The Serotonergic Hypothesis for Depression in Parkinson's Disease: an Experimental Approach

Leentjens, Albert F.G.; Scholtissen, Bart; Vreeling, F.W.; Verhey, Frans R.J.

doi:10.1038/sj.npp.1300914

Cited by 45 publications

(32 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It should be mentioned though that evidence against the model has been found in an ATD study in Parkinson's disease (PD) patients. 383 This study found no support for SV in PD patients, although these patients generally have reduced 5-HT activity and an increased risk of depression. These results may debilitate the model, although there may be several possible explanations for the negative finding.…”

Section: Limitations Of the Modelcontrasting

confidence: 54%

Serotonergic vulnerability and depression: assumptions, experimental evidence and implications

et al. 2006

View full text Add to dashboard Cite

In recent years, the term serotonergic vulnerability (SV) has been used in scientific literature, but so far it has not been explicitly defined. This review article attempts to elucidate the SV concept. SV can be defined as increased sensitivity to natural or experimental alterations of the serotonergic (5-HTergic) system. Several factors that may disrupt the 5-HTergic system and hence contribute to SV are discussed, including genetic factors, female gender, personality characteristics, several types of stress and drug use. It is explained that SV can be demonstrated by means of manipulations of the 5-HTergic system, such as 5-HT challenges or acute tryptophan depletion (ATD). Results of 5-HT challenge studies and ATD studies are discussed in terms of their implications for the concept of SV. A model is proposed in which a combination of various factors that may compromise 5-HT functioning in one person can result in depression or other 5-HT-related pathology. By manipulating 5-HT levels, in particular with ATD, vulnerable subjects may be identified before pathology initiates, providing the opportunity to take preventive action. Although it is not likely that this model applies to all cases of depression, or is able to identify all vulnerable subjects, the strength of the model is that it may enable identification of vulnerable subjects before the 5-HT related pathology occurs. Molecular Psychiatry ( Keywords: serotonin; mood disorders; stress; genetics; sex; tryptophan Involvement of serotonin in depressionMood disorders are one of the most prevalent forms of mental illness. 1 According to the DSM-IV, the lifetime risk for major depressive disorder is between 10 and 25% for women and between 5 and 12% for men. 2 Depression has been studied intensively during the last few decades, but the psychological and neurobiological determinants of depression have not yet been precisely defined. Although several factors are known to contribute to the etiology of depression, it is not clear how these factors cause depression, and why some subjects become depressed while others remain unaffected. In terms of biological factors in the etiology of depression, there are several hypotheses. These include neurotransmitter dysfunctions (serotonin, 5-HT; dopamine, DA; norepinephrine, NE); dysregulations in hypothalamic-pituitary-adrenal (HPA) axis activity; and immune system imbalance. The aim of this article is not to discuss all of these hypotheses in detail, but to evaluate the role that serotonin may play within these hypothesized mechanisms.It is widely accepted that diminished serotonergic (5-HTergic) function is involved in the onset and course of depression. 3,4 The 5-HTergic system is a large and complex system. Although nearly all cell bodies of 5-HTergic neurons are located in the raphe nuclei in the brain stem, the axons of these neurons innervate almost the entire brain. The actions of 5-HT are mediated by 16 types and subtypes of receptors. 5 As the 5-HTergic system is assumed to be a modulatory system, the exact func...

show abstract

Section: Limitations Of the Modelcontrasting

confidence: 54%

Serotonergic vulnerability and depression: assumptions, experimental evidence and implications

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Depression and apathy in PD may be associated to different factors: depression is probably related to the dysfunction of different neurotransmitters, including dopamine, serotonin and norepinephrine [65][66][67][68][69][70][71], to the effects of dopaminergic therapies on other neurotransmitters [72] and to the amygdalar dysfunction [73][74][75] that affects patients since the early stages of PD and is considered an hallmark of depression [76]. Apathy is probably more related to the hypostimulation of OFC, an area involved in affective processing, which is affected in PD patients in moderate/advanced stages of the disease [49][50][51][52].…”

Section: Discussionmentioning

confidence: 99%

Affective symptoms and cognitive functions in Parkinson's disease

Poletti

Rosa

Bonuccelli

2012

Journal of the Neurological Sciences

View full text Add to dashboard Cite

“…HA and PD could be caused by shared genetic and/or early environmental risk factors that predispose subjects, independently, to both PD and certain personality traits: therefore the presence of affective disorders in PD may be characterized as a part of a chronic maladaptive strategy belonging to an affective/ personality trait, rather than being state dependent [86][87][88][89]. Conversely, the increased HA could be state dependent and due to the presence of affective disorders; in this perspective many factors could contribute to the high tendency toward negative affect of PD patients, resulting in high rates of affective disorders and high HA: the deficit of serotonin [90][91][92] that characterizes this clinical population since the early clinical stages [93]; the early amygdala dysfunction of PD [94][95][96] which is considered a hallmark of depression and anxiety [97,98]; the executive dysfunction that characterizes PD patients from the early clinical stages [99] and that represents a risk factor for the development of depression in the elderly [100].…”

Section: High Harm Avoidancementioning

confidence: 99%

Personality traits in patients with Parkinson’s disease: assessment and clinical implications

Poletti

Bonuccelli

2011

J Neurol

View full text Add to dashboard Cite

This study reviews empirical evidence on the association between personality traits and Parkinson's disease (PD), with a twofold aim. First, to better identify non-motor symptoms, such as affective symptoms and personality changes, that could help to define the pre-motor phase of PD; second, to better understand the neurobiological bases of personality traits, a goal that is not fully accomplished by a purely anatomical approach. A literature review was performed on studies of personality traits in PD patients, in electronic databases ISI Web of Knowledge, Medline and PsychInfo, conducted in July 2011. We found evidence that the existence of a characteristic premorbid personality profile of PD patients is not actually sustained by robust empirical evidence, mainly due to the methodological bias of the retrospective assessment of personality; PD patients present a personality profile of low novelty seeking and high harm avoidance. We concluded that the definition of a pre-motor phase of PD, based on non-motor symptoms, should search for the presence of concomitant affective disorders and for a positive psychiatric history for affective disorders rather than for a typical personality profile or personality changes. The low novelty seeking profile is probably related to the dopaminergic deficit, while the high harm avoidance profile is probably associated with the presence of affective disorders. Clinical implications of these findings, in regard to personality assessment and pharmacological treatments in PD, are also discussed.

show abstract

The Serotonergic Hypothesis for Depression in Parkinson's Disease: an Experimental Approach

Cited by 45 publications

References 53 publications

Serotonergic vulnerability and depression: assumptions, experimental evidence and implications

Serotonergic vulnerability and depression: assumptions, experimental evidence and implications

Affective symptoms and cognitive functions in Parkinson's disease

Personality traits in patients with Parkinson’s disease: assessment and clinical implications

Contact Info

Product

Resources

About