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

Humanistic burden in schizophrenia: a literature review.

Objectives of the study and background: Schizophrenia is a complex disease that affects 1% of the population. This disease has a considerable impact not only on patients' health and well-being but also on their surrounding environment. The costs of the disease's management remain large for individuals and society. While literature on the economic impact of schizophrenia is abundant, few studies have focused on its humanistic burden. This does not only concern patients, but also caregivers, relatives, neighbours and others in a patient's daily life. This burden appears through several dimensions, including treatment side effects and the impact on caregivers and features of the patient's environment. The aim of this review is to consider, compile and describe the humanistic burden of schizophrenia as documented in the literature. Materials and methods: We conducted a literature review asse…

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Major depressive disorder in DSM-5: implications for clinical practice and research of changes from DSM-IV.

The changes in diagnostic criteria for major depressive disorder (MDD) from the fourth to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM) may appear small but have important consequences for how the diagnosis is used. In DSM-5, MDD is part of the new "Depressive disorders" section, which is separate from "Bipolar disorders", marking a division in what had been known as "Mood disorders". A small wording change has expanded the core mood criterion to include hopelessness, potentially broadening the diagnosis. The replacement of an operationalized bereavement exclusion with a call for clinical judgment in distinguishing normal reactions to significant loss from a disorder in need of clinical attention makes the diagnosis less objective and complicates investigations of the relationship between adversity and depression. A new persistent depressive disorde…

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Psychosocial predictors of health outcomes in colorectal cancer: a comprehensive review.

Background: A diagnosis of colorectal cancer (CRC) and its long-term treatment may lead to significant psychological distress and impaired health-related quality of life (HRQoL) for a significant proportion of patients. Methods: We searched the PubMed/MEDLINE electronic database for available literature on the associations between personality characteristics, depression, psychological distress and HRQoL in CRC. Additional references were identified through the citation tracking of the included articles. Results: Recent evidence indicates that Type-D (distressed) personality may predict distress among CRC patients. Additionally, other personality traits, such as specific ego defense mechanisms, influence the coping responses and HRQoL. Although the presence of a stoma has been linked to the development of depressive symptoms and impairment in HRQoL in CRC patients, more prospective studie…

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Microglial dysregulation in psychiatric disease.

Microglia, the brain's resident immune cells, are phagocytes of the macrophage lineage that have a key role in responding to inflammation and immune challenge in the brain. More recently, they have been shown to have a number of important roles beyond immune surveillance and response, including synaptic pruning during development and the support of adult neurogenesis. Microglial abnormalities have been found in several neuropsychiatric conditions, though in most cases it remains unclear whether these are causative or are a reaction to some other underlying pathophysiology. Here we summarize postmortem, animal, neuroimaging, and other evidence for microglial pathology in major depression, schizophrenia, autism, obsessive-compulsive disorder, and Tourette syndrome. We identify gaps in the existing literature and important areas for future research. If microglial pathology proves to be an i…

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A review of lifestyle factors that contribute to important pathways associated with major depression: diet, sleep and exercise.

Research on major depression has confirmed that it is caused by an array of biopsychosocial and lifestyle factors. Diet, exercise and sleep are three such influences that play a significant mediating role in the development, progression and treatment of this condition. This review summarises animal- and human-based studies on the relationship between these three lifestyle factors and major depressive disorder, and their influence on dysregulated pathways associated with depression: namely neurotransmitter processes, immuno-inflammatory pathways, hypothalamic-pituitary-adrenal (HPA) axis disturbances, oxidative stress and antioxidant defence systems, neuroprogression, and mitochondrial disturbances. Increased attention in future clinical studies on the influence of diet, sleep and exercise on major depressive disorder and investigations of their effect on physiological processes will help…

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The neuroprogressive nature of major depressive disorder: pathways to disease evolution and resistance, and therapeutic implications.

In some patients with major depressive disorder (MDD), individual illness characteristics appear consistent with those of a neuroprogressive illness. Features of neuroprogression include poorer symptomatic, treatment and functional outcomes in patients with earlier disease onset and increased number and length of depressive episodes. In such patients, longer and more frequent depressive episodes appear to increase vulnerability for further episodes, precipitating an accelerating and progressive illness course leading to functional decline. Evidence from clinical, biochemical and neuroimaging studies appear to support this model and are informing novel therapeutic approaches. This paper reviews current knowledge of the neuroprogressive processes that may occur in MDD, including structural brain consequences and potential molecular mechanisms including the role of neurotransmitter systems,…

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Comparative efficacy of seven psychotherapeutic interventions for patients with depression: a network meta-analysis.

