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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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551 to 575 of 1,632
Pankhurst NW (2011)reviewMEDLINE-indexed journal, not yet read by usGeneral and comparative endocrinology177 citations

The endocrinology of stress in fish: an environmental perspective.

Much of the understanding of the endocrine basis of stress in fish comes from studies of cultured stocks of teleosts; there is comparatively little information on stress responses in wild stock, and less still on chondrosteans and elasmobranchs. This understanding is being refined through increasing understanding of molecular processes underlying endocrine events, with molecular tools offering ready examination of parts of the endocrine pathway that have been resistant to easy measurement of hormone products. An assessment of the timecourse of activation of the hypothalamic-pituitary-interrenal axis shows generally strong independence of temperature, with most teleosts showing measurable increase in plasma cortisol within 10 min of stress. Chondrostean and elasmobranch responses are less well described, but in chondrosteans at least, the response pattern appears to be similar to teleosts

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Roth TL, Sweatt JD (2011)reviewMEDLINE-indexed journal, not yet read by usHormones and behavior132 citations

Epigenetic marking of the BDNF gene by early-life adverse experiences.

Studies over the past half-century have made it clear that environmental influences in development, particularly stress and traumatic experiences, can remain pervasive across the lifespan. Though it has been hypothesized for some time that the long-term consequences of early-life adversity represent epigenetic influences, it has not been until recently that studies have begun to provide empirical support of experience-driven epigenetic modifications to the genome. Here we focus on this theme, and review current knowledge pertaining to the epigenetics of behavioral development. At the center of our discussion is the brain-derived neurotrophic factor (BDNF) gene, as abnormal BDNF gene activity is a leading etiological hypothesis by which early-life adverse experiences persistently modify brain and behavioral plasticity.

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Decety J (2010)reviewMEDLINE-indexed journal, not yet read by usDevelopmental neuroscience287 citations

The neurodevelopment of empathy in humans.

Empathy, which implies a shared interpersonal experience, is implicated in many aspects of social cognition, notably prosocial behavior, morality and the regulation of aggression. The purpose of this paper is to critically examine the current knowledge in developmental and affective neuroscience with an emphasis on the perception of pain in others. It will be argued that human empathy involves several components: affective arousal, emotion understanding and emotion regulation, each with different developmental trajectories. These components are implemented by a complex network of distributed, often recursively connected, interacting neural regions including the superior temporal sulcus, insula, medial and orbitofrontal cortices, amygdala and anterior cingulate cortex, as well as autonomic and neuroendocrine processes implicated in social behaviors and emotional states. Decomposing the co

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Romeo RD (2010)reviewMEDLINE-indexed journal, not yet read by usFrontiers in neuroendocrinology179 citations

Pubertal maturation and programming of hypothalamic-pituitary-adrenal reactivity.

Modifications in neuroendocrine function are a hallmark of pubertal development. These changes have many short- and long-term implications for the physiological and neurobehavioral function of an individual. The purpose of the present review is to discuss our current understanding of how pubertal development and stress interact to affect the hypothalamic-pituitary-adrenal (HPA) axis, the major neuroendocrine axis that controls the hormonal stress response. A growing body of literature indicates that puberty is marked by dramatic transitions in stress reactivity. Moreover, recent studies indicate that exposure to stressors during pubertal maturation may result in enduring changes in HPA responsiveness in adulthood. As puberty is marked by a substantial increase in many stress-related psychological and physiological disorders (e.g., depression, anxiety, drug abuse), it is essential to unde

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Nader N, Chrousos GP, Kino T (2010)reviewMEDLINE-indexed journal, not yet read by usTrends in endocrinology and metabolism: TEM299 citations

Interactions of the circadian CLOCK system and the HPA axis.

Organisms have developed concurrent behavioral and physiological adaptations to the strong influence of day/night cycles, as well as to unforeseen, random stress stimuli. These circadian and stress-related responses are achieved by two highly conserved and interrelated regulatory networks, the circadian CLOCK and stress systems, which respectively consist of oscillating molecular pacemakers, the Clock/Bmal1 transcription factors, and the hypothalamic-pituitary-adrenal (HPA) axis and its end-effector, the glucocorticoid receptor. These systems communicate with one another at different signaling levels and dysregulation of either system can lead to development of pathologic conditions. In this review, we summarize the mutual physiologic interactions between the circadian CLOCK system and the HPA axis, and discuss their clinical implications.

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Aluru N, Vijayan MM (2009)reviewMEDLINE-indexed journal, not yet read by usGeneral and comparative endocrinology168 citations

Stress transcriptomics in fish: a role for genomic cortisol signaling.

