Abstract：
:It was hypothesized decades ago that reduced levels of brain monoamines such as serotonin or norepinephrine form, at least in part, a pathophysiological basis for major depression. Consistent with this hypothesis, a conventional strategy used, with varying success, to treat major depression involves administering antidepressant drugs that are thought to boost the synaptic concentration of serotonin and/or norepinephrine. While the reduced monoamine hypothesis is well known but highly controversial and widely considered to be incomplete or simply incorrect, the possibility that elevated monoamines are an etiological factor in some cases of major depression (rather than or in addition to hypomania or mania) has received little attention at all. This paper puts forth the novel hypothesis elevated brain levels of three monoamines - serotonin, norepinephrine, dopamine - are each etiological factors in some cases of major depression. In support of this hypothesis, the paper very briefly reviews relevant data on each of these neurotransmitter systems, including: transporter knockout mice, human genetic association studies, and pharmaceutical studies that enhance or diminish transmitter signaling in either rodents or humans. While all of the published data do not support the hypothesis, there are studies that do for each of the three transmitter systems. The etiological basis of the putative effect of monoamines on depression may be mediated both through genetics and exposure to psychological stress. If the elevated monoamine hypothesis is correct for some persons, pharmaceutical treatment of depression may be significantly improved if the particular elevated monoamine(s) could be identified and then altered on a personalized basis, or perhaps for different putative subtypes of depression. One possibility is that atypical depression involves elevated noradrenergic signaling.
journal_name
Med Hypothesesjournal_title
Medical hypothesesauthors
Fitzgerald PJdoi
10.1016/j.mehy.2013.03.023subject
Has Abstractpub_date
2013-06-01 00:00:00pages
823-6issue
6eissn
0306-9877issn
1532-2777pii
S0306-9877(13)00142-4journal_volume
80pub_type
杂志文章abstract：:Synthetic ligands of the retinoid X receptor (RXR) have shown antidiabetic activity in mice, apparently owing to the fact that they stimulate the transcriptional activity of PPAR-gamma/RXR heterodimers, much like thiazolidinedione drugs. The chlorophyll metabolite phytanic acid has been shown to be a natural ligand fo...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1054/mehy.2000.1153
更新日期：2001-02-01 00:00:00
abstract：:An association between Alzheimer's Disease (AD) and low CSF and serum vitamin B12 (B12) has recently been described (1, 2, 3). This is apparently independent of nutritional intake (4). It has been suggested that such patients may exhibit an atypical form of cobalamin deficiency (3, 4). It is therefore proposed that th...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(92)90074-m
更新日期：1992-03-01 00:00:00
abstract：:The limb remote ischaemia postconditioning (RIPOC), a newly conceived idea of applying brief limb ischaemic stimulus after onset of the myocardial ischaemia but prior to the reperfusion, can offer the possibility of applying this cardioprotective strategy to the patients with acute myocardial infraction. Although incr...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2009.04.004
更新日期：2009-09-01 00:00:00
abstract：:Despite important advances in understanding its pathophysiology, therapy for septic shock remains largely symptomatic and supportive. Aiming to elevate the systemic arterial blood pressure by using vasoconstrictor manoeuvers are preferred without paying much attention to the ischaemia produced at the peripheral tissue...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2003.11.009
更新日期：2004-01-01 00:00:00
abstract：:An unexpected and novel finding is described and discussed here concerning the synaptic physiology of hippocampal slices during the period of recovery after brain dissection. Contrary to the common notion that the amplitude of synaptic responses recovers in a single exponential rising fashion, we found that synaptic r...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2011.09.010
更新日期：2011-12-01 00:00:00
abstract：:Nearly two million people suffer traumatic brain injury in the US each year. These injuries alter adversely the metabolism of myelin, a major lipid material in brain, both in people and in experimental injuries of animals. A newly discovered and severe human neuropathy from copper deficiency provides evidence that som...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2013.09.011
更新日期：2013-12-01 00:00:00
abstract：:In a survey based on the biographical sketches, obituary notes and eulogies of notable scientists, eight were identified as belonging to an elite group, having authored more than 1000 research publications, which include books, monographs and patents. They were, in chronological order, Thomas Alva Edison, Paul Karrer,...
