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

Depression is not a consistent syndrome: An investigation of unique symptom patterns in the STAR*D study.

Background: The DSM-5 encompasses a wide range of symptoms for Major Depressive Disorder (MDD). Symptoms are commonly added up to sum-scores, and thresholds differentiate between healthy and depressed individuals. The underlying assumption is that all patients diagnosed with MDD have a similar condition, and that sum-scores accurately reflect the severity of this condition. To test this assumption, we examined the number of DSM-5 depression symptom patterns in the "Sequenced Treatment Alternatives to Relieve Depression" (STAR*D) study. Methods: We investigated the number of unique symptom profiles reported by 3703 depressed outpatients at the beginning of the first treatment stage of STAR*D. Results: Overall, we identified 1030 unique symptom profiles. Of these profiles, 864 profiles (83.9%) were endorsed by five or fewer subjects, and 501 profiles (48.6%) were endorsed by only one indiv…

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Implicit motives and cognitive variables: specific links to vulnerability for unipolar or bipolar disorder.

Cognitive variables contribute to the etiology of affective disorders. With the differentiation between explicit and implicit measures some studies have indicated underlying depressogenic schemata even in bipolar disorders. We tested for differences in implicit motives and cognitive variables between patients with remitted unipolar and bipolar disorder compared to controls and in a high-risk sample. Additionally we investigated whether affective symptoms relate to those variables. We cross-sectionally examined N=164 participants (53 with bipolar disorder, 58 with major depression, and 53 without affective disorders) and a high-risk sample (N=49) of adolescent children of either parents with unipolar or bipolar disorder or of healthy parents. The Multi-Motive-Grid was used to measure the implicit motives achievement, affiliation, and power, in addition to the cognitive measures of self-es…

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Blunted neural response to rewards prospectively predicts depression in adolescent girls.

The prevalence of depression increases substantially during adolescence. Several predictors of major depressive disorder have been established, but their predictive power is limited. In the current study, the feedback negativity (FN), an event-related potential component elicited by feedback indicating monetary gain versus loss, was recorded in 68 never-depressed adolescent girls. Over the following 2 years, 24% of participants developed a major depressive episode (MDE); illness onset was predicted by blunted FN at initial evaluation. Lower FN amplitude predicted more depressive symptoms during the follow-up period, even after controlling for neuroticism and depressive symptoms at baseline. This is the first prospective study to demonstrate a link between a neural measure of reward sensitivity and the first onset of an MDE. The current results suggest that low reward sensitivity may be a…

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Depression among Chinese university students: prevalence and socio-demographic correlates.

The purpose of the present study was to estimate the prevalence of depression in Chinese university students, and to identify the socio-demographic factors associated with depression in this population. A multi-stage stratified sampling procedure was used to select university students (N = 5245) in Harbin (Heilongjiang Province, Northeastern China), who were aged 16-35 years. The Beck Depression Inventory (BDI) was used to determine depressive symptoms of the participants. BDI scores of 14 or higher were categorized as depressive for logistic regression analysis. Depression was diagnosed by the Structured Clinical Interview (SCID) for the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV). 11.7% of the participants had a BDI score 14 or higher. Major Depressive Disorder was seen in 4.0% of Chinese university students. There were no statistical differences in th…

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Rumination, anxiety, depressive symptoms and subsequent depression in adolescents at risk for psychopathology: a longitudinal cohort study.

Background: A ruminative style of responding to low mood is associated with subsequent high depressive symptoms and depressive disorder in children, adolescents and adults. Scores on self-report rumination scales correlate strongly with scores on anxiety and depression symptom scales. This may confound any associations between rumination and subsequent depression. Methods: Our sample comprised 658 healthy adolescents at elevated risk for psychopathology. This study applied ordinal item (non-linear) factor analysis to pooled items from three self-report questionnaires to explore whether there were separate, but correlated, constructs of rumination, depression and anxiety. It then tested whether rumination independently predicted depressive disorder and depressive symptoms over the subsequent 12 months, after adjusting for confounding variables. Results: We identified a single rumination f…

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Rumination as a vulnerability factor to depression during the transition from early to middle adolescence: a multiwave longitudinal study.

