Jacqueline Hoeppner

Relationship of brainstem raphe echogenicity and clinical findings in depressive states

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.

Modulation of transcallosally mediated motor inhibition in children with attention deficit hyperactivity disorder (ADHD) by medication with methylphenidate (MPH)

Motor hyperactivity is one of the most outstanding symptoms of attention deficit hyperactivity disorder (ADHD) which might be caused by a disturbed inhibitory motor control. Using focal transcranial magnetic stimulation (TMS) we tested the cortico-callosal inhibition (duration and latency of the ipsilateral Silent Period, iSP) in 23 children with ADHD (mean age 11+/-2.6 years) before and on treatment with methylphenidate (MPH). iSP latency was age correlated, whereas iSP duration as well as Conners scores were age independent. Analyses of mean differences revealed a significant prolongation of iSP duration (p=0.001), shortening of iSP latency (p=0.027) and reduction of Conners score (p=0.001) under medication. Increase of iSP duration and reduction of Conners score under medication were significantly correlated (t=-9.87, p=0.016). Reduced iSP duration and prolonged iSP latency in ADHD children could be the result of a disturbed transcallosally mediated inhibition, most probable due to a combination of maturation deficits of callosal fiber tracts as well as neuronal synaptical transmission within the neuronal network between ipsilaterally stimulated cortex layer III--the origin of transcallosal motor-cortical fibers--and contralateral layer V, the origin of the pyramidal tract. MPH may indirectly improve the dysbalance between excitatory and inhibitory interneuronal activities of this neuronal network via dopaminergic modulatory effects of the striato-thalamo-cortical loop.

Impaired transcallosally mediated motor inhibition in adults with attention-deficit/hyperactivity disorder is modulated by methylphenidate

Using transcranial magnetic stimulation (TMS) in children with ADHD, an impaired transcallosally mediated motor inhibition (ipsilateral silent period, iSP) was found, and its restoration was correlated with improvement of hyperactivity under medication with methylphenidate (MPH). Hyperactivity has been reported to decrease during transition into adulthood, although some motor dysfunction might persist. As one underlying neurophysiological process, a development-dependent normalization of motor cortical excitability might be postulated. In order to test this hypothesis, we measured the iSP in 21 adult ADHD patients and twenty-one sex- and age-matched healthy controls. In 16 of these patients, a second TMS was performed under treatment with MPH. Our results indicate a persistence of impaired transcallosally mediated motor cortical inhibition (shortened duration) in ADHD adults, which was correlated with clinical characteristics of hyperactivity and restlessness, and was restored by MPH. In contrast to ADHD in childhood, the iSP latency was not impaired, suggesting a partial development-dependent normalization of motor cortical excitability in ADHD adults. ISP duration appears to be a sensitive parameter for the assessment of disturbed intercortical inhibition in adults with ADHD.