Systematic overview of neuroanatomical differences in ADHD: Definitive evidence

Objectives: This article seeks to identify neuroanatomical differences in ADHD through an overview of systematic reviews that report encephalic differences compared to a control group in volume, area, activation likelihood or chemical composition.

Methods: We conducted a systematic search using Cochrane guidelines and PRISMA criteria in PubMed, Scopus, Web of Science, Cochrane Database of Systematic Reviews and Database of Abstracts of Reviews of Effects.

Results: Results revealed broad encephalic involvement that includes a functional frontal and cingulate hypoactivation and structural differences in corpus callosum, cerebellum and basal nuclei.

Conclusions: ADHD symptoms might be due to a multi-network unbalanced functioning hypothesis.     

Discriminating between first- and second-order cognition in first-episode paranoid schizophrenia*

Introduction: An impairment of visually perceiving backward masked stimuli is commonly observed in patients with schizophrenia, yet it is unclear whether this impairment is the result of a deficiency in first or higher order processing and for which subtypes of schizophrenia it is present.

Methods: Here, we compare identification (first order) and metacognitive (higher order) performance in a visual masking paradigm between a highly homogenous group of young first-episode patients diagnosed with paranoid schizophrenia (N?=?11) to that of carefully matched healthy controls (N?=?13).

Results: We find no difference across groups in first-order performance, but find a difference in metacognitive performance, particularly for stimuli with relatively high visibility.

Conclusions: These results indicate that the masking deficit is present in first-episode patients with paranoid schizophrenia, but that it is primarily an impairment of metacognition.     

Emotion recognition and social skills in child and adolescent offspring of parents with schizophrenia

Introduction: Emotion recognition, a social cognition domain, is impaired in people with schizophrenia and contributes to social dysfunction. Whether impaired emotion recognition emerges as a manifestation of illness or predates symptoms is unclear. Findings from studies of emotion recognition impairments in first-degree relatives of people with schizophrenia are mixed and, to our knowledge, no studies have investigated the link between emotion recognition and social functioning in that population.

Methods: This study examined facial affect recognition and social skills in 16 offspring of parents with schizophrenia (familial high-risk/FHR) compared to 34 age- and sex-matched healthy controls (HC), ages 7–19.

Results: As hypothesised, FHR children exhibited impaired overall accuracy, accuracy in identifying fearful faces, and overall recognition speed relative to controls. Age-adjusted facial affect recognition accuracy scores predicted parent’s overall rating of their child’s social skills for both groups.

Conclusions: This study supports the presence of facial affect recognition deficits in FHR children. Importantly, as the first known study to suggest the presence of these deficits in young, asymptomatic FHR children, it extends findings to a developmental stage predating symptoms. Further, findings point to a relationship between early emotion recognition and social skills. Improved characterisation of deficits in FHR children could inform early intervention.     

Temporal processing deficit leads to impaired multisensory binding in schizophrenia

Introduction: Schizophrenia has been characterised by neurodevelopmental dysconnectivity resulting in cognitive and perceptual dysmetria. Hence patients with schizophrenia may be impaired to detect the temporal relationship between stimuli in different sensory modalities. However, only a few studies described deficit in perception of temporally asynchronous multisensory stimuli in schizophrenia.

Methods: We examined the perceptual bias and the processing time of synchronous and delayed sounds in the streaming–bouncing illusion in 16 patients with schizophrenia and a matched control group of 18 participants.

Results: Equal for patients and controls, the synchronous sound biased the percept of two moving squares towards bouncing as opposed to the more frequent streaming percept in the condition without sound. In healthy controls, a delay of the sound presentation significantly reduced the bias and led to prolonged processing time whereas patients with schizophrenia did not differentiate between this condition and the condition with synchronous sound.

Conclusion: Schizophrenia leads to a prolonged window of simultaneity for audiovisual stimuli. Therefore, temporal processing deficit in schizophrenia can lead to hyperintegration of temporally unmatched multisensory stimuli.     

Category fluency in schizophrenia: opposing effects of negative and positive symptoms?

Introduction: Category fluency is associated with speed-, executive- and semantic impairments in schizphrenia. It has traditionally been linked to negative symptoms, whereas the relation to positive symptoms is mixed. Associations to the consensus negative, positive and disorganisation factors have not been analysed before.

Methods: Animal fluency was administered to 81 patients with schizophrenia. Measures of overall performance and applied strategies were analysed in relation to the Wallwork five-factor PANSS-model.

