Worsening of the Toxic Effects of (±)Cis-4,4'-DMAR Following Its Co-Administration with (±)Trans-4,4'-DMAR: Neuro-Behavioural, Physiological, Immunohistochemical and Metabolic Studies in Mice.

4,4'-Dimethylaminorex (4,4'-DMAR) is a new synthetic stimulant, and only a little information has been made available so far regarding its pharmaco-toxicological effects. The aim of this study was to investigate the effects of the systemic administration of both the single (±)cis (0.1-60 mg/kg) and (±)trans (30 and 60 mg/kg) stereoisomers and their co-administration (e.g., (±)cis at 1, 10 or 60 mg/kg + (±)trans at 30 mg/kg) in mice. Moreover, we investigated the effect of 4,4'-DMAR on the expression of markers of oxidative/nitrosative stress (8-OHdG, iNOS, NT and NOX2), apoptosis (Smac/DIABLO and NF-κB), and heat shock proteins (HSP27, HSP70, HSP90) in the cerebral cortex. Our study demonstrated that the (±)cis stereoisomer dose-dependently induced psychomotor agitation, sweating, salivation, hyperthermia, stimulated aggression, convulsions and death. Conversely, the (±)trans stereoisomer was ineffective whilst the stereoisomers' co-administration resulted in a worsening of the toxic (±)cis stereoisomer effects. This trend of responses was confirmed by immunohistochemical analysis on the cortex. Finally, we investigated the potentially toxic effects of stereoisomer co-administration by studying urinary excretion. The excretion study showed that the (±)trans stereoisomer reduced the metabolism of the (±)cis form and increased its amount in the urine, possibly reflecting its increased plasma levels and, therefore, the worsening of its toxicity.

Structural brain abnormalities in patients with psychogenic nonepileptic seizures.

OBJECTIVES: We assessed the relationship between the clinical features of patients with psychogenic nonepileptic seizures (PNES) and referrals for brain imaging tests. We also hypothesized that some clinical factors might be associated with structural brain imaging abnormalities in these patients. METHODS: In this retrospective study, patients with PNES, who were investigated at Shiraz Comprehensive Epilepsy Center, Iran, from 2008 until 2019, were studied. RESULTS: One hundred thirty-two patients had a brain magnetic resonance imaging (MRI) study available. Forty-seven patients (36%) had abnormal finding(s) in their MRI. Age (odds ratio = 1.040, p = 0.02), and comorbid epilepsy (odds ratio = 3.006, p = 0.005) were significantly associated with having an abnormal brain MRI. In a subanalysis, we excluded the patients with comorbid epilepsy (46 patients). From the remaining 86 patients (with PNES only), 23 patients (26.7%) had abnormal findings on their MRIs. Common epileptogenic structural brain abnormalities (e.g., tumors, mesial temporal sclerosis, encephalomalacia, and developmental anomalies) were common in patients with comorbid PNES and epilepsy (in 19 out of 46 patients; 41%), but not in those with PNES only (in 4 out of 86 patients; 5%) (p = 0.00001). CONCLUSION: While the evidence is convergent on the relatively high prevalence of structural brain abnormalities in patients with PNES, the data so far is suboptimal. In order to investigate the significance of structural brain abnormalities in the development of PNES, future well-designed multicenter studies, which include a large number of patients with a unified methodology of imaging, are desirable.

[Psychosomatic mechanism in pathogenesis bronchial asthma and ulcerous disease].

The objective of this article was to study individual capabilities of intrapsychic processing psycho-traumatic events and their impact on somatic health. Clinical characteristics of bronchial asthma patients and those with ulcerous disease were compared. General pathological background for development of psihosomatic pathology was identified.

[Chronic musculoskeletal pain syndrome in primary hyperparathyroidism]. / Chronisches muskuloskelettales Schmerzsyndrom bei primärem Hyperparathyreoidismus.

Chronic somatic pain disorders with somatic and mental factors (ICD-10: F45.41) are common among psychosomatic patients. In the present case, due to the close temporal association with a trauma and the subsequent development of symptoms including depressive symptoms, a chronic pain disorder with a relevant somatoform component was suspected. However, after a period of several months without significant somatic findings, targeted diagnostic approaches resulted in the diagnoses of primary hyperparathyroidism and a papillary thyroid carcinoma. Surgical therapy resulted in an almost complete decline of symptoms within a short period of time.

