Imaging pain in patients: is it meaningful?

PURPOSE OF REVIEW: Neuroimaging methods are widely used by researchers and clinicians interested in better understanding the functioning of the human brain in health and disease. Advances have been made in understanding how nociceptive processing within the healthy human central nervous system generates a conscious perception of pain. The focus has now shifted towards patient-related research, harnessing earlier developments to test specific hypotheses in a broad range of chronic pain disorders. The timing is ideal to assess the utility of data generated from these studies. RECENT FINDINGS: This review discusses how clinical pain is represented in the human brain as compared with the processing of acute pain in healthy controls. The imaging literature is reviewed for hypotheses that have been tested in patients regarding mechanisms that might contribute towards the development of chronic pain. Issues related to plasticity, central sensitization, psychological confounds, genetics, and necrosis are examined. SUMMARY: Results to date strongly support the notion that neuroimaging will aid our understanding of basic mechanisms contributing to the generation of chronic pain states. These techniques might help diagnose a patient's pain condition in a more objective and robust way, enabling better targeting of therapies and rapid development of compounds to alleviate pain.     

Psychopathy in childhood: is it a meaningful diagnosis?

Psychopathy is not included in either of the main classification systems (ICD-10 or DSM-IV). Research has now extended the concept of psychopathy to childhood and has produced evidence that it is meaningfully distinct from antisocial behaviour. It is proposed that psychopathy should be accepted as a meaningful diagnosis in childhood.     

Tumour vasculature and angiogenic profile of paediatric pilocytic astrocytoma; is it much different from glioblastoma?

M. Sie, E. S. J. M. de Bont, F. J. G. Scherpen, E. W. Hoving and W. F. A. den Dunnen (2010) Neuropathology and Applied Neurobiology 36, 636–647
Tumour vasculature and angiogenic profile of paediatric pilocytic astrocytoma; is it much different from glioblastoma? Aims: Pilocytic astrocytomas are the most frequent brain tumours in children. Because of their high vascularity, this study aimed to obtain insights into potential angiogenic related therapeutic targets in these tumours by characterization of the vasculature and the angiogenic profile. In this study 59 paediatric pilocytic astrocytomas were compared with 62 adult glioblastomas, as a prototype of tumour angiogenesis. Methods: Microvessel density, vessel maturity in terms of basement membrane and pericyte coverage, and turnover of both endothelial and tumour cells, and vascular endothelial growth factor (VEGF) expression were evaluated in tumour tissue, immunohistochemically stained with, respectively, CD34, collagen IV, smooth muscle actin, Ki67/CD34, caspase‐3/CD34 and VEGF(‐A–D). As an indicator for vessel stability the angiopoietin (ANGPT)‐1/ANGPT‐2 balance was calculated using Real Time RT‐PCR. Results: Pilocytic astrocytoma and glioblastoma showed similar fractions of vessels covered with basement membrane and pericytes. Overlapping ANGPT‐1/ANGPT‐2 balance and VEGF‐A expression were found. Pilocytic astrocytoma had fewer but wider vessels compared with glioblastoma. Turnover of endothelial and tumour cells were relatively lower in pilocytic astrocytoma. Within pilocytic astrocytoma, higher ANGPT‐1/ANGPT‐2 balance was correlated with fewer apoptotic endothelial cells. Lower numbers of vessels were correlated with higher VEGF‐A expression. Conclusions: Despite the fact that pilocytic astrocytoma showed a different vessel architecture compared with glioblastoma, a critical overlap in vessel immaturity/instability and the angiogenic profile was seen between both tumours. These findings suggest encouraging possibilities for targeting angiogenesis (for instance with anti‐VEGF) as a therapeutic strategy in pilocytic astrocytoma.     

Polypharmacy: when is it rational?

In this article, the authors discuss when it makes sense to consider using more than one medication to treat a single condition. They give a brief history of the use of polypharmacy in psychiatry and discuss how new discoveries in psychotropic drug development are making polypharmacy an increasingly important topic today. The authors then present a list of 10 criteria to guide the rational use of psychotropic polypharmacy and explain each in detail with examples drawn from clinical practice.     

Mechanism of acute tryptophan depletion: is it only serotonin?

The method of acute tryptophan depletion (ATD), which reduces the availability of the essential amino acid tryptophan (TRP), the dietary serotonin (5-hydroxytryptamine (5-HT)) precursor, has been applied in many experimental studies. ATD application leads to decreased availability of TRP in the brain and its synthesis into 5-HT. It is therefore assumed that a decrease in 5-HT release and subsequent blunted neurotransmission is the underlying mechanism for the behavioural effects of ATD. However, direct evidence that ATD decreases extracellular 5-HT concentrations is lacking. Furthermore, several studies provide support for alternative underlying mechanisms of ATD. This may question the utility of the method as a selective serotonergic challenge tool. As ATD is extensively used for investigating the role of 5-HT in cognitive functions and psychiatric disorders, the potential of alternative mechanisms and possible confounding factors should be taken into account. It is suggested that caution is required when interpreting ATD effects in terms of a selective serotonergic effect.     