The current study examined vulnerability to depression during the transition from early to middle adolescence from the perspective of the response styles theory. During an initial assessment, 382 adolescents (ages 11-15 years) completed self-report measures assessing rumination and depressive symptoms as well as a semistructured clinical interview assessing current and past major depressive episodes. Every 3 months for the subsequent 2 years, adolescents completed self-report measures assessing depressive symptoms and negative events. Every 6 months, adolescents completed a semistructured clinical interview assessing the onset of new major depressive episodes. Higher levels of rumination were associated with a greater likelihood of exhibiting a past history of major depressive episodes, a greater likelihood of experiencing the onset of a future major depressive episode, and greater durat…

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Intolerance of uncertainty, worry, and rumination in major depressive disorder and generalized anxiety disorder.

Intolerance of uncertainty (IU) can be defined as a cognitive bias that affects how a person perceives, interprets, and responds to uncertain situations. Although IU has been reported mainly in literature relating to worry and anxiety symptoms, it may be also important to investigate the relationship between IU, rumination, and depression in a clinical sample. Furthermore, individuals who are intolerant of uncertainty easily experience stress and could cope with stressful situations using repetitive thought such as worry and rumination. Thus, we investigated whether different forms of repetitive thought differentially mediate the relationship between IU and psychological symptoms. Participants included 27 patients with MDD, 28 patients with GAD, and 16 patients with comorbid GAD/MDD. Even though worry, rumination, IU, anxiety, and depressive symptoms correlated substantially with each ot…

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Depressive symptoms, omega-6:omega-3 fatty acids, and inflammation in older adults.

Objective: To address how interactions between polyunsaturated fatty acid (PUFA) levels and depressive symptoms were related to proinflammatory cytokine synthesis. Depression and stress promote proinflammatory cytokine production. Dietary intakes of omega-3 (n-3) and omega-6 (n-6) PUFAs also influence inflammation; high n-6:n-3 ratios enhance proinflammatory cytokine production, although n-3 has anti-inflammatory properties. Methods: Blood samples from 43 older adults (mean age = 66.67 years, SD = 10.09) provided data on PUFAs and tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-6 soluble receptor (sIL-6r). Depressive symptoms were assessed by the Center for Epidemiological Studies Depression Scale. Results: Depressive symptoms and n-6:n-3 ratios worked together to enhance proinflammatory cytokines beyond the contribution provided by either variable alone, with substantial v…

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Clinical depression versus distress among patients with type 2 diabetes: not just a question of semantics.

Objective: We sought to determine differences between structured interviews, symptom questionnaires, and distress measures for assessment of depression in patients with diabetes. Research design and methods: We assessed 506 diabetic patients for major depressive disorder (MDD) by a structured interview (Composite International Diagnostic Interview [CIDI]), a questionnaire for depressive symptoms (Center for Epidemiological Studies Depression Scale [CESD]), and on the Diabetes Distress Scale. Demographic characteristics, two biological variables (A1C and non-HDL cholesterol), and four behavioral management measures (kilocalories, calories of saturated fat, number of fruit and vegetable servings, and minutes of physical activity) were assessed. Comparisons were made between those with and without depression on the CIDI and the CESD. Results: Findings showed that 22% of patients reached CES…

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Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study.

