Cortical thickness across the cingulate gyrus in schizophrenia and its association to illness duration and memory performance.

Schizophrenia has been associated with structural brain abnormalities and cognitive deficits that partly change during the course of illness. In the present study, cortical thickness in five subregions of the cingulate gyrus was assessed in 44 patients with schizophrenia-spectrum disorder and 47 control persons and related to illness duration and memory capacities. In the patients group, cortical thickness was increased in the posterior part of the cingulate gyrus and related to illness duration whereas cortical thickness was decreased in anterior parts unrelated to illness duration. In contrast, cortical thickness was related to episodic and working memory performance only in the anterior but not posterior parts of the cingulate gyrus. Our finding of a posterior cingulate increase may point to either increased parietal communication that is accompanied by augmented neural plasticity or to effects of altered neurodegenerative processes in schizophrenia.

Look into my eyes: Investigating joint attention using interactive eye-tracking and fMRI in a developmental sample.

Joint attention, the shared attentional focus of at least two people on a third significant object, is one of the earliest steps in social development and an essential aspect of reciprocal interaction. However, the neural basis of joint attention (JA) in the course of development is completely unknown. The present study made use of an interactive eye-tracking paradigm in order to examine the developmental trajectories of JA and the influence of a familiar interaction partner during the social encounter. Our results show that across children and adolescents JA elicits a similar network of "social brain" areas as well as attention and motor control associated areas as in adults. While other-initiated JA particularly recruited visual, attention and social processing areas, self-initiated JA specifically activated areas related to social cognition, decision-making, emotions and motivational/reward processes highlighting the rewarding character of self-initiated JA. Activation was further enhanced during self-initiated JA with a familiar interaction partner. With respect to developmental effects, activation of the precuneus declined from childhood to adolescence and additionally shifted from a general involvement in JA towards a more specific involvement for self-initiated JA. Similarly, the temporoparietal junction (TPJ) was broadly involved in JA in children and more specialized for self-initiated JA in adolescents. Taken together, this study provides first-time data on the developmental trajectories of JA and the effect of a familiar interaction partner incorporating the interactive character of JA, its reciprocity and motivational aspects.

[Diagnosis and Therapeutic Interventions in Autism Spectrum Disorders in Adulthood]. / Zur Diagnostik und Behandlung von Autismus-Spektrum-Störungen im Erwachsenenalter.

Autism spectrum disorders (ASD) are characterized by disturbed social interaction and communication as well as stereotyped or repetitive behaviors and interests. Although adults with ASD often acquire complex compensatory strategies that help them master social situations in a rule-based fashion, they still show impairments in intuitive processing of social signals and especially nonverbal communication in complex everyday situations. This constitutes a particular challenge for the psychotherapy of ASD. Psychotherapists are required to explicitly inform and act as an agent of the non-autistic world to enable patients to acquire the ability to take different perspectives. The overall aim of cognitive behavioral therapy interventions addressing ASD in adulthood is to extend the patients' behavioral repertoire to improve their quality of life. Thus, besides psychoeducation on ASD and its frequently associated comorbidities, psychotherapy for adults with ASD should focus on the training and development of social-communicative skills. Furthermore, dealing with stress in everyday situations is an important aspect of psychotherapy of these patients.

Toward the development of a supported employment program for individuals with high-functioning autism in Germany.

Human-human interactions are of central relevance for the success in professional and occupational environments, which also substantially influence quality of life. This is especially true in the case of individuals with high-functioning autism (HFA), who experience deficits in social cognition that often lead to social exclusion and unemployment. Despite good education and high motivation, individuals with HFA do not reach employment rates that are substantially higher than 50 %. This is an alarmingly high rate of unemployment considering that the United Nations have recently emphasized the inclusion of handicapped persons as a mandatory human right. To date, the specific needs of autistic persons with respect to their working environment are largely unexplored. It remains moreover an open question how support systems and activities, including newly developed communication devices for professional environments of individuals with HFA, should look like. The German health and social care systems are not adequately prepared for the proper support of this population. This leads us to suggest that supported employment programs should be developed for adults with HFA that specifically address their needs and requirements. Such programs should comprise (1) the adequate assessment of HFA, including a neuropsychological profile and an individual matching of persons' preferences with requirements of the working place, (2) on-the-job coaching activities that include systematic communication and interaction training, and (3) instruction of non-autistic peers, including colleagues and supervisors, about weaknesses and strengths of HFA.

