Addiction Rehab: Genetic Background Influences the Effects of Withdrawal From Chronic Nicotine on Learning and High-Affinity Nicotinic Acetylcholine Receptor Binding in the Dorsal and Ventral Hippocampus.

Genetic background influences the effects of withdrawal from chronic nicotine on learning and high-affinity nicotinic acetylcholine receptor binding in the dorsal and ventral hippocampus.

Filed under: Addiction Rehab

Psychopharmacology (Berl). 2012 Jul 27;
Wilkinson DS, Turner JR, Blendy JA, Gould TJ

RATIONALE: The effects of nicotine on cognitive processes may play an important role in nicotine addiction. Nicotine withdrawal impairs hippocampus-dependent learning and genetic factors influence this effect. However, the neural changes that contribute to these impairments are unknown. Chronic nicotine upregulates hippocampal nicotinic acetycholine receptors (nAChRs), which may contribute to cognitive deficits when nicotine administration ceases. If nAChR upregulation underlies withdrawal deficits in learning, then strains of mice exhibiting withdrawal deficits in hippocampus-dependent learning should also show upregulation of hippocampal nAChRs. OBJECTIVES: Here, we examined the effects of nicotine withdrawal on fear conditioning and [(3)H]epibatidine binding in the dorsal and ventral hippocampus in two inbred mouse strains and their F1 hybrids. METHODS: Male C57BL/6NTac, 129S6/SvEvTac, and B6129SF1/Tac mice were administered chronic nicotine (18 mg/kg/day) for 12 days through osmotic pumps and then were trained and tested in fear conditioning 24 h after cessation of nicotine treatment. RESULTS: Nicotine withdrawal impaired hippocampus-dependent contextual conditioning in C57BL/6NTac mice but not 129S6/SvEvTac or B6129SF1/Tac mice; no changes were observed in hippocampus-independent cued fear conditioning. Upregulated [(3)H]epibatidine binding was found in the dorsal, but not ventral, hippocampus of C57BL/6NTac mice and in the ventral hippocampus of B6129SF1/Tac mice after chronic nicotine. CONCLUSIONS: Upregulation of high-affinity binding sites in the dorsal hippocampus of C57BL/6NTac mice, the only strain that exhibited nAChR upregulation in this region and withdrawal deficits in contextual conditioning, suggests that upregulation of high-affinity binding sites in the dorsal hippocampus mediates, in part, nicotine withdrawal deficits in contextual conditioning and genetic background modulates these effects.
HubMed – addiction

 

Brain glutamate levels measured by magnetic resonance spectroscopy in patients with bipolar disorder: a meta-analysis.

Filed under: Addiction Rehab

Bipolar Disord. 2012 Aug; 14(5): 478-87
Gigante AD, Bond DJ, Lafer B, Lam RW, Young LT, Yatham LN

Gigante AD, Bond DJ, Lafer B, Lam RW, Young LT, Yatham LN. Brain glutamate levels measured by magnetic resonance spectroscopy in patients with bipolar disorder: a meta-analysis. Bipolar Disord 2012: 14: 478-487. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objectives:? Bipolar disorder (BD) is a common and highly disabling disease characterized by substantial cognitive and functional impairment. The exact neurobiological mechanisms underlying the expression of symptoms in this condition remain unknown but there is growing evidence that glutamate might play an important role. Using proton magnetic resonance spectroscopy ((1) H-MRS), a number of studies have examined brain glutamate/glutamine levels in patients with bipolar disorder, but they have produced conflicting results. The objective of this paper was to conduct a systematic review and meta-analysis of the literature on brain glutamate/glutamine in BD as measured by (1) H-MRS. Methods:? A Medline search for the period January 1980-April 2010 was conducted to identify published studies that used (1) H-MRS to measure glutamate?+?glutamine (Glx), the Glx/creatine (Cr) ratio, glutamate (Glu), or the Glu/Cr ratio in any brain region in adult or child/adolescent patients with BD and healthy subjects. A meta-analysis of the pooled data was conducted. Results:? BD patients were found to have increased Glx compared to healthy subjects when all brain areas were combined. This finding remained true in medicated and non-medicated patients, and in frontal brain areas in adults. There was a non-significant trend (p?=?0.09) for an increase in whole-brain Glx/Cr and Glu in patients compared with healthy subjects. No significant difference was found in Glu/Cr. Conclusions:? The results of this meta-analysis suggest that brain Glx levels are elevated in BD patients and support the idea that glutamate might play an important role in the pathophysiology of BD.
HubMed – addiction

 

Cigarette Smoking and Neonatal Outcomes in Depressed and Non-Depressed Opioid-Dependent Agonist-Maintained Pregnant Patients.

