Sito in Italia dove è possibile acquistare la consegna acquisto Viagra a buon mercato e di alta qualità in ogni parte del mondo.

Onsm.ces.edu.co

Reviews and Overviews
Substance Use Disorders in Patients With Posttraumatic
Stress Disorder: A Review of the Literature
Leslie K. Jacobsen, M.D.
Objective: Alcohol use disorders and
dence, physiologic arousal resulting from Steven M. Southwick, M.D.
posttraumatic stress disorder (PTSD). This article reviews studies pertaining to the Thomas R. Kosten, M.D.
work has led to the proposal that in PTSD, adrenergic systems may interact such that Method: Studies were identified by means
the stress response is progressively aug- of computerized and manual searches.
notics, or alcohol in an effort to interrupt Conclusions: Vigorous control of with-
Results: High rates of comorbidity sug-
substance use disorders. Inclusion of pa- and in clinical trials will be critical for de- velopment of effective treatments for this severely symptomatic patient population.
(Am J Psychiatry 2001; 158:1184–1190)
Substance use disorders, particularly abuse of and de- substance use leading to failure to fulfill work, school, or pendence on central nervous system (CNS) depressants, home obligations; legal problems; and substance-related are common in patients with posttraumatic stress disor- interpersonal problems. Substance dependence further der (PTSD). This article reviews clinical, epidemiologic, includes tolerance, withdrawal symptoms upon cessation and neurobiologic studies relevant to the problem of co- of use, unsuccessful efforts to control use, and continued morbid PTSD and substance use disorders and discusses use despite persistent substance-related physical or psy- the clinical implications of these findings.
Persons with PTSD have elevated rates of comorbid psy- Clinical Phenomenology
chiatric disorders. Studies of both combat veterans and ci- and Epidemiology
vilians with PTSD have demonstrated that, among menwith PTSD, alcohol abuse or dependence is the most com- PTSD develops in some people after exposure to a severe mon co-occurring disorder, followed by depression, other traumatic event. The DSM-IV diagnosis of PTSD consists of anxiety disorders, conduct disorder, and nonalcohol sub- symptoms in three clusters: 1) reexperiencing symptoms, stance abuse or dependence (1, 2). Among women with including intrusive recollections of the trauma that are PTSD, rates of comorbid depression and other anxiety dis- triggered by exposure to cues symbolizing the trauma; orders are highest, followed by alcohol abuse and depen- 2) avoidance symptoms, which involve diminished partici- dence (1, 2). High rates of comorbidity of PTSD and sub- pation in activities and avoidance of thoughts, people, stance use disorders were first reported in war-related places, and memories associated with the trauma; and studies, in which as many as 75% of combat veterans with 3) arousal symptoms, which include difficulty sleeping, ir- lifetime PTSD also met criteria for alcohol abuse or depen- ritability, difficulty concentrating, hypervigilance, and ex- dence (2). Among civilian populations, estimates of the prevalence of lifetime substance use disorders have Although intoxication and withdrawal symptoms vary ranged from 21.6% to 43.0% in persons with PTSD, com- across abused substances, all substance use disorders pared with 8.1% to 24.7% in persons without PTSD (1, 3, 4).
share key features. They include a maladaptive pattern of Similarly, among substance abusers in the general popula- Am J Psychiatry 158:8, August 2001 JACOBSEN, SOUTHWICK, AND KOSTEN
tion, the reported rate of PTSD is 8.3% (5). Rates of PTSD FIGURE 1. Symptoms of Increased Arousal in PTSD and
appear to be higher among patients in inpatient sub- Symptoms Associated With Withdrawal From CNS Depres-
santsa

stance abuse treatment (up to 42.5%) (6) and among preg-nant women in residential treatment for substance abuse(62%) (7). Surveys of substance-dependent adolescents PTSD Symptoms of
Symptoms of CNS
Increased Arousal
Depressant Withdrawal
have also found rates of PTSD ranging up to 19.2% (8).
Patients with both PTSD and a substance use disorder have significantly higher rates of comorbid axis I and IIdisorders, psychosocial and medical problems, sub- stance- or alcohol-related inpatient admissions, and re- lapse to substance use, compared with patients whosesubstance use is not complicated by PTSD (4, 9). Further- more, patients with PTSD and substance use disorders tend to suffer from more severe PTSD symptoms, particu- larly those in the avoidance and arousal symptom clus-ters, than do patients with PTSD alone (10). Conversely, one longitudinal study of patients with PTSD and a co- morbid substance use disorder found at 6-month post-treatment follow-up that patients whose PTSD symptoms a From the DSM-IV criteria for PTSD, alcohol withdrawal, and seda- had remitted reported significantly less substance use tive, hypnotic, or anxiolytic withdrawal.
than did patients with unremitted PTSD (11).
experience. For example, PTSD patients with alcohol de- Relationship of Substance Use
pendence exhibit significantly more arousal symptoms to PTSD Symptoms
that do PTSD patients with cocaine dependence (10).
