Neuropsychopharmacology of Auditory Hallucinations
Until recently, the main treatment target of all antipsychotic drugs has been the dopaminergic D2 receptors, and monotherapy is generally recommended in all leading schizophrenia treatment guidelines. This is probably about to change in the coming years. Following the rather conservative approach from the pharmaceutical industry thus far, with only minor modifications to the well-established treatment mechanism, there is now a new wave of schizophrenia drugs which target receptors outside the dopaminergic system. The most promising ones include drugs that address glutamatergic and cholinergic receptor systems, but other drugs under investigation include also anti-inflammatory drugs and cannabis receptor antagonists, as well as others. A third possibility, also mentioned above, is of interacting transmitter systems, for example glutamate and GABA with glutamate to play a role in the spontaneous elicitation of an auditory hallucination, and GABA to play a role in the failure of cognitive inhibition of the 'voice' once initiated. Importantly, it seems unlikely that one particular pharmacological agent will be sufficient to treat all aspects of the psychotic disorders. More likely, drugs with different receptor profiles may act in concert, addressing different subsyndromes in a synergistic manner. Speculatively, by using a multifaceted work-up in each individual patient including pharmacological fMRI, assessments of white matter integrity, and spectroscopy among others, one might move from the phenomenological/symptomatic level of the disorders to the underlying biological pathology unique to each patient. Hypothetically, a patient presenting predominantly with AVH may, based on the full work-up, profit from an individually tailored antipsychotic drug combination regimen which may be different from that prescribed for another patient with AVH but with a slightly different profile of underlying biological alterations. This development will be supported by more widespread usage of advanced brain imaging analysis methods which will enable to make best use of the considerable quantities of data which an fMRI scan yields. In particular, clearer insight into connectivity patterns within fMRI data, their disturbances in psychotic disorders and response to pharmacological manipulation can be expected to be the topics in which research efforts are probably to provide important advances to the current knowledge. Also, although outside the scope of the present review, neuroimaging studies of other treatment modalities for AVH such as psychotherapy and transcranial magnetic stimulation are to the best knowledge of the authors scarce, but could further expand our knowledge of the biological underpinnings of the neuropsychopharmacology of AVH, see for example.
Rapid advances can be expected in the study of intrinsic (task-free) connectivity, as such data sets can be with relative ease integrated across different centers in large-scale collaboration projects. While a dominant approach in the current research is attempting to find structural and functional connectivity patterns which can be generalized over entire populations, interindividual variation in connectivity is attracting interest.
Five-year View
Until recently, the main treatment target of all antipsychotic drugs has been the dopaminergic D2 receptors, and monotherapy is generally recommended in all leading schizophrenia treatment guidelines. This is probably about to change in the coming years. Following the rather conservative approach from the pharmaceutical industry thus far, with only minor modifications to the well-established treatment mechanism, there is now a new wave of schizophrenia drugs which target receptors outside the dopaminergic system. The most promising ones include drugs that address glutamatergic and cholinergic receptor systems, but other drugs under investigation include also anti-inflammatory drugs and cannabis receptor antagonists, as well as others. A third possibility, also mentioned above, is of interacting transmitter systems, for example glutamate and GABA with glutamate to play a role in the spontaneous elicitation of an auditory hallucination, and GABA to play a role in the failure of cognitive inhibition of the 'voice' once initiated. Importantly, it seems unlikely that one particular pharmacological agent will be sufficient to treat all aspects of the psychotic disorders. More likely, drugs with different receptor profiles may act in concert, addressing different subsyndromes in a synergistic manner. Speculatively, by using a multifaceted work-up in each individual patient including pharmacological fMRI, assessments of white matter integrity, and spectroscopy among others, one might move from the phenomenological/symptomatic level of the disorders to the underlying biological pathology unique to each patient. Hypothetically, a patient presenting predominantly with AVH may, based on the full work-up, profit from an individually tailored antipsychotic drug combination regimen which may be different from that prescribed for another patient with AVH but with a slightly different profile of underlying biological alterations. This development will be supported by more widespread usage of advanced brain imaging analysis methods which will enable to make best use of the considerable quantities of data which an fMRI scan yields. In particular, clearer insight into connectivity patterns within fMRI data, their disturbances in psychotic disorders and response to pharmacological manipulation can be expected to be the topics in which research efforts are probably to provide important advances to the current knowledge. Also, although outside the scope of the present review, neuroimaging studies of other treatment modalities for AVH such as psychotherapy and transcranial magnetic stimulation are to the best knowledge of the authors scarce, but could further expand our knowledge of the biological underpinnings of the neuropsychopharmacology of AVH, see for example.
Rapid advances can be expected in the study of intrinsic (task-free) connectivity, as such data sets can be with relative ease integrated across different centers in large-scale collaboration projects. While a dominant approach in the current research is attempting to find structural and functional connectivity patterns which can be generalized over entire populations, interindividual variation in connectivity is attracting interest.
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