Filed under: Addiction Rehab

Addict Disord Their Treat. 2011 Dec; 10(4): 180-187
Chisolm MS, Acquavita SP, Kaltenbach K, Winklbaur B, Heil SH, Martin PR, Stine SM, Coyle M, Leoutsakos JM, Tuten M, Jansson LM, Backer PM, Jones HE

AIMS: To investigate whether cigarette smoking and/or depression contribute to neonatal abstinence syndrome (NAS) severity. DESIGN: Cohort study analyzing data from a randomized, controlled trial of methadone versus buprenorphine. SETTING: Seven study sites that randomized patients to study conditions and provided comprehensive addiction treatment to pregnant patients. PARTICIPANTS: 119 of 131 opioid-dependent pregnant patients who completed the MOTHER study. MEASUREMENTS: Smoking data and depression status were obtained from the Addiction Severity Index and Mini International Neuropsychiatric Interview, respectively. Neonatal outcomes (birth weight, preterm delivery and NAS pharmacologic treatment) were collected from the medical charts. Study site was a fixed-effect factor in all analyses. FINDINGS: Cigarette smoking was reported by 94% of participants and depression identified in 35%. Smoking was associated with low birth weight, preterm delivery, and NAS pharmacologic treatment in both depressed and non-depressed participants. The association between smoking and NAS treatment differed significantly between depressed and non-depressed participants. Among non-depressed participants, adjusting for site and illicit drug use, each additional average cigarette per day (CPD) increased the odds of NAS treatment by 12% [95%CI: (1.02-1.23), p=0.02]. Among depressed participants, each additional average CPD did not statistically increase the odds of NAS treatment [OR: 0.94, 95% CI: (0.84-1.04), p=0.23]. CONCLUSIONS: These results are consistent with the hypothesis that NAS expression is influenced by many factors. The relationship between CPD and NAS pharmacologic treatment is attenuated among depressed women in this study for reasons currently unknown. Further investigations are needed to clarify the complex relationships among maternal smoking, depression, and NAS.
HubMed – addiction

 

Moderators and Mediators in Social Work Research: Toward a More Ecologically Valid Evidence Base for Practice.

Filed under: Addiction Rehab

J Soc Work (Lond). 2011 Oct 16; 11(4): 387-401
Magill M

SUMMARY: Evidence-based practice involves the consistent and critical consumption of the social work research literature. As methodologies advance, primers to guide such efforts are often needed. In the present work, common statistical methods for testing moderation and mediation are identified, summarized, and corresponding examples, drawn from the substance abuse, domestic violence, and mental health literature, are provided. FINDINGS: While methodologically complex, analyses of these third variable effects can provide an optimal fit for the complexity involved in the provision of evidence-based social work services. While a moderator may identify the trait or state requirement for a causal relationship to occur, a mediator is concerned with the transmission of that relationship. In social work practice, these are questions of “under what conditions and for whom?” and of the “how?” of behavior change. IMPLICATIONS: Implications include a need for greater attention to these methods among practitioners and evaluation researchers. With knowledge gained through the present review, social workers can benefit from a more ecologically valid evidence base for practice.
HubMed – addiction

 

TCF4 sequence variants and mRNA levels are associated with neurodevelopmental characteristics in psychotic disorders.

Filed under: Addiction Rehab

Transl Psychiatry. 2012 Feb 21; 2: e112
Wirgenes KV, Sønderby IE, Haukvik UK, Mattingsdal M, Tesli M, Athanasiu L, Sundet K, Røssberg JI, Dale AM, Brown AA, Agartz I, Melle I, Djurovic S, Andreassen OA

TCF4 is involved in neurodevelopment, and intergenic and intronic variants in or close to the TCF4 gene have been associated with susceptibility to schizophrenia. However, the functional role of TCF4 at the level of gene expression and relationship to severity of core psychotic phenotypes are not known. TCF4 mRNA expression level in peripheral blood was determined in a large sample of patients with psychosis spectrum disorders (n=596) and healthy controls (n=385). The previously identified TCF4 risk variants (rs12966547 (G), rs9960767 (C), rs4309482 (A), rs2958182 (T) and rs17512836 (C)) were tested for association with characteristic psychosis phenotypes, including neurocognitive traits, psychotic symptoms and structural magnetic resonance imaging brain morphometric measures, using a linear regression model. Further, we explored the association of additional 59 single nucleotide polymorphisms (SNPs) covering the TCF4 gene to these phenotypes. The rs12966547 and rs4309482 risk variants were associated with poorer verbal fluency in the total sample. There were significant associations of other TCF4 SNPs with negative symptoms, verbal learning, executive functioning and age at onset in psychotic patients and brain abnormalities in total sample. The TCF4 mRNA expression level was significantly increased in psychosis patients compared with controls and positively correlated with positive- and negative-symptom levels. The increase in TCF4 mRNA expression level in psychosis patients and the association of TCF4 SNPs with core psychotic phenotypes across clinical, cognitive and brain morphological domains support that common TCF4 variants are involved in psychosis pathology, probably related to abnormal neurodevelopment.
HubMed – addiction

 


 

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