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Shared genetic risk and causal associations between Post-traumatic stress disorder and migraine with antithrombotic agents and other medications.

Post-traumatic stress disorder (PTSD) is a psychiatric disorder that frequently co-occurs with pain disorders including migraine. There are proposed biological, genetic and environmental factors associated with both PTSD and migraine suggesting shared etiology. Genome-Wide Association Studies (GWAS) have been used to identify genomic risk loci associated with various disorders and to investigate genetic overlap between traits. There is a significant genetic correlation between PTSD and migraine with no evidence of a causal relationship that could be attributed to pleiotropy. Cross-disorder genetic analyses were applied to investigate the genetic overlap and causal associations using GWAS summary statistics of PTSD (n&#xa0;=&#xa0;214408), migraine (n&#xa0;=&#xa0;873341) and 23 medication use traits (n&#xa0;=&#xa0;78808-305913) including anti-depressants, anti-migraine preparations and beta-blocking agents. Across the entire genome, anti-thrombotic agents had a significant and negative genetic correlation with PTSD (rG&#xa0;=&#xa0;-0.2, P FDR&#xa0;=&#xa0;0.032) and a positive genetic correlation with migraine (rG&#xa0;=&#xa0;0.26, P FDR&#xa0;=&#xa0;2.23 x 10-8). PTSD showed significant genetic correlation with 11 other medication use traits including beta blocking agents (rG&#xa0;=&#xa0;-0.11, P FDR&#xa0;=&#xa0;0.034). Of the 2495 genomic regions tested, PTSD showed significant local genetic correlation with 12 medication use traits at 43 loci; while migraine showed significant genetic correlation with only anti-inflammatory agents and anti-rheumatic products at locus 12:57522282-57607142 (DAB1) (P&#xa0;<&#xa0;2 x 10-5). The genetic liability to PTSD had a causal effect on increased risk of using pain medication such as opioids (&#x3b2; ivw&#xa0;=&#xa0;0.59, P&#xa0;=&#xa0;5.21 x 10-5) while the genetic liability to migraine had a causal effect on the increased risk of using anti-thrombotic agents (&#x3b2; ivw&#xa0;=&#xa0;0.59, P&#xa0;=&#xa0;1.69 x 10-7). The genes in the genomic regions shared between PTSD and medication use traits were enriched in neural-related pathways such as neuron development, neurogenesis and protein kinase activity. These results provide further insight into the genetically controlled biological and environmental factors underlying the shared etiology between PTSD and migraine. The identified biomarkers can be used as a basis for investigation as potential drug targets for both disorders. These findings are significant for drug re-purposing and treatment of PTSD and migraine using monotherapy.

GWAS

Minor tranquillizers in somatic disorders.

Conclusive evidence of improved outcome due to adjunctive anxiolytic therapy in some somatic conditions is lacking. However, such therapy may facilitate patient management without being "curative". The resulting improved feeling of well-being may be of value in the management of gastrointestinal disorders, migraine and myocardial infarction. Negative effects may be observed in acute respiratory conditions, especially during acute exacerbations of chronic conditions, with the administration of benzodiazepines; hence they should be used with caution. The use of these agents in treating persons with hypertension seems to be of no value and may even be detrimental. Careful evaluation of each case is desirable, and treatment should be planned with its termination in mind.

Angina Pectoris

Complex Genetics and Regulatory Drivers of Hypermobile Ehlers-Danlos Syndrome: Insights from Genome-Wide Association Study Meta-analysis.

BACKGROUND: Hypermobile Ehlers-Danlos syndrome (hEDS) is the most common subtype of EDS, a group of heritable connective tissue disorders. Clinically, hEDS is defined by generalized joint hypermobility and chronic musculoskeletal pain, but its impact extends beyond the musculoskeletal system. Affected individuals frequently experience autonomic, gastrointestinal, immune, and neuropsychiatric involvement, highlighting both the multisystemic nature of the condition and challenges of diagnosis. In contrast to other EDS subtypes with defined genetic causes, the molecular basis of hEDS has remained elusive. METHODS: We conducted a genome-wide association study (GWAS) of hEDS across three case controls studies, including 1,815 cases and 5,008 ancestry-matched controls. Fixed-effects meta-analysis of 6.2 million variants was complemented with LDAK gene-based association testing, transcriptome-wide association studies, and integrative annotation across multiple tissues and cell types including eQTLs, enhancer marks and open chromatin accessibility profiles, supported by luciferase assays on one candidate variant. LD-score genetic correlations were assessed between hEDS and 19 frequently reported comorbid conditions. RESULTS: Two loci reached genome-wide significance, including a regulatory region near the atypical chemokine receptor 3 gene (ACKR3) on chromosome 2. Functional annotation supports ACKR3 risk alleles colocalize with eQTLs in tibial nerve, alter enhancer activity, and generate a de novo AHR transcription factor regulatory site, implicating neuroimmune and pain signaling pathways. Gene-based and transcriptome-wide analyses identified common variants in a locus containing multiple candidates, including SLC39A13, a zinc transporter critical for connective tissue development previously implicated in a rare form of EDS, and PSMC3, a gene involved in central nervous system development. LD-score regression revealed significant genetic correlations between hEDS and joint hypermobility, myalgic encephalomyelitis/chronic fatigue syndrome, fibromyalgia, depression, anxiety, autism spectrum disorder, migraine, and gastrointestinal diseases. CONCLUSIONS: These results establish the first evidence of common variant contributions to hEDS, supporting a complex, multisystem model involving neuroimmune-stromal dysregulation. Our findings add novel indications to hEDS pathogenesis and provide solid foundations for future molecular definition and therapeutic discovery.

