Depression and low mood الاكتئاب

وَتَوَلَّىٰ عَنۡهُمۡ وَقَالَ يَٰٓأَسَفَىٰ عَلَىٰ يُوسُفَ وَٱبۡيَضَّتۡ عَيۡنَاهُ مِنَ ٱلۡحُزۡنِ فَهُوَ كَظِيمࣱ‏

and he turned away from them, saying, ‘Alas for Joseph!’ His eyes went white with grief and he was filled with sorrow

وَقَالُواْ ٱلۡحَمۡدُ لِلَّهِ ٱلَّذِيٓ أَذۡهَبَ عَنَّا ٱلۡحَزَنَۖ إِنَّ رَبَّنَا لَغَفُورࣱ شَكُورٌ

They will say, ‘Praise be to God, who has separated us from all sorrow! Our Lord is truly most forgiving, most appreciative

إِذۡ تَمۡشِيٓ أُخۡتُكَ فَتَقُولُ هَلۡ أَدُلُّكُمۡ عَلَىٰ مَن يَكۡفُلُهُۥۖ فَرَجَعۡنَٰكَ إِلَىٰٓ أُمِّكَ كَيۡ تَقَرَّ عَيۡنُهَا وَلَا تَحۡزَنَۚ وَقَتَلۡتَ نَفۡسࣰ ا فَنَجَّيۡنَٰكَ مِنَ ٱلۡغَمِّ وَفَتَنَّٰكَ فُتُونࣰ اۚ فَلَبِثۡتَ سِنِينَ فِيٓ أَهۡلِ مَدۡيَنَ ثُمَّ جِئۡتَ عَلَىٰ قَدَرࣲ يَٰمُوسَىٰ

Your sister went out, saying, “I will tell you someone who will nurse him,” then We returned you to your mother so that she could rejoice and not grieve. Later you killed a man, but We saved you from distress and tried you with other tests. You stayed among the people of Midian for years, then you came here as I ordained

أَهَٰٓؤُلَآءِ ٱلَّذِينَ أَقۡسَمۡتُمۡ لَا يَنَالُهُمُ ٱللَّهُ بِرَحۡمَةٍۚ ٱدۡخُلُواْ ٱلۡجَنَّةَ لَا خَوۡفٌ عَلَيۡكُمۡ وَلَآ أَنتُمۡ تَحۡزَنُونَ

And are these the people you swore God would never bless? [Now these people are being told], “Enter the Garden! No fear for you, nor shall you grieve.”’

۞إِذۡ تُصۡعِدُونَ وَلَا تَلۡوُۥنَ عَلَىٰٓ أَحَدࣲ وَٱلرَّسُولُ يَدۡعُوكُمۡ فِيٓ أُخۡرَىٰكُمۡ فَأَثَٰبَكُمۡ غَمَّۢا بِغَمࣲّ لِّكَيۡلَا تَحۡزَنُواْ عَلَىٰ مَا فَاتَكُمۡ وَلَا مَآ أَصَٰبَكُمۡۗ وَٱللَّهُ خَبِيرُۢ بِمَا تَعۡمَلُونَ

You fled without looking back while the Messenger was calling out to you from behind, and God rewarded you with sorrow for sorrow. [He has now forgiven you] so that you may not grieve for what you missed or for what happened to you. God is well aware of everything you do

ثُمَّ أَنزَلَ عَلَيۡكُم مِّنۢ بَعۡدِ ٱلۡغَمِّ أَمَنَةࣰ نُّعَاسࣰ ا يَغۡشَىٰ طَآئِفَةࣰ مِّنكُمۡۖ وَطَآئِفَةࣱ قَدۡ أَهَمَّتۡهُمۡ أَنفُسُهُمۡ يَظُنُّونَ بِٱللَّهِ غَيۡرَ ٱلۡحَقِّ ظَنَّ ٱلۡجَٰهِلِيَّةِۖ يَقُولُونَ هَل لَّنَا مِنَ ٱلۡأَمۡرِ مِن شَيۡءࣲۗ قُلۡ إِنَّ ٱلۡأَمۡرَ كُلَّهُۥ لِلَّهِۗ يُخۡفُونَ فِيٓ أَنفُسِهِم مَّا لَا يُبۡدُونَ لَكَۖ يَقُولُونَ لَوۡ كَانَ لَنَا مِنَ ٱلۡأَمۡرِ شَيۡءࣱ مَّا قُتِلۡنَا هَٰهُنَاۗ قُل لَّوۡ كُنتُمۡ فِي بُيُوتِكُمۡ لَبَرَزَ ٱلَّذِينَ كُتِبَ عَلَيۡهِمُ ٱلۡقَتۡلُ إِلَىٰ مَضَاجِعِهِمۡۖ وَلِيَبۡتَلِيَ ٱللَّهُ مَا فِي صُدُورِكُمۡ وَلِيُمَحِّصَ مَا فِي قُلُوبِكُمۡۚ وَٱللَّهُ عَلِيمُۢ بِذَاتِ ٱلصُّدُورِ

