Relationship of brainstem raphe echogenicity and clinical findings in depressive states
Introduction
Major depressive disorder (MDD) and adjustment disorder with depressed mood (ADDM) are currently regarded as distinct disease entities (American Psychiatric Association, 1994). Especially, DSM axis-II comorbidity and suicidal behavior have been reported to differ between MDD and ADDM (Spalletta et al., 1996, Polyakova et al., 1998). However, a considerable overlap in psychosocial variables and symptom presentation, equal response to antidepressant therapy, and similar neurophysiological findings have been reported (Hirschfeld et al., 1987, Jones et al., 1999, Hameed et al., 2005, Kessing, 2005; Bar et al., 2006). In unipolar depression, there is a diffuse decrease in serotonin transporter binding throughout the dorsoventral extent of the prefrontal cortex (Austin et al., 2002, Meyer et al., 2004). Serotonergic innervation of the prefrontal cortex arises predominantly from neurons in the brainstem dorsal raphe nucleus. Pathoanatomic and positron emission tomographic (PET) studies suggest morphological and functional alterations of the dorsal raphe nucleus in MDD, with decreased serotonin type 1A receptor binding and fewer neurons expressing serotonin transporter mRNA compared with controls (Arango et al., 2001, Meltzer et al., 2004). There is recent evidence suggesting that serotonin transporter availability measured with single photon emission computed tomography predicts treatment response to serotonin reuptake inhibitors (Kugaya et al., 2004).
Transcranial sonography (TCS) displays tissue echogenicity of the brain through the intact skull. TCS revealed reduced echogenicity of brainstem raphe (BR) in MDD and in depression associated with Parkinson's or Wilson's disease, but not in healthy adults, bipolar affective disorders, schizophrenia, or Parkinson's disease without depression (Becker et al., 1994, Becker et al., 1995, Becker et al., 1997, Berg et al., 1999, Walter et al., 2005, Walter et al., 2007). Reduced BR echogenicity could be correlated to signal alteration on MRI and was suggested to reflect structural disruption of the BR, resulting in impaired serotonergic innervation (Becker et al., 2001).
Here, we wanted to find out whether BR echogenicity discriminates between patients with MDD and patients with ADDM, and whether TCS findings relate to treatment responsivity.
Section snippets
Patients
Fifty-two patients treated at the Department of Psychiatry of the University of Rostock were eligible for inclusion. Inclusion criteria were 1) present inpatient treatment of current depressive symptoms, 2) unequivocal classification of a depressive state according to DSM-IV diagnostic categories as specified below (American Psychiatric Association, 1994), and 3) transcranial insonability. Exclusion criteria were 1) organic psychiatric disorders or 2) recent concomitant neurological disorders.
Relation between BR echogenicity and diagnostic category
Reduced BR echogenicity was found in 54% of the patients with MDD and ADDM, but only in four (8%) of the healthy control subjects (U-test, P < 0.001) (Fig. 1). The interrater reliability was high with regard to assessment of BR echogenicity (Cohen's kappa = 0.82, P < 0.001). BR echogenicity scores did not differ among patients with MDDs, MDDr, or ADDM. The mean BR echogenicity score in MDDs patients was 2.3 ± 0.6, in MDDr patients 2.4 ± 0.6, and in ADDM patients 2.3 ± 0.8 (t-test, P > 0.5 for each group
Discussion
TCS findings of this study show that reduced echogenicity of pontomesencephalic BR is frequent in depressive states, irrespective of diagnostic category, but only rare in healthy subjects without any history of psychiatric disorder. BR echogenicity does not discriminate between MDDs, MDDr, and ADDM. BR echogenicity scores, however, are significantly lower in SSRI responders compared with SSRI non-responders. Reduced BR echogenicity indicates SSRI responsivity with a positive predictive value of
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2017, Journal of Affective DisordersCitation Excerpt :Hypothesized structural pathology has been backed by an increase of the brainstem midline signal intensity on the T2-weighted MRI in MDD patients when compared to controls, but also patients with bipolar disorder (Berg et al., 1999). Lack of correlation between BR echogenicity and severity of depression in majority of previous studies (including our own) (Table 2) (Becker et al., 1994, 1995; Walter et al., 2007a, 2007c), led Walter et al. (2007a) to imply that TCS findings of the BR hypo-/anechogenicity might indicate “a vulnerability factor for development of depressive states”. Changes in BR echogenicity have been proposed through several lines of evidence to be linked to 5-HT transmission (Meyer et al., 2006).