Depression neurobiology

Sevarino KA, Oliveto A, Kosten TR Neurobiological adaptations to psychostimulants and opiates as a basis of treatment development. Ann N Y Acad Sci 909 51 —87,2000 Silberman EK, Reus VI, Jimerson DC, et al Heterogeneity of amphetamine response in depressed patients. AmJ Psychiatry 138 1302—1307, 1981 Sofuoglu M, Brown S, Babb DA, et al Depressive symptoms modulate the subjective and physiological response to cocaine in humans. Drug Alcohol Depend 63 131-137, 2001... 

Nortriptyline. Nortriptyhne, a tricychc antidepressant, has been shown in double-blind, placebo-controlled randomized trials to be superior to placebo for smoking cessation (Prochazka et al. 1998). Nortriptyline appears to have efficacy comparable to that of bupropion for smoking cessation (Hall et al. 2002). The efficacy of this agent may be improved with more intensive behavioral therapies (Hall et al. 1998). Nortriptyline s mechanism of action is thought to relate to its noradrenergic and serotonergic reuptake blockade, because these two neurotransmitters have been implicated in the neurobiology of nicotine dependence. Side effects of nortiptyline are typical of tricyclic antidepressants and include dry mouth, blurred vision, constipation, and orthostatic hypotension. Nortriptyline appears to have some utility for smokers with a past history of major depression, and it can be recommended as a second-... 

Finally, there is little or no clinical evidence that morphine causes psychological dependence or drug-seeking behaviour, tolerance or problematic respiratory depression in patients. These events simply do not occur when opioids are used to control pain. The reason is likely to be that the actions of morphine and the context of its use in a person in pain are neurobiologically quite different from the effects of opioids in street use. These actions of opioids are described in more detail in Chapter 23. 

Attempts to find the cause(s) of depression have adopted two main approaches. One is to look for the neurobiological basis of depression in human subjects and animal models of this condition. The second is to investigate the pharmacology of established antidepressant agents to see whether they consistently augment some, and ideally the same, neurobiological targets in the brain. 

A second objective is to produce behavioural changes in animals that are analogous to depression so that the model can be used to discover its neurobiological cause(s). This is a far more demanding problem and its success rests on satisfying at least three criteria (see Willner 1984) face validity (i.e. the behaviour looks like depression), construct validity (i.e. the causes and consequences of the behavioural change are the same as in depression) and predictive validity (i.e. the behaviour is reliably prevented only by drugs which have antidepressant effects in humans). 

Procedures that have been suggested as models of depression and used to look for neurochemical changes that parallel the onset of the behavioural change, as well as to test how antidepressants affect the behaviour, are listed in Table 20.3. Those that have been used most, either as a drug screen or in research into the neurobiology of depression, are as follows. 

Department of Psychiatry and Behavorial Neurobiology University of Alabama at Birmingham Birmingham, Alabama Chapter 35 Major Depressive Disorder... 

Leonard BE (1975). Neurochemical and neuropharmacological aspects of depression. International Review of Neurobiology, 18, 357-387. 

Manji HK, Drevets WC and Charney DS (2001). The cellular neurobiology of depression. 

The reason most likely lies in genetic and developmental effects having created a neurobiological diathesis for recurrent episodes of major depression or mania. It is of note that the clinical picture of major depression varies greatly... 

Lopez, J. F., Chalmers, D. T., Little, K, Y. and Watson, S. J. A. E. Bennett Research Award. Regulation of serotonin 1 A, glucocorticoid, and mineralocorticoid receptor in rat and human hippocampus implications for the neurobiology of depression. Biol. Psych. 43 547-573,1998. 

Eison MS. (1990). Serotonin a common neurobiologic substrate in anxiety and depression. J Clin Psychopharmacol. 10(3) SuppI 26S-30S. 

Paul SM. (1988). Anxiety and depression a common neurobiological substrate J Clin Psychiatry. 49(suppl) 13-16. 

Balfour DJK, Ridley DL (2000) The effects of nicotine on neural pathways implicated in depression a factor in nicotine addiction Pharmacol Biochem Behav 66 79-85 Balfour DJK, Birrell CE, Moran RJ, Benwell MEM (1996) Effects of acute D-CPPene on mesoac-cumbens dopamine responses to nicotine in the rat. Eur J Pharmacol 316 153-156 Balfour DJK, Wright AE, Benwell MEM, BirreU CE (2000) The putative role of extra-synaptic mesolimbic dopamine in the neurobiology of nicotine dependence. Behav Brain Res 113 73-83... 

One hypothesis is that an impairment ofserotonergic transmission through hippocampal 5-HTia receptors may underlie the low mood seen in depression. In addition, the reduced activation of hippocampal 5-HTia receptors may decrease the inhibitory control of the HPA axis mediated by the hippocampus leading to hypercortisolaemia and a neuropsychological impairment. An alternative hypothesis is that the primary neurobiological disturbance in depression is an abnormality of GRs leading to an impaired feedback control of the HPA axis and hypercortisolaemia. This in turn may lead to neuropsychological dysfunction. Reduced functional activity of GRs may increase the autoinhibitory action of somatodendritic 5-HTja receptors, decrease 5-HTia receptor num-... 

Manahan-Vaughan D, Braunewell KH (1999) Novelty acquisition is associated with induction of hippocampal long-term depression. Proc Natl Acad Sci U S A 96 8739-8744 Maren S (2001) Neurobiology of Pavlovian fear conditioning. Annu Rev Neimosci 24 897-931 Maren S, Holt W (2000) The hippocampus and contextual memory retrieval in Pavlovian conditioning. Behav Brain Res 110 97-108... 

Prog Neuropsychopharmacol Biol Psychiatry 25 141-166 Henn FA, Johnson J, Edwards E, Anderson D (1985) Melancholia in rodents neurobiology and pharmacology. Psychopharmacol Bull 21 443-446 Henn FA, Edwards E, Muneyyird J (1993) Animal models in depression. Clin Nemosci 1 152-156... 

Here we shall summarize the neurobiology of adult depression and anxiety disorders and compare these findings to the consequences of early-life stress. For information on the neurobiology of childhood mental disorders, we refer to Part I-C in this book. Notably, there are marked differences in the neurobiology of childhood depression, as compared to adulthood depression, and there appears to exist a subtype of childhood depression that is related to early trauma and has a distinct neurobiology. 

In this chapter we review extant data on the neurobiology of unipolar and bipolar depressive disorders in children and adolescents. A complement to two recent reviews (Kaufman and Ryan, 1999 Kaufman et ah, 2001), this chapter places primary emphasis on those studies in which neuroimaging techniques have been used. Unfortunately, such studies are few and far between. Preclinical models that have guided research on the neurobiology of affective disorders in adults are discussed, and, given the limits in the application of these models to juvenile samples, especially in the case of unipolar disorder, the need for more developmentally focused preclinical work is emphasized. 

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