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Stress physiology and inflammation

How stress registers in the body over time.

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Qurʾān

القرآن6 shown

Verses named for this subject by hand come first. The rest are found by the subject’s own Arabic and English senses and are shown as lexical matches, not as anchors anyone has confirmed.

Qur'ān 21:76Arabic sense: الكرب, كرب

وَنُوحًا إِذۡ نَادَىٰ مِن قَبۡلُ فَٱسۡتَجَبۡنَا لَهُۥ فَنَجَّيۡنَٰهُ وَأَهۡلَهُۥ مِنَ ٱلۡكَرۡبِ ٱلۡعَظِيمِ

Long before that, We answered Noah when he cried out to Us: We saved him and his family from the great calamity

Qur'ān 37:115Arabic sense: الكرب, كرب

وَنَجَّيۡنَٰهُمَا وَقَوۡمَهُمَا مِنَ ٱلۡكَرۡبِ ٱلۡعَظِيمِ

We saved them and their people from great distress

Qur'ān 37:76Arabic sense: الكرب, كرب

وَنَجَّيۡنَٰهُ وَأَهۡلَهُۥ مِنَ ٱلۡكَرۡبِ ٱلۡعَظِيمِ

We saved him and his people from great distress

Qur'ān 6:64Arabic sense: كرب

قُلِ ٱللَّهُ يُنَجِّيكُم مِّنۡهَا وَمِن كُلِّ كَرۡبࣲ ثُمَّ أَنتُمۡ تُشۡرِكُونَ

Say, ‘God rescues you from this and every distress; yet still you worship others beside Him.’

Qur'ān 12:22Arabic sense: شده

وَلَمَّا بَلَغَ أَشُدَّهُۥٓ ءَاتَيۡنَٰهُ حُكۡمࣰ ا وَعِلۡمࣰ اۚ وَكَذَٰلِكَ نَجۡزِي ٱلۡمُحۡسِنِينَ

When he reached maturity, We gave him judgement and knowledge: this is how We reward those who do good

Qur'ān 6:152Arabic sense: شده

وَلَا تَقۡرَبُواْ مَالَ ٱلۡيَتِيمِ إِلَّا بِٱلَّتِي هِيَ أَحۡسَنُ حَتَّىٰ يَبۡلُغَ أَشُدَّهُۥۚ وَأَوۡفُواْ ٱلۡكَيۡلَ وَٱلۡمِيزَانَ بِٱلۡقِسۡطِۖ لَا نُكَلِّفُ نَفۡسًا إِلَّا وُسۡعَهَاۖ وَإِذَا قُلۡتُمۡ فَٱعۡدِلُواْ وَلَوۡ كَانَ ذَا قُرۡبَىٰۖ وَبِعَهۡدِ ٱللَّهِ أَوۡفُواْۚ ذَٰلِكُمۡ وَصَّىٰكُم بِهِۦ لَعَلَّكُمۡ تَذَكَّرُونَ

Stay well away from the property of orphans, except with the best [intentions], until they come of age; give full measure and weight, according to justice’- We do not burden any soul with more than it can bear- ‘ when you speak, be just, even if it concerns a relative; keep any promises you make in God’s name. This is what He commands you to do, so that you may take heed’

Tafsīr

التفسير6 shown

Commentary on the verses above, at most two editions per verse.

en-al-jalalayn on 21:76en-al-jalalayncommentary on an ayah this subject surfaced

And mention Noah what follows Nūhan substitutes for it when he called when he supplicated to God against his people — with the words My Lord do not leave upon the earth any inhabitant from among the disbelievers … to the end of the verse Q. 7126 before that is before the time of Abraham and Lot. And We responded to him and delivered him and his people who were in the Ark with him from the great agony namely from drowning and his people’s denial of him.

en-al-jalalayn on 37:115en-al-jalalayncommentary on an ayah this subject surfaced

and We delivered them and their people the Children of Israel from the great distress namely Pharaoh’s enslavement of them.

en-al-jalalayn on 37:76en-al-jalalayncommentary on an ayah this subject surfaced

And We delivered him and his family from the great distress which was the drowning

en-tafisr-ibn-kathir on 21:76en-tafisr-ibn-kathircommentary on an ayah this subject surfaced

And (remember) Nuh, when he cried (to Us) aforetime. We answered to his invocation and saved him and his family from the great distress (76)We helped him against the people who denied Our Ayat. Verily, they were a people given to evil. So We drowned them all (77) Nuh and His People Allah tells us how He responded to His servant and Messenger Nuh, peace be upon him, when he prayed to Him against his people for their disbelief in him: فَدَعَا رَبَّهُ أَنِّي مَغْلُوبٌ فَانتَصِرْ (Then he invoked his Lord (saying): "I have been overcome, so help (me)!")(54:10) وَقَالَ نُوحٌ رَّبِّ لَا تَذَرْ عَلَى الْأَرْضِ مِنَ الْكَافِرِينَ دَيَّارًا - إِنَّكَ إِن تَذَرْهُمْ يُضِلُّوا عِبَادَكَ وَلَا يَلِدُوا إِلَّا فَاجِرًا كَفَّارًا (And Nuh said: "My Lord! Leave not any inhabitant of the disbelievers on the earth! If You leave them, they will mislead Your servants, and they will beget none but wic

en-tafisr-ibn-kathir on 37:115en-tafisr-ibn-kathircommentary on an ayah this subject surfaced

And, indeed We gave Our grace to Musa and Harun (114)And We saved them and their people from the great distress (115)And helped them, so that they became the victors (116)And We gave them the clear Scripture (117)And guided them to the right path (118)And We left for them among the later generations (119)"Salam (peace!) be upon Musa and Harun! (120)Verily, thus do We reward the doers of good (121)Verily, they were two of Our believing servants (122) Musa and Harun Allah tells us how He blessed Musa and Harun with prophethood and how He saved them, along with those who believed, from the oppression of Fir'awn and his people, who had persecuted them by killing their sons and sparing their women, and by forcing them to do the most menial tasks, then ultimately He caused them to prevail over them and to seize their lands and their wealth and all that they had spent their entire lives amass

en-tafisr-ibn-kathir on 37:76en-tafisr-ibn-kathircommentary on an ayah this subject surfaced

