scholarly journals Allelic variation in 5-HTTLPR and the effects of citalopram on the emotional neural network

2015 ◽  
Vol 206 (5) ◽  
pp. 385-392 ◽  
Author(s):  
Yina Ma ◽  
Bingfeng Li ◽  
Chenbo Wang ◽  
Wenxia Zhang ◽  
Yi Rao ◽  
...  

BackgroundSelective serotonin reuptake inhibitors (SSRIs), such as citalopram, which selectively block serotonin transporter (5-HTT) activity, are widely used in the treatment of depression and anxiety disorders. Numerous neuroimaging studies have examined the effects of SSRIs on emotional processes. However, there are considerable inter-individual differences in SSRI effect, and a recent meta-analysis further revealed discrepant effects of acute SSRI administration on neural responses to negative emotions in healthy adults.AimsWe examined how a variant of the serotonin-transporter polymorphism (5-HTTLPR), which affects the expression and function of 5-HTT, influenced the acute effects of an SSRI (citalopram) on emotion-related brain activity in healthy adults.MethodCombining genetic neuroimaging, pharmacological technique and a psychological paradigm of emotion recognition, we scanned the short/short (s/s) and long/long (l/l) variants of 5-HTTLPR during perception of fearful, happy and neutral facial expressions after the acute administration of an SSRI (i.e. 30mg citalopram administered orally) or placebo administration.ResultsWe found that 5-HTTLPR modulated the acute effects of citalopram on neural responses to negative emotions. Specifically, relative to placebo, citalopram increased amygdala and insula activity in l/l but not s/s homozygotes during perception of fearful faces. Similar analyses of brain activity in response to happy faces did not show any significant effects.ConclusionsOur combined pharmacogenetic and functional imaging results provide a neurogenetic mechanism for discrepant acute effects of SSRIs.

2014 ◽  
Vol 45 (4) ◽  
pp. 841-854 ◽  
Author(s):  
A. J. Skilleter ◽  
C. S. Weickert ◽  
A. Vercammen ◽  
R. Lenroot ◽  
T. W. Weickert

Background.Brain-derived neurotrophic factor (BDNF) is an important regulator of synaptogenesis and synaptic plasticity underlying learning. However, a relationship between circulating BDNF levels and brain activity during learning has not been demonstrated in humans. Reduced brain BDNF levels are found in schizophrenia and functional neuroimaging studies of probabilistic association learning in schizophrenia have demonstrated reduced activity in a neural network that includes the prefrontal and parietal cortices and the caudate nucleus. We predicted that brain activity would correlate positively with peripheral BDNF levels during probabilistic association learning in healthy adults and that this relationship would be altered in schizophrenia.Method.Twenty-five healthy adults and 17 people with schizophrenia or schizo-affective disorder performed a probabilistic association learning test during functional magnetic resonance imaging (fMRI). Plasma BDNF levels were measured by enzyme-linked immunosorbent assay (ELISA).Results.We found a positive correlation between circulating plasma BDNF levels and brain activity in the parietal cortex in healthy adults. There was no relationship between plasma BDNF levels and task-related activity in the prefrontal, parietal or caudate regions in schizophrenia. A direct comparison of these relationships between groups revealed a significant diagnostic difference.Conclusions.This is the first study to show a relationship between peripheral BDNF levels and cortical activity during learning, suggesting that plasma BDNF levels may reflect learning-related brain activity in healthy humans. The lack of relationship between plasma BDNF and task-related brain activity in patients suggests that circulating blood BDNF may not be indicative of learning-dependent brain activity in schizophrenia.


2010 ◽  
Vol 21 (7) ◽  
pp. 931-937 ◽  
Author(s):  
C. Nathan DeWall ◽  
Geoff MacDonald ◽  
Gregory D. Webster ◽  
Carrie L. Masten ◽  
Roy F. Baumeister ◽  
...  

Pain, whether caused by physical injury or social rejection, is an inevitable part of life. These two types of pain—physical and social—may rely on some of the same behavioral and neural mechanisms that register pain-related affect. To the extent that these pain processes overlap, acetaminophen, a physical pain suppressant that acts through central (rather than peripheral) neural mechanisms, may also reduce behavioral and neural responses to social rejection. In two experiments, participants took acetaminophen or placebo daily for 3 weeks. Doses of acetaminophen reduced reports of social pain on a daily basis (Experiment 1). We used functional magnetic resonance imaging to measure participants’ brain activity (Experiment 2), and found that acetaminophen reduced neural responses to social rejection in brain regions previously associated with distress caused by social pain and the affective component of physical pain (dorsal anterior cingulate cortex, anterior insula). Thus, acetaminophen reduces behavioral and neural responses associated with the pain of social rejection, demonstrating substantial overlap between social and physical pain.