After sorrow, He caused calm to descend upon you, a sleep that overtook some of you. Another group, caring only for themselves, entertained false thoughts about God, thoughts more appropriate to pagan ignorance, and said, ‘Do we get a say in any of this?’ [Prophet], tell them, ‘Everything to do with this affair is in God’s hands.’ They conceal in their hearts things they will not reveal to you. They say, ‘If we had had our say in this, none of us would have been killed here.’ Tell them, ‘Even if you had resolved to stay at home, those who were destined to be killed would still have gone out to meet their deaths.’ God did this in order to test everything within you and in order to prove what is in your hearts. God knows your innermost thoughts very well

" Oh, my grief for Joseph! " And his eyes turned white because of the sorrow that he was suppressing. Revelation came from the Compeller of all engendered beings: " O Jacob! You grieve so much for him, but you do not grieve for what you are missing of Me by being busy with grief for him! " O Jacob, how long this sorrow and regret at separation from Joseph? How long will you suffer grief and coldly sigh? Do you not suffer grief that you are held back from Me while busy with him? " With two kiblahs you can't walk straight on the road of tawḤīd- either the Friend's approval, or your own caprice. [DS 488] " O Jacob! Be careful not to pass Joseph's name over your tongue any more, or I will remove your name from the register of the prophets. " The Pir of the Tariqah said, " Jacob's remembrance of Joseph was the seed of heartache, and Joseph's remembrance of Jacob was the seed of ease. Since Ja

And they shall say, “Praise belongs to God, who has put away sorrow from us.” O chevalier! The worth of the antidote is known by the snake-bitten, the worth of burning fire is known by the moth, the worth of Joseph's shirt is known by grieving Jacob. When someone is de- luded by his own safety and is given the antidote, how will he know its worth? If you want some- one to know the worth and gravity of the antidote, you need him whose spirit has reached his lips. A poor man is needed, broken-hearted, suffering pain, and burdened with grief to know the worth of this caress and the exaltedness of this address: “Praise belongs to God, who has put away sorrow from us.” Wait until tomorrow when that wounded-hearted poor man is placed on the throne of joy in the palisade of holiness while the serving boys and servants act like his slaves to spread the carpet before the seat of his good fortune.

And We tried thee with trials. In other words, “We cooked you well with trial until you became limpid and immaculate, then We took you totally to Ourselves, so that you would not belong to any other.” “O Moses, We took you to the oven of trial and put you into self-purification so that nothing would remain in your heart but My love and nothing on your tongue but My remembrance.” What were those trials and troubles that sat on his head? When he was first born he was born in secrecy, in a house without lamp, poor, without pleasures. His mother could not have a son be- cause of fear of Pharaoh, who was killing sons. She put him into the casket and threw it in the river. His first home was the river. His second home was the sword, the execution ground, and seeing the enemy. His third home was fear of the Egyptians, because he had killed one of them. Then he fled looking back at them, his hea

And he turned away from them no longer addressing them and said ‘Alas my grief for Joseph!’ yā asafā the final alif of asafā has taken the place of the possessive yā’ of genitive annexation sc. yā asafī in other words it means yā huznī ‘O my sorrow’. And his eyes turned white their dark colour was effaced and became white on account of his tears with grief for him such that he was filled with suppressed agony anguished and grief-stricken but not manifesting his grief.

And they will say ‘Praise be to God Who has removed all grief from us. Truly our Lord is Forgiving of sins Appreciative of obedience

Are these the ones of whom you swore that God would never grant them mercy?’ it has already been said to them ‘Enter Paradise; no fear shall come upon you nor shall you grieve’ a variant reading for udkhulū ‘enter’ imperative second person plural has the passive udkhilū ‘they have been admitted’ or dakhalū ‘they entered’; the negation clause ‘no fear shall come upon you nor shall you grieve’ is a circumstantial qualifier in other words they enter Paradise while this is being said to them.