And indeed Nuh invoked Us, and We are the best of those who answer (75)And We rescued him and his family from the great distress (76)And, his progeny, them We made the survivors (77)And left for him (a goodly remembrance) among the later generation (78)"Salam (peace!) be upon Nuh among the all creatures! (79)Verily, thus We reward the gooddoers (80)Verily, he [Nuh] was one of Our believing servants (81)Then We drowned the others (82) Nuh and His People When Allah tells us about how most of the early people went astray from the path of salvation, He starts the detailed explanation of that with the story of Nuh and the rejection of his people. Only a few of Nuh's people believed in him, despite the long period of time he spent among them. He stayed among them for one thousand years less fifty, and after he stayed among them for so long and their disbelief became too much for him to bear

Ḥadīth

الحديث4 shown

Sound narrations only, and never matched by text. A narration appears here because a compiler filed it under a chapter this subject maps to, or because someone read it and anchored it. Each row says which.

Sahih al-Bukhari 5642Patientsfiled here by the compiler

حَدَّثَنِي عَبْدُ اللَّهِ بْنُ مُحَمَّدٍ، حَدَّثَنَا عَبْدُ الْمَلِكِ بْنُ عَمْرٍو، حَدَّثَنَا زُهَيْرُ بْنُ مُحَمَّدٍ، عَنْ مُحَمَّدِ بْنِ عَمْرِو بْنِ حَلْحَلَةَ، عَنْ عَطَاءِ بْنِ يَسَارٍ، عَنْ أَبِي سَعِيدٍ الْخُدْرِيِّ، وَعَنْ أَبِي هُرَيْرَةَ، عَنِ النَّبِيِّ صلى الله عليه وسلم قَالَ ‏ "‏ مَا يُصِيبُ الْمُسْلِمَ مِنْ نَصَبٍ وَلاَ وَصَبٍ وَلاَ هَمٍّ وَلاَ حُزْنٍ وَلاَ أَذًى وَلاَ غَمٍّ حَتَّى الشَّوْكَةِ يُشَاكُهَا، إِلاَّ كَفَّرَ اللَّهُ بِهَا مِنْ خَطَايَاهُ ‏"‏‏.‏

Narrated Abu Sa`id Al-Khudri and Abu Huraira:The Prophet (ﷺ) said, "No fatigue, nor disease, nor sorrow, nor sadness, nor hurt, nor distress befalls a Muslim, even if it were the prick he receives from a thorn, but that Allah expiates some of his sins for that

Sahih al-Bukhari 5644Patientsfiled here by the compiler

حَدَّثَنَا إِبْرَاهِيمُ بْنُ الْمُنْذِرِ، قَالَ حَدَّثَنِي مُحَمَّدُ بْنُ فُلَيْحٍ، قَالَ حَدَّثَنِي أَبِي، عَنْ هِلاَلِ بْنِ عَلِيٍّ، مِنْ بَنِي عَامِرِ بْنِ لُؤَىٍّ عَنْ عَطَاءِ بْنِ يَسَارٍ، عَنْ أَبِي هُرَيْرَةَ ـ رضى الله عنه ـ قَالَ قَالَ رَسُولُ اللَّهِ صلى الله عليه وسلم ‏ "‏ مَثَلُ الْمُؤْمِنِ كَمَثَلِ الْخَامَةِ مِنَ الزَّرْعِ مِنْ حَيْثُ أَتَتْهَا الرِّيحُ كَفَأَتْهَا، فَإِذَا اعْتَدَلَتْ تَكَفَّأُ بِالْبَلاَءِ، وَالْفَاجِرُ كَالأَرْزَةِ صَمَّاءَ مُعْتَدِلَةً حَتَّى يَقْصِمَهَا اللَّهُ إِذَا شَاءَ ‏"‏‏.‏

Narrated Abu Huraira:Allah's Messenger (ﷺ) said, "The example of a believer is that of a fresh tender plant; from whatever direction the wind comes, it bends it, but when the wind becomes quiet, it becomes straight again. Similarly, a believer is afflicted with calamities (but he remains patient till Allah removes his difficulties.) And an impious wicked person is like a pine tree which keeps hard and straight till Allah cuts (breaks) it down when He wishes." (See Hadith No. 558, Vol)

Jami' at-Tirmidhi 2036Medicinefiled here by the compiler

حَدَّثَنَا مُحَمَّدُ بْنُ يَحْيَى، قال حَدَّثَنَا إِسْحَاقُ بْنُ مُحَمَّدٍ الْفَرْوِيُّ، قال حَدَّثَنَا إِسْمَاعِيلُ بْنُ جَعْفَرٍ، عَنْ عُمَارَةَ بْنِ غَزِيَّةَ، عَنْ عَاصِمِ بْنِ عُمَرَ بْنِ قَتَادَةَ، عَنْ مَحْمُودِ بْنِ لَبِيدٍ، عَنْ قَتَادَةَ بْنِ النُّعْمَانِ، أَنَّ رَسُولَ اللَّهِ صلى الله عليه وسلم قَالَ ‏ "‏ إِذَا أَحَبَّ اللَّهُ عَبْدًا حَمَاهُ الدُّنْيَا كَمَا يَظَلُّ أَحَدُكُمْ يَحْمِي سَقِيمَهُ الْمَاءَ ‏"‏ ‏.‏ قَالَ أَبُو عِيسَى وَفِي الْبَابِ عَنْ صُهَيْبٍ وَأُمِّ الْمُنْذِرِ ‏.‏ وَهَذَا حَدِيثٌ حَسَنٌ غَرِيبٌ ‏.‏ وَقَدْ رُوِيَ هَذَا الْحَدِيثُ عَنْ مَحْمُودِ بْنِ لَبِيدٍ عَنِ النَّبِيِّ صلى الله عليه وسلم مُرْسَلاً ‏.‏ حَدَّثَنَا عَلِيُّ بْنُ حُجْرٍ، قال أَخْبَرَنَا إِسْمَاعِيلُ بْنُ جَعْفَرٍ، عَنْ عَمْرِو بْنِ أَبِي عَمْرٍو، عَنْ عَاصِمِ بْنِ عُمَرَ بْنِ قَتَادَةَ، عَنْ مَحْمُودِ بْنِ لَبِيدٍ، عَنِ النَّبِيِّ صلى الله عليه وسلم نَحْوَهُ وَلَمْ يَذْكُرْ فِيهِ عَنْ قَتَادَةَ بْنِ النُّعْمَانِ ‏.‏ قَالَ أَبُو عِيسَى وَقَتَادَةُ بْنُ النُّعْمَانِ الظَّفَرِيُّ هُوَ أَخُو أَبِي سَعِيدٍ الْخُدْرِيِّ لأُمِّهِ وَمَحْمُودُ بْنُ لَبِيدٍ قَدْ أَدْرَكَ النَّبِيَّ صلى الله عليه وسلم وَرَآهُ وَهُوَ غُلاَمٌ صَغِيرٌ ‏.‏

