Innovative potential treatment strategies for schizophrenia and biomarkers for Alzheimer’s disease

Abstract

In this issue, we are starting with a series of invited reviews on innovative and potential future therapeutic strategies in schizophrenia and affective disorders. Hasan et al. [1] outline that cognitive symptoms do not respond to antipsychotic treatment and are a main predictor for poor social and functional outcome in schizophrenia. During the last years, epigenetic mechanisms mediating the influence of environmental factors on chromatin regulation and gene expression have been reported to play an important role in the pathophysiology of the disease. Therefore, histone deacetylase (HDAC) inhibitors might be potential epigenetic targets in the treatment of schizophrenia. After clarification of target selectivity, adverse effects and identification of eligible patients, future clinical studies should follow this trail. DNA-methylation is a further epigenetic mechanism in which the relationship with environmental experience and brain activation has to be assessed [2]. Aripiprazole is a potent atypical antipsychotic drug with high effectivity and tolerability [3]. Besides its well-known effects on the dopamine system, aripiprazole may also influence other neurotransmitter systems which currently is under investigation. Peselmann et al. [4] treated rats chronically with aripiprazole in different doses and found the vesicular c-amino-butyric (GABA) transporter and the GABA synthesizing enzyme GAD67 to be induced in the hippocampus, amygdala and cerebral cortex. Since reduced expression of GAD67 and a dysfunctional GABA ergic system possibly are involved in the pathophysiology of schizophrenia, alterations of regulatory connections between the dopaminergic, serotonergic and GABA ergic system may play a role in the mode of action of aripiprazole. However, alterations in GAD-immunoreactive neurons have also been shown to occur in patients with bipolar I depression [5], suggesting a neurobiological overlap within the affective-schizophrenia continuum. Poor outcome, often a hallmark of schizophrenia, might be related to patients’ impaired insight into their condition and awareness of need for treatment. Pijnenborg et al. [6] show a strong contribution of affective empathy to insight, suggesting that being able to feel empathy with other peoples’ feelings may enhance insight. Alcohol-induced psychotic disorder is a rare complication of alcohol use disorder, but has an extremely high rehospitalization rate indicating a more chronic course and worse prognosis [7]. Single psychiatric symptoms such as hallucination involving the oral area are categorized as delusional disorder. In a SPECT study, Umezaki et al. [8] revealed right [ left brain perfusion asymmetry in frontal and temporal brain areas in these patients. The rate of transition of mild cognitive impairment (MCI) to Alzheimer’s disease (AD) is an important measure. Thus, the use of biomarkers according to the likelihood of the presence of AD pathology could help classifying patients with increased risk for developing dementia. In a follow-up study, Guo et al. [9] show that neuroimaging (PET, structural MRI) can contribute to identify MCI patients with high, intermediate or low likelihood of the presence of AD pathology and investigated progression toward AD. MCI-high patients had a higher risk of developing AD than the other subgroups. Therefore, the new clinical research criteria of the National Institute on Aging-Alzheimer’s Association (NIA-AA) represent a valuable research instrument in diagnosing MCI. In line A. Schmitt (&) P. Falkai Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University Munich, Nusbaumstr. 7, 80336 Munich, Germany e-mail: Andrea.Schmitt@med.uni-muenchen.de