حَدَّثَنَا هَدَّابُ بْنُ خَالِدٍ، حَدَّثَنَا حَمَّادُ بْنُ سَلَمَةَ، ح وَحَدَّثَنِي زُهَيْرُ بْنُ حَرْبٍ، حَدَّثَنَا مُعَاذُ بْنُ مُعَاذٍ الْعَنْبَرِيُّ، ح وَحَدَّثَنِي مُحَمَّدُ بْنُ عَبْدِ الأَعْلَى، حَدَّثَنَا الْمُعْتَمِرُ، ح وَحَدَّثَنَا إِسْحَاقُ، بْنُ إِبْرَاهِيمَ أَخْبَرَنَا جَرِيرٌ، كُلُّهُمْ عَنْ سُلَيْمَانَ التَّيْمِيِّ، ح وَحَدَّثَنَا أَبُو كَامِلٍ، فُضَيْلُ بْنُ حُسَيْنٍ - وَاللَّفْظُ لَهُ - حَدَّثَنَا يَزِيدُ بْنُ زُرَيْعٍ، حَدَّثَنَا التَّيْمِيُّ، عَنْ أَبِي عُثْمَانَ، عَنْ أُسَامَةَ بْنِ زَيْدٍ، قَالَ قَالَ رَسُولُ اللَّهِ صلى الله عليه وسلم ‏ "‏ قُمْتُ عَلَى بَابِ الْجَنَّةِ فَإِذَا عَامَّةُ مَنْ دَخَلَهَا الْمَسَاكِينُ وَإِذَا أَصْحَابُ الْجَدِّ مَحْبُوسُونَ إِلاَّ أَصْحَابَ النَّارِ فَقَدْ أُمِرَ بِهِمْ إِلَى النَّارِ وَقُمْتُ عَلَى بَابِ النَّارِ فَإِذَا عَامَّةُ مَنْ دَخَلَهَا النِّسَاءُ ‏"‏ ‏.‏

Usama b. Zaid reported that Allah's Messenger (way peace be upon him) said:I stood at the door of Paradise and I found that the overwhelming majority of those who entered therein was that of poor persons and the wealthy persons were detained to get into that. The denizens of Hell were commanded to get into Hell, and I stood upon the door of Fire and the majority amongst them who entered there was that of women

حَدَّثَنَا أَبُو كُرَيْبٍ، حَدَّثَنَا أَبُو أُسَامَةَ، عَنْ سَعِيدِ بْنِ أَبِي عَرُوبَةَ، سَمِعَ أَبَا رَجَاءٍ، عَنِ ابْنِ عَبَّاسٍ، قَالَ قَالَ رَسُولُ اللَّهِ صلى الله عليه وسلم فَذَكَرَ مِثْلَهُ ‏.‏

This hadith is narrated likewise through another chain of transmitters

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

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)

حَدَّثَنَا عَبْدُ اللَّهِ بْنُ مَسْلَمَةَ بْنِ قَعْنَبٍ، حَدَّثَنَا سُلَيْمَانُ، - يَعْنِي ابْنَ بِلاَلٍ - عَنْ جَعْفَرٍ، عَنْ أَبِيهِ، عَنْ جَابِرِ بْنِ عَبْدِ اللَّهِ، أَنَّ رَسُولَ اللَّهِ صلى الله عليه وسلم مَرَّ بِالسُّوقِ دَاخِلاً مِنْ بَعْضِ الْعَالِيَةِ وَالنَّاسُ كَنَفَتَهُ فَمَرَّ بِجَدْىٍ أَسَكَّ مَيِّتٍ فَتَنَاوَلَهُ فَأَخَذَ بِأُذُنِهِ ثُمَّ قَالَ ‏"‏ أَيُّكُمْ يُحِبُّ أَنَّ هَذَا لَهُ بِدِرْهَمٍ ‏"‏ ‏.‏ فَقَالُوا مَا نُحِبُّ أَنَّهُ لَنَا بِشَىْءٍ وَمَا نَصْنَعُ بِهِ قَالَ ‏"‏ أَتُحِبُّونَ أَنَّهُ لَكُمْ ‏"‏ ‏.‏ قَالُوا وَاللَّهِ لَوْ كَانَ حَيًّا كَانَ عَيْبًا فِيهِ لأَنَّهُ أَسَكُّ فَكَيْفَ وَهُوَ مَيِّتٌ فَقَالَ ‏"‏ فَوَاللَّهِ لَلدُّنْيَا أَهْوَنُ عَلَى اللَّهِ مِنْ هَذَا عَلَيْكُمْ ‏"‏ ‏.‏

Jabir b. Abdullah reported that Allah's Apostle (ﷺ) happened to walk through the bazar coming from the side of 'Aliya and the people were on both his sides. There he found a dead lamb with very short ears. He took hold of his ear and said:Who amongst you would like to have this for a dirham? They said: We do not like to have it even for less than that as it is of no use to us. He said: Do you wish to have it (free of any cost)? They said: By Allah, even if it were alive (we would not have liked to possess that), for there is defect in it as its ear is very short; now it is dead also. Thereupon Allah's Messenger (ﷺ) said: By Allah, this world is more insignificant in the eye of Allah than it (this dead lamb) is in your eye

حَدَّثَنِي مُحَمَّدُ بْنُ الْمُثَنَّى الْعَنَزِيُّ، وَإِبْرَاهِيمُ بْنُ مُحَمَّدِ بْنِ عَرْعَرَةَ السَّامِيُّ، قَالاَ حَدَّثَنَا عَبْدُ الْوَهَّابِ، - يَعْنِيَانِ الثَّقَفِيَّ - عَنْ جَعْفَرٍ، عَنْ أَبِيهِ، عَنْ جَابِرٍ، عَنِ النَّبِيِّ صلى الله عليه وسلم ‏.‏ بِمِثْلِهِ غَيْرَ أَنَّ فِي حَدِيثِ الثَّقَفِيِّ فَلَوْ كَانَ حَيًّا كَانَ هَذَا السَّكَكُ بِهِ عَيْبًا ‏.‏

