Disturbances In Schizophrenia Research Articles

Subjective-Objective Sleep Discrepancy in Schizophrenia

ABSTRACT Objective/Background Subjective methods are often employed for sleep assessment due to their ease of use, but the results may not concur with objective findings. This discrepancy may be present in schizophrenia; however, limited data are available. We performed a secondary analysis to evaluate the agreement between 1-week actigraphy and sleep diary-derived parameters and factors that contribute to subjective-objective sleep discrepancy. Participants 66 outpatients with schizophrenia (mean age = 44.08 years; 45.45% males). Methods Agreement between subjective-objective parameters was assessed using two-way repeated measures ANOVA, Pearson’s correlation, and Bland-Altman plot. The magnitude of discrepancy was quantified using Cohen’s d. Pearson’s correlation was used to determine the significant factors of subjective-objective sleep discrepancy. Benjamini-Hochberg adjustment was performed to account for multiple testing. Results On average, sleep diaries overestimated sleep onset latency by 20.45 min, total sleep time by 37.63 min, and sleep efficiency by 4.29%, but underestimated wake after sleep onset by 33.28 min. Cohen’s d ranged between 0.61 and 1.41. Subjective-objective discrepancies were significantly associated with marital and employment status, self-reported sleep disturbance, delayed sleep-wake phase disorder, chronotype, and psychosocial functioning (r = 0.32–0.44; Benjamini-Hochberg corrected p < .05). Conclusions Our findings show that differences between subjective and objective measurements of sleep are present in schizophrenia. Although actigraphy is not a standard procedure for sleep disturbance in schizophrenia, clinical judgment should be used if patients are suspected to have overestimated their sleep difficulties. Further studies should examine whether feedback based on actigraphy can benefit patients with schizophrenia and comorbid sleep disturbances.

Deictic Navigation Network: Linguistic Viewpoint Disturbances in Schizophrenia.

This paper introduces the Deictic Navigation Network, a cognitive-linguistic framework to analyze and clarify the nature of viewpoint disturbances in language, applied to schizophrenia. We argue that such disturbances have linguistic counterparts in the use of deixis: linguistic elements of which the interpretation relies on the situational context of the discourse and their connection to a subject-bound perspective. The DNN connects such linguistic phenomena to three viewpoint disturbances, which can manifest in different degrees of extremity: (i) the reduced capacity to recognize one’s own subjective perspective and the subjective perspectives of others; (ii) the reduced capacity to separate present perspectives from distinct past, future, and hypothetical perspectives; and (iii) the reduced capacity to integrate projected viewpoint structures into the actual here-and-now. We explain how application of the DNN to language in schizophrenia enables the localization of perspectivization disturbances and helps to clarify the nature of disturbances in the ability to build complex viewpoint structures in language as well as cognition.

Self and world experience in non-affective first episode of psychosis

A disturbance of “minimal self,” — of the immediate sense of mine-ness inherent in experience—is hypothesized to be the core disturbance in schizophrenia. Research with the Examination of Anomalous Self Experience (EASE) has demonstrated the selective aggregation of anomalous self-experiences in the schizophrenia spectrum. Conceptual research suggests that anomalous world experiences, including changes in the experience of space, time, and other persons, occur alongside anomalous self-experiences and are an important aspect of subjectivity in schizophrenia. The Examination of Anomalous World Experience (EAWE) is a recently published interview format designed to explore changes in world experience in schizophrenia. In the current study, 24 hospital outpatients with non-affective first-episode psychosis and 24 healthy-control participants were assessed with the EAWE and the EASE. First episode psychosis patients had total EAWE and EASE scores that were both, on average, significantly higher than the healthy-control group. EAWE and EASE scores were highly correlated, even after removing overlapping items. The distribution of EAWE items and subtypes in the first-episode psychosis sample was heterogeneous. We conclude that anomalous world experiences represent a relevant aspect of first-episode psychosis, and that they may be related to the self-disturbances thought to underlie schizophrenia spectrum disorders.