Background: Psilocybin is a serotonin receptor agonist that occurs naturally in some mushroom species. Recent studies have assessed the therapeutic potential of psilocybin for various conditions, including end-of-life anxiety, obsessive-compulsive disorder, and smoking and alcohol dependence, with promising preliminary results. Here, we aimed to investigate the feasibility, safety, and efficacy of psilocybin in patients with unipolar treatment-resistant depression. Methods: In this open-label feasibility trial, 12 patients (six men, six women) with moderate-to-severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 mg and 25 mg, 7 days apart) in a supportive setting. There was no control group. Psychological support was provided before, during, and after each session. The primary outcome measure for feasibility was patient-reported intensity of ps…

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Evidence-based interventions to improve the palliative care of pain, dyspnea, and depression at the end of life: a clinical practice guideline from the American College of Physicians.

RECOMMENDATION 1: In patients with serious illness at the end of life, clinicians should regularly assess patients for pain, dyspnea, and depression. (Grade: strong recommendation, moderate quality of evidence.) RECOMMENDATION 2: In patients with serious illness at the end of life, clinicians should use therapies of proven effectiveness to manage pain. For patients with cancer, this includes nonsteroidal anti-inflammatory drugs, opioids, and bisphosphonates. (Grade: strong recommendation, moderate quality of evidence.) RECOMMENDATION 3: In patients with serious illness at the end of life, clinicians should use therapies of proven effectiveness to manage dyspnea, which include opioids in patients with unrelieved dyspnea and oxygen for short-term relief of hypoxemia. (Grade: strong recommendation, moderate quality of evidence.) RECOMMENDATION 4: In patients with serious illness at the end …

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The role of exercise in the treatment of depression: biological underpinnings and clinical outcomes.

Globally, depression is a leading cause of disability and has remained so for decades. Antidepressant medications have suboptimal outcomes and are too frequently associated with side effects, highlighting the need for alternative treatment options. Although primarily known for its robust physical health benefits, exercise is increasingly recognized for its mental health and antidepressant benefits. Empirical evidence indicates that exercise is effective in treating individuals with depression; however, the mechanisms by which exercise exerts anti-depressant effects are not fully understood. Acute bouts of exercise have been shown to transiently modulate circulating levels of serotonin and norepinephrine, brain-derived neurotrophic factor, and a variety of immuno-inflammatory mechanisms in clinical cohorts with depression. However, exercise training has not been demonstrated to consistent…

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Inflammation, Lifestyle Factors, and the Microbiome-Gut-Brain Axis: Relevance to Depression and Antidepressant Action.

Depression is considered a major public health concern, where existing pharmacological treatments are not equally effective across all patients. The pathogenesis of depression involves the interaction of complex biological components, such as the immune system and the microbiota-gut-brain axis. Adjunctive lifestyle-oriented approaches for depression, including physical exercise and special diets are promising therapeutic options when combined with traditional antidepressants. However, the mechanisms of action of these strategies are incompletely understood. Accumulating evidence suggests that physical exercise and specific dietary regimens can modulate both the immune system and gut microbiota composition. Here, we review the current information about the strategies to alleviate depression and their crosstalk with both inflammatory mechanisms and the gut microbiome. We further discuss th…

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Molecular mechanisms underlying the antidepressant actions of arketamine: beyond the NMDA receptor.

The discovery of robust antidepressant actions exerted by the N-methyl-D-aspartate receptor (NMDAR) antagonist (R,S)-ketamine has been a crucial breakthrough in mood disorder research. (R,S)-ketamine is a racemic mixture of equal amounts of (R)-ketamine (arketamine) and (S)-ketamine (esketamine). In 2019, an esketamine nasal spray from Johnson & Johnson was approved in the United States of America and Europe for treatment-resistant depression. However, an increasing number of preclinical studies show that arketamine has greater potency and longer-lasting antidepressant-like effects than esketamine in rodents, despite the lower binding affinity of arketamine for the NMDAR. In clinical trials, non-ketamine NMDAR-related compounds did not exhibit ketamine-like robust antidepressant actions in patients with depression, despite these compounds showing antidepressant-like effects in rodents. T…

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Neurotrophic Factor BDNF, Physiological Functions and Therapeutic Potential in Depression, Neurodegeneration and Brain Cancer.