Jabir reported Allah's Apostle (ﷺ) narrating a hadith like this with a slight variation of wording

الرابع أصوات النياحة ونغماتها وتأثيرها في تهييج الحزن والبكاء وملازمة الكآبة والحزن قسمان محمود ومذموم

ومن له قوت يوم بيوم فهو في سلامة من جميع ذلك، وهذا سوى ما يقاسيه أرباب الأموال في الدنيا، من الخوف والحزن والهم والغم والتعب.

وأما الاكتئاب فهو افتعال من الكآبة وهي سوء الحال والانكسار من الحزن وقد كئب الرجل يكأب كأبة وكآبة كرأفة ورآفة ونشأة ونشاءة فهو كئيب وامرأة كئيبة وكأباء أيضا قال الراجز

| الفصل السابع عشر في اذكار الكرب والغم والحزن والهم

وكان بعض السلف يقول: الزهد في الدنيا يريح القلب والبدن، والرغبة فيها تكثر الهم والحزن. ### | 7 فصل في درجات الزهد وأقسامه

وقال ابن مسعود رضى الله عنه: إن الله تعالى بقسطه وعمله جعل الروح والفرح في اليقين والرضى، وجعل الهم والحزن في الشك والسخط.

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Identification of depression and anxiety during pregnancy: A systematic review and meta-analysis of test accuracy.: Introduction: Depression and anxiety are significant contributors to maternal perinatal morbidity and a range of negative child outcomes. This systematic review and meta-analysis aimed to review and assess the diagnostic test accuracy of selected screening tools (Edinburgh Postnatal Depression Scale [EPDS], EPDS-3A, Patient Health Questionnaire [PHQ-9]-, PHQ-2, Matthey Generic Mood Question [MGMQ], Generalized Anxiety Disorder scale [GAD-7], GAD-2, and the Whooley questions) used to identify wom

Characterization of gut microbiome in mice model of depression with divergent response to escitalopram treatment.

Depression is a common and heterogeneous mental disorder. Although several antidepressants are available to treat the patients with depression, the factors which could affect and predict the treatment response remain unclear. Here, we characterize the longitudinal changes of microbial composition and function during escitalopram treatment in chronic unpredictable mild stress (CUMS) mice model of depression based on 16 S rRNA sequencing and metabolomics. Consequently, we found that escitalopram (ESC) administration serves to increase the alpha-diversity of the gut microbiome in ESC treatment group. The microbial signatures between responder (R) and non-responder (NR) groups were significantly different. The R group was mainly characterized by increased relative abundances of genus Prevotellaceae_UCG-003, and depleted families Ruminococcaceae and Lactobacillaceae relative to NR group. More…

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Incidence and prevalence of primary care antidepressant prescribing in children and young people in England, 1998-2017: A population-based cohort study.

Background: The use of antidepressants in children and adolescents remains controversial. We examined trends over time and variation in antidepressant prescribing in children and young people in England and whether the drugs prescribed reflected UK licensing and guidelines. Methods and findings: QResearch is a primary care database containing anonymised healthcare records of over 32 million patients from more than 1,500 general practices across the UK. All eligible children and young people aged 5-17 years in 1998-2017 from QResearch were included. Incidence and prevalence rates of antidepressant prescriptions in each year were calculated overall, for 4 antidepressant classes (selective serotonin reuptake inhibitors [SSRIs], tricyclic and related antidepressants [TCAs], serotonin and norepinephrine reuptake inhibitors [SNRIs], and other antidepressants), and for individual drugs. Adjuste…

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Antidepressant-like effect induced by P2X7 receptor blockade in FSL rats is associated with BDNF signalling activation.

Background: P2X7 receptors (P2X7R) are ligand-gated ion channels activated by adenosine 5'-triphosphate (ATP), which are involved in processes that are dysfunctional in stress response and depression, such as neurotransmitter release, and neuroimmune response. Genetic and pharmacological inhibition of the P2X7R induce antidepressant-like effects in animals exposed to stress. However, the effect of P2X7R antagonism in an animal model of depression based on selective breeding has not previously been studied, and the mechanism underling the antidepressant-like effect induced by the P2X7R blockade remains unknown. Aims: The present study aimed to: (1) determine whether P2X7R blockade induces antidepressant-like effects in the Flinders Sensitive Line (FSL) rats and, (2) investigate whether brain-derived neurotrophic factor (BDNF) signalling in the frontal cortex and hippocampus is involved in…

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Fish oil supplementation attenuates neuroinflammation and alleviates depressive-like behavior in rats submitted to repeated lipopolysaccharide.