Qatadah bin An-Nu'man narrated that the Messenger of Allah (s.a.w) said:"When Allah loves a slave, He prevents him from the world, just as one of you prevents his sick from water." Another chain reports a similar narration

Jami' at-Tirmidhi 2037Medicinefiled here by the compiler

حَدَّثَنَا عَبَّاسُ بْنُ مُحَمَّدٍ الدُّورِيُّ، قال حَدَّثَنَا يُونُسُ بْنُ مُحَمَّدٍ، قال حَدَّثَنَا فُلَيْحُ بْنُ سُلَيْمَانَ، عَنْ عُثْمَانَ بْنِ عَبْدِ الرَّحْمَنِ التَّيْمِيِّ، عَنْ يَعْقُوبَ بْنِ أَبِي يَعْقُوبَ، عَنْ أُمِّ الْمُنْذِرِ، قَالَتْ دَخَلَ عَلَىَّ رَسُولُ اللَّهِ صلى الله عليه وسلم وَمَعَهُ عَلِيٌّ وَلَنَا دَوَالٍ مُعَلَّقَةٌ قَالَتْ فَجَعَلَ رَسُولُ اللَّهِ صلى الله عليه وسلم يَأْكُلُ وَعَلِيٌّ مَعَهُ يَأْكُلُ ‏.‏ فَقَالَ رَسُولُ اللَّهِ صلى الله عليه وسلم لِعَلِيٍّ ‏"‏ مَهْ مَهْ يَا عَلِيُّ فَإِنَّكَ نَاقِهٌ ‏"‏ ‏.‏ قَالَ فَجَلَسَ عَلِيٌّ وَالنَّبِيُّ صلى الله عليه وسلم يَأْكُلُ ‏.‏ قَالَتْ فَجَعَلْتُ لَهُمْ سِلْقًا وَشَعِيرًا فَقَالَ النَّبِيُّ صلى الله عليه وسلم ‏"‏ يَا عَلِيُّ مِنْ هَذَا فَأَصِبْ فَإِنَّهُ أَوْفَقُ لَكَ ‏"‏ ‏.‏ قَالَ أَبُو عِيسَى هَذَا حَدِيثٌ حَسَنٌ غَرِيبٌ لاَ نَعْرِفُهُ إِلاَّ مِنْ حَدِيثِ فُلَيْحٍ ‏.‏ وَيُرْوَى عَنْ فُلَيْحٍ عَنْ أَيُّوبَ بْنِ عَبْدِ الرَّحْمَنِ ‏.‏ حَدَّثَنَا مُحَمَّدُ بْنُ بَشَّارٍ، قال حَدَّثَنَا أَبُو عَامِرٍ، وَأَبُو دَاوُدَ قَالاَ حَدَّثَنَا فُلَيْحُ بْنُ سُلَيْمَانَ، عَنْ أَيُّوبَ بْنِ عَبْدِ الرَّحْمَنِ، عَنْ يَعْقُوبَ، عَنْ أُمِّ الْمُنْذِرِ الأَنْصَارِيَّةِ، فِي حَدِيثِهِ قَالَتْ دَخَلَ عَلَيْنَا رَسُولُ اللَّهِ صلى الله عليه وسلم فَذَكَرَ نَحْوَ حَدِيثِ يُونُسَ بْنِ مُحَمَّدٍ إِلاَّ أَنَّهُ قَالَ ‏"‏ أَنْفَعُ لَكَ ‏"‏ ‏.‏ وَقَالَ مُحَمَّدُ بْنُ بَشَّارٍ وَحَدَّثَنِيهِ أَيُّوبُ بْنُ عَبْدِ الرَّحْمَنِ ‏.‏ هَذَا حَدِيثٌ جَيِّدٌ غَرِيبٌ ‏.‏

Umm Al-Mundhir said:"The Messenger of Allah (ﷺ) entered upon me, while `Ali was with him, and we had a cluster of unripe dates hanging." She said: "The Messenger of Allah (ﷺ) began eating, and `Ali ate with him. The Messenger of Allah (ﷺ) said to `Ali: 'Stop, stop, for you are still recovering.' So `Ali sat and the Prophet (ﷺ) ate." She said: "I made some chard and barley for them, so the Prophet (ﷺ) said: 'O `Ali eat from this, for indeed it will be more suitable for you." Another chain reports a similar narration

Classical works

كتب التراث6 shown

Arabic originals, reached through the subject’s Arabic senses. Interpretive sources, never proof of a ruling.

