Schizophrenia spectrum and related neuropathology.

Abstract

mostly blunted affect, conceptual disorganization and social withdrawal. Those symptoms were related to severity of side effects, functioning at discharge and risk of relapse. Thus, residual symptoms are clinically defined, yet the underlying neuropathology is poorly understood. In a postmortem study of the dorsal raphe nucleus, the main source of serotonergic innervation of forebrain limbic structures, Krzyzanowska et al. [3] found transcriptional activity of ribosomal DNA to be increased in residual versus paranoid schizophrenia patients. This effect was not related to suicide or antipsychotic medication. It may represent a compensatory mechanism to overcome prefrontal serotonergic hypofunction in this patient group. Beside general DNA activity, risk genes such as diacylglycerol kinase eta (DGKH) have been replicated in major psychiatric disorders and gene expression of this variant has been found to be increased in patients with bipolar disorder and schizophrenia. Kittel-Schneider et al. [4] investigated the influence of a risk haplotype of DGKH on the amygdala volume and found an association with increased amygdala volume, a key region implicated in emotional regulation and processing, in bipolar disorder, but not schizophrenia patients or healthy controls. Hass et al. [5] again via fMRI found three complexin2 (CPLX2) SNPs to be associated with increased activity of the dorsolateral prefrontal cortex and intraparietal sulcus in schizophrenia patients compared to controls during a working memory task. This suggests that CPLX2 variants, which are coding for presynaptic proteins involved in neurotransmitter release, may contribute to impaired brain function in schizophrenia. However, to date, it is unclear whether deficits in working memory may also be based on effects of antipsychotic treatment. Potvin et al. [6] investigated symptoms, neurocognition and Focussing on the new DSM-5 classification system, Moller et al. [1] present the second part of their two-piece invited review on changes with reference to the bipolar, schizophrenia spectrum, anxiety and other disorders plus possible consequences under consideration of previous psychiatric classifications. Some important alterations in criteria were made, e.g., in schizophrenia spectrum and related disorders with special consideration of Kurt Schneider’s first-rank symptoms. Moreover, the subtypes of schizophrenia have been removed because of insufficient course stability. However, cognitive impairment defined by neuropsychological tests has not been included in DSM-5. Changes in diagnostic criteria are discussed under aspects of rationality, evidence base, usefulness and possible consequences. The new classification system may help to improve differential diagnosis of psychiatric syndromes, but against original intentions, a more neurobiological approach has not been included, probably due to the lack of robust biomarkers for neuropsychiatric disorders. Since schizophrenia is regarded as spectrum disorder, identification of residual symptoms is needed since most patients considered to be remitted by consensus criteria of the remission in Schizophrenia Working Group present mild psychopathological symptoms. In a naturalistic study with 399 schizophrenia patients, Schennach et al. [2] investigated residual symptoms along suggested consensus criteria as defined by any symptom being present at remission and confirmed that indeed, 94 % of the patients suffered from at least one residual symptom,