Brain-derived neurotrophic factor (BDNF) is one of the most distributed and extensively studied neurotrophins in the mammalian brain. BDNF signals through the tropomycin receptor kinase B (TrkB) and the low affinity p75 neurotrophin receptor (p75NTR). BDNF plays an important role in proper growth, development, and plasticity of glutamatergic and GABAergic synapses and through modulation of neuronal differentiation, it influences serotonergic and dopaminergic neurotransmission. BDNF acts as paracrine and autocrine factor, on both pre-synaptic and post-synaptic target sites. It is crucial in the transformation of synaptic activity into long-term synaptic memories. BDNF is considered an instructive mediator of functional and structural plasticity in the central nervous system (CNS), influencing dendritic spines and, at least in the hippocampus, the adult neurogenesis. Changes in the rate of…

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The future of rodent models in depression research.

Currently, over 300 million people worldwide have depression, and the socioeconomic burden of this debilitating disorder is anticipated to increase markedly over the coming decades against a background of increasing global turmoil. Despite this impending crisis, we are still waiting for improved therapeutic options for this disorder to emerge, which has led to increasing criticism of the role and value of preclinical models of depression. In this Review, we examine this landscape, focusing firstly on issues related to the terminology used in this context and the myriad of preclinical approaches to modelling and assaying aspects of depression in rodents. We discuss the importance of sex as a biological variable and the controversial idea of intergenerational and transgenerational transmission of depressive-like traits. We then examine the technical strategies available to dissect these mo…

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Bipolar depression: the clinical characteristics and unmet needs of a complex disorder.

Objective: We reviewed important clinical aspects of bipolar depression, a progressive psychiatric condition that is commonly treated in primary care. Bipolar depression is associated with considerable burden of illness, high suicide risk, and greater morbidity and mortality than bipolar mania. Methods: We identified articles relevant to our narrative review using a multistep search of the literature and applying terms that were relevant to bipolar depression or bipolar disorder. Results: Bipolar depression accounts for the majority of time spent unwell for patients with bipolar disorder; high rates of morbidity and mortality arise from full symptomatic episodes and interepisode subsyndromal symptoms. Bipolar depression is an important contributor to long-term dysfunction for patients with bipolar disorder due to psychosocial impairment, loss of work productivity and high rates of substa…

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The Influence of Antidepressants on the Immune System.

Depression is one of the most frequently diagnosed condition in psychiatry. Despite the availability of many preparations, over 30% of treated patients do not achieve remission. Recently the emphasis is put on the contribution of the body's inflammatory response as one of the causes of depression. The interactions between nervous and immune systems are the main issue addressed by psychoneuroimmunology. In patients suffering from depression changes in the plasma concentrations of cytokines and in the number and level of activation of immune cells has been found. Attention is paid to the high levels of pro-inflammatory cytokines, the prevalence of Th1 responses to Th2, weakening of NK cell cytotoxicity and changes in lymphocyte proliferation and apoptosis. A number of studies focus on influence of antidepressants and non-standard methods of depression treatment, such as ketamine infusion, …

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Altered Connectivity in Depression: GABA and Glutamate Neurotransmitter Deficits and Reversal by Novel Treatments.

The mechanisms underlying the pathophysiology and treatment of depression and stress-related disorders remain unclear, but studies in depressed patients and rodent models are beginning to yield promising insights. These studies demonstrate that depression and chronic stress exposure cause atrophy of neurons in cortical and limbic brain regions implicated in depression, and brain imaging studies demonstrate altered connectivity and network function in the brains of depressed patients. Studies of the neurobiological basis of the these alterations have focused on both the principle, excitatory glutamate neurons, as well as inhibitory GABA interneurons. They demonstrate structural, functional, and neurochemical deficits in both major neuronal types that could lead to degradation of signal integrity in cortical and hippocampal regions. The molecular mechanisms underlying these changes have no…

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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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Immunoregulatory natural compounds in stress-induced depression: An alternative or an adjunct to conventional antidepressant therapy?

