Adiponectin Gene Polymorphisms: A Case-Control Study on Their Role in Late-Onset Alzheimer's Disease Risk.

Adiponectin, a hormone secreted by adipose tissue, plays a complex role in regulating metabolic homeostasis and has also garnered attention for its potential involvement in the pathogenesis of late-onset Alzheimer's disease (LOAD). The objective of this study was to investigate the association of ADIPOQ variants with plasma adiponectin levels and LOAD risk in subjects from the Slovak Caucasian population. For this purpose, 385 LOAD patients and 533 controls without cognitive impairment were recruited and genotyped for a total of eighteen ADIPOQ single nucleotide polymorphisms (SNPs). Both single-locus and haplotype-based logistic regression analyses were employed to assess the association of SNPs with LOAD risk, while linear regression analysis was used to explore their influence on adiponectin levels in LOAD patients. ADIPOQ variants rs822395 and rs2036373 in intron 1 were found to significantly elevate total adiponectin levels after accounting for several potential confounders. Additional SNPs in the 5' region and intron 1 exhibited a non-significant trend of association with adiponectin. However, none of the ADIPOQ SNPs showed an association with LOAD risk, neither in the whole-group analysis nor in subgroup analyses after stratification for sex or the APOE ε4 allele, a well-established LOAD risk factor. In summary, while adiponectin has emerged as a potential contributor to the development of LOAD, this study did not unveil any significant involvement of its gene variants in susceptibility to the disease.

TREM2 coding variants in Slovak Alzheimer's disease patients.

BACKGROUND: Triggering receptor expressed on myeloid cells 2 (TREM2) is an important modulator of innate immune responses. In the human brain, TREM2 is primarily expressed on microglia and is involved in cell survival, phagocytosis, and regulation of inflammation. TREM2 dysfunction has been linked to the pathogenesis of various neurodegenerative diseases including Alzheimer's disease (AD). Rare coding variants of the TREM2 gene have been reported to modulate AD risk in several populations, however, data on their association with susceptibility to AD in the Slovak population have been missing. METHODS: We have analyzed 10 non-synonymous coding variants located in TREM2 exon 2 by direct sequencing in 270 late-onset Alzheimer's disease (LOAD) patients and 331 controls. RESULTS: Four out of 10 TREM2 mutant variants have been identified in the analyzed groups, namely rs75932628 C > T (R47H), rs142232675 C > T (D87N), rs143332484 C > T (R62H), and rs2234253 G > T (T96K). R47H was found only in the AD group, while T96K was present only in the controls. Although no significant association between TREM2 coding variants and LOAD susceptibility has been detected, the observed odds ratio (OR) of 3.69 for R47H carriers suggests an increased risk of LOAD for this variant in the Slovak population. Moreover, we also found a higher OR for the rs143332484-T allele in APOEε4 non-carriers (1.99) when compared to APOEε4 carriers (0.62). CONCLUSIONS: Our results suggest an impact of specific TREM2 rare coding variants on AD risk in the Slovak population.

Self-Amputation in Patient with Body Integrity Dysphoria in Comorbidity with Gender Dysphoria: A Case Report.

We present a rare, atypical case of a 24-year-old transgender male (assigned as a female at birth) admitted to the hospital after the planned self-amputation of his left hand. The patient described his motivation for this self-amputation as coming from deep-rooted and persistent feelings that this hand was not a part of his body. He identified himself as having, according to internet peer group definition, body integrity identity disorder. This condition is now referred to as body integrity dysphoria (BID). This patient was later diagnosed as having gender dysphoria and other conditions, including bipolar disorder and gaming disorder. The follow-up 2 years after self-amputation is presented, during which, despite antipsychotic and antidepressant treatment, the symptoms of BID remained unchanged and the high variability of other psychopathology was observed. This is an unusual case of BID simply because several other comorbidities are presented. Like many other rare clinical situations, this case also presents a particular challenge to our understanding of the dynamics and interrelationships between comorbidities, raising concerns and questions.

Diagnostic criteria for enduring sexual dysfunction after treatment with antidepressants, finasteride and isotretinoin.

BACKGROUND: A set of enduring conditions have been reported in the literature involving persistent sexual dysfunction after discontinuation of serotonin reuptake inhibiting antidepressants, 5 alpha-reductase inhibitors and isotretinoin. OBJECTIVE: To develop diagnostic criteria for post-SSRI sexual dysfunction (PSSD), persistent genital arousal disorder (PGAD) following serotonin reuptake inhibitors, post-finasteride syndrome (PFS) and post-retinoid sexual dysfunction (PRSD). METHODS: The original draft was designed using data from two published case series (Hogan et al., 2014 and Healy et al., 2018), which represent the largest public collections of data on these enduring conditions. It was further developed with the involvement of a multidisciplinary panel of experts. RESULTS: A set of criteria were agreed upon for each of the above conditions. Features of PSSD, PFS and PRSD commonly include decreased genital and orgasmic sensation, decreased sexual desire and erectile dysfunction. Ancillary non-sexual symptoms vary depending on the specific condition but can include emotional blunting and cognitive impairment. PGAD presents with an almost mirror image of unwanted sensations of genital arousal or irritability in the absence of sexual desire. A new term, post-SSRI asexuality, is introduced to describe a dampening of sexual interest and pleasure resulting from a pre-natal or pre-teen exposure to a serotonin reuptake inhibitor. CONCLUSIONS: These criteria will help in both clinical and research settings. As with all criteria, they will likely need modification in the light of developments.

Impact of MMP2 rs243865 and MMP3 rs3025058 Polymorphisms on Clinical Findings in Alzheimer's Disease Patients.

