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

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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

Professional Stigma of Mental Health Issues: Physicians Are Both the Cause and Solution.

After a medical student prompted medical faculty to tell their stories of depression and related mental health issues, the author wrote this article with the aim of decreasing the stigma of mental illness and encouraging treatment, as needed, in the medical profession. The professional culture of the house of medicine not only mimics society in attributing stigma to people with mental health issues but may also contribute to high rates of suicide in the ranks of health care professionals by leading to a delay in seeking treatment. Acculturation accelerates in the first year of medical school such that medical students experience an increase in burnout and depressive symptoms from prematriculation levels. It follows that faculty have a responsibility to improve the learning environment. Survey data from medical faculty at the author's institution showed that depression decreased responden…

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Are perceived barriers to accessing mental healthcare associated with socioeconomic position among individuals with symptoms of depression? Questionnaire-results from the Lolland-Falster Health Study, a rural Danish population study.

Objective: To evaluate if perceived barriers to accessing mental healthcare (MHC) among individuals with symptoms of depression are associated with their socio-economic position (SEP). Design: Cross-sectional questionnaire-based population survey from the Lolland-Falster Health Study (LOFUS) 2016-17 of 5076 participants. Participants: The study included 372 individuals, with positive scores for depression according to the Major Depression Inventory (MDI), participating in LOFUS . Interventions: A set of five questions on perceived barriers to accessing professional care for mental health problem was posed to individuals with symptoms of depression (MDI score >20). Outcomes: The association between SEP (as measured by educational attainment, employment status and financial strain) and five different types of barriers to accessing MHC were analysed in separate multivariable logistic regres…

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Early life stress leads to sex differences in development of depressive-like outcomes in a mouse model.

Childhood trauma and neglect influence emotional development and increase the risk for and severity of mental illness. Women have a heightened susceptibility to the effects of early life stress (ELS) and are twice as likely as men to develop debilitating, stress-associated disorders later in life, such as major depressive disorder (MDD). Until now, mouse models of depression have been largely unsuccessful at replicating the diverse symptomatology of this disease and the sex bias in vulnerability. From P4 to P11, a limited bedding model that leads to fragmented maternal care, was used to induce ELS. Early adolescent and young adult mice were tested on an array of assays to test for depressive-like behavior. This included our newly developed automated home cage behavioral recognition system, where the home cage behavior of ELS and control mice could be monitored over a continuous 5-10 day …

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Antidepressant treatment resistance is associated with increased inflammatory markers in patients with major depressive disorder.

Background: One third of patients with major depressive disorder (MDD) fail to respond to currently available antidepressant medications. Inflammation may contribute to treatment non-response through effects on neurotransmitter systems relevant to antidepressant efficacy. In post-hoc analyses, increased concentrations of inflammatory markers prior to treatment predict poor antidepressant response. However, limited data exists on whether depressed patients with multiple failed treatment trials in their current episode of depression exhibit increased inflammation. Methods: Plasma concentrations of inflammatory markers were measured in unmedicated, medically stable patients with MDD (n = 98) and varying numbers of adequate antidepressant treatment trials in the current depressive episode as measured by the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire. Covar…

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Sodium butyrate abolishes lipopolysaccharide-induced depression-like behaviors and hippocampal microglial activation in mice.

Patients with major depressive disorder have elevated peripheral inflammation; the degree of this increase correlates with the severity of the disorder. Chronic psychological stress increases pro-inflammatory cytokines and promotes microglial activation, leading to stress vulnerability. Epigenetics, including DNA methylation and histone modification, are also related to the pathophysiology of major depressive disorder. Sodium butyrate (SB), a histone deacetylase inhibitor, exerts an antidepressant effect by altering gene expression in the hippocampus. In this study, we investigated whether lipopolysaccharide (LPS)-induced depressive-like behaviors in mice are affected by the repeated treatment with SB. Intraperitoneal injection of LPS (5 mg/kg) induced cytokines and ionized calcium-binding adaptor molecule 1(Iba1), a marker of microglial activation, in the hippocampus. It also increased …

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Association of translocator protein total distribution volume with duration of untreated major depressive disorder: a cross-sectional study.

