Anxiety is associated with reduced central serotonin transporter availability in unmedicated patients with unipolar major depression: a [11C]DASB PET study

Abstract

Serotonergic dysfunction may contribute to negative mood states in affective disorders. Some in vivo imaging studies showed reduced availability of serotonin transporters (5-HTT) in the brainstem and thalamus of patients with major depression. We tested the hypothesis that 5-HTT availability is reduced in unmedicated unipolar patients with major depression compared to healthy control subjects matched for gender, age, genotype and smoking status. Availability of 5-HTT was measured in vivo with positron emission tomography and [(11)C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile (DASB) in the midbrain, thalamus and amygdala. DASB binding was correlated with the severity of depression (Beck's Depression Inventory), anxiety (Spielberger's State-Trait Anxiety Inventory) and personality traits (Temperament and Character Inventory). Patients with major depression displayed reduced 5-HTT availability in the thalamus (P=0.005). In patients, low serotonin transporter availability correlated with high anxiety (thalamus: r=-0.78, P=0.004; midbrain: r=-0.78, P=0.004; amygdala: r=-0.80, P=0.003). Correlations with severity of depression were weaker and did not survive correction for multiple testing. These results support the hypothesis that central serotonergic dysfunction is associated with negative mood states in affective disorders. In the thalamus, a low serotonin reuptake capacity may interfere with thalamic control of cortical excitability and contribute to anxiety rather than depression per se in major depression.

Temperament, character and serotonin activity in the human brain: a positron emission tomography study based on a general population cohort

“…Excluding subjects with mental disorders from this study limits the generalizability of the results to the healthy population. Exclusion of subjects with mental disorders is a valid approach, as some reports suggest decreased in vivo 5-HTT binding in major depression although this remains controversial with possible state-dependent phenomena involved (Bhagwagar et al 2007 ;Cannon et al 2007 ;Meyer, 2007 ;Reimold et al 2008 ;Selvaraj et al 2011). It is known that high HA predisposes to psychiatric disorders, especially in the mood and anxiety spectrum (see Miettunen & Raevuori, 2012).…”

“…A total of six published studies have used PET or single photon emission computed tomography to examine the correlation of serotonergic neurotransmission with HA (Rabiner et al 2002 ;Moresco et al 2002 ;Borg et al 2003 ;Van Heeringen et al 2003 ;Reimold et al 2008 ;Karlsson et al 2009 (Rabiner et al 2002 ;Borg et al 2003 ;Karlsson et al 2009) and one examining serotonin transporter 5-HTT with (Reimold et al 2008) in healthy subjects found no correlation between serotonin function and HA.…”

“…with affective disorders (Reimold et al 2008 ;Selvaraj et al 2011). A validated tracer [ 11 C]N,Ndimethyl-2-(2-amino-4-methylphenylthio)benzylamine ([ 11 C]MADAM) and a three-dimensional PET technique were used to assess the 5-HTT density (binding potential ; BP ND ) (Lundberg et al , 2006.…”

Age and sex effects on 5-HT4 receptors in the human brain: A [11C]SB207145 PET study

“…A decline with age is described for the 5-HT 1A receptors in both genders (Moller et al, 2007;Tauscher et al, 2001), in women only (Costes et al, 2005) and men only (Cidis Meltzer et al, 2001;Rabiner et al, 2002). Studies involving the serotonin transporter have described localized decreases with age in varying regions (Kalbitzer et al, 2009;Meyer et al, 2001;Reimold et al, 2008).…”

Challenges for PET Neuroimaging of Depressive Disorders

“…Ten PET studies published in recent years have used [ 11 C]McNeil 5652 or [ 11 C]DASB to assess the serotonin transporter in depressed subjects and healthy controls. Four of those studies, plus a data re-analysis, noted less binding by the serotonin transporter in brain regions of depressed subjects Oquendo et al 2007;Parsey et al 2006a;Reimold et al 2008;Miller et al 2009b), four studies found more binding by the serotonin transporter in depressed subjects (Reivich et al 2004;Cannon et al 2006b;Cannon et al 2007;Boileau et al 2008), and two studies found no difference between depressed subjects and healthy controls in binding by serotonin transporters in brain regions Bhagwagar et al 2007). Discrepancies are also apparent in the outcome of recent PET studies carried out with [ 11 C]WAY-100635 or [ 18 F]FCWAY to assess serotonin type 1A receptors in depressed subjects and healthy controls.…”