Emotions on the cerebellum Abstract: Many of the mental illnesses, mainly the psychoses such as schizophrenia have hormonal etiological components. Recent studies on epidemiological and life-cycle show distinct differences in the occurrence of schizophrenia in both men and women. This suggests that there is a protective role played by oestrogen. In-vitro and in-vivo preclinical research have indicated oestrodial’s interactions with the central neurotransmitter systems indicated in the pathogenesis of schizophrenia.
Although researches on the involvement of the oestrogen in the development and life cycle of schizophrenia have proved promising, research is still being done on other neuroactive hormones which have an effect on the mental state.It is however hoped that with continuous research and trials, the oestrogen hypothesis can be turned into effective clinical practice. The use of genetic imagery has been put in place in order to establish the relationship between the subject variants and the disorder. The onset and continuation of schizophrenia mainly occurs during adolescence or during the entire reproductive period.
Psychotic disorders are mental disorders that cause abnormal thinking and perceptions. Two main symptoms experienced by patients of psychoses include hallucination s and delusion. Schizophrenia, which this paper seeks to discuss, is an example of a psychotic disorder. Treatment of the psychoses largely depends on the causes. Some of the methods used involve drugs and talk therapy (Bengston 2009, p. 1). Psychoses like schizophrenia are prevalent and devastating conditions with their current treatments only being partially effective and come with high risks on the side effects. New therapeutic strategies are required to address the issue. Hormones such as oestrogen could come in as viable options. Schizophrenia is a mental disorder which is characterized by problems with the thought processes and poor emotional responses.
The cause of schizophrenia has not been established yet. However, the genes, environment and brain chemistry are some of the contributory factors. Research earlier on proposed that psychoses could be caused by an imbalance of the sexual hormones. However, it is recently that researchers suggested an “oestrogen protection hypothesis.” This suggests that oestrogen protects women from suffering from severe mental illnesses at an early age, unlike men. In predisposed women, the fluctuation and final decline of oestrogen during menopause can result into a late onset of schizophrenia. This paper seeks to use hormones as the biological strategy to explain schizophrenia.
Imaging research in schizophrenia
The use of imaging genetics in trying to understand the neurogenetic mechanisms of schizophrenia has experienced an explosive growth of interest. The imaging genetics used apply structural and functional neuroimaging to study the subjects bearing the genetic risk variant factors that relate to a psychiatric disorder. Schizophrenia is a highly inheritable disorder. Catechol-o-methyltransferase, widely known as COMT, has been the most studied within schizophrenia imagine genetics literature. With a comparison to the functional findings, investigations of the effects of the genetic variations within COMT on the brain structure have been less consistent (Munafo & Attwood & Flint 2008, p.150).
Despite the unclear and the often convergent effect on the imaging phenotypes, the effectiveness of using the candidate genes on trying to understand schizophrenia is under debate. This is because the priori-hypothesized variants depict inconsistent impacts on the categorical disease phenotype itself. The candidate genes used in the imaging genetics are mostly concerned about the single genetic variants on the brain phenotypes. Present data disqualifies the use of these genetic findings in the prediction of phenotypes. The use of imaging genetics is therefore evolving towards addressing the key questions originating from the complex nature of schizophrenia genes. Discussed below are three of such frontiers. Future works of neuroimaging will take into consideration epistatic effects of the multiple and common variants, and the use of the imaging data to discover new genetic contributions to neural structure and function which can result in new treatment.
Epistasis refers to the interaction between the genes. Schizophrenia genetics are quite complex. With the high level of heritability, research stipulates that there is no single variant that is so frequent such that by itself it increases the disease risk by 30%. Simulation studies suggest that thousands of the risk genes may be the cause of the high heritability within the complex genetics of schizophrenia. Epistasis may therefor playa vital role within the disorder, and at the same time, be a contributory factor to the interaction with the environment. The level of complexity for the genetic variations concerning schizophrenia constitutes the effects of thousands of variants. It requires a great effort of methodological effort to characterize the interactions between the larger sets of genes as they affect the imaging data. Studies provide proof of concept of the applicability of the multivariate methods in imaging genetics.
Copy number variants
There has been an insight from the last waves of genome. Studies of schizophrenia involve structural variations of the genome. Here, larger segments constituting up to several megabases of the genetic material are either microduplications (duplicated) or microdeletions (missing). Such are more common in schizophrenia than in general population. There is higher risk associated with copy number variants which can lead to an increase in the disease risk of up to ten fold.More effort that takes into account the epistatic and transacting effects into account need to be employed in order to extend the findings.
Forward genetics-discovery science
This is an important future perspective of imaging genetics. It is useful in finding new variants that are associated with brain phenotypes. Within the high level of neuroimaging, there is an escalated penetrance of the common genetic variants. The new approach requires the use of neuroimaging with genome, and a considerably smaller number of subjects than during the use of clinical phenotypes. The new kind of research strategy has a greater potential in identifying new molecular targets that affect the relevant brain systems. However, this works if the systems (and the ideally genetic variants), can both be linked to schizophrenia. It will also provide a much-needed incentive for discovery of a drug for the still insufficiently treatable psychiatric disorder.