Background: People with major depressive disorder frequently exhibit increasing persistence of major depressive episodes. However, evidence for neuroprogression (ie, increasing brain pathology with longer duration of illness) is scarce. Microglial activation, which is an important component of neuroinflammation, is implicated in neuroprogression. We examined the relationship of translocator protein (TSPO) total distribution volume (VT), a marker of microglial activation, with duration of untreated major depressive disorder, and with total illness duration and antidepressant exposure. Methods: In this cross-sectional study, we recruited participants aged 18-75 years from the Toronto area and the Centre for Addiction and Mental Health (Toronto, ON, Canada). Participants either had major depressive episodes secondary to major depressive disorder or were healthy, as confirmed with a structur…

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Treatment received and treatment adequacy of depressive disorders among young adults in Finland.

Background: Under-treated depression may be especially harmful in early adulthood. The aims of this study are to describe treatments received for depressive disorders, to define factors associated with treatment adequacy and dropouts from treatment in a Finnish general population sample of young adults. Methods: A nationally representative two-stage cluster sample of 1894 Finns aged 19 to 34 years was sent a questionnaire containing several mental health screens. All screen positives and a random sample of screen negatives were invited to participate in a mental health assessment including a SCID interview. Case records from mental health treatments for the same sample were obtained for the final diagnostic assessment. Based on all available information, receiving antidepressant pharmacotherapy for at least two months with at least four visits with any type of physician or at least eight…

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Telomerase dysregulation in the hippocampus of a rat model of depression: normalization by lithium.

Background: Telomeres are protective DNA-protein complexes at the ends of each chromosome, maintained primarily by the enzyme telomerase. Shortening of the blood leukocyte telomeres is associated with aging, several chronic diseases, and stress, eg, major depression. Hippocampus is pivotal in the regulation of cognition and mood and the main brain region of telomerase activity. Whether there is telomere dysfunction in the hippocampus of depressed subjects is unknown. Lithium, used in the treatment and relapse prevention of mood disorders, was found to protect against leukocyte telomere shortening in humans, but the mechanism has not been elucidated. To answer the questions whether telomeres are shortened and the telomerase activity changed in the hippocampus and whether lithium could reverse the process, we used a genetic model of depression, the Flinders Sensitive Line rat, and treated …

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Increased amygdala response to shame in remitted major depressive disorder.

Proneness to self-blaming moral emotions such as shame and guilt is increased in major depressive disorder (MDD), and may play an important role in vulnerability even after symptoms have subsided. Social psychologists have argued that shame-proneness is relevant for depression vulnerability and is distinct from guilt. Shame depends on the imagined critical perception of others, whereas guilt results from one's own judgement. The neuroanatomy of shame in MDD is unknown. Using fMRI, we compared 21 participants with MDD remitted from symptoms with no current co-morbid axis-I disorders, and 18 control participants with no personal or family history of MDD. The MDD group exhibited higher activation of the right amygdala and posterior insula for shame relative to guilt (SPM8). This neural difference was observed despite equal levels of rated negative emotional valence and frequencies of induce…

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The Personalized Advantage Index: translating research on prediction into individualized treatment recommendations. A demonstration.

Background: Advances in personalized medicine require the identification of variables that predict differential response to treatments as well as the development and refinement of methods to transform predictive information into actionable recommendations. Objective: To illustrate and test a new method for integrating predictive information to aid in treatment selection, using data from a randomized treatment comparison. Method: Data from a trial of antidepressant medications (N = 104) versus cognitive behavioral therapy (N = 50) for Major Depressive Disorder were used to produce predictions of post-treatment scores on the Hamilton Rating Scale for Depression (HRSD) in each of the two treatments for each of the 154 patients. The patient's own data were not used in the models that yielded these predictions. Five pre-randomization variables that predicted differential response (marital sta…

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A treatment-resistant default mode subnetwork in major depression.

