Towards a psychopathology specific to Substance Use Disorder: Should emotional responses to life events be included?

INTRODUCTION: The severity of emotional responses to life events (PTSD spectrum) as part of Post Traumatic Stress Disorder (PTSD) in Substance Use Disorder (SUD) patients has often been considered from a unitary perspective. Light has also been shed on the possible definition of a specific psychopathology of SUD patients. This psychopathology has been proved to be independent of treatment choice, of being active in using substances, of lifetime psychiatric comorbidity and primary substance of abuse (heroin, alcohol, cocaine). METHODS: To further support this unitary perspective, in this study we have compared the severity and typology of the five psychopathological dimensions found in SUD patients, by dividing 93 HUD patients (77.4% males and 22.6% females), characterized by the lifetime absence of exposure to actual or threatened death, serious injury, or sexual violence, on the basis of the severity of their PTSD spectrum. We used the cut-off that differentiated people developing (High PTSD spectrum; H-PTSD/S) or not developing (Low PTSD spectrum; L-PTSD/S) a PTSD after the earthquake that hit L'Aquila, Italy, in April 2009. RESULTS: Using a canonical correlation analysis, the significant (p<0.001) canonical variate set-one (psychopathology) is saturated negatively by "panic anxiety" and positively by the "worthlessness-being trapped" and "violence-suicide" dimensions. Set-two (PTSD spectrum) is saturated negatively by "emotional, physical and cognitive responses to loss and traumas", and positively by "grief reactions", "re-experiencing numbing", "arousal symptoms" and "personality traits". When comparing the two groups, all five psychopathological dimensions were significantly more severe in H-PTSD/S patients, who were distinguished by higher values of worthlessness-being trapped, sensitivity-psychoticism and violence-suicide symptomatology. No differences were observed regarding the typology of psychopathology. CONCLUSIONS: This study further supports the SUD-PTSD spectrum unitary perspective and argues in favor of the inclusion of the PTSD spectrum in the psychopathology of SUD.

Cyclooxygenase isoenzymes and patency of ductus arteriosus.

Prenatal patency of the ductus arteriosus is maintained mainly by prostaglandin (PG) E(2). Accordingly, the vessel is endowed in its muscular component with a complete, cyclooxygenase (COX) and PGE synthase (PGES), system for the synthesis of the compound. COX1 is better expressed than COX2, particularly in the premature, but COX2 is more extensively coupled with microsomal PGES (mPGES). No evidence was obtained of either COX being coupled with cytosolic PGES (cPGES). Functionally, these data translate into a differential constrictor response of the ductus to dual, COX1/COX2, vs. COX2-specific inhibitors (indomethacin vs. L-745,337), with the latter being less effective specifically prior to term. This difference, however, subsides upon treatment with endotoxin and the attendant upregulation of COX2 and mPGES. Furthermore, when studied separately, COX1 and COX2 prove to be unevenly responsive to indomethacin, and an immediate and fast developing contraction of the vessel occurs only when COX2 is inhibited. Deletion of either COX gene results into upregulation of NO synthase, and a similar compensatory reaction is expected when enzymes are suppressed pharmacologically. We conclude that PGE(2) and NO can function synergistically in keeping the ductus patent. This arrangement provides a possible explanation for failures of indomethacin or ibuprofen treatment in the management of the prematurely born infant with persistent ductus. Coincidentally, it opens the way to new therapeutic possibilities being based on interference with the NO effector or a more selective disruption, possibly having mPGES as a target, of the PGE(2) synthetic cascade.

Cytochrome c oxidase and mitochondrial F1F0-ATPase (ATP synthase) activities in platelets and brain from patients with Alzheimer's disease.

Evidence suggests that mitochondrial dysfunction is prominent in Alzheimer's disease (AD). A failure of one or more of the mitochondrial electron transport chain enzymes or of F(1)F(0)-ATPase (ATP synthase) could compromise brain energy stores, generate damaging reactive oxygen species (ROS), and lead to neuronal death. In the present study, cytochrome c oxidase (COX) and F(1)F(0)-ATPase activities of isolated mitochondria from platelets and postmortem motor cortex and hippocampus from AD patients and age-matched control subjects were assayed. Compared with controls, COX activity was decreased significantly in platelets (-30%, P < 0.01, n = 20) and hippocampus (-35 to -40%, P < 0.05, n = 6), but not in motor cortex from the AD patients. In contrast, in AD platelets and brain tissues, F(1)F(0)-ATP hydrolysis activity was not significantly changed. Moreover, the ATP synthesis rate was similar in mitochondria of platelets from AD patients and controls. These results demonstrate that COX but not F(1)F(0)-ATPase is a mitochondrial target in AD, in both a brain association area and in platelets. A reduced COX activity may make the tissue vulnerable to excitotoxicity or reduced oxygen availability.