riyad-salihin §81riyad-salihinArabic sense: الشدة, الكرب, كرب

62 الثالث عن ابن عباس رضي الله عنهما قال كنت خلف النبي صلى الله عليه وسلم يوما فقال يا غلام إني أعلمك كلمات احفظ الله يحفظك احفظ الله تجده تجاهك إذا سألت فاسأل الله وإذا استعنت فاستعن بالله واعلم أن الأمة لو اجتمعت على أن ينفعوك بشيء لم ينفعوك إلا بشيء قد كتبه الله لك وإن اجتمعوا على أن يضروك بشيء لم يضروك إلا بشيء قد كتبه الله عليك رفعت الأقلام وجفت الصحف رواه الترمذي وقال حديث حسن صحيح وفي رواية غير الترمذي احفظ الله تجده أمامك تعرف إلى الله في الرخاء يعرفك في الشدة واعلم أن ما أخطأك لم يكن ليصيبك وما أصابك لم يكن ليخطئك واعلم أن النصر مع الصبر وأن الفرج مع الكرب وأن مع العسر يسرا

wabil-sayyib §331wabil-sayyibArabic sense: الشدة, شده, كرب

التاسعة والخمسون ان ذكر الله عز وجل يسهل الصعب وييسر العسير ويخفف المشاق فما ذكر الله عز وجل على صعب الا هان ولا على عسير الا تيسر ولا مشقة الا خفت ولا شدة الا زالت ولا كربه الا انفرجت فذكر الله تعالى هو الفرج بعد الشدة واليسر بعد العسر والفرج بعد الغم والهم يوضحه

ighathat §3074ighathatArabic sense: الكرب, كرب

وقالت أسماء بنت عميس : علمني رسول اللهكلمات أقولها عند الكرب : الله الله ربي لا أشرك به شيئا

madarij §5739madarijArabic sense: الكرب, كرب

التنفيس هو الترويح يقال نفس الله عنك الكرب أي اراحك منه وفي الحديث الصحيح من نفس عن مؤمن كربة من كرب الدنيا نفس الله عنه كربة من كرب يوم القيامة

mukhtasar-minhaj §3358mukhtasar-minhajArabic sense: الكرب, كرب

وفى "صحيح البخاري" من حديث أنس رضي الله عنه قال: لما ثقل النبي صلى الله عليه وآله وسلم، جعل يتغشاه الكرب، فقالت فاطمة رضي الله عنها: واكرب أبتاه! فقال لها: "ليس على أبيك كرب بعد اليوم".

rawdat-muhibbin §1061rawdat-muhibbinArabic sense: الكرب, كرب

خليلي ما من ساعة تذكرانها % من الدهر إلا فرجت عني الكربا

Research library

المكتبة البحثية1,632 works held

Peer-reviewed work held with its DOI and abstract, labelled with the study design its publication types report. None of it has been read or assessed, so nothing here may be cited as showing anything. Retracted work is held for the record but never listed; a review that a later version replaced is listed under its replacement and marked.

10.1073/pnas.1410401111Proceedings of the National Academy of Sciences of the United States of America (2014)MEDLINE-indexed journal, not yet read by us; matched on Allostasis, Stress, Physiological, allostatic load, Inflammation

Disruption of multisystem responses to stress in type 2 diabetes: investigating the dynamics of allostatic load.: Psychological stress-related processes are thought to contribute to the development and progression of type 2 diabetes, but the biological mechanisms involved are poorly understood. Here, we tested the notion that people with type 2 diabetes experience chronic allostatic load, manifest as dynamic disturbances in reactivity to and recovery from stress across multiple (cardiovascular, neuroendocrine, inflammatory, metabolic) biological systems, coupled with heightened experience of chronic life st

10.1016/j.jad.2018.05.027Journal of affective disorders (2018)MEDLINE-indexed journal, not yet read by us; matched on C-Reactive Protein, Cytokines, Oxidative Stress, Inflammation, Oxidative Stress

The influences of vitamin D and omega-3 co-supplementation on clinical, metabolic and genetic parameters in women with polycystic ovary syndrome.: Objective: The aim of this study was to evaluate the effect of the co-administration of vitamin D and omega-3 fatty acid on clinical, metabolic and genetic parameters in women with polycystic ovary syndrome (PCOS). Methods: This randomized, double-blinded, placebo-controlled clinical trial was conducted on 60 subjects, aged 18-40 years old with PCOS. Subjects were randomly allocated to take either 50,000 IU vitamin D every 2 weeks plus 2000 mg/day omega-3 fatty acid from fish oil (n = 30) or pla

10.1007/s10787-023-01213-0Inflammopharmacology (2023)MEDLINE-indexed journal, not yet read by us; matched on Inflammation, C-Reactive Protein, Oxidative Stress, Oxidative Stress

The effect of Nigella sativa (black seed) on biomarkers of inflammation and oxidative stress: an updated systematic review and meta-analysis of randomized controlled trials.: Objective: This study was conducted to assess the effect of Nigella sativa (N. sativa) supplementation on inflammatory and oxidative markers among the adult population. Methods: We carried out a comprehensive, systematic search of Scopus, Embase, Cochrane Library, Web of Science, PubMed, and Google Scholar till December 2022. A random-effects model was used to estimate the overall effect size. Results: In total, twenty trials consisting of 1086 participants were included in the meta-analysis. Fi

10.1016/j.bbi.2015.06.001Brain, behavior, and immunity (2015)MEDLINE-indexed journal, not yet read by us; matched on Inflammation, C-Reactive Protein, C-Reactive Protein, Inflammation Mediators, inflammatory markers

Cumulative meta-analysis of interleukins 6 and 1β, tumour necrosis factor α and C-reactive protein in patients with major depressive disorder.: Cumulative meta-analyses are used to evaluate the extent to which further studies are needed to confirm or refute a hypothesis. We used this approach to assess observational evidence on systemic inflammation in individuals with major depressive disorder. We identified 58 studies of four common inflammatory markers in a literature search of PubMed, Embase and PsychInfo databases in May 2014. Pooled data from the earliest eight studies already showed an association between interleukin-6 concentrat

10.1016/j.psyneuen.2023.106117Psychoneuroendocrinology (2023)MEDLINE-indexed journal, not yet read by us; matched on Allostasis, C-Reactive Protein, allostatic load

Towards a consensus definition of allostatic load: a multi-cohort, multi-system, multi-biomarker individual participant data (IPD) meta-analysis.: Background: Allostatic load (AL) is a multi-system composite index for quantifying physiological dysregulation caused by life course stressors. For over 30 years, an extensive body of research has drawn on the AL framework but has been hampered by the lack of a consistent definition. Methods: This study analyses data for 67,126 individuals aged 40-111 years participating in 13 different cohort studies and 40 biomarkers across 12 physiological systems: hypothalamic-pituitary-adrenal (HPA) axis, s

10.1016/j.schres.2017.04.015Schizophrenia research (2018)MEDLINE-indexed journal, not yet read by us; matched on C-Reactive Protein, Cytokines, Inflammation, inflammatory markers

Cytokines and C-reactive protein alterations with respect to cognitive impairment in schizophrenia and bipolar disorder: A systematic review.: Background: The aim of this article was to perform a systematic review of studies investigating the association between peripheral levels of cytokines and C-reactive protein (CRP), cytokine gene polymorphisms and cognition in patients with schizophrenia and bipolar disorder (BD). Methods: The following databases: PubMed, CINAHL Complete, Academic Search Complete, ERIC and Health Source: Nursing/Academic Edition databases were searched according to the PRISMA guidelines. We included studies that

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626 to 650 of 1,632
Slavich GM (2020)reviewMEDLINE-indexed journal, not yet read by usAnnual review of clinical psychology270 citations

Social Safety Theory: A Biologically Based Evolutionary Perspective on Life Stress, Health, and Behavior.