In the second model, withdrawal from substances, par- Elevated rates of comorbid depressive and anxiety dis- ticularly CNS depressants, may initiate a cycle that perpet- orders in patients with PTSD greatly complicate any effort uates relapse and continued substance use. The with- to develop a model of the relationship between PTSD and drawal syndromes associated with many CNS depressants substance use. High rates of comorbidity suggest thatPTSD and substance use disorders are functionally related overlap extensively with the arousal symptoms of PTSD to one another. Two primary pathways have been de- (15) (Figure 1). Substances may be taken initially to ame- scribed to explain these high rates of comorbidity. In the liorate PTSD symptoms. As noted earlier, patients with first, substance abuse precedes PTSD. To sustain their PTSD have reported that CNS depressants acutely provide habit, some substance abusers repetitively place them- symptom relief (14). Furthermore, objectively measured selves in dangerous situations and, as a result, experience startle responses are reduced by alcohol (16). However, the high levels of physical and psychological trauma (5). For physiologic arousal resulting from substance withdrawal example, in a study of patients with PTSD and comorbid may have an additive effect with arousal symptoms stem- cocaine abuse, patients whose cocaine abuse developed ming from PTSD. The resulting hyperaroused state may first later developed PTSD as a result of trauma sustained serve as a conditioned reminder of traumatic events and in the context of procurement and use of cocaine (12).
thus precipitate an increase in reexperiencing symptoms.
Given that chronic substance use can lead to higher levels Exacerbation of PTSD symptoms may then prompt re- of arousal and anxiety as well as to sensitization of neuro- lapse to substance use in an attempt to self-medicate.
biologic stress systems (13), substance abuse may result in Thus, for the PTSD patient who already has symptoms of a higher level of vulnerability to development of PTSD af- arousal, the additional arousal that accompanies with- drawal from substances may be intolerable. Alternatively, In the second pathway, PTSD precedes development of substances may be used to cope with the traumatic event substance use disorders. In this model, the use of sub- itself (17). This pattern may particularly apply when stances is a form of self-medication. Patients report that trauma that leads to PTSD occurs during adulthood. The CNS depressants, such as alcohol, cannabis, opioids, and initial calming effects from substance use may cue pa- benzodiazepines acutely improve PTSD symptoms (14).
tients to resume substance use when PTSD symptoms Consistent with this, patients with PTSD report that onset and severity of substance abuse parallel the onset and es- Most published data support the second model, in calation of PTSD symptoms (14). In addition, clinical evi- which substance use follows or parallels traumatic expo- dence suggests that the choice of substances of abuse (CNS sure and the development of PTSD (18). In a longitudinal depressants versus CNS stimulants) may stem from the study conducted by Chilcoat and Breslau (19), 1,007 adults particular constellation of PTSD symptoms that patients were reevaluated 3 and 5 years after an initial assessment.
Am J Psychiatry 158:8, August 2001 SUBSTANCE USE AND PTSD
The researchers found that preexisting substance abuse toward drug self-administration (25). Initial work on the did not increase subjects’ risk of subsequent exposure to pathophysiology of this phenomenon indicated that trauma or their risk of developing PTSD after exposure to stress-induced or stress-enhanced drug self-administra- trauma. The relationship between exposure to trauma and tion is mediated by corticosterone (26).
increased risk for development of a substance use dis- Evidence has accumulated to support a role for CRH in order was found to be specific to PTSD, as exposure to mediating the effects of stress on drug self-administration.
trauma without subsequent development of PTSD did not Central, but not peripheral, administration of CRH has increase risk for development of a substance use disorder been shown to induce a long-lasting enhancement (sensi- (19). Of note, one study of patients with cocaine depen- tization) of the locomotor response to d-amphetamine dence and PTSD found that patients in whom PTSD pre- (27), and pretreatment with a CRH antagonist has been ceded the onset of cocaine use were significantly more shown to block the development of stress-induced sensiti- likely to suffer from comorbid major depression and to zation to d-amphetamine (28). Indeed, central adminis- use benzodiazepines and opiates than were patients in tration of anti-CRH antibody or the CRH receptor antago- whom PTSD developed after the onset of cocaine use (12).
nist α-helical CRH has been found to block the locomotorhyperactivity induced by cocaine (29).
