Serotonergic neurotransmission plays a key role in seasonal changes of mood and behaviour. Higher serotonin transporter availability in healthy human subjects in times of lesser light has been reported in recent studies. Furthermore, seasonal alterations of postsynaptic serotonin-1A receptors have been suggested by a recent animal study. Following that, this study aimed at identifying seasonal alterations of serotonin-1A receptor binding in the living human brain.

Thirty-six healthy, drug-naïve subjects were investigated using PET and the specific tracer [carbonyl-11C]WAY-100635. Regional serotonin-1A receptor binding (5-HT1A BPND) was related to the individual exposure to global radiation. Furthermore, the subjects were divided into two groups depending on individual exposure to global radiation, and the group differences in regional 5-HT1A BPND were determined.

Correlation analysis controlled for age and gender revealed highly significant positive correlations between regional postsynaptic 5-HT1A BPND and global radiation accumulated for 5 days (r=.32 to .48, p=.030 to .002). Highly significant differences in 5-HT1A BPND binding between subjects with low compared to high exposure to global radiation were revealed (T=-2.63 to -3.77, p .013 to .001). 20% to 30% lower 5-HT1A BPND was found in the subject group exposed to lower amount of global radiation.

Seasonal factors such as exposure to global radiation influence postsynaptic serotonin-1A receptor binding in various brain regions in healthy human subjects. In combination with seasonal alterations in serotonin turnover and 5-HTT availability revealed in recent studies, our results provide an essential contribution of molecular mechanisms in seasonal changes of human serotonergic neurotransmission.

Dysfunction in the basal ganglia has been related to impaired reward processing and anhedonia, a core symptom of Major Depressive Disorder (MDD). In particular, the ventral striatum including the nucleus accumbens is increasingly implicated in the pathophysiology of MDD, but evidence for a specific role during episodes of full remission is lacking so far.

To investigate functional connectivity patterns of resting-state activity in patients in the remitted phase of MDD (rMDD).

To determine whether rMDD is related to disruptions of functional coupling between the ventral striatum and cortical regions.

Forty-three remitted depressed patients and thirty-five healthy controls were recruited at Medical University of Vienna, Vienna, Austria, and performed a six minute resting-state fMRI scan. Seed time series were extracted from the preprocessed data using individual masks for ventral striatum and correlated with all nodes in a surface based analysis using FreeSurfer, AFNI and SUMA. The resulting correlation coefficients were then Fishertransformed, group results were determined by comparing group mean smoothed z-scores with a two-sample ttest.

Increased resting-state functional connectivity was revealed between ventral striatum (seed region) and anterior cingulate cortex as well as orbitofrontal cortex in the rMDD group compared to healthy controls.

Our preliminary data is in accordance with the idea that increased functional coupling between the ventral striatum and two major emotion processing regions, the anterior cingulate cortex and the orbitofrontal cortex, may represent a neural mechanism contributing to the maintenance of full remission of MDD.

Maximal serotonin transporter (5-HTT) densities have been found in the cingulate cortex, a cortical region that has been critically implicated in emotion processing and the pathophysiology of Major Depressive Disorder. Furthermore, serotonin (5-HT) re-uptake inhibition is the first line strategy in the treatment of depression.

Since 5-HTTs are not restricted to neuronal cells, 5-HT uptake velocity (Vmax) can be easily measured on blood platelets subserving as peripheral model of neuronal 5-HTT function and related measures of neural activation.

To determine whether peripheral 5-HTT uptake velocity is related to neural activation in the cingulate cortex during emotion processing.

48 healthy subjects underwent an fMRI paradigm comprising emotional (angry/fearful faces and scenes) and neutral stimuli (simple shapes). 5-HT Vmax was determined in platelets. Subjects were genotyped for a common triallelic polymorphism in the promoter region of the 5-HTT gene (5-HTTLPR).

Significant negative correlations between Vmax and BOLD-signal in the anterior and posterior portion of the cingulate cortex have been found. Cluster maxima within both regions were detected in the subgenual anterior cortex (−1.5, 28.5, −3.5, t = −3.77) and the ventral posterior cingulate cortex (−4.5, −49.5,14.5, t = −3.06). Genotype did not impact on this relationship.