24.1 VERBAL COMMUNICATION DISORDERS IN SCHIZOPHRENIA SPECTRUM PATIENTS: SYMPTOM AND SIDE EFFECT

Background: Verbal communication disturbances are a key diagnostic feature of schizophrenia. These disturbances present in different aspects, which can be assessed by looking at form and meaning. However, research on this topic is often confounded by the effects of antipsychotic medication. It therefore remains unclear which aspects of language production are influenced by antipsychotics, and which disturbances can be viewed as true psychotic symptoms. Automated language analysis has recently shown to be a useful tool to characterize verbal communication disturbances in schizophrenia. Methods: The spoken language of 42 healthy controls and 48 patients with a schizophrenia spectrum disorder was recorded using a semi-structured interview designed to elicit spontaneous speech in a natural setting. The audio was analyzed for measures of speed and quantity. For a subset of participants, the transcribed interview was analyzed using a novel Natural Language Processing (NLP) word2vec model to quantify incoherence. For patients, dopamine receptor affinity of their antipsychotic drug was estimated. Symptom severity was assessed by means of the Positive and Negative Syndrome Scale (PANSS). Results: Overall, schizophrenia spectrum patients spoke slower and produced fewer words than the healthy controls. Language measures revealed medium to strong correlations with PANSS negative and general scores. Usage of antipsychotics with strong D2 receptor affinity was found to have the strongest effect on speech. Word2vec trained models were able to differentiate between patients and controls. Conclusions: Automated assessments of aspects of verbal communication show promise in elucidating and quantifying various symptoms. Our results indicate that usage of antipsychotic medication has a marked effect on verbal communication in addition to disturbances that are better interpreted as part of the illness. These medication-effects should be taken into account when analyzing language disturbances in schizophrenia. Word2vec proved to be a useful tool to differentiate between subjects and controls, reflecting disturbances in both meaning and structure in verbal communication. This research illustrates the possibilities in automated assessment of language which can serve as measures of symptom severity, medication effects and open the door to diagnosis and prognosis.

Abnormalities of oligodendrocyte clusters in supra- and infragranular layers of the prefrontal cortex in schizophrenia

A deficit of cortical gray matter myelination in the frontal lobes has been reported in schizophrenia in neuroimaging studies. Previously the decrease in the numerical density (Nv) of oligodendrocytes (NvOl) in layers 3 and 5 in area 10 of the prefrontal cortex (PFC) has been reported in schizophrenia. Oligodendrocyte progenitors proliferate in the adult human brain and form oligodendrocyte clusters for functional-dependent adaptive myelination. We aimed to estimate the NvOl and Nv of oligodendrocyte clusters (NvOlC) in supra- and infragranular sublayers of the PFC in schizophrenia and healthy controls. 17 chronic schizophrenia subjects and 20 healthy matched controls were studied in Nissl-stained sections in sublayers 3a- 3c and 5a of the PFC by stereological optical dissector method. The NvOl and the NvOlC were significantly decreased in supra- (32%, p<0.02) and infragranular sublayers (50%, p<0.001) of the PFC in the schizophrenia group as compared to controls. The Nv OlC/Nv Ol ratio decreased significantly in the schizophrenia group only in sublayers 3a (p=0.015) and 5a (p<0.001). In the control group, the NvOlC was positively correlated with the NvOl in sublayers 3b, 3c and 5a (R≥0.59; p≤0.006). In the schizophrenia group, a significant correlation between the parameters was found only in sublayer 5a (R=0.8; p<0.001). The deficit of oligodendrocyte clusters might be associated with altered proliferation and/or maturation of oligodendrocyte progenitors in schizophrenia. Specific alterations of the Nv OlC/Nv Ol ratio might be due to different connectivity of supra- and infragranular sublayers of the PFC and their disturbances in schizophrenia.

