Psychiatric treatment seeking and psychosocial impairment among young adults with depression

BACKGROUND: We report data on 1-year prevalence and comorbidity of depression, related impairment, treatment need, and psychiatric treatment among young adults. METHODS: A sample of young urban adults (n=245) mean age 21.8 years was screened from a baseline population of 706 high-school students and given a semistructured clinical interview to evaluate 12-month prevalence of depression, psychosocial functioning according to DSM-IV GAF scale, need for psychiatric treatment, and use of mental health services. RESULTS: One in 10 young adults suffered from depression with associated psychosocial impairment, the female-to-male-ratio being approximately 2:1. Most depressive disorders were comorbid with other DSM-IV disorders, depression usually occurring secondary to other disorders. Comorbidity was related to impairment, treatment need, and treatment contacts. Less than half of the depressed young adults had ever contacted mental health services, and less than one-third reported treatment contacts during the index episode. Males were less likely than females to report previous treatment contacts or intention to refer to mental health services for their problems, but treatment contacts during the index episode were reported equally often by both sexes. CONCLUSIONS: A minority of the severely depressed young adults with associated impairment had sought treatment. Except for subjects with dysthymia, no gender difference emerged in treatment contact rates during the 12-month depression episode. Comorbidity showed important clinical implications by its relation to severity of depression and treatment contacts.     

Cognitive functioning in substance abuse and dependence: a population-based study of young adults

Aims   To investigate whether substance use disorders (SUDs) are associated with verbal intellectual ability, psychomotor processing speed, verbal and visual working memory, executive function and verbal learning in young adults, and to study the associations of SUD characteristics with cognitive performance.
Participants   A population-based sample ( n  = 466) of young Finnish adults aged 21–35 years.
Measurements   Diagnostic assessment was based on all available information from a structured psychiatric interview (SCID-I) and in- and out-patient medical records. Established neuropsychological tests were used in the cognitive assessment. Confounding factors included in the analyses were comorbid psychiatric disorders and risk factors for SUDs, representing behavioural and affective factors, parental factors, early initiation of substance use and education-related factors.
Findings   Adjusted for age and gender, life-time DSM-IV SUD was associated with poorer verbal intellectual ability, as measured with the Wechsler Adult Intelligence Scale–Revised (WAIS-R) vocabulary subtest, and slower psychomotor processing, as measured with the WAIS-R digit symbol subtest. Poorer verbal intellectual ability was accounted for by parental and own low basic education, whereas the association with slower psychomotor processing remained after adjustment for SUD risk factors. Poorer verbal intellectual ability was related to substance abuse rather than dependence. Other SUD characteristics were not associated with cognition.
Conclusions   Poorer verbal intellectual ability and less efficient psychomotor processing are associated with life-time alcohol and other substance use disorders in young adulthood. Poorer verbal intellectual ability seems to be related to parental and own low basic education, whereas slower psychomotor processing is associated with SUD independently of risk factors.     

Angiogenic potential of human mesenchymal stromal cell and circulating mononuclear cell cocultures is reflected in the expression profiles of proangiogenic factors leading to endothelial cell and pericyte differentiation

Endothelial progenitors found among the peripheral blood (PB) mononuclear cells (MNCs) are interesting cells for their angiogenic properties. Mesenchymal stromal cells (MSCs) in turn can produce proangiogenic factors as well as differentiate into mural pericytes, making MSCs and MNCs an attractive coculture setup for regenerative medicine. In this study, human bone marrow‐derived MSCs and PB‐derived MNCs were cocultured in basal or osteoblastic medium without exogenously supplied growth factors to demonstrate endothelial cell, pericyte and osteoblastic differentiation. The expression levels of various proangiogenic factors, as well as endothelial cell, pericyte and osteoblast markers in cocultures were determined by quantitative polymerase chain reaction. Immunocytochemistry for vascular endothelial growth factor receptor‐1 and α‐smooth muscle actin as well as staining for alkaline phosphatase were performed after 10 and 14 days. Messenger ribonucleic acid expression of endothelial cell markers was highly upregulated in both basal and osteoblastic conditions after 5 days of coculture, indicating an endothelial cell differentiation, which was supported by immunocytochemistry for vascular endothelial growth factor receptor‐1. Stromal derived factor‐1 and vascular endothelial growth factor were highly expressed in MSC‐MNC coculture in basal medium but not in osteoblastic medium. On the contrary, the expression levels of bone morphogenetic protein‐2 and angiopoietin‐1 were significantly higher in osteoblastic medium. Pericyte markers were highly expressed in both cocultures after 5 days. In conclusion, it was demonstrated endothelial cell and pericyte differentiation in MSC‐MNC cocultures both in basal and osteoblastic medium indicating a potential for neovascularization for tissue engineering applications.     

