Original Article
Stress in the brain: implications for treatment of depression
- Er de Kloet
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- Published online by Cambridge University Press:
- 11 July 2016, pp. 155-166
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A fundamental question in stress research is when the glucocorticoid stress hormone (cortisol in man) stops being neuroprotective and becomes harmful to the brain with negative consequences for cognition and mood. To address this question Section 1 focuses on the action mechanism of glucocorticoids. These hormones act via high and low affinity nuclear receptors, which regulate gene transcription in a coordinate manner. The receptors are expressed abundantly in hippocampus, amygdala and frontal cortex involved in cognitive processes. In Section 2 hypercortisolism is considered a potential disease factor for about 50% of the patients suffering from major depression. Recent data show that these patients recover within a few days when excess cortisol action is blocked with high doses of an antiglucocorticoid. Section 3 concerns animal models with ‘depression-like’ features of hypercorticism generated by manipulation of gene X environment inputs. Using gene expression profiling technology in the hippocampal transcriptome of these animals we identified about 700 potential targets for antidepressants out of 30 000 detectable gene products. One of our models is based on early life programming of the stress system. Rats exposed as pups to maternal deprivation display at senescence an enhanced individual difference in cognitive performance. The maternally deprived senescent animals age either successfully or become senile, at the expense of the average performance of non-deprived controls. The essay is concluded with the notion that the new generation of antidepressants ameliorates specific psychic dysfunctions (e.g. cognitive performance) linked to aberrant stress hormone action in discrete brain regions.
Which depressions are related to life stress?
- E. S. Paykel
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- Published online by Cambridge University Press:
- 24 June 2014, pp. 167-172
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This paper examines the relationship of recent life events to specific kinds of depression using published studies and the author's own work. An overall effect of life events on depression has been found consistently and is moderate in degree. In suicide attempts there are stronger and more immediate effects than in depression. Life events precede both non-melancholic and melancholic depressions. It is only in recurrent depressions that life events are less common with melancholic pictures. Life events influence bipolar disorder as well as unipolar. Mania may be preceded by life events, particularly those involving social rhythm disruption, but it is harder to rule out events which are consequences of insidious development of illness. There are strong effects of life events and social support in postpartum depressions but in postpartum psychoses these effects are absent. Events precede depression comorbid with other disorders as well as pure depression. The course of depression is also influenced by life stress with less remission where negative events occur after onset and better outcome where earlier adverse events are neutralized. Relapse is related to immediately preceding life events. However, where depressions are both severe and recurrent life stress effects weaken and as the number of episodes increases preceding life events lessen. These findings suggest that some kinds of depression are more related to psychosocial causation and some are more biological in origin.
Stress, norepinephrine and depression
- Brian E. Leonard
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- Published online by Cambridge University Press:
- 24 June 2014, pp. 173-180
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Experimental and clinical evidence implicates stress as a major predisposing factor in depression and other severe psychiatric disorders. In this review, evidence is presented to show how the impact of stress on the central sympathetic system leads to changes in the endocrine, immune and neurotransmitter axes which underlie the main clinical symptoms of depression. Thus it can be shown that the noradrenergic system is dysfunctional in depression, a situation which reflects the chronic hypersecretion of glucocorticoids and inflammatory mediators within the brain in addition to an enhanced activity of the locus ceruleus. With regard to the actions of antidepressants in modulating the stress response and alleviating depression it is now evident that, irrespective of the presumed specificity of the antidepressants for the noradrenergic or serotonergic systems, they all normalize noradrenergic function. This action is due partly to the regulation of tyrosine hydroxylase activity in the locus ceruleus but also enhances neuronal sprouting which counteracts the neurodegenerative effects of chronic stress.
Neuroticism, alexithymia, negative affect and positive affect as predictors of medically unexplained symptoms in primary care1
- V. De Gucht
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- Published online by Cambridge University Press:
- 24 June 2014, pp. 181-185
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Background:
Somatization has been defined in a number of ways. Despite their differences, these definitions have one element in common, namely the presence of somatic symptoms that cannot be explained (adequately) by organic findings.
Objective:The primary objectives of the dissertation were to gain a better insight into the concept of somatization, and to study (prospectively) the relationship between neuroticism and alexithymia, two personality traits that have been shown to be related to somatization, the affective state dimensions positive and negative affect (or psychological distress) and medically unexplained symptoms.