Self\u2013other recognition impairments in individuals with schizophrenia: a new experimental paradigm using a double mirror

Clinical observations suggest early self-consciousness disturbances in schizophrenia. A double mirror combining the images of two individuals sitting on each side of the mirror was used to study self–other differentiation in 12 individuals with early onset schizophrenia (EOS) and 15 individuals with adult onset schizophrenia (AOS) compared to 27 typically developing controls (TDC) matched on age and sex. The effects of intermodal sensory perception (visual–tactile and visual–kinesthetic) on self–other recognition were also studied. The results showed that EOS and AOS individuals, independently of age and schizophrenia severity, were centered on their own image compared to TDC, with both significant earlier self-recognition and delayed other-recognition during the visual recognition task. In addition, there was no significant effect of intermodal sensory stimulation on self–other recognition in EOS and AOS patients, whereas self-centered functioning was significantly increased by visual–tactile stimulation and decreased by visual–kinesthetic stimulation in TDC. The findings suggest that self–other recognition impairments might be a possible endophenotypic trait of schizophrenia.

Regulation of obesity-associated metabolic disturbance by the antipsychotic drug olanzapine: Role of the autophagy-lysosome pathway

Metabolic disturbance is commonly observed in schizophrenia patients, and the metabolic impacts of atypical antipsychotics such as olanzapine (OLA) have received much attention. Drug naive schizophrenia patients display metabolic abnormality to varying degrees, but how this shapes the metabolic responses to chronic OLA exposure is unknown. Using high-fat diet (HFD, 8 weeks) induced obesity, here we explored the metabolic outcome of chronic OLA exposure in conditions of pre-existing metabolic disturbance. OLA treatment (2 mg/kg) for 4 weeks led to markedly reduced body weight and adiposity in obese mice, concomitant with reduced adipose inflammation and hepatic steatosis. No significant change was observed on insulin sensitivity or energy expenditure after OLA exposure. Mechanistically, OLA restored autophagic clearance in the subcutaneous adipose tissue of obese mice, in line with its potentiation of lysosomal function in adipocytes. The metabolic phenotypes induced by OLA were partially reversed by chemical suppression of autolysosome. Together, these data uncover distinct metabolic effects of OLA in obesity involving the regulation of adipose tissue autophagy, and suggest a complicated link between OLA therapy and metabolic disturbance in schizophrenia.

Posterior pituitary neurohormonal disturbances in schizophrenia and role of oxytocin in treatment &amp;ndash; need for more short- and long-term studies

Posterior pituitary neurohormonal disturbances in schizophrenia and role of oxytocin in treatment &amp;ndash; need for more short- and long-term studies

Altered gyrification in schizophrenia and its relation to other morphometric markers

Schizophrenia is modelled as a neurodevelopmental disease with high heritability. However, established markers like cortical thickness and grey matter volume are heavily influenced by post-onset changes and thus provide limited possibility of accessing early pathologies. Gyrification on the other side is assumed to be more specifically determined by genetic and early developmental factors. Here, we compare T1 weighted 3 Tesla MRI scans of 51 schizophrenia patients and 102 healthy controls (matched for age and gender) using a unified processing pipeline with the CAT12 toolbox. Our study provides a direct comparison between 3D gyrification, cortical thickness, and grey matter volume. We demonstrate that significant (p < 0.05, FWE corrected) results only partially overlap between modalities. Gyrification is altered in bilateral insula, temporal pole and left orbitofrontal cortex, while cortical thickness is additionally reduced in the prefrontal cortex, precuneus, and occipital cortex. Grey matter volume (VBM) was reduced in bilateral medial temporal lobes including the amygdala as well as medial and dorsolateral prefrontal cortices and cerebellum. Our results lend further support for altered gyrification as a marker of early neurodevelopmental disturbance in schizophrenia and show its relation to other morphological markers.

Ipseity at the Intersection of Phenomenology, Psychiatry and Philosophy of Mind: Are we Talking about the Same Thing?

