress, and hormone release. TK signaling also regulates lipid metabolism" – for starters. </p><div class="undefined ib"><div class="FI_PH"></div></div><p class="sd tm lb tn to tp">Men with abnormal TACR3 may <a class="sy sz ta tb jb kv tc td te tf tg th sg fo jo jp" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3890219/" target="_blank" referrerpolicy="no-referrer-when-downgrade">exhibit micropenis</a>, cryptorchidism (absence of one or both testicles) and/or hypogonadism (testicular dysfunction). Their testosterone production may be deficient to nonexistent, and puberty may be impaired or never happen. They may also suffer from depression – and heightened anxiety. </p><div class="undefined ib"><div class="FI_PH"></div></div><p class="sd tm lb tn to tp">Rats too. In short, the most striking thing about the ultra-anxious rats was low to no TACR3 levels, and low testosterone. Meanwhile, rats with high testosterone didn't give a damn: maze on! </p><div class="undefined ib"><div class="FI_PH"></div></div><figure class="} bu ib f cn sd"><div class="dd bu rz"><button type="button" class="dg sa sb sc sd hm ic ps hz dd se sf sg dv sh si"><svg width="1em" height="1em" viewBox="0 0 256 256" class="cu sj cv sk ib fx" data-test="IconZoomIn"> <path fill="currentColor" d="M165.9 153.6c7.8-10.8 12.5-24.1 12.5-38.5 0-36.3-29.5-65.8-65.7-65.8S47 78.9 47 115.1c0 36.3 29.5 65.8 65.7 65.8 14.7 0 28.3-4.9 39.3-13.1l51.6 51.6 14.1-14.1-51.8-51.7zM148 120h-28v28h-16v-28H76v-16h28V76h16v28h28v16z"></path></svg><span class="cz da ii ij db dc dd de dg ik df gz">Open gallery view</span></button><div class="nv vd bu f nx"></div></div><div class="sm sn do fd es rl tr is aq nk nl ro rp"><span class="nb">Two brown rats boldly walking through water at night</span><span class="bi cn sw is aq nk nl">Credit: Rudmer Zwerver / Shutterstock.com</span></div></figure><p class="sd tm lb tn to tp"><strong class="fd">See the light</strong></p><div class="undefined ib"><div class="FI_PH"></div></div><p class="sd tm lb tn to tp">Now, if male rats with TACR3 and testosterone deficiency are given testosterone (by injection) – they go through puberty and are okay. The expression of TACR3 in their brains picks up and they lose the anxiety disorder. Testosterone cures the little creatures, Knafo sums up.</p><div class="undefined ib"><div class="FI_PH"></div></div><p class="sd tm lb tn to tp">Talk about chickens and eggs. Moreover, the team found that if one tests TACR3 expression in the hippocampus from age zero (embryo) to adulthood (okay, a 3-month-old rat, but it counts because the rat can reach puberty at about six to ten weeks) – the increase in TACR3 expression during puberty is a hundredfold. </p><div class="undefined ib"><div class="FI_PH"></div></div><p class="sd tm lb tn to tp">So are toddler rats with low TACR3 and testosterone highly anxious? Yes they are, Knafo says. Aha. </p><div class="undefined ib"><div class="FI_PH"></div></div><p class="sd tm lb tn to tp">By the way, there was a snag in testing the young rats: the adult mazes weren't the right size, but the team solved that by using mazes built for mice. </p><div class="undefined ib"><div class="FI_PH"></div></div><p class="sd tm lb tn to tp">In lady rats, they found that TACR3 expression fluctuates with the oestrus cycle, Knafo says.</p><div class="undefined ib"><div class="FI_PH"></div></div><p class="sd tm lb tn to tp">She adds that "testosterone replacement therapy" has been known to help men with "mood disorders" too – <a class="sy sz ta tb jb kv tc td te tf tg th sg fo jo jp" href="https://pubmed.ncbi.nlm.nih.gov/32800673/" target="_blank" referrerpolicy="no-referrer-when-downgrade">clinical trials are underway</a>. </p><div class="undefined ib"><div class="FI_PH"></div></div><p class="sd tm lb tn to tp">So what have we? TACR3 and testosterone are in a mutual regulation situation, the team found. Testosterone and TACR3 deficiency is associated with elevated anxiety caused by biology, not psychology or reading Reddit. 