Results: Negative and disorganisation symptoms were negatively related to overall fluency performance. Positive symptoms were positively related to overall performance when controlling for disorganisation symptoms. Negative symptoms were related to fewer switches, less repetitions, less single animals intrusions, and both less rare and common animals. Positive symptoms were related to more effective retrieval of sub-category exemplars following a sub-category title, whereas there were no relation between symptoms and exemplars when the title was not retrieved. The Beta values of negative and positive symptoms were opposite.

Conclusion: This is the first study showing that positive symptoms are related to increased fluency performance when disorganisation is controlled for. Like previous studies, negative symptoms were found to depress fluency. Strategy measures indicated that negative symptoms predispose for rigidity, whereas positive symptoms facilitate more efficient associative pathways.     

Language abnormality in deaf people with schizophrenia: a problem with classifiers

Introduction: Although there is evidence for language abnormality in schizophrenia, few studies have examined sign language in deaf patients with the disorder. This is of potential interest because a hallmark of sign languages is their use of classifiers (semantic or entity classifiers), a reference-tracking device with few if any parallels in spoken languages. This study aimed to examine classifier production and comprehension in deaf signing adults with schizophrenia.

Method: Fourteen profoundly deaf signing adults with schizophrenia and 35 age- and IQ-matched deaf healthy controls completed a battery of tests assessing classifier and noun comprehension and production.

Results: The patients showed poorer performance than the healthy controls on comprehension and production of both nouns and entity classifiers, with the deficit being most marked in the production of classifiers. Classifier production errors affected handshape rather than other parameters such as movement and location.

Conclusions: The findings suggest that schizophrenia affects language production in deaf patients with schizophrenia in a unique way not seen in hearing patients.     

Neurocognitive insight and executive functioning in schizophrenia

Introduction. This study explored whether integrity of executive functioning is required for good neurocognitive insight (NI) in subjects with schizophrenia.

Methods. NI was measured by subtracting executive difficulties (errors in the Modified Card Sorting Task) from executive cognitive complaints (Subjective Scale to Investigate Cognition in Schizophrenia) in 40 outpatients with schizophrenia and 42 normal controls. The schizophrenia sample was a priori divided into two subgroups on the basis of executive level. Multivariate analyses were conducted to compare groups and to control for potential confounding factors.

Results. Only the schizophrenia dysexecutive subgroup had a poorer NI compared to normal controls. Group differences remained significant after adjustment for potential confounding factors (education, depression, anxiety and self-esteem).

Conclusion. These results provide support for the hypothesis that executive dysfunctioning is a limiting factor for NI, independently from depressive and anxiety symptoms.     

Do patients with different psychiatric disorders show altered social decision-making? A systematic review of ultimatum game experiments in clinical populations

Background: Impairments in social functioning are a common feature of psychiatric disorders. Game paradigms pose a unique way for studying how people make decisions in interpersonal contexts. In the last decade, researchers have started to use these paradigms to study social decision-making in patients with psychiatric disorders.

Purpose: The aim of this systematic literature review is to summarise the currently available evidence on the behaviour of patients with psychiatric disorders in the commonly used Ultimatum Game (UG).

Method: A systematic literature search including MEDLINE, PsycINFO, PSYNDEXplus Tests, PSYNDEXPLUS Literature, EBM Reviews—Cochrane Central Register of Controlled Trials, Embase and PASCAL was performed via the Ovid interface.

Results: We found evidence for alterations in UG behaviour for patients with frontotemporal dementia, schizophrenia, affective disorders, alcohol, cocaine, heroin and 3,4-methylenedioxymethamphetamine consumption, alcohol dependence, anxiety disorders, borderline personality disorder, autism, Tourette syndrome and oppositional defiant disorder.

Conclusion: There is some evidence that different psychiatric disorders might go along with alterations in social decision-making. However, in general, data are currently limited and studies are hard to compare due to differences in methodologies.     

Evidence of absence: no relationship between behaviourally measured prediction error response and schizotypy

Introduction: The predictive processing framework has attracted much interest in the field of schizophrenia research in recent years, with an increasing number of studies also carried out in healthy individuals with nonclinical psychosis-like experiences. The current research adopted a continuum approach to psychosis and aimed to investigate different types of prediction error responses in relation to psychometrically defined schizotypy.

Methods: One hundred and two healthy volunteers underwent a battery of behavioural tasks including (a) a force-matching task, (b) a Kamin blocking task, and (c) a reversal learning task together with three questionnaires measuring domains of schizotypy from different approaches.

Results: Neither frequentist nor Bayesian statistical methods supported the notion that alterations in prediction error responses were related to schizotypal traits in any of the three tasks.

Conclusions: These null results suggest that deficits in predictive processing associated with clinical states of psychosis are not always present in healthy individuals with schizotypal traits.     