In recent years, phenomenologically informed philosophers, psychologists and psychiatrists have attempted to import philosophical notions associated with the self into the empirical study of pathological (self-)experience. In particular, so-called ipseity disturbances have been put forward as generative of symptoms of schizophrenia, and several attempts have been made to operationalize and measure kinds and degrees of ipseity disturbances in schizophrenia. However, we find that this work faces challenges caused by the fact that (a) the notion of ipseity is used ambiguously, both in the philosophical and in the empirical discussion, and (b) the methods employed to operationalize ipseity often portray a rather different understanding of the notion from that found in the (phenomenological) literature that is cited as providing the philosophical foundation for the studies in question. In particular, according to the definitions found in the philosophical literature, while being phenomenologically available, the self is not represented in ipseity. However, when it comes to the empirical study of ipseity and its disturbances, the object of investigation is often a kind of explicit self-representation. As a result, it is unclear whether different researchers are really talking about the same thing. Future progress in this area will require more careful conceptual distinctions; the present article aims to contribute to this task.

18.4 CHARACTERIZING LARGE-SCALE NETWORK DYSCONNECTIVITY IN SCHIZOPHRENIA: MODELING ALTERED E/I BALANCE

BackgroundNeuropsychiatric disorders alter the structure and function of neural circuits and distributed neural networks, which leads to profound behavioral disability such as working memory impairment. Non-invasive neuroimaging tools have matured to reliably detect neural systems-level disturbances in neuropsychiatric disorders. However, mechanistic mapping from neural circuit pathology to abnormal behavior remains out of reach for most psychiatric conditions. We focus on the emerging field of ‘computational psychiatry’ to close these gaps from the perspective of E/I imbalance in schizophrenia with an emphasis on understanding large-Scale network dysconnectivity in schizophrenia.MethodsFirst, we apply computational microcircuit models to understand cognitive and neural system-level disturbances in schizophrenia as a function of altered E/I balance. In turn, the focus is placed on pharmacological neuroimaging as a powerful causal tool to probe neural circuit perturbations. Specific recent neuroimaging studies are discussed that use the NMDA receptor antagonist, ketamine, to probe glutamate synaptic dysfunction associated with schizophrenia. We leverage resting-state neuroimaging advances to inform biomarker development for network alterations in schizophrenia given its ease of data collection and lack of task-based confounds.ResultsPharmacological and clinical results implicate alterations in cortico-striato-thalamic circuits, which might constitute a final common pathway of neural system disturbances in schizophrenia. Results indicate that this functional marker appears in at-risk states, chronic patients, and following pharmacological manipulations following ketamine. Computational simulations implicate altered E/I balance in cortical microcircuits as a parsimonious upstream mechanism.DiscussionThe combined use of biophysical computational modeling, extended to large-scale neural system simulations, has proven particularly powerful to draw inferences about neural circuit alterations that may be ‘driving’ the resting-state dysconnectivity and cognitive deficits in schizophrenia. In summary, present data illustrates a framework for linking experimental studies in humans with computational models and pharmacological probes will advance to effort to bridge cellular, systems, and clinical neuroscience approaches to psychiatric disorders.

28. BEYOND VOICES: MULTISENSORY BODILY SELF DISTURBANCES ACROSS THE SCHIZOPHRENIA SPECTRUM

Overall : Aberrant bodily self experiences are highly salient and disruptive to individuals with schizophrenia. Given that these self disturbances are already present at prodromal stage, persist throughout the course of illness, and impact functional outcome, they should be precisely targeted for intervention. However, in contrast to the prominence of auditory hallucination in schizophrenia research, bodily self disturbances have been largely neglected. This symposium aims to bridge this gap with new theoretical and experimental advances that allow us to capture the full extent of the phenomenology, and at the same time, mechanistically specify the etiology and nature of self disorders with an eye toward implementing new treatments.Nelson & Sass will present their revised theory of self disturbances in schizophrenia that reconciles phenomenology with neuropsychological and empirical evidence. Raballo and Poletti will present a comprehensive analysis of recent developmental psychopathological studies of self disorders in the schizophrenia spectrum. Giersch and colleagues provide the crucial experimental evidence for the close link between weakened temporal expectancy and the disruption of continuous and unitary self in schizophrenia. Temporal expectancy helps to link and transform a chain of discrete events into our perceptual experience of continuous flow of time, but it is disrupted in schizophrenia. These results point toward potential intervention strategies. Park and colleagues present exteroceptive, proprioceptive and interoceptive contributions to abnormal mapping of bodily sensation and peripersonal space in the schizophrenia-spectrum and argue that the core problems may lie in prediction coding errors across multisensory systems. Potential intervention may lie in studying trained “sensorimotor experts” (athletes) who show precise and sharpened awareness of embodied sensations. The discussant (Ferri) will integrate these findings to highlight a new framework and multi-level approaches for understanding the etiologies of self disturbances in the schizophrenia-spectrum.