Author(s):  
Tetsuya Hirono ◽  
Tome Ikezoe ◽  
Masashi Taniguchi ◽  
Momoko Yamagata ◽  
Jun Umehara ◽  
...  

2018 ◽  
Vol 31 (1) ◽  
pp. 46-51
Author(s):  
S. Melker Hagsäter ◽  
Johan Thorén ◽  
Robert Pettersson ◽  
Elias Eriksson

AbstractObjectiveWhereas long-term administration of selective serotonin reuptake inhibitors (SSRIs) is effective for the treatment of anxiety disorders, acute administration of these drugs may exert a paradoxical anxiogenic effect. The aim of the present study was to explore the possible effect of an SSRI in situations of unconditioned or limited conditioned fear.MethodsMale Sprague Dawley rats were administered a single dose of an SSRI, escitalopram, before acquisition or expression of context conditioned fear, where noise bursts were used as the unconditioned stimulus. Freezing was assessed as a measure of unconditioned fear (=the acute response to noise bursts) or conditioned fear (=the response to the context), respectively.ResultsNoise bursts elicited an acute increase in freezing but no robust conditioned response 7 days after exposure. Administration of escitalopram before testing exacerbated the freezing response during presentation of the unconditioned stimulus and also unmasked a conditioned response; in contrast, administration of escitalopram prior to acquisition did not influence the conditioned response.ConclusionThe data suggest that freezing in rats exposed to a stimulus inducing relatively mild fear may be enhanced by acute pretreatment with an SSRI regardless of whether the freezing displayed by the animals is an acute unconditioned response to the stimulus in question or a conditioned response to the same stimulus.


2011 ◽  
Vol 26 (S2) ◽  
pp. 2186-2186
Author(s):  
S. Kasper

Depression is one of the thoroughly evaluated diseases in psychiatry with regard to diagnosis as well as treatment variables. Like in other medical conditions, early treatment should be aimed and watchful waiting which is for instance also not done in the treatment of high blood pressure or diabetes, has not been proven to be a sophisticated approach based on neurobiological considerations. Like in other diseases, it is apparent that days of untreated depression may result in brain damage like reduced volume size of the hypocampus. The course of illness of depression shows that life events are less important in later stages of the illness than in earlier. The introduction of the group of selective serotonin reuptake inhibitors (SSRI) marked a revolution in the treatment of depression, since it was possible to treat patient for the first time effectively with a more minor side effect profile with this approach. Substantially more patients could be reached and the association with this phenomenon and the reduction of the suicide rates in different countries like Sweden, Austria and Hungary has been discussed. Dual reuptake inhibitors effecting both the serotonergic as well as the noradrenergic pathways and the dopaminergic noradrenergic medication bupropion have been introduced in the filed with specific angles of treatment goals like pain or somatic symptoms. With the introduction of agomelatine, a unique mechanism of action with the combination of melatonergic agonistic as well as serotonergic antagonistic activities has been achieved. With this approach a more potent influence on the circadian rhythm has been shown compared to other, previously used antidepressant properties. Deep brain stimulation and vagus nerve stimulation for treatment refractory depressed patients yield promising results. More thorough characterisation of the underlying pathophysiology of depression including brain imaging results as well as molecular biological variables will yield further inside of the understanding and treatment of depression.


2008 ◽  
Vol 39 (2) ◽  
pp. 255-265 ◽  
Author(s):  
J. Barrett ◽  
J. L. Armony

BackgroundWe examined how individual differences in trait anxiety (TA) influence the neural responses associated with the acquisition and extinction of anticipatory anxiety elicited through a context conditioning paradigm, with particular focus on the amygdala and the subgenual anterior cingulate cortex (sgACC).MethodDuring two sessions of echo-planar functional magnetic resonance imaging (fMRI), 18 healthy volunteers completed a decision-making task with two randomly alternating 28-s to 32-s background screen colour blocks. One of the colours was associated with the presentation of an aversive noise (CTX+) and the other colour was ‘safe’ (CTX−). In the first session (Acquisition), 33% of CTX+ colour blocks were paired with noise and in the second session (Extinction) no noise was presented.ResultsThe amygdala displayed an increased response to CTX+ compared to CTX− colour blocks during the Acquisition and Extinction sessions and the ACC displayed an increased response to CTX+ compared to CTX− colour blocks during Extinction only. In addition, a greater conditioned response (CTX+ minus CTX−) was observed in the ACC when comparing the Extinction and Acquisition sessions. Correlation analyses further showed that higher levels of TA were associated with a higher conditioned response in the amygdala during Extinction as well as a greater differential conditioned response (i.e. Extinction>Acquisition) in the ACC.ConclusionsOur results support the idea that individuals with high levels of anxiety-relevant traits and vulnerable to developing an anxiety disorder display a more resilient anxiety response during extinction that is characterized by hyper-responsivity in the amygdala.


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