Alzheimer's disease (AD) is a chronic neurodegenerative disease of the central nervous system with higher prevalence in elderly people. Despite numerous research studies, the etiopathogenesis of AD remains unclear. Matrix metalloproteinases (MMPs) are endopeptidases involved in the cleavage of extracellular matrix proteins and basement membrane compounds. In the brain, the pathological role of MMPs includes the disruption of the blood-brain barrier leading to the induction of neuroinflammation. Among various MMPs, MMP-2 and MMP-3 belong to candidate molecules related to AD pathology. In our study, we aimed to evaluate the association of MMP2 rs243865 and MMP3 rs3025058 polymorphisms with AD susceptibility and their influence on age at onset and MoCA score in patients from Slovakia. Both MMP gene promoter polymorphisms were genotyped in 171 AD patients and 308 controls by the PCR-RFLP method. No statistically significant differences in the distribution of MMP2 rs243865 (-1306 C>T) and MMP3 rs3025058 (-1171 5A>6A) alleles/genotypes were found between AD patients and the control group. However, correlation with clinical findings revealed later age at disease onset in MMP2 rs243865 CC carriers in the dominant model as compared to T allele carriers (CC vs. CT+TT: 78.44 ± 6.28 vs. 76.36 ± 6.39, p = 0.036). The results of MMP3 rs3025058 analysis revealed that 5A/6A carriers in the overdominant model tended to have earlier age at disease onset as compared to other MMP3 genotype carriers (5A/6A vs. 5A/5A+6A/6A: 76.61 ± 5.88 vs. 78.57 ± 6.79, p = 0.045). In conclusion, our results suggest that MMP2 rs243865 and MMP3 rs3025058 promoter polymorphisms may have influence on age at onset in AD patients.

Association of CD33 rs3865444:C˃A polymorphism with a reduced risk of late-onset Alzheimer's disease in Slovaks is limited to subjects carrying the APOE ε4 allele.

CD33 rs3865444:C>A single nucleotide polymorphism (SNP) has been previously associated with the risk of late-onset Alzheimer's disease (LOAD); however, the results have been inconsistent across different populations. CD33 is a transmembrane receptor that plays an important role in AD pathogenesis by inhibiting amyloid ß42 uptake by microglial cells. In this study, we aimed to validate the association between rs3865444 and LOAD risk in the Slovak population and to evaluate whether it was affected by the carrier status of the major LOAD risk allele apolipoprotein (APOE) ε4. CD33 rs3865444 and APOE variants were genotyped in 206 LOAD patients and 487 control subjects using the polymerase chain reaction-restriction fragment length polymorphism method and direct sequencing, respectively. Logistic regression analysis revealed a significant association of rs3865444 A allele with a reduced LOAD risk that was only present in APOE ε4 allele carriers (AA + CA versus CC: p = .0085; OR = 0.45; 95% CI = 0.25-0.82). On the other hand, no such association was found in subjects without the APOE ε4 (p = .75; OR = 0.93; 95% CI = 0.61-1.42). Moreover, regression analysis detected a significant interaction between CD33 rs3865444 A and APOE ε4 alleles (p = .021 for APOE ε4 allele dosage and p = .051 for APOE ε4 carriage status), with synergy factor (SF) value of 0.49 indicating an antagonistic effect between the two alleles in LOAD risk. In conclusion, our results suggest that CD33 rs3865444:C˃A substitution may reduce the risk of LOAD in Slovaks by antagonizing the effect conferred by the major susceptibility allele APOE ε4.

A Novel Association of Polymorphism in the ITGA4 Gene Encoding the VLA-4 α4 Subunit with Increased Risk of Alzheimer's Disease.

Alzheimer's disease (AD) is the most prevalent cause of dementia in elderly people worldwide. Many studies support the hypothesis that the inflammation of the CNS contributes to the neurodegeneration and disease progression. The integrin molecule α4ß1, also known as very late antigen 4 (VLA-4), belongs to adhesion molecules that activate the inflammatory process through the migration of immune cells into the CNS. Therefore, the objective of our study was to analyze the association between two polymorphisms located in the ITGA4 gene encoding the α4 subunit of VLA-4 and the risk of AD. 104 late-onset AD patients and 206 control subjects from Slovakia were genotyped for ITGA4 gene SNP polymorphism rs113276800 (-269C/A) and rs1143676 (+3061A/G). The same study cohorts were also genotyped for the APOE-ε4, which is a known genetic factor associated with increased risk of AD developing. ITGA4 polymorphism analysis revealed significantly higher frequency of the +3061AG carriers in AD group compared to the controls (P ≤ 0.05). Following the APOE-ε4 stratification of study groups, the association remained significant only in APOE-ε4 noncarriers. Our study suggests a novel association of ITGA4 +3061A/G polymorphism with AD and its possible contribution to the disease pathology.

Electroconvulsive Therapy Treatment in a Patient With Neurosyphilis and Psychotic Disorder: Case Report and Literature Review.

Syphilis is an infectious disease caused by Treponema pallidum that presents clinically in different ways. Over recent years, an upsurge of new cases of syphilis has been reported, often in combination with human immunodeficiency virus infection. The clinical picture is changing because of the widespread use of antibiotics, and psychiatric manifestations may be the main reason why patients seek medical help. In most cases, treatment with penicillin and psychotropic medication is effective. Electroconvulsive therapy (ECT) is rarely used for the psychiatric manifestations of neurosyphilis: we identified only 19 cases in the literature. We report here on a 40-year-old man newly diagnosed with neurosyphilis during hospitalization for a psychotic state with depression and also review the literature. He was treated with 2 courses of penicillin and several antipsychotics. The ECT was indicated because he failed to respond well to antipsychotic treatment and developed a high risk of dangerous behavior. A series of 8 sessions of ECT rapidly relieved the psychotic symptoms.