Confabulations in schizophrenia

Introduction. Current theories of confabulation are based primarily on the observation of neurological patients. The present paper evaluates these theories based on evidence from schizophrenia. Schizophrenia is unique in that it presents with a pathophysiology which differs from that of other neuropsychiatric conditions, and yet the candidate's deficits that various theories of confabulation implicate are often simultaneously present in schizophrenia.

Methods. A selective review of literature on schizophrenic and neurological confabulations was undertaken.

Results. Schizophrenic confabulation differs from neurological confabulation in terms of its characteristic features and association with symptoms, cognition and linguistic functions. Current evidence also suggests that confabulation may be conceptualized as a special class of delusions pertaining to memory phenomena.

Conclusions. Schizophrenia presents with confabulations that cannot be fully accounted for by the existing theories. It also presents with confabulations with unique features, which have different cognitive correlates and relation to other symptoms of the condition.     

Impaired facial and vocal emotion decoding in schizophrenia is underpinned by basic perceptivo-motor deficits*

Introduction: Emotional decoding impairments have been largely demonstrated in schizophrenia for facial and prosodic stimuli, when presented separately. Nevertheless, the exploration of crossmodal integration has been far less considered, despite its omnipresence in daily social interactions. Moreover, the role played by basic visuo-motor impairments in unimodal and crossmodal decoding remains unexplored.

Methods: Thirty-two patients were compared with 32 matched controls in an emotional decoding task including unimodal (visual and auditory) and crossmodal (congruent and incongruent) conditions. A control perceptive task was also conducted to take potential low-level perceptual deficits into account.

Results: Schizoprenic patients presented lower performance and higher reaction times for both unimodal tasks (visual and auditory) and crossmodal conditions. Moreover, reaction times for the visuo-perceptive task were also significantly longer for patients compared to controls.

Conclusions: The consistency of the results across unimodal and crossmodal tasks suggests a globalised emotional impairment in schizophrenia, independent of the sensorial modality and crossmodal nature of the stimuli. Centrally, given the results in the visuo-perceptive task, the impairments observed for emotional recognition appears at least partly explained by primary cognitive deficits, namely reduced processing speed.     

ALK protein expression in pulmonary adenocarcinoma of Tunisian patients

Background. It is now necessary to determine ALK status in order to use targeted therapy. Aim: herein, we assess immunohistochemical profile of ALK protein in a series of Tunisian patients with pulmonary adenocarcinoma.

Materials and Methods. ALK protein expression was studied applying the D5F3 antibody with a fully automated Ventana CDx technique on a series of 19 patients.

Results. Positive ALK expression was found in one case (5.2%) corresponding to a papillary adenocarcinoma which showed a strong granular and homogenous cytoplasmic staining. The patient was a 30-years-old woman.

Conclusion. The frequency of positive ALK expression based on immunohistochemistry in our series was similar to that reported in the world literature.     

Down the rabbit hole: assessing the influence of schizotypy on the experience of the Barbie Doll Illusion

Introduction: “Body swapping” illusions have been used to explore factors contributing to the experience of “owning” an artificial body. Preliminary research indicated that those people diagnosed with schizophrenia experience more vivid illusions of this kind than do “normal” individuals.

Objectives: Here, we explored whether participants who rated themselves “high” on the cognitive-perceptual factor of the Schizotypal Personality Questionnaire (SPQ) experienced a more compelling sense of immersion in a variation of the body swapping illusion: The Barbie Doll Illusion. We also hypothesised that these individuals would experience a change in size perception when immersed in the illusion.

Method: Forty-four participants wore a pair of Head-Mounted Display goggles connected to a video-camera, and thus a doll’s body replaced their own body in their visual field. In two conditions, touch was either applied synchronously or asynchronously to the doll’s and each participant’s leg. After each condition, participants filled out a questionnaire relating to their experience in the illusion. When both conditions were completed, they filled out the SPQ.

Results: Our first hypothesis was confirmed, which suggested that people with higher cognitive-perceptual SPQ scores do indeed experience a more compelling Barbie Doll Illusion; however, our second hypothesis was not supported.

Conclusion: Our study demonstrated, for the first time, that proneness to the positive and interpersonal factors of schizotypy in a normal population is sufficient to produce a compelling sense of swapping bodies.     

Symptom-related attributional biases in schizophrenia and bipolar disorder

Introduction: Biases in causal attributions and evidence integration have been implicated in delusions, but have not been investigated simultaneously to examine additive or multiplicative effects. It was hypothesised that paranoid delusions would correlate with self-serving and personalising biases (“defence” model of paranoia), particularly when these biases were disconfirmed.