The physiological responses to stressors, including hormonal profiles and associated tissue responsiveness have been extensively studied in teleosts, but the molecular mechanisms associated with this adaptive response are not well understood. The advent of cDNA microarray technology has transformed the field of functional genomics by revealing global gene expression changes in response to stressor exposures even in non-mammalian vertebrates, including fish. A unifying response in studies related to stressor exposure is activation of the hypothalamus-pituitary-interrenal (HPI) axis in fish, leading to cortisol release into the circulation. Here we will discuss the implications of some of the gene expression changes observed in response to acute stress in fish, while highlighting a role for cortisol in this adaptive stress response. As liver is a key organ for metabolic adjustments to stre

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Johnston GR, Webster NR (2009)reviewMEDLINE-indexed journal, not yet read by usBritish journal of anaesthesia136 citations

Cytokines and the immunomodulatory function of the vagus nerve.

Cytokine synthesis and release is an essential component of the innate immune system, but inappropriate, excessive production results in a generalized systemic inflammatory response which damages distant organs. Recent research has identified an immunomodulatory function of the vagus nerve whereby activation of the efferent arm results in regulation of cytokine production. Termed the 'cholinergic anti-inflammatory pathway', this neuro-immune communication provides the host with a fast, discrete, and localized means of controlling the immune response and preventing excessive inflammation. Stimulation of the vagus nerve attenuates cytokine production and improves survival in experimental sepsis, haemorrhagic shock, ischaemia-reperfusion injury, and other conditions of cytokine excess and research is now underway in developing new and novel therapeutics aimed at stimulating the vagus nerve

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Alsop D, Vijayan MM (2009)reviewMEDLINE-indexed journal, not yet read by usComparative biochemistry and physiology. Part A, Molecular & integrative physiology121 citations

Molecular programming of the corticosteroid stress axis during zebrafish development.

The functions of the hypothalamus-pituitary-interrenal (HPI) axis in teleosts have been studied primarily in juvenile and adult fish, whereas little is known about the molecular events leading to the onset of the stressor-induced cortisol response during development. Here we summarize a number of studies that have examined changes in the expression of genes encoding proteins critical for the functioning of the HPI axis, and the associated cortisol response in developing zebrafish embryos and larvae. The mRNA transcripts for some of these genes, including corticotropin releasing factor (CRF), proopiomelanocortin (POMC), melanocortin 2 receptor (MC2R), steroidogenic acute regulatory protein (StAR) and cytochrome P450 side chain cleavage (P450scc) have been detected during embryogenesis prior to hatch. The mRNA levels of MC2R, StAR and P450scc are up-regulated immediately prior to the drama

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Alsop D, Vijayan M (2009)reviewMEDLINE-indexed journal, not yet read by usGeneral and comparative endocrinology157 citations

The zebrafish stress axis: molecular fallout from the teleost-specific genome duplication event.

The teleost-specific whole genome duplication event 350 million years ago resulted in a variety of duplicated genes that exist in fish today. In this review, we examine whether molecular components involved in the functioning of the hypothalamus-pituitary-interrenal (HPI) axis are present as single or duplicate genes. Specifically, we looked at corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and the glucocorticoid receptor (GR). The focus is on zebrafish but a variety of species are covered whenever data is available through literature or genomic database searches. Duplicate CRH genes are retained in the salmoniformes and cypriniformes, and the peptide sequences are very similar or identical. Zebrafish, along with the Acanthopterygii, are the exceptions as they have a single CRH gene. Also, two copies of the proopiomelanocortin (POMC) gene, which encodes for ACT

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Weaver IC (2009)reviewMEDLINE-indexed journal, not yet read by usBirth defects research. Part C, Embryo today : reviews65 citations

Shaping adult phenotypes through early life environments.

A major question in the biology of stress and environmental adaptation concerns the neurobiological basis of how neuroendocrine systems governing physiological regulatory mechanisms essential for life (metabolism, immune response, organ function) become harmful. The current view is that a switch from protection to damage occurs when vulnerable phenotypes are exposed to adverse environmental conditions. In accordance with this theory, sequelae of early life social and environmental stressors, such as childhood abuse, neglect, poverty, and poor nutrition, have been associated with the emergence of mental and physical illness (i.e., anxiety, mood disorders, poor impulse control, psychosis, and drug abuse) and an increased risk of common metabolic and cardiovascular diseases later in life. Evidence from animal and human studies investigating the associations between early life experiences (i

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Papadimitriou A, Priftis KN (2009)reviewMEDLINE-indexed journal, not yet read by usNeuroimmunomodulation216 citations

Regulation of the hypothalamic-pituitary-adrenal axis.