The role of interpersonal synchrony in forming impressions of autistic and non-autistic adults.

When people meet, they almost instantaneously form an impression of each other. First impressions of character traits and rapport are less favourable when people with autism spectrum condition (ASC) are judged compared to non-autistic people. Little is known about the behavioural differences that drive these altered impressions. In the present study, we investigated the influence of interpersonal synchrony on impression formation of autistic and non-autistic people. Specifically, we used lagged cross-correlations to assess how much each interactant's motion energy, a measure which can be determined from video recordings, influenced the other interactant's motion energy. In short, silent clips of dyadic conversations, we asked non-autistic participants to rate their impression of one of the two interactants, which was solely based on the outlines of both interactants. We expected that the amount of leading of the target interactant, their diagnostic status as well as the interaction of these factors would influence impression formation. We found that while the amount of leading had a positive effect on the impressions of non-autistic interactants, this was not true for interactants with ASC. This suggests that interpersonal synchrony of motion energy is one driver of less favourable impressions of autistic compared to non-autistic people.

[Psychosocial functioning of adults with late diagnosed autism spectrum disorders--a retrospective study]. / Das psychosoziale Funktionsniveau spätdiagnostizierter Patienten mit Autismus-Spektrum-Störungen--eine retrospektive Untersuchung im Erwachsenenalter.

BACKGROUND: The first time diagnosis of autism spectrum disorder (ASD) after passing childhood and adolescence is still considered a rare event. However, in recent years an increasing demand for diagnostic clarifications with suspected ASD in adulthood challenges this view. There is insufficient knowledge about the neuropsychological characterisation and psychosocial outcome of this adult subgroup in the autistic spectrum. AIM: To determine the psychosocial functioning (living status, partnerships, level of education, psychiatric history) of adult patients with late diagnosed ASD. METHODS: In a retrospective study, a chart review was conducted on 178 consecutively diagnosed individuals at a specialised outpatient clinic for adults with ASD. Global ratings of psychosocial functioning, assessment of psychiatric history and neuropsychological and psychopathological investigations were evaluated. RESULTS: The majority of patients (92 %) diagnosed with ASD suffered from high-functioning autism (HFA)/Asperger syndrome (AS) according to the criteria of ICD-10 (F84.5). The gender ratio was 2:1 favouring males. Mean age at diagnosis (34.1 ± 9.5 years), general intelligence (HAWIE-R, global-IQ 115 ± 20) and self-rated autistic symptoms (autism spectrum quotient [AQ] 39 ± 6) were not discriminative to gender. The psychiatric history revealed a lifetime consultation rate of 78 %, most frequently with depression (50 %). The self-report instrument Beck depression inventory (BDI) identified 30 % of individuals presenting with depressive symptoms in clinical relevant intensity (BDI > 17). Achievement of an independent living status was reported by 68 % of individuals, 58 % reported about current or past intimate partnerships and almost two-thirds of the patients had achieved a higher educational status. DISCUSSION: The majority of ASD diagnosed late in lifetime turned out to be HFA/AS, presenting with high psychosocial adjustment with regard to independent living, educational status and partnerships. The high level of global intelligence supports the hypothesis of cognitively compensated autistic disturbances leading to the diagnosis comparably late in lifetime. The lifetime rate of psychiatric consultations is high, reflecting the importance to consider a diagnosis of ASD even late in life.

Brief Report: Preferred Processing of Social Stimuli in Autism: A Perception Task.

