Psychiatry - December 2008 - (Page 53)

[update on blood brain barrier] Figure 1. Direction of temperature: a factor dependent on Ca++ influx. or external demands. The psychiatric patient population appears more vulnerable to changes in thermoregulation as compared to others. Are these developmental changes due to increased susceptiblity or genetic make-up manifesting later in adolescence? Or are these physiological changes due to metabolic or pharmacological interventions seen with advancing age or onset of diseases? These questions necessitate further exploration. DISCUSSION Thermoregulation is a developmental process. According to one experimental study, development of thermoregulatory mechanisms start during the prenatal ontogeny.13 Relevance of this study to human in-utero thermoregulatory mechanisms, however, is unclear. Febrile seizures, therefore, serve as an example of poor developmental responses to thermoregulatory mechanisms. NMS and MH, on the other hand, are seen later, both in young adults and the elderly. Genetic predisposition seems to be one independent underlying factor for both conditions. It appears that only a certain population expresses symptoms consistent with NMS or MH. Cell wall damage, potentially a result of medications or hypoxia due to metabolic deficiencies described in this article, is a factor that may contribute to calcium overload of cellular mitochondria14 leading to cytotoxicity and cell death in the hypothalamis compromising the intactness of the BBB. These processes may be independent of genetic predisposition in some, and dependent genetically by cytoprotective mechanisms, such as apoptosis,15 in others. External factors, therefore, could play a significant role by quickly unbalancing the metabolic internal mechanisms maintaining normal physiological body requirements and vice versa—all of which may result in extreme variations in body temperatures, particularly in individuals in whom the intactness of the BBB is compromised. Minor variations in any of the factors described in this article, therefore, could generate a huge impact on body temperatures due to a shift in the neurotransmitter balance via altered calcium signalling. Resulting feedback neurotransmitter response is one example of shifting the thermoregulatory balance toward hypothermia by blocking the 5HT2 receptors and activating D2 receptors, respectively, as with the case of the second-generation, atypical antipsychotic risperidone. Conversely, the balance shifting toward thermoregulatory hyperthermia secondary to [VOLUME 5, dopamine blockade and serotonergic activation has been observed with the first-generation typical antipsychotic haloperidol. This may in part explain the similarities in clinical manifestations, which are common to both NMS and serotonin syndrome (SS). In summary, researchers have made enormous progress in their efforts to understand psychopharmacology at a molecular level; however, associating thermoregulatory feedback mechanisms in the particular context of psychopharmacology remains under-recognized. The potential of psychiatric patients being more vulnerable to thermoregulatory changes either inherently or related to unknown factors compromising the BBB in hypothalamic region warrants further exploration and research. CONCLUSION From a practicing psychiatrist’s point of view, monitoring vital signs routinely in outpatient settings as with inpatient settings may provide better insights into the relationship between thermoregulatory mechanisms and psychopharmacology. Secondly, use of receptor modulators capable of stabilizing CNS calcium homeostasis, such as centrally acting calcium channel blockers, in conjunction with antipsychotics may provide a safer treatment approach 12, DECEMBER] NUMBER Psychiatry 2008 53

Table of Contents Feed for the Digital Edition of Psychiatry - December 2008

Psychiatry - December 2008 Editor’s Message Contents Editorial Advisory Board Antidepressant Prescribing by Specialty and Treatment of Premenstrual Dysmorphic Disorder Pain, Pain, Go Away: Antidepressants and Pain Management Why Psychotherapy Helps the Patient in Chronic Pain General Medical Drugs Associated with Depression Katatonia: A New Conceptual Understanding of Catatonia and a New Rating Scale Thermoregulation and the Role of Calcium Signalling in Neurotransmission Cognition and Schizophrenia: Is There a Role for Cognitive Assessments in Diagnosis and Treatment? Journal Watch Information for Authors

Psychiatry - December 2008

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