journal_title：Medical hypotheses
pub_type： 历史文章,杂志文章
doi：10.1016/0306-9877(92)90179-g
更新日期：1992-10-01 00:00:00
abstract：:Primary headaches include migraine, tension, cluster headaches, paroxysmal hemicrania and miscellaneous headaches unassociated with structural lesions. A putative role of the retino-hypothalamic-pineal (RHP) axis in the pathophysiology of primary headaches is reviewed in terms of (1) retinal dysfunction, (2) hypothala...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2005.12.026
更新日期：2006-01-01 00:00:00
abstract：:High blood pressure is an important component of pre-eclampsia. The underlying mechanism of development of hypertension in pre-eclampsia is complicated and still remains obscure. Several theories have been advanced including endothelial dysfunction, uteroplacental insufficiency leading to generalized vasoconstriction,...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2009.03.007
更新日期：2009-08-01 00:00:00
abstract：:Submagnetic domain magnetic fluid particles of approximately 10 nm average diameter complexed with CD4 or monoclonal antibody and then injected into the patient, will localize to the cell membrane of the target cell. These ferrofluid particles will interact with an externally applied rotating magnetic field of rapidly...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/s0306-9877(96)90226-1
更新日期：1996-01-01 00:00:00
abstract：:The most important obstacle for preventing hypertension is the belief that systemic hypertension has no identifiable cause. This belief, hiding the main offender, sodium chloride, causes too much time wasting for combating against hypertension. Accepting that sodium chloride is a drug and re-evaluating the situation a...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2006.02.024
更新日期：2006-01-01 00:00:00
abstract：:There are many observations regarding the behaviour of melanoma which points away from sunshine as the main cause of this tumour. Incidence data shows that the increase is mostly seen for thin melanomas which cannot be attributed to sun exposure but increasing screening over the last 20 years. Melanoma behaves in a si...
journal_title：Medical hypotheses
pub_type： 杂志文章,评审
doi：10.1016/j.mehy.2013.05.031
更新日期：2013-11-01 00:00:00
abstract：:Viral infections are often the etiological agents of severe acute and chronic human diseases. Their peculiar biology usually leads to the need of design specific therapies for each virus, and the eradication of the viruses and the healing of the patients very often are not reached also after decades of theoretical and...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2012.06.004
更新日期：2012-09-01 00:00:00
abstract：:It is suggested that chronic fatigue syndrome/fibromyalgia is caused by virus injury to the calcium channels leading to larger quantities than usual of calcium ions entering the striated muscle cells. Should this be true, then treatment with a calcium antagonist (CA) may possibly be of value. ...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(94)90049-3
更新日期：1994-07-01 00:00:00
abstract：:In the recent hypothesis that hair loss might be a manifestation of metabolic abnormalities particularly hyperglicemia. It has been reported various environmental risk factors affecting hair loss. There is growing evidence on the relationship between prediabetes and worse metabolic profile. However, there are few stud...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2012.09.014
更新日期：2012-12-01 00:00:00
abstract：:A new three barrier, four compartment model for sodium transport in high resistance urinary epithelia is presented. This model provides a unified and simplified mechanistic explanation for sodium transport and its quantitative regulation. Sodium enters the epithelial cell by passive diffusion. Active extrusion occurs ...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(76)90050-5
更新日期：1976-05-01 00:00:00
abstract：:Alzheimer's disease (AD) is the most common neurodegenerative disease and oligodendrocyte degeneration and white matter damage play a critical role in the pathogenesis of AD. FGF/FGF receptor signaling have been implicated in diverse cellular processes including cell apoptosis, survival, adhesion, migration, different...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2012.12.008
更新日期：2013-04-01 00:00:00
abstract：:Periodontal disease is a chronic multifactorial infectious and inflammatory disease associated with several chronic systemic diseases, such as diabetes, cardiovascular diseases (CVD), chronic obstructive pulmonary disease, hypertension, Alzheimer's disease and so on. These same systemic diseases have been associated w...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2020.110276
更新日期：2020-11-01 00:00:00