Background: Previous studies have suggested that the default mode network (DMN) plays a central role in the physiopathology of major depressive disorder (MDD). However, the effect of antidepressant treatment on functional connectivity within the DMN has yet to be established. Considering the very high rates of relapse in recovered subjects, we hypothesized that abnormalities in DMN functional connectivity would persist in recovered MDD subjects. Methods: Resting state functional magnetic resonance imaging images were collected from 24 MDD patients and 29 healthy control subjects. After 12 weeks of antidepressant treatment, 18 recovered MDD subjects were scanned again. Group independent component analysis was performed to decompose the resting state images into spatially independent components. Default mode subnetworks were identified using a template based on previous studies. Group diff…

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Dysregulated relationship of inflammation and oxidative stress in major depression.

Chronic inflammation and oxidative stress have been implicated in the pathophysiology of Major Depressive Disorder (MDD), as well as in a number of chronic medical conditions. The aim of this study was to examine the relationship between peripheral inflammatory and oxidative stress markers in un-medicated subjects with MDD compared to non-depressed healthy controls and compared to subjects with MDD after antidepressant treatment. We examined the relationships between IL-6, IL-10, and the IL-6/IL-10 inflammatory ratio vs. F2-isoprostanes (F2-IsoP), a marker of oxidative stress, in un-medicated MDD patients (n=20) before and after 8 weeks of open-label sertraline treatment (n=17), compared to healthy non-depressed controls (n=20). Among the un-medicated MDD subjects, F2-IsoP concentrations were positively correlated with IL-6 concentrations (p<0.05) and were negatively correlated with IL-1…

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Variant brain-derived neurotrophic factor Val66Met polymorphism alters vulnerability to stress and response to antidepressants.

Brain-derived neurotrophic factor (BDNF) plays important roles in cell survival, neural plasticity, learning, and stress regulation. However, whether the recently found human BDNF Val66Met (BDNF(Met)) polymorphism could alter stress vulnerability remains controversial. More importantly, the molecular and structural mechanisms underlying the interaction between the BDNF(Met) polymorphism and stress are unclear. We found that heterozygous BDNF(+/Met) mice displayed hypothalamic-pituitary-adrenal axis hyperreactivity, increased depressive-like and anxiety-like behaviors, and impaired working memory compared with WT mice after 7 d restraint stress. Moreover, BDNF(+/Met) mice exhibited more prominent changes in BDNF levels and apical dendritic spine density in the prefrontal cortex and amygdala after stress, which correlated with the impaired working memory and elevated anxiety-like behaviors…

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Prevalence, treatment, and control of depressive symptoms in the United States: results from the National Health and Nutrition Examination Survey (NHANES), 2005-2008.

Background: depression remains a major public health problem that is most often evaluated and treated in primary care settings. The objective of this study was to examine the prevalence, treatment, and control of depressive symptoms in a national data sample using a common primary care screening tool for depression. Methods: we analyzed a sample of adults (n = 4836) from 2005 to 2008 National Health and Nutrition Examination Survey data. Depressive symptoms were assessed using the Patient Health Questionnaire (PHQ-9) to determine the overall prevalence, rates of treatment, and antidepressant control of mild, moderate, moderately severe, and severe depressive symptoms. Results: of the sample, 20.1% reported significant depressive symptoms (PHQ-9) score, ≥ 5), the majority of whom had mild depressive symptoms (PHQ-9) score, 5-9). Even among individuals with severe depressive symptoms, a la…

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Dietary intake of n-3 and n-6 fatty acids and the risk of clinical depression in women: a 10-y prospective follow-up study.

Background: The associations between different sources of dietary n-3 (omega-3) and n-6 (omega-6) fatty acids and the risk of depression have not been prospectively studied. Objective: The objective was to examine the relation between different n-3 and n-6 types with clinical depression incidence. Design: We prospectively studied 54,632 US women from the Nurses' Health Study who were 50-77 y of age and free from depressive symptoms at baseline. Information on diet was obtained from validated food-frequency questionnaires. Clinical depression was defined as reporting both physician-diagnosed depression and regular antidepressant medication use. Results: During 10 y of follow-up (1996-2006), 2823 incident cases of depression were documented. Intake of long-chain n-3 fatty acids from fish was not associated with depression risk [relative risk (RR) for 0.3-g/d increment: 0.99; 95% CI: 0.88, …

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Linking the cytokine and neurocircuitry hypotheses of depression: a translational framework for discovery and development of novel anti-depressants.

