//概要//---
日本の若い人(15歳から39歳まで)の死因のトップは自殺です。
自殺と関連性の深い疾患は鬱です。
アメリカ合衆国では死因の第2位が鬱によるとされています(4)。
この鬱に関して、アメリカ合衆国では
13歳から18歳までの11%が経験するといわれています(5)。
これは世界各国と比べて高い数字です。
疫学的には女性が多いとされています。
一方、新型コロナウィルスのパンデミックによって
不安や鬱の有病率が高くなっていることも指摘されています(6)。
人とのコミュニケーションの機会が制限されたり、
外出制限により運動や太陽に浴びる機会が減る事によって、
心のバランスを保ちにくくなっています。
社会活動制限によるストレスから
様々な事象についてネガティブバイアスが入りやすくなります。
それに対してメタ認知を働かせて、
自分の感情を制御するための再評価をすることの重要性が
コロナ禍の中、国際的な研究グループによって提唱されています(7)。
しかしながら、鬱や不安に対する認知療法も限界があることから
薬物治療や身体的な活動による介入も必要です。
若い間に精神疾患によって神経系にダメージが入ると
その影響は中年以降も続く可能性も考えられます。
一方で、鬱症状は発熱のように数字で客観的に確認しづらいことから
本人が自発的に精神科に通院する事が困難です。
周りの人が気づいて通院を促すことが必要ですが、
その場合においても本人が拒む場合もあります。
精神科に対する社会的な偏見も存在するからです。
しかしながら、その後の将来の事も考える必要があります。
重症化する前の早い段階で適切な治療を受ける事ができれば、
脳神経に入る傷跡を小さくすることができ、
また専門的な助言に基づく生活や考え方の見直しもできます。
それによってその後の生活が有症の状態に対して
劇的に改善する事も考えられます。
但し、精神疾患に対する治療というのは
生物学的にはブラックボックスの部分もあることから
医療を提供する側にも改善の余地が大きくあると考えられます。
医療を提供する側は、薬物治療を選択するケースが多いですが、
薬物治療で心の状態の「基礎」が回復した状態で
認知、心理、作業、学習、運動などの介入、助言をすることで
相乗効果が見込める可能性があります(8)。
但し、鬱症状に対する「根本的な原因」が存在する場合があります。
例えば、コロナ禍において
大学生が故郷を離れ、一人暮らしをしている場合に
孤独感、学業、生活面など経済的な不安から生じている場合もあります。
その場合にはこのような原因を、治療を提供する側が理解して
それに対して適切に向き合うことができるような環境を整える事が必要です。
このような事は薬物による治療を超えた領域となります。
もう一つ、青年期の鬱に関して大切な事だと思う事があります。
おそらく小さい時に親、友人、その他の人、社会から
多くの恐怖体験を経験すると脳の発達において問題が生じる可能性があります。
特に身近な親の虐待が脳の発達に影響を与える可能性があります。
そのような恐怖と鬱症状において
鬱症状を示す脳の特質と影響を受ける脳の部位の説明から
一定の因果を見出すことができるからです。
しかし、子育ては欠点だらけでいいと言われています。
そういった自分の欠点、ボロを出せる事が大事だと述べられています。
大昔、人はグループで子育てをしていたのですから。
ということです。
一方、脳の構造を決める発達期において
「ある閾値を超えるストレスを受ける」と
大人になって組織が安定状態に近づくときの
構造上の特性に影響を与える可能性は
現時点で私はあるのではないかと考えています。
今後、調査が必要ですが
コロナ禍で自宅待機の時間が多くなっています。
子供と親の双方向において避けられないストレスをうまく分散しながら、
うまく関係を形成していく事が大事だと考えられます。
//Background, Clinical brief review(1)//---
In
Japan, the first leading cause of death from 15 years old to 39 years old is
suicide. Depression in adolescent is highly associated to suicide. In the
United States, the second leading cause of death among adolescent is depression(4).
About 11% of adolescent 13-18 years experiences depression in the United
States, which is higher rate than the other countries(5). Epidemiologically,
women are higher than men.
On
the other hand, prevalence of anxiety and depression becomes high in COVID-19
pandemic (6). It is hard to control our mind positively due to many limitations
including human communication, exercise and basking in sunlight. Additionally,
economic burden jeopardizes our mental and physical health. In such situation,
we tend to have negative bias for social affair, leading some social conflict.
To combat such global situation, international collaborating team shows
importance for re-evaluation of our negative mood to control our mood(7).
However, cognitive therapy is not sufficient especially against depression, so
pharmacologic treatment and behavioral therapy are also needed. “Mental scarring” due to depression could be
associated with “Neural scarring”, which may be permanent scarring. Therefore, early treatment before
becoming severe is effective. However, awareness of depression is difficult, so
depression is frequently left as it is stands. Hence, the following guideline(#1-11)(1,9)
to measure the symptom is important.