Negative Symptoms and Reward Disturbances in Schizophrenia Before and After Antipsychotic Monotherapy.

Negative symptoms (NS) are a central part of the symptomatology of schizophrenia, which is highly correlated to the functional outcome. Disturbances of the brain reward system are suggested to be central in the pathogenesis of NS by decreasing motivation and hedonic experiences. In this study, we compared reward-related brain activity in patients improving and not improving in NS after treatment with amisulpride. Thirty-nine antipsychotic-naive patients and 49 healthy controls completed functional magnetic resonance imaging with a modified monetary incentive delay task. Psychopathology of the patients was characterised with Positive and Negative Syndrome Scale (PANSS), and they were treated with individual doses of amisulpride (mean 271 mg) for 6 weeks, after which the examinations were repeated. Patients improved on positive, general, and total PANSS score after treatment ( P < .001). Fourteen patients had ≥20% improvement of NS, whereas 25 patients improved <20%. At baseline, one-way analysis of variance showed group difference bilaterally in the caudate nucleus and in the right nucleus accumbens (all P < .002), which was caused by decreased reward anticipation activity in the nonimproving patients compared to healthy controls. There was a significant group × time interaction, with the healthy controls and the improvers decreasing and the nonimprovers increasing in reward anticipation activity after treatment, most pronounced in the left caudate nucleus ( P = .001). Patients improving in NS score had a less aberrant reward system at baseline, but reward related activity was reduced over time. Patients not improving in NS showed decreased striatal reward-activity at baseline, which improved over time. Whether this is associated with alteration in working memory and reward learning or with pronounced symptoms within specific domains of NS may be addressed in future studies.

Modeling a linkage between blood transcriptional expression and activity in brain regions to infer the phenotype of schizophrenia patients

Hundreds of genetic loci participate to schizophrenia liability. It is also known that impaired cerebral connectivity is directly related to the cognitive and affective disturbances in schizophrenia. How genetic susceptibility and brain neural networks interact to specify a pathological phenotype in schizophrenia remains elusive. Imaging genetics, highlighting brain variations, has proven effective to establish links between vulnerability loci and associated clinical traits. As previous imaging genetics works in schizophrenia have essentially focused on structural DNA variants, these findings could be blurred by epigenetic mechanisms taking place during gene expression. We explored the meaningful links between genetic data from peripheral blood tissues on one hand, and regional brain reactivity to emotion task assayed by blood oxygen level-dependent functional magnetic resonance imaging on the other hand, in schizophrenia patients and matched healthy volunteers. We applied Sparse Generalized Canonical Correlation Analysis to identify joint signals between two blocks of variables: (i) the transcriptional expression of 33 candidate genes, and (ii) the blood oxygen level-dependent activity in 16 region of interest. Results suggested that peripheral transcriptional expression is related to brain imaging variations through a sequential pathway, ending with the schizophrenia phenotype. Generalization of such an approach to larger data sets should thus help in outlining the pathways involved in psychiatric illnesses such as schizophrenia.

Il sé nella schizofrenia

In this article, we explore the self and its disturbance in schizophrenia. An accumulating amount of empirical studies testify that the self is disturbed in schizophrenia spectrum disorders but not in other mental disorders. This raises at least two important questions: what concept of self is implied in the self-disturbance in schizophrenia, and how, more specifically, is the self disturbed? Since the literature is ripe with different and proliferating concepts of the self, we present first a brief overview of three major views on the self, i.e. the ‘no-self’ view, the narrative view, and the experiential view. Against this backdrop, we explore how the selfdisturbance typically manifests in incipient schizophrenia and finally we specify the nature of the self-disturbance in schizophrenia.

