A Review on Attachment and Adolescent Substance Abuse: Empirical Evidence and Implications for Prevention and Treatment

Background: This paper reviews research on the relation of attachment and substance use disorders (SUD) in adolescence. Based on a theoretical introduction, we review evidence for a possible general link between SUD and insecure attachment, for links between specific forms of SUD and specific patterns of attachment, and for studies on family patterns of attachment in adolescence. Methods: Using medical and psychological databases, we identified 10 studies on adolescent SUD and another 13 studies on adult SUD. Results: Empirical evidence strongly supports the assumption of insecure attachment in SUD samples. With regard to specific patterns of attachment, results mainly point towards fearful and dismissing-avoidance, whereas single studies report preoccupied and unresolved patterns. Results indicate different patterns of attachment in different groups of substance abusers, that is, fearful-avoidant attachment in heroin addicts and more heterogeneous results in abusers of other substances. Explorative data suggest different types of insecure family attachment patterns, which might imply different functions of substance abuse and lead to different treatment recommendations. Methodological problems such as poor assessment of SUD and the use of different measures of attachment limit comparability. Conclusions: Although a lot of research is still needed to address the unknowns in the relation between attachment and SUD, there is strong evidence for a general link between SUD and insecure attachment. Data on connections between different patterns of attachment and different pathways towards SUD are less conclusive but mainly point to disorganized and externalizing pathways. Evidence suggests that fostering attachment security might improve the outcome of state-of-the-art approaches in both early interventional treatment and prevention. Implications for individual and family approaches are outlined.     

Tamoxifen inhibits acidification in cells independent of the estrogen receptor

Tamoxifen has been reported to have numerous physiological effects that are independent of the estrogen receptor, including sensitization of resistant tumor cells to many chemotherapeutic agents. Drug-resistant cells sequester weak base chemotherapeutics in acidic organelles away from their sites of action in the cytosol and nucleus. This work reports that tamoxifen causes redistribution of weak base chemotherapeutics from acidic organelles to the nucleus in drug-resistant cells. Agents that disrupt organelle acidification (e.g., monensin, bafilomycin A1) cause a similar redistribution. Measurement of cellular pH in several cell lines reveals that tamoxifen inhibits acidification of endosomes and lysosomes without affecting cytoplasmic pH. Similar to monensin, tamoxifen decreased the rate of vesicular transport though the recycling and secretory pathways. Organellar acidification is required for many cellular functions, and its disruption could account for many of the side effects of tamoxifen.     

Selective Na+/H+ exchange inhibition by cariporide reduces liver fibrosis in the rat

The aim of this study was to evaluate the effect of cariporide, a selective Na(+)/H(+) exchange inhibitor, on isolated and cultured hepatic stellate cells (HSCs) and in 2 in vivo models of rat liver fibrosis. Platelet-derived growth factor (PDGF)-induced HSC proliferation, evaluated by measuring the percentage of bromodeoxyuridine-positive cells, was significantly inhibited by cariporide, with a maximal effect at 10 micromol/L. Incubation with cariporide did not inhibit PDGF-induced extracellular-regulated kinase 1/2 (ERK1/2), Akt (a downstream component of the phosphatidylinositol [PI]-3 kinase pathway), and protein kinase C (PKC) activation but reduced PDGF-induced activation of the Na(+)/H(+) exchanger, with a maximal effect at 10 micromol/L. Rats treated with dimethylnitrosamine (DMN; 10 mg/kg) for 1 and 5 weeks received a diet with or without 6 ppm cariporide. Treatment with cariporide reduced the degree of liver injury, as determined by alanine aminotransferase (ALT) values, also when administered after the induction of hepatic damage. This was associated with reduced HSC activation and proliferation and reduced collagen deposition, as determined by morphometric evaluation of alpha-smooth muscle actin (SMA)/proliferating cell nuclear antigen-positive cells and percentage of Sirius red-positive parenchyma, respectively. Moreover, cariporide was also able to reduce alpha(1)I procollagen messenger RNA (mRNA) expression. Similar effects were observed in bile duct-ligated (BDL) rats. In conclusion, selective inhibition of the Na(+)/H(+) exchanger by cariporide may represent an effective therapeutic strategy in the treatment of hepatic fibrosis.     

Acute lymphoblastic leukemia of childhood: identification of two distinct regions of deletion on the short arm of chromosome 12 in the region of TEL and KIP1

Cytogenetic analysis of acute lymphoblastic leukemia (ALL) of childhood identified nonrandom chromosomal abnormalities of the short arm of chromosome 12. The alterations include deletions that are thought to be indicative of the presence of a tumor suppressor gene that is mutated on the remaining allele. To refine further the chromosomal localization of this gene, we analyzed the loss of heterozygosity (LOH) of chromosome 12 in 100 primary ALL samples using 22 polymorphic markers and identified two distinct smallest common deleted regions on chromosome 12p13. One region is flanked by D12S77 and D12S98 and has a size of 4 cM. Twenty-six percent of informative patients showed LOH in this region. This region may contain the TEL gene. The other region is flanked by D12S269 and D12S308 including the KIP1 gene. Forty-four percent of informative patients showed LOH in this second region. Mutational analysis of KIP1 using polymerase chain reaction-single- strand conformation polymorphism analysis and Southern blot analysis showed no homozygous deletions and point mutations suggesting that the altered gene in this second region is not the KIP1. Clinical data showed that LOH of 12p was demonstrated more frequently in precursor-B ALLs (32 of 80; 40%) than in T-ALLs (1 of 20; 5%) (P = .0027). Furthermore, patients with 12p LOH were younger (P = .013), with a lower DNA index (P = .046), but they had the same survival rates at 3 years. In summary, these data suggest that two different tumor suppressor genes are on chromosome arm 12p, which act separately in the development of childhood precursor-B ALLs. One of the tumor suppressor genes is in the region the KIP1 gene, but our data suggest this gene is not abnormal. The other target is in the region of the TEL gene; and this candidate deserves further study.     

Reactions of stroke patients to their health status

Coping patterns of two groups of stroke patients related to their health condition are compared: one group participated in a rehabilitation programme, while the consisted of long-term care patients who had suffered a stroke ten to twenty years before the interview was second group. Similarities and differences between the response hierarchies of the two groups are demonstrated and discussed with special emphasis on the complex cognition and motivation interactions determining success and failure in coping.