Charles B Nemeroff CB

....

..This article reviews the findings implicating the GABA system in the pathophysiology of anxiety disorders and describes the potential role of agents that modulate GABA neurotransmission in the treatment of these disorders...

..Last, because of the extensive literature on NT/DA interactions available in the rat, our discussion will be based primarily on studies using this species...

..The preclinical and clinical studies evaluating the consequences of early-life stress are reviewed...

....

..Our results suggest that psychotherapy may be an essential element in the treatment of patients with chronic forms of major depression and a history of childhood trauma...

..Given the public health importance of TRD, the relative absence of adequately powered, double-blind trials is striking...

..Subsequent clinical trials led to the widespread, but short-lived, use of iproniazid for treatment of depression in 1957 and demonstration of its monoamine oxidase inhibitor properties...

..The mechanisms of action of available medications are directing the field toward new research avenues. This review highlights those areas we believe will influence the field and soon lead to better treatment...

..Further clarification of the precise neurobiological changes occurring in depression has implications for the use and development of novel effective treatments for this disorder...

..Finally, imaging studies with positron emission tomography confirm significant differences between quetiapine and typical antipsychotics that may be indicative of their differences in mechanism of action and propensity for producing EPS...

..The potential for excessive weight gain as a side effect of certain psychopharmacologic agents remains a concern to both clinicians and patients...

..The long-sought-after class of anxiolytics that are both effective and safe may be found in the new research being conducted with agents that selectively target GABA receptors and their subtypes...

..Each SSRI apparently has its own unique pharmacologic properties that likely underlie their observed differences in clinical use...

..To compare venlafaxine and selective serotonin reuptake inhibitors (SSRIs; fluoxetine, sertraline, paroxetine, fluvoxamine, and citalopram) in the treatment of depression...

..Mechanisms that mediate the beneficial effects of VNS therapy for treatment-resistant depression remain obscure. Suggestions for future research directions are described...

..The compilation of data suggests that NT receptor agonists may represent a novel class of antipsychotic drugs for the treatment of schizophrenia...

..The findings of clinical trials evaluating platelet responses to antidepressant treatment are described, and recommendations for future studies are proposed...

..This monograph summarizes the efficacy, tolerability, and safety of oral ziprasidone in the treatment of schizophrenia, schizoaffective disorder, and bipolar mania...

..Further double-blind, placebo-controlled studies of augmentation of antidepressants with atypical antipsychotics in refractory depression and anxiety are justified based on the available literature...

..Other recent approaches have included several anticonvulsant agents, as well as conventional and atypical antipsychotic agents...

....

..The efficacy profile of fluoxetine was somewhat less consistent. It is strongly recommended that future studies of comparative antidepressant efficacy be adequately powered to detect modest between-drug differences in efficacy...

..Improved knowledge and treatment approaches for severe depression are necessary to facilitate remission, the ideal treatment goal...

..In addition, studies of the CRF system have suggested molecular targets for new drug development, biological risk factors, and predictors of treatment response...

..Psychopharmacology Bulletin. 2004;38(Suppl 1): 38-45...

..Psychopharmacology Bulletin. 2004;38(Suppl 1): 14-20...

..Clinicians encountering patients with depressive disorders should be proficient in the assessment and treatment of depression with suicidality...

..CONCLUSIONS: Milnacipran's binding and uptake inhibition profile more closely resembles that of the tricyclic antidepressants than that of duloxetine. Whether these differences observed in vitro manifest themselves in vivo is not clear...

....

..Although both compounds displayed high affinity and selectivity for the human NET in vitro, these compounds did not enter the CNS in adequate amounts to be used in PET imaging studies...

....

..Prolonged, daily maternal separation of rat pups induces several behavioral, endocrine and neurochemical changes similar to those observed in human depression...

....

..These data support an effect of time of day and estrous cycle stage on PPI in female rats. The estrous cycle variations in PPI are mediated in part by endogenous NT...

..The distinct actions of each drug on CRF systems may underlie their synergistic clinical effects...

....

..Despite high in vitro affinity for the human NET, the uptake of [(11)C]3-BrPA in the brain and the heart was not displaceable with pharmacological doses of NET antagonists...

..Additional studies are required to elucidate the functional consequences and mechanisms of this interaction...

..Both genetic and environmental factors are contributory, with child abuse providing significant risk liability...

..Arterial plasma metabolites of HOMADAM were analyzed in a rhesus monkey by HPLC and displayed a single peak that corresponded to unmetabolized HOMADAM. CONCLUSION: HOMADAM is an excellent candidate for PET primate imaging of brain SERTs...

..The results indicate that both atypical antipsychotic medications provided significant additional improvement in symptom severity in patients with schizophrenia previously on conventional antipsychotic agents...

....

..The discussion will be framed in regards to a stress-diathesis model in which early adverse events result in a sensitized stress axis that predisposes individuals to develop mood disorders...

..Switching to an agent of a different class is probably optimal for those patients who fail to respond to first-line therapy...

..To establish a nonhuman primate model of cytokine-induced depression, we examined the effects of IFN-alpha on rhesus monkeys...

..Our findings suggest that a history of childhood abuse per se is related to increased neuroendocrine stress reactivity, which is further enhanced when additional trauma is experienced in adulthood...

..These results suggest that the mood stabilizing effects of valproic acid may be mediated in part by alterations in CRF neuronal activity...

..These results provide evidence that the effects of antipsychotic drugs (APDs) may be differentially affected by the state of NT neurotransmission and, moreover, that APDs differ in their dependence on an intact NT system...

..The authors review the history of techniques used to assess the functions of the HPA axis, evidence for hypercortisolemia as a state rather than trait component of depression, and treatment implications...

