Dopaminergic dysfunction: Role for genetic & epigenetic testing in the new psychiatry.

Reward Deficiency Syndrome (RDS), particularly linked to addictive disorders, costs billions of dollars globally and has resulted in over one million deaths in the United States (US). Illicit substance use has been steadily rising and in 2021 approximately 21.9% (61.2 million) of individuals living in the US aged 12 or older had used illicit drugs in the past year. However, only 1.5% (4.1 million) of these individuals had received any substance use treatment. This increase in use and failure to adequately treat or provide treatment to these individuals resulted in 106,699 overdose deaths in 2021 and increased in 2022. This article presents an alternative non-pharmaceutical treatment approach tied to gene-guided therapy, the subject of many decades of research. The cornerstone of this paradigm shift is the brain reward circuitry, brain stem physiology, and neurotransmitter deficits due to the effects of genetic and epigenetic insults on the interrelated cascade of neurotransmission and the net release of dopamine at the Ventral Tegmental Area -Nucleus Accumbens (VTA-NAc) reward site. The Genetic Addiction Risk Severity (GARS) test and pro-dopamine regulator nutraceutical KB220 were combined to induce "dopamine homeostasis" across the brain reward circuitry. This article aims to encourage four future actionable items: 1) the neurophysiologically accurate designation of, for example, "Hyperdopameism /Hyperdopameism" to replace the blaming nomenclature like alcoholism; 2) encouraging continued research into the nature of dysfunctional brainstem neurotransmitters across the brain reward circuitry; 3) early identification of people at risk for all RDS behaviors as a brain check (cognitive testing); 4) induction of dopamine homeostasis using "precision behavioral management" along with the coupling of GARS and precision Kb220 variants; 5) utilization of promising potential treatments include neuromodulating modalities such as Transmagnetic stimulation (TMS) and Deep Brain Stimulation(DBS), which target different areas of the neural circuitry involved in addiction and even neuroimmune agents like N-acetyl-cysteine.

Detection Rate and Radiological Features of Asymptomatic Intracranial Dural Arteriovenous Fistula: Analysis of Magnetic Resonance Imaging Data of 11745 Individuals in the Japanese Brain Check-Up System.

Objective: Asymptomatic intracranial dural arteriovenous fistula (DAVF) is a rare disease that is often undiagnosed before symptom onset. The present study aimed to examine the detection rate and radiological features of asymptomatic intracranial DAVF using brain MRI data obtained from the Japanese brain check-up system. Methods: We retrospectively identified 11745 individuals who underwent brain MRI between January 2010 and December 2014. After a routine brain MRI screening, a definite diagnosis was made based on DSA. Data regarding sex, age, disease location, classification type, and treatment method were extracted from the system database and patients' medical records. Results: Six individuals (0.05%; mean age, 61.0 ± 9.7 years) were diagnosed with definite intracranial DAVF. The intracranial DAVFs were located in the transverse sinus, confluence, and tentorial sinus in 2, 1, and 3 case(s), respectively. Cortical venous reflux was confirmed in four cases (66.7%), and none of the cases had intracranial hemorrhage or venous congestion. All cases had infratentorial lesions and two-thirds were Borden type II/III. Conclusion: The detection rate of asymptomatic intracranial DAVF was 0.05% based on the analysis of MRI data from the brain check-up system. Low-flow shunt and tiny cortical venous reflux were likely missed on MRI.

Detection rates and sites of unruptured intracranial aneurysms according to sex and age: an analysis of MR angiography-based brain examinations of 4070 healthy Japanese adults.

OBJECTIVIE: The purpose of this study was to evaluate the detection rate and occurrence site according to patient sex and age of unruptured intracranial aneurysms detected through MRI and MR angiography (MRA). METHODS: A total of 4070 healthy adults 22 years or older (mean age [± SD] 50.6 ± 11.0 years; 41.9% women) who underwent a brain examination known as "Brain Dock" in the central Tokyo area between April 2014 and March 2015 were checked for unruptured saccular aneurysm using 3-T MRI/MRA. The following types of cases were excluded: 1) protrusions with a maximum diameter < 2 mm at locations other than arterial bifurcations, 2) conical protrusions at arterial bifurcations with a diameter < 3 mm, and 3) cases of suspected aneurysms with unclear imaging of the involved artery. When an aneurysm was definitively diagnosed, the case was included in the aneurysm group. The authors also investigated the relationship between aneurysm occurrence and risk factors (age, sex, smoking history, hypertension, diabetes, and hyperlipidemia). RESULTS: One hundred eighty-eight aneurysms were identified in 176 individuals (detection rate 4.32%), with the detection rate for women being significantly higher (6.2% vs 3.0%, p < 0.001). The average age in the aneurysm group was significantly higher than in the patients in whom aneurysms were not detected (53.0 ± 11.1 vs 50.5 ± 11.0 years). The detection rate tended to increase with age. The detection rates were 3.6% for people in their 30s, 3.5% for those in their 40s, 4.1% for those in their 50s, 6.9% for those in their 60s, and 6.8% for those in their 70s. Excluding persons in their 20s and 80s­age groups in which no aneurysms were discovered­the detection rate in women was higher in all age ranges. Of the individuals with aneurysms, 12 (6.81%) had multiple cerebral aneurysms; no sex difference was observed with respect to the prevalence of multiple aneurysms. Regarding aneurysm size, 2.0­2.9 mm was the most common size range, with 87 occurrences (46.3%), followed by 3.0­3.9 mm (67 [35.6%]) and 4.0­4.9 mm (20 [10.6%]). The largest aneurysm was 13 mm. Regarding location, the internal carotid artery (ICA) was the most common aneurysm site, with 148 (78.7%) occurrences. Within the ICA, C1 was the site of 46 aneurysms (24.5%); C2, 57 (30.3%); and C3, 29 (15.4%). The aneurysm detection rates for C2, C3, and C4 were 2.23%, 1.23%, and 0.64%, respectively, for women and 0.68%, 0.34%, and 0.21%, respectively, for men; ICA aneurysms were significantly more common in women than in men (5.27% vs 2.20%, p < 0.001). Multivariate logistic regression analysis revealed that age (p < 0.001, OR 1.03, 95% CI 1.01­1.04), female sex (p < 0.001, OR 2.28, 95% CI 1.64­3.16), and smoking history (p = 0.011, OR 1.52, 95% CI 1.10­2.11) were significant risk factors for aneurysm occurrence. CONCLUSIONS: In this study, both female sex and older age were independently associated with an increased aneurysm detection rate. Aneurysms were most common in the ICA, and the frequency of aneurysms in ICA sites was markedly higher in women.