In this study we investigate whether persons with autism spectrum disorder (ASD) perceive social images differently than control participants (CON) in a graded perception task in which stimuli emerged from noise before dissipating into noise again. We presented either social stimuli (humans) or non-social stimuli (objects or animals). ASD were slower to recognize images during their emergence, but as fast as CON when indicating the dissipation of the image irrespective of its content. Social stimuli were recognized faster and remained discernable longer in both diagnostic groups. Thus, ASD participants show a largely intact preference for the processing of social images. An exploratory analysis of response subsets reveals subtle differences between groups that could be investigated in future studies.

[Autism spectrum disorders in adulthood: clinical and neuropsychological findings of Aspergers syndrome diagnosed late in life]. / Autismus-Spektrum-Störungen im Erwachsenenalter: Klinische und Neuropsychologische Befunde Spätdiagnostizierter Asperger-Syndrome.

INTRODUCTION: High-functioning autism (HFA) and Aspergers syndrome (AS) are autism spectrum disorders (ASD) characterised by disturbances in social interaction, both verbal and non-verbal communication and repetitive and/or restrictive behaviour since early childhood. Symptoms appear generally during early childhood and adolescence. The increasing need to clarify diagnostic queries in advanced age led to the constitution of specialised outpatient clinics for adults involving a growing amount of HFA/AS subjects diagnosed late in life. However, thus far neuropsychological data about this group are scarce. METHODS: We present a subgroup of 39 patients with HFA/AS (mean age at diagnosis 31.1 ± 8.9 years) who were consecutively diagnosed at the autism outpatient clinic at the Department of Psychiatry at the University Hospital Cologne. Autistic symptoms (autism spectrum quotient; AQ), depressive symptoms (Beck depression inventory; BDI), general intelligence (HAWIE-R), social cognition ("theory of mind", ToM) and executive functioning (COWAT) were systematically studied in comparison to a control group matched for age, education, gender and intelligence (n = 39). RESULTS: HFA/AS subjects presented higher AQ scores (40.4 ± 5.2) as opposed to the healthy controls (13.5 ± 4.8). Neuropsychologically, patients showed deficits in social cognition, executive functions and in subtests of HAWIE-R related to verbal comprehension and perceptual organisation as opposed to the healthy control group. DISCUSSION: The diagnosis of autistic disorders in adulthood basically relies on the clinical assessment of autistic core symptoms which were corroborated by high AQ values. The self-rating instrument AQ was found to be highly discriminative between the HFA/AS group and the healthy control group. The neuropsychological profile of adult HFA/AS patients diagnosed late in life is compatible with that of previously investigated HFA/AS populations. These findings show that such basic autism-associated deficits persist until adulthood, although patients are able to learn social rules.

[Expectations concerning psychotherapy of high-functioning adults with autism spectrum disorders]. / Erwartungen an eine Psychotherapie von hochfunktionalen erwachsenen Personen mit einer Autismus-Spektrum-Störung.

BACKGROUND: In recent years there has been a strong increase in psychiatric diagnoses belonging to the autism spectrum in adulthood. For this diagnostic group of patients, often characterised by normal or above-average intelligence, i.e, high-functioning autism or Asperger syndrome, only few adequate psychotherapeutic treatment options exist. In order to develop a disorder-specific psychotherapeutic group training in a demand-oriented manner, we surveyed adults with autism spectrum disorders (ASD) concerning their needs and expectations relating to psychotherapy. METHODS: A two-step analysis of needs was carried out: First, after a set of open questions written descriptions of 33 individuals with ASD were analysed using the qualitative content analysis according to Mayring. The resulting category system provided the basis for the closed questionnaire EPAS ("Expectations Psychotherapy Autism Spectrum"). In a second step, 64 individuals with ASD were assessed by EPAS to confirm the relevance of the qualitatively derived dimensions. RESULTS: Both the results of the qualitative and the quantitative analysis confirmed the initial hypothesis that adults with ASD expressed problems associated with disorder-specific core symptoms. Moreover, the quantitative analysis demonstrated that in addition to deficits in social competence and identity formation, the lack of stress management skills represents a crucial load factor. Also, the therapist-associated variables were reported to play an important role for the patients. DISCUSSION: The analysis of needs indicates that psychotherapy for adults with ASD should focus on the training and development of social-communicative skills. Furthermore, dealing with stress in everyday situations and identity formation after diagnosis should also be considered. Psychotherapists can refer to well-established techniques from cognitive behavioural therapy, which are known to be effective in the identified fields and should have sufficient disorder-specific knowledge, not least in order to prevent misunderstandings within the therapeutic working relationship.

