Relationship of brainstem raphe echogenicity and clinical findings in depressive states

Abstract

Transcranial sonography (TCS) revealed reduced brainstem raphe (BR) echogenicity in major depressive disorder (MDD). Here, it was studied whether BR echogenicity discriminates MDD and adjustment disorder with depressed mood (ADDM), and whether BR echogenicity relates to depression severity or treatment responsivity. For this, 15 patients with single episodes of MDD (MDDs), 22 with recurrent MDD (MDDr), 15 with ADDM, and 50 healthy controls were investigated with TCS. Frequency of reduced BR echogenicity was similar in groups MDDs (53%), MDDr (50%) and ADDM (60%), but significantly lower in the controls (8%). Patients with reduced BR echogenicity had lower scores on the 21-item Hamilton Depression Rating Scale and the Motor Retardation Scale, compared with patients with normal BR echogenicity. BR echogenicity scores were significantly lower in SSRI responders to serotonin reuptake inhibitors (SRI) than in non-responders. Reduced BR echogenicity indicated SSRI responsivity with 70% sensitivity, 88% specificity and a positive predictive value of 88%. No impact of age, gender or antidepressant medication on BR echogenicity was found. These results indicate that reduced BR echogenicity is not related to diagnostic category of depressive state. Reduced BR echogenicity might reflect a pathology predisposing to a certain subtype of depression characterized by less psychomotor retardation and better responsivity to SRI.

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.