Methods: Constrained principal component analysis was used to investigate differences between schizophrenia patients (paranoid vs. non-paranoid), bipolar disorder patients, and healthy controls, as well as to examine the extent to which psychotic symptoms could predict patterns of responding on a novel attributional bias task (Attributional Style BADE, or ASB) that requires integrating contextual information.

Results: Although no group differences were found, disorganisation and manic symptoms correlated with situation attributions and self-blame when such attributions were unsupported by the available evidence, and depression and anxiety correlated with other-person and self attributions (not situation attributions) when confirmed by the available evidence, regardless of diagnosis.

Conclusions: While group differences accounted for little variance in responses on the ASB task, a transdiagnostic association between symptoms of psychosis and the ASB task was observed. This highlights the importance of considering symptom profiles rather than diagnostic groupings when investigating cognitive biases and related non-pharmacological treatments.     

Enlarged temporal integration window in schizophrenia indicated by the double-flash illusion

Introduction: In the present study we were interested in the processing of audio-visual integration in schizophrenia compared to healthy controls. The amount of sound-induced double-flash illusions served as an indicator of audio-visual integration. We expected an altered integration as well as a different window of temporal integration for patients.

Methods: Fifteen schizophrenia patients and 15 healthy volunteers matched for age and gender were included in this study. We used stimuli with eight different temporal delays (stimulus onset asynchronys (SOAs) 25, 50, 75, 100, 125, 150, 200 and 300?ms) to induce a double-flash illusion. Group differences and the widths of temporal integration windows were calculated on percentages of reported double-flash illusions.

Results: Patients showed significantly more illusions (ca. 36–44% vs. 9–16% in control subjects) for SOAs 150–300. The temporal integration window for control participants went from SOAs 25 to 200 whereas for patients integration was found across all included temporal delays. We found no significant relationship between the amount of illusions and either illness severity, chlorpromazine equivalent doses or duration of illness in patients.

Conclusions: Our results are interpreted in favour of an enlarged temporal integration window for audio-visual stimuli in schizophrenia patients, which is consistent with previous research.     

Effort discounting and its association with negative symptoms in schizophrenia

Introduction. Deficits in the initiation and persistence of goal-directed behaviour are key aspects of schizophrenia. In this study, the association between these motivational deficits and discounting of reward value in function of increasing physical effort costs was investigated.

Methods. Effort-based decision-making was investigated in 40 patients with a DSM-IV diagnosis of schizophrenia and 30 age- and sex-matched healthy control subjects by means of an effort discounting task. To assess negative symptom severity, we made use of the Scale for the Assessment of Negative Symptoms as well as objective measurements of hedonic response to stimuli and motor activity levels.

Results. Patients as well as control subjects discounted the subjective value of rewards significantly with increasing physical effort costs. However, we failed to find a difference in the discounting curves between patients and controls. Furthermore, effort discounting was not associated with any of the negative symptoms measures.

Conclusions. Physical effort discounting was not found to be associated with motivational symptoms in schizophrenia if other decision costs are constant. However, recent findings show that more cognitive effort and/or an interaction between effort and other decision costs (e.g. temporal delay or uncertainty) are associated with negative symptoms in schizophrenia. This should be investigated further in future research.     

External application of NF-κB inhibitor DHMEQ suppresses development of atopic dermatitis-like lesions induced with DNCB/OX in BALB/c mice

Context: Dehydroxymethylepoxyquinomicin (DHMEQ) which is originally developed as an analog of antibiotic epoxyquinomicin C is a specific and potent inhibitor of NF-κB and has been shown to possess promising potential as an anti-inflammatory and anti-tumor agent.

Objective: This study examines DHMEQ’s effect on therapeutic potential for atopic dermatitis (AD)-like lesions.

Materials and methods: AD lesions were chronically induced by the repetitive and alternative application of 2,4-dinitrochlorobenzene (DNCB) and oxazolone (OX) on ears in BALB/c mice. The mice were then externally treated with DHMEQ ointment. Macroscopic and microscopic changes of the skin lesions were observed and recorded.

Results: DHMEQ inhibited ear swelling and relieved clinical symptoms of the AD-like lesions induced by DNCB/OX in BALB/c mice. Histopathology examination illustrated that it significantly decreased DNCB/OX-induced epidermal thickness, the infiltration of inflammatory cells, and the count of mast cell. The elevated level of immunoglobulin E (IgE) in serum and the mRNA levels of interferon γ (IFN-γ), interleukin 4 (IL-4) and IL-13 in the ear tissues, were also suppressed by DHMEQ.

Discussion and conclusion: This study indicated that DHMEQ would be useful for the treatment of AD.