Purpose: Depression is frequently associated with inflammation, whereas omega-3 polyunsaturated fatty acids (PUFAs) primarily found in fish oil possess anti-inflammatory properties. Although converging studies suggest an antidepressant effect of PUFAs, there is limited evidence directly linking the neuro-immune modulating features of PUFAs to the antidepressant actions. Methods: Therefore, we assessed the effects of fish oil (FO) supplementation on behavioral changes, inflammatory cytokine expression and oxidative reactions in frontal cortex and hippocampus of rats following repeated peripheral immune challenge by lipopolysaccharide (LPS) for 2 weeks (500 μg/kg every other day). Results: Repeated LPS administration induced the rats to a depressive-like state and increased mRNA expression of pro-inflammatory cytokines, including 1L-1β, 1L-6 and TNF-α, in frontal cortex and hippocampus. FO…

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Targeting the Microbiota-Gut-Brain Axis: Prebiotics Have Anxiolytic and Antidepressant-like Effects and Reverse the Impact of Chronic Stress in Mice.

Background: The realization that the microbiota-gut-brain axis plays a critical role in health and disease, including neuropsychiatric disorders, is rapidly advancing. Nurturing a beneficial gut microbiome with prebiotics, such as fructo-oligosaccharides (FOS) and galacto-oligosaccharides (GOS), is an appealing but underinvestigated microbiota manipulation. Here we tested whether chronic prebiotic treatment modifies behavior across domains relevant to anxiety, depression, cognition, stress response, and social behavior. Methods: C57BL/6J male mice were administered FOS, GOS, or a combination of FOS+GOS for 3 weeks prior to testing. Plasma corticosterone, microbiota composition, and cecal short-chain fatty acids were measured. In addition, FOS+GOS- or water-treated mice were also exposed to chronic psychosocial stress, and behavior, immune, and microbiota parameters were assessed. Results…

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Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants.

Depression is a common, devastating illness. Current pharmacotherapies help many patients, but high rates of a partial response or no response, and the delayed onset of the effects of antidepressant therapies, leave many patients inadequately treated. However, new insights into the neurobiology of stress and human mood disorders have shed light on mechanisms underlying the vulnerability of individuals to depression and have pointed to novel antidepressants. Environmental events and other risk factors contribute to depression through converging molecular and cellular mechanisms that disrupt neuronal function and morphology, resulting in dysfunction of the circuitry that is essential for mood regulation and cognitive function. Although current antidepressants, such as serotonin-reuptake inhibitors, produce subtle changes that take effect in weeks or months, it has recently been shown that …

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e-CBT (myCompass), Antidepressant Medication, and Face-to-Face Psychological Treatment for Depression in Australia: A Cost-Effectiveness Comparison.

Background: The economic cost of depression is becoming an ever more important determinant for health policy and decision makers. Internet-based interventions with and without therapist support have been found to be effective options for the treatment of mild to moderate depression. With increasing demands on health resources and shortages of mental health care professionals, the integration of cost-effective treatment options such as Internet-based programs into primary health care could increase efficiency in terms of resource use and costs. Objective: Our aim was to evaluate the cost-effectiveness of an Internet-based intervention (myCompass) for the treatment of mild-to-moderate depression compared to treatment as usual and cognitive behavior therapy in a stepped care model. Methods: A decision model was constructed using a cost utility framework to show both costs and health outcome…

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Interferon-alpha treatment induces depression-like behaviour accompanied by elevated hippocampal quinolinic acid levels in rats.

Immunotherapy with the cytokine interferon-alpha (IFN-α) can induce symptoms of depression, and it is likely that the tryptophan-kynurenine pathway may be involved in this regard. In this study we investigated the effects of IFN-α on depression-like behaviour and central metabolites of the tryptophan-kynurenine pathway in rats. Secondly, we explored the modulating effects of an antidepressant (imipramine) and anti-inflammatory drug (celecoxib) on IFN-α-induced behavioural and pathophysiological changes in the brain. The following treatment groups were used: Control (saline), IFN-α (6×10(4)IU/kg s.c.), IFN-α+imipramine or IFN-α+celecoxib. Drugs were administered daily for 1 week. IFN-α treatment induced depression-like behaviour by increasing immobility in the forced swim test (FST), and decreased tryptophan levels in the brain. There was a trend for an increased kynurenine/tryptophan rat…

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Chaperoning epigenetics: FKBP51 decreases the activity of DNMT1 and mediates epigenetic effects of the antidepressant paroxetine.