The interplay of chronic stress, neuroinflammation and altered immune reactivity has been shown to be important for the pathophysiology of brain disorders such as schizophrenia, depressive disorders and post-traumatic stress disorder. This immuno-inflammatory theory has been extensively studied in the past three decades leading to the formation of the integrative discipline of psychoneuroimmunology. Targeting of the central nervous system by conventional pharmacotherapeutic methods is mainly through modulation of neuroendocrine systems such as the dopaminergic, GABA-ergic, adrenergic and serotoninergic systems. In recent years an increasing number of both experimental and clinical studies have shown that antidepressants can affect the immune system by reducing the production of pro-inflammatory cytokines such as IL-1β, IL-6 and TNF-α. However, due to the serious adverse effects accompany…

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Bipolar disorders.

Bipolar disorders are chronic and recurrent disorders that affect >1% of the global population. Bipolar disorders are leading causes of disability in young people as they can lead to cognitive and functional impairment and increased mortality, particularly from suicide and cardiovascular disease. Psychiatric and nonpsychiatric medical comorbidities are common in patients and might also contribute to increased mortality. Bipolar disorders are some of the most heritable psychiatric disorders, although a model with gene-environment interactions is believed to best explain the aetiology. Early and accurate diagnosis is difficult in clinical practice as the onset of bipolar disorder is commonly characterized by nonspecific symptoms, mood lability or a depressive episode, which can be similar in presentation to unipolar depression. Moreover, patients and their families do not always understand…

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Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression.

Depression is a major health problem with a high prevalence and a heavy socioeconomic burden in western societies. It is associated with atrophy and impaired functioning of cortico-limbic regions involved in mood and emotion regulation. It has been suggested that alterations in neurotrophins underlie impaired neuroplasticity, which may be causally related to the development and course of depression. Accordingly, mounting evidence suggests that antidepressant treatment may exert its beneficial effects by enhancing trophic signaling on neuronal and synaptic plasticity. However, current antidepressants still show a delayed onset of action, as well as lack of efficacy. Hence, a deeper understanding of the molecular and cellular mechanisms involved in the pathophysiology of depression, as well as in the action of antidepressants, might provide further insight to drive the development of novel…

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The Link between Depression and Chronic Pain: Neural Mechanisms in the Brain.

Chronic pain, as a stress state, is one of the critical factors for determining depression, and their coexistence tends to further aggravate the severity of both disorders. Unfortunately, their association remains unclear, which creates a bottleneck problem for managing chronic pain-induced depression. In recent years, studies have found considerable overlaps between pain- and depression-induced neuroplasticity changes and neurobiological mechanism changes. Such overlaps are vital to facilitating the occurrence and development of chronic pain and chronic pain-induced depression. In this review, we summarized the role of neuroplasticity in the occurrence and development of the two disorders in question and explored individualized application strategies of analgesic drugs and antidepressants that have different pharmacological effects in the treatment of chronic pain-induced depression. Th…

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Inflammation in Depression and the Potential for Anti-Inflammatory Treatment.

Accumulating evidence supports an association between depression and inflammatory processes, a connection that seems to be bidirectional. Clinical trials have indicated antidepressant treatment effects for anti-inflammatory agents, both as add-on treatment and as monotherapy. In particular, nonsteroidal anti-inflammatory drugs (NSAIDs) and cytokine-inhibitors have shown antidepressant treatment effects compared to placebo, but also statins, poly-unsaturated fatty acids, pioglitazone, minocycline, modafinil, and corticosteroids may yield antidepressant treatment effects. However, the complexity of the inflammatory cascade, limited clinical evidence, and the risk for side effects stress cautiousness before clinical application. Thus, despite proof-of-concept studies of anti-inflammatory treatment effects in depression, important challenges remain to be investigated. Within this paper, we r…

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