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href="https://www.haaretz.co.il/news/security/2025-02-13/ty-article-magazine/.premium/00000194-fe7c-df1c-ad94-ff7e52d90000" class="zx">רוגלה ישראלית</a></li><li class="zx"><a data-test="link" href="https://www.haaretz.co.il/news/2023-11-23/ty-article-magazine/0000018b-4196-d242-abef-53b654760000" class="zx">שמות החטופים</a></li><li class="zx"><a data-test="link" href="https://www.haaretz.co.il/news/security/2025-02-11/ty-article/00000194-f3e3-d542-ad9e-f3f7bfde0000" class="zx">מכרז הנשק</a></li><li class="zx"><a data-test="link" href="https://www.haaretz.co.il/gallery/television/2023-10-31/ty-article-static-ext/0000018a-5eed-d845-adfe-feedb1dc0000" class="zx">סדרות מומלצות</a></li><li class="zx"><a data-test="link" href="https://www.haaretz.co.il/gallery/cinema/2023-06-07/ty-article-static-ext/00000188-1e0e-df77-afe9-5fceba2b0000" class="zx">סרטים חדשים בקולנוע</a></li><li class="zx"><a data-test="link" href="https://www.haaretz.co.il/2022-04-11/ty-article-static-ext/0000017f-a795-d7c6-a37f-ff9777ad0000" class="zx">מפלס הכנרת</a></li><li class="zx"><a data-test="link" href="https://www.haaretz.co.il/news/magazine/2024-07-07/ty-article-magazine/.highlight/00000190-7e1e-d7c8-a9fb-ffde182f0000" class="zx">7 באוקטובר</a></li><li class="zx"><a data-test="link" href="https://www.haaretz.co.il/news/world/america/us-election" class="zx"> בחירות בארה"ב</a></li></ul></section><section class="agf agg agh"><h2 class="zx on">Partnerships</h2><ul><li class="zx"><a data-test="link" href="/haaretz-labels" class="zx">Haaretz Labels</a></li><li class="zx"><a data-test="link" href="/haaretz-labels/real-estate" class="zx">Home for Sale in Israel</a></li></ul></section></div></div><div class="is aq it iu">Haaretz.com, the online English edition of Haaretz Newspaper in Israel, gives you breaking news, analyses and opinions about Israel, the Middle East and the Jewish World.<br/>© Haaretz Daily Newspaper Ltd. All Rights Reserved<br/></div></div></div></footer></div></div><script type="application/ld+json">{"@context":"http://schema.org","@type":"NewsArticle","author":[{"@context":"http://schema.org","@type":"Person","description":"Ruth Schuster is Senior Editor for archaeology and science at the Haaretz English Edition. Schuster has worked in writing, editing and translation for English and Hebrew-language publications for more than three decades. She holds a BSc in biology from the Hebrew University of Jerusalem. She lives in Israel and promotes animal rights.","email":"ruth.schuster@themarker.com","name":"Ruth Schuster","url":"/ty-WRITER/0000017f-da24-d249-ab7f-fbe4b5f00000"}],"articleBody":"Low testosterone is associated with high anxiety, research has found. Why exactly had never been understood, but now the link has been elucidated in a groundbreaking study recently published in the journal of Molecular Psychiatry. With the help of the radicals in the community – namely, the shrinking violets and members devoid of any anxiety whatsoever – a team at Be'er Sheva's Ben-Gurion University of the Negev led by Prof. Shira Knafo, head of the Molecular Cognition Laboratory, discovered the missing link between anxiety and the male hormone. Knafo and the team worked on rats, chiefly males, and chiefly because science frowns on experimentation on and dissection of men. But their findings apply broadly. In any given population of people/rodents, some will be emotional outliers: some will be prone to high anxiety, while others will feel none at all. In hope of shedding light on the difference and how that connects with male hormone levels, Knafo and the team looked at rats at the extremes of the spectrum, she explained in a phone interview. How does one evaluate anxiety in the rat? By its behavior in a maze. If the rodent skulks in dark corners, it is anxious. If it boldly struts out into the light and solves the maze, it's sanguine. The missing link between our mental state and testosterone levels turned out to be a key receptor in the brain called \"tachykinin receptor 3\" or TACR3, Knafo and the team revealed for the first time. When your rat doesn't give a damn The occasional bout of anxiety is rational. It falls into the category of disorder, though, when the anxiety becomes uncontrollable. Low testosterone isn't the cause of all irrational anxiety, but it can be a significant contributor. Knafo and the team knew that rats can suffer from anxiety disorder as well. That is sad. Among related rats, within the family, some siblings are bold and some are nervous wrecks. \"Most rats show a normal distribution of anxiety, but from time to time you see a really anxious rat and sometimes see a rat who isn't anxious at all,\" the professor elaborates. About 5 to 10 percent of rats are emotional outliers, she estimates. Knafo wondered what made the brash rats and anxious rats different. So the team chose the most radical cases based on their behavior in the maze, subsequently led these radicals to their Maker and analyzed gene expression in their hippocampi – because the hippocampus is thought to be related to anxiety. There were differences in the expression of several genes, but the tachykinin receptor TACR3 stood out, Knafo says. Anxious boy rats turned out consistently to have low expression of TACR3 in the hippocampus. Brash rats consistently had high expression (lots of testosterone receptor in their hippocampi). Tachykinins are a nervous system protein that exists in all bilateral animals – you, fish, dogs, worms. They are involved in a vast array of roles. A 2019 study describing tachykinins in the fruit fly, for instance, said they are involved in \"early olfactory processing, neuromodulation in circuits controlling locomotion and food search, nociception, aggression, metabolic stress, and hormone release. TK signaling also regulates lipid metabolism\" – for starters. Men with abnormal TACR3 may exhibit micropenis, cryptorchidism (absence of one or both testicles) and/or hypogonadism (testicular dysfunction). Their testosterone production may be deficient to nonexistent, and puberty may be impaired or never happen. They may also suffer from depression – and heightened anxiety. Rats too. In short, the most striking thing about the ultra-anxious rats was low to no TACR3 levels, and low testosterone. Meanwhile, rats with high testosterone didn't give a damn: maze on! See the light Now, if male rats with TACR3 and testosterone deficiency are given testosterone (by injection) – they go through puberty and are okay. The expression of TACR3 in their brains picks up and they lose the anxiety disorder. Testosterone cures the little creatures, Knafo sums up. Talk about chickens and eggs. Moreover, the team found that if one tests TACR3 expression in the hippocampus from age zero (embryo) to adulthood (okay, a 3-month-old rat, but it counts because the rat can reach puberty at about six to ten weeks) – the increase in TACR3 expression during puberty is a hundredfold. So are toddler rats with low TACR3 and testosterone highly anxious? Yes they are, Knafo says. Aha. By the way, there was a snag in testing the young rats: the adult mazes weren't the right size, but the team solved that by using mazes built for mice. In lady rats, they found that TACR3 expression fluctuates with the oestrus cycle, Knafo says. She adds that \"testosterone replacement therapy\" has been known to help men with \"mood disorders\" too – clinical trials are underway. So what have we? TACR3 and testosterone are in a mutual regulation situation, the team found. Testosterone and TACR3 deficiency is associated with elevated anxiety caused by biology, not psychology or reading Reddit. And in the future, the discoveries in this paper could lead to novel approaches to rats suffering from high anxiety due to testosterone deficiency – and humans too.","breadcrumb":{"@context":"http://schema.org","@type":"BreadcrumbList","itemListElement":[{"@context":"http://schema.org","@type":"ListItem","item":"https://www.haaretz.com/","name":"Haaretz.com - Homepage","position":1},{"@context":"http://schema.org","@type":"ListItem","item":"https://www.haaretz.com/israel-news","name":"Israel News","position":2},{"@context":"http://schema.org","@type":"ListItem","item":"https://www.haaretz.com/israel-news/science","name":"Science ","position":3}]},"url":"https://www.haaretz.com/israel-news/science/2024-01-25/ty-article/israeli-scientists-discover-missing-link-between-anxiety-and-low-testosterone/0000018d-40b2-d02c-a79f-43bb44b50000","dateModified":"2024-01-25T15:32:00+0200","datePublished":"2024-01-25T15:32:00+0200","description":"Male hormone deficiency was known to be associated with anxiety, and now we know how. The discovery suggests a new approach to male angst","hasPart":{"isAccessibleForFree":"false","cssSelector":".article-body-wrapper","@type":"WebPageElement"},"image":[{"@context":"http://schema.org","@type":"ImageObject","height":3744,"url":"https://img.haarets.co.il/bs/0000018d-40b2-d02c-a79f-43bb404b0000/4c/69/df80e6fb45eb93d87383aa0850ad/55318361.JPG?precrop=3744,3744,x957,y0","width":5616}],"inLanguage":"en","isAccessibleForFree":"false","mainEntityOfPage":{"@type":"WebPage","@id":"https://www.haaretz.com/israel-news/science/2024-01-25/ty-article/israeli-scientists-discover-missing-link-between-anxiety-and-low-testosterone/0000018d-40b2-d02c-a79f-43bb44b50000"},"name":"Israeli scientists discover missing link between anxiety and low testosterone","publisher":{"@type":"Organization","name":"Haaretz","logo":{"@type":"ImageObject","url":"https://img.haarets.co.il/bs/00000180-a718-d12e-a9e7-bf3a013a0001/3e/9d/d81bd9254075867ccdac58dc7a59/hdclogo-copy.png?width=500&height=500","width":500,"height":500},"url":"https://www.haaretz.com","sameAs":["https://en.wikipedia.org/wiki/Haaretz","https://www.facebook.com/haaretzcom","https://twitter.com/haaretzcom","https://www.youtube.com/user/haaretzcom"]},"articleSection":"Science ","headline":"Israeli scientists discover missing link between anxiety and low testosterone"}</script></div><script id="__NEXT_DATA__" type="application/json">{"props":{"isWebView":false,"isDarkMode":false,"pageProps":{},"query":{"path":"/israel-news/science/2024-01-25/ty-article/israeli-scientists-discover-missing-link-between-anxiety-and-low-testosterone/0000018d-40b2-d02c-a79f-43bb44b50000","isBlock":false,"paywallType":"open","isPreview":false,"articleType":"standardArticle","isWebView":false,"isDarkMode":false,"articleId":"0000018d-40b2-d02c-a79f-43bb44b50000","isLabel":false,"dateFormat":"dd-MM-yyyy","isBot":false,"print":false,"platform":"desktop"},"asPath":"/israel-news/science/2024-01-25/ty-article/israeli-scientists-discover-missing-link-between-anxiety-and-low-testosterone/0000018d-40b2-d02c-a79f-43bb44b50000","pathname":"/article","apolloState":{"ROOT_QUERY":{"pageType":"Article","ariaLive":{"type":"id","generated":true,"id":"$ROOT_QUERY.ariaLive","typename":"AriaLive"},"hostname":"hdc-app.haaretz.com","scroll":{"type":"id","generated":true,"id":"$ROOT_QUERY.scroll","typename":"Scroll"},"user":{"type":"id","generated":true,"id":"$ROOT_QUERY.user","typename":"HtzUser"},"listDuplicationIds":{"type":"json","json":[]},"personalListPq":{"type":"json","json":[]},"googleAnalyticsId":{"type":"id","generated":true,"id":"$ROOT_QUERY.googleAnalyticsId","typename":"GoogleAnalyticsId"},"a11yToggle":false,"isAnimationReduced":false,"articleId":"0000018d-40b2-d02c-a79f-43bb44b50000","articleType":"standardArticle","authorsContentId":"0000017f-da24-d249-ab7f-fbe4b5f00000","articleSection":{"type":"id","generated":true,"id":"$ROOT_QUERY.articleSection","typename":"ArticleSection"},"canonicalUrl":"https://www.haaretz.com/israel-news/science/2024-01-25/ty-article/israeli-scientists-discover-missing-link-between-anxiety-and-low-testosterone/0000018d-40b2-d02c-a79f-43bb44b50000","path":"/israel-news/science/2024-01-25/ty-article/israeli-scientists-discover-missing-link-between-anxiety-and-low-testosterone/0000018d-40b2-d02c-a79f-43bb44b50000","isBot":false,"commentsElementId":"0000018d-40b2-d02c-a79f-43bb44cb0000","isMouseStory":false,"isOsakaDisplayed":false,"isOsakaDisabled":false,"isMastheadSticky":false,"isStickyMastheadDisabled":false,"pageGallery":{"type":"id","generated":true,"id":"$ROOT_QUERY.pageGallery","typename":"PageGallery"},"osakaCanRender":false,"platform":null,"isBlocked":false,"isSuperContent":false,"zenMode":false,"isPremiumContent":false,"isCloseArticle":false,"pageDateTimeString":null,"sectionId":null,"twitterTitle":"Israeli scientists discover missing link between anxiety and low testosterone","fbScriptLoaded":false,"isLabel":false,"isReadyToRenderExternals":true,"htzUser":{"type":"id","generated":true,"id":"$ROOT_QUERY.htzUser","typename":"UserHtz"},"Page({\"id\":\"0000018d-40b2-d02c-a79f-43bb44b50000\"})":{"type":"id","generated":false,"id":"PageLayout:0000018d-40b2-d02c-a79f-43bb44b50000","typename":"PageLayout"},"title":"Israeli Scientists Discover Missing Link Between Anxiety and Low Testosterone - 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Schuster has worked in writing, editing and translation for English and Hebrew-language publications for more than three decades. She holds a BSc in biology from the Hebrew University of Jerusalem. She lives in Israel and promotes animal rights.\",\"email\":\"ruth.schuster@themarker.com\",\"name\":\"Ruth Schuster\",\"url\":\"/ty-WRITER/0000017f-da24-d249-ab7f-fbe4b5f00000\"}],\"articleBody\":\"Low testosterone is associated with high anxiety, research has found. Why exactly had never been understood, but now the link has been elucidated in a groundbreaking study recently published in the journal of Molecular Psychiatry. With the help of the radicals in the community – namely, the shrinking violets and members devoid of any anxiety whatsoever – a team at Be'er Sheva's Ben-Gurion University of the Negev led by Prof. Shira Knafo, head of the Molecular Cognition Laboratory, discovered the missing link between anxiety and the male hormone. Knafo and the team worked on rats, chiefly males, and chiefly because science frowns on experimentation on and dissection of men. But their findings apply broadly. In any given population of people/rodents, some will be emotional outliers: some will be prone to high anxiety, while others will feel none at all. In hope of shedding light on the difference and how that connects with male hormone levels, Knafo and the team looked at rats at the extremes of the spectrum, she explained in a phone interview. How does one evaluate anxiety in the rat? By its behavior in a maze. If the rodent skulks in dark corners, it is anxious. If it boldly struts out into the light and solves the maze, it's sanguine. The missing link between our mental state and testosterone levels turned out to be a key receptor in the brain called \\\"tachykinin receptor 3\\\" or TACR3, Knafo and the team revealed for the first time. When your rat doesn't give a damn The occasional bout of anxiety is rational. It falls into the category of disorder, though, when the anxiety becomes uncontrollable. Low testosterone isn't the cause of all irrational anxiety, but it can be a significant contributor. Knafo and the team knew that rats can suffer from anxiety disorder as well. That is sad. Among related rats, within the family, some siblings are bold and some are nervous wrecks. \\\"Most rats show a normal distribution of anxiety, but from time to time you see a really anxious rat and sometimes see a rat who isn't anxious at all,\\\" the professor elaborates. About 5 to 10 percent of rats are emotional outliers, she estimates. Knafo wondered what made the brash rats and anxious rats different. So the team chose the most radical cases based on their behavior in the maze, subsequently