Serotonin transporter binding is reduced in seasonal affective disorder following light therapy

Tyrer, Andrea; Levitan, Robert D.; Houle, Sylvain; Wilson, Alan A.; Nóbrega, José N.; Rusjan, Pablo; Meyer, Jeffrey H.

doi:10.1111/acps.12632

Cited by 31 publications

(20 citation statements)

References 64 publications

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“…These findings are a fundament of the hyposerotonergic hypothesis of depression 4 , 6 . Furthermore, extensive evidence demonstrates that the human serotonergic system is affected by season 8 , 11 and light 7 , 9 , 10 . Seasonality of symptoms in SAD has been linked to the influence of light 27 which is underscored by the efficacy of BLT 3 .…”

Section: Discussionmentioning

confidence: 99%

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Brain monoamine oxidase A in seasonal affective disorder and treatment with bright light therapy

et al. 2018

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Increased cerebral monoamine oxidase A (MAO-A) levels have been shown in non-seasonal depression using positron emission tomography (PET). Seasonal affective disorder (SAD) is a sub-form of major depressive disorder and is typically treated with bright light therapy (BLT). The serotonergic system is affected by season and light. Hence, this study aims to assess the relevance of brain MAO-A levels to the pathophysiology and treatment of SAD. Changes to cerebral MAO-A distribution (1) in SAD in comparison to healthy controls (HC), (2) after treatment with BLT and (3) between the seasons, were investigated in 24 patients with SAD and 27 HC using [11C]harmine PET. PET scans were performed in fall/winter before and after 3 weeks of placebo-controlled BLT, as well as in spring/summer. Cerebral MAO-A distribution volume (VT, an index of MAO-A density) did not differ between patients and HC at any of the three time-points. However, MAO-A VT decreased from fall/winter to spring/summer in the HC group (F1, 187.84 = 4.79, p < 0.050), while SAD showed no change. In addition, BLT, but not placebo, resulted in a significant reduction in MAO-A VT (F1, 208.92 = 25.96, p < 0.001). This is the first study to demonstrate an influence of BLT on human cerebral MAO-A levels in vivo. Furthermore, we show that SAD may lack seasonal dynamics in brain MAO-A levels. The lack of a cross-sectional difference between patients and HC, in contrast to studies in non-seasonal depression, may be due to the milder symptoms typically shown by patients with SAD.

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Section: Discussionmentioning

confidence: 99%

“…This treatment scheme was based on previous studies 3 , 21 . Three weeks were chosen as the treatment time-frame because changes to other serotonergic molecules have been shown after a similar time-period of BLT 10 . To promote compliance, therapy was addressed at following visits.…”

Section: Methodsmentioning

confidence: 99%

Brain monoamine oxidase A in seasonal affective disorder and treatment with bright light therapy

et al. 2018

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“…In patients with non‐seasonal depression and in healthy subjects, light augmented blood 5‐HT throughout the day (Rao et al., ), with platelet paroxetine and imipramine binding decreasing significantly after treatment (Mellerup, Errebo, Molin, Plenge, & Dam, ). Light therapy decreased 5‐HT transporter binding by a radioligand in anterior cingulate and prefrontal cortex (Tyrer et al., ), thus counteracting its excessive winter seasonal increase in patients with SAD (Tyrer et al., ). These mechanisms are necessary for the antidepressant effect, because both rapid tryptophan/5‐HT depletion and catecholamine depletion reverse the antidepressant effect of LT in SAD (Lam et al., ; Neumeister et al., ).…”

Section: Where Are We Today?mentioning

confidence: 99%

“…; Benedetti, Radaelli, et al., ; Benedetti et al., ; Benedetti, Serretti, et al., ; Dallaspezia et al., , ; Serretti et al., ; Serretti, Cusin, et al., ). Examples from human neuroimaging include seasonal variation of the brain 5‐HT transporter, which is normally higher in winter and lower in summer (Praschak‐Rieder, Willeit, Wilson, Houle, & Meyer, ), but which, in patients with SAD, has higher seasonal amplitude (Tyrer et al., ), is directly related with the severity of the depressive syndrome (Mc Mahon et al., ), and is a target for treatment (Harrison et al., ; Tyrer et al., ).…”

