Global Journal of Medical Research, A: Neurology & Nervous System, Volume 23 Issue 3

identifying the trait are complex and multi-faceted. Some, but not all, will be discussed here for the purpose of illustration. The most fundamental reason that the neuronal hyperexcitability trait has been so difficult to identify is that the trait has heretofore been undetectable by any form of laboratory testing, neuroimaging, or electroencephalography. Hyperexcitable neurons, like a hive of irritable bees, cannot be distinguished from normoexcitable neurons until the metaphorical bees are disturbed. However, even then, the brain does not become hyperactive as a whole. Rather, the pathological hyperactivity occurs in the brain’s microcircuitry [81], where it can easily be overlooked or considered to be normal on diagnostic studies. The same challenge is experienced clinically, as carriers of the trait can be completely asymptomatic until something or someone begins to stress them. However, even when symptoms begin to appear, they are commonly accepted as normal both because the neuronal hyperexcitability trait is harbored by such a large fraction of society and because the symptoms primarily involve the same cognitive-emotional states that every person may experience from time to time. Another reason that the neuronal hyperexcitability trait has remained so difficult to identify is that stress-inducing circumstances are highly specific to the individual and, in most cases, only really known by the individual. This makes it difficult to assess the appropriateness of the symptoms to the circumstances that seem to precipitate them. Also, due to the variable time-course of kindling, symptom-onset can be delayed by days, weeks, or months [82], thus adding to the difficulty of assessing the appropriateness of the symptoms. Yet another reason that the neuronal hyperexcitability trait has remained so elusive is that the diagnosis of psychiatric disorders has traditionally been symptom-based rather than pathology-based. Hence, the signs and symptoms of neuronal hyperexcitability, which can be highly diverse due to the high diversity of neuronal circuits and firing patterns, are generally viewed as different syndromes rather than as exacerbations of a shared neurophysiological abnormality [83, 84]. This, in turn, has treatment implications that can lead clinicians even further down the wrong path due to current prescribing habits. Since the development of the monoamine hypothesis of depression, prescribers have been strongly entrained to treat most psychiatric disorders with antidepressants. However, based on resting vital-sign measurements (the diagnostic value of which will be discussed later), the neuronal hyperexcitability trait is harbored by approximately 4 out of 10 persons [67, 85, 86]. This estimate is corroborated by the fact that anticonvulsants and other brain-calming drugs had, throughout most of recorded history, been the mainstay of medical treatment for a wide range of emotional and physical ailments [87]. Today, in the wake of the antidepressant revolution, the use of anticonvulsants has been relegated to bipolar spectrum disorder [67, 88]. The problem with this diagnostically-based change is that bipolar spectrum disorder is often misdiagnosed as unipolar depressive disorder [89-92]. This error is further complicated by the fact that antidepressants can have beneficial effects in bipolar spectrum patients despite the fact that they do not address the core physiological abnormality in the disorder [72]. All of these barriers to recognizing the neuronal hyperexcitability trait underscore the need to more easily identify the trait. VI. T oward an O bjective M ethod of I dentifying the N euronal H yperexcitability T rait In recent years, an explosion of clinical studies has identified an association between resting vital-sign measurements and the later development of various psychiatric and general medical conditions. In a longitudinal study involving more than one million men in Sweden, Latvala et al. [93] found that subtle elevations in resting heart rate (RHR) were predictive of the later development of generalized anxiety disorder, obsessive- compulsive disorder, and schizophrenia. Similarly, Blom et al. [94] found that adolescent girls with emotional disorders had increased resting respiratory rates (RRR) in comparison to healthy controls. Persons with higher resting heart and respiratory rates have also been found to be at increased risk of developing a wide range of chronic physical illnesses, including diabetes [95-98], high blood pressure [99-101], cardiovascular disease [102-107], cerebrovascular disease [108-110], cancer [110-112], dementia [113], and all-cause mortality [110, 114]. The subtle vital-sign elevations with which these illnesses are associated are thought to be the consequence of a tonic elevation in basal neurological activity in those persons who inherit the genes for neuronal hyperexcitability [115]. This is the MCNH explanation for why the lifespan of persons with severe mental illness tends to be much shorter than the general population [115]. The reason that psychiatric and “functional” physical symptoms would tend to precede the development of diagnosable physical abnormalities is that the cognitive-emotional system is more expressive of neuronal excitation than other organs and systems of the body [116]. The physical consequences would tend to be delayed because they would express the gradual erosive effects of neuronal hyperexcitability, which can take years or even decades to occur [115]. Thus, there is mounting evidence that the neuronal hyperexcitability trait can be identified objectively [67, 115]. It has been estimated that, in the absence of any significant cardiorespiratory disease, confounding medications, or substances of abuse, an RHR above 75 9 Year 2023 Global Journal of Medical Research Volume XXIII Issue III Version I ( D ) A © 2023 Global Journals Untangling Psychology from Biology in the Treatment of Psychiatric Disorders