Brain processes revealed through imaging research in schizophrenia
Epidemiological and Life-cycle Evidence
The occurrence and course of schizophrenia was earlier on assumed to be similar between both sexes. Currently, results from research carried out suggest that schizophrenia is a sexually dimorphic disease(Gavrilidis, Hayes &Kulkarni, p. 2). The incidence is 40% higher in men than in women. It also occurs about four years earlier than their female counterparts. Study has shown that premenopausal women tend to exhibit a benign course of illness as compared to men. After the age of 45, women experience a resurgence and increased chances of relapse. The second spike incident after menopause in women is believed to come with severity and resistance to treatment. This is because of the falling levels of oestrogen during menopause. In addition to that, in women with schizophrenia, the symptoms tend to fluctuate throughout the menstrual cycle. The high-oestrogen luteal phase has been associated with improvements in psychopathology.The observations here serve as evidence that oestrogen offers protection from severe psychosis to the pregnant women during child bearing years (Meyer-Lindenberg 2010, p. 452).
Oestrogen, for many years has been known to perform primary endocrine and reproductive functions. However, it has significant actions in the Central Nervous System. Oestrogen receptors are found in large abundance within the extrahypothalamic regions, throughout the brain. The limbic system is rich in oestrogen receptors particularly. Similar is the case with the cerebral cortex. It is through classical genomic and rapid non-genomic interactions with the receptors that oestrogen functions as a neuroactive steroid. It influences signaling pathways and neurodegenerative processes in the central nervous system (CNS). However much speculation there is concerning the role of oestrogen in influencing the mental state, current research has shed light on the neuromodulatory and neuroprotective characteristics of oestrogen (Meyer-Lindenberg 2010, p. 448)..
It has been proved that other neurotransmitter systems such as glutamate and serotonin are also involved in the pathophysiology of the disorder, schizophrenia. Effects that oestrogen has on the doperminergic system are still not understood. Studies express great variations concerning the direction, extent and specificity of oestrogen-dopamine interactions. Discoveries have also been made that oestrogen affects the serotonergic system at multiple levels. Various recently published studies indicate oestrogen’s involvement with the central neurotransmitter mechanisms and resultant antipsychotic –like activity.
The pathogenesis of schizophrenia is under consideration by a large population to involve a progressive neurodegenerative component. Patients with schizophrenia have been reported to possess several anatomical abnormalities. Such include reduced grey matter in frontal, limbic, striatal and thalamic regions of the brain. The patients also suffer from ventricular enlargement and abnormalities of the medial temporal lobe and prefrontal cortex. Research states that the psychoprotective characteristics of oestrogen might result from their preservation and improvement of neuronal mitochondrial function during injurious circumstances. Mitochondria are responsible for regulating the viability and death of neurons.
Schizophrenia and the reproductive circuits of the brain
Study has provided evidence of the altered excitability of the neurons in the basal forebrain in schizophrenia. The onset of schizophrenia at the beginning of or withinthe continuation of the reproductive period suggest that there is a relationship between the disorder and the changes that take place in the brain during the fertility period (Stevens 2012, p. 5). Some of the changes that take place during adolescence include the activation and an escalated pumped release of gonadotropin-releasing (luteinizing) hormone. The increase of circulation of androgens and oestrogens in the body is associated with sexual maturation. There are also changes in physical, physiologic and behavioral changes.
In conclusion, understanding the cause, courses and the treatment of schizophrenia continues to puzzle both the health officials and the public. Among those infected with schizophrenia, 80% of the population experience the onset of the schizophrenia during the reproductive period. Neuroendocrine and physiologic events that occur in the basal forebrain at the start and the continuation of the reproductive period initiate the onset of schizophrenia. There is a flow of oestrogen and testosterone during puberty and throughout the reproductive period.The development of schizophrenia during the adolescence period and through the period of fertility provides evidence that the disorder is related to a disturbance in the balance one or more of the inhibitory or excitatory factors. This comes about as a response to the flood of reproductive hormones.
Even though there is no anatomic disturbance in physiology that is pathogmonic or is crucial to the development of schizophrenia, recordings from the basal forebrain nuclei in patients with schizophrenia show unusual levels of electronic activity within the areas. The maximum occurrence of the disorder during the period of reproduction and the extent of response to different antipsychotic agents by different people stipulate that the imbalance is associated with a pathologic extension of physiologic inhibition by one or more inhibitory factors beyond the basal forebrain in response to the flood of excitatory hormones to the brain during the reproductive period.
Bengston, M. (2009). Schizophrenia and Psychosis; Schizophrenia Information and Treatment
Introduction, London: SAGE
Meyer-Lindenberg, A. (2010). Imaging genetics of schizophrenia, New York: Prentice Hall Munafo MR., Attwood AS., Flint J. (2008). Bias in genetic association studies: effects of
research location and resources. Psychol Med, 38:1213–1214.
Stevens, R. J. (2012). Schizophrenia; Reproductive Hormones and the brain. The American
journal of Psychiatry, 8(4); 121-134