..Randomized, placebo-controlled trials of adequate power seeking to determine efficacy of antidepressants in the United States for the treatment of women with breast cancer and comorbid depression remain of paramount importance...

..The marked increase in CRFergic neurotransmission is hypothesized to play a major role in benzodiazepine withdrawal...

..However, antidepressant therapy may be beneficial for patients who cannot tolerate high serum lithium levels or who have symptoms that are refractory to the antidepressant effects of lithium...

..Adherence to a few guidelines for the design of dosage regimens should limit the effect of drug-drug interactions on patient status and contribute to optimal pharmacotherapy with risperidone...

....

....

....

..Clearly, additional investigation into the role of neuropeptide systems in the etiology, pathophysiology, and treatment of schizophrenia is warranted...

..All of these factors can be evaluated and addressed to limit neuropsychiatric morbidity during HCV treatment...

....

..This paper provides a review of several studies that have evaluated the role of the SERT in the pathophysiology of suicide...

..This study compared efficacy of nefazodone, psychotherapy, and their combination in improving psychosocial functioning in chronically depressed outpatients...

..The improvements in assay specificity, signal-to-noise ratios, biomatrix compatibility and assayable sample volume compared to non-enrichment HPLC-EC are discussed...

....

..If replicated, the association of lower adult CSF OT levels with childhood trauma might indicate that alterations in central OT function may be involved in the adverse outcomes of childhood adversity...

..These results demonstrate that there is a critical time point in development before which the NT system does not respond to antipsychotic drug administration in the same manner as the mature rat...

..However, the accumulation of radioactivity in the brain for both radiotracers was very low at all time points of the study, which demonstrated the difficulties for these radiopharmaceuticals to penetrate the blood brain barrier (BBB)...

..The ongoing clinical trials with NK(1) receptor antagonists have served as an impetus for much needed, basic research in this field...

..Molecular Psychiatry (2009) 14, 37-50; doi:10.1038/mp.2008.91; published online 12 August 2008...

..In-depth characterization of these variants will likely be important in furthering our understanding of the long-term consequences of adverse experience...

..Focal brain stimulation therapies include vagus nerve stimulation (VNS), transcranial magnetic stimulation (TMS), magnetic seizure therapy (MST), transcranial direct current stimulation (tDCS), and deep brain stimulation (DBS)...

..The application of these findings of in vivo NET inhibition by paroxetine in the treatment of mood and anxiety disorders will be informed by further clinical studies...

..These are just two of the many new directions that will likely lead to the development of antidepressants in the near future...

..However, treatment associated improvements in memory and cognition did not achieve statistical significance. These findings suggest that phenytoin treatment may be associated with changes in brain structure in patients with PTSD...

..The effects of the NT receptor antagonist were paralleled by its effects on catalepsy in olanzapine--but not haloperidol--treated animals...

..The goal of this article is to describe the key biological similarities and differences between anxiety disorders...

..These physiological maladaptations likely represent long-term risk factors for the development of psychopathology after exposure to additional stress...

..The identification of the neurobiological substrates of early adverse experience is of paramount importance for the development of novel treatments for children, adolescents, and adults...

..Subsequent clinical studies of the plasma concentration versus effect relationships for quetiapine may help to further define guidelines for dosage regimen design...

..Appropriate treatment of depression can result in improvement in emotional, cognitive, and behavioral symptoms of depression and reduce psychosocial impairment, disability, and associated medical morbidity...

..On subsequent stress exposure, women with a history of childhood abuse may hypersecrete CRF, resulting in down-regulation of adenohypophyseal CRF receptors and symptoms of depression and anxiety...

..In a pilot study, this deficit predicted treatment response to an experimental antidepressant. These findings support the hypothesis that alterations in 5-HT neurons play a role in the pathophysiology of depression...

..These findings indicate that activation of glutamate receptors may indirectly stimulate neurotensin release...

..CONCLUSIONS: Higher than normal plasma IL-6 concentrations were associated with a diagnosis of major depression in cancer patients. IL-6 may contribute to sickness behavior that has overlapping symptoms with major depression...

..85). The incidence of adverse events was similar in the two groups. CONCLUSIONS: In patients with malignant melanoma, pretreatment with paroxetine appears to be an effective strategy for minimizing depression induced by interferon alfa...

....

..Child abuse and trauma alter the endogenous stress response, principally corticotropin-releasing hormone and its downstream effectors, suggesting that a gene x environment interaction at this locus may be important in depression...

..1 and 64.1%, respectively (p < or = 0.05). Open-label risperidone augmentation substantially enhanced response in treatment-resistant patients, but the longer-term benefits of augmentation were not demonstrated in this study...

..We evaluated the comparative efficacy and safety of venlafaxine extended release (ER) and fluoxetine in the acute and continuation phases of treatment...

..To test the long-term efficacy and safety of venlafaxine extended-release (ER) in preventing recurrence in patients with major depression...

....

..We reviewed evidence regarding a possible relationship between mood disorders and obesity to better inform mental health professionals about their overlap...

..Recognition of these adaptations begins to define the brain regions, and neural circuitry, associated with persistent alterations induced by early life stressors and the development of mood disorders...

..Global patient ratings such as the PGI-I, as opposed to specific item-based ratings, provide less valid findings...

..To determine the efficacy and tolerability of aripiprazole, a dopamine D2 and 5-HT1A receptor partial agonist, as augmentation of antidepressant treatment of partially responding and nonresponding patients with major depressive disorder...

..To report second-year results from the 2-year maintenance phase of a long-term study to evaluate the efficacy and safety of venlafaxine extended release (ER) in preventing recurrence of depression...

..abstract_text> ..

..abstract_text> ..