Glucocorticoids (GCs) are essential for the maintenance of homeostasis and enable the organism to prepare for, respond to and manage stress, either physical or emotional. Cortisol, the principal GC in humans, is synthesized in the adrenal cortex. It is released in the circulation in a pulsatile and circadian pattern. GC secretion is governed by hypothalamus and pituitary. The hypothalamus senses changes in the external and internal environment that may disrupt the homeostatic balance of the organism (i.e. stressors), and responds by releasing corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) from parvocellular neurons projecting from the paraventricular nucleus to the median eminence. These neurohormones are released into the anterior pituitary where they act synergistically via specific receptors (CRH-R1 and V1B receptor, respectively) to trigger the release of the ad

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Binder EB (2009)reviewMEDLINE-indexed journal, not yet read by usPsychoneuroendocrinology734 citations

The role of FKBP5, a co-chaperone of the glucocorticoid receptor in the pathogenesis and therapy of affective and anxiety disorders.

FK506 binding protein 51 or FKBP5 is a co-chaperone of hsp90 which regulates glucocorticoid receptor (GR) sensitivity. When it is bound to the receptor complex, cortisol binds with lower affinity and nuclear translocation of the receptor is less efficient. FKBP5 mRNA and protein expression are induced by GR activation via intronic hormone response elements and this provides an ultra-short feedback loop for GR-sensitivity. Polymorphisms in the gene encoding this co-chaperone have been shown to associate with differential upregulation of FKBP5 following GR activation and differences in GR sensitivity and stress hormone system regulation. Alleles associated with enhanced expression of FKBP5 following GR activation, lead to an increased GR resistance and decreased efficiency of the negative feedback of the stress hormone axis in healthy controls. This results in a prolongation of stress horm

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Dedovic K, Duchesne A, Andrews J, Engert V, Pruessner JC (2009)reviewMEDLINE-indexed journal, not yet read by usNeuroImage451 citations

The brain and the stress axis: the neural correlates of cortisol regulation in response to stress.

The hypothalamic-pituitary-adrenal (HPA) axis is the major endocrine stress axis of the human organism. Cortisol, the final hormone of this axis, affects metabolic, cardiovascular and central nervous systems both acutely and chronically. Recent advances in neuroimaging techniques have led to the investigation of regulatory networks and mechanisms of cortisol regulation in the central nervous system in human populations. In the following review, results from human and animal studies are being presented that investigate the specific role of hippocampus (HC), amygdala (AG), prefrontal cortex (PFC), and brainstem nuclei in cortisol regulation in response to stress. In general, the types of stressors need to be distinguished when discussing the contributions of these structures in regulating the HPA axis. We propose a basic framework on how these structures communicate as a network to regulat

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Chida Y, Hamer M (2008)reviewMEDLINE-indexed journal, not yet read by usPsychological bulletin381 citations

Chronic psychosocial factors and acute physiological responses to laboratory-induced stress in healthy populations: a quantitative review of 30 years of investigations.

This meta-analysis included 729 studies from 161 articles investigating how acute stress responsivity (including stress reactivity and recovery of hypothalamic-pituitary-adrenal [HPA] axis, autonomic, and cardiovascular systems) changes with various chronic psychosocial exposures (job stress; general life stress; depression or hopelessness; anxiety, neuroticism, or negative affect; hostility, aggression, or Type-A behavior; fatigue, burnout, or exhaustion; positive psychological states or traits) in healthy populations. In either the overall meta-analysis or the methodologically strong subanalysis, positive psychological states or traits were associated with reduced HPA reactivity. Hostility, aggression, or Type-A behavior was associated with increased cardiovascular (heart rate or blood pressure) reactivity, whereas anxiety, neuroticism, or negative affect was associated with decreased

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Valentino RJ, Van Bockstaele E (2008)reviewMEDLINE-indexed journal, not yet read by usEuropean journal of pharmacology438 citations

Convergent regulation of locus coeruleus activity as an adaptive response to stress.

Although hypothalamic-pituitary-adrenal axis activation is generally considered to be the hallmark of the stress response, many of the same stimuli that initiate this response also activate the locus coeruleus-norepinephrine system. Given its functional attributes, the parallel engagement of the locus coeruleus-norepinephrine system with the hypothalamic-pituitary-adrenal axis serves to coordinate endocrine and cognitive limbs of the stress response. The elucidation of stress-related afferents to the locus coeruleus and the electrophysiological characterization of these inputs are revealing how the activity of this system is fine-tuned by stressors to facilitate adaptive cognitive responses. Emerging from these studies, is a picture of complex interactions between the stress-related neuropeptide, corticotropin-releasing factor (CRF), endogenous opioids and the excitatory amino acid neuro

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Nelson PT, Wang WX, Rajeev BW (2008)reviewMEDLINE-indexed journal, not yet read by usBrain pathology (Zurich, Switzerland)272 citations

MicroRNAs (miRNAs) in neurodegenerative diseases.