Genome-wide association study

Genetic study of infantile spasm with hypsarrhythmia.

Infantile spasms (IS) appear to be a distinct syndrome complicated by heterogeneous etiology. Family data support a multifactorial model involving a polygenic determination of susceptibility to IS but requiring environmental factors such as anoxia, birth trauma, or immunization to precipitate seizures. The empiric recurrence risk among siblings was estimated to be 15 +/- 3 and for all first degree relatives as 7 +/- 5 per 1,000. These risks should be interpreted with caution since possible heterogeneity of IS may result in the occurrence of families in which cases are presumably totally environmental, and other rare families which may be segregating for an autosomal recessive disorder. Careful review of involved medical and family histories and a thorough physical examination should permit discrimination among these possibilities.

Epilepsy

Migraine: A blood disorder?

It is suggested that a primary abnormality of platelet function can account for the diverse clinical, biochemical, and pathological findings reported in migraine.

Animals

The potential use of videotape in teaching psychosomatics.

Psychosomatists should admit that so far they have largely failed in communicating their knowledge and skills to those outside a limited circle. As a result many sick people suffer more than they need. Students of animal behaviour have made better use of sound and videotape to illustrate the normal and abnormal than students of human behaviour. Some of the reasons for this are examined. In teaching and learning psychosomatics the potential of videotape has yet to be realised. The article presents some such possibilities and is illustrated by edited versions of the author's experience over four years in a busy outpatient clinic of (1) characteristic life situations and attitudes in three disorders: Multiple Sclerosis, Migraine and auto immune disease, (2) the psychological management of an intractable case of Asthma over two years (approx. 32h of therapy).

Adolescent

Stress and disease: the missing link. A vasospastic theory. III. Stress, vasospasm and general disease.

The potential importance of vasospasm, with or without consequent thrombosis, as a mechanism in general disease is discussed and the evidence examined in one organ, namely the brain. It is concluded that vasospasm might be important in a number of neurological disorders, including migraine, epilepsy, and even some of the schizophrenia-like illnesses. Repeated ischaemic cell damage from vasospasm is also discussed as a possible factor initiating autoimmune disease and cancer. The similarities between viral transformation and neoplasia have led to the proposition that much cancer might be explained if as a species we have evolved by the gradual build-up of viruses.

Arteries

A study of agoraphobic housewives.

Thirty married agoraphobic women referred to out-patient clinics in Edinburgh were compared with 'normal' controls (selected from GP records and screened for the absence of psychiatric symptoms) matched on age, sex social class and marital status. The agoraphobics' husbands were similarly compared with the husbands of the controls. On most measures of attitudes, behaviour, domestic organization and marital interaction, the 2 groups were strikingly similar.

Adolescent

[Attacks of acute headache (author's transl)].

Acute headaches are in most cases significant symptoms or premonitary signs of a neurological condition. From a semiological point of view, they may be: (i) isolated, (ii) associated with neurological symptoms (ophtalmoplegia, hemiplegia, hemianesthesia...). From an etiological point of view, the haemorragic conditions are predominant (30%): encephalic vascular malformation with or without subarachnoidal haemorragia (21%), subarachnoidal haemorragia without malformation (6%) and subdural haematoma (3%). Two types of conditions are also frequently observed: ischemic attacks (22,3%) and inflammatory meningeal syndromes (12%). Rare cases with hypophyseal adenomas, ischemic attacks under oestro-progestative treatment, accidents of mono-amine-oxydase inhibitors and multiple sclerosis are observed. 23,8% of the cases remained without any precise diagnosis. One of the interesting points in the acute headache issue is the possibility of discovering an encephalic vascular malformation without any important bleeding and, therefore, good conditions for surgery.

Acute Disease