Section: What Are the Perspectives?mentioning

confidence: 99%

Perspectives in affective disorders: Clocks and sleep

Wirz‐Justice

Benedetti

2019

Eur J of Neuroscience

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Mood disorders are often characterised by alterations in circadian rhythms, sleep disturbances and seasonal exacerbation. Conversely, chronobiological treatments utilise zeitgebers for circadian rhythms such as light to improve mood and stabilise sleep, and manipulations of sleep timing and duration as rapid antidepressant modalities. Although sleep deprivation (“wake therapy”) can act within hours, and its mood‐elevating effects be maintained by regular morning light administration/medication/earlier sleep, it has not entered the regular guidelines for treating affective disorders as a first‐line treatment. The hindrances to using chronotherapeutics may lie in their lack of patentability, few sponsors to carry out large multi‐centre trials, non‐reimbursement by medical insurance and their perceived difficulty or exotic “alternative” nature. Future use can be promoted by new technology (single‐sample phase measurements, phone apps, movement and sleep trackers) that provides ambulatory documentation over long periods and feedback to therapist and patient. Light combinations with cognitive behavioural therapy and sleep hygiene practice may speed up and also maintain response. The urgent need for new antidepressants should hopefully lead to reconsideration and implementation of these non‐pharmacological methods, as well as further clinical trials. We review the putative neurochemical mechanisms underlying the antidepressant effect of sleep deprivation and light therapy, and current knowledge linking clocks and sleep with affective disorders: neurotransmitter switching, stress and cortico‐limbic reactivity, clock genes, cortical neuroplasticity, connectomics and neuroinflammation. Despite the complexity of multi‐system mechanisms, more insight will lead to fine tuning and better application of circadian and sleep‐related treatments of depression.

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“…In contrast to studies of radioligand binding to SERT in postmortem OFC and other prefrontal cortex in depression, a meta-analysis of neuroimaging studies in living subjects with MDD reported no significant change in SERT binding in the frontal cortex (Gryglewski et al, 2014). However, intriguing PET studies note greater SERT binding in prefrontal cortical regions in a subgroup of depressed patients with more highly negativistic dysfunctional attitudes (Meyer et al, 2004) and a greater seasonal increase in SERT binding in patients with more severe symptoms of seasonal affective disorder which is reversible by light therapy (Tyrer et al, 2016a; b). However, a limitation of the present study is that negativistic dysfunctional attitudes cannot be extracted from the retrospective questionnaires used for psychopathology.…”

Section: Discussionmentioning

confidence: 99%

Length of axons expressing the serotonin transporter in orbitofrontal cortex is lower with age in depression

et al. 2017

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Studies of major depressive disorder (MDD) in postmortem brain tissue report enhanced binding to inhibitory serotonin-1A autoreceptors in midbrain dorsal raphe and reductions in length of axons expressing the serotonin transporter (SERT) in dorsolateral prefrontal cortex. The length density of axons expressing SERT in the orbitofrontal cortex (OFC) was determined in 18 subjects with MDD and 17 age-matched control subjects. A monoclonal antibody was used to immunohistochemically label the SERT in fixed sections of OFC. The 3-dimensional length density of SERT-immunoreactive (ir) axons in layer VI of OFC was estimated. The age of subjects with MDD was negatively correlated with SERT axon length (r=−0.77, p<0.0005). The significant effect of age persisted when removing four depressed subjects with an antidepressant medication present at the time of death, or when removing nine depressed subjects that had a recent prescription for an antidepressant medication. Neither gender, tissue pH, postmortem interval, 5-HTTLPR genotype, time in fixative, nor death by suicide had a significant effect on axon length. The age-related decrease in SERT-ir axon length in MDD may reflect pathology of ascending axons passing through deep white matter hyperintensities. Greater length of axons expressing SERT in younger subjects with MDD may result in a significant deficit in serotonin availability in OFC.

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Serotonin transporter binding is reduced in seasonal affective disorder following light therapy

Abstract: These results demonstrate that light therapy reaches an important therapeutic target in the treatment of SAD and provide a basis for improvement of this treatment via application of [ C]DASB PET.

Cited by 31 publications

References 64 publications

Brain monoamine oxidase A in seasonal affective disorder and treatment with bright light therapy

Brain monoamine oxidase A in seasonal affective disorder and treatment with bright light therapy

Perspectives in affective disorders: Clocks and sleep

Length of axons expressing the serotonin transporter in orbitofrontal cortex is lower with age in depression

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