Gender effects on outcomes of psychosomatic rehabilitation are reduced.

OBJECTIVE: The study examined whether psychiatric/psychosomatic rehabilitation continues to have a better course of treatment for women than men. METHODS: We compared the course of global symptom severity, health-related quality of life and functioning between admission and discharge in patients (848 men, 1412 women) at an Austrian psychiatric/psychosomatic rehabilitation clinic. RESULTS: Gender-specific differences in the course of treatment were all too small to be clinically relevant. The differences were smallest in the middle-aged cohort. However, at the time of admission, women reported a slightly higher symptom burden. CONCLUSION: Overall, the results show a gender-fair effectiveness of the rehabilitation. The new findings could be explained by changes in living conditions, gender roles, or better treatment methods.

Genetic architecture of human pain perception.

Pain is emotionally detrimental and consciously avoided; however, it is absolutely crucial for our survival. Pain perception is one of the most complicated measurable traits because it is an aggregate of several phenotypes associated with peripheral and central nervous system dynamics, stress responsiveness and inflammatory state. As a complex trait, it is expected to have a polygenic nature shaped by environmental pressures. Here we discuss what is known about these contributing genetic variants, including recent discoveries that show a crucial role of voltage-gated sodium channel Nav1.7 in pain perception and how we can advance our understanding of the pain genetic network. We propose how both rare deleterious genetic variants and common genetic polymorphisms are mediators of human pain perception and clinical pain phenotypes.

Female primary and secondary psychopathic variants show distinct endocrine and psychophysiological profiles.

Research with predominantly male samples supports primary and secondary developmental pathways to psychopathy that are phenotypically indistinguishable on aggressive and antisocial behavior. The aim of this study was to examine whether female variants of psychopathy show divergent endocrine (i.e., cortisol, dehydroepiandrosterone [DHEA], testosterone, and their ratios) and psychophysiological (i.e., heart rate variability [HRV]) reactivity to social provocation. We also tested whether variants differed on reactive aggression when performing a competitive reaction time task against the fictitious participant who previously insulted them. Latent profile analyses on 101 undergraduate women oversampled for high psychopathic traits identified a high-anxious, maltreated secondary variant (n=64) and a low-anxious primary variant (n=37). Although variants did not differ on aggression, secondary variants showed higher cortisol, testosterone, cortisol-to-DHEA ratios, and HRV following social provocation relative to primary variants. Findings suggest that the neurobiological mechanisms underpinning aggression in psychopathy may differ between women on primary versus secondary developmental pathways.

Stendhal syndrome: a clinical and historical overview.

It could be argued that one of the few unifying qualities all human beings share is the ability to appreciate beauty. While the object of beauty may change from one person to another, the awe and the thrill experienced by an enthralled beholder remains the same. Sometimes, this experience can be so overwhelming it can bring someone to the edge of existence. A very rare condition, known as aesthetic syndrome and, more commonly, Stendhal syndrome, entails a clinical phenomenon in which the presence of a beautiful piece of work or architecture causes dysautonomic symptoms such as tachycardia, diaphoresis, chest pains and loss of consciousness. We present an historical and clinical review of this condition.

Psychogenic memory deficits associated with functional cerebral changes: an FMRI study.

We studied a case of psychogenic amnesia by means of a functional magnetic resonance imaging (fMRI) experiment involving the retrieval of autobiographical memories. The 38-year-old patient was unable to access most of her autobiographical memories from her childhood up to 16 years of age. Compared with the forgotten period, evocation of the normally retrieved memories elicited increased activity in medial temporal and dorso-lateral frontal regions. Evocation of the preserved scattered recollections was associated with bilaterally distributed temporo-parieto-occipital loci of activations. These functional changes seem to support the idea of common mechanisms involved in both organic and psychogenic amnesias.

Bodily symptoms: new approaches to classification.

OBJECTIVE: To examine the current approach to classifying bodily symptoms in both psychiatry and medicine and to suggest better alternatives. METHODS: Theoretical analysis, narrative review, and theoretical proposal. RESULTS: The assumptions that (a) bodily pathology can always explain bodily symptoms, (b) psychopathology can always explain bodily symptoms in the absence of bodily pathology, and (c) dichotomizing bodily symptoms into "medical" and "psychiatric" types is clinically useful were all found to have questionable validity and utility. CONCLUSION: Alternative multiaxial diagnostic approaches for the classification of bodily symptoms are proposed. These are intended to (a) give greater prominence to bodily symptoms in their own right, (b) allow etiology to be conceptualized in terms of multiple factors, and (c) provide the basis for integrating medical and psychiatric approaches to patient care.