Aging-related neurodegenerative diseases (NDs) are the culmination of many different genetic and environmental influences. Prior studies have shown that RNAs are pathologically altered during the inexorable course of some NDs. Recent evidence suggests that microRNAs (miRNAs) may be a contributing factor in neurodegeneration. miRNAs are brain-enriched, small ( approximately 22 nucleotides) non-coding RNAs that participate in mRNA translational regulation. Although discovered in the framework of worm development, miRNAs are now appreciated to play a dynamic role in many mammalian brain-related biochemical pathways, including neuroplasticity and stress responses. Research about miRNAs in the context of neurodegeneration is accumulating rapidly, and the goal of this review is to provide perspective for these new data that may be helpful to specialists in either field. An overview is provided

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Koob G, Kreek MJ (2007)reviewMEDLINE-indexed journal, not yet read by usThe American journal of psychiatry611 citations

Stress, dysregulation of drug reward pathways, and the transition to drug dependence.

This review provides a neuroadaptive perspective regarding the role of the hormonal and brain stress systems in drug addiction with a focus on the changes that occur during the transition from limited access to drugs to long-term compulsive use of drugs. A dramatic escalation in drug intake with extended access to drug self-administration is characterized by a dysregulation of brain reward pathways. Hormonal studies using an experimenter-administered cocaine binge model and an escalation self-administration model have revealed large increases in ACTH and corticosterone in rats during an acute binge with attenuation during the chronic binge stage and a reactivation of the hypothalamic-pituitary-adrenal axis during acute withdrawal. The activation of the hypothalamic-pituitary-adrenal axis with cocaine appears to depend on feed-forward activation of the mesolimbic dopamine system. At the s

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Ben-Eliyahu S, Page GG, Schleifer SJ (2007)reviewMEDLINE-indexed journal, not yet read by usBrain, behavior, and immunity45 citations

Stress, NK cells, and cancer: Still a promissory note.

Although the last decades have provided ample evidence for deleterious effects of stress on immunity and on cancer development and suggested mediating mechanisms, no psychoneuroimmunology (PNI)-related intervention has become a standard of care in conventional cancer treatment. We believe the reasons for this include the unique nature of cancer evolvement and interactions with the immune system, and the many conceptual and technical obstacles to studying stress effects on immune activity and their implications for human resistance to malignancy. However, the numerous and diverse interactions between malignant tissue and immunocytes are now better understood, and suggestions can be made with respect to certain critical periods to be investigated in cancer-PNI research. Animal models of cancer progression are instrumental in suggesting neuroendocrine and immunological mediators of stress e

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Seckl JR, Holmes MC (2007)reviewMEDLINE-indexed journal, not yet read by usNature clinical practice. Endocrinology & metabolism496 citations

Mechanisms of disease: glucocorticoids, their placental metabolism and fetal 'programming' of adult pathophysiology.

Epidemiological evidence suggests that an adverse prenatal environment permanently 'programs' physiology and increases the risk of cardiovascular, metabolic, neuroendocrine and psychiatric disorders in adulthood. Prenatal stress or exposure to excess glucocorticoids might provide the link between fetal maturation and adult pathophysiology. In a variety of animal models, prenatal stress, glucocorticoid exposure and inhibition (or knockout of) 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2)--the fetoplacental barrier to maternal glucocorticoids--reduce birth weight and cause increases in adult blood pressure, glucose levels, hypothalamic-pituitary-adrenal (HPA) axis activity and anxiety-related behaviors. In humans, mutations in the gene that encodes 11beta- hydroxysteroid dehydrogenase type 2 are associated with low birth weight. Babies with low birth weight have higher plasma co

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Fumagalli F, Molteni R, Racagni G, Riva MA (2007)reviewMEDLINE-indexed journal, not yet read by usProgress in neurobiology152 citations

Stress during development: Impact on neuroplasticity and relevance to psychopathology.