Pathophysiology
Withdrawal from chronic cocaine or alcohol adminis- tration in rats produces anxiety-like behavior and de- Our review of the literature on the pathophysiologic ba- creased exploration that is associated with selective in- sis of comorbid PTSD and addiction selectively focuses on creases in CRH in the hypothalamus, amygdala, and basal studies of the hypothalamic-pituitary-adrenal (HPA) axis forebrain (30, 31). Pretreatment with anti-CRH immun- and the noradrenergic system, as these have been most oserum or α-helical CRH, blocking the effects of CRH, extensively studied in PTSD. It must be emphasized that completely prevents the development of these with- many other neurobiological systems are involved in both drawal-associated behaviors (30). Consistent with these the acute and chronic adaptation to stress and to sub-stance use. These systems include the dopaminergic, γ- observations, CSF CRH is elevated in humans in acute al- aminobutyric acid, benzodiazepine, and serotonergic sys- cohol withdrawal and then normalizes or decreases below tems, as well as the thyroid axis. Interactions among these normal levels with extended abstinence and resolution of systems in patients with comorbid PTSD and substance withdrawal symptoms (32). Shaham and colleagues (33) dependence are enormously complex. Thus, the potential found that intracerebroventricular injection of CRH rein- relationships we discuss between the HPA axis, the norad- stated heroin seeking after extinction in rats trained to renergic system, and symptoms in patients with comorbid self-administer the drug. In addition, α-helical CRH atten- PTSD and substance use disorders should be viewed as uated the reinstatement effect of footshock stress (33).
one part of a far more complex whole.
Neither adrenalectomy nor chronic or acute exposure tothe corticosterone synthesis inhibitor metyrapone inter- HPA Axis in PTSD and Addiction
fered with the reinstatement effects of priming injections In humans and animals, acute stress elicits a cascade of of heroin or of footshock stress. A potent, selective CRF1 neurohormonal events, including increased turnover of receptor antagonist, CP-154,526, has been found to atten- norepinephrine in terminal projection regions of the locus uate reinstatement of drug seeking induced by footshock ceruleus and liberation of hypothalamic corticotropin-re- stress after up to 14 days of extinction in rats trained to leasing hormone (CRH) into the pituitary portal system, self-administer heroin or cocaine (34).
which stimulates release of ACTH from the pituitary, Findings from both animal and human studies of the ef- which in turn triggers release of cortisol (human) or corti- fects of chronic stress or of PTSD on HPA axis function costerone (rat) from the adrenals (20). Animal and human vary depending on the experimental paradigm used or the research has implicated this cascade in the pathophysiol- population studied. In patients with PTSD, elevated (35), ogy of both substance use disorders and PTSD.
reduced (36), and normal (37) levels of cortisol secretion Humans with substance dependence most frequently have been reported. A series of studies performed by Ye- identify stress and negative mood states as reasons for re- huda and colleagues demonstrated that patients with lapse and ongoing substance abuse (21). Recently, a per- PTSD have an elevated number of lymphocyte glucocorti- sonalized stress imagery task was shown to reliably in- coid receptors (38), enhanced suppression of cortisol after crease cocaine craving and salivary cortisol in cocaine- administration of dexamethasone (39), a greater than nor- dependent patients (22). Animal studies have shown that mal decrease in the number of lymphocyte glucocorticoid stress induces relapse to heroin and to cocaine self-ad- receptors after administration of dexamethasone (39), and ministration in rats trained to self-administer these sub- higher than normal increases in ACTH after metyrapone stances and then subjected to a prolonged drug-free blockade of cortisol synthesis (40). All of these findings period (23, 24). Similarly, in animals naive to illicit sub- suggest that glucocorticoid negative feedback is enhanced stances, a large range of stressors increases the proclivity Am J Psychiatry 158:8, August 2001 JACOBSEN, SOUTHWICK, AND KOSTEN
Animal studies examining the effects of uncontrollable Thus, elevated levels of CRH in the brain in PTSD may me- stress on HPA axis function have reported initial increases diate both the symptoms of hyperarousal as well as the in- of corticosterone secretion, followed by normalization of creased risk for substance abuse and dependence seen in corticosterone secretion with ongoing chronic stress (41).
this disorder. More specifically, elevated levels of CRH in However, some investigators have failed to demonstrate the brain in PTSD may enhance the euphorigenic proper- normalization of corticosterone secretion with chronic ties of certain drugs, such as stimulants, and may worsen uncontrollable stress (42), particularly in animals that the severity of withdrawal symptoms, thereby prompting have been reared under stressful conditions (43) or when patients to relapse to drug use. Conversely, brain CRH ele- levels of chronic stress are high (44). In a pattern similar to vations induced by withdrawal from substance use may that found in humans with PTSD, animals subjected to a exacerbate symptoms of hyperarousal, which could trig- single episode of prolonged stress and then briefly re- ger other symptoms of PTSD, prompting relapse to sub- stressed after a stress-free period showed enhancement of glucocorticoid negative feedback (45).