Recent studies suggest a model of depression that links the cytokine hypothesis from the field of psychoneuroimmunology with the neurocircuitry hypothesis derived from burgeoning insight into neurophysiological changes observed in depressed patients. According to the neurocircuitry hypothesis of depression, failure of homeostatic synaptic plasticity in cortical-striatal-limbic nodes of a distributed network of neural circuits involving the sub-genual anterior cingulate cortex is responsible for core symptoms of depression: loss of interest or pleasure (anhedonia) and depressed mood (sadness). According to the cytokine hypothesis of depression, inflammatory cytokines act on neural circuits to evoke the behavioral and physiological changes observed in depression. Synthesis of these hypotheses implicates cytokines released during injury, infection, illness, or psychological stress as a caus…

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Plasma and erythrocyte fatty acid patterns in patients with recurrent depression: a matched case-control study.

Background: The polyunsaturated fatty acid (PUFA) composition of (nerve) cell membranes may be involved in the pathophysiology of depression. Studies so far, focussed mainly on omega-3 and omega-6 PUFAs. In the present study, saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs) and PUFAs of the omega-3, -6 and -9 series in plasma and erythrocytes of patients with recurrent major depressive disorder (MDD-R) were compared with controls. Methodology and principal findings: We carried out a case-control study. The sample consisted of 137 patients with MDD-R and 65 matched non-depressed controls. In plasma and erythrocytes of patients with MDD-R the concentrations of most of the SFAs and MUFAs, and additionally erythrocyte PUFAs, all with a chain length > 20 carbon (C) atoms, were significantly lower than in the controls. In contrast, the concentrations of most of the shorter cha…

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Why do you need to move beyond first-line therapy for major depression?

Primary care clinicians need to move beyond first-line therapy for major depression. While initial treatment is ineffective in about two-thirds of patients, patients who have not responded to such initial treatments can be managed effectively. The severity of depression is as high in primary care as in specialty care settings. The risk of depression is currently elevated because economic hardship, job insecurity, and low socioeconomic status increase the likelihood of depression and treatment resistance. Depression worsens outcomes for medical comorbidities, such as cardiac disease, chronic obstructive pulmonary disease, and diabetes mellitus, and it increases the risk of rehospitalization. When depression is treatment-resistant (generally defined as not responding to 2 courses of treatment of adequate dose and duration), morbidity and mortality are increased, quality of life and functio…

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Cortico-limbic response to personally challenging emotional stimuli after complete recovery from depression.

People vulnerable to depression are at increased risk of relapse if they live in highly critical family environments. To explore this link, we used neuroimaging methods to examine cortico-limbic responding to personal criticisms in healthy participants and participants with known vulnerability to major depression. Healthy controls and fully recovered participants with a past history of major depression were scanned while they heard praising, critical, and neutral comments from their own mothers. Prior to scanning, the formerly depressed and the control participants were indistinguishable with respect to self-reported positive, negative, or anxious mood. They also reported similar mood changes after being praised or criticized. However, formerly depressed participants responded to criticism with greater activation in the amygdala and less activation in the dorsolateral prefrontal cortex (…

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STAR*D: revising conventional wisdom.

The STAR*D (Sequenced Treatment Alternatives to Relieve Depression) study used a series of sequenced, randomized treatment trials following a first and, if needed, subsequent treatment steps to define the tolerability and effectiveness of various options in both acute and longer term treatment. Adult outpatients (n=4041) with nonpsychotic major depressive disorder, substantial chronic and recurrent depression, and co-morbid psychiatric and general medical conditions were enrolled in 41 representative primary and specialty care settings. About one-third of participants remitted in first step treatment with citalopram, 50% of these within 6 weeks. Poorer outcomes were associated with minority status, socioeconomic disadvantage, more axis I and III co-morbid disorders, lower function and quality of life, and anxious and melancholic features. In step 2 medication switch, there were no signif…

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Reduced amygdala-prefrontal coupling in major depression: association with MAOA genotype and illness severity.

