Pediatric Acute-onset Neuropsychiatric Syndrome and Mycoplasma Pneumoniae Infection: A Case Report Analysis with a Metabolomics Approach.

Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) is a clinical condition characterized by a sudden and dramatic obsessive-compulsive disorder with a suggested post-infectious immune-mediated etiology. This condition is accompanied by an extensive series of relatively serious neuropsychiatric symptoms. The diagnosis of PANS is made by "exclusion", as the individual PANS symptoms overlap with a multiplicity of psychiatric disorders with the onset in childhood. A number of researchers accumulated evidence to support the hypothesis that PANS was closely associated with a number of infections. In the last decade, metabolomics played an essential role in improving the knowledge of complex biological systems and identifying potential new biomarkers as indicators of pathological progressions or pharmacologic responses to therapy. The metabolome is considered the most predictive phenotype, capable of recognizing epigenetic differences, reflecting more closely the clinical reality at any given moment and thus providing extremely dynamic data. In the present work, the most recent hypothesis and suggested mechanisms of this condition are reviewed and the case of a 10 - year-old girl with PANS is described, before and after clarithromycin treatment. The main results of this case report are discussed from a metabolomics point of view. The alteration of several metabolic pathways concerning the microbial activity highlights the possible role of the microbiome in the development of PANS. Furthermore, different metabolic perturbations at the level of protein biosynthesis, energy and amino acid metabolisms are observed and discussed. Based on our observations, it is believed that metabolomics is a promising technology to unravel the mysteries of PANS in the near future.

Deep brain stimulation for obsessive-compulsive disorder is associated with cortisol changes.

Deep brain stimulation (DBS) is an effective treatment for obsessive-compulsive disorder (OCD), but its mechanism of action is largely unknown. Since DBS may induce rapid symptomatic changes and the pathophysiology of OCD has been linked to the hypothalamic-pituitary-adrenal (HPA) axis, we set out to study whether DBS affects the HPA axis in OCD patients. We compared a stimulation ON and OFF condition with a one-week interval in 16 therapy-refractory OCD patients, treated with DBS for at least one year, targeted at the nucleus accumbens (NAc). We measured changes in 24-h urinary excretion of free cortisol (UFC), adrenaline and noradrenaline and changes in obsessive-compulsive (Y-BOCS), depressive (HAM-D) and anxiety (HAM-A) symptom scores. Median UFC levels increased with 53% in the OFF condition (from 93 to 143nmol/24h, p=0.12). There were no changes in urinary adrenaline or noradrenaline excretion. The increase in Y-BOCS (39%), and HAM-D (78%) scores correlated strongly with increased UFC levels in the OFF condition. Our findings indicate that symptom changes following DBS for OCD patients are associated with changes in UFC levels.

Psycho-pharmacotherapy for anxiety and obsessive-compulsive disorder: the issue of prolonged barbiturate retention.

The authors report the case of a 32-year-old man who had been treated for anxiety and obsessive-compulsive disorder and had received 800 mg methylphenobarbital (MPB). After switching to a barbiturate-free schedule, his condition continued to be unstable for more than 21 MPB half-lives (approx. 30 days) and did not stabilize until MPB-metabolites dropped below their urinary detection limit. Considering that this article provides findings from a single patient, the authors use this experience to discuss and emphasize the importance of clinical control of barbiturates in psychiatry.

Marcadores biologicos en Psiquiatria / Biological markers in Psychiatry

In order to determine wheter psycopathology is associated with charactheristic neurochemical changes of psychiatric patients, Noradrenergic; Dopaminergic and Serotoninergic urine compounds were quantified in 50 patients (32 females and 18 males) between 20 and 60 years old. They were classified in four groups, according to DSM-IV criteria; in MAJOR DEPRESSION (MD) 30 cases, OBSESSIVE COMPULSIVE DISEASE (OCD) 9 cases, BIPOLAR DEPRESSION (BD)4 cases and SCHIZOPHRENIA (SZ) 7 cases. The following Amine metabolites were determined in 24 hours urine samples Phenylethilamine (PEA); 3-Metho-4-Hidroxy Phenilglycol (MHPG); 5-Hidroxy-indol acetic acid (5HIAA) Homovanilic acid (HVM); Bufotenine (BU); Ometil Bufotenine (OMBU) and 3-5 Metoxy-NN-Dymethyltryptamine (MNNDMT). The results showed a dicrease of Pea levels in 43 per cent of DM; 33 per cent of OCD; 25 per cent of BP and 42 per cent SZ. MOPEG levels were disminished in 53 per cent of DM; 66 per cent of OCD; 25 per cent of BP and 85 per cent of SZ. There was an increase of HVM levels in 10 per cent of DM; 11 per cent of OCD and 25 per cent of BP. There was a dicrease of 5-HIAA levels in 10 per cent of DM while it was increased in 33 per cent and 14 per cent of SZ, BU, OMBU and NNDMT were positive in 71 per cent of SZ; 46 per cent of DM; 55 per cent of OCD and 50 per cent of BP. Our findings are consistent with the hypothesis that PEA; MHPG; 5-HIAA and HVM compounds could be "State markers"of DM and HVM of BP and SZ patients. There is further evidence to support a close interrelationship between the three systems and the urinary excretion of methylates compounds specially in SZ and in DM, OCD and BP patients.

Obsessive-compulsive symptom clusters and urinary amine correlates in Tourette syndrome.