Stress management: what is it?

Stress management (SM) is a widely used term with a seemingly obvious meaning. The research literature contains many studies evaluating its effectiveness, but it is not clear how many different forms of SM exist and how efficacious they are for which target problem. One hundred and fifty-three studies on SM were analyzed to determine consensus in definitions and therapy protocols. Results showed that a typical delivery format exists (mostly group form, 8-10 sessions in length and multitechnique), but the number of techniques used was very large, techniques were inconsistently labeled are often poorly described. It is concluded that in outcome research, the term "stress management" is operationally defined with such variability that comparisons of SM outcome studies are not meaningful at this time.     

Treatment of the schizophrenia prodrome: is it presently ethical?

Although the devastating consequences of schizophrenia have long been known, interest in preventive intervention has only recently emerged. The shift in focus toward early treatment has been encouraged by findings suggesting that the longer psychosis remains untreated, the poorer the prognosis, and by the recent introduction of novel antipsychotic medications with a more benign side effect profile than conventional neuroleptics. In this paper, we argue that interest in prevention has outpaced the necessary scientific and ethical underpinnings for clinical trials involving the schizophrenia prodrome. Specifically, we maintain that the prodromal phase of schizophrenia is, at present, essentially a retrospective construct and that, as a result, the defining signs and symptoms currently in use must be validated in naturalistic, longitudinal studies. In particular, it is essential to establish solid base rates for schizophrenia in prodromal individuals before early treatment can be effectively evaluated. Additional ethical/scientific issues discussed include: (1) the need for an exit strategy (i.e. the determination of when to discontinue treatment in an individual who does not develop schizophrenia), (2) the advisability of pharmacological interventions that specifically target neurocognitive deficits, and (3) the possibility that antidepressant medications may be as effective or more effective, with fewer side effects, than antipsychotic medication for prodromal individuals.     

Five-factor model of schizophrenic psychopathology: how valid is it?

Aim of the study was to examine the consistency of the five-factor model of schizophrenic symptoms, assess its validity and evaluate its dimensional factor structure using confirmatory factor (CFA) analysis. A sample of 258 randomly assigned DSM-III R patients with schizophrenic disorders were studied by means of the structured clinical interview for the Greek validated Positive and Negative Syndrome Scale (PANSS) and were rated on its 30 items. Patients' scores were subjected to principal component analysis (PCA) with varimax rotation. Internal consistency for each of the components was determined by the use of Cronbach's alpha. External validity of the model derived was investigated by searching for possible relationships between the components and sociodemographic characteristics with the aid of canonical correlation analysis. Confirmatory factor analysis (CFA) was also performed. Using the scree plot criterion PCA revealed a five-factor model. These factors were interpreted as representing--in a decreasing order of relative importance--the following dimensions of schizophrenic psychopathology: negative, excitement, depression, positive and cognitive impairment. The model was comparable with six previous factor analytic studies. Internal consistency was quite satisfactory whereas external validity was found to be not so powerful. CFA did not show that the proposed model yields an adequate factor structure.     

Subependymal giant cell astrocytoma (SEGA): Is it an astrocytoma? Morphological,immunohistochemical and ultrastructural study

Subependymal giant‐cell astrocytoma (SEGA) is a rare intra‐ventricular low‐grade tumor which frequently occurs as a manifestation of tuberous sclerosis complex. The histogenesis of SEGA is controversial and its astrocytic nature has been doubted. First studies suggested the astrocytic nature of SEGA while several recent reports demonstrate its glio‐neuronal nature. In spite of this, in the recently revised WHO classification of the CNS tumors, SEGA has been still included in the group of astrocytomas. We studied nine tuberous sclerosis complex‐associated SEGAs. Patients were 1–18 years old. Eight patients (89%) had a solitary lesion located in the lateral ventricle close to of the head of the caudate nucleus, the remaining patient (11%) had two tumors, one located close to the head of the left caudate nucleus and the other in the central part of the right lateral ventricle. Histologically, tumors were composed of three types of cells: spindle, gemistocytic and ganglion‐like. Four tumors (44%) had a prominent vascularization and three (33%) showed an angiocentric pattern. Calcifications were observed in six cases (66%). By immunohistochemistry, the majority of the tumors were GFAP‐ (9; 100%), neurofilament‐ (8, 89%), neuron‐specific enolase‐ (9, 100%), and synaptophysin‐ (8; 89%) positive. Ultrastructural studies were performed on four cases. In all four there were glial cell processes filled with intermediate filaments. In one case dense core putative neurosecretory granules were appreciable. Our results emphasize the glio‐neuronal nature of SEGA. We suggest moving it into the group of mixed glio‐neuronal tumors under the denomination of subependymal giant cell tumor.     

Is it possible to develop a cerebellar reserve?

The concept of neural plasticity accounts for the now well clarified brain ability to react to internal and external stimuli by transforming its structure and function.The translation of whatever experience in specific electrical signals that run through our neural networks induces a number of plastic changes at both functional and structural levels.