Manolis Markianos

Aims: Bladder dysfunction is frequent during the course of multiple sclerosis (MS), observed in up to 75% of patients. Urinary symptomatology can be a feature of the first episode of MS in a minority of cases, and most often shows characteristics of an overactive bladder (OAB), with voiding symptoms seen less frequently, often in combination with OAB. The neural control of micturition is complex, involving systems located in the brain, spinal cord, and periphery, and implicating central noradrenergic, serotonergic, and dopaminergic activities. Urinary disorders are also linked to anxiety and depression, conditions connected to hypothalamus–pituitary–adrenal axis activity. In this study we aimed to investigate neurochemical and neuroendocrine correlates of bladder dysfunction in early MS.Methods: We included 101 patients at first demyelinating episode suggestive of MS that were drug‐free at assessment. We evaluated the presence of urinary symptomatology and estimated CSF levels of the main metabolites of noradrenaline, serotonin, and dopamine, as well CSF‐ACTH and serum cortisol.Results: In total, 15 patients (15%) reported urinary dysfunction suggestive of OAB. Four of these had coexistent voiding symptomatology. The serotonin metabolite 5‐HIAA was significantly reduced (P = 0.017) in patients with OAB syndrome, while there were no differences in the metabolites of noradrenaline (MHPG) and of dopamine (HVA). Additionally, significantly lower serum cortisol (P = 0.009) and borderline lower CSF‐ACTH (P = 0.08) were found in patients with OAB.Conclusions: MS patients with OAB syndrome at the first demyelinating episode show reductions in central serotonergic activity and stress hormones. Whether the same changes persist at later disease stages remains to be investigated. Neurourol. Urodynam. 35:955–958, 2016.

Major Depression with severe anxiety has been proposed as a distinct clinical variant of Major Depressive Disorder (MDD). This proposal invites the investigation of the differential biological correlates of the anxious versus non-anxious MDD. One such research area might be their possible differential associations with androgens. Plasma total testosterone and dehydroepiandrosterone were assessed in adequately matched female inpatients with anxious MDD, non-anxious MDD and normal controls. Androgen levels were significantly lower in both patient groups compared to those of controls. Moreover, they were significantly lower in anxious MDD patients compared to those of their non-anxious MDD counterparts. The limitations of this study were cross-sectional design of the study, the small sample size of the study sample and the outpatient status of the control group. In addition, free testosterone levels were not measured. Our findings indicate that female major depression is associated with lower androgen levels, a deficiency aggravated by the severity of their concomitant anxiety.

Body weight and height of patients with relapsing-remitting multiple sclerosis (RRMS) or clinically isolated syndrome suggesting MS (CIS) in the age range 18 to 60 years (154 males and 315 females) were compared with those of subjects (146 males and 212 females) free of any major neurological disease. In drug-free patients, CSF levels of the metabolites of noradrenaline (MHPG), serotonin (5-HIAA), and dopamine (HVA), neurotransmitters involved in eating behavior, were estimated in searching for associations with body mass index (BMI). Statistical evaluations were done separately for males and females. Lower BMI was found in female MS patients compared to female controls, more pronounced in RRMS. BMI was not associated with duration of illness, smoking, present or previous drug treatment, or disability score. Body height showed a shift towards greater values in MS patients compared to controls. Patients in the lower BMI quartile (limits defined from control subjects) had lower 5-HIAA and HVA compared to patients in the upper quartile. The results provide evidence for weight reduction during disease process in MS, possibly related to deficits in serotoninergic and dopaminergic activities that develop during disease course, resulting in impairments in food reward capacity and in motivation to eat.

Objective. Anxious major depressive disorder (A‐MDD) is differentially diagnosed from nonanxious MDD (NA‐MDD) as MDD with a cut‐off score ≥7 on the HAM‐D anxiety‐somatization factor (ASF). We investigated whether additional HAM‐D items discriminate A‐MDD from NA‐MDD. Moreover, we tested the validity of ASF criterion against HAM‐A, gold standard of anxiety severity assessment. Methods. 164 consecutive female middle‐aged inpatients, diagnosed as A‐MDD (n = 92) or NA‐MDD (n = 72) by the normative HAM‐A score for moderate‐to‐severe anxiety (≥25), were compared regarding 17‐item HAM‐D scores. The validity of ASF ≥7 criterion was assessed by receiver‐operating characteristics (ROC) analysis. Results. We found medium and large effect size differences between A‐MDD and NA‐MDD patients in only four out of the six ASF items, as well as in three further HAM‐D items, namely, those of agitation, middle insomnia, and delayed insomnia. Furthermore, the ASF cut‐off score ≥9 provided the optimal trade‐off between sensitivity and specificity for the differential diagnosis between A‐MDD and NA‐MDD. Conclusion. Additional HAM‐D items, beyond those of ASF, discriminate A‐MDD from NA‐MDD. The ASF ≥7 criterion inflates false positives. A cut‐off point ≥9 provides the best trade‐off between sensitivity and specificity of the ASF criterion, at least in female middle‐aged inpatients.