Even animal studies have suggested that tryptophan itself "when ingested by susceptible individuals either alone or in combination with some other component in the product, results in the pathological features in EMS".At the time of the outbreak, Showa Denko had recently made alterations to its manufacturing procedures that were thought to be linked to the possible origin of the contaminants detected in the affected lots of tryptophan. A key change was the reduction of the amount of activated charcoal used to purify each batch from >20 kg to 10 kg. A portion of the contaminated batches had also bypassed another filtration step that used reverse-osmosis to remove certain impurities. Additionally, the bacterial culture used to synthesize tryptophan was a strain of Bacillus amyloliquefaciens that had been genetically engineered to increase tryptophan production. Although the prior four generations of the genetically engineered strain had been used without incident, the fifth generation used for the contaminated batches was thought to be a possible source of the impurities that were detected. This has been misused to argue that the genetic engineering itself was the primary cause of the contamination, a stance that was heavily criticized for overlooking the other known non-GMO causes of contamination, as well as for its use by anti-GMO activists as a way to threaten the development of biotechnology with false information.
The symptoms are severe enough to cause significant distress or significant impairment in personal, family, social, educational, occupational or other important areas of functioning and do not represent the exacerbation of a mental disorder. Royal College of Obstetricians and Gynecologists and the International Society for the Study of Premenstrual Disorders
Other organizations that have published diagnostic criteria for PMDD include the Royal College of Obstetricians and Gynecologists and the International Society for the Study of Premenstrual Disorders (ISPMD). The ISPMD was a consensus group established by an international multidisciplinary group of experts. The groups diagnostic criteria for PMDD focuses on the cyclic nature of the symptoms occurring during the luteal phase of the menstrual cycle, as well as the symptoms being absent after menstruation and before ovulation and causing significant impairment. The ISPMD diagnostic criteria for PMDD do not specify symptom characteristics or number of symptoms. Differential diagnosis
A critical part of diagnosing PMDD is ruling out underlying psychiatric disorder or physical illness that can cause similar symptoms. That exhibits premenstrual exacerbation, the menopausal transition, hyperthyroidism, hypothyroidism, as well as other mood disorders. Furthermore, many medical disorders are worsened prior to ordering menses, but these typically do not present strictly during the luteal phase. Mood disorders – there is potential for patients to have psychiatric disorders with superimposed PMDD or psychiatric disorders.