Brief Report: Social Anxiety in Autism Spectrum Disorder is Based on Deficits in Social Competence.

This study differentially examined the relation between two clinical constructs: "social anxiety" and "social competence" in autism spectrum disorder (ASD). Employing two questionnaires (SASKO; IU), individuals with ASD (n = 23) showed increased scores of SOCIAL ANXIETY (SASKO) and of INTOLERANCE OF UNCERTAINTY (IU), compared to a non-clinical comparison group (NC; n = 25). SOCIAL ANXIETY scores were equally increased for ASD and a reference population of individuals with social anxiety disorder (SAD; n = 68). However, results showed increased SOCIAL COMPETENCE DEFICITS in ASD compared to SAD and NC groups. This study allows drawing the conclusion that social anxiety symptoms in ASD can be traced back to autism-specific deficits in social skills and are therefore putatively based on different, substantially "deeper" implemented cognitive mechanisms.

Animated brain: a functional neuroimaging study on animacy experience.

Previous research used animated geometric figures to investigate social cognitive processes involved in ascribing mental states to others (e.g. mentalizing). The relationship between animacy perception and brain areas commonly involved in social cognition, as well as the influence of particular motion patterns on animacy experience, however, remains to be further elucidated. We used a recently introduced paradigm for the systematic variation of motion properties, and employed functional magnetic resonance imaging to identify the neural mechanisms underlying animacy experience. Based on individual ratings of increased animacy experience the following brain regions of the "social neural network" (SNN), known to be involved in social cognitive processes, were recruited: insula, superior temporal gyrus, fusiform gyrus, parahippocampal gyrus and the ventromedial prefrontal cortex bilaterally. Decreased animacy experience was associated with increased neural activity in the inferior parietal and inferior frontal gyrus, key constituents of the human "mirror neuron system" (hMNS). These findings were corroborated when analyses were based on movement patterns alone, irrespective of subjective experience. Additionally to the areas found for increased animacy experience, an increase in interactive movements elicited activity in the amygdala and the temporal pole. In conclusion, the results suggest that the hMNS is recruited during a low-level stage of animacy judgment representing a basic disposition to detect the salience of movements, whereas the SNN appears to be a high-level processing component serving evaluation in social and mental inference.

Visuospatial perspective taking in a dynamic environment: perceiving moving objects from a first-person-perspective induces a disposition to act.

Spatial perspective taking is an everyday cognitive process that is involved in predicting the outcome of goal directed behavior. We used dynamic virtual stimuli and fMRI to investigate at the neural level whether motion perception interacts with spatial perspective taking in a life-like design. Subjects were asked to perform right-left-decisions about the position of either a motionless, hovering (STATic) or a flying ball (DYNamic), either from their own (1PP) or from the perspective of a virtual character (avatar, 3PP). Our results showed a significant interaction of STIMULUS TYPE and PERSPECTIVE with significantly increased activation in right posterior intraparietal sulcus (IPS) for 1PPDYN condition. As the IPS is critically involved in the computation of object-directed action preparation, we suppose that the simple perception of potentially action-relevant dynamic objects induces a 'readiness for (re)action', restricted to the 1PP. Results are discussed against the background of current theories on embodiment and enactive perception.

Reduced nonverbal interpersonal synchrony in autism spectrum disorder independent of partner diagnosis: a motion energy study.