White matter diffusion abnormalities in patients with psychogenic non-epileptic seizures.

The purpose of this study was to conduct a preliminary investigation of the white matter characteristics in patients with psychogenic non-epileptic seizures (PNES). Diffusion Tensor Imaging (DTI) data were collected at 3T in 16 patients with PNES and 16 age- and sex-matched healthy controls (HC). All patients with PNES had their diagnosis confirmed via video/EEG monitoring; HCs had no comorbid neurological or psychiatric conditions. DTI indices including fractional anisotropy (FA), and mean diffusivity (MD) were calculated and compared between patients with PNES and HCs using Tract-Based Spatial Statistics (TBSS). Significantly higher FA values were observed in patients with PNES in the left corona radiata, left internal and external capsules, left superior temporal gyrus, as well as left uncinate fasciculus (UF) (P<0.05; corrected for multiple comparisons). There was no significant change in other indices between patients with PNES and HCs. These findings suggest that patients with PNES have significantly altered white matter structural connectivity when compared to age- and sex-matched HCs. These abnormalities are present in left hemispheric regions associated with emotion regulation and motor pathways. While the relationship between the pathophysiology of PNES and these abnormalities is not entirely clear, this work provides an initial basis to guide future prospective studies.

New insights into psychogenic nonepileptic seizures 2011-2014.

PURPOSE: There has been a rapid increase in the rate of publications about psychogenic nonepileptic seizures (PNES). This review summarises insights from the 50 most important original articles about PNES published since 2011 and describes the advances made in the understanding of PNES over the last 3 years. METHOD: We carried out a systematic literature search of all English language publications about PNES published between October 2011 and October 2014 on Scopus, Ovid Medline and Web of Knowledge, and inspected all abstracts. Having excluded all review articles, case reports, conference abstracts, articles exploring PNES in children, and articles not actually focussing on PNES, we considered 150 papers for inclusion in this review. We assessed the quality of the identified studies and used expert judgement to identify the 50 most important publications from the review period and composed a narrative review based on these original papers. RESULTS: Almost one half of the studies initially identified only provided Class 4 evidence. Recent work has provided more support for a biopsychosocial account of PNES. It has illustrated the heterogeneity of PNES, identifying varying and distinct psychological profiles of individuals with this disorder. These findings suggest that intervention needs to be flexible or adaptive if it is appropriately to target the different mechanisms which may give rise to PNES. Several educational and psychotherapeutic interventions for PNES have been described, but sufficiently powered randomised controlled trials are yet to be undertaken. Recent research using social, economic and quality of life indicators has provided further evidence of the societal and individual burden of PNES. CONCLUSION: The research into PNES published over the last 3 years has deepened our understanding of the condition as a biopsychosocial disorder which is neither a "physical" nor a "psychological" condition. A number of small studies have demonstrated the potential of educational and psychotherapeutic treatments, but rigorous and sufficiently large trials still need to be conducted to determine the effectiveness of these interventions.

Cortical thickness, surface area and folding in patients with psychogenic nonepileptic seizures.

OBJECTIVE: To determine cortical thickness (CTh), cortical surface area (CSA), curvature and sulcal depth (SD) in patients with psychogenic nonepileptic seizures (PNES). METHODS: Freesurfer software was used to identify differences between active and control group in Cth, CSA, curvature, and SD. Neuropsychological tests intending to document possible frontal lobe deficit were applied. RESULTS: We included 37 patients with PNES (age 37.3±13.8; female/male 31/6; age of disease onset 26.1±10.6; age of disease duration 11.1±11.1), and 37 healthy controls (age 38.4; ±12.7; female/male 26/11). No difference in CSA and curvature was detected between groups. Patients with PNES had increased CTh in the left insula, left and right medial-orbitofrontal, and left lateral-orbitofrontal, and decreased CTh in the left and right precentral, right enthorinal, and right lateral-occipital region than healthy controls. SD was increased at the level of the left and right insula, right rostral anterior cingulate, right posterior cingulate, and left cuneus, and reduced at the level of the right and left medial-orbitofrontal sulci in patients with PNES compared to healthy controls. CONCLUSION: Individuals with PNES display a distinct profile of changes in CTh, in association with increase in SD in both insula as compared to controls. Our results may contribute to the understanding of the neurobiological background of PNES. Further research, to include replication of the findings and directed to understand the role of insula is needed.

Frontal lobe partial seizures and psychogenic seizures: comparison of clinical and ictal characteristics.

Of all partial seizures, those of frontal lobe origin (FLPS) are most bizarre and are often mistaken for psychogenic seizures (PS). The reverse can also be true. To clarify the confusing clinical presentation of these different seizure types, we compared the clinical ictal characteristics of 63 FLPS in 11 patients with 29 PS in 12 patients. Patients with PS had significantly later age at onset and longer ictal duration. There was no statistically significant difference between the two groups with respect to history of psychiatric disorder, ictal pelvic thrusting, rocking of body, side-to-side head movements, or rapid postictal recovery, all of which previously have been reported as characteristic features of PS. Turning to a prone position during the seizure occurred only in FLPS. Nocturnal occurrence, short ictal duration, younger age at onset, stereotyped patterns of movements, and MRI and EEG abnormality suggested FLPS.

Early detection of glaucomatous damage. I. Psychophysical disturbances.

In summary, automated perimetry and other psychophysical tests currently provide the most sensitive, reliable and reproducible means of clinically detecting early glaucomatous changes. Compared to optic disk and nerve fiber layer evaluation, such procedures provide a consistent, quantitative method of distinguishing between early abnormalities and normal variations.

Central representation of the sympathetic nervous system in the cerebral cortex.

The sympathetic-related regions of the cerebral cortex were identified in rats after pseudorabies virus injections were made in functionally different targets: adrenal gland, stellate ganglion which regulates the heart, or celiac ganglion which innervates the gastrointestinal tract. Extensive transneuronal labeling was found in limbic system areas: (1) extended amygdaloid complex, (2) lateral septum, and (3) infralimbic, insular, and ventromedial temporal cortical regions (viz., ectorhinal cortex=Brodmann's area 36, perirhinal cortex=area 35, lateral entorhinal=area 28, and ventral temporal association cortex=Te3 region). Deep temporal lobe structures were prominently labeled, including the amygdalopiriform and amygdalohippocampal transition areas, ventral hippocampus and ventral subiculum. The cortical circuits mediating emotional-autonomic changes (i.e., mind-body control) are discussed.

[Psychosomatic disorders considered from an internist viewpoint. I. Nosographic aspects and diagnostic problems]. / I disturbi psicosomatici considerati dal versante internistico. Nota I. Aspetti nosografici e problemi diagnostici.

After a brief introduction regarding the nosography of psychosomatic disorders and the main reasons that have little by little discouraged non-psychiatric physicians to deal with this type of pathology, considering its high incidence among all the areas of general practice, the Authors go on discussing the diagnostic problems and pointing out the most important aspects concerned with these. The Authors conclude by warning not to over-value the effects obtained with an antidepressant especially when it is set up only on the basis of the ex-juvantibus principle. The Authors also invite their colleagues general practitioners to take greater care in the fight for prevention and treatment of these disorders, side by side with the psychiatrist.

[Psychosomatic and mental pathology as essential and interrelated parts of general human pathology]. / Psikhosomaticheskaia i psikhicheskaia patologiia kak neobkhodimye i vzaimosviazannye chasti obshchei patologii cheloveka.

The authors suggest extending the list of conventionally studied general pathological processes with psychosomatic and mental variants of pathology. These variants are relatively new in respect to evolution, are characteristic only for man and, in much lesser degree, for higher animals and have gained recognition in the last 50-100 years by defining the modern specificity of the nosological principle in medicine. The analysis of psychosomatic and psychic aspects of diseases may be of key importance for further development of general human pathology as a science.

Distinctive spontaneous regional neural activity in patients with somatoform pain disorder: a preliminary resting-state fMRI study.

This resting-state functional magnetic resonance imaging study found that nine patients with somatoform pain disorder exhibited atypical precentral gyrus activation compared with 20 healthy controls. The role of the precentral gyrus in pain-related processing is discussed.