This study was conducted to identify clusters of obsessive-compulsive characteristics in Tourette syndrome subjects and to explore their neurochemical correlates. Patients completed a 40-item questionnaire assessing obsessive-compulsive symptoms. Each subject had a 24-hour urine specimen collected and analyzed for a variety of biogenic amines and their metabolites. Factor analysis identified eight symptom clusters, the majority of which appeared to reflect obsessive symptoms. Consistent relationships were observed between symptom clusters and levels of catecholamine and indolamine amines and metabolites. Overall, the primary metabolite of serotonin, 5-hydroxyindoleacetic acid, appeared to be the most highly correlated with the individual obsessive-compulsive symptoms.

Monoamine activity reflected in urine of young patients with obsessive compulsive disorder, psychosis with and without reality distortion and healthy subjects: an explorative analysis.

Positive psychotic symptoms are reported to be associated with high, negative symptoms with low dopamine (DA) activity and serotonin (5HT) activity may be altered in obsessive-compulsive disorder (OCD). We analysed 24 h urine samples in these patient groups and in healthy controls for supportive evidence. Young unmedicated OCD subjects excreted more adrenaline (AD) and homovanillic acid (HVA) and showed a higher HVA/MHPG ratio and metabolic rate than healthy controls. Independent of general metabolic rate they showed higher HVA concentrations which suggests that the relative activity of catecholamine systems in OCD (HVA/MHPG) is due more to high DA than to low noradrenergic (NA) activity. Concentrations of 5HT were also high in OCD patients. In psychotic patients low levels of DA, HVA, NA and MHPG probably resulted from neuroleptic medication. Patients diagnosed with paranoid psychosis showed higher DA utilization than controls and those with few paranoid symptoms showed high 5HT utilization. These results support studies suggesting that paranoid psychosis is associated more with increased DA activity (discussed in the context of neuroleptic reactivity), that non-paranoid forms are associated more with increased 5HT activity and that OCD patients are unusually aroused with high levels of Ad, 5HT and HVA.

Urinary indoleamines in Tourette syndrome patients with obsessive-compulsive characteristics.

Tourette syndrome patients with high levels of obsessive-compulsive symptoms were compared with patients without these symptoms on urinary measures of serotonin and its major metabolite, 5-hydroxyindoleacetic acid (5HIAA). Both groups were compared with normal controls, and it was hypothesized that patients with obsessive-compulsive symptoms would have lower levels of serotonin. Both groups of Tourette syndrome patients had lower levels than controls, but there was no difference between them. Obsessive symptoms were related to higher levels of 5HIAA and to a higher turnover of serotonin.

Paranoid schizophrenics may not use irrelevant signals. The use of measures of blocking and of urinary dopamine.

Conditioned blocking tests for the use of superfluous (irrelevant) information in task-solving. Paranoid psychotic, obsessive-compulsive and healthy subjects usually showed normal blocking, but non-paranoid subjects tended to learn about the superfluous stimulus. Attenuated blocking was usually associated with increased dopamine utilization measured in 24h urine samples. This may reflect poor stabilization of response to neuroleptic medication.

Urinary free cortisol levels in obsessive-compulsive disorder.

Seventeen obsessive-compulsive disorder (OCD) patients and 25 normal control subjects submitted 24-hour urine samples for measurement of urinary free cortisol (UFC). Thirteen of the 17 OCD patients submitted a second 24-hour urine collection after a 10-week trial of either clomipramine (n = 6) or placebo (n = 7). At baseline, the OCD patients had significantly higher UFC levels than the control group. After 10 weeks of clomipramine or placebo, however, the UFC levels for both OCD groups decreased and were comparable with those of the control group. Obsessive-compulsive symptomatology, as assessed by the Yale-Brown and the NIMH Global Obsessive-Compulsive Scales, improved in the clomipramine group but did not improve in the placebo group. There was a relationship between UFC levels and depressive symptoms.

Urinary cortisol during exposure in obsessive-compulsive ritualizers.

Nineteen obsessive-compulsive (OC) ritualizers were exposed to both brief and prolonged neutral and aversive stimuli (the latter evoked a significant urge to ritualize). Urinary cortisol and subjective anxiety were measured over 3 1/2 hours throughout the experiment, and cortisol secretion was compared to a control session the previous day. Both groups showed higher cortisol secretion after exposure compared to the control session. Only the group that received prolonged aversive stimuli, in addition to brief aversive and neutral stimuli, showed significantly higher urinary cortisol levels after the session. Cortisol response correlated with subjective anxiety reports during prolonged aversive stimulation only.

Chromatographic profiles at E-280 nm for urinary precipitates in morbus Rett.

Previously we have observed different characteristic chromatographic ultraviolet absorbancy profiles at 280 nm for urinary protein precipitates from patients with behavioral disorders. The purpose with this study was to look for similar changes in urinary protein excretion from the grossly disabled patients with the Rett syndrome. Benzoic acid precipitates from the urine from 20 patients were chromatographed on a Sephadex G-25 gel column. There appeared 3 different profiles: 6 as observed in normal controls, 5 like that in compulsive behavior, and 9 were similar to those observed for autistiform-schizophreniform patients. The profiles did not mirror the behavioral observations for the patients, although the first group of 6 patients were the least disabled, whereas the last 9 patients were the most seriously ill. In conclusion the chromatographic profiles suggest a heterogeneous group of patients, but we need more observations for several patients over time, as there may be a change with the exacerbation of the disease.

[Types of adrenograms in neuroses]. / Tipy adrenogramm pri nevrozakh.

A total of 714 adrenograms (graphic depiction of adrenalin and noradrenalin excretion in relation to the circadian rhythm) obtained from neurotic patients were analyzed. The authors succeeded in ascertaining the differences of their types in patients suffering from hysterical neurosis, neurasthenia and obsessive neurosis. The adrenographic method is believed to be capable of serving as an additional diagnostic criterion in the differential diagnosis of these pathological forms.