Social Safety Theory hypothesizes that developing and maintaining friendly social bonds is a fundamental organizing principle of human behavior and that threats to social safety are a critical feature of psychological stressors that increase risk for disease. Central to this formulation is the fact that the human brain and immune system are principally designed to keep the body biologically safe, which they do by continually monitoring and responding to social, physical, and microbial threats in the environment. Because situations involving social conflict, isolation, devaluation, rejection, and exclusion historically increased risk for physical injury and infection, anticipatory neural-immune reactivity to social threat was likely highly conserved. This neurocognitive and immunologic ability for humans to symbolically represent and respond to potentially dangerous social situations is u

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Aslam H, Green J, Jacka FN, Collier F, Berk M, Pasco J, Dawson SL (2020)reviewMEDLINE-indexed journal, not yet read by usNutritional neuroscience94 citations

Fermented foods, the gut and mental health: a mechanistic overview with implications for depression and anxiety.

Mental disorders including depression and anxiety are often comorbid with gut problems, suggesting a bidirectional relationship between mental health and gut function. Several mechanisms might explain this comorbidity, such as inflammation and immune activation; intestinal permeability; perturbations in the hypothalamic-pituitary-adrenal axis; neurotransmitter/neuropeptide dysregulation; dietary deficiencies; and disturbed gut microbiome composition. The potential of modulating the microbiome-gut-brain axis, and subsequently mental health, through the use of functional foods, is an emerging and novel topic of interest. Fermented foods are considered functional foods due to their putative health benefits. The process of microbial fermentation converts food substrates into more nutritionally and functionally rich products, resulting in functional microorganisms (probiotics), substrates tha

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Calis Z, Mogulkoc R, Baltaci AK (2020)reviewMEDLINE-indexed journal, not yet read by usMini reviews in medicinal chemistry131 citations

The Roles of Flavonols/Flavonoids in Neurodegeneration and Neuroinflammation.

The inflammatory process in the human body is a physiological response involving many cellular types and mediators. It results in scar formation to separate the damaged area from the surrounding healthy tissue. Because of increased blood-brain barrier permeability following inflammation, leukocytes infiltrate the CNS and are also supplemented by proinflammatory mediators. However, an acute inflammatory process after cerebral trauma or stroke may also result in a prolonged lesion formation, leading to a severe neuronal loss. The prolonged inflammatory process in the CNS may cause serious damage to the neuronal system. It may lead to CNS damage in such a way that endangers functional integration and proinflammatory system balance. Effects of different flavonoid species on ischemia-reperfusion injury and cognition and function have also been shown in experimental studies. Flavonoids are pre

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Zhou YX, Gong XH, Zhang H, Peng C (2020)reviewMEDLINE-indexed journal, not yet read by usBiomedicine & pharmacotherapy = Biomedecine & pharmacotherapie134 citations

A review on the pharmacokinetics of paeoniflorin and its anti-inflammatory and immunomodulatory effects.

Increasing pharmacological evidence supports that paeoniflorin, a water-soluble monoterpene glycoside isolated from Paeonia lactiflora Pall. (Shaoyao in Chinese), has a wide range of medicinal properties including anti-inflammatory, antioxidant, antithrombotic, anticonvulsive, analgesic, cardioprotective, neuroprotective, hepatoprotective, antidepressant-like, antitumoral, and immune-regulatory activities; as well as enhancing cognition and attenuating learning impairment. In addition to pharmacodynamic studies, information on pharmacokinetics is also significant for the further development and utilization of paeoniflorin. The present review focuses on the absorption, distribution, metabolism, and excretion of paeoniflorin, especially main pharmacological activities of paeoniflorin on inflammation and immune function. According to the findings obtained both in vitro and in vivo, a broad

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Komorowska-Müller JA, Schmöle AC (2020)reviewMEDLINE-indexed journal, not yet read by usInternational journal of molecular sciences113 citations

CB2 Receptor in Microglia: The Guardian of Self-Control.

Microglia are key to maintaining the homeostasis of the brain. These immune cells of the brain can be our biggest ally in fighting infections, but can worsen pathology or hinder recovery when uncontrolled. Thus, understanding how microglia contribute to neuroinflammatory processes and how their activity can be controlled is of great importance. It is known that activation of endocannabinoid system, and especially the cannabinoid type 2 receptor (CB2R), decreases inflammation. Alongside its non-psychoactive effect, it makes the CB2R receptor a perfect target for treating diseases accompanied by neuroinflammation including neurodegenerative diseases. However, the exact mechanisms by which CB2R regulates microglial activity are not yet understood. Here, we review the current knowledge on the roles of microglial CB2R from in vitro and in vivo studies. We look into CB2R function under physiol

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Wehkamp J, Stange EF (2020)reviewMEDLINE-indexed journal, not yet read by usFrontiers in immunology79 citations

An Update Review on the Paneth Cell as Key to Ileal Crohn's Disease.