(#1): Changes in sleep (insomnia or
hypersomnia)
The neural link to disturb sleep is formed
by negative emotions. Therefore, sleep is one of the important criteria in
mental health.
(#2): Changes in appetite or weight
(#3): Poor concentration
The person experiencing depression may be
governed exclusively by negative affair.
(#4): Indecision
Indecision may be associated with anxiety.
(#5): Fatigue
Fatigue may be associated with sleep
disturbance.
(#6): Low energy
(#7): Psychomotor slowing
(#8): Agitation
(#9): Feelings of worthlessness
(#10): Inappropriate guilt
(#11): Recurrent thoughts of death or
suicide
Anxiety often precedes depression in common in
adolescent, so chronic anxiety is risk factor. If so, they need to take
measures including consulting, stress relief and improving lifestyle.
On
the other hand, we need to know that depression is treatable medical
illness(1), but there is recurrent risks if treatment is abandoned prematurely(10).
The
mainstay of treatment against adolescent depression is a regular daily
schedule/good nutrition/moderate levels of activity or exercise/pharmacologic
intervention/psychotherapy. Therefore, both physical and mental health is
needed for treatment.
As
pharmacologic treatment, selective Serotonin Reuptake Inhibitors(SSRI) is
generally used. As of 2009 in Japan, over 1 million persons are prescribed. In
depression, serotonin transport between synapses is inhibited due to
reabsorption, and SSRI inhibits this reabsorption, resulting that it enhances
serotonin transport. However, depression is highly heterogeneity(2), there are
the cases that SSRI is not suitable to treatment. On the other hand, the
landmark Treatment for Adolescents with Depression Study show positive clinical
outcome for fluoxetine (SSRI) compared to placebo (Response rate, 61% vs 35%)
in adolescent. In psychotherapy and cognitive therapy, objectively knowing
their emotion/situation is one of the targets, and interpersonal communication
is recommended(1).
//Structural analysis of prefrontal cortex(2)//---
Reduced volume(atrophy) and reduced
interconnection of the frontal lobes with other brain regions is observed in
the patient diagnose with mental disorder, with chronic stress(11), those who
excessively consume sexually explicit materials(12) suicides(13) and daily male
cannabis users(15). Cannabis is the most commonly used illicit drug in
adolescence, and its use is associated with depression and suicidal behavior(1,14).
Therefore, dysfunction of prefrontal cortex could be associated with depression.
On structural and physiological change in the prefrontal cortex, medial
prefrontal cortex becomes less-connective including dendric shrinkage, spine
loss, demyelination, orbitofrontal cortex may be less-connective ability, and
prefrontal cortex networks increases functional connectivity, meaning that
increases inter-region connectivity(?)(2). On the other hand, how is biological
mechanism of brain atrophy, death of neuron/glia cell including metabolic,
immune change? As treatment, deep brain stimulation, optical stimulation,
inhibition of de-acetylase, adrenergic receptor antagonists, inactivation of
reward-related dopamine is a part of candidates.
//Neuroimmune system(3)//---
In
depression, prefrontal cortex experience neuronal atrophy, and nucleus
accumbens do neuronal hypertrophy(See Figure1). Chronic psychological stress
has a profound impact on peripheral immune responses and microglia, which leads
to be neuronal atrophy and hypertrophy. Activated microglial cell makes
dendritic spine density decrease, and synaptic engulfment increase, resulting
atrophy. On the other hand, ramified microglial cell makes dendritic spine
density increase, and homeostatic surveillance, resulting hypertrophy (See
Figure 4). Furthermore, some cytokines including IL-1β,
IL-6, TNF, BDNF affect neural system. Actually, in blood of the patient with
depression, inflammatory cytokine and immune cell over activation are confirmed(16,17).
Stress causing depression could affect systemic immune function including bone
marrow, spleen, blood and brain(See Figure 2).
//Discussion//---
Depression highly indicates heterogeneity.
Therefore, precise diagnosis based on both the biological evidence and clinical
symptom is needed for each patient. In biological evidence, image-based
analysis including MRI and biomarker showing immune landscape are a candidate
for diagnosis. Under current situation, even if precise diagnosis is made,
providing medical care in line with precise diagnosis may be difficult.
However, such perspective could be the future target for improvement of depression
care. If the goal is determined, we can pave the way to achieve the target. We
need to understand individual pathology firstly through multiple analysis also
in human model.
(Reference)
(1)
Leslie Miller, M.D., and John V. Campo,
M.D.
Depression in Adolescents
The New England Journal of Medicine 2021;
385:445-449
---
Author Affiliations
From the Department of Psychiatry and
Behavioral Sciences, Johns Hopkins University School of Medicine (L.M.,
J.V.C.), and the Kennedy Krieger Institute (J.V.C.) — both in Baltimore.