Noradrenergic System in PTSD and Addiction
Although both animal and human studies have sug- gested that glucocorticoid negative feedback may be en- During chronic uncontrollable stress, norepinephrine hanced in PTSD, the implications of these observations for turnover increases in specific brain regions, including the CRH secretion in this disorder are unclear. As noted ear- locus ceruleus, hypothalamus, hippocampus, amygdala, lier, CRH-producing cells and CRH receptors exist both in and cerebral cortex (51). Evidence for noradrenergic dys- the hypothalamus and in extrahypothalamic sites. Find- regulation in patients with PTSD has included elevated 24- ings from some studies have suggested that hypothalamic hour urinary epinephrine and norepinephrine excretion, and extrahypothalamic CRH-producing cells may re- a lower than normal number of platelet α2-adrenergic re- spond differently to corticosterone. Specifically, corticos- ceptors, elevated 24-hour plasma norepinephrine, and terone appears to restrain hypothalamic CRH-producing exaggerated cardiovascular and 3-methoxy-4-hydroxy- cells while stimulating extrahypothalamic CRH-produc- phenylglycol (MHPG) (a norepinephrine metabolite) re- ing cells, particularly those in the amygdala (46). Replace- sponses to intravenous yohimbine (52). Noradrenergic ment of corticosterone in adrenalectomized rats de- dysregulation has also been reported during states of creases CRH production in the parvocellular nucleus of withdrawal from chronic self-administration of alcohol the hypothalamus while increasing CRH production in the and other abused substances. The levels of noradrenaline, central nucleus of the amygdala (47). This region-specific norepinephrine, and MHPG in both plasma and CSF have pattern of regulation is also seen in adrenally intact rats been found to be increased and the number of platelet α2- treated with high-stress levels of corticosterone for ex- adrenergic receptors decreased in alcoholics during acute tended periods of time (48). Thus, while glucocorticoid withdrawal (53, 54). The severity of alcoholic withdrawal feedback may decrease CRH production and release in the symptoms has been positively correlated with the concen- hypothalamus, it may stimulate CRH production and re- tration of MHPG in CSF (54). Evidence for noradrenergic lease in other brain regions, including the amygdala. This dysregulation in opiate withdrawal has included findings possibility has been addressed in two studies of patients of elevated plasma MHPG in humans and elevated plasma with PTSD, one that examined CSF concentrations of CRH and brain MHPG in animals (55, 56). In animals, the level at a single time point (49) and one that examined CSF con- of noradrenergic activity was significantly correlated with centrations of CRH at serial time points over a 6-hour pe- the severity of withdrawal symptoms (56). These findings riod (37). Both found significantly higher levels of CSF have prompted the use of the α2-adrenergic receptor ago- CRH in patients with PTSD than in normal comparison nist clonidine in the treatment of both opiate withdrawal subjects. However, although elevated CSF CRH suggests that brain CRH may be elevated, the specific brain tissuesproducing CRH elevations cannot be determined from Noradrenergic System/HPA Axis Interactions
Evidence that brain CRH and noradrenergic systems The possibility that brain CRH levels are elevated in modulate each other has been reported. Stress has been PTSD is of great interest because of a rich preclinical liter- shown to increase CRH levels in the locus ceruleus (59), a ature indicating that elevated levels of CRH in the brain, primary source of noradrenergic projections to all cortices particularly in the amygdala, potentiate fear-related be- as well as to the thalamus and hypothalamus, while intra- havioral responses, including the startle response (50).
ventricular administration of CRH has been found to in- These anxiogenic effects of CRH are reversed by adminis- crease the discharge rates of locus ceruleus neurons and tration of CRH antagonists (50). As noted earlier, findings to increase norepinephrine turnover in hippocampus, hy- from animal and human studies have supported a role for pothalamus, and prefrontal cortex (60–62). Conversely, CRH in mediating some effects of drugs of abuse, includ- stress-induced activation of the locus ceruleus has been ing stress- or priming-induced relapse to drug self-admin- blocked by administration of CRH antagonists (63). Simi- istration and symptoms of withdrawal (27, 28, 32–34).
lar evidence exists for the interaction of the CRH and nor- Am J Psychiatry 158:8, August 2001 SUBSTANCE USE AND PTSD
adrenergic systems in the hypothalamus (64) and the states. Further, CRH antagonists reduce both the anxiety amygdala, where stress induces increases in both CRH and the enhanced response to illicit substances (sensitiza- and norepinephrine (65). Furthermore, norepinephrine in tion) that are induced by higher levels of brain CRH. These the amygdala appears to stimulate release of CRH (66).
observations suggest that CRH antagonists could poten- These observations have prompted the proposal by tially have a role in the treatment of patients with PTSD Koob (20) that interactions of the CRH and noradrenergic and comorbid substance dependence. Although at systems in the brain may, under some conditions, function present no CRH antagonist has been approved for human as a feed-forward system, leading to the progressive aug- use, a series of CRH antagonists that can be administered mentation of the stress response with repeated stress expo- peripherally have been developed and have been shown sure that is characteristic of PTSD. This progressive aug- to cross the blood brain barrier (34, 69). These agents will mentation of response with repeated stress has previously be important tools for further defining the potential role of been conceptualized as kindling (67). A feed-forward inter- CRH antagonism in the treatment of patients with PTSD action between the CRH and noradrenergic systems may and substance dependence and will hopefully lead to de- represent one neurobiologic underpinning of both PTSD velopment of orally active preparations.