The Paneth cells reside in the small intestine at the bottom of the crypts of Lieberkühn, intermingled with stem cells, and provide a niche for their neighbors by secreting growth and Wnt-factors as well as different antimicrobial peptides including defensins, lysozyme and others. The most abundant are the human Paneth cell α-defensin 5 and 6 that keep the crypt sterile and control the local microbiome. In ileal Crohn's disease various mechanisms including established genetic risk factors contribute to defects in the production and ordered secretion of these peptides. In addition, life-style risk factors for Crohn's disease like tobacco smoking also impact on Paneth cell function. Taken together, current evidence suggest that defective Paneth cells may play the key role in initiating inflammation in ileal, and maybe ileocecal, Crohn's disease by allowing bacterial attachment and invasion

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Abdoli A, Mirzaian Ardakani H (2020)reviewMEDLINE-indexed journal, not yet read by usMetabolic brain disease8 citations

Potential application of helminth therapy for resolution of neuroinflammation in neuropsychiatric disorders.

Neuropsychiatric disorders (NPDs) are among the major debilitating disorders worldwide with multiple etiological factors. However, in recent years, psychoneuroimmunology uncovered the role of inflammatory condition and autoimmune disorders in the etiopathogenesis of different NPDs. Hence, resolution of inflammation is a new therapeutic target of NPDs. On the other hand, Helminth infections are among the most prevalent infectious diseases in underdeveloped countries, which usually caused chronic infections with minor clinical symptoms. Remarkably, helminths are among the master regulator of inflammatory reactions and epidemiological studies have shown an inverse association between prevalence of autoimmune disorders with these infections. As such, changes of intestinal microbiota are known to be associated with inflammatory conditions in various NPDs. Conversely, helminth colonization alt

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Physical exercise in the prevention and treatment of Alzheimer's disease.

Dementia is one of the greatest global challenges for health and social care in the 21st century. Alzheimer's disease (AD), the most common type of dementia, is by no means an inevitable consequence of growing old. Several lifestyle factors may increase, or reduce, an individual's risk of developing AD. Much has been written over the ages about the benefits of exercise and physical activity. Among the risk factors associated with AD is a low level of physical activity. The relationship between physical and mental health was established several years ago. In this review, we discuss the role of exercise (aerobic and resistance) training as a therapeutic strategy for the treatment and prevention of AD. Older adults who exercise are more likely to maintain cognition. We address the main protective mechanism on brain function modulated by physical exercise by examining both human and animal s

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Ting EY, Yang AC, Tsai SJ (2020)reviewMEDLINE-indexed journal, not yet read by usInternational journal of molecular sciences277 citations

Role of Interleukin-6 in Depressive Disorder.

Major depressive disorder (MDD), which is a leading psychiatric illness across the world, severely affects quality of life and causes an increased incidence of suicide. Evidence from animal as well as clinical studies have indicated that increased peripheral or central cytokine interleukin-6 (IL-6) levels play an important role in stress reaction and depressive disorder, especially physical disorders comorbid with depression. Increased release of IL-6 in MDD has been found to be a factor associated with MDD prognosis and therapeutic response, and may affect a wide range of depressive symptomatology. However, study results of the IL6 genetic effects in MDD are controversial. Increased IL-6 activity may cause depression through activation of hypothalamic-pituitary-adrenal axis or influence of the neurotransmitter metabolism. The important role of neuroinflammation in MDD pathogenesis has c

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Cruz-Pereira JS, Rea K, Nolan YM, O'Leary OF, Dinan TG, Cryan JF (2020)reviewMEDLINE-indexed journal, not yet read by usAnnual review of psychology238 citations

Depression's Unholy Trinity: Dysregulated Stress, Immunity, and the Microbiome.

Depression remains one of the most prevalent psychiatric disorders, with many patients not responding adequately to available treatments. Chronic or early-life stress is one of the key risk factors for depression. In addition, a growing body of data implicates chronic inflammation as a major player in depression pathogenesis. More recently, the gut microbiota has emerged as an important regulator of brain and behavior and also has been linked to depression. However, how this holy trinity of risk factors interact to maintain physiological homeostasis in the brain and body is not fully understood. In this review, we integrate the available data from animal and human studies on these three factors in the etiology and progression of depression. We also focus on the processes by which this microbiota-immune-stress matrix may influence centrally mediated events and on possible therapeutic inte

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Leigh SJ, Morris MJ (2020)reviewMEDLINE-indexed journal, not yet read by usBiochimica et biophysica acta. Molecular basis of disease148 citations

Diet, inflammation and the gut microbiome: Mechanisms for obesity-associated cognitive impairment.

Poor diet and obesity are associated with cognitive impairment throughout adulthood, and increased dementia risk in aging. Here we review the current literature interrogating the mechanisms by which diets high in fat, or fat and sugar lead to cognitive impairment, focusing on changes to gut microbiome composition, inflammatory signalling and blood-brain barrier integrity. Preclinical studies indicate weight gain is not necessary for diet-induced cognitive impairment. Rather, gut microbiome composition, and systemic and central inflammatory processes appear to contribute to diet-induced cognitive impairment. While both obese humans and rodents exhibit reduced blood-brain barrier integrity, cognitive impairments precede these changes, suggesting other mechanisms may underly diet-induced cognitive changes. Other potential candidates include hormone, glucoregulatory and cardiovascular change

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Parker BJ, Wearsch PA, Veloo ACM, Rodriguez-Palacios A (2020)reviewMEDLINE-indexed journal, not yet read by usFrontiers in immunology1,361 citations

The Genus Alistipes: Gut Bacteria With Emerging Implications to Inflammation, Cancer, and Mental Health.

Alistipes is a relatively new genus of bacteria isolated primarily from medical clinical samples, although at a low rate compared to other genus members of the Bacteroidetes phylum, which are highly relevant in dysbiosis and disease. According to the taxonomy database at The National Center for Biotechnology Information, the genus consists of 13 species: Alistipes finegoldii, Alistipes putredinis, Alistipes onderdonkii, Alistipes shahii, Alistipes indistinctus, Alistipes senegalensis, Alistipes timonensis, Alistipes obesi, Alistipes ihumii, Alistipes inops, Alistipes megaguti, Alistipes provencensis, and Alistipes massiliensis. Alistipes communis and A. dispar, and the subspecies A. Onderdonkii subspecies vulgaris (vs. onderdonkii subsp.) are the newest strains featured outside that list. Although typically isolated from the human gut microbiome various species of this genus have been is

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Shahar G, Rogers ML, Shalev H, Joiner TE (2020)reviewMEDLINE-indexed journal, not yet read by usJournal of personality11 citations

Self-criticism, interpersonal conditions, and biosystemic inflammation in suicidal thoughts and behaviors within mood disorders: A bio-cognitive-interpersonal hypothesis.