The amygdala plays a pivotal role in a cortico-limbic circuitry implicated in emotion processing and regulation. In the present study, functional connectivity of the amygdala with prefrontal areas involved in emotion regulation was investigated during a facial expression processing task in a sample of 34 depressed inpatients and 31 healthy controls. All patients were genotyped for a common functional variable number tandem repeat (VNTR) polymorphism in the promoter region of the monoamine oxidase A gene (MAOA u-VNTR) which has been previously associated with major depression as well as reduced cortico-limbic connectivity in healthy subjects. In our control group, we observed tight coupling of the amygdala and dorsal prefrontal areas comprising the dorsolateral prefrontal cortex (DLPFC), dorsal parts of the anterior cingulate cortex (dACC), and lateral orbitofrontal cortex. Amygdala-prefr…

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'Been there, experienced that': A qualitative study on the experiences and perceptions of online peer volunteers in supporting Singaporean mothers at risk of depression.

Background: Online peer support is a useful source of support for parents during the perinatal period, associated with improved psychological outcomes. Past research has found that peer support providers themselves gain from providing peer support as well, making it mutually beneficial. As current maternity care services are insufficient to meet the support needs of parents, the Supportive Parenting App (SPA) intervention was developed to offer them informational, appraisal and emotional support during the perinatal period. It consists of mobile health application-based educational support and online peer support provided by trained peer volunteers, to prevent the development of postnatal depression. Objective: To explore the experiences of peer volunteers with providing online peer support to parents during the perinatal period, as well as to identify areas of improvement for the SPA in…

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Perinatal mood and anxiety disorders: biomarker discovery using plasma proteomics.

Background: Perinatal mood and anxiety disorders encompass a range of mental health disorders that occur during pregnancy and up to 1 year postpartum, affecting approximately 20% of women. Traditional risk factors, such as a history of depression and pregnancy complications including preeclampsia, are known. Their predictive utility, however, is not specific or sensitive enough to inform clinical decision-making or prevention strategies for perinatal mood and anxiety disorders. Better diagnostic and prognostic models are needed for early identification and referral to treatment. Objective: This study aimed to determine if a panel of novel third-trimester plasma protein biomarkers in pregnant women can be used to identify those who have a high predisposed risk for perinatal mood and anxiety disorders within 3 months postpartum. Study design: We studied 52 women (n=34 with a risk for perin…

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Trial of a patient-directed eHealth program to ameliorate perinatal depression: the MomMoodBooster2 practical effectiveness study.

Background: Depression is one of the most common complications of childbirth, and is experienced by approximately 17% of pregnant women and 13% of postpartum women. An estimated 85% of these women go untreated-an alarming statistic given the serious consequences for the mother, her child, other family members, and society. Professional societies (the American College of Obstetricians and Gynecologists and American Academy of Pediatrics) have recommended improvements in screening and treatment. Meta-analyses indicate that cognitive behavioral therapy eHealth interventions are efficacious for depression, generally, and for perinatal depression, specifically. Earlier controlled trials have established the effectiveness and acceptability of MomMoodBooster (including an Australian version, MumMoodBooster), an eHealth program for ameliorating postpartum depression. Objective: This study aimed …

matched on Depression (mesh), Depression, Postpartum (mesh)

Depression, anxiety, and stress in pregnancy and postpartum: A longitudinal study during the COVID-19 pandemic.

Introduction: Symptoms of depression, anxiety, and stress in pregnant women are generally highest in the first trimester and then decrease throughout pregnancy, reaching their lowest point in the postpartum period. Pregnant women are a high-risk population for mortality and mental health symptoms due to COVID-19. However, the extent to which the chronic stress of the COVID-19 pandemic alters the trajectory of depression, anxiety and stress symptoms in pregnant/postpartum women is unknown. Methods: Women (N=127) who were pregnant or who had given birth less than one month prior were recruited via online advertising during the COVID-19 pandemic. Participants were assessed up to three times during the pregnancy and at 1-month postpartum for depression (Edinburgh Postnatal Depression Scale), anxiety, and stress (Depression, Anxiety, and Stress Scale-21). Random intercepts models examined sym…

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