and substance use disorders. More specifically, stress, in- Evidence of noradrenergic dysregulation in both PTSD cluding stress related to self-administration of or with- and in withdrawal from CNS depressants has prompted drawal from substances, may stimulate CRH release in the the use of the α2-adrenoceptor agonist clonidine in both locus ceruleus, leading to activation of the locus ceruleus disorders (57, 58). Data from both preclinical and clinical and release of norepinephrine in the cortex, which in turn research suggest that this agent, as well as the selective α2- may stimulate the release of CRH in the hypothalamus and adrenoceptor agonist guanfacine, would be effective in re- amygdala (20). Such an interaction between the brain nor- ducing noradrenergic hyperactivity in patients with PTSD adrenergic and CRH systems may mediate the symptoms and comorbid substance dependence. Guanfacine, given of hyperarousal seen in PTSD, including exaggerated star- its greater selectivity, may offer a more favorable side ef- tle response. The proclivity toward misuse of CNS depres- fect profile. Given the dearth of established treatments for sants by patients with PTSD may reflect an attempt to this patient population, controlled clinical trials to estab- interrupt this feed-forward interaction by suppressing ac- lish the efficacy of these agents are clearly indicated.
tivity of the locus ceruleus with these agents (68).
Finally, although preclinical work has resulted in con- siderable progress toward delineating the contributions of Conclusions
the HPA axis and noradrenergic systems to the pathophys-iologic underpinnings of PTSD with comorbid substance Clinical and epidemiologic studies confirm that comor- dependence, few neurobiologic studies have been con- bidity of PTSD with substance use disorders is common ducted in this patient population. The inclusion of sub- and that the symptoms of patients with this comorbidity jects with this comorbidity may render such studies more tend to be more severe and more refractory to treatment complicated, but the data emerging from this work would than those of patients suffering from either disorder alone.
better inform the clinical management of the difficult-to- Despite the frequency with which patients with both diag- treat symptoms of these frequently encountered patients.
noses present for treatment, no systematic treatment ap- At the minimum, patients who participate in studies of proach of proven efficacy has been developed for this pop- PTSD or of substance dependence must be thoroughly ulation. Furthermore, little is known about the impact on evaluated for the presence of this comorbidity to permit substance use disorder outcomes of the medications and adequate control of the effects of the comorbid condition psychosocial interventions commonly used to treat PTSD, on the neurobiologic processes under study.
These limitations notwithstanding, the research con- Received May 11, 2000; revision received Aug. 22, 2000; accepted Nov. 17, 2000. From the Department of Psychiatry, Yale University ducted to date can inform both clinical practice and future School of Medicine, New Haven, Conn., and the VA Connecticut clinical and preclinical research. For example, clinical re- Healthcare System. Address correspondence to Dr. Jacobsen, Depart- search suggests that PTSD patients with substance depen- ment of Psychiatry (116A), VA Connecticut Healthcare System, YaleUniversity–West Haven Campus, 950 Campbell Ave., West Haven, CT dence, particularly those who are addicted to CNS depres- 06516; leslie.jacobsen@yale.edu (e-mail). sants, may find the physiologic arousal resulting from Supported in part by grants DA-00167, DA-04060, and DA-09250 substance withdrawal intolerable due to additive effects from the National Institute on Drug Abuse.
with preexisting arousal symptoms related to PTSD. Suc-cessful detoxification of these patients may thus require References
inpatient admission to permit vigorous control of with-drawal and PTSD-related arousal symptoms.
1. Kessler RC, Sonnega A, Bromet E, Hughes M, Nelson CB: Post- traumatic stress disorder in the National Comorbidity Survey.
Neurobiologic research indicates that high levels of CRH in the brain, particularly in the amygdala, may be 2. Kulka RA, Schlenger WE, Fairbank JA, Hough RL, Jordan BK, common to both PTSD and to substance withdrawal Marmar CR, Weiss DS: Trauma and the Vietnam War Genera- Am J Psychiatry 158:8, August 2001 JACOBSEN, SOUTHWICK, AND KOSTEN
tion: Report of Findings From the National Vietnam Veterans 22. Sinha R, Catapano D, O’Malley S: Stress-induced craving and Readjustment Study. New York, Brunner/Mazel, 1990 stress response in cocaine dependent individuals. Psychophar- 3. Breslau N, Davis GC, Andreski P, Peterson E: Traumatic events and posttraumatic stress disorder in an urban population of 23. Shaham Y, Stewart J: Stress reinstates heroin-seeking in drug- young adults. Arch Gen Psychiatry 1991; 48:216–222 free animals: an effect mimicking heroin, not withdrawal. Psy- 4. Breslau N, Davis GC, Peterson EL, Schultz L: Psychiatric se- chopharmacology (Berl) 1995; 119:334–341 quelae of posttraumatic stress disorder in women. Arch Gen 24. Erb S, Shaham Y, Stewart J: Stress reinstates cocaine-seeking behavior after prolonged extinction and a drug-free period.