Epigenetic processes, such as DNA methylation, and molecular chaperones, including FK506-binding protein 51 (FKBP51), are independently implicated in stress-related mental disorders and antidepressant drug action. FKBP51 associates with cyclin-dependent kinase 5 (CDK5), which is one of several kinases that phosphorylates and activates DNA methyltransferase 1 (DNMT1). We searched for a functional link between FKBP51 (encoded by FKBP5) and DNMT1 in cells from mice and humans, including those from depressed patients, and found that FKBP51 competed with its close homolog FKBP52 for association with CDK5. In human embryonic kidney (HEK) 293 cells, expression of FKBP51 displaced FKBP52 from CDK5, decreased the interaction of CDK5 with DNMT1, reduced the phosphorylation and enzymatic activity of DNMT1, and diminished global DNA methylation. In mouse embryonic fibroblasts and primary mouse astro…

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Nitric oxide involvement in the antidepressant-like effect of ketamine in the Flinders sensitive line rat model of depression.

Objective: We investigated whether the nitric oxide (NO) precursor, L-arginine, can prevent the antidepressant-like action of the fast-acting antidepressant, ketamine, in a genetic rat model of depression, and/or induce changes in the glutamate (Glu)/N-methyl-D-aspartate receptor (NMDAR)/NO/cyclic guanosine monophosphate (cGMP) signalling pathway. Hereby it was evaluated whether the NO signalling system is involved in the antidepressant mechanism of ketamine. Methods: Flinders sensitive line (FSL) rats received single i.p. injections of ketamine (15 mg/kg) with/without pre-treatment (30 min prior) with L-arginine (500 mg/kg). Depression-like behaviour was assessed in the forced swim test (FST) in terms of immobility, and the activation state of the Glu/NMDAR/NO/cGMP pathway was evaluated ex vivo in the frontal cortex and hippocampus regions in terms of total constitutive NOS (cNOS) activ…

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Antidepressant-like Effects of Electroconvulsive Seizures Require Adult Neurogenesis in a Neuroendocrine Model of Depression.

Background: Neurogenesis continues throughout life in the hippocampal dentate gyrus. Chronic treatment with monoaminergic antidepressant drugs stimulates hippocampal neurogenesis, and new neurons are required for some antidepressant-like behaviors. Electroconvulsive seizures (ECS), a laboratory model of electroconvulsive therapy (ECT), robustly stimulate hippocampal neurogenesis. Hypothesis: ECS requires newborn neurons to improve behavioral deficits in a mouse neuroendocrine model of depression. Methods: We utilized immunohistochemistry for doublecortin (DCX), a marker of migrating neuroblasts, to assess the impact of Sham or ECS treatments (1 treatment per day, 7 treatments over 15 days) on hippocampal neurogenesis in animals receiving 6 weeks of either vehicle or chronic corticosterone (CORT) treatment in the drinking water. We conducted tests of anxiety- and depressive-like behavior …

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Inhibition of stress-induced hepatic tryptophan 2,3-dioxygenase exhibits antidepressant activity in an animal model of depressive behaviour.

The role of hepatic tryptophan 2,3 dioxygenase (TDO) was assessed in the provocation of stress-induced depression-related behaviour in the rat. TDO drives tryptophan metabolism via the kynurenine pathway (KP) and leads to the production of neuroactive metabolites including kynurenine. A single 2 h period of restraint stress in adult male Sprague-Dawley rats provoked an increase in circulating concentrations of the glucocorticoid corticosterone and induction of hepatic TDO expression and activity. Repeated exposure to stress (10 d of 2 h restraint each day) provoked an increase in immobility in the forced swimming test (FST) indicative of depression-related behaviour. Immobility was accompanied by an increase in the circulating corticosterone concentrations, expression and activity of hepatic TDO and increase in the expression of TDO in the cerebral cortex. Increased TDO activity was asso…

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In vivo properties of KNT-127, a novel δ opioid receptor agonist: receptor internalization, antihyperalgesia and antidepressant effects in mice.

Background and purpose: Activation of δ opioid (DOP) receptors regulates pain and emotional responses, and also displays ligand-biased agonism. KNT-127 (1,2,3,4,4a,5,12,12a-octahydro-2-methyl-4aβ,1β-([1,2]benzenomethano)-2,6-diazanaphthacene-12aβ,17-diol) is a novel DOP receptor agonist inducing analgesia and antidepressant effects in mice. Here, we have assessed KNT-127 for (i) analgesia against chronic inflammatory pain; (ii) effects on depression, locomotion and DOP receptor internalization; and (iii) for cross-tolerance to analgesic and antidepressant effects of acute treatment by other DOP receptor agonists. Experimental approach: Inflammatory pain was induced by complete Freund's adjuvant injection into tail or hindpaw, and thermal and mechanical sensitivities were determined in mice. Locomotor and antidepressant-like effects were measured using actimetry and forced swim test respe…

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Serotonergic receptor mechanisms underlying antidepressant-like action in the progesterone withdrawal model of hormonally induced depression in rats.