Background: Previous meta-analyses comparing the efficacy of psychotherapeutic interventions for depression were clouded by a limited number of within-study treatment comparisons. This study used network meta-analysis, a novel methodological approach that integrates direct and indirect evidence from randomised controlled studies, to re-examine the comparative efficacy of seven psychotherapeutic interventions for adult depression. Methods and findings: We conducted systematic literature searches in PubMed, PsycINFO, and Embase up to November 2012, and identified additional studies through earlier meta-analyses and the references of included studies. We identified 198 studies, including 15,118 adult patients with depression, and coded moderator variables. Each of the seven psychotherapeutic interventions was superior to a waitlist control condition with moderate to large effects (range d =…

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New targets for rTMS in depression: a review of convergent evidence.

Although rTMS is moving steadily into the mainstream as a treatment for medically refractory depression, its efficacy continues to lag behind that of more invasive neuromodulation treatments such as ECT or DBS. Here we review evidence to suggest that a fruitful, but neglected, strategy for improving rTMS efficacy may be to explore alternatives to the conventional stimulation target in the dorsolateral prefrontal cortex (DLPFC). The convergent evidence of lesion, stimulation, connectivity, and correlative neuroimaging studies suggests that the DLPFC may have a relatively peripheral role in mood regulation, at least compared to several alternative areas within the prefrontal cortex. In particular, we consider the evidence base in support of four new potential targets for rTMS in depression: dorsomedial prefrontal cortex (DMPFC), frontopolar cortex (FPC), ventromedial prefrontal cortex (VMP…

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An attentional scope model of rumination.

Rumination, defined as repetitive thinking about negative information, has been found to lead to serious maladaptive consequences, including longer and more severe episodes of major depression. In this review, we present and discuss research findings motivated by the formulation that individual differences in cognitive processes that control how information is processed influence the likelihood that thoughts will become repetitive and negative. Several studies have demonstrated that a tendency to ruminate (i.e., trait rumination) is related to difficulties updating working memory (WM) and disengaging from and forgetting no-longer-relevant information. Other investigators have documented that trait rumination is also associated with an enhanced ability to ignore distracting information and with more stable maintenance of task-relevant information. In contrast to trait rumination, a state …

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Understanding the somatic consequences of depression: biological mechanisms and the role of depression symptom profile.

Depression is the most common psychiatric disorder worldwide. The burden of disease for depression goes beyond functioning and quality of life and extends to somatic health. Depression has been shown to subsequently increase the risk of, for example, cardiovascular, stroke, diabetes and obesity morbidity. These somatic consequences could partly be due to metabolic, immuno-inflammatory, autonomic and hypothalamic-pituitary-adrenal (HPA)-axis dysregulations which have been suggested to be more often present among depressed patients. Evidence linking depression to metabolic syndrome abnormalities indicates that depression is especially associated with its obesity-related components (for example, abdominal obesity and dyslipidemia). In addition, systemic inflammation and hyperactivity of the HPA-axis have been consistently observed among depressed patients. Slightly less consistent observati…

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Childhood maltreatment and psychopathology: A case for ecophenotypic variants as clinically and neurobiologically distinct subtypes.

Objective: Childhood maltreatment increases risk for psychopathology. For some highly prevalent disorders (major depression, substance abuse, anxiety disorders, and posttraumatic stress disorder) a substantial subset of individuals have a history of maltreatment and a substantial subset do not. The authors examined the evidence to assess whether those with a history of maltreatment represent a clinically and biologically distinct subtype. Method: The authors reviewed the literature on maltreatment as a risk factor for these disorders and on the clinical differences between individuals with and without a history of maltreatment who share the same diagnoses. Neurobiological findings in maltreated individuals were reviewed and compared with findings reported for these disorders. Results: Maltreated individuals with depressive, anxiety, and substance use disorders have an earlier age at onse…

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Heartache and heartbreak--the link between depression and cardiovascular disease.

The close, bidirectional relationship between depression and cardiovascular disease is well established. Major depression is associated with an increased risk of coronary artery disease and acute cardiovascular sequelae, such as myocardial infarction, congestive heart failure, and isolated systolic hypertension. Morbidity and mortality in patients with cardiovascular disease and depression are significantly higher than in patients with cardiovascular disease who are not depressed. Various pathophysiological mechanisms might underlie the risk of cardiovascular disease in patients with depression: increased inflammation; increased susceptibility to blood clotting (owing to alterations in multiple steps of the clotting cascade, including platelet activation and aggregation); oxidative stress; subclinical hypothyroidism; hyperactivity of the sympatho-adrenomedullary system and the hypothalam…

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Rediscovering trazodone for the treatment of major depressive disorder.