BACKGROUND: One of the main diagnostic features of individuals with autism spectrum disorders is nonverbal behaviour difficulties during naturalistic social interactions. The 'Interactional Heterogeneity Hypothesis' of ASD proposes that the degree to which individuals share a common ground substantially influences their ability to achieve smooth social interactions. METHODS: To test this hypothesis, we filmed 29 autistic and 29 matched typically developed adults engaged in several conversational tasks. Windowed cross-lagged correlations were computed using the time series of motion energy of both individuals in a dyad. These coefficients were then compared across the three dyad types that were homo- or heterogenous with respect to diagnosis: pairs of two autistic individuals, two typically developed individuals or pairs of one autistic and one typically developed person. RESULTS: We found that all dyad types achieved above-chance interpersonal synchrony, but that synchrony was more expressed in typical dyads compared to both autistic and mixed dyads. LIMITATIONS: The method presented here provides only one, albeit objective and robust, approach to explore synchrony. The methodological choices as well as the lack of consideration for other communication modalities may limit our interpretation of the findings. Moreover, the sample size is small with respect to exploring associations between synchrony and various outcome and social skill measures. CONCLUSIONS: The present results do not provide support for the Interactional Heterogeneity Hypothesis given that autistic individuals do not coordinate better when interacting with another autistic individual, compared to when interacting with a typical individual.

Disturbed time experience during and after psychosis.

Disturbances in time experience have been argued to play a significant, if not causative role in the clinical presentation of schizophrenia. Phenomenological considerations suggest a fragmented or dis-articulated time experience causing both primary symptoms such as hallucinations, delusions, and self-disorders, as well as an intersubjective desynchronization. We employed content analysis on material collected from patients diagnosed with schizophrenia using the Time Questionnaire to generate hypotheses on possible disturbances of time experience in schizophrenia. As a key result we find evidence for the distinction between acute psychotic and post-psychotic syndromes. Acute psychosis is predominantly a disturbance of the passage of time, whereas the remission from psychosis is primarily defined by changes in the experience of the explicit structure of time integrating past, present, and future. We discuss our findings with regards to previous insights and observations on time experience and time perception. We suggest our findings hold significance for the diagnostic and therapeutic understanding of schizophrenia as well as for future integrative research on time experience in general.

Young adolescents with autism show abnormal joint attention network: A gaze contingent fMRI study.

Behavioral research has revealed deficits in the development of joint attention (JA) as one of the earliest signs of autism. While the neural basis of JA has been studied predominantly in adults, we recently demonstrated a protracted development of the brain networks supporting JA in typically developing children and adolescents. The present eye-tracking/fMRI study now extends these findings to adolescents with autism. Our results show that in adolescents with autism JA is subserved by abnormal activation patterns in brain areas related to social cognition abnormalities which are at the core of ASD including the STS and TPJ, despite behavioral maturation with no behavioral differences. Furthermore, in the autism group we observed increased neural activity in a network of social and emotional processing areas during interactions with their mother. Moreover, data indicated that less severely affected individuals with autism showed higher frontal activation associated with self-initiated interactions. Taken together, this study provides first-time data of JA in children/adolescents with autism incorporating the interactive character of JA, its reciprocity and motivational aspects. The observed functional differences in adolescents ASD suggest that persistent developmental differences in the neural processes underlying JA contribute to social interaction difficulties in ASD.

Interpersonal predictive coding, not action perception, is impaired in autism.

This study was conducted to examine interpersonal predictive coding in individuals with high-functioning autism (HFA). Healthy and HFA participants observed point-light displays of two agents (A and B) performing separate actions. In the 'communicative' condition, the action performed by agent B responded to a communicative gesture performed by agent A. In the 'individual' condition, agent A's communicative action was substituted by a non-communicative action. Using a simultaneous masking-detection task, we demonstrate that observing agent A's communicative gesture enhanced visual discrimination of agent B for healthy controls, but not for participants with HFA. These results were not explained by differences in attentional factors as measured via eye-tracking, or by differences in the recognition of the point-light actions employed. Our findings, therefore, suggest that individuals with HFA are impaired in the use of social information to predict others' actions and provide behavioural evidence that such deficits could be closely related to impairments of predictive coding.

Right frontal hypergyria differentiation in affected and unaffected siblings from families multiply affected with schizophrenia: a morphometric mri study.

OBJECTIVE: The authors used magnetic resonance imaging to corroborate the postmortem finding of right frontal hypergyