Diseases of the Nervous System Mini-Review


It​ ​is​ ​clear​ ​socially,​ ​academically,​ ​and​ ​financially​ ​that​ ​today’s​ ​generation​ ​has​ ​an​ ​increased​ ​number of​ ​individuals​ ​with​ ​stress​ ​than​ ​previous​ ​generations.​ ​Most​ ​of​ ​this​ ​stress​ ​falls​ ​under​ ​chronic​ ​stress which​ ​interferes​ ​with​ ​people’s​ ​ability​ ​to​ ​function​ ​normally​ ​long​ ​term.​ ​The​ ​highest​ ​stress​ ​level​ ​is currently​ ​found​ ​in​ ​millennials​ ​born​ ​from​ ​1984-1999,​ ​aged​ ​18-33​ ​years​ ​old​ ​with​ ​an​ ​even​ ​higher concentration​ ​in​ ​college​ ​students.​ ​Common​ ​symptoms​ ​that​ ​occur​ ​are​ ​mood​ ​swings,​ ​lack​ ​of​ ​or excessive​ ​amounts​ ​of​ ​sleep,​ ​drug​ ​or​ ​alcohol​ ​abuse,​ ​social​ ​withdrawal,​ ​lack​ ​of​ ​motivation, anxiety,​ ​and​ ​feeling​ ​overwhelmed.​ ​However,​ ​at​ ​what​ ​point​ ​does​ ​it​ ​stop​ ​being​ ​college/young​ ​adult stress​ ​factors​ ​and​ ​actually​ ​becomes​ ​a​ ​mental​ ​challenge​ ​that​ ​gets​ ​in​ ​the​ ​way​ ​of​ ​daily​ ​activities. The​ ​symptoms​ ​typically​ ​used​ ​to​ ​describe​ ​depression​ ​include​ ​all​ ​of​ ​the​ ​ones​ ​previously​ ​mentioned from​ ​stress,​ ​however​ ​at​ ​a​ ​more​ ​profound​ ​emotional​ ​state​ ​and​ ​includes​ ​anhedonia,​ ​the​ ​lack​ ​of anything​ ​pleasurable,​ ​and​ ​also​ ​when​ ​an​ ​individual​ ​seems​ ​capable​ ​of​ ​harming​ ​themself​ ​or​ ​others. It​ ​is​ ​often​ ​common​ ​for​ ​individuals​ ​in​ ​high​ ​demand​ ​jobs​ ​or​ ​those​ ​with​ ​pressure​ ​in​ ​daily​ ​tasks​ ​and assignments​ ​to​ ​brush​ ​off​ ​serious​ ​symptoms​ ​in​ ​behavior​ ​and​ ​just​ ​call​ ​it​ ​stress​ ​in​ ​fear​ ​of​ ​seeing​ ​a mental​ ​health​ ​professional​ ​because​ ​of​ ​lack​ ​of​ ​time​ ​or​ ​being​ ​accustomed​ ​to​ ​their​ ​concerns​ ​being trivialized​ ​by​ ​others.​ ​A​ ​social​ ​initiative​ ​to​ ​be​ ​properly​ ​trained​ ​in​ ​recognizing​ ​factors​ ​across students,​ ​faculty,​ ​instructors,​ ​bosses,​ ​and​ ​friendly​ ​strangers​ ​can​ ​help​ ​give​ ​the​ ​individual​ ​support and​ ​to​ ​not​ ​fear​ ​asking​ ​for​ ​help​ ​when​ ​it​ ​is​ ​necessary.​ ​This​ ​review​ ​will​ ​focus​ ​on​ ​finding​ ​if​ ​there​ ​is​ ​a correlation​ ​between​ ​stress​ ​and​ ​depression,​ ​as​ ​well​ ​as​ ​what​ ​differentiates​ ​them​ ​and​ ​how​ ​further research​ ​can​ ​help​ ​find​ ​ways​ ​to​ ​lessen​ ​the​ ​amount​ ​of​ ​stress​ ​or​ ​depression​ ​in​ ​individuals​ ​and​ ​how to​ ​combat​ ​it.

What​ ​is​ ​depression?

Depression​ ​has​ ​been​ ​mentioned​ ​in​ ​literature​ ​since​ ​the​ ​pre-Hippocrates​ ​era.​ ​Greek​ ​mythology recognized​ ​mania​ ​and​ ​melancholy​ ​as​ ​abnormal​ ​mood​ ​states.​ ​Aretaeus​ ​of​ ​Cappadocia,​ ​a​ ​medical scholar​ ​from​ ​the​ ​first​ ​century​ ​A.D.,​ ​described​ ​the​ ​commonality​ ​between​ ​melancholia​ ​as​ ​the beginning​ ​of​ ​mania​ ​and​ ​the​ ​two​ ​as​ ​counterparts.​ ​A​ ​Persian​ ​physician​ ​in​ ​the​ ​eleventh​ ​century described​ ​symptoms​ ​that​ ​included​ ​anxiety,​ ​phobias,​ ​and​ ​suspicions​ ​of​ ​other​ ​systems.​ ​Emil Kraepelin​ ​in​ ​1896​ ​made​ ​the​ ​key​ ​distinction​ ​in​ ​defining​ ​depression​ ​from​ ​schizophrenia​ ​as​ ​having manic​ ​and​ ​depressed​ ​phases​ ​however,​ ​without​ ​any​ ​intellectual​ ​deterioration.​ ​Freud​ ​declared​ ​a connection​ ​between​ ​melancholia​ ​and​ ​mourning​ ​or​ ​grief​ ​in​ ​1917.​ ​In​ ​the​ ​mid​ ​1970s,​ ​the​ ​possibility of​ ​depression​ ​occurring​ ​due​ ​to​ ​a​ ​chemical​ ​imbalance​ ​in​ ​neurotransmitters​ ​of​ ​the​ ​brain​ ​came​ ​to light​ ​and​ ​was​ ​called​ ​major​ ​depressive​ ​disorder.​ ​Today,​ ​15​ ​million​ ​Americans​ ​a​ ​year​ ​struggle​ ​with depression​ ​by​ ​itself​ ​and​ ​along​ ​with​ ​other​ ​mental​ ​and​ ​physical​ ​health​ ​concerns​ ​that​ ​affect​ ​bodily functions​ ​such​ ​as​ ​disruption​ ​of​ ​sleep,​ ​appetite,​ ​and​ ​weight.​ ​While​ ​there​ ​is​ ​no​ ​distinct​ ​cure, depression​ ​is​ ​highly​ ​treatable,​ ​even​ ​and​ ​especially​ ​if​ ​it​ ​is​ ​focused​ ​in​ ​treating​ ​according​ ​to​ ​each individual.

Depression​ ​however,​ ​is​ ​not​ ​the​ ​same​ ​as​ ​sadness​ ​or​ ​unhappiness.​ ​It​ ​includes​ ​an​ ​extended period​ ​of​ ​time​ ​in​ ​a​ ​profound​ ​emotional​ ​state​ ​of​ ​feelings​ ​such​ ​as​ ​worthlessness,​ ​desperation,​ ​and hopelessness​ ​to​ ​the​ ​point​ ​where​ ​one​ ​loses​ ​libido​ ​and​ ​energy​ ​and​ ​has​ ​suicidal​ ​or​ ​harmful​ ​thoughts. Different​ ​forms​ ​of​ ​depression​ ​can​ ​be​ ​broken​ ​down​ ​into​ ​subcategories​ ​such​ ​as​ ​grieving,​ ​secondary depression,​ ​clinical​ ​depression​ ​and​ ​bipolar​ ​depression,​ ​as​ ​organized​ ​by​ ​Harold​ ​Sontheimer. Grieving​ ​differs​ ​since​ ​it​ ​typically​ ​lasts​ ​up​ ​to​ ​12​ ​weeks​ ​after​ ​losing​ ​a​ ​loved​ ​one​ ​or​ ​dealing​ ​with life​ ​struggles​ ​such​ ​as​ ​being​ ​laid​ ​off​ ​or​ ​financial​ ​struggles​ ​where​ ​daily​ ​motivation​ ​is​ ​hard​ ​to​ ​come by.​ ​Secondary​ ​depression​ ​is​ ​associated​ ​with​ ​the​ ​difficulty​ ​in​ ​dealing​ ​with​ ​illness​ ​where treatments​ ​or​ ​solutions​ ​are​ ​uncertain.​ ​Clinical​ ​depression​ ​tends​ ​to​ ​occur​ ​in​ ​young​ ​adults​ ​but​ ​is twice​ ​as​ ​common​ ​in​ ​women​ ​as​ ​it​ ​is​ ​in​ ​men​ ​and​ ​has​ ​a​ ​direct​ ​correlation​ ​as​ ​age​ ​increases.​ ​Bipolar depression​ ​includes​ ​unexplained​ ​mood​ ​swings​ ​that​ ​can​ ​vary​ ​between​ ​euphoria​ ​and​ ​depression. Individuals​ ​can​ ​have​ ​states​ ​of​ ​severe​ ​mania​ ​with​ ​paranoia​ ​and​ ​delusions​ ​or​ ​be​ ​in​ ​a​ ​manic​ ​state​ ​or high​ ​states​ ​of​ ​enthusiasm,​ ​expectations​ ​and​ ​energy.​ ​It​ ​is​ ​the​ ​leading​ ​disability​ ​for​ ​young​ ​adults from​ ​the​ ​ages​ ​of​ ​20​ ​to​ ​30​ ​and​ ​affects​ ​males​ ​and​ ​females​ ​equally.​ ​It​ ​is​ ​also​ ​believed​ ​that​ ​higher depression​ ​rates​ ​in​ ​this​ ​age​ ​group​ ​could​ ​be​ ​an​ ​underlying​ ​factor​ ​explaining​ ​higher​ ​rates​ ​of substance​ ​abuse​ ​of​ ​recreational​ ​drugs,​ ​alcohol​ ​and​ ​smoking.​ ​Individuals​ ​often​ ​experience changes​ ​in​ ​cognitive​ ​function​ ​which​ ​in​ ​turn​ ​affects​ ​cognitive​ ​performance​ ​in​ ​executive​ ​functions, attention,​ ​memory,​ ​and​ ​psychomotor​ ​speed​ ​(Hammar​ ​&​ ​Årdal,​ ​2009).

On​ ​the​ ​molecular​ ​level,​ ​depression​ ​has​ ​been​ ​associated​ ​with​ ​region​ ​specific​ ​neuronal​ ​cell loss​ ​and​ ​retraction​ ​of​ ​dendrites​ ​which​ ​causes​ ​changes​ ​in​ ​synaptic​ ​activity.​ ​This​ ​has​ ​been​ ​seen​ ​in the​ ​effect​ ​of​ ​antidepressant​ ​drugs​ ​in​ ​imaging​ ​studies.​ ​The​ ​neural​ ​circuits​ ​that​ ​are​ ​primarily affected​ ​in​ ​the​ ​brain​ ​include​ ​the​ ​prefrontal​ ​cortex,​ ​the​ ​hippocampus,​ ​and​ ​the​ ​limbic​ ​system​ ​and its​ ​structures​ ​including​ ​the​ ​ventral​ ​tegmental​ ​area,​ ​nucleus​ ​accumbens,​ ​locus​ ​coeruleus, thalamus,​ ​hippocampus,​ ​and​ ​amygdala.​ ​There​ ​are​ ​all​ ​structures​ ​known​ ​to​ ​affect​ ​and​ ​regulate emotions,​ ​reward​ ​feelings,​ ​motivation​ ​and​ ​executive​ ​functions.​ ​Patients​ ​with​ ​chronic​ ​depression have​ ​shown​ ​enhanced​ ​activity​ ​of​ ​the​ ​amygdala,​ ​decreased​ ​gray​ ​matter​ ​volume​ ​in​ ​the​ ​prefrontal cortex​ ​and​ ​hippocampus​ ​​​which​ ​also​ ​leads​ ​to​ ​a​ ​reduction​ ​in​ ​size​ ​of​ ​pyramidal​ ​neurons​ ​and​ ​a​ ​loss of​ ​GABAergic​ ​interneurons​ ​as​ ​well​ ​as​ ​a​ ​decline​ ​of​ ​astrocytes​ ​and​ ​oligodendrocytes​ ​in​ ​the prefrontal​ ​cortex.​ ​Antidepressant​ ​drugs​ ​prescribed​ ​today​ ​focus​ ​on​ ​changing​ ​the​ ​concentration​ ​of monoamines​ ​in​ ​the​ ​brain​ ​and​ ​balancing​ ​the​ ​connectivity​ ​of​ ​neural​ ​circuits​ ​and​ ​their​ ​signaling cascades​ ​in​ ​the​ ​networks​ ​of​ ​emotion​ ​as​ ​shown​ ​in​ ​Figure​ ​1.​ ​The​ ​blockage​ ​of​ ​serotonin​ ​reuptake causes​ ​the​ ​activation​ ​of​ ​G-protein-coupled​ ​receptors​ ​leading​ ​to​ ​enhanced​ ​cAMP​ ​signaling​ ​which leads​ ​to​ ​transcriptional​ ​changes​ ​in​ ​the​ ​cAMP-protein​ ​kinase​ ​response​ ​element​ ​binding​ ​pathway also​ ​known​ ​as​ ​the​ ​CREB​ ​pathway.​ ​This​ ​pathway​ ​is​ ​responsible​ ​for​ ​increasing​ ​or​ ​decreasing​ ​the transcription​ ​of​ ​downstream​ ​genes.​ ​A​ ​number​ ​of​ ​genes​ ​including​ ​neurotrophic​ ​factors​ ​such​ ​as BDNF​ ​(brain​ ​derived​ ​neurotrophic​ ​factors)​ ​are​ ​transcribed.​ ​Chronic​ ​treatments​ ​of​ ​antidepressant medication​ ​increase​ ​BDNF-mediated​ ​signaling​ ​because​ ​BDNF​ ​transcription​ ​and​ ​signaling​ ​in​ ​the hippocampus​ ​has​ ​been​ ​shown​ ​to​ ​be​ ​reduced​ ​in​ ​patients​ ​with​ ​stress​ ​and​ ​in​ ​post-mortem hippocampus​ ​of​ ​humans​ ​with​ ​depression​ ​(Krishnan​ ​&​ ​Nestler,​ ​2008).​ ​Understanding​ ​the molecular​ ​pathways​ ​of​ ​depression​ ​is​ ​a​ ​continuous​ ​process​ ​with​ ​tremendous​ ​amount​ ​of information​ ​still​ ​unknown.

Figure​ ​1:

A​ ​greater​ ​lifetime​ ​risk​ ​of​ ​mood​ ​disorders​ ​has​ ​been​ ​reported​ ​as​ ​well​ ​as​ ​an​ ​increase​ ​in​ ​each successive​ ​generation.​ ​In​ ​longitudinal​ ​studies​ ​done​ ​by​ ​Compton​ ​et​ ​al.,​ ​the​ ​prevalence​ ​of depression​ ​in​ ​U.S.​ ​adults​ ​rose​ ​from​ ​3.33%​ ​to​ ​7.06%​ ​between​ ​1991-2​ ​and​ ​2001-2.​ ​In​ ​college students​ ​and​ ​young​ ​adults,​ ​it​ ​was​ ​found​ ​that​ ​their​ ​psychopathology​ ​score​ ​on​ ​the​ ​clinical depression​ ​scale​ ​in​ ​2007​ ​compared​ ​to​ ​1938​ ​was​ ​6-8​ ​times​ ​more​ ​likely​ ​to​ ​meet​ ​the​ ​cutoff.​ ​In​ ​a Swedish​ ​population​ ​study​ ​1947,​ ​1957,​ ​and​ ​1972,​ ​researchers​ ​observed​ ​the​ ​increased​ ​risk​ ​of depression​ ​for​ ​all​ ​age​ ​groups​ ​however,​ ​young​ ​adults​ ​exhibited​ ​a​ ​tenfold​ ​increased​ ​risk​ ​from​ ​1957 to​ ​1972​ ​(Compton​ ​et​ ​al,​ ​2006).​ ​The​ ​rise​ ​in​ ​depression​ ​amongst​ ​individuals​ ​has​ ​been​ ​credited​ ​to the​ ​changes​ ​in​ ​diagnosis​ ​criteria​ ​that​ ​fail​ ​to​ ​include​ ​and​ ​recognize​ ​the​ ​variation​ ​of​ ​symptoms​ ​to classify​ ​the​ ​normal​ ​response​ ​of​ ​sadness​ ​as​ ​a​ ​mental​ ​disorder​ ​(Hidaka,​ ​2012).​ ​However,​ ​it​ ​can also​ ​be​ ​attributed​ ​to​ ​change​ ​in​ ​societal​ ​concepts​ ​and​ ​culture​ ​that​ ​the​ ​youth​ ​face​ ​when​ ​growing​ ​up and​ ​learn​ ​to​ ​yearn​ ​for​ ​a​ ​feeling​ ​of​ ​acceptance​ ​or​ ​of​ ​fitting​ ​in​ ​throughout​ ​social​ ​media​ ​platforms, in​ ​friend​ ​groups,​ ​or​ ​within​ ​their​ ​family​ ​and​ ​community.​ ​An​ ​increase​ ​in​ ​alcohol​ ​and​ ​drug​ ​usage found​ ​more​ ​commonly​ ​in​ ​young​ ​adults​ ​may​ ​​​also​ ​be​ ​a​ ​factor​ ​as​ ​to​ ​higher​ ​depression​ ​rates amongst​ ​this​ ​age​ ​group.​ ​“Anxiety​ ​in​ ​children​ ​and​ ​college​ ​students​ ​has​ ​increased​ ​almost​ ​one standard​ ​deviation​ ​from​ ​the​ ​1950’s​ ​to​ ​the​ ​1990’s”​ ​(Twenge,​ ​2000).​ ​A​ ​direct​ ​correlation​ ​amongst developed​ ​countries​ ​and​ ​the​ ​prevalence​ ​of​ ​psychiatric​ ​disorders​ ​has​ ​been​ ​observed​ ​as​ ​urban citizens​ ​have​ ​higher​ ​mood​ ​and​ ​anxiety​ ​disorders​ ​compared​ ​to​ ​rural​ ​citizens.​ ​Since​ ​young​ ​adults and​ ​college​ ​students​ ​are​ ​at​ ​the​ ​forefront​ ​of​ ​modernization​ ​in​ ​lifestyle,​ ​social​ ​networks,​ ​media​ ​and more,​ ​a​ ​higher​ ​depression​ ​prevalence​ ​and​ ​risk​ ​can​ ​be​ ​associated.​ ​Along​ ​with​ ​modernization, western​ ​culture​ ​has​ ​gained​ ​the​ ​reputation​ ​for​ ​not​ ​being​ ​as​ ​health​ ​conscious​ ​in​ ​terms​ ​of​ ​nutrition and​ ​physical​ ​health​ ​and​ ​fitness.​ ​A​ ​poor​ ​diet​ ​with​ ​low​ ​levels​ ​of​ ​physical​ ​activity​ ​and​ ​distractions that​ ​lead​ ​to​ ​more​ ​time​ ​inside​ ​and​ ​less​ ​sleep​ ​can​ ​all​ ​lead​ ​to​ ​the​ ​imbalance​ ​of​ ​body​ ​functions related​ ​to​ ​the​ ​endocrine​ ​and​ ​nervous​ ​system.​ ​It​ ​is​ ​commonly​ ​known​ ​that​ ​most​ ​young​ ​adults​ ​and especially​ ​college​ ​students​ ​lack​ ​proper​ ​nutrition​ ​as​ ​they​ ​are​ ​now​ ​responsible​ ​in​ ​providing​ ​their own​ ​meals​ ​and​ ​also​ ​rarely​ ​reach​ ​the​ ​recommended​ ​hours​ ​of​ ​sleep​ ​for​ ​their​ ​age​ ​range.​ ​The​ ​higher the​ ​level​ ​of​ ​stress​ ​the​ ​body​ ​faces,​ ​the​ ​higher​ ​its​ ​successability​ ​to​ ​depression​ ​(Wood​ ​&​ ​Bhatnagar, 2014).​ ​There​ ​is​ ​a​ ​difference​ ​with​ ​clinical​ ​depression​ ​and​ ​the​ ​large​ ​amounts​ ​of​ ​stress​ ​that​ ​can​ ​be obtained​ ​from​ ​jobs​ ​and​ ​school​ ​that​ ​leads​ ​to​ ​similar​ ​symptoms,​ ​however​ ​detecting​ ​the​ ​difference is​ ​the​ ​main​ ​concern​ ​of​ ​this​ ​review.

What​ ​is​ ​stress?
Stress​ ​is​ ​the​ ​body’s​ ​natural​ ​response​ ​to​ ​a​ ​pressure​ ​or​ ​threat.​ ​In​ ​small​ ​amounts​ ​it​ ​can​ ​be motivational,​ ​especially​ ​in​ ​the​ ​work​ ​environment​ ​as​ ​it​ ​keeps​ ​individuals​ ​alert,​ ​focused​ ​and energetic.​ ​However,​ ​in​ ​large​ ​amounts,​ ​it​ ​becomes​ ​easier​ ​for​ ​the​ ​body​ ​to​ ​be​ ​in​ ​a​ ​continuous heightened​ ​state​ ​of​ ​stress​ ​that​ ​can​ ​lead​ ​to​ ​health​ ​problems.​ ​As​ ​an​ ​individual’s​ ​age​ ​increases, stress​ ​commonly​ ​accumulates​ ​in​ ​a​ ​direct​ ​correlation​ ​as​ ​more​ ​responsibilities​ ​are​ ​assigned​ ​to​ ​the individual.​ ​It​ ​is​ ​mostly​ ​done​ ​at​ ​a​ ​manageable​ ​rate​ ​where​ ​the​ ​individual​ ​accustoms​ ​to​ ​the increasing​ ​amount​ ​and​ ​is​ ​not​ ​fully​ ​aware​ ​as​ ​to​ ​the​ ​levels​ ​of​ ​stress​ ​they​ ​endure​ ​until​ ​it​ ​begins​ ​to take​ ​a​ ​noticeable​ ​toll.​ ​This​ ​toll​ ​affects​ ​and​ ​suppress​ ​the​ ​immune​ ​system,​ ​digestive​ ​and reproductive​ ​system​ ​as​ ​well​ ​as​ ​circadian​ ​rhythms,​ ​it​ ​increases​ ​the​ ​risk​ ​of​ ​heart​ ​attacks​ ​and​ ​speeds up​ ​the​ ​aging​ ​process.​ ​It​ ​leaves​ ​individuals​ ​more​ ​susceptible​ ​to​ ​anxiety,​ ​depression,​ ​and​ ​other mental​ ​health​ ​problems.

There​ ​are​ ​different​ ​kinds​ ​of​ ​stressors​ ​that​ ​individuals​ ​will​ ​encounter.​ ​Primarily​ ​in​ ​young adults,​ ​intrapersonal​ ​sources​ ​of​ ​stress​ ​are​ ​the​ ​most​ ​frequent​ ​and​ ​reported​ ​source.​ ​Changes​ ​in sleep​ ​habits,​ ​breaks,​ ​eating​ ​habits,​ ​workload,​ ​and​ ​new​ ​responsibilities​ ​are​ ​what​ ​causes​ ​the​ ​highest amounts​ ​of​ ​stress​ ​(Ross​ ​et​ ​al,​ ​1999).​ ​A​ ​study​ ​done​ ​on​ ​the​ ​association​ ​between​ ​computer​ ​use​ ​and mental​ ​health​ ​symptoms​ ​in​ ​young​ ​adults​ ​found​ ​sleep​ ​disturbances​ ​due​ ​to​ ​high​ ​and​ ​medium computer​ ​usage​ ​in​ ​men,​ ​and​ ​high​ ​email​ ​and​ ​chat​ ​usage​ ​in​ ​women​ ​(Thomée​ ​et​ ​al,​ ​2012.). Computer​ ​usage​ ​can​ ​be​ ​synonymous​ ​to​ ​smartphone​ ​usage​ ​as​ ​it​ ​has​ ​become​ ​the​ ​most​ ​common and​ ​easiest​ ​mode​ ​of​ ​access​ ​to​ ​media.​ ​For​ ​college​ ​students,​ ​the​ ​transition​ ​to​ ​college​ ​is​ ​a​ ​natural stressor​ ​in​ ​itself​ ​as​ ​students​ ​try​ ​to​ ​fit​ ​in​ ​and​ ​become​ ​accustomed​ ​to​ ​life​ ​on​ ​their​ ​own​ ​while​ ​older students​ ​deal​ ​with​ ​the​ ​challenge​ ​of​ ​earning​ ​their​ ​degree,​ ​finding​ ​a​ ​job​ ​or​ ​in​ ​some​ ​cases​ ​a​ ​potential life​ ​partner.​ ​Regardless,​ ​all​ ​students​ ​deal​ ​with​ ​the​ ​common​ ​frequent​ ​stressors​ ​such​ ​as​ ​evaluations,

tests,​ ​critiques​ ​from​ ​professors​ ​or​ ​coaches,​ ​and​ ​sometimes​ ​it’s​ ​even​ ​more​ ​daunting​ ​when​ ​a student​ ​feels​ ​uncomfortable​ ​in​ ​the​ ​classroom​ ​or​ ​surroundings​ ​that​ ​they​ ​are​ ​in,​ ​or​ ​in​ ​relationships with​ ​faculty​ ​members.​ ​Ultimately,​ ​perceived​ ​stress​ ​is​ ​an​ ​important​ ​risk​ ​factor​ ​for​ ​low​ ​mental health​ ​and​ ​suggest​ ​that​ ​mastery​ ​and​ ​self-esteem​ ​are​ ​important​ ​protective​ ​factors​ ​of​ ​mental​ ​health among​ ​young​ ​adults​ ​(Bovier​ ​et​ ​al,​ ​2004).​ ​It​ ​is​ ​important​ ​for​ ​students,​ ​faculty,​ ​family​ ​members and​ ​really​ ​anyone​ ​to​ ​be​ ​able​ ​to​ ​recognize​ ​the​ ​difference​ ​between​ ​stress​ ​and​ ​depression​ ​before​ ​it​ ​is too​ ​late.
Call​ ​to​ ​action

So,​ ​what​ ​should​ ​be​ ​done?​ ​

Beginning​ ​with​ ​the​ ​people​ ​who​ ​spend​ ​the​ ​most​ ​time​ ​with​ ​young​ ​adults and​ ​students,​ ​faculty​ ​and​ ​staff​ ​of​ ​schools​ ​and​ ​colleges,​ ​camps,​ ​and​ ​community​ ​areas​ ​should​ ​all​ ​be aware​ ​of​ ​symptoms​ ​and​ ​make​ ​the​ ​individuals​ ​know​ ​that​ ​they​ ​are​ ​welcomed​ ​and​ ​always​ ​available as​ ​a​ ​listening​ ​source​ ​that​ ​can​ ​also​ ​provide​ ​the​ ​individual​ ​with​ ​connections​ ​or​ ​further​ ​resources​ ​if needed.​ ​Counseling​ ​services​ ​in​ ​the​ ​wellness​ ​center​ ​need​ ​to​ ​be​ ​able​ ​to​ ​accommodate​ ​appointments for​ ​all​ ​the​ ​students​ ​who​ ​come​ ​to​ ​them,​ ​and​ ​also​ ​create​ ​a​ ​common​ ​practice​ ​of​ ​speaking​ ​to​ ​the student​ ​body​ ​about​ ​recognizing​ ​the​ ​different​ ​symptoms​ ​within​ ​themselves​ ​and​ ​peers​ ​as​ ​well​ ​as destroying​ ​any​ ​taboo​ ​misconceptions​ ​that​ ​mental​ ​health​ ​is​ ​a​ ​myth​ ​or​ ​something​ ​that​ ​they​ ​can​ ​just get​ ​over​ ​with​ ​on​ ​their​ ​own.​ ​Having​ ​resources​ ​such​ ​as​ ​creating​ ​a​ ​stress​ ​management​ ​program​ ​may also​ ​be​ ​very​ ​beneficial​ ​as​ ​a​ ​different​ ​course​ ​of​ ​action​ ​for​ ​individuals​ ​who​ ​don’t​ ​know​ ​where​ ​to start​ ​or​ ​wish​ ​to​ ​improve​ ​their​ ​mental​ ​health.​ ​Assessing​ ​the​ ​different​ ​stressors​ ​to​ ​individuals including​ ​the​ ​ones​ ​that​ ​accumulate​ ​over​ ​time.​ ​The​ ​College​ ​Chronic​ ​Life​ ​Stress​ ​Survey​ ​created​ ​in 1996​ ​by​ ​Towbes​ ​and​ ​Cohen​ ​focused​ ​on​ ​the​ ​frequency​ ​of​ ​chronic​ ​stress​ ​in​ ​the​ ​lives​ ​of​ ​college students​ ​and​ ​evaluated​ ​how​ ​many​ ​times​ ​students​ ​dealt​ ​with​ ​these​ ​stresses​ ​on​ ​a​ ​weekly​ ​basis. They​ ​found​ ​that​ ​first​ ​year​ ​students​ ​had​ ​higher​ ​levels​ ​of​ ​chronic​ ​stress​ ​than​ ​the​ ​other​ ​students. Keeping​ ​an​ ​updated​ ​survey​ ​like​ ​this​ ​can​ ​be​ ​beneficial​ ​in​ ​helping​ ​faculty​ ​or​ ​school​ ​counselors realize​ ​where​ ​different​ ​individuals​ ​stand​ ​and​ ​assist​ ​them​ ​in​ ​an​ ​individualized​ ​matter.​ ​It​ ​can​ ​also help​ ​boards​ ​of​ ​higher​ ​institutions​ ​evaluate​ ​these​ ​results​ ​to​ ​see​ ​if​ ​there​ ​is​ ​a​ ​commonality​ ​amongst the​ ​students​ ​that​ ​is​ ​causing​ ​repeated​ ​high​ ​levels​ ​of​ ​stress​ ​and​ ​possibly​ ​adjust​ ​to​ ​accommodate​ ​the student​ ​body​ ​as​ ​a​ ​whole.​ ​Providing​ ​workshops​ ​or​ ​educational​ ​lectures​ ​that​ ​teach​ ​students​ ​how​ ​to recognize​ ​symptoms​ ​is​ ​important​ ​as​ ​many​ ​students​ ​would​ ​rather​ ​talk​ ​and​ ​confide​ ​in​ ​a​ ​friend before​ ​reaching​ ​out​ ​to​ ​a​ ​professional.​ ​Close​ ​friends​ ​can​ ​also​ ​detect​ ​abnormal​ ​behaviors​ ​in​ ​the individual​ ​that​ ​act​ ​as​ ​a​ ​signal​ ​for​ ​them​ ​to​ ​step​ ​in​ ​and​ ​help.​ ​They​ ​don’t​ ​have​ ​to​ ​become​ ​their friend’s​ ​therapist​ ​or​ ​certified​ ​counselor,​ ​however​ ​they​ ​can​ ​help​ ​by​ ​finding​ ​resources​ ​and​ ​in​ ​more serious​ ​cases,​ ​they​ ​can​ ​take​ ​action​ ​by​ ​reaching​ ​out​ ​to​ ​professionals​ ​for​ ​their​ ​friend​ ​or​ ​by practicing​ ​the​ ​concepts​ ​of​ ​QPR​ ​training​ ​which​ ​stands​ ​for​ ​question,​ ​persuade,​ ​and​ ​refer.​ ​This practice​ ​is​ ​a​ ​training​ ​done​ ​by​ ​many​ ​colleges​ ​or​ ​wellness​ ​centers​ ​to​ ​teach​ ​others​ ​how​ ​to​ ​recognize and​ ​help​ ​those​ ​at​ ​risk​ ​of​ ​suicide​ ​or​ ​who​ ​have​ ​thoughts​ ​of​ ​suicide.​ ​It​ ​can​ ​be​ ​applied​ ​to​ ​depression by​ ​gently​ ​confronting​ ​or​ ​bringing​ ​up​ ​the​ ​topic​ ​to​ ​their​ ​friend​ ​in​ ​mentioning​ ​that​ ​they​ ​have​ ​noticed a​ ​difference​ ​and​ ​are​ ​there​ ​to​ ​help​ ​them.​ ​Providing​ ​reassurance​ ​to​ ​the​ ​individual​ ​and​ ​helping​ ​them escape​ ​their​ ​doubts​ ​until​ ​a​ ​professional​ ​may​ ​be​ ​reached​ ​is​ ​a​ ​simple​ ​way​ ​a​ ​friend​ ​can​ ​help.​ ​Aside from​ ​educational​ ​staff​ ​and​ ​friends,​ ​family​ ​members​ ​and​ ​society​ ​as​ ​a​ ​whole​ ​needs​ ​to​ ​be​ ​reminded and​ ​educated​ ​that​ ​mental​ ​health​ ​is​ ​a​ ​real​ ​thing.​ ​It​ ​is​ ​not​ ​“just​ ​a​ ​phase”​ ​that​ ​one​ ​can​ ​easily​ ​get​ ​over with​ ​after​ ​a​ ​few​ ​days.​ ​Providing​ ​education​ ​and​ ​facts​ ​and​ ​reaching​ ​out​ ​to​ ​the​ ​public​ ​is​ ​the​ ​most essential​ ​way​ ​to​ ​get​ ​the​ ​message​ ​across​ ​which​ ​in​ ​turn​ ​creates​ ​a​ ​larger​ ​push​ ​for​ ​more​ ​research​ ​in labs​ ​and​ ​medication​ ​for​ ​individuals.

In​ ​research,​ ​finding​ ​better​ ​or​ ​more​ ​animal​ ​models​ ​that​ ​correlate​ ​to​ ​human’s​ ​mechanisms​ ​of actions​ ​may​ ​assist​ ​in​ ​further​ ​understanding​ ​both​ ​stress​ ​and​ ​depression​ ​in​ ​individuals.​ ​It​ ​is​ ​also important​ ​to​ ​keep​ ​in​ ​mind​ ​that​ ​young​ ​adults​ ​are​ ​not​ ​the​ ​only​ ​ones​ ​dealing​ ​with​ ​mental​ ​disorders. Frequently,​ ​individuals​ ​have​ ​struggled​ ​growing​ ​up​ ​but​ ​have​ ​never​ ​reached​ ​out​ ​or​ ​been​ ​told​ ​to seek​ ​help.​ ​There​ ​is​ ​a​ ​high​ ​percentage​ ​of​ ​older​ ​adults​ ​with​ ​mental​ ​disorders​ ​that​ ​still​ ​struggle​ ​on​ ​a daily​ ​basis​ ​who​ ​have​ ​just​ ​as​ ​many​ ​rights​ ​to​ ​access​ ​in​ ​resources​ ​and​ ​medications​ ​at​ ​their​ ​point​ ​of life​ ​as​ ​well​ ​(Kennedy​ ​&​ ​Ceϊde,​ ​2017).​ ​Being​ ​able​ ​to​ ​recognize​ ​any​ ​symptoms​ ​or​ ​disabilities related​ ​with​ ​depression,​ ​anxiety,​ ​stress,​ ​and​ ​impaired​ ​cognition​ ​earlier​ ​on​ ​can​ ​lead​ ​to​ ​an​ ​easier​ ​or better​ ​appreciated​ ​lifestyle​ ​further​ ​on.



Works​ ​Cited

Bovier,​ ​P.A.,​ ​Chamot,​ ​E.​ ​&​ ​Perneger,​ ​T.V.​ ​Qual​ ​Life​ ​Res​ ​(2004)​ ​13:​ ​161. https://doi.org/10.1023/B:QURE.0000015288.43768.e4

Compton​ ​WM,​ ​M.D.,​ ​M.P.E.,​ ​Conway​ ​KP,​ ​Ph.D.,​ ​Stinson​ ​FS,​ ​Ph.D.,​ ​and​ ​Grant​ ​BF,​ ​Ph.D. (2006).​ ​Changes​ ​in​ ​the​ ​prevalence​ ​of​ ​major​ ​depression​ ​and​ ​comorbid​ ​substance​ ​use disorders​ ​in​ ​the​ ​United​ ​States​ ​between​ ​1991-1992​ ​and​ ​2001-2002.​ ​American​ ​Journal​ ​of Psychiatry.​ ​Doi:​ ​​10.1176/ajp.2006.163.12.2141

Hammar,​ ​Å.,​ ​&​ ​Årdal,​ ​G.​ ​(2009).​ ​Cognitive​ ​Functioning​ ​in​ ​Major​ ​Depression​ ​–​ ​A​ ​Summary. Frontiers​ ​in​ ​Human​ ​Neuroscience​,​ ​​3​,​ ​26.​ ​http://doi.org/10.3389/neuro.09.026.2009

Hidaka,​ ​B.​ ​H.​ ​(2012).​ ​Depression​ ​as​ ​a​ ​disease​ ​of​ ​modernity:​ ​explanations​ ​for​ ​increasing prevalence.​ ​​Journal​ ​of​ ​Affective​ ​Disorders​,​ ​​140​(3),​ ​205–214. http://doi.org/10.1016/j.jad.2011.12.036

Krishnan,​ ​V.,​ ​&​ ​Nestler,​ ​E.​ ​J.​ ​(2008).​ ​The​ ​molecular​ ​neurobiology​ ​of​ ​depression.​ ​​Nature​, 455​(7215),​ ​894–902.​ ​​http://doi.org/10.1038/nature07455

Kennedy,​ ​G.​ ​J.,​ ​&​ ​Ceïde,​ ​M.​ ​E.​ ​(2017).​ ​Screening​ ​Older​ ​Adults​ ​for​ ​Mental​ ​Disorders.​ ​​Clinics​ ​in Geriatric​ ​Medicine​.​ ​DOI:​ ​​10.1016/j.cger.2017.09.005

Ross,​ ​S.​ ​E.,​ ​Niebling,​ ​B.​ ​C.,​ ​&​ ​Heckert,​ ​T.​ ​M.​ ​(1999).​ ​Sources​ ​of​ ​stress​ ​among​ ​college​ ​students. Social​ ​psychology​,​ ​​61​(5),​ ​841-846.

Sontheimer,​ ​H.​ ​(2015).​ ​​Diseases​ ​of​ ​the​ ​Nervous​ ​System​.​ ​Academic​ ​Pr.

Thomée,​ ​S.,​ ​Härenstam,​ ​A.,​ ​&​ ​Hagberg,​ ​M.​ ​(2012).​ ​Computer​ ​use​ ​and​ ​stress,​ ​sleep​ ​disturbances, and​ ​symptoms​ ​of​ ​depression​ ​among​ ​young​ ​adults​ ​–​ ​a​ ​prospective​ ​cohort​ ​study.​ ​​BMC Psychiatry​,​ ​​12​,​ ​176.​ ​​http://doi.org/10.1186/1471-244X-12-176 Towbes,​ ​L.C.​ ​&​ ​Cohen,​ ​L.H.​ ​J​ ​Youth​ ​Adolescence​ ​(1996)​ ​25:​ ​199. https://doi.org/10.1007/BF01537344

Twenge,​ ​J.​ ​M.​ ​(2000).​ ​The​ ​age​ ​of​ ​anxiety?​ ​The​ ​birth​ ​cohort​ ​change​ ​in​ ​anxiety​ ​and​ ​neuroticism, 1952–1993.​ ​​Journal​ ​of​ ​Personality​ ​and​ ​Social​ ​Psychology,​ ​79​(6),​ ​1007-1021.

Wood,​ ​S.​ ​K.,​ ​&​ ​Bhatnagar,​ ​S.​ ​(2015).​ ​Resilience​ ​to​ ​the​ ​effects​ ​of​ ​social​ ​stress:​ ​Evidence​ ​from clinical​ ​and​ ​preclinical​ ​studies​ ​on​ ​the​ ​role​ ​of​ ​coping​ ​strategies.​ ​​Neurobiology​ ​of​ ​stress​,​ ​1, 164-173.​ ​​https://doi.org/10.1016/j.ynstr.2014.11.002

Neuroendocrinology Mini-Review

8 May 2017

Metformin treatment for diseases aside from Diabetes: Focus on Addison’s disease, adrenal glands and thyroid glands

Word count: 2856


Adrenal insufficiencies lead to increased rates of morbidity and mortality. In order to address these insufficiencies, glucocorticoid replacement has been the primary treatment of choice. However, side effects are intense and patients are more prone to developing metabolic complications. Therefore, this has lead researchers to look for alternate treatments and one that has been repeatedly experimented with is metformin. Metformin is most commonly used and known for the treatment of diabetes. However, studies have shown that it has also contributed to alleviating symptoms and side effects of corticosterone treatments, especially in Addison’s disease and Polycystic ovary syndrome (PCOS). In Addison’s disease, there is not enough cortisol and aldosterone hormone production, and in PCOS, high levels of plasma concentration of androgen and insulin resistance is common. Metformin’s mechanism of action occurs in the liver and peripheral tissues and functions to reduce the amount of gluconeogenesis, glucose secreted, and fatty acid synthesis from the liver, while simultaneously enhancing the glucose uptake and fatty acids oxidation of the peripheral tissue when it is needed. Each individual patient will react differently to the treatments however, the majority from tests and clinical trials have shown a decreased state of adrenal insufficiency. Metformin has also shown to alleviate thyroid problems, specifically with the production of thyroid stimulating hormone (TSH), Triiodothyronine, T3, and Thyroxin, T4, as well as patients with insulin resistance and thyroid nodules on thyroid glands.


Addison’s disease is the result of the lack of cortisol and aldosterone hormone production from the adrenal cortex of the adrenal glands in the body. Cortisol’s primary function is to assist the body in its response to stress and it is produced in the middle layer of the adrenal cortex. It also controls the usage of macronutrients, and helps maintain blood pressure and control inflammation. Aldosterone assists the kidneys in regulating sodium and potassium ions in the blood, and water and electrolyte balance in the body. Addison’s disease is also known as primary or secondary adrenal insufficiency, which can be life threatening in all age groups and sexes (Dorin et al, 2003). In primary adrenal insufficiency, the adrenal glands do not produce enough of the hormone cortisol. In secondary adrenal insufficiency, there is a problem with the signal that the brain sends to the adrenal glands instructing them on how to make cortisol. This can also happen with people who consume corticosteroids for treatment of chronic conditions such as asthma or arthritis and abruptly stop consumption. Once these hormone levels start to decrease, symptoms begin to appear and include irritability, extreme fatigue, low blood pressure, low blood sugar (hypoglycemia), depression, muscle or joint pains, weight loss and decreased appetite, salt craving, nausea, diarrhea, vomiting, darkening of skin, as well as body hair loss or sexual dysfunction in women. In the case of acute adrenal failure, also known as addisonian crisis, which can be caused by an injury, infection or illness, or a physical stress, symptoms such as pain in your lower back, abdomen or legs, severe vomiting and diarrhea, high potassium and low sodium, low blood pressure, and loss of consciousness may appear suddenly. At 70% of the time, the primary cause of an autoimmune disease, where the body attacks itself, is due to failure of the hormones production from the adrenal glands. This can be a result of tuberculosis, HIV, spread of cancer, other infections, and bleeding into the adrenal glands. Tuberculosis is the most common cause of Addison’s disease worldwide, and is a bacterial infection that affects the lungs and other parts of the body and can damage the adrenal glands. The adrenal glands will provide the steroid hormones of cortisol and aldosterone until 90% of the adrenal cortex is destroyed. This mini-review primarily focuses on the alternative method that metformin provides in response to the effects of glucocorticoid treatment in diseases such as Addison’s disease which deals with the adrenal glands and as well as its implications in diseases related to the thyroid gland.

Neuroendocrinology of adrenal glands:

The adrenal glands are two organs located on top of each kidney. They have two primary parts, the outer part known as the adrenal cortex, and the inner part known as the adrenal medulla. Each part secretes different hormones. The adrenal cortex produces glucocorticoids, which is triggered by the hypothalamus and the pituitary gland, and mineralocorticoids which are released by signals from the kidney. The lack of, or hyposecretion, of the adrenal cortex hormones begins at the hypothalamus where corticotropin releasing hormone (CRH) is released into the pituitary gland. The pituitary gland is then activated to secrete adrenocorticotropic hormone (ACTH) into the adrenal glands which then releases glucocorticoids such as cortisol and catecholamines such as epinephrine, norepinephrine, and aldosterone. This pathway is called the hypothalamic pituitary adrenal (HPA) axis. However, when there is an abnormality in the negative feedback mechanism, the secretion of CRH or ACTH is shut off or the intensity is lessened which leads to the hyposecretion of cortisol and aldosterone. The deficit in ACTH can lead to secondary adrenal insufficiency and a deficiency in CRH due to an injury in the hypothalamus. This also leads to a lesser production of cortisol in the adrenal glands and can potentially become an adrenal insufficiency. Primary adrenal insufficiency is typically due to a damaged part of the adrenal cortex which is the outer layer of the adrenal glands.

Treatment of adrenal insufficiency:

Typical treatments commonly include daily medications that replace the lack and loss of hormones. Aldosterone is replaced with an oral mineralocorticoid, commonly known as fludrocortisone, as well as a doctor’s recommendation of an increased sodium intake.

Cortisol is replaced with an oral synthetic glucocorticoid or an oral hydrocortisone and is taken once or twice a day in order to provide the minimum amount of glucocorticoid needed to replace the body’s natural cortisol production levels (Johannsson et al, 2012). Glucocorticoids bind to glucocorticoid receptors in the cytoplasm which are a type of nuclear receptor that is activated by ligand bonding. They may increase the transcription of genes coding for anti-inflammatory proteins or result in the regulation of gene expression. This mechanism is commonly known as Transactivation (Figure 1). Glucocorticoids inhibit the expression of multiple inflammatory genes and is mostly due to a direct inhibitory interaction between activated glucocorticoid receptors and activated transcription factors. It is also common that glucocorticoids change the chromatin structure and interact with CREB-bind protein which is a co-activator of transcription (Matfin, 2010).


Figure 1: Transactivation of glucocorticoids. Cortisol binds to the glucocorticoid receptor (GR) in the cytoplasm, after which the ligand-bound GR can migrate into the nucleus. The GR binds to glucocorticoid-response element (GRE) to transactivate gene expression.

These glucocorticoids are a type of corticosteroids which are a class of steroid hormones, hormones made in the adrenal cortex. Steroid hormones help control metabolism, inflammation, immune function, salt and water balance, and more in their target cells. They are known to be lipophilic and readily cross the lipid cell membrane in order to recognize and bind to a particular protein receptor. Once this binding occurs, the steroid-receptor complex binds to DNA and manages to increase or decrease the transcription of specific genes and have the ability to switch on a gene for synthesis of a certain protein. They are effective in stopping damaging inflammation caused by many immune system disorders as they are part of the feedback mechanism in the immune system that reduces certain aspects, of immune function. Addisonian or adrenal crisis requires more urgent medical attention, and can be fatal if not treated correctly and quickly. Treatment commonly includes an intravenous injection of glucocorticoid, salt water (saline) and sugar (dextrose) in order to stabilize the patient. While Addison’s disease is a rare but serious disorder, most patients live normal lives and medications that help to boost cortisol hormone levels are required for life and can help the patient feel healthy. However, there are occurrences where too much of these medications lead to unwanted and harmful side effects. Blood sugar levels can be increased and trigger diabetes, suppress the ability to absorb calcium leading to osteoporosis, increase cholesterol and triglyceride levels, increase risk of ulcers and gastritis, delay of healing in wounds, and suppress the immune system and make individuals more prone to infections. The new and more comprehensive understandings of glucocorticoid mechanisms may lead to the development of novel steroids with a lesser risk of side effects. A study was done to develop a once-daily (OD) oral hydrocortisone dual-release table with a more physiological exposure-time cortisol profile in order to decrease the morbidity and mortality rate of patients with adrenal insufficiencies. 64 adults with a primary adrenal insufficiency were compared after half were given conventional TID (thrice-daily) and the experimental group, OD.  The OD treatment showed a sustained serum cortisol profile after the morning intake and reduced the late afternoon and the 24-hour cortisol exposure. There was a decrease in the mean weight, systolic, and diastolic blood pressure and improved glucose metabolism after 12 weeks (Johannsson et al, 2012).

Metformin as choice of drug to combat glucocorticoid therapy side effects:

Metformin is a novel treatment in the case of using it outside of diabetic medication. According to Korbonits et. al, from the London NHS Trust, nearly 1% of the general population is treated with long-term glucocorticoids. Currently, multiple clinical trials are in process. Metformin is one of the most widely prescribed antihyperglycemic agents for diabetes. Compared to other medications, it is unique because of its effect on glycemic control by addressing insulin resistance. It is most commonly used to treat diabetes, however it has been proven to help other diabetes associated conditions such as polycystic ovary disease, cardiovascular issues, and unbalanced thyroid function levels. Metformin’s mechanism of action occurs in the liver and peripheral tissues and functions to reduce the amount of gluconeogenesis, glucose secreted, and fatty acid synthesis from the liver, and simultaneously enhance the glucose uptake and fatty acids oxidation of the peripheral tissues ( et al, 2017).  Different studies have led to show how metformin can affect various parts of the body leading to available treatments for diseases. In an animal model, investigators have shown that by altering adenosine-monophosphate-activated protein (AMPK) activity, metformin prevents the development of metabolic complications of glucocorticoid excess (Korbonits et. Al). In a human study, a double-blind, placebo-controlled trial, patients who were beginning glucocorticoid treatments were randomized to receive a certain amount of metformin each week and the other group, a placebo. All patients underwent a baseline and a four-week assessment and in the first trial of targeting metabolic complication in patients needing glucocorticoid therapy, there was a beneficial effect of metformin on glycemic control in 29 of 34 randomized non-diabetic patients at the completion of the trial (Seelig et Al, 2017).

Figure 2: Metformin’s effects on different glands of the body

Organ Metformin Effect
Liver Decreases hepatic glucose production
Skeletal muscle Improves peripheral glucose uptake
Pancreas Improves insulin secretion
Fat Improves peripheral glucose uptake
Gut Decreases appetite and caloric intake


Metformin’s effects in TSH axis

Interestingly, studies have shown the effects of metformin on other parts of the endocrine systems as well. In the thyroid gland, it affects TSH, thyroid stimulating hormone, but a lack of effect on the thyroid hormones T3, Triiodothyronine, and T4,, Thyroxin. This raises interest as the HPT (hypothalamic-pituitary-thyroid) axis secretes TSH from the anterior pituitary to the thyroid gland which is then activated to secrete T4, and T3 which increases or decreases metabolism. In the regular feedback mechanism of the HPT axis, a change in TSH regularly leads to a change in T4, and T3 levels. High levels of TSH without change in T4,and T3 can be referred to as subclinical hypothyroidism. In the recent study of Cappelli et al, patients with existing hypothyroidism were started on metformin and for their levels of T4, and T3 remained unchanged over one year but demonstrated a statistically significant difference in the level of TSH (P < 0.05) while the euthyroid patients had an unchanged TSH. Another study done by Vella S. et al from Malta studied 138 individuals with type 2 diabetes where about half were on metformin. TSH was lower in the metformin treated patients and T4, was higher in the females who were on metformin compared to the control group. Both studies concluded that metformin is likely affecting the thyroid function through inhibition of the peripheral conversion of thyroxine to triiodothyronine (Abdelgadir et al, 2017). It has also been shown that patients with insulin resistance (IR) have a higher prevalence of thyroid nodules and bigger thyroid glands (Rezzónico et al., 2011). 66 women with IR and nodular hyperplasia were separated into four different groups which consisted of group one being treated with metformin, group two treated with metformin and levothyroxine (L- T4,), thyroid medicine that treats hypothyroidism, group three treated with L- T4, and group four without any treatment. The results showed that group two and three dropped in TSH levels, group one and two normalized the homeostasis model assessment (HOMA) index after treatment, and group one and two, the two groups that contained metformin, showed significant reduction in the nodule sizes while patients from group three and four did not have any significant reduction in nodule sizes. Rezzónico et al. concluded that metformin produced a significant decrease in the nodular sizes in patients with IR and small thyroid nodules.

Effects of Metformin on Polycystic Ovary Syndrome:

Polycystic ovary syndrome (PCOS) is an endocrine system disorder among women that can include enlarged ovaries that contain small collections of fluid. This can lead to infrequent or prolonged menstrual periods, excess hair growth, acne, and obesity. In patients with PCOS, high levels of plasma concentration of androgen and insulin resistance is common. Hyperinsulinemia in women with PCOS affects adrenal production by an increase in ACTH secretion. Metformin is associated with increased menstrual cyclicity, improved ovulation, and a reduction in circulating androgen levels. Fourteen women who were diagnosed with PCOS and had less than six menstrual periods in the previous year, were studied according to their plasma concentrations of progesterone and were administered ACTH to obtain blood samples. Metformin was then given at a dosage of 500 mg, three times a day for 30 days. The administration lead to ovulation occurring in 2 women (14%) and no significant change in basal levels of cortisol or in the response of cortisol in response to the month of metformin therapy. (Marca A. et al, 1999). Findings included that metformin caused the reduction in basal plasma concentrations of free testosterone and in the adrenal secretion of androgens in response to ACTH and reducing insulin levels. This study mainly agreed that the main effect of metformin was on the liver with increased secretion of sex hormone-binding globulin (SHBG and the reduction in free testosterone was most likely a secondary effect. Another study aimed to use a double-blind, placebo controlled with detailed assessment of ovarian activity such as two blood samples per week to assess the validity of metformin therapies. Out of 94 patients, 45 received metformin, the rest placebo. There was a rapid effect of follicular maturation and an inverse relationship between body mass and treatment efficacy in the metformin therapy group after fourteen weeks in comparison to the placebo therapy group. It is conclusive that metformin provides a beneficial effect on improving ovarian function in women with polycystic ovaries by increasing ovulation rates as well as significant weight loss and an associated change in high-density lipoprotein (HDL) cholesterol (Fleming et al, 2002).


So far, the replacing of the lack of cortisol and aldosterone is the best known solution for Addison’s disease. However, the uprising goal is to find a treatment that does not have as many troubling side effects, or to find a way to correct the lack or loss of signal(s) throughout the HPA axis. So far, metformin has provided promising results that ameliorate the effects of corticosterone treatment in Addison’s disease as well as regulating ovarian function in women with Polycystic Ovary Syndrome. In relation to the thyroid gland and the HPT axis, metformin’s ability to lower TSH without changing T3 and T4 levels continues to be instrumental in helping individuals with type 2 diabetes. Also in the thyroid gland, metformin has helped reduce the size of thyroid nodules in patients with insulin resistance. There are some other beginning research and clinical stages for alternate metformin uses such that include it as an anti-inflammatory agent, an anti-oxidant, improving endothelial function, a weight reducing agent, the nervous system, blood homeostasis, HIV treatment-related side effects, and cancers which includes liver, pancreatic, breast, colorectal, prostate, lung, thyroid, endometrial cervical, renal cell, and melanoma. This has made metformin one of the most prescribed antihyperglycemic agents and even though it is one of the older drugs that has been on the market for a while, it continues to provide some of the best results due to its effect on glycemic control by addressing insulin resistance. Further interest and studies need to be conducted in order to gain full understanding and explanation of how metformin can have all of these effects on a variety of symptoms.



Abdelgadir, E., Ali, R., Rashid, F., & Bashier, A. (2017, May). Effect of Metformin on Different Non-Diabetes Related Conditions, a Special Focus on Malignant Conditions: Review of Literature. Retrieved April 20, 2017

Barnes, P. J. (1998, June). Anti-inflammatory actions of glucocorticoids: molecular mechanisms. Retrieved April 06, 2017

Barts & London N&H Trust. (n.d.). Prevention of Metabolic Complications of Glucocorticoid Excess. Retrieved April 06, 2017

Dorin, R. I., Qualls, C. R., & Crapo, L. M. (2003, August 05). Diagnosis of Adrenal Insufficiency. Retrieved May 08, 2017,

Fleming, R., Hopkinson, Z. E., Wallace, A. M., Greer, I. A., & Sattar, N. (2002, February 01). Ovarian Function and Metabolic Factors in Women with Oligomenorrhea Treated with Metformin in a Randomized Double Blind Placebo-Controlled Trial. Retrieved April 20, 2017

Johannsson, G., Nilsson, A. G., Bergthorsdottir, R., Burman, P., Dahlqvist, P., Ekman, B., . . . Skrtic, S. (2012, February 01). Improved Cortisol Exposure-Time Profile and Outcome in Patients with Adrenal Insufficiency: A Prospective Randomized Trial of a Novel Hydrocortisone Dual-Release Formulation. Retrieved May 08, 2017

Marca, A. L., M.D., Morgante, G., M.D., Paglia, T., B.Sc., Ciotta, L., M.D., Cianci, A., M.D., & Leo, V. D., M.D. (1999, December). Effects of metformin on adrenal steroidogenesis in women … Retrieved April 20, 2017

Matfin, G. (2010, June). Something old, something new…. Retrieved April 06, 2017

Seelig1*, E., Meyer1*, S., Timper12, K., Nigro1, N., Bally3, M., Pernicova4, I., . . . And, M. K. (2017, March 01). Metformin prevents metabolic side effects during systemic glucocorticoid treatment. Retrieved April 06, 2017

Rezzónico, J., Rezzónico, M., Pusiol, E., Pitoia, F., & Niepomniszcze, H. (2011). Metformin treatment for small benign thyroid nodules in patients with insulin resistance. Metabolic syndrome and related disorders9(1), 69-75.

Seibel, M. J., Cooper, M. S., & Zhou, H. (2013). Glucocorticoid-induced osteoporosis: mechanisms, management, and future perspectives. The Lancet Diabetes & Endocrinology1(1), 59-70.


SUMMIT Learning Outcomes

Summit is a unique college experience in which every student, regardless of major, is prepared to lead effectively in a global society through a curriculum and co-curriculum focused on global learning and leadership development. Participating in SUMMIT will prepare students for a multitude of paths after their time at Agnes Scott by helping them achieve the following knowledge and skills:

Below are Agnes Scott’s SUMMIT Learning Outcomes. Throughout them there are links to experiences I have had during my time at Agnes Scott.

  1. Identify, explain, and analyze global themes, processes, and systems
  2. Demonstrate knowledge and skills essential for global engagement
  3. Critically examine the relationship between dominant and marginalized cultures, subcultures or group
  4. Communicate effectively through writing and speaking, especially across cultural or linguistic differences
  5. Recognizes, analyze, and evaluate arguments
  6. Articulate and appraise problems and solutions from multiple perspectives, critically considering diverse sources of information
  7. Recognize, analyze, and employ effective teamwork
  8. Identify and assess one’s values, interests and abilities
  9. Practice or interpret creative expression or probe fundamental questions of value and meaning
  10. Interpret quantitative information or demonstrate the methods of inquiry appropriate for investigating the natural world
  11. Analyze human behavior or social relations
  12. Cultivate and maintain interpersonal relationships and networks
  13. Demonstrate confidence and motivation to effect change
  14. Practice continual improvement of one’s whole person and seek and utilize feedback
  15. Identify, evaluate and strategically utilize campus and community resources
  16. Demonstrate honorable and ethical behavior and civic engagement


  • This information has been taken from my SUMMIT 400 class curriculum

Emory Winship Cancer Institute

Throughout my years in college, I have had the opportunity to volunteer for Emory Winship Cancer Institute. I have worked in different departments including the front desk, volunteer family services, the infusion lab, lab check-in, patient transporter, and as floater, which attends to whoever needs assistance. All of these positions have allowed me to learn endlessly about healthcare professional work relationships for the efficacy, efficiency, and quality of healthcare.

Children’s Healthcare of Atlanta

Ever since high school and throughout college, I have had the opportunity to volunteer for Children’s Healthcare of Atlanta. I have worked for multiple locations and in two different positions assisting in the Bilingual Department as an interpreter and in the Emergency Department assisting Child Life Specialists. I have also had the amazing opportunity to work for their “Carpe Diem” summer camp .

As a volunteer, my job has been to visit Spanish speaking patients in all departments of the hospitals. I could interpret anything non-medical for them and healthcare providers, as well as let them know what resources they have available to them during their stay. Once I began to shadow medical translators, my eyes were opened to the importance and need for these positions. So much so that during my gap year, I intend to become certified as one. Seeing the faces of confusion, desperation, and anxiety displayed across patients and their family members’ faces when they do not understand what the doctor is saying to them or how to go about treatment once discharged is heart wrenching. As an immigrant and native Spanish speaker, as well as my parents, I am aware of the difficulty and the challenge one endures when beginning a new chapter of life in a new country with a new language.

Working in the Emergency Department, I can continue to use my bilingual skills as I interact with each patient in their rooms. I also ask parents if they need anything such as a break to get some food, some water, or if I can give the child some toys or coloring pages to help pass the time. Its a small gesture that goes a long way, especially considering the setting and stress of being in a hospital. I have been able to observe how nurses, doctors, child life specialists, and other healthcare providers and staff work together to provide the best possible stay at the hospital for their patients.

In May, 2018, I was selected as a volunteer and camp counselor for CHOA’s summer camp, “Carpe Diem”. It is a camp for children with epilepsy to meet others with similar medical conditions. Through team-building activities, the campers and I built supporting relationships and lasting memories. I even got to celebrate my 21st birthday in the middle of the week where the entire camp sang Happy Birthday to me and covered me in gold star stickers. It has been an unforgettable experience and I eagerly look forward to participating in it year after year.

Credit “Birthday star sticker attack by children at CHOA Camp” By Iara Moran is licensed under CC BY 4.0


SUMMIT Learning Outcomes associated with this reflection:

  • 8. Identify and assess one’s values, interests and abilities
  • 9. Practice or interpret creative expression or probe fundamental questions of value and meaning
  • 11. Analyze human behavior or social relations
  • 12. Cultivate and maintain interpersonal relationships and networks

One Love

Since my first year at Agnes Scott, I have been involved with HERO (Health Education and Resource Organization), a club on campus that focuses on the mental, emotional, and physical health and well being of Agnes Scott’s student body. This year, I accomplished one of the goals I set as a freshman, I became president of the club. I have always been very interested in the subject and activities around public health and thought what better way to be involved than with this club. This has allowed me to become heavily involved with the student body and student life coordinators on campus where I even became trained in bystander awareness through the wellness center on campus. This has allowed me to lead training of other campus leaders and communities on campus in bystander awareness and sexual assault awareness trainings.

Credit “SPArC/RespectCon” by Iara Moran is licensed under CC BY 4.0

I have also participated in workshops and events at other colleges and conferences such as Oglethorpe University One Love Campaign and Emory 2018 RespectCon where I have learned about the prevalence of campus sexual assaults and the culture around it throughout different universities in the United States. There is a huge student movement bringing greater awareness to campus officials and asking for proper action. This is sill a huge work of progress but in the midst of it all, I am always inspired at how students work together in the past, now, and in the future for their rights. This is something I wish to continue to be a part of for the rest of my life and has greatly impacted the role I would like to play as a future pediatric physician and representative for children and young adults everywhere.  


SUMMIT Learning Outcomes associated with this reflection:

  • 6. Articulate and appraise problems and solutions from multiple perspectives critically considering diverse sources of information
  • 7. Recognize, analyze, and employ effective teamwork
  • 11. Analyze human behavior or social relations
  • 12. Cultivate and maintain interpersonal relationships and netoworks
  • 15. Identify, evaluate and strategically utilize campus and community resources
  • 16. Demonstrate honorable and ethical behavior and civic engagement

How To Not Kill A Tomagotchi

The summer after my freshman year of college, I applied to a program called EBICS (Emergent Behaviors of Integrated Cellular Systems) and received the opportunity to participate in paid undergraduate research at the Massachusetts Institute of Technology for ten weeks in Boston.

Credit “Massachusetts Institute of Technology” by Iara Moran is licensed under CC BY 4.0

I worked under a P.h.D candidate at MIT in a biosynthetic lab in the bioengineering department. The entire experience was exciting from start to finish but as I had just finished my freshman year of college, I was still very new and not really knowledgeable in the type of science that was being worked with in the lab. A clear memory I have from my time there was hearing MIT’s president talk at an event where he used the analogy of the amount being taken in by a student there is like being hit with the water pressure of a broken fire hydrant. I related to this quite strongly. I had no idea how to read genetics on paper. Each part of a gene has a different symbol and name that consists of blocks, triangles, arrows, and various colors. Along with reading 10 page articles, I had to learn what each symbol meant and how to recognize them as well. Aside from the literature, I also learned how to take care of cells and lab techniques. However, I didn’t just work with any kind of regular cell line. I was given stem cells. These are some of the hardest, most expensive, and fragile cells to work with as they are in a state where they can become any kind of cell before they develop into their assigned function, also known as differentiation, in scientific terms. My mentor named this cell line tamagotchi. I had to feed them, nurture them, let them grow, and most important of all, not let them die, just like my own baby tamagotchi. The countless hours spent in that lab every day for those 10 weeks was enough for me to run PCR in a blindfold. My lab skills improved dramatically and became an ease to the point that when I went back to school the following semester, I was the designated lab technician for my science classes at Agnes Scott. At the end of the 10 weeks, I was able to present my work on a poster and attend the EBICS conference in Chicago and also SPArC at Agnes Scott.

Credit “MIT Poster Presentation” by Iara Moran is licensed under CC BY 4.0

I really enjoyed this experience and the opportunity to do such important and prevalent work. I believe that this experience helped me decide to become a Neuroscience major. However, it also helped me realize that this path of wet lab research is not for me. The long and usually lonely hours with just you, the cells, and machines whirring around you are not for me. I prefer the clinical side of science and medicine, which is just as important but has more human interaction. This  has allowed me to focus more on working in hospitals, clinics, or private practice settings to acquire more experience this way earlier on in my medical career and in the fields of work that I enjoy.


SUMMIT Learning Outcomes associated with this reflection:

  • 4. Communicate effectively through writing and speaking
  • 5. Recognize, analyze, and evaluate arguments
  • 7. Recognize, analyze, and evaluate arguments
  • 8. Identify and assess one’s values, interests, and abilities
  • 10. Interpret quantitative information or demonstrate the methods of inquiry appropriate for investigating the natural world
  • 12. Cultivate and maintain interpersonal relationships and networks
  • 14. Practice continual improvement of one’s whole person and seek and utilize feedback
  • 16. Demonstrate honorable and ethical behavior and civic engagement

Along the Beaches of Normandy


Credit: “Omaha Beach” by Anton Bielousov is licensed under  CC BY 2.0

This past July I studied abroad in Caen, France, a small city in the northwestern region of Normandy. For three weeks I was able to immerse myself with the locals and delve into the language and the long and important history of the region.

I had been eagerly looking forwards to this experience as I have traveled to France before but had mostly seen Paris and a few other small cities in the South. This experience was longer, academic, and eye opening.

I have studied French since the eighth grade and it is now my minor at Agnes Scott as well as my third spoken language. Studying this language is something I value culturally and globally in being able to communicate and learn from more people around this world. At the end of my studies, I took the DELF exam which is the French exam for non-native French speakers. I passed the B2 level meaning that if, in the future, I decide to pursue more education in France, I would be considered fluent enough to take French classes with no assistance. This has sparked my interest and curiosity in possibly completing a masters in France.

Apart from the language, I learned a vast amount about the culture and patrimony of Normandy. The program frequently took us to excursions around the city of Caen explaining how they rebuilt after World War II as well as showing us the important buildings and figures that withstood the war and are still standing to this day. They varied from family homes to the religious and impressive abbeys. Throughout it all, it was as if I was traveling back in time to the simpler countryside of France that overlooks the Atlantic Ocean.

Credit “L’étrat” by Iara Moran is licensed under CC BY 4.0

Now that I’m back in the United States, I did have a bit of a cultural readjustment from simple things such as how strong the air conditioning is here, and also larger things such as the pace and enjoyment of life which seems much more rushed here. I enjoy sharing my experience with other students and faculty, especially those in my French literature class where we are reading about French Female writers and one in particular, Annie Erneaux, who is from Normandy and so my class in France studied her and her works greatly and now I can connect what I learn from both classes in France and back at Agnes Scott.

My love of the French language and culture will continue to grow as I am sure that in the future I will continue to visit the beautiful country and hopefully live and study there some for some time as well.


SUMMIT Learning Outcomes associated with this reflection:

  • 1. Identify, explain and analyze global themes, processes, and systems
  • 2. Demonstrate knowledge and skills essential for global engagement
  • 4. Communicate effectively through writing and speaking, especially across cultural or linguistic differences
  • 8. Identify and assess one’s values, interests, and abilities
  • 14. Practice continual improvement of one’s whole person and seek and utilize feedback

Dominican Republic

My GBL 101 class my first semester of Agnes Scott consisted entirely of the Dominican Republic’s history, society, politics, and current events. We mostly focused on their ongoing relationship and conflicts with Haiti, and the country’s healthcare system since our class was led and taught by public health professor. Being from a hispanic country as well, most of the “shocking” events having to do with politics, society, corruption, economics, and more, did not surprise me much in comparison to my classmates. While I did learn a few new things about the DR in particular, it was nice to see my classmates learn and have their eyes open to just a little part of the world outside of the United States. It was as if they gained the two-sided perspective that I had grown up with while growing up in the United States but having my Argentinian language and culture at home.

Credit “Santo Domingo, DR” by Iara Moran is licensed under CC BY 4.0

Having learned as much as possible, the weeks leading up to the trip were buzzing with excitement. We flew from Hartsfield Jackson to the dreaded Miami airport before flying to Santo Domingo. We were greeted

by our Peacework ambassador who surprised us by giving us water in bags since the local water isn’t potable. We traveled by bus to our hostel in the center of the city were we spend the following 2-3 days getting to do a little bit of tourism and embrace the Dominican culture and food especially.

The second half of the week, we travelled across the country to a smaller city called Puerto Plata. Here, we stayed in an Ecolodge at the top of a rocky mountain. I had never been so glad to have dramamine on hand. The view from this ecolodge over the luscious forest of the Dominican were unlike anything I had ever seen before. The photo doesn’t do it justice but it can give you an idea.

Credit “View of Puerto Plata, DR from Ecolodge” by Iara Moran is licensed under CC BY 4.0

Aside from exploring the beauty that the DR has to offer, we dove deeper into its society by visiting a woman’s health clinic and a Haitian community. In the woman’s health clinic we were able to see what resources are available to mothers and their children, sex workers, and also homosexual individuals. Being a predominantly traditional and Catholic-affiliated country, a lot of healthcare and resources are denied to these people. While the woman who ran the clinic could speak a little bit of Spanish, some of the medical terms can easily get lost as most are not cognates to English words. Fortunately, my experience shadowing the Spanish translator at a hospital for the entirety of the previous summer came into good use and I was able to translate most of the lady’s presentation. This was a very interesting presentation that allowed us students, used to the healthcare system in the United States to reflect on their experiences and compare the differences in society.

Credit “Haitian Community in Puerto Plata, DR” by Iara Moran is licensed under CC BY 4.0

When we went to visit the local Haitian community, the main focus of going there was not to act as missionaries or have a superior “God-saving complex” to us. This is a focus I appreciated greatly that our class professor and Agnes Scott emphasize while teaching us to become global citizens and not tourists. Our purpose in visiting the community was to learn about the conflict between Haitian citizens in the Dominican Republic. Many Haitians face the same problem that immigrants to the United States face. They were brought over to another country at a very young age and grew up there without any knowledge or connections to their “native” country. The Dominican Republic’s government began to deny citizenship to those in this situation and even deporting them back across the border. These communities have helped many Haitians in this situation thanks to non-profit organizations and health workers that are like ambassadors between the community and the Dominican government to make sure that people continue to receive basic and necessary resources for living. To make our visit somewhat beneficial to the community, the students that were bilingual in Spanish or French assisted the health worker by going from house to house, more realistically, from shack to shack, and inquiring about the number of children in that household below the age of 12. This allowed for the health worker to have a census of the children population that would be needing vaccinations.

Credit “Haitian Community Children” by Iara Moran is licensed under CC BY 4.0

We played soccer with the children, we thanked and paid the mothers of the village who fed us, we shopped at the community’s artist’s home, and we even helped the educators teach the children how to make recyclable trash cans from used water bottles and barbed wire.

It was honestly very mind-opening. Even for me, someone who thinks they have seen it all of poverty, third-world countries, discrimination, racism, and more. However, it never ends, and there will always be an abundance of it in this world for a while. The thing that surprised us all the most, that even in the conditions that these people live in, who know the status of their lives depends on the country’s daily decision to send them past a river, still wake up every day with a smile on their faces and count their blessings for their health and the family that surrounds them.

Credit “DR Group Photo” by Iara Moran is licensed under CC BY 4.0



SUMMIT Learning Outcomes associated with this reflection:

  • 1. Identify, explain, and analyze global themes, process and systems
  • 2. Demonstrate knowledge and skills essential for global engagement
  • 3. Critically examine the relationship between dominant and marginalized cultures, subcultures or groups
  • 4. Communicate effectively through writing and speaking, especially across cultural or linguistic differences