Reduced Echogenicity of Brainstem Raphe Specific to Unipolar Depression: A Transcranial Color-Coded Real-Time Sonography Study Georg Becker, Thomas Becker, Michael Struck, Alfred Lindner, Klaus Burzer, Wolfgang Retz, Ulrich Bogdahn, and Helmut Beckmann Echogenicity of the brainstem raphe was assessed in patients with major depression, bipolar affective disorders, and schizophrenia and compared with healthy adults employing transcran- ial color-coded real-time sonography. Forty probands were enrolled in each group. A highly significant reduction in raphe echogenicity was detected only in patients suffering from major depression. Echogenicity of the raphe was independent of age or sex and did not correlate with severity of the depressive syndrome or patient state. These findings are suggestive of structural desintegration of the brainstem raphe in unipolar depression, an anatomical region assumed to be a biological focus in the pathogenesis of depressive syndromes. Key Words: Transcranial color-coded real-time sonography (TCCS), brainstem raphe, de- pression, schizophrenia, ultrasound Introduction Transcranial color-coded real-time sonography (TCCS) is a new, noninvasive method, providing a two-dimensional dis- play of brain parenchyma through the intact adult skull (Becker and Bogdahn 1993). TCCS allows an unequivocal illustration of central nervous system (CNS) topographic anatomy and reveals depiction of cerebral nuclei and fiber tracts such as red nucleus, internal capsule, and brainstem raphe (Becker and Bogdahn 1993). The brainstem raphe is a subtle, hyperecho- genic midline structure related to echoreflection at raphe nuclei and sagittally running fiber tracts within the midline of the mesencephalon and rostral pons (Lang 1993). From Neurologische Universit~tsklinik W0rzburg, Germany (GB, AL, KB. UB), Psychiatrische Universit~itsklinik Wiirzburg, Germany (TB. MS, WR, HB); and Ciba-Geigy Clinical Research Department CNS Basel, Switzerland (MS). Address reprint requests to Georg Becker, MD, Department of Neurology, Josef Schneider Str. 11,97080 Wt~rzburg, Germany. Received March 30, 1994; revised September 14. 1994. In a pilot study, the echogenicity of the brainstem raphe was examined by TCCS in 20 patients with unipolar depres- sion and 20 healthy adult controls (Becker et al, 1994). A marked reduction of raphe echogenicity in depressed pa- tients was found. The present study was performed to re- evaluate these findings and to compare raphe echogenicity in other types of psychiatric disorders, such as schizophre- nia and bipolar disorders, with findings in unipolar depres- sion and healthy adults. Methods and Materials All in patients treated at the Department of Psychiatry of the University of Wiarzburg during the year 1992 and at the Bezirkskrankenhaus Lohr during September 1993 were eli- gible for inclusion. Inclusion criteria were 1) present psy- chiatric inpatient treatment, 2) the unequivocal clinical classification of psychiatric disorder according to DSM-III- © 1995 Society of Biological Psychiatry 0006-3223195/$09.50 SSDI 0006-3223(94)00263-3