led these radicals to their Maker and analyzed gene expression in their hippocampi – because the hippocampus is thought to be related to anxiety. There were differences in the expression of several genes, but the tachykinin receptor TACR3 stood out, Knafo says. Anxious boy rats turned out consistently to have low expression of TACR3 in the hippocampus. Brash rats consistently had high expression (lots of testosterone receptor in their hippocampi). Tachykinins are a nervous system protein that exists in all bilateral animals – you, fish, dogs, worms. They are involved in a vast array of roles. A 2019 study describing tachykinins in the fruit fly, for instance, said they are involved in \\\"early olfactory processing, neuromodulation in circuits controlling locomotion and food search, nociception, aggression, metabolic stress, and hormone release. TK signaling also regulates lipid metabolism\\\" – for starters. Men with abnormal TACR3 may exhibit micropenis, cryptorchidism (absence of one or both testicles) and/or hypogonadism (testicular dysfunction). Their testosterone production may be deficient to nonexistent, and puberty may be impaired or never happen. They may also suffer from depression – and heightened anxiety. Rats too. In short, the most striking thing about the ultra-anxious rats was low to no TACR3 levels, and low testosterone. Meanwhile, rats with high testosterone didn't give a damn: maze on! See the light Now, if male rats with TACR3 and testosterone deficiency are given testosterone (by injection) – they go through puberty and are okay. The expression of TACR3 in their brains picks up and they lose the anxiety disorder. Testosterone cures the little creatures, Knafo sums up. Talk about chickens and eggs. Moreover, the team found that if one tests TACR3 expression in the hippocampus from age zero (embryo) to adulthood (okay, a 3-month-old rat, but it counts because the rat can reach puberty at about six to ten weeks) – the increase in TACR3 expression during puberty is a hundredfold. So are toddler rats with low TACR3 and testosterone highly anxious? Yes they are, Knafo says. Aha. By the way, there was a snag in testing the young rats: the adult mazes weren't the right size, but the team solved that by using mazes built for mice. In lady rats, they found that TACR3 expression fluctuates with the oestrus cycle, Knafo says. She adds that \\\"testosterone replacement therapy\\\" has been known to help men with \\\"mood disorders\\\" too – clinical trials are underway. So what have we? TACR3 and testosterone are in a mutual regulation situation, the team found. Testosterone and TACR3 deficiency is associated with elevated anxiety caused by biology, not psychology or reading Reddit. 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In short, the most striking thing about the ultra-anxious rats was low to no TACR3 levels, and low testosterone. Meanwhile, rats with high testosterone didn't give a damn: maze on! 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","tag":"p"},"HtmlNode:p-22":{"__typename":"HtmlNode","id":"p-22","attributes":null,"content":"In lady rats, they found that TACR3 expression fluctuates with the oestrus cycle, Knafo says.","tag":"p"},"HtmlNode:p-23":{"__typename":"HtmlNode","id":"p-23","attributes":null,"content":"She adds that \"testosterone replacement therapy\" has been known to help men with \"mood disorders\" too – \u003ca class=\"#a#\" href=\"https://pubmed.ncbi.nlm.nih.gov/32800673/\" target=\"_blank\" referrerpolicy=\"no-referrer-when-downgrade\"\u003eclinical trials are underway\u003c/a\u003e. ","tag":"p"},"HtmlNode:p-24":{"__typename":"HtmlNode","id":"p-24","attributes":null,"content":"So what have we? TACR3 and testosterone are in a mutual regulation situation, the team found. Testosterone and TACR3 deficiency is associated with elevated anxiety caused by biology, not psychology or reading Reddit. 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