Hormonally induced mood disorders such as premenstrual dysphoric disorder (PMDD) are characterized by a range of physical and affective symptoms including anxiety, irritability, anhedonia, social withdrawal and depression. Studies demonstrated rodent models of progesterone withdrawal (PWD) have a high level of constructive and descriptive validity to model hormonally-induced mood disorders in women. Here we evaluate the effects of several classes of antidepressants in PWD female Long-Evans rats using the forced swim test (FST) as a measure of antidepressant activity. The study included fluoxetine, duloxetine, amitriptyline and an investigational multimodal antidepressant, vortioxetine (5-HT(3), 5-HT(7) and 5-HT(1D) receptor antagonist; 5-HT(1B) receptor partial agonist; 5-HT(1A) receptor agonist; inhibitor of the serotonin transporter (SERT)). After 14 days of administration, amitriptyli…

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Social, demographic, and health outcomes in the 10 years following adolescent depression.

Purpose: Little attention has been paid to the sociodemographic profiles of depressed youth during the vulnerable transition from adolescence to early adulthood. This study aimed to determine and describe the social, demographic, and health outcomes of adolescent depression during a 10-year period of transition into early adulthood, using a population-based cohort of Canadian teenagers. Methods: Depression status on 1,027 adolescents aged 16-17 years was ascertained from the National Population Health Survey. Social and health outcomes (i.e., employment status, marital status, personal income, education, social support, self-perceived stress, heavy drinking, smoking, migraine headaches, adult depression, antidepressant use, self-rated health, and physical activity) were measured every 2 years until the ages of 26-27 years. Logistic regression was combined with a generalized linear mixed-…

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A Pill for the Ill? Patients' Reports of Their Experience of the Medical Encounter in the Treatment of Depression.

Background: Starting in the 1960s, a broad-based patients' rights movement began to question doctors' paternalism and to demand disclosure of medical information, informed consent, and active participation by the individual in personal health care. According to scholars, these changes contributed to downplay the biomedical approach in favor of a more patient-oriented perspective. The Swedish non-profit organization Consumer Association for Medicines and Health (KILEN) has offered the possibility for consumers to report their perceptions and experiences from their use of medicines in order to strengthen consumer rights within the health care sector. Methodology: In this paper, qualitative content analysis was used to analyze 181 KILEN consumer reports of adverse events from antidepressant medications in order to explore patients' views of mental ill health symptoms and the doctor-patient …

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Parents bereaved by offspring suicide: a population-based longitudinal case-control study.

CONTEXT Suicide bereavement remains understudied and poorly understood. OBJECTIVES To examine outcomes of parents bereaved by the suicide death of their offspring and to compare these with both nonbereaved parent controls and parents who had offspring die in a motor vehicle crash (MVC). DESIGN Population-based case-control study. Suicide-bereaved parents were compared with nonbereaved matched control parents in the general population (n = 1415) and with MVC-bereaved parents (n = 1132) on the rates of physician-diagnosed mental and physical disorders, social factors, and treatment use in the 2 years after death of the offspring. Adjusted relative rates (ARRs) were generated by generalized estimating equation models and adjusted for confounding factors. SETTING Manitoba, Canada. PARTICIPANTS All identifiable parents who had an offspring die by suicide between 1996 and 2007 (n = 1415). MAIN…

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Pregnancy as a major determinant for discontinuation of antidepressants: an analysis of data from The Health Improvement Network.

Background: Potential adverse effects of antidepressants during pregnancy have caused concern about their use. There are, however, very limited detailed data on patterns of antidepressant prescribing in pregnancy. Objective: To examine secular trends in prescribing during pregnancy, to assess whether pregnancy is a major determinant for stopping antidepressants, and to identify characteristics of those who stopped antidepressants during pregnancy. Method: In this cohort study, we obtained data on 114,999 pregnant women (median age at delivery, 30.5 years [interquartile range, 26-34 years]) who had a live birth between 1992 and 2006 and 22,677 nonpregnant women from The Health Improvement Network primary care database, one of the largest sources of continuous anonymized primary care data in the United Kingdom and broadly representative of UK general practice. This database includes inform…

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Antidepressant-like effect induced by systemic and intra-hippocampal administration of DNA methylation inhibitors.

Background and purpose: Epigenetic modifications are thought to play an important role in the neurobiology of depression. Antidepressant treatment induces histone acetylation in the hippocampus, which is associated with transcriptional activation, whereas stress increases DNA methylation, which is associated with transcriptional repression. Because the specific involvement of DNA methylation in the regulation of depressive-like behaviours is not yet known, we have investigated the effects induced by systemic or intra-hippocampal administration of inhibitors of DNA methyltransferase (DNMT) in rats submitted to a range of behavioural tests. Experimental approach: Rats received i.p. injections of 5-aza-2-deoxycytidine (5-azaD, 0.1-0.8 mg·kg(-1) ), 5-azacytidine (5-azaC, 0.4-3.2 mg·kg(-1) ), imipramine (15 mg·kg(-1) ) or vehicle and were submitted to the forced swimming test (FST) or open fi…

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Expected value and prediction error abnormalities in depression and schizophrenia.