The Meaning and Relevance of Minkowski’s ‘Loss of Vital Contact with Reality’

Eugene Minkowski is among the most prominent figures in phenomenological psychopathology. His notion of the ‘loss of vital contact with reality’ remains a key concept in the phenomenological description of schizophrenia. However, the precise meaning and relevance of this concept is unclear. Consequently, its use in psychopathological research is questionable. The purpose of this article is to investigate the meaning of the concept, and to evaluate its relevance in the contemporary research on intersubjectivity. The results of this thematic interpretation show that the notion can be deconstructed into three building blocks: ‘reality,’ ‘contact with reality,’ and ‘vital contact.’ Their respective philosophical and psychopathological meanings are discussed in detail. This interpretation allows us to challenge specific ideas on social cognition, and it sheds a new light on the phenomenological description of schizophrenia as a self-disorder. Despite the inherent limitations, Minkowski’s notion provides tools for investigating the form and specificity of intersubjectivity disturbances in schizophrenia. This article offers the first step in this process.

Body Image and Body Experience Disturbances in Schizophrenia: an Attempt to Introduce the Concept of Body Self as a Conceptual Framework

Disturbances in body experience are described as key schizophrenia symptoms and early disease predictors. In case studies, different disorders relating to body experience are presented, but only a few empirical studies have aimed to distinguish the characteristics of body experience in schizophrenia, and these have been selected arbitrarily and without reference to cohesive theoretical model. To integrate this fragmentary approach, we propose a body self (BS) model, composed of: functions; representations (e.g., body image); and sense of body identity. The aim of the study was to determine whether the BS differentiates schizophrenic patients from healthy controls, and to investigate the relations between aspects of BS and a history of illness and clinical characteristics. The Body Self Questionnaire and the Positive and Negative Syndrome Scale were administered to 63 schizophrenic patients and 63 healthy subjects. The difference was found in the functions of the body-self (perceiving, interpreting, and regulating body experience), in the sense of body identity, and in one of three aspects of body image explored (e.g., acceptance of biological sex). Disturbances in BS were related to positive symptoms and to the number of hospitalizations for other diseases. Together, the results demonstrate that schizophrenia is more body experience than body image disorder, since the negative emotional attitude towards the body and acceptance of fitness were not distinctive for schizophrenia. The link between the disturbances in BS and the number of nonpsychiatric hospitalizations suggests that misinterpretation of body experiences in schizophrenia can promote a search for medical attention.

Reliability and diagnostic validity for schizophrenia of the Japanese version of the Bonn Scale for Assessment of Basic Symptoms (BSABS).

Schizophrenia is defined by operative diagnostic criteria in DSM-IV with some typical symptoms as hallucinations and duration of the disease. Huber focused on the subjective experience of patients and coined the term "basic symptoms" and created BSABS. Our study investigated the reliability and the diagnostic validity of the 5 clusters of BSABS for DSM-IV-based diagnosis of schizophrenia with a cohort of 105 patients. Good inter-rater reliability was obtained except for one item D.10. As evaluated by Spearman's rank correlation coefficients, among the 5 clusters excluding Cluster 2, internal consistency was good. This suggests that, although each cluster is heterogeneous, cluster symptoms are the expression of physiological and biological disturbances of schizophrenia. Receiver Operating Characteristic Curve analysis was also used to show the ability of each cluster to discriminate schizophrenia. Results showed that the area representing the powers in discriminate schizophrenia of Cluster 4 "Adynamia", which is considered related to the dynamic aspect of thinking, was highest, at 0.739. Cluster 1 "Information processing disturbances" which has a predictive ability for schizophrenia showed 0.714 and Cluster 3 "Impaired tolerance to normal stress" showed 0.711. Our findings suggest that, although these clusters symptoms differ from DSM-IV criteria, they are related to fundamental process of schizophrenia. Use of some of these three clusters with other neurophysiological markers could allow clinical evaluation of schizophrenia from a new perspective.

Dysfluent Handwriting in Schizophrenic Outpatients.

