Depression Treatment: Roles of Nucleus Accumbens CREB and Dynorphin in Dysregulation of Motivation.

Roles of Nucleus Accumbens CREB and Dynorphin in Dysregulation of Motivation.

Filed under: Depression Treatment

Cold Spring Harb Perspect Med. 2013 Jan 4;
Muschamp JW, Carlezon WA

Psychostimulants such as amphetamine and cocaine are believed to produce dependence by causing rapid, supraphysiological elevations in synaptic dopamine (DA) within the nucleus accumbens (NAc) (Volkow et al. 2009, Neuropharmacology 56: 3-8). These changes in forebrain DA transmission are similar to those evoked by natural reinforcers (Louilot et al. 1991, Brain Res 553: 313-317; Roitman et al. 2004, J Neurosci 24: 1265-1271), but are of greater magnitude and longer duration. Repeated drug exposure causes compensatory neuroadaptations in neurons of the NAc, some of which may modulate excess DA in a homeostatic fashion. One such adaptation is the activation of the transcription factor CREB (cAMP response element-binding protein) within neurons of the NAc. Although elevated levels of transcriptionally active CREB appear to attenuate DA transmission by increasing expression of the endogenous ? opioid receptor (KOR) ligand dynorphin, increased dynorphin transmission may ultimately have undesirable effects that contribute to drug withdrawal states as well as comorbid psychiatric illnesses such as depression. This state may prompt a return to drug use to mitigate the adverse effects of withdrawal. This article summarizes our current understanding of how CREB and dynorphin contribute to the dysregulation of motivation and describes novel therapeutic strategies that derive from preclinical research in this area.
HubMed – depression



Filed under: Depression Treatment

Depress Anxiety. 2013 Jan 4;
Mavrides N, Nemeroff C

BACKGROUND AND OBJECTIVES: Depression in patients with Cardiovascular Disease (CVD) is extremely common, with a prevalence of 17-47%, and is associated with increased risk of morbidity and mortality. Treatment of depression has been hypothesized to reduce cardiac mortality. Pharmacologic and psychotherapeutic interventions have been studied and appear to be safe and in some studies effective in reducing depressive symptoms in patients with cardiac disease. The impact on cardiac outcomes remains unclear. This review briefly focuses on the prevalence of depression in patients with CVD, the physiological links between depression and CVD, and largely is concerned with the clinical trials that seek to demonstrate efficacy and safety of antidepressant medications and psychotherapy in this patient population. METHODS: PubMed and PsycINFO databases were searched through July 2012. Publications were included if they were in English, a review article, or a clinical trial in the CVD population with comorbid depression. The search was completed with key words of antidepressants, CVD, coronary artery syndrome, SSRIs, depression, treatment of depression, post-MI (where MI is myocardial infarction), major depression, and cardiac disease. Trials were included if the patients were above the age of 18, both male and female genders, and had cardiac comorbidity. No trials were excluded. RESULTS: A total of 61 articles and/or book chapters were included. The majority were from North America and Europe. There were 7 clinical trials of tricyclic antidepressants (TCAs), one of TCAs and bupropion, and 10 trials of selective serotonin reuptake inhibitors (SSRIs). We also evaluated five trials involving psychotherapeutic techniques and/or collaborative care. CONCLUSIONS: There is considerable evidence from randomized controlled clinical trials that antidepressants, especially SSRIs, are safe in the treatment of major depression in patients with CVD. Although efficacy has been demonstrated in some, but not all, trials for both antidepressants and certain psychotherapies, large, well-powered trials are urgently needed. There are virtually no data available on predictors of antidepressant response in depressed patients with CVD. Whether successful treatment of depression is associated with a reduction in cardiac morbidity and mortality remains unknown.
HubMed – depression


Predicting a ‘Combined Treatment Outcome’ in Chronic Schizophrenia: The Role of Demographics, Symptomatology, Functioning and Subjective -Well-being.

Filed under: Depression Treatment

Pharmacopsychiatry. 2013 Jan 4;
Naber D, Kollack-Walker S, Chen J, Stauffer VL, Kinon BJ, Case M, Ascher-Svanum H, Kapur S, Kane JM

The aim of this study was to determine what variables predict a ‘combined treatment outcome’ (COMBOUT) in patients with chronic schizophrenia.This analysis (n=522) was based on a randomized, double-blind, flexible-dose, 12-week study that enrolled chronically-ill patients diagnosed with schizophrenia or a related disorder. COMBOUT was assessed using the PANSS for symptoms, CGI-S for overall clinical status, MADRS for depressive symptoms, QLS for functioning/QOL, and SWN-K for subjective well-being. Possible predictors included demographics as well as baseline scores (Model I), and early change (week 2) scores (Model II).Model I: significantly better outcome (higher COMBOUT score) was observed in patients with lower MADRS (T=?-?6.36; p<0.001) or higher QLS (T=5.05; p<0.001) scores at baseline. Model II: significantly better COMBOUT was observed in patients with early improvement of QLS (T=4.93; p<0.001), SWN-K (T=3.88; p<0.001), PANSS (T=?-?2.32; p=0.021) and CGI-S scores (T=?-?2.22; p=0.027). Changes in EPS were not predictors of COMBOUT in the models tested.COMBOUT at endpoint was predicted by lower depressive symptom score and higher QOL at baseline and by early improvement in psychopathology, quality of life and subjective well-being. HubMed – depression



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