An association study between Heme oxygenase-1 genetic variants and Parkinson's disease.

The blood-brain barrier (BBB) supplies brain tissues with nutrients, filters harmful compounds from the brain back to the bloodstream, and plays a key role in iron homeostasis in the human brain. Disruptions of the BBB are associated with several neurodegenerative conditions including Parkinson's disease (PD). Oxidative stress, iron deposition and mitochondrial impaired function are considered as risk factors for degeneration of the central nervous system. Heme oxygenase (HMOX) degrades heme ring to biliverdin, free ferrous iron and carbon monoxide being the rate-limiting activity in heme catabolism. The isoform HMOX1 is highly inducible in response to reactive oxygen species, which induce an increase in BBB permeability and impair its pathophysiology. Consequently, an over- expression of this enzyme may contribute to the marked iron deposition found in PD. We analyzed the HMOX1 SNPs rs2071746, rs2071747, and rs9282702, a microsatellite (GT) n polymorphism and copy number variations in 691 patients suffering from PD and 766 healthy control individuals. Copy number variations in the HMOX1 gene exist, but these do not seem to be associated with PD risk. In contrast two polymorphisms that modify the transcriptional activity of the gene, namely a VNTR (GT) n and the SNP rs2071746, are strongly associated with PD risk, particularly with the classic PD phenotype and with early onset of the disease. This study indicates that HMOX1 gene variants are associated to the risk of developing some forms of PD, thus adding new information that supports association of HMOX gene variations with PD risk.

A polymorphism located at an ATG transcription start site of the heme oxygenase-2 gene is associated with classical Parkinson's disease.

AIM: Oxidative stress and iron deposition is related to Parkinson's disease (PD). Heme oxygenase 2 (HMOX2) catalyzes the cleavage of the heme ring to form biliverdin with release of iron and carbon monoxide. This study aims to analyze variations in the HMOX2 gene in patients with PD. MATERIALS AND METHODS: We mapped four single nucleotide polymorphisms (SNPs) and copy number variations of the HMOX2 gene in 691 patients with PD and 747 healthy individuals. RESULTS: We identified a highly homogeneous association of the HMOX2 SNP rs2270363 homozygous G/G genotype with patients with classical PD phenotype compared with healthy individuals. We identified three patients with PD and two control individuals with a single copy of the HMOX2 gene. No individuals with zero or more than two gene copies were identified. CONCLUSION: We describe for the first time, copy number variations in the HMOX2 gene and an association of the SNP rs2270363 with PD risk.

LINGO1 gene analysis in Parkinson's disease phenotypes.

BACKGROUND: Parkinson's disease (PD) and essential tremor (ET) may share some etiopathogenic factors. A genome-wide association study has shown that LINGO1 gene variants are associated with increased risk of ET. We hypothesized that LINGO1 variants could increase susceptibility to PD. METHODS: A large series of PD subjects and healthy controls were genotyped for rs9652490 and rs11856808 LINGO1 single nucleotide polymorphisms (SNPs). RESULTS: We found an increased frequency of the rs11856808(T/T) genotype in PD compared with controls (odds ratio = 1.46; corrected P value = 0.02). A recessive genetic model was the best fit for rs11856808 influence on PD (recessive gene action test: corrected P value = 0.01). Stratification analysis showed that rs11856808(T/T) genotype frequency was higher in the tremor-dominant PD and the classical PD (C-PD) subgroups (recessive gene action test for the C-PD subgroup: corrected P value = 0.004). DISCUSSION: Our results indicate that LINGO1 variants could increase risk of PD, specifically those presenting the non-rigid-akinetic phenotypes, which suggests that LINGO1 may have a role in the etiology of tremor in PD at least in the Spanish population.

48,XXYY in a General Adult Psychiatry Department.

The 48,XXYY syndrome is a distinct clinical and genetic entity, with an incidence of 1:17,000 to 1:50,000 newborns. Patients often access mental healthcare services due to behavior problems, such as aggressiveness and impulsiveness, and are frequently intellectually disabled. We report a case of a patient with 48,XXYY syndrome treated in a general adult psychiatry department.A 23-year-old man was frequently admitted to our inpatient psychiatric unit (14 admissions in five years) due to disruptive behavior, including self harm, aggression to objects and animals, and fire-setting behavior, in a context of dysphoric mood and marked impulsivity. Upon observation, the patient had mild intellectual disability, with prominent impulsive and aggressive features and very low tolerance to frustration. His physical examination revealed hypertelorism, increased thickness of neck, acne, sparse body hair, triangular pubic hair distribution, fifth digit clinodactyly, small testicles and penis, and gynecoid pelvis. Laboratory analysis revealed endocrine abnormalities (low plasma testosterone and subclinical hypothyroidism). Cardiac Doppler sonogram was normal. Electroencephalogram revealed only a diffuse slowing electrogenesis, with no etiological specificity. Clinical suspicion of a chromosomal disorder was confirmed by a 48,XXYY karyotype. Subsequent magnetic resonance imaging detected discrete bilateral reduction of the hippocampal formations, possibly related to temporal dysgenesia. Psychopharmacological treatment options met moderate success, with lack of adherence. Other psychosocial treatment interventions ensued, including family therapy and psychoeducation. We underscore the need to be alert for chromosomal disorders, even in a general adult psychiatry department, as a minority of patients may reach adult care without proper diagnosis.

[Depression in cancer patients: diagnostic and therapeutic considerations]. / Depressão no doente oncológico: considerações diagnósticas e terapéuticas.

BACKGROUND AND AIMS: Oncologic diseases currently have a high prevalence and present as one of the leading causes of death in the western world. Clinical depression and emotional distress are often the outcome of the threat these diseases present to individual existence. Although its precise determination is hampered by methodological problems, up to 50% of cancer patients may become clinically depressed and experience intense personal distress. We performed a literature review on screening and evaluating clinical depression in cancer patients (risk factors, instruments and strategies) and its treatment (psychotherapy, drug treatment and care management). METHODS: Non-systematic literature review. The search was performed on Pubmed with the following keywords in title/abstract fields: cancer, oncology, depression, psychiatry, morbidity, screening, treatment, psychotherapy, psychiatric status rating scales, with no time restriction. Articles written in Portuguese, English and Castilian were included. A cross-reference search yielded additional included articles. CONCLUSIONS: Several risk factors for an increased likelihood of clinical depression in oncologic diseases have been identified which, together with screening strategies, including validated scales such as Hospital Anxiety and Depression Scale (HADS), may enhance our ability to detect cases. While not having, for the moment, the highest possible evidence for effectiveness from randomized trials, the treatment strategies for clinical depression in this population should be available and make use of multidisciplinary interventions, including psychopharmacological and psychotherapeutic options. The need for health care workers to spend adequate time with patients is underscored. This not only enhances their ability to detect and treat depression cases but also allows for an empathic and understanding relationship, validating the existence and suffering of the patient.

Heart failure and depression: an association with clinical importance.

Major depression is found in one fifth of heart failure patients, and clinically significant depressive symptoms in almost half. The association of depression and heart failure appears to be related both to the psychological aspects of severe heart disease, and to pathophysiological and psychosocial mechanisms. The presence of depression is associated with a worsening of the prognosis, and increased risk of death, rehospitalization, and functional decline. Detection and treatment of depression should be part of a comprehensive approach to heart failure patients by cardiologists and family doctors. Good quality cardiac care should include psychosocial assessment, strengthening of the doctor-patient relationship and of family and social bonds, and, when appropriate, antidepressants and psychotherapy. Selective serotonin reuptake inhibitors are effective and safe antidepressants in cardiac patients. They should be prescribed in therapeutic doses until sustained remission is obtained. Collaboration between psychiatrists and other specialists at primary and secondary care levels is recommended and contributes to better quality care.

Genetic variability of histamine receptors in patients with Parkinson's disease.

BACKGROUND: Changes in the density and expression of histamine receptors (HRH) have been detected in Parkinson's disease (PD) patients, and HRH antagonists bring about improvements in motor and other symptoms, thus suggesting that HRH play a role in the clinical response of PD patients. This study is aimed to analyse polymorphic variations of HRH in patients with PD. METHODS: Leukocytary DNA from 195 PD patients and a control group of 231 unrelated healthy individuals was studied for the nonsynonymous HRH1Leu449Ser and the promoter HRH2G-1018A polymorphisms by using amplification-restriction analyses. RESULTS: The HRH1Leu449Ser amino acid substitution was identified in two women with late-onset PD whereas it was not observed among healthy subjects. The HRH2G-1018A polymorphism was observed with allele frequencies = 3.59 (95% CI = 1.74-5.44) and 5.0 (95% CI = 3.00-6.96) for patients with PD and healthy controls, respectively. These frequencies were independent of gender and age of onset of the disease. Multiple comparison analyses revealed that differences were not statistically significant. CONCLUSION: These results indicate that the polymorphisms analyzed are not a major risk factor for PD, although the HRH1Leu449Ser amino acid substitution might be related to PD.

Nonsynonymous polymorphisms of histamine-metabolising enzymes in patients with Parkinson's disease.

OBJECTIVE: To analyze genetically based impairment in histamine-metabolising enzymes in patients with Parkinson's disease (PD). METHODS: Leukocytary DNA from 214 PD patients and a control group of 295 unrelated healthy individuals was studied for nonsynonymous histamine N-methyltransferase (HNMT) and diamine oxidase (ABP1) polymorphisms by using amplification-restriction analyses. RESULTS: An association of the HNMT Thr105Ile polymorphism, but not of the ABP1 His645Asp polymorphism, with PD was observed. Patients with PD showed a higher frequency of homozygous HNMT genotypes leading to high activity with a gene-dose effect (P < 0.001), as compared to healthy subjects. These findings were independent of gender, but the association with the HNMT polymorphism is higher among patients with late-onset PD (P < 0.0001). CONCLUSION: These results, combined with previous findings indicating alterations in histamine levels in patients with PD, suggest that alterations of histamine homeostasis in the SNC are associated with the risk for PD.