Hypothalamic-pituitary-adrenal axis function and hypothalamic-pituitary-thyroid axis function in mentally retarded oatients with and without self-injurious and/or aggressive behaviour - Van Zyl, Paulina Maria (University of the Free State, 2003)
The etiology of aggression and self-injuring behaviour in low functioning mentally retarded patients is multi-factorial and may reflect the presence of undiagnosed psychiatric conditions, unapparent due to the degree of the patient's impairment. It may also reflect hyperactivity of the stress response. The intricacies of diagnosis in this group of patients call for the development of biological markers to aid in diagnosis, therapy selection and drug response monitoring. Measuring and determining the relative contribution of individual neurotransmitters in the problem behaviour is complex and impractical. An alternative route may be to evaluate the functions of the hypothalamic-pituitary axis, which has extensive connections with the limbic area and is relatively easy to assess. The hypothalamic-pituitary system controls the behavioural, endocrine, autonomic and immunological responses to stress. The dexamethasone suppression test (OST) as adapted by Carroll and the thyroid-releasing hormone stimulation test (TRHST) has been extensively used in research on biological markers in major depression. Stress is known to activate the hypothalamic-pituitary-adrenal (HPA) axis, reflected by elevated cortisol levels. The study is a matched control study comparing hypothalamic-pituitary-adrenal axis function and hypothalamic-pituitary-thyroid axis function in 44 institutionalised mentally retarded patients with and without self-injuring and aggressive behaviour through the measurement of baseline cortisol levels and the application of the dexamethasone suppression test and the thyroid-releasing hormone stimulation test. The groups were matched according to gender, age and level of functioning. The mean age of the aggressive group 106 was 44,1 years (±SO 9,8) and the mean age of the non-aggressive group was 44,2 years (±SO 10,5). Baseline hypercortisolaemia occurred in five of the 22 aggressive subjects (22,7 %) and in two of the 22 non-aggressive subjects (9,1 %). Cortisol nonsuppression with the OST occurred in two subjects in the aggressive group (9,1 %) and one subject in the non-aggressive group (4,5 %). The OST did not demonstrate a difference in the two groups, yet there were more individuals in the aggressive group with abnormal high baseline cortisol, as well as a tendency towards a higher baseline cortisol in the aggressive group, suggesting an abnormal or more reactive stress response. Higher baseline cortisol levels were not related to age or the type of aggression, yet subjects with more recent aggressive activity showed higher baseline cortisol levels. The TRHST was generally well tolerated by the subjects. Side effects were few and transient. There were two male subjects in the aggressive group showing a blunted TRHST. Primary hypothyroidism was demonstrated in one of the female subjects in the non-aggressive group and subclinical hypothyroidism in two subjects in the non-aggressive group, as well as in one subject in the aggressive group. Longitudinal studies are needed to determine cortisol levels in unmedicated patients, in addition to comparing cortisol levels during different kinds of treatment.

Die etiologie van aggressiewe en selfbeserende gedrag in laag funksionerende verstandelik vertraagde pasiënte is multi-faktoriaal en mag moontlik die teenwoordigheid van ongediagnoseerde psigiatriese toestande insluit wat nie herken word nie weens die graad van die pasiënt se gestremdheid. Dit mag ook hiperreaktiwiteit van die stresrespons insluit. Biologiese merkers mag van groot waarde wees om te help met diagnose, seleksie van terapie en middelmonitering in hierdie pasiënte. Die meting van en bepaling van die relatiewe bydrae van individuele neurotransmittors tot die probleemgedrag is egter kompleks en onprakties. As' n alternatief mag dit van waarde wees om die funksies van die hipotalamus-hipofise-as te evalueer, aangesien die as uitgebreide verbindings met die limbiese area het en relatief maklik geëvalueer kan word. Die hipotalamus-hipofisesisteem beheer die gedrags-, endokriene, outonome en immunologiese response tot stres. Die deksametasoononderdrukkingstoets (DST) soos aangepas deur Carroll en die tiroïedvrystellingshormoonstimulasietoets (TRHST) word lank reeds gebruik in navorsing oor biologiese merkers in major depressie. Dit is bekend dat stres die hipotalamus-hipofise-bynieras aktiveer, soos gereflekteer deur verhoogde kortisolvlakke . Die studie is 'n gepaarde kontrolestudie waarin die hipotalamus-hipofisebynierasfunksie en die hipotalamus-hipofise-tiroïedasfunksie in 44 geïnstitusionaliseerde verstandelik vertraagde pasiënte met en sonder selfbeserende en/of aggressiewe gedrag met mekaar vergelyk word. Daar word gebruik gemaak van die meting van basislynkortisolvlakke, die deksametasoononderdrukkingstoets soos aangepas deur Carroll en die tiroïedvrystellingshormoonstimulasietoets. Die groepe is gepaar met betrekking tot geslag, ouderdom en vlak van funksionering. Die gemiddelde ouderdom van die aggressiewe groep was 44,1 jaar (±SD 9,8) en die gemiddelde ouderdom van die nie-aggressiewe groep was 44,2 jaar (±SD 10,5). Basislynhiperkortisolemie het voorgekom in vyf van die 22 aggressiewe (22,7 %) en in twee van die 22 nie-aggressiewe proefpersone (9,1 %). Kortisol-nieonderdrukking tydens die DST het in twee proefpersone in die aggressiewe groep (9,1 %) voorgekom en in een proefpersoon in die nie-aggressiewe groep (4,5 %). Die DST kon nie' n onderskeid tussen die twee groepe aantoon nie. Daar was egter meer indiwidue in die aggressiewe groep met abnormale hoë basislynkortisolvlakke sowel as 'n algemene geneigdheid tot hoër basislyn kortisolvlakke in die aggressiewe groep, wat moontlik mag dui op , n abnormale of meer reaktiewe stresrespons. Die hoër kortisolvlakke toon nie' n korrelasie met ouderdom of die tipe aggressie nie, maar proefpersone met meer onlangse aggressiewe aktiwiteit het wel hoër kortisolvlakke getoon. Die TRHST is oor die algemeen goed verdra deur die proefpersone. Newe effekte was min en van verbygaande aard. Daar was twee manlike proefpersone in die aggressiewe groep wat' n afgeplatte TRHST getoon het. Primêre hipotiroïedisme het in een vroulike proefpersoon voorgekom en subkliniese hipotiroïedisme in twee proefpersone in die nie-aggressiewe groep, asook in een proefpersoon in die aggressiewe groep. Longitudinale studies word benodig waarin kortisolvlakke in ongemedikeerde pasiënte bepaal word en gemonitor en vergelyk word tydens behandeling met verskillende modaliteite en verskillende geneesmiddels.
Dissertation (M.Med.Sc. (Pharmacology))--University of the Free State, 2003
Keywords: Aggression; Self-injuring behaviour; Mental retardation; Dual diagnosis; Stress response; Biological marker; Hypothalamic-pituitary-adrenal axis; Hypothalamic-pituitary-thyroid axis; Dexamethasone suppression test; Thyroid-releasing hormone stimulation test; Antidepressants; People with mental disabilities; Adrenocortical hormones; Thyrotropin