Classical Neurotransmitters and Neuropeptides Involved in Schizoaffective Disorder: Focus on Prophylactic Medication

PREFACE

Patients with a schizoaffective disorder are met regularly in the psychiatrist’s practice and in psychiatric wards. Schizophrenic and affective symptoms show a great variety and the courses of the disease can have different outcomes. For patients’ rehabilitation and social integration into the familiar and, in some cases working lives, a prophylactic medication is of great importance. Because we have been working on classical neurotransmitters and Neuropeptide es involved in schizophrenia and in affective diseases, we describe here the alterations of these neuroactive substances in the brain regions involved in the schizophrenic and affective symptoms. In that way, possibilities of finding new agents acting at specific receptors of classical neurotransmitters and Neuropeptide es are pointed out. The schizoaffective disorder, which has a Prevalence of 0.5% in the population, is undoubtedly an inheritable disease with an environment-gene interaction. Some of the discovered susceptibility genes and the functions of the encoded neuroactive substances involved in the pathophysiology of the disease are pointed out. We have established the relationships between the hypothalamic-adrenal axis and the altered neural networks found in the brain areas involved in schizophrenic and affective symptoms. Because we have published several review articles about neural networks in schizophrenia and major depression, we extended here these neural networks to the brain regions involved in schizophrenic and affective symptoms. An essential chapter has been focused on the prophylactic medication. The different prophylactic medications consider the different forms of the disease. Besides, adverse effects and disease symptoms are mentioned, and the additional pharmacotherapies of these adverse effects and symptoms are mentioned, including the current Available drugs. Some recently developed antipsychotic drugs such as lurasidone and cariprazine with a different mechanism of action are included as well. Patients’ well being is very important. Therefore, it is essential to choose an appropriate prophylactic drug and to support the patients’ adherence to the pharmacotherapy through psychoeducation and a social integration. Moreover, this e-book gives a hint to pharmaceutical firms to improve the prophylactic medication by presenting the specific subreceptors involved, on which new pharmacological agents could exert an improved or additional therapeutic effect.

ACKNOWLEDGEMENTS

The authors would like to thank Mr. Nikolas Skinner (University of Salamanca, Spain) for revising the English language.

CONFLICT OF INTEREST

The authors declare that this ebook contents have no conflicts of interest.

Classical Neurotransmitters and Neuropeptide es Involved in Schizoaffective Disorder: Focus on Prophylactic Medication

INTRODUCTION

While schizophrenia, a chronic disabling disorder has a Prevalence of 1%, schizoaffective disorder has a Prevalence of 0.5%. Schizophrenia, which is associated with positive (paranoia, acoustic hallucinations, illusions), negative (social withdrawal, autism, mutism) and cognitive symptoms, becomes manifest as an acute psychosis with mostly positive symptoms after a prodromal phase of about 7 years [1 - 3]. Patients suffering from acute psychosis are mostly in their early adolescence years, and men tend to be younger than women when first-episode schizophrenia is diagnosed [4]. When a schizoaffective disorder is diagnosed, positive schizophrenic symptoms are combined with affective symptoms: for example, depressive, manic or bipolar symptoms [5]. An important issue in all this is the reason for the appearance of schizoaffective disorder. In most cases, susceptibility genes have been found. While common susceptibility genes, which encode dopamine hyperactivity through decreased dopamine breakdown or which encode GABA or glutamate hypofunction [4], cause disease symptoms that can be treated with conventional antipsychotic drugs, rare genes also have an important effect [4]. The severity of acute psychosis is enhanced by environmental factors (e.g., childhood trauma) or the use of psychotomimetic substances (e.g., cannabinoid exposure) [6], since there are gene-environment interactions [4]. In acute psychosis, alterations in neurotransmitters, for example dopamine and serotonin hyperactivity, occur in the mesolimbic system, the hippocampus and the prefrontal cortex. Stressful life events can enhance neurotransmitter alterations in these brain regions. Dopamine hyperactivity is correlated with a dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis and with increased cortisol levels. Consequently, alterations in cortisol levels and increased levels of corticotropin-releasing hormone (CRH) are correlated with increased dopamine levels in the mesolimbic system and hippocampus [4]. This coherence is discussed below, where the neural networks in the brain regions involved in schizophrenia are described. In most schizophrenic or schizoaffective patients, increased cortisol levels are found and the dexamethasone stress test reveals the non-suppression of cortisol levels. Dysfunction of the HPA axis is correlated with psychotic symptoms and cognitive deficits [4]. Moreover, HPA axis dysfunction is associated with patients’ vulnerability in stressful situations. In schizoaffective patients, alterations in neurotransmitter and Neuropeptide e levels can be found in different brain regions [7, 8]. Affective symptoms, for example depressive and manic symptoms, may be associated with a dysfunction of the HPA axis. The correlation between increased CRH levels in the hypothalamus and decreased serotonin levels in the brainstem will be addressed in the chapter about neural networks in the brain regions involved in affective symptoms [7]. In the mesolimbic system and hippocampus, positive schizophrenic symptoms are correlated via D2 and 5-HT2A receptors with dopamine and serotonin hyperactivity [8]. Moreover, in these brain regions a multi-neurotransmitter system has been reported, in which a hypofunction of GABAergic and glutaminergic neurons exerting a presynaptic inhibitory action occurs. In the prefrontal cortex, an antagonistic interaction between M4 muscarinic cholinergic and D1 dopaminergic neurons has been described, while agonism at M4 receptors and a D1 antagonistic effect exert antipsychotic properties. In the midbrain and hippocampus, the monoamines serotonin, noradrenaline and dopamine play an important role in the pathophysiology of depressive and manic symptoms [8]. In the midbrain and hippocampus, a multi-neurotransmitter system will be described, including postsynaptic excitatory neurotransmitters (serotonin, noradrenaline, dopamine, acetylcholine); presynaptic inhibitory neurotransmitters (GABA), and neurotransmitters (glutamate) that exert an excitotoxic and a partly presynaptic inhibitory action [8].

Among the susceptibility genes for schizophrenic symptoms, the common genes encode dopamine hyperactivity through a decreased dopamine breakdown or encode GABA and glutamate hypoactivity [8]. The depressive or manic symptoms are mostly correlated with polymorphisms of the monoamine transporter genes [7]. In this e-book, the relationship between the function of the susceptibility genes and the cellular mechanisms involved will be addressed.

Patients with psychotic symptoms show a worsening of the psychopathology when they are exposed to stressful events or trauma [9]. Patients suffering from acute psychosis should be treated in a psychiatric ward, since it is difficult to reintegrate them into social life and motivate them to return to work [4]. Among the antipsychotic drugs, second-generation antipsychotic drugs (SGAs) are the compounds of choice to treat these patients [10]. Although schizoaffective disorder has a somewhat better outcome than schizophrenia, the number of schizoaffective patients who cannot be reintegrated into social and professional life has not yet been reduced to any meaningful extent [4, 5]. Among the three patients described here in the case reports, two of them are the beneficiaries of a state pension and the other one receives half a pension and performs a part-time