Effect of carboxylesterase 1 c.428G?>?A single nucleotide variation on the pharmacokinetics of quinapril and enalapril

Aim

The aim of the present study was to investigate the effects of the carboxylesterase 1 (CES1) c.428G > A (p.G143E, rs71647871) single nucleotide variation (SNV) on the pharmacokinetics of quinapril and enalapril in a prospective genotype panel study in healthy volunteers.

Methods

In a fixed-order crossover study, 10 healthy volunteers with the CES1 c.428G/A genotype and 12 with the c.428G/G genotype ingested a single 10 mg dose of quinapril and enalapril with a washout period of at least 1 week. Plasma concentrations of quinapril and quinaprilat were measured for up to 24 h and those of enalapril and enalaprilat for up to 48 h. Their excretion into the urine was measured from 0 h to 12 h.

Results

The area under the plasma concentration–time curve from 0 h to infinity (AUC_0–∞) of active enalaprilat was 20% lower in subjects with the CES1 c.428G/A genotype than in those with the c.428G/G genotype (95% confidence interval of geometric mean ratio 0.64, 1.00; P = 0.049). The amount of enalaprilat excreted into the urine was 35% smaller in subjects with the CES1 c.428G/A genotype than in those with the c.428G/G genotype (P = 0.044). The CES1 genotype had no significant effect on the enalaprilat to enalapril AUC_0–∞ ratio or on any other pharmacokinetic or pharmacodynamic parameters of enalapril or enalaprilat. The CES1 genotype had no significant effect on the pharmacokinetic or pharmacodynamic parameters of quinapril.

Conclusions

The CES1 c.428G > A SNV decreased enalaprilat concentrations, probably by reducing the hydrolysis of enalapril, but had no observable effect on the pharmacokinetics of quinapril.     

The effect of atorvastatin treatment on serum oxysterol concentrations and cytochrome P450 3A4 activity

Aims

Atorvastatin is known to both inhibit and induce the cytochrome P450 3A4 (CYP3A4) enzyme in vitro. Some clinical studies indicate that atorvastatin inhibits CYP3A4 but there are no well-controlled longer term studies that could evaluate the inducing effect of atorvastatin. We aimed to determine if atorvastatin induces or inhibits CYP3A4 activity as measured by the 4β-hydroxycholesterol to cholesterol ratio (4βHC : C).

Methods

In this randomized, double-blind, placebo-controlled 6 month study we evaluated the effects of atorvastatin 20 mg day⁻¹ (n = 15) and placebo (n = 14) on oxysterol concentrations and determined if atorvastatin induces or inhibits CYP3A4 activity as assessed by the 4βHC : C index. The respective 25-hydroxycholesterol and 5α,6α-epoxycholesterol ratios were used as negative controls.

Results

Treatment with atorvastatin decreased 4βHC and 5α,6α-epoxycholesterol concentrations by 40% and 23%, respectively. The mean 4βHC : C ratio decreased by 13% (0.214 ± 0.04 to 0.182 ± 0.04, P = 0.024, 95% confidence interval (CI) of the difference –0.0595, –0.00483) in the atorvastatin group while no significant change occurred in the placebo group. The difference in change of 4βHC : C between study arms was statistically significant (atorvastatin –0.032, placebo 0.0055, P = 0.020, 95% CI of the difference –0.069, –0.0067). The ratios of 25-hydroxycholesterol and 5α,6α-epoxycholesterol to cholesterol did not change.

Conclusions

The results establish atorvastatin as an inhibitor of CYP3A4 activity. Furthermore, 4βHC : C is a useful index of CYP3A4 activity, including the conditions with altered cholesterol concentrations.     

Effectiveness of a Brief Group Intervention Program for Young Adults with Gaming-Related Problems

International Journal of Mental Health and Addiction - Excessive digital gaming can have unfavorable effects on gamers’ well-being and everyday functioning. The aims of this study were to...     

Central Nervous System and Ocular Manifestations in Puumala Hantavirus Infection

Puumala hantavirus (PUUV), carried and spread by the bank vole (Myodes glareolus), causes a mild form of hemorrhagic fever with renal syndrome (HFRS) called nephropathia epidemica (NE). Acute high fever, acute kidney injury (AKI), thrombocytopenia, and hematuria are typical features of this syndrome. In addition, headache, blurred vision, insomnia, vertigo, and nausea are commonly associated with the disease. This review explores the mechanisms and presentations of ocular and central nervous system involvement in acute NE.