Endogenous Opioid Activity Is Associated with Obsessive-Compulsive Symptomology in Individuals with a Family History of Alcoholism

Abstract

Endogenous opioid activity has been associated with the regulation of mood and inhibition of the hypothalamicpituitary-adrenal (HPA) axis. We assessed differences in psychological symptomology and naloxone sensitivity in non-alcoholic males and females with a family history of alcoholism (FHP) and without a family history of alcoholism (FHN).Family history of alcohol dependence is a strong predictor of risk for the future development of alcoholism (Goodwin 1985;Cloninger 1981;McGue et al. 1992). Adult sons of alcoholic fathers have a three to four-fold higher risk for this disorder compared to the male offspring of non-alcoholic fathers (Schuckit 1981).These findings have led investigators to examine the presence of a wide range of possible psychological as well as neurobiological mediators for the development of alcoholism in individuals with a positive family history (FHP) for alcoholism (Pihl et al. 1990;Martin and Sher 1994;Baker and Stephenson 1995). A wide range of psychological differences have been specifically associated with FHP males relative to controls, including impulsivity (Saunders and Schuckit 1981;Schulsinger et al. 1985), conduct disorder (Nylander and Rydelius 1982), antisocial personality with or without hyperactivity (Alterman et al. 1983), attention deficit disorder (Gillen and Hesselbrock 1992;Deckel et al. 1995), and aggressiveness (Windle 1990 NO . 6 family history for alcoholism compared with normals (Newlin and Thomson 1990;Schuckit et al. 1988Schuckit et al. ,1996Waltman et al. 1994).A growing body of literature suggests that the endogenous opioid system modulates a wide range of psychological symptomology, as well as the functioning of the Hypothalamic-Pituitary-Adrenal (HPA) axis (Pickar et al. 1982;Olson et al. 1996). It has been speculated that the interplay between environmental and genetic determinants generates a spectrum of endogenous opioid activity in the human population which, in the extreme ranges of opioid expression, lead to disturbances in mood, behavior and neuroendocrine function (Wand et al. 1998;Wand 1999;Blevins et al. 1994). Major behavioral alterations have been induced by opioid blockade with naloxone, suggesting the involvement of the endogenous opioid system in the tonic regulation of mood, behavior and cognition in normal (Cohen et al. 1983;Martin del Campo et al. 1992) and psychiatric populations (Insel and Pickar 1983;Sandyk 1987;Pickar et al. 1982). Some clinical studies suggest that in addition to the serotonergic system, the opioidergic system may be implicated in obsessive-compulsive symptomology (Carrion 1995;Insel and Pickar 1983;Keuler et al. 1996;Rapoport et al. 1992). Plasma B-endorphin levels have been found to be significantly lower in OCD subjects than in controls (Weizman et al. 1990). Studies with OCD subjects have shown naloxone decreases obsessional doubt and compulsive behaviors at low doses (Insel and Pickar 1983;Keuler et al. 1996) and decreases at higher doses (Sandyk 1987) in a small subgroup of subjects. Furthermore, opioid agent...

Hypothalamic-Pituitary-Adrenocortical (HPA) Axis Response and Biotransformation of Oral Naltrexone Preliminary Examination of Relationship to Family History of Alcoholism

“…Finally, although our sample was small, we demonstrated these findings in a more racially diverse (60% non-Caucasian in the present study vs. 15% in other studies) and older (mean age 33 yrs vs. 21 yrs) group of participants than in many previous studies (Wand et al 1998(Wand et al , 1999aMangold et al 2000), thereby increasing the generalizability of these neuroendocrine effects to more representative samples. In addition to HPA axis differences, we also showed enhanced FHϩ sensitivity to naltrexone in terms of greater mood response, i.e., significant decreases in vigor ratings, which were not present in the FHϪ group.…”

“…Also, several recent studies have demonstrated that opioidergic hypothalamic sensitivity is greater in high-risk, FHϩ persons (Wand et al 1998(Wand et al , 2001) and may vary as a function of gender (Wand et al 1999a) and degree of obsessive-compulsive symptomatology (Mangold et al 2000). Circadian rhythmicity of cortisol has been found to be similar in FHϩ and FHϪ groups, as well as responses to direct adrenal gland provocation (Wand et al 1999b).…”

Role of atypical opiates in OCD. Experimental approach through the study of 5-HT2A/C receptor-mediated behavior

“…More specifically, tics are presumably due to failed inhibition within cortico-striato-thalamo-cortical circuits. Dysregulation of this circuitry, which is also involved in opiate reward (Mangold et al 2000), may cause a relative lack of serotonin in the feedback loop between the thalamus and the orbito-frontal cortex, the caudate nucleus, and globus pallidus and produce a compensatory increase in 5-HT2A receptor. This mechanism probably underlies the increase in 5-HT2A receptor binding that has been found in the caudate nuclei of untreated patients with OCD (Adams et al 2005).…”

Treatment Refractory OCD Which Entered Remission After Heroin Use: Case Report

“…3,14 Son yıl lar da ya pı lan pla se bo kon trol lü bir ça lış ma da; en az iki SGİ' ne ce vap verme yen OKB has ta la rın da te da vi yi güç len dir me de tek doz oral mor fin ve ril di ğin de pla se bo ya gö re anlam lı dü zel me ler ol du ğu be lir til miş tir. 10 APA 2007 OKB te da vi al go rit ma sın da ce vap ver me yen va kalar da de ne ne bi le cek al ter na tif te da vi ola rak öne rilmiş tir. 5 Ol gu muz da ise, ero i ni bı rak tık tan son ra OKB be lir ti le rin de şid det len me görülürken, ero i ne tekrar baş la dı ğın da OKB be lir ti le ri nin kay bol ma sı, yuka rı da ki ça lış ma la rı des tek ler ni te lik te dir.…”

“…9 So nuç ola rak; korti ko-lim bik-ba zal gang li yon yo la ğı nın hem OKB hem de opi o id ödül mer ke zi nin kul lan dı ğı or tak yolak olup bu gö rün güy le iliş ki len di ril miş tir. 10 Bi zim va ka mız, psi ko far ma ko lo jik te da vi ye cevap ver me yen OKB has ta sı nın so kak ero i ni kul lanı mı son ra sı re mis yo na gir me si açı sın dan fark lı lık gös te ren bir ol gu dur. Ay rı ca ol gu nun kan şeke ri ni dü şür mek ama cıy la fark lı bir dü şün ce ile ero i ne baş la mış ol ma sı da il gi çe ki ci dir.…”