The dopamine system has been linked to anhedonia in depression and both the positive and negative symptoms of schizophrenia, but it remains unclear how dopamine dysfunction could mechanistically relate to observed symptoms. There is considerable evidence that phasic dopamine signals encode prediction error (differences between expected and actual outcomes), with reinforcement learning theories being based on prediction error-mediated learning of associations. It has been hypothesized that abnormal encoding of neural prediction error signals could underlie anhedonia in depression and negative symptoms in schizophrenia by disrupting learning and blunting the salience of rewarding events, and contribute to psychotic symptoms by promoting aberrant perceptions and the formation of delusions. To test this, we used model based functional magnetic resonance imaging and an instrumental reward-lea…

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Sociodemographic factors contribute to the depressive affect among African Americans with chronic kidney disease.

Depression is common in end-stage renal disease and is associated with poor quality of life and higher mortality; however, little is known about depressive affect in earlier stages of chronic kidney disease. To measure this in a risk group burdened with hypertension and kidney disease, we conducted a cross-sectional analysis of individuals at enrollment in the African American Study of Kidney Disease and Hypertension Cohort Study. Depressive affect was assessed by the Beck Depression Inventory II and quality of life by the Medical Outcomes Study-Short Form and the Satisfaction with Life Scale. Beck Depression scores over 14 were deemed consistent with an increased depressive affect and linear regression analysis was used to identify factors associated with these scores. Among 628 subjects, 166 had scores over 14 but only 34 were prescribed antidepressants. The mean Beck Depression score …

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Decreased numbers of progenitor cells but no response to antidepressant drugs in the hippocampus of elderly depressed patients.

Imaging studies have consistently documented hippocampal volume reductions in depression. Although depressive disorders are traditionally considered to have a neurochemical basis, recent studies suggest that impairments of structural plasticity contribute to the volume reductions and the related cognitive changes. This might result from repeated periods of stress that are a wellknown risk factor for depression. Adult neurogenesis is a prominent example of neuroplasticity that in rodents, is reduced by stress but stimulated by antidepressant drugs. Although reductions in neurogenesis have been proposed to contribute to the etiology of depression, only two studies have so far examined hippocampal cytogenesis in depression, but this was in a limited number of subjects with considerable interindividual variation, and these studies came to different conclusions. We therefore collected hippoca…

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Subgenual cingulate and visual cortex responses to sad faces predict clinical outcome during antidepressant treatment for depression.

Background: Previous follow-up studies indicate that increased visual cortical, ventral cingulate and subcortical responses of depressed individuals to sad facial stimuli, but not happy stimuli could represent reversible markers of disease severity. We hypothesized that greater responses in these areas to sad stimuli, but not happy stimuli, would predict better subsequent clinical outcome. We also explored areas that would predict a poor outcome. Methods: Twelve melancholically depressed individuals in the early stages of antidepressant treatment in a secondary care setting participated in two experiments comparing responses to varying intensities of sad and happy facial stimuli, respectively, using event related functional MRI. They repeated the experiments after a mean delay of 12 weeks of treatment. Results: There was a variation in response to treatment. Greater right visual cortex a…

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Effects of the probiotic Bifidobacterium infantis in the maternal separation model of depression.

The concept that intestinal microbial composition not only affects the health of the gut, but also influences centrally-mediated systems involved in mood, is supported by a growing body of literature. Despite the emergent interest in brain-gut communication and its possible role in the pathogenesis of psychiatric disorders such as depression, particularly subtypes with accompanying gastrointestinal (GI) symptoms, there are few studies dedicated to the search for therapeutic solutions that address both central and peripheral facets of these illnesses. This study aims to assess the potential benefits of the probiotic Bifidobacterium infantis in the rat maternal separation (MS) model, a paradigm that has proven to be of value in the study of stress-related GI and mood disorders. MS adult rat offsprings were chronically treated with bifidobacteria or citalopram and subjected to the forced sw…

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Longitudinal evidence for unfavorable effects of antidepressants on heart rate variability.

Background: It was previously shown that antidepressants are associated with diminished vagal control over the heart. Longitudinal studies are needed to test the causality of this association further. Methods: Longitudinal data were obtained in the Netherlands Study of Depression and Anxiety. At baseline and at 2-year follow-up, heart rate and cardiac vagal control as indexed by respiratory sinus arrhythmia were measured in 2114 subjects (mean age = 42.0 years; 66.2% female), who either used antidepressants at one or two time points (n = 603) or did not use antidepressants at any time point (n = 1511). Linear mixed-model analyses were conducted to compare changes in respiratory sinus arrhythmia and heart rate over time across antidepressant-naive subjects, subjects who started using an antidepressant during follow-up, subjects who stopped using an antidepressant, and persistent antidepre…

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