Classical Neurotransmitters and Neuropeptides Involved in Schizoaffective Disorder

Schizoaffective disorder has a prevalance of 0.5 %. In this disease, psychotic symptoms are combined with affective, i.e. depressive, manic or bipolar symptoms. The disease is encoded in susceptibility genes, which can be enhanced by stresssful life events or psychotomimitic substances. The neurotransmitter and neuropeptide alterations are described in the involved brain regions in schizophrenic and affective symptoms. In these brain regions, neural networks are described including a multi-neurotransmitter system. The coherence between the hypothalamic-pituitary-adrenal axis and the neurotransmitter alterations will be pointed out. The current pharmacotherapy is reviewed, and some new antipsychotic drugs will be examined critically. The importance of additional sociotherapies and psychoeducaction is underlined, because it enables the schizoaffective patients to be reintegrated into social and perhaps professional lifes.

Here, we describe the forms of schizoaffective disorder with schizophrenic and affective symptoms, for example depressive or manic symptoms or the bipolar form. Prognosis of the schizoaffective disorder is better than that of schizophenia and there are three different outcomes: a schizoaffective psychosis with a total remission, recurrent psychoses with a residual condition and recurrent psychoses with a deficiency condition. Three case reports are given with recurrent psychoses of the bipolar form and with recurrent schizomanic psychoses. The course of the disease is pointed out, and the patients’ treatment with a prophylactic medication is described. The three patients remain stable under this treatment, and, this is important to note, they are socially integrated.

Here, we describe the alterations of classical neurotransmitters and neuropeptides, acting at specific subreceptors, in the brain regions involved in affective and schizophrenic symptoms in the schizoaffective disorder. In schizophrenic symptoms, alterations of the postsynaptic excitatory neurotransmitters dopamine and serotonin and hypoactivity of the presynaptic inhibitory neurotransmitter GABA and of glutamate occur in the mesolimbic system, hippocampus and prefrontal cortex. Neuropeptides, such as neurotensin, cholecystokinin and substance P act as neuromodulators. In depressive symptoms, brain regions such as the brainstem, hypothalamus and hippocampus are involved. Serotonin, dopamine, acetylcholine, GABA and glutamate play an important role. Neuropeptides such as galanin, neuropeptide Y and substance P are involved in the pathophysiology of the affective symptoms. Because schizophrenic and affective symptoms can be enhanced by stressful events or traumatisms, the hypothalamic-adrenal axis and its efferent connections to the brainstem and hippocampus are considered. We suggest additional pharmacotherapies for the treatment of the disease interfering with specific subreceptors of the classical neurotransmitters and neuropeptides described.

The schizoaffective disorder is a heritable disease and some susceptibility genes have been discovered. Risk genes that may encode psychotic symptoms are for example, dysbindin-1 and neuregulin-1 which encode glutamate hypoactivity, catechol- O-methyl transferase and monoamine oxidase A/B which encode dopamine hyperactivity through a decreased dopamine breakdown, and GAD 67 which encodes GABA hypoactivity. The PACAP gene is as well a risk gene for psychotic symptoms. Animals lacking the PACAP gene show behavioral abnormalities which can be ameliorated after administration of 5-HT2A antagonists. The proline hydroxylase is also a risk gene for psychotic symptoms. One haplotype of this gene causes deficits in prepulse inhibition. Rare risk genes for psychotic symptoms may cause a psychosis which begins in the early adolescence and may be treatment-resistant. Environmentgene interactions and epigenetic mechanisms can concern dopaminergic, serotonergic, GABAergic and glutaminergic neurons. Depressive symptoms may be due to alterations of the serotonin and noradrenaline transporter genes. Manic symptoms can be encoded by the genes monoamine oxidase A/B and catechol-O-methyl transferase.

In schizophrenic and affective symptoms of the schizoaffective disorder, neural networks are described in the brain regions involved. In schizophrenic symptoms, neural interactions are described in the ventral tegmental area, A10 cell group, hippocampus, prefrontal cortex and hypothalamus. In the hippocampus, the dopamine and serotonin dysfunction is considered. In depressive symptoms, neural networks in the brainstem, including the “mood center” and the center for the circadian rhythm, the hippocampus and the hypothalamus are pointed out. The interaction between the hypothalamic-adrenal axis and the serotonergic system located in the brainstem is included. The involvement of the specific subreceptors of neurotransmitters and neuropeptides, on which prophylactic drugs could exert a therapeutic effect, is discussed.

The schizoaffective disorder is mainly treated with second-generation antipsychotic drugs as a prophylactic medication. In this sense, the commonly used second-generation antipsychotic drugs are risperidone, olanzapine, quetiapine and aripiprazole. Whereas risperidone has a good antipsychotic, antimanic and therapeutic effect on positive schizophrenic symptoms, olanzapine also exerts a good therapeutic effect on negative schizophrenic symptoms. Quetiapine exerts a good antipsychotic and antidepressant effect. Aripiprazole with a different mechanism of action can improve the outcome of the disease in a long-acting injectable form. Lurasidone is a recently developed antipsychotic drug which can improve cognitive functions as well. Among the mentioned antipsychotic drugs, risperidone causes more often extrapyramidal side effects than the other antipsychotic drugs. When patients suffer from a schizoaffective disorder with a bipolar form, mood-stabilizing drugs can be chosen. Lithium can be administered, because it exerts a secure effect. Other mood-stabilizing drugs are carbamazepine, valproic acid and lamotrigine. Additional pharmacotherapies are sedating neuroleptics, benzodiazepines and anticholinergics or NMDA antagonists to treat the extrapyramidal symptoms. Psychoeducation can improve patient’s adherence to the prophylactic medication. At the end of the chapter, the specific subreceptors, on which new drugs could exert an antipsychotic or antidepressant effect, are summarized according to the preceeding chapters.

After a schizoaffective disorder is diagnosed, a prophylactic medication is administered in most cases. The second-generation antipsychotic drugs risperidone, olanzapine, quetiapine and aripiprazole are the commonly prescribed drugs in the prophylaxis of psychotic and affective symptoms. Risperidone is an appropriate antipsychotic drug to treat schizophrenic and manic symptoms. Olanzapine has a safe therapeutic effect and the lowest discontinuation rate. Quetiapine can be used to treat schizophrenic and depressive symptoms. The long-acting injectable form of aripiprazole is a prophylactic medication which enhances adherence to the pharmacotherapy. Clozapine is a reserve antipsychotic drug for treatment-resistant psychoses. Under this treatment, a 3 weekly blood cell count should be taken in order to exclude a decreased white cell blood count. It is possible to combine second-generation antipsychotic drugs with each other, for example risperidone and quetiapine. The schizoaffective disorder should be treated with a prophylactic monotherapy, but second-generation antipsychotic drugs could be combined with mood-stabilizing drugs, while lithium is given preferentially in a bipolar form. Psychoeducation and a social integration are of great importance in order to achieve a patients’ insight in the disease and to enhance their adherence to the pharmacotherapy.