We review the theoretical and empirical literature on the role of self-concept in suicidal behavior in the context of mood disorders (i.e., unipolar depression and bipolar spectrum disorders). The main themes emanating from this review are then juxtaposed against (a) the Interpersonal-Psychological Theory of Suicide and (b) biological research on the role of inflammatory processes in suicidality. Such a juxtaposition paves the way for a bio-cognitive-interpersonal hypothesis. Pathologies of the self-concept-primarily self-criticism-propel mood disorder sufferers to generate interpersonal stress that culminates in two proximal causes of suicidality: thwarted belongingness and perceived burdensomeness. In turn, these two interpersonal conditions set in motion systemic biosystemic inflammation, serving as a proximal cause for suicidality in mood disorders. We conclude by describing a resear

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Beurel E, Toups M, Nemeroff CB (2020)reviewMEDLINE-indexed journal, not yet read by usNeuron1,664 citations

The Bidirectional Relationship of Depression and Inflammation: Double Trouble.

Depression represents the number one cause of disability worldwide and is often fatal. Inflammatory processes have been implicated in the pathophysiology of depression. It is now well established that dysregulation of both the innate and adaptive immune systems occur in depressed patients and hinder favorable prognosis, including antidepressant responses. In this review, we describe how the immune system regulates mood and the potential causes of the dysregulated inflammatory responses in depressed patients. However, the proportion of never-treated major depressive disorder (MDD) patients who exhibit inflammation remains to be clarified, as the heterogeneity in inflammation findings may stem in part from examining MDD patients with varied interventions. Inflammation is likely a critical disease modifier, promoting susceptibility to depression. Controlling inflammation might provide an ov

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Lin X, Chen Y, Zhang P, Chen G, Zhou Y, Yu X (2020)reviewMEDLINE-indexed journal, not yet read by usExperimental gerontology224 citations

The potential mechanism of postoperative cognitive dysfunction in older people.

Postoperative cognitive dysfunction (POCD) is a common disorder following surgery, which seriously threatens the quality of patients' life, especially the older people. Accumulating attention has been paid to POCD worldwide in pace with the popularization of anesthesia/surgery. The development of medical humanities and rehabilitation medicine sets higher demands on accurate diagnosis and safe treatment system of POCD. Although the research on POCD is in full swing, underlying pathogenesis is still inconclusive due to these conflicting results and controversial evidence. Generally, POCD is closely related to neuropsychiatric diseases such as dementia, depression and Alzheimer's disease in molecular pathways. Researchers have come up with various hypotheses to reveal the mechanisms of POCD, including neuroinflammation, oxidative stress, autophagy disorder, impaired synaptic function, lacki

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Grundy L, Erickson A, Brierley SM (2019)reviewMEDLINE-indexed journal, not yet read by usAnnual review of physiology183 citations

Visceral Pain.

Most of us live blissfully unaware of the orchestrated function that our internal organs conduct. When this peace is interrupted, it is often by routine sensations of hunger and urge. However, for >20% of the global population, chronic visceral pain is an unpleasant and often excruciating reminder of the existence of our internal organs. In many cases, there is no obvious underlying pathological cause of the pain. Accordingly, chronic visceral pain is debilitating, reduces the quality of life of sufferers, and has large concomitant socioeconomic costs. In this review, we highlight key mechanisms underlying chronic abdominal and pelvic pain associated with functional and inflammatory disorders of the gastrointestinal and urinary tracts. This includes how the colon and bladder are innervated by specialized subclasses of spinal afferents, how these afferents become sensitized in highly dyna

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Sochocka M, Donskow-Łysoniewska K, Diniz BS, Kurpas D, Brzozowska E, Leszek J (2019)reviewMEDLINE-indexed journal, not yet read by usMolecular neurobiology452 citations

The Gut Microbiome Alterations and Inflammation-Driven Pathogenesis of Alzheimer's Disease-a Critical Review.

One of the most important scientific discoveries of recent years was the disclosure that the intestinal microflora takes part in bidirectional communication between the gut and the brain. Scientists suggest that human gut microflora may even act as the "second brain" and be responsible for neurodegenerative disorders like Alzheimer's disease (AD). Although human-associated microbial communities are generally stable, they can be altered by common human actions and experiences. Enteric bacteria, commensal, and pathogenic microorganisms, may have a major impact on immune system, brain development, and behavior, as they are able to produce several neurotransmitters and neuromodulators like serotonin, kynurenine, catecholamine, etc., as well as amyloids. However, brain destructive mechanisms, that can lead to dementia and AD, start with the intestinal microbiome dysbiosis, development of loca

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Milaneschi Y, Simmons WK, van Rossum EFC, Penninx BW (2019)reviewMEDLINE-indexed journal, not yet read by usMolecular psychiatry726 citations

Depression and obesity: evidence of shared biological mechanisms.

Depression and obesity are common conditions with major public health implications that tend to co-occur within individuals. The relationship between these conditions is bidirectional: the presence of one increases the risk for developing the other. It has thus become crucial to gain a better understanding of the mechanisms responsible for the intertwined downward physiological spirals associated with both conditions. The present review focuses specifically on shared biological pathways that may mechanistically explain the depression-obesity link, including genetics, alterations in systems involved in homeostatic adjustments (HPA axis, immuno-inflammatory activation, neuroendocrine regulators of energy metabolism including leptin and insulin, and microbiome) and brain circuitries integrating homeostatic and mood regulatory responses. Furthermore, the review addresses interventional oppor

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McGrattan AM, McGuinness B, McKinley MC, Kee F, Passmore P, Woodside JV, McEvoy CT (2019)reviewMEDLINE-indexed journal, not yet read by usCurrent nutrition reports289 citations

Diet and Inflammation in Cognitive Ageing and Alzheimer's Disease.