Method:A selective review was conducted regarding conceptual and methodological issues related to somatization. A total number of 318 patients, presenting to their primary care physician with medically unexplained symptoms, participated in the prospective study. Both at baseline and at 6-month follow-up a number of measures were filled out with respect to somatization, neuroticism, alexithymia, negative and positive affect, anxiety and depression.
Results:The concept of somatization was clarified, thereby making use of the distinction between presenting and functional somatization. The personality traits neuroticism and alexithymia were found to have an indirect influence on symptom reports. Both the cross-sectional and follow-up data pointed to the importance of positive and negative affect as determinants of (changes in) number of symptoms (over time). Negative affect, together with the alexithymia dimension measuring difficulty identifying feelings, predicted symptom persistence.
Conclusions:The theoretical as well as therapeutic implications of the present paper may give an impetus to new research in the domain of somatization.
Stress, cortisol and memory as markers of serotonergic vulnerability
- Wim J. Riedel, Sjacko Sobczak, Nancy Nicolson, Adriaan Honig
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- 24 June 2014, pp. 186-191
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Objective:
In the present paper the association of stress-induced cortisol with memory impairment is discussed
Methods:An experiment is described in which an attempt is made to block stress-induced cortisol by lowering 5-HT neurotransmission by means of acute tryptophan depletion (ATD). Forty-five healthy control subjects participated in the experiment.
Results:Stress-induced peak cortisol and immediate memory performance were negatively associated. ATD tended to block stress-induced cortisol response. ATD also blocked the association between peak cortisol response and memory impairment.
Conclusions:Stress-induced cortisol and its association with memory impairment is mediated at least partially by serotonin.
The clinical application of the stress concept
- F. Koerselman
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- 24 June 2014, pp. 192-195
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Background:
Knowledge on fundamental aspects of the influence of ‘stress’ on animal and human organisms is accumulating. In clinical situations, however, psychiatrists still do not use apropriate instruments to recognize and handle the impact of daily life stress. DSM-IV is insufficient in this respect.
Objective:A different approach is sketched for clinicians to be able to integrate knowledge from research more effectively.
Method:Application of a ‘broad’ biological view may reveal the significance of interpretation, emotion, impulse and reaction as stages of a ‘mental tract’, which is involved in processing the input of stressful situations.
Result:This may lead to a more rational ‘targeting’ of pharmacological and psychotherapeutic strategies in clinical practice.
Conclusion:A re-orientation of clinical psychiatry from mere classification towards a ‘broad’ biological approach may pave the way for a more rational and purposeful application of research findings to therapy.
Clinical models of stress
- Mjajm Hoes
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- Published online by Cambridge University Press:
- 24 June 2014, pp. 196-201
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Background:
Here we propose a stress model with disease-specific aspects and aspecific factors. The latter are subdivided into load (perception, psychic defence mechanisms), strain (psychophysiological responses) and stress sensu strictu (biological and behavioural compensation). Insufficiently compensated strain will result in being sick and precipitation of a specific disease according to one's predisposition. In the clinical practice, multiconditionality requires a multidimensional analysis, the the five-axial DSM-system being designed especially for this purpose. Multidisciplinary treatment is then organized accordingly, i.e. Axis I: case management, medication; Axis II, (focal) psychotherapy; Axis III, somatic specialists; Axis IV, social worker; Axis V, psychotherapy for coping deficits.
Objective:To test the efficacy of this multimethodical approach.
Method:In a 1-year prospective study of 257 admissions in a department of psychiatry in a general hospital, the General Health Questionnaire (30 items) was filled out at admission, discharge and first polyclinical visit post-discharge.
Results:The 213 evaluable questionnaires at admission did not show differences (17–18.9) between the four groups, mood disorders (62%), alcoholism (17%), psychoses (15%) and anxiety disorders (6%). At discharge all four groups had reached the cut-off value for ‘not-sick’ (< 6), this remaining so at follow-up; the three measurements differed significantly throughout the patient groups. Hospitalization was definitely 28.2 days shorter than the Dutch mean of 42 days.
Conclusions:Working to the proposed clinical model for multiconditionalty is effective on intensity and duration of disorders, sustained improvement is attained.