Trazodone is a triazolopyridine derivative that belongs to the class of serotonin receptor antagonists and reuptake inhibitors (SARIs). The drug is approved and marketed in several countries worldwide for the treatment of major depressive disorder (MDD) in adult patients. In clinical studies, trazodone has demonstrated comparable antidepressant activity to other drug classes, including tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline (norepinephrine) reuptake inhibitors (SNRIs). Moreover, the SARI action of trazodone may overcome the tolerability issues that are often associated with second-generation antidepressants such as SSRIs (i.e. insomnia, anxiety and sexual dysfunction). Recent focus has been placed on the development of a new prolonged-release once-a-day formulation of trazodone (TzCOAD), which may provide improved tol…

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Getting straight about grief.

Acute grief is emotionally intense, cognitively preoccupying, and disruptive, but grief is not an illness; major depression and anxiety disorders are. Grief and mourning have a purpose. They provide an intense, focused opportunity to reregulate emotion and to engage in a learning process that is aimed at reconfiguring life without the deceased—both the internal life of the mind, and ongoing life in the world. A bereaved person needs to figure out how to find meaning, purpose, joy, and satisfaction in life without someone who has previously been central to these feelings. This reconfiguration is a very natural process that tends to occur in fits and starts as bereaved people move forward and deal with everyday life. Nevertheless, a knowledgeable, empathic and supportive clinician can foster good adjustment. Successful mourning is, however, not a given. For some people, the mourning proces…

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Depression: an inflammatory illness?

Major depressive disorder (MDD) is associated with significant morbidity and mortality. Findings from preclinical and clinical studies suggest that psychiatric illnesses, particularly MDD, are associated with inflammatory processes. While it is unlikely that MDD is a primary 'inflammatory' disorder, there is now evidence to suggest that inflammation may play a subtle role in the pathophysiology of MDD. Most of the evidence that links inflammation to MDD comes from three observations: (a) one-third of those with major depression show elevated peripheral inflammatory biomarkers, even in the absence of a medical illness; (b) inflammatory illnesses are associated with greater rates of MDD; and (c) patients treated with cytokines are at greater risk of developing major depressive illness. We now know that the brain is not an immune privileged organ. Inflammatory mediators have been found to a…

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Positive psychological attributes and cardiac outcomes: associations, mechanisms, and interventions.

Background: Intervention research at the intersection of psychiatry and cardiology has primarily focused on the relationship between negative psychological syndromes (e.g., depression) and cardiac outcomes, with less emphasis on positive psychological attributes, such as optimism, gratitude, and well-being, as they relate to cardiac disease. Methods: Literature is reviewed in three specific areas regarding positive attributes and cardiac disease: (1) associations between positive attributes and cardiac outcomes, (2) potential mechanisms-both behavioral and physiologic-by which positive psychological states may impact cardiovascular health, and (3) interventions aimed at cultivating positive psychological attributes in healthy and medically ill persons. Results: There is significant evidence that positive psychological attributes--especially optimism--may be independently associated with …

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The costs of depression.

The data reported herein show clearly that major depression is a commonly occurring and burdensome disorder. The high prevalence, early age of onset, and high persistence of MDD in the many different countries where epidemiologic surveys have been administered confirm the high worldwide importance of depression. Although evidence is not definitive that MDD plays a causal role in its associations with the many adverse outcomes reviewed here, there is clear evidence that depression has causal effects on a number of important mediators, making it difficult to assume anything other than that depression has strong causal effects on many dimensions of burden. These results have been used to argue for the likely cost -effectiveness of expanded depression treatment from a societal perspective. Two separate, large-scale, randomized, workplace depression treatment effectiveness trials have been ca…

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Anxiety, depression and stress in pregnancy: implications for mothers, children, research, and practice.

Purpose of review: To briefly review results of the latest research on the contributions of depression, anxiety, and stress exposures in pregnancy to adverse maternal and child outcomes, and to direct attention to new findings on pregnancy anxiety, a potent maternal risk factor. Recent findings: Anxiety, depression, and stress in pregnancy are risk factors for adverse outcomes for mothers and children. Anxiety in pregnancy is associated with shorter gestation and has adverse implications for fetal neurodevelopment and child outcomes. Anxiety about a particular pregnancy is especially potent. Chronic strain, exposure to racism, and depressive symptoms in mothers during pregnancy are associated with lower birth weight infants with consequences for infant development. These distinguishable risk factors and related pathways to distinct birth outcomes merit further investigation. Summary: Thi…

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Using Support Vector Machine to identify imaging biomarkers of neurological and psychiatric disease: a critical review.

Standard univariate analysis of neuroimaging data has revealed a host of neuroanatomical and functional differences between healthy individuals and patients suffering a wide range of neurological and psychiatric disorders. Significant only at group level however these findings have had limited clinical translation, and recent attention has turned toward alternative forms of analysis, including Support-Vector-Machine (SVM). A type of machine learning, SVM allows categorisation of an individual's previously unseen data into a predefined group using a classification algorithm, developed on a training data set. In recent years, SVM has been successfully applied in the context of disease diagnosis, transition prediction and treatment prognosis, using both structural and functional neuroimaging data. Here we provide a brief overview of the method and review those studies that applied it to the…

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Is chronic insomnia a precursor to major depression? Epidemiological and biological findings.