abstract：:Epidural haematoma in newborn infants is rare, and few specific obstetrical data related to its formation are available in the literature. The aim of this study is to discuss the pathophysiology of this condition. EDH is always a post traumatic lesion and it is only possible if the insult has produced a cleavage of th...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2005.08.045
更新日期：2006-01-01 00:00:00
abstract：:Many embryonic genes may be sets of repeated genes. Processes of differentiation where the quantity of gene activity changes during embryogenesis may not reflect the transcription rate per se but instead be a result of the state of expression of constitutive repeated genes. Such repeated genes (in fact or theory) is d...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(91)90220-s
更新日期：1991-03-01 00:00:00
abstract：:The morphological changes used to confirm a diagnosis of coeliac disease (CD) are precisely those predicted if the surface energy of the interface between duodenal epithelium and the luminal contents were raised to levels comparable to those demonstrated by the hydrophobic nature of the stomach wall. This hypothesis p...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(90)90126-y
更新日期：1990-07-01 00:00:00
abstract：:We develop here the hypothesis that polycystic kidneys (PCK) may maintain, to a certain extent, the ability to perform endocrine functions. We know that patients with adult polycystic kidney disease (APCKD) produce more erythropoietin and maintain a higher hematocrit than patients with other primary diseases of the ki...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(89)90127-8
更新日期：1989-09-01 00:00:00
abstract：:Recently, a mini-review was published in the Medical Hypotheses journal by Usul Afsar entitled 2019-nCoV-SARS-CoV-2 (COVID-19) infection: Cruciality of Furin and relevance with cancer. Previous studies have pointed out that disruption of the proteolytic cleavage of proteins can promote infectious and non-infectious di...
journal_title：Medical hypotheses
pub_type： 信件
doi：10.1016/j.mehy.2020.109893
更新日期：2020-10-01 00:00:00
abstract：:The dominant role of the physical and chemical environment in the development of cancer is challenged. Analyses of the etiology of skin, bladder, respiratory and gastric cancers are presented which demonstrate the considerable extent to which one's health status may modify the initiation and promotion of environmental...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(79)90058-6
更新日期：1979-01-01 00:00:00
abstract：:In Burkitt's lymphoma, dental structures may provide the route for Epstein-Barr virus (EBV) in saliva to penetrate the jaws, thereby promoting tumor formation. In children, EBV could enter tooth sockets exposed following deciduous tooth loss and thereby contact jaw marrow lymphocytes stimulating neoplastic transformat...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(83)90105-6
更新日期：1983-12-01 00:00:00
abstract：:The internal thoracic arteries (ITAs) are a source of "noncoronary collateral circulation" (NCCC), or "noncoronary collateral blood flow" (NCCBF). The hypothesis herein is that enhancement of NCCC may represent an alternative means of myocardial blood supply: (1) Ligature of the ITAs creates a local hypertensive statu...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2009.08.027
更新日期：2010-01-01 00:00:00
abstract：:Patients with chronic kidney disease (CKD) experience co-morbid illnesses, including cardiovascular disease and retinopathy. Sevelamer hydrochloride (Renagel®); a non-calcium phosphate binder reduces coronary artery and aortic calcification as compared to calcium containing phosphate binders and additionally effects i...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2012.12.035
更新日期：2013-04-01 00:00:00
abstract：:Intra-peritoneal adhesions ensuing from surgery or infection may lead to chronic pelvic pain, bowel obstruction, infertility and additional invasive surgery to resolve adhesion-related complications. As a result adhesions are a major clinical, social and economic concern. The cumulative year-on-year direct costs of ad...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2010.11.020
更新日期：2011-03-01 00:00:00
abstract：:In recent years a male-specific but species non-specific mammalian cell surface antigen, the H-Y antigen, has been demonstrated on somatic cells as well as on sperm. This raises some questions regarding unforeseen risks of certain medical procedures, notably blood transfusion. It is stressed that especially the possib...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/0306-9877(80)90132-2
更新日期：1980-11-01 00:00:00
abstract：:Contributory risk factors to premature coronary artery disease (CAD) in premenopausal women are poorly understood and data on this subset of women is lacking. There is growing evidence that the process of inflammation is a part of the atherosclerotic process. Mechanistic insights from animal work suggest that the prof...
journal_title：Medical hypotheses
pub_type： 杂志文章
doi：10.1016/j.mehy.2017.09.010
更新日期：2017-11-01 00:00:00