Taking into account findings in the literature, the author aimed to test whether specific graphical characteristics of handwriting can distinguish patients diagnosed with schizophrenic disorders from healthy controls. Handwriting samples (one sample from each person) from 60 outpatients (29 women, 31 men; age M = 28.5, SD = 5.4) with paranoid schizophrenia were analyzed by three documents examiners and were compared to samples from 60 controls (30 men, 30 women, age M = 28.0, SD = 3.0) without psychiatric disorders. Document examiners assessed 32 graphical features potentially related to schizophrenia. The comparisons between groups revealed that only 7 out of 32 handwriting properties were significantly different in the handwriting of schizophrenic outpatients from controls: the calligraphic forms of letters, loops in ovals, lacking of dots, tremor, sinusoidal baseline, and irregularities size of lower zone. These findings are discussed in terms of motor disturbances in schizophrenia and in relation to the previous research on handwriting of other mental disorders. Similarities between the graphical patterns of handwriting of schizophrenic patients and those of other mental disorders and/or other mental states have been demonstrated.

Editorial: 5-HT2A/2B/2C Receptors, Memory, and Neuropsychiatric Disorders.

It is very well known that memory formation and forgetting represent important cognitive functions modulated by several neurotransmitters, including serotonin (5-hydroxytryptamine, 5-HT) (e.g., Fioravanti and Di Cesare, 1992; Wagner and Davachi, 2001; Wixted, 2004; Mansuy, 2005; Hardt et al., 2013; Hupbach; Callaghan et al., 2014; Li et al., 2015; Meneses), and memory dysfunction is present in several neuropsychiatric disorders (Meyer-Lindenberg et al., 2012; Millan et al., 2012, 2014). How does the brain become dysfunctional? Such a question has intrigued neuroscientists for many years. Over recent decades, neuroscience research has shed light on this complex issue and growing evidence is providing important insights. For instance, several lines of evidence demonstrate that dysfunctions in memory processes occur in several neuropsychiatric disorders, including Alzheimer's disease (AD), characterized by memory deficits and dementia; however, dysfunctional memory is observed in other age-related neurodegenerative disorders, such as schizophrenia, post-traumatic stress disorder, stroke, etc. (Millan et al., 2014; Hashimoto, 2015). So far, no effective treatment for dysfunctional memory exists (e.g., Millan et al., 2012, 2014; Sun et al., 2015); this area is hampered by the absence of neural markers associated to memory. Hence, progress in the fields relating to memory, amnesia, forgetting (e.g., Tellez et al., 2012) and AD (e.g., McConathy and Sheline, 2015; Muenchhoff et al., 2015; Scarr et al., 2015) as well as mild cognitive impairment (Eshkoor et al., 2015) would be facilitated considerably by identification of suitable neural markers. Serotonin is involved in several physiological and pathophysiological processes in mammals and in the treatment of psychiatric disorders (Meneses). It is very well known that 5-HT receptor heterogeneity allows for greater advances, and 5-HT 2A∕2B∕2C receptors are emerging as important tools for preclinical and clinical investigation. This special issue provides a deep overview of important advances on cerebral modifications associated with neuropsychiatric alterations, including dysfunctional memory. In particular, some papers analyse the role of serotonin and dopamine receptors in motivational and cognitive disturbances of schizophrenia (Sumiyoshi et al.), while others are focused on the missing link of the central serotonin-2A 5-HT2A receptor dysfunction in depression and epilepsy (Guiard and Di Giovanni) and on the activity-regulated cytoskeleton-associated protein's putative role in regulating dendritic plasticity, cognitive processes, and mood in animal models of depression is presented (Li et al.). Moreover, a critical evaluation of serotonin mediation of early memory formation via 5-HT2B receptor-induced glycogenolysis in the day-old chick is provided (Gibbs and Hertz). An important subject is the neuronal localization of the 5-HT2 receptor family in the amygdaloid complex and emotion memories (Bombardi). Modeling dysfunctional memory, mitochondrial energy metabolism in different regions of the brain and potential treatments is illustrated (Singh and Kumar). In short, the translational feature of this special issue may expand our knowledge on brain dysfunctions and inspire further investigation, thus leading to a better management of psychiatric diseases.