Insomnia has been found to be a clinical predictor of subsequent depression. Nevertheless the biological processes underlying this causal relationship are yet not fully understood. Both conditions share a common imbalance of the arousal system. Patients with insomnia present fragmented REM sleep, which probably interferes with basal processes of emotion regulation. The interaction between the arousal and the affective system with the persistence of the disorder could slowly alter also the cognitive system and lead to depression. Although preliminary results seem to support this hypothesis, data are still too few to make valid conclusions.

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Medial prefrontal cortex and the self in major depression.

Self-focus (i.e. the process by which one engages oneself in self-referential processing) is a core issue in the psychopathology of major depression. The cortical midline structures, including the medial prefrontal cortex (MPFC), play a key role in self-referential processing in healthy subjects. Four functional magnetic resonance imaging studies recently found either an increased or a decreased MPFC activation during self-referential processing in depressed patients compared to healthy controls. Building on critical differences in experimental settings, we argue that these conflicting results are indeed consistent with two modes of elevated MPFC activation in major depression. An elevated tonic ventral MPFC activation, as uncovered by an event-related design, may embody automatic aspects of depressive self-focus, such as attracting attention to self-relevant incoming information. An ele…

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Effects of exercise and physical activity on depression.

Introduction: Depression is a very prevalent mental disorder affecting 340 million people globally and is projected to become the leading cause of disability and the second leading contributor to the global burden of disease by the year 2020. Aim: In this paper, we review the evidence published to date in order to determine whether exercise and physical activity can be used as therapeutic means for acute and chronic depression. Topics covered include the definition, classification criteria and treatment of depression, the link between β-endorphin and exercise, the efficacy of exercise and physical activity as treatments for depression, properties of exercise stimuli used in intervention programs, as well as the efficacy of exercise and physical activity for treating depression in diseased individuals. Conclusions: The presented evidence suggests that exercise and physical activity have b…

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A topographical map of the causal network of mechanisms underlying the relationship between major depressive disorder and coronary heart disease.

Objective: Major depressive disorder (MDD) and coronary heart disease (CHD) are both clinically important public health problems. Depression is linked with a higher incidence of ischaemic cardiac events and MDD is more prevalent in patients with CHD. No single comprehensive model has yet described the causal mechanisms linking MDD to CHD. Several key mechanisms have been put forward, comprising behavioural mechanisms, genetic mechanisms, dysregulation of immune mechanisms, coagulation abnormalities and vascular endothelial dysfunction, polyunsaturated omega-3 free fatty acid deficiency, and autonomic mechanisms. It has been suggested that these mechanisms form a network, which links MDD and CHD. The aim of this review is to examine the causal mechanisms underlying the relationship between MDD and CHD, with the aim of constructing a topological map of the causal network which describes th…

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Beyond the serotonin hypothesis: mitochondria, inflammation and neurodegeneration in major depression and affective spectrum disorders.

For many years, a deficiency of monoamines including serotonin has been the prevailing hypothesis on depression, yet research has failed to confirm consistent relations between brain serotonin and depression. High degrees of overlapping comorbidities and common drug efficacies suggest that depression is one of a family of related conditions sometimes referred to as the "affective spectrum disorders", and variably including migraine, irritable bowel syndrome, chronic fatigue syndrome, fibromyalgia and generalized anxiety disorder, among many others. Herein, we present data from many different experimental modalities that strongly suggest components of mitochondrial dysfunction and inflammation in the pathogenesis of depression and other affective spectrum disorders. The three concepts of monoamines, energy metabolism and inflammatory pathways are inter-related in many complex manners. For…

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An intriguing and hitherto unexplained co-occurrence: Depression and chronic fatigue syndrome are manifestations of shared inflammatory, oxidative and nitrosative (IO&NS) pathways.

There is a significant 'comorbidity' between depression and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Depressive symptoms frequently occur during the course of ME/CFS. Fatigue and somatic symptoms (F&S), like pain, muscle tension, and a flu-like malaise, are key components of depression. At the same time, depression and ME/CFS show major clinical differences, which allow to discriminate them with a 100% accuracy. This paper aims to review the shared pathways that underpin both disorders and the pathways that discriminate them. Numerous studies have shown that depression and ME/CFS are characterized by shared aberrations in inflammatory, oxidative and nitrosative (IO&NS) pathways, like systemic inflammation and its long-term sequels, including O&NS-induced damage to fatty acids, proteins and DNA; dysfunctional mitochondria; lowered antioxidant levels, like zinc and coen…

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