Development represents a critical moment for shaping adult behavior and may set the stage to disease vulnerability later in life. There is now compelling evidence that stressful experiences during gestation or early in life can lead to enhanced susceptibility for mental illness. In this paper we review the data from experimental studies aimed at investigating behavioral, hormonal, functional and molecular consequences of exposure to stressful events during prenatal or early postnatal life that might contribute to later psychopathology. The use of the newest methodology in the field and the intensive efforts produced by researchers have opened the possibility to reveal the complex, finely tuned and previously unappreciated sets of molecular interactions between different factors that are critical for neurodevelopment thus leading to important discoveries regarding perinatal life. The majo

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Neurobiology of exercise.

Voluntary physical activity and exercise training can favorably influence brain plasticity by facilitating neurogenerative, neuroadaptive, and neuroprotective processes. At least some of the processes are mediated by neurotrophic factors. Motor skill training and regular exercise enhance executive functions of cognition and some types of learning, including motor learning in the spinal cord. These adaptations in the central nervous system have implications for the prevention and treatment of obesity, cancer, depression, the decline in cognition associated with aging, and neurological disorders such as Parkinson's disease, Alzheimer's dementia, ischemic stroke, and head and spinal cord injury. Chronic voluntary physical activity also attenuates neural responses to stress in brain circuits responsible for regulating peripheral sympathetic activity, suggesting constraint on sympathetic resp

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Fox C, Merali Z, Harrison C (2006)reviewMEDLINE-indexed journal, not yet read by usBehavioural brain research183 citations

Therapeutic and protective effect of environmental enrichment against psychogenic and neurogenic stress.

Environmental enrichment (EE) has beneficial neurobiological, physiological and behavioral effects. The purpose of the present paper is to review the animal research literature pertaining to the impact of EE on altering physiological and behavioral anxiety outcomes. Evidence supports the view that EE attenuates responses to certain anxiety provoking situations, and that these effects persist over time. Specifically, EE attenuates behavioral anxiety-type responses and endocrine responses mediated via the hypothalamic-pituitary-adrenal (HPA) axis evoked by psychogenic and/or neurogenic stressors. EE is not only able to protect from excessive anxiety in response to a present stressor, but also attenuates the enduring or persistent effects engendered by past psychogenic stressor(s) such as prenatal stress or neonatal maternal separation. It is noteworthy that the protective effects of EE are

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Fenoglio KA, Brunson KL, Baram TZ (2006)reviewMEDLINE-indexed journal, not yet read by usFrontiers in neuroendocrinology163 citations

Hippocampal neuroplasticity induced by early-life stress: functional and molecular aspects.

Whereas genetic factors contribute crucially to brain function, early-life events, including stress, exert long-lasting influence on neuronal function. Here, we focus on the hippocampus as the target of these early-life events because of its crucial role in learning and memory. Using a novel immature-rodent model, we describe the deleterious consequences of chronic early-life 'psychological' stress on hippocampus-dependent cognitive tasks. We review the cellular mechanisms involved and discuss the roles of stress-mediating molecules, including corticotropin releasing hormone, in the process by which stress impacts the structure and function of hippocampal neurons.

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Sanchez MM (2006)reviewMEDLINE-indexed journal, not yet read by usHormones and behavior191 citations

The impact of early adverse care on HPA axis development: nonhuman primate models.

This review presents supporting evidence that early disruptions in mother-infant relationship in primates, including infant maltreatment, are important risk factors for the development of psychopathology and pathophysiology during childhood and adolescence. Current research in this field is trying to identify important aspects of early adverse experiences such as the timing, frequency, duration, "perceived" intensity of the stressful or traumatic events, the role of social support (e.g., nurturing caregiver) in buffering the deleterious outcomes of early adversity, as well as the role of sex and genetic factors on individual variability in vulnerability. The use of nonhuman primate models of early adverse caregiving is helping to put the pieces of the puzzle together to fully understand the causes and consequences of similar experiences in humans. These models are essential to characteri

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Smith SM, Vale WW (2006)reviewMEDLINE-indexed journal, not yet read by usDialogues in clinical neuroscience1,105 citations

The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress.

Animals respond to stress by activating a wide array of behavioral and physiological responses that are collectively referred to as the stress response. Corticotropin-releasing factor (CRF) plays a central role in the stress response by regulating the hypothalamic-pituitary-adrenal (HPA) axis. In response to stress, CRF initiates a cascade of events that culminate in the release of glucocorticoids from the adrenal cortex. As a result of the great number of physiological and behavioral effects exerted by glucocorticoids, several mechanisms have evolved to control HPA axis activation and integrate the stress response. Glucocorticoid feedback inhibition plays a prominent role in regulating the magnitude and duration of glucocorticoid release. In addition to glucocorticoid feedback, the HPA axis is regulated at the level of the hypothalamus by a diverse group of afferent projections from lim

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