Our results indicate a clear dependency between a peripheral marker, platelet 5-HT uptake velocity, and neural activity in portions of the cingulate cortex for the first time.

Converging evidence suggests alterations of neural activation in the basal ganglia to represent neural correlates of Major Depressive Disorder (MDD). While a previous study reported increases of functional connectivity in resting state activity between the caudate nuclei and the posterior cingulate cortex in acutely depressed patients, it remains unclear whether this finding persists during full remission once antidepressant treatment has been discontinued.

To investigate patterns of functional coupling between the basal ganglia and cortical regions during resting-state conditions.

To determine whether increases of functional connectivity between caudate nuclei, putamen, and pallidum with cortical regions, in particular the cingulate cortex, pertain during remission of MDD.

Forty-three remitted depressed (rMDD) patients and thirty-five healthy controls were recruited at Medical University of Vienna, Vienna, Austria, and performed a six minute resting-state fMRI scan. Seed time series were extracted from the preprocessed data using individual masks for the basal ganglia and correlated with all nodes in a surface based analysis using FreeSurfer, AFNI and SUMA. The resulting correlation coefficients were then Fisher-transformed, group results were determined by comparing group mean smoothed z-scores with a two-sample t-test.

Increased resting-state functional connectivity was revealed between basal ganglia and cingulate as well as prefrontal cortex in the rMDD group compared to healthy controls.

Our preliminary results revealed increased functional coupling between the basal ganglia and wide parts of the cingulate and prefrontal cortex to possibly represent a specific neural pattern during remission of MDD.

While most neuroimaging studies have investigated acutely depressed patients, neural mechanisms underlying stable remission are rarely examined. Furthermore, the majority of previous functional MRI (fMRI) studies have focused on task-induced neural activity, while resting-state activity may be more reproducible across study centers.

To clarify patterns of functional coupling between subcortical structures and cortical resting state activity.

To determine whether alterations of functional coupling between the amygdala and cortical emotion processing regions characterize patients in the remitted phase of Major Depressive Disorder (rMDD).

Forty-three remitted depressed patients and thirty-five healthy controls were recruited at Medical University of Vienna, Vienna, Austria, and performed a six minute resting-state fMRI scan. The scans were corrected for slice timing and motion, as well as for mean white matter, mean CSF, and median gray matter signals. Seed time series were extracted using individual amygdala masks and correlated with all nodes in a surface based analysis using FreeSurfer, AFNI and SUMA. The resulting correlation coefficients were then Fisher-transformed, group results were determined by comparing group mean smoothed (to 8 mm FWHM) z-scores with a two-sample t-test.

Increased resting-state functional connectivity was revealed between amygdala (seed region) and posterior cingulate cortex as well as orbitofrontal cortex in the rMDD group compared to healthy controls.

Our preliminary results suggest altered functional coupling between amygdala and cortical emotion processing areas during resting state conditions, possibly representing a neural mechanism contributing to the maintenance of stable remission of MDD.

The natural course of Major Depressive Disorder (MDD) encompasses the occurrence of alternating intervals of major depressive episodes and remission. While several abnormalities in neural circuits related to acute MDD have been identified, the neural mechanisms underlying stable remission remain obscure.

Acute MDD is characterized by increased amygdala and subgenual anterior cingulate cortex (sACC) activation and decreased connectivity between the amygdala and the sACC. Consequently, we expect those regions to be affected during remission.

To determine whether active counter-regulatory mechanisms are implicated in the maintenance of full remission once antidepressant treatment has been discontinued.

Functional and structural magnetic resonance imaging was used to measure brain activation and volume of the amygdala and the sACC. Images were obtained from 38 healthy subjects without any psychiatric life-time diagnosis and 38 gender-matched drug-free remitted MDD patients. Furthermore, correlation analyses were performed with clinical variables.

Patients with rMDD exhibited lower activation in the amygdala and the sACC and increased functional coupling between the amygdala and sACC compared to controls. This connectivity was particularly pronounced in patients characterized by a long cumulated time of depressive episodes. Similarly, structural connectivity results showed increased association between the amygdala and sACC volume in rMDD patients compared to controls.

Remitted MDD is related to neural alterations within a neural circuit encompassing the amygdala and the sACC compared to controls. These findings suggest active counter-regulatory mechanisms likely contributing to the maintenance of remission once treatment has been discontinued.