(2)
Diego A. Pizzagalli & Angela C. Roberts
Prefrontal cortex and depression
Neuropsychopharmacology (2021)
---
Author information
Author notes
These authors contributed equally: Diego A.
Pizzagalli, Angela C. Roberts.
Affiliations
Department of Psychiatry, Harvard Medical
School & McLean Hospital, Belmont, MA, USA
Diego A. Pizzagalli
Department of Physiology, Development and
Neuroscience, University of Cambridge, Cambridge, UK
Angela C. Roberts
(3)
Eric S. Wohleb, Tina Franklin, Masaaki
Iwata & Ronald S. Duman
Integrating neuroimmune systems in the
neurobiology of depression
Nature Reviews Neuroscience volume 17,
pages497–511 (2016)
---
Author information
Affiliations
Departments of Psychiatry and Neurobiology,
Yale University School of Medicine, New Haven, 06519, Connecticut, USA
Eric S. Wohleb, Tina Franklin & Ronald
S. Duman
Division of Neuropsychiatry, Department of
Brain and Neurosciences, Tottori University Faculty of Medicine, 86 Nishi-cho,
Yonago, Tottori, 683-8503, Japan
Masaaki Iwata
(4)
Web-based Injury Statistics Query and
Reporting System (WISQARS).
Centers for Disease Control and Prevention,
National Center for Injury Prevention and Control, 2018
(https://www . cdc . gov/ injury/
images/ lc - charts/ leading_causes_of_death
_by_age_group_2018_1100w850h . jpg).
(5)
Avenevoli S, Swendsen J, He JP, Burstein M,
Merikangas KR.
Major depression in the national
comorbidity survey-adolescent supplement: prevalence, correlates,
and treatment.
J Am Acad Child Adolesc Psychiatry 2015;
54(1): 37-44.e2.
(6)
Iman A. Basheti ,Qassim N. Mhaidat,Hala N.
Mhaidat
Prevalence of anxiety and depression during
COVID-19 pandemic among healthcare students in Jordan and its effect on their
learning process: A national survey
PLOS ONE April 5,2021
(7)
Ke Wang, Amit Goldenberg, Charles A.
Dorison et al.
A multi-country test of brief reappraisal
interventions on emotions during the COVID-19 pandemic
Nature Human Behaviour (2021)
(8)
Brent
D, Emslie G,
Clarke G, et al.
Switching to another SSRI or to venlafaxine
with or without cognitive behavioral therapy
for adolescents with
SSRI-resistant depression: the TORDIA randomized controlled trial.
JAMA 2008; 299: 901-13.
(9)
Diagnostic and statistical manual of mental
disorders, fifth edition.
Arlington, VA: American
Psychiatric Association, 2013.
(10)
Emslie GJ, Heiligenstein JH, Hoog SL, et
al.
Fluoxetine treatment for prevention of
relapse of depression in children and adolescents: a double-blind,
placebo-controlled study.
J
Am Acad Child
Adolesc Psychiatry 2004; 43: 1397-405.
(11)
Liston C, Miller MM, Goldwater DS, Radley JJ,
Rocher AB, Hof PR, et al. (July 2006).
"Stress-induced alterations in
prefrontal cortical dendritic morphology predict selective impairments in
perceptual attentional set-shifting".
The Journal of Neuroscience. 26 (30):
7870–4.
(12)
"Viewers of pornography have a smaller
reward system".
MAX-PLANCK-GESELLSCHAFT. 2 June 2014.
Retrieved 2 July 2018.
(13)
Rajkowska G (December 1997).
"Morphometric methods for studying the
prefrontal cortex in suicide victims and psychiatric patients".
Annals of the New York Academy of Sciences.
836 (1): 253–68. Bibcode:1997NYASA.836..253R.
(14)
Gobbi G, Atkin T, Zytynski T, et al.
Association
of cannabis use
in adolescence and risk of depression,
anxiety, and suicidality in young adulthood: a systematic review and
meta-analysis.
JAMA Psychiatry 2019; 76: 426-34.
(15)
Hermann D, Sartorius A, Welzel H, Walter S,
Skopp G, Ende G, Mann K (June 2007).
"Dorsolateral prefrontal cortex
N-acetylaspartate/total creatine (NAA/tCr) loss in male recreational cannabis
users".
Biological Psychiatry. 61 (11): 1281–9.
(16)
Howren, M. B.,
Lamkin, D. M. & Suls, J.
Associations of depression with C‑reactive protein, IL‑1, and IL‑6: a metaanalysis.
Psychosom. Med. 71, 171–186 (2009).
(17)
Dowlati, Y. et al.
A meta‑analysis of
cytokines in major depression.
Biol. Psychiatry 67, 446–457 (2010).
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