Purpose of review: Nutrition is known to modulate the immune system and may alter neuroinflammatory processes implicated in the pathogenesis of Alzheimer's disease (AD) and progression of neurodegeneration. Here, we review the evidence for healthy dietary patterns and age-related cognition and discuss potential neuroinflammatory actions of diet on cognitive function. Recent findings: Anti-inflammatory dietary patterns such as the Mediterranean diet (MD) and dietary approaches to stop hypertension (DASH) may be neuroprotective. Several dietary components consumed in the MD and DASH (omega-3 fatty acids, antioxidants and polyphenols) can inhibit neuroinflammation associated with AD. Anti-inflammatory diets may also attenuate neuroinflammation via indirect immune pathways from the gut microbiome and systemic circulation. Diet may influence cognitive ageing via several inflammatory pathways.

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Lee CH, Giuliani F (2019)reviewMEDLINE-indexed journal, not yet read by usFrontiers in immunology444 citations

The Role of Inflammation in Depression and Fatigue.

Depression and fatigue are conditions responsible for heavy global societal burden, especially in patients already suffering from chronic diseases. These symptoms have been identified by those affected as some of the most disabling symptoms which affect the quality of life and productivity of the individual. While many factors play a role in the development of depression and fatigue, both have been associated with increased inflammatory activation of the immune system affecting both the periphery and the central nervous system (CNS). This is further supported by the well-described association between diseases that involve immune activation and these symptoms in autoimmune disorders, such as multiple sclerosis and immune system activation in response to infections, like sepsis. Treatments for depression also support this immunopsychiatric link. Antidepressants have been shown to decrease

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Peirce JM, Alviña K (2019)reviewMEDLINE-indexed journal, not yet read by usJournal of neuroscience research286 citations

The role of inflammation and the gut microbiome in depression and anxiety.

The study of the gut microbiome has increasingly revealed an important role in modulating brain function and mental health. In this review, we underscore specific pathways and mechanisms by which the gut microbiome can promote the development of mental disorders such as depression and anxiety. First, we review the involvement of the stress response and immune system activation in the development of depression and anxiety. Then, we examine germ-free murine models used to uncover the role of the gut microbiome in developing and modulating pertinent activity in the brain and the immune system. We also document multiple pathways by which stress-induced inflammation harms brain function and ultimately affects mental health, and review how probiotic and prebiotic treatments have shown to be beneficial. Lastly, we provide an overview of gut microbiome-derived compounds (short-chain fatty acids,

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Delzenne NM, Knudsen C, Beaumont M, Rodriguez J, Neyrinck AM, Bindels LB (2019)reviewMEDLINE-indexed journal, not yet read by usThe Proceedings of the Nutrition Society90 citations

Contribution of the gut microbiota to the regulation of host metabolism and energy balance: a focus on the gut-liver axis.

This review presents mechanistic studies performed in vitro and in animal models, as well as data obtained in patients that contribute to a better understanding of the impact of nutrients interacting with the gut microbiota on metabolic and behavioural alterations linked to obesity. The gut microbiota composition and function are altered in several pathological conditions including obesity and related diseases i.e. non-alcoholic fatty liver diseases (NAFLD). The gut-liver axis is clearly influenced by alterations of the gut barrier that drives inflammation. In addition, recent papers propose that specific metabolites issued from the metabolic cooperation between the gut microbes and host enzymes, modulate inflammation and gene expression in the liver. This review illustrates how dietary intervention with prebiotics or probiotics influences host energy metabolism and inflammation. Indeed,

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Hori H, Kim Y (2019)reviewMEDLINE-indexed journal, not yet read by usPsychiatry and clinical neurosciences250 citations

Inflammation and post-traumatic stress disorder.

While post-traumatic stress disorder (PTSD) is currently diagnosed based solely on classic psychological and behavioral symptoms, a growing body of evidence has highlighted a link between this disorder and alterations in the immune and inflammatory systems. Epidemiological studies have demonstrated that PTSD is associated with significantly increased rates of physical comorbidities in which immune dysregulation is involved, such as metabolic syndrome, atherosclerotic cardiovascular disease, and autoimmune diseases. In line with this, a number of blood biomarker studies have reported that compared to healthy controls, individuals with PTSD exhibit significantly elevated levels of proinflammatory markers, such as interleukin-1β, interleukin-6, tumor necrosis factor-α, and C-reactive protein. Moreover, various lines of animal and human research have suggested that inflammation is not only a

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Pape K, Tamouza R, Leboyer M, Zipp F (2019)reviewMEDLINE-indexed journal, not yet read by usNature reviews. Neurology362 citations

Immunoneuropsychiatry - novel perspectives on brain disorders.

Immune processes have a vital role in CNS homeostasis, resilience and brain reserve. Our cognitive and social abilities rely on a highly sensitive and fine-tuned equilibrium of immune responses that involve both innate and adaptive immunity. Autoimmunity, chronic inflammation, infection and psychosocial stress can tip the scales towards disruption of higher-order networks. However, not only classical neuroinflammatory diseases, such as multiple sclerosis and autoimmune encephalitis, are caused by immune dysregulation that affects CNS function. Recent insight indicates that similar processes are involved in psychiatric diseases such as schizophrenia, autism spectrum disorder, bipolar disorder and depression. Pathways that are common to these disorders include microglial activation, pro-inflammatory cytokines, molecular mimicry, anti-neuronal autoantibodies, self-reactive T cells and distu

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Nerurkar L, Siebert S, McInnes IB, Cavanagh J (2019)reviewMEDLINE-indexed journal, not yet read by usThe lancet. Psychiatry281 citations

Rheumatoid arthritis and depression: an inflammatory perspective.

The coexistence of immune-mediated inflammatory diseases with depression has long been recognised. Data that illustrate the intimate associations between peripheral and brain immune responses raise the possibility of shared pathophysiological mechanisms. These associations include the negative effects of proinflammatory cytokines on monoaminergic neurotransmission, neurotrophic factors, and measures of synaptic plasticity. The evidence supporting this association is accumulating and includes findings from clinical trials of immunomodulatory therapy, indicating that these interventions can provide benefits to mental health independent of improvements in physical disease scores. In this Review, we assess this evidence in relation to rheumatoid arthritis and depression, with a focus on innate immune and molecular responses to inflammation, and discuss the challenges of assessing causation i

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