5. Cottler LB, Compton WM III, Mager D, Spitznagel EL, Janca A: Psychopharmacology (Berl) 1996; 128:408–412 Posttraumatic stress disorder among substance users from the 25. Piazza PV, Deminiere JM, Le Moal M, Simon H: Stress- and phar- general population. Am J Psychiatry 1992; 149:664–670 macologically-induced behavioral sensitization increases vul- 6. Dansky BS, Saladin ME, Brady KT, Kilpatrick DG, Resnick HS: nerability to acquisition of amphetamine self-administration.
Prevalence of victimization and posttraumatic stress disorder among women with substance use disorders: comparison of 26. Deroche V, Marinelli M, LeMoal M, Piazza PV: Glucocorticoids telephone and in-person assessment samples. Int J Addict and behavioral effects of psychostimulants, II: cocaine intrave- nous self-administration and reinstatement depend on gluco- 7. Thompson MP, Kingree JB: The frequency and impact of vio- corticoid levels. J Pharmacol Exp Ther 1997; 281:1401–1407 lent trauma among pregnant substance abusers. Addict Behav 27. Cador M, Cole BJ, Koob GF, Stinus L, Le Moal M: Central admin- istration of corticotropin releasing factor induces long-term 8. Deykin EY, Buka SL: Prevalence and risk factors for posttrau- sensitization to d-amphetamine. Brain Res 1993; 606:181–186 matic stress disorder among chemically dependent adoles- 28. Cole BJ, Cador M, Stinus L, Rivier J, Vale W, Koob GF, Le Moal M: cents. Am J Psychiatry 1997; 154:752–757 Central administration of a CRF antagonist blocks the develop- 9. Najavits LM, Gastfriend DR, Barber JP, Reif S, Muenz LR, Blaine ment of stress-induced behavioral sensitization. Brain Res J, Frank A, Crits-Christoph P, Thase M, Weiss RD: Cocaine depen- dence with and without PTSD among subjects in the National 29. Sarnyai Z, Hohn J, Szabo G, Penke B: Critical role of endoge- Institute on Drug Abuse Collaborative Cocaine Treatment nous corticotropin-releasing factor (CRF) in the mediation of Study. Am J Psychiatry 1998; 155:214–219 the behavioral action of cocaine in rats. Life Sci 1992; 51:2019– 10. Saladin ME, Brady KT, Dansky BS, Kilpatrick DG: Understanding comorbidity between PTSD and substance use disorders: two 30. Sarnyai Z, Biro E, Gardi J, Vecsernyes M, Julesz J, Telegdy G: preliminary investigations. Addict Behav 1995; 20:643–655 Brain corticotropin-releasing factor mediates “anxiety-like” be- 11. Ouimette PC, Brown PJ, Najavits LM: Course and treatment of havior induced by cocaine withdrawal in rats. Brain Res 1995; patients with both substance use and posttraumatic stress dis- 31. Merlo-Pich E, Koob GF, Heilig M, Menzaghi F, Vale W, Weiss F: 12. Brady KT, Dansky BS, Sonne SC, Saladin ME: Posttraumatic Corticotropin-releasing factor release from mediobasal hypo- stress disorder and cocaine dependence. Am J Addict 1998; 7: thalamus of the rat as measured by microdialysis. Neuro- 13. Aouizerate B, Schluger JH, Perret G, McClary K, Ho A, Piazza PV, 32. Adinoff B, Anton R, Linnoila M, Guidotti A, Nemeroff CB, Bis- Kreek MJ: Enhanced sensitivity to negative glucocorticoid feed- sette G: Cerebrospinal fluid concentrations of corticotropin- back in methadone patients with ongoing cocaine depen- releasing hormone (CRH) and diazepam-binding inhibitor (DBI) dence, in Proceedings of the College on Problems of Drug De- during alcohol withdrawal and abstinence. Neuropsychophar- pendence Annual Meeting. Bethesda, Md, National Institute 33. Shaham Y, Funk D, Erb S, Brown TJ, Walker C-D, Stewart J: Cor- 14. Bremner JD, Southwick SM, Darnell A, Charney DS: Chronic ticotropin-releasing factor, but not corticosterone, is involved PTSD in Vietnam combat veterans: course of illness and sub- in stress-induced relapse to heroin-seeking in rats. J Neurosci stance abuse. Am J Psychiatry 1996; 153:369–375 15. van der Kolk B, Greenberg M, Boyd H, Krystal J: Inescapable 34. Shaham Y, Erb S, Leung S, Buczek Y, Stewart J: CP-154,526, a se- shock, neurotransmitters, and addiction to trauma: toward a lective, non-peptide antagonist of the corticotropin-releasing psychobiology of post traumatic stress. Biol Psychiatry 1985; factor 1 receptor attenuates stress-induced relapse to drug seeking in cocaine- and heroin-trained rats. Psychopharmacol- 16. Hutchison KE, Rohsenow D, Monti P, Palfai T, Swift R: Prepulse inhibition of the startle reflex: preliminary study of the effects 35. Maes M, Lin A, Bonaccorso S, van Hunsel F, Van Gastel A, of a low dose of alcohol in humans. Alcohol Clin Exp Res 1997; Delmeire L, Biondi M, Bosmans E, Kenis G, Scharpe S: In- creased 24-hour urinary cortisol excretion in patients with 17. Mirin SM, McKenna GJ: Combat zone adjustment: the role of post-traumatic stress disorder and patients with major depres- marihuana use. Mil Med 1975; 140:482–485 sion, but not in patients with fibromyalgia. Acta Psychiatr 18. Keane TM, Gerardi RJ, Lyons JA, Wolfe J: The interrelationship of substance abuse and posttraumatic stress disorder: epidemio- 36. Mason JW, Giller EL, Kosten TR, Ostroff RB, Podd L: Urinary free- logical and clinical considerations. Recent Dev Alcohol 1988; 6: cortisol levels in posttraumatic stress disorder patients. J Nerv 19. Chilcoat HD, Breslau N: Posttraumatic stress disorder and drug 37. Baker DG, West SA, Nicholson WE, Ekhator NN, Kasckow JW, Hill disorders: testing causal pathways. Arch Gen Psychiatry 1998; KK, Bruce AB, Orth DN, Geracioti TD Jr: Serial CSF corticotropin- releasing hormone levels and adrenocortical activity in com- 20. Koob GF: Corticotropin-releasing factor, norepinephrine, and bat veterans with posttraumatic stress disorder. Am J Psychia- stress. Biol Psychiatry 1999; 46:1167–1180 21. Brewer DD, Catalano RF, Haggerty K, Gainey RR, Fleming CB: A 38. Yehuda R, Lowy MT, Southwick SM, Shaffer D, Giller EL Jr: meta-analysis of predictors of continued drug use during and Lymphocyte glucocorticoid receptor number in posttraumatic after treatment for opiate addiction. Addiction 1998; 93:73–92 stress disorder. Am J Psychiatry 1991; 148:499–504 Am J Psychiatry 158:8, August 2001 SUBSTANCE USE AND PTSD
39. Yehuda R, Boisoneau D, Lowy MT, Giller EL: Dose-response 55. Charney DS, Redmond DE, Galloway MP, Kleber HD, Heninger changes in plasma cortisol and lymphocyte glucocorticoid re- GR, Murberg M, Roth RH: Naltrexone precipitated opiate with- ceptors following dexamethasone administration in combat drawal in methadone addicted human subjects: evidence for veterans with and without posttraumatic stress disorder. Arch noradrenergic hyperactivity. Life Sci 1984; 35:1263–1272 56. Swann AC, Elsworth JD, Charney DS, Jablons DM, Roth RH, Red- 40. Yehuda R, Levengood RA, Schmeilder J, Wilson S, Guo LS, Ger- mond DE, Maas JW: Brain catecholamine metabolites and be- ber D: Increased pituitary activation following metyrapone ad- havior in morphine withdrawal. Eur J Pharmacol 1982; 86: ministration in post-traumatic stress disorder. Psychoneuroen- 57. Agren H: Clonidine treatment of the opiate withdrawal syn- 41. Kant GJ, Bauman RA, Anderson SM, Mougey EH: Effects of con- drome: a review of clinical trials of a theory. Acta Psychiatr trollable vs uncontrollable chronic stress on stress-responsive plasma hormones. Physiol Behav 1992; 51:1285–1288 58. Harmon RJ, Riggs PD: Clonidine for posttraumatic stress disor- 42. Irwin J, Ahluwalia P, Zacharko RM, Anisman H: Central norepi- der in preschool children. J Am Acad Child Adolesc Psychiatry nephrine and plasma corticosterone following acute and chronic stressors: influence of social isolation and handling.
59. Chappell PB, Smith MA, Hilts CD, Bissette G, Ritchie J, Andersen Pharmacol Biochem Behav 1986; 24:1151–1154 C, Nemeroff CB: Alterations in corticotropin-releasing factor- 43. Gamallo A, Villanua A, Trancho G, Fraile A: Stress adaptation like immunoreactivity in discrete rat brain regions after acute and adrenal activity in isolated and crowded rats. Physiol Be- and chronic stress. J Neurosci 1986; 10:2908–2916 60. Valentino RJ, Foote SL, Aston-Jones G: Corticotropin-releasing 44. Young EA, Akana S, Dallman MF: Decreased sensitivity to gluco- factor activates noradrenergic neurons of the locus coeruleus.
corticoid fast feedback in chronically stressed rats. Neuroendo- 61. Zhang JJ, Swiergiel AH, Palamarchouk VS, Dunn AJ: Intracere- 45. Liberzon I, Krstov M, Young EA: Stress-restress: effects on ACTH broventricular infusion of CRF increases extracellular concen- and fast feedback. Psychoneuroendocrinology 1997; 22:443– trations of norepinephrine in the hippocampus and cortex as determined by in vivo voltametry. Brain Res Bull 1998; 47: 46. Schulkin J, Gold PW, McEwen BS: Induction of corticotropin- releasing hormone gene expression by glucocorticoids; impli- 62. Lavicky J, Dunn AJ: Corticotropin-releasing factor stimulates cation for understanding the states of fear and anxiety and al- catecholamine release in hypothalamus and prefrontal cortex lostatic load. Psychoneuroendocrinology 1998; 23:219–243 in freely moving rats as assessed by microdialysis. J Neurochem 47. Makino S, Gold PW, Schulkin J: Corticosterone effects on corti- cotropin-releasing hormone mRNA in the central nucleus of 63. Valentino RJ, Page ME, Curtis AL: Activation of noradrenergic the amygdala and the parvocellular region of the paraventric- locus coeruleus neurons by hemodynamic stress is due to local ular nucleus of the hypothalamus. Brain Res 1994; 640:105– release of corticotropin-releasing factor. Brain Res 1991; 555: 48. Makino S, Gold PW, Schulkin J: Effects of corticosterone on CRH 64. Pacak K, Palkovits M, Kopin IJ, Goldstein DS: Stress-induced mRNA and content in the bed nucleus of the stria terminalis; norepinephrine release in the hypothalamic paraventricular comparison with the effects in the central nucleus of the nucleus and pituitary-adrenocortical and sympathoadrenal ac- amygdala and the paraventricular nucleus of the hypothala- tivity: in vivo microdialysis studies. Front Neuroendocrinol 49. Bremner JD, Licinio J, Darnell A, Krystal JH, Owens MJ, South- 65. Pich EM, Lorang M, Yeganeh M, Rodriquez de Fonseca F, Raber wick SM, Nemeroff CB, Charney DS: Elevated CSF corticotropin- J, Koob GF, Weiss F: Increase of extracellular corticotropin- releasing factor concentrations in posttraumatic stress disor- releasing factor-like immunoreactivity levels in the amygdala of awake rats during restraint stress and ethanol withdrawal as 50. Swerdlow NR, Britton KT, Koob GF: Potentiation of acoustic measured by microdialysis. J Neurosci 1995; 15:5439–5447 startle by corticotropin-releasing factor (CRF) and by fear are 66. Raber J, Koob GF, Bloom FE: Interleukin-2 (IL-2) induces corti- both reversed by alpha-helical CRF (9-41). Neuropsychophar- cotropin-releasing factor (CRF) release from the amygdala and involves a nitric oxide-mediated signaling: comparison with 51. Tanaka T, Yokoo H, Mizoguchi K, Yoshida M, Tsuda A, Tanaka the hypothalamic response. J Pharmacol Exp Ther 1995; 272: M: Noradrenaline release in the rat amygdala is increased by stress: studies with intracerebral microdialysis. Brain Res 1991; 67. Post RM, Weiss SRB, Smith M, Li H, McCann U: Kindling versus quenching; implications for the evolution and treatment of 52. Southwick SM, Bremner JD, Rasmusson A, Morgan CA, Arnsten posttraumatic stress disorder. Ann NY Acad Sci 1997; 821:285– A, Charney DS: Role of norepinephrine in the pathophysiology and treatment of posttraumatic stress disorder. Biol Psychiatry 68. Kosten TR, Krystal J: Biological mechanisms in posttraumatic stress disorder: relevance for substance abuse. Recent Dev Al- 53. Smith AJ, Brent PJ, Henry DA, Foy A: Plasma noradrenaline, platelet alpha 2-adrenoceptors, and functional scores during 69. Arai K, Ohata H, Shibasaki T: Non-peptidic corticotropin-releas- ethanol withdrawal. Alcohol Clin Exp Res 1990; 14:497–502 ing hormone receptor type 1 antagonist reverses restraint 54. Hawley RJ, Major LF, Schulman EA, Linnoila M: Cerebrospinal stress-induced shortening of sodium pentobarbital-induced fluid 3-methoxy-4-hydroxyphenylglycol and norepinephrine sleeping time of rats: evidence that an increase in arousal in- levels in alcohol withdrawal: correlations with clinical signs.
duced by stress is mediated through CRH receptor type 1. Neu- Am J Psychiatry 158:8, August 2001

Source: http://onsm.ces.edu.co/uploads/files/1141412_drogas-stresspostraumatico.pdf

Microsoft word - smgemaf04_0708_-press.doc

Metabolic Assessment Form Name: ____________________________________________________ Age: ______ Sex: _____ Date: ______________ PART I Please list the 5 major health concerns in your order of importance: 1. _____________________________________________________________________________________________ 2. _____________________________________________________________________________

Microsoft word - elisir ed maggio 2008 tar 400i011 pv stb 5p0.doc

POPOLARE VITA - “Popolare Vita Elisir ed. maggio 2008” Codice prodotto: T400I011 Rete: BPV-SGSP (cod. 8408) Index ramo III – Capitale differito a premio unico con controassicurazione speciale e cedola annuale. In caso di vita: • A scadenza: premio versato al netto della spesa di • Ad ogni ricorrenza annuale: cedole fisse o variabili In caso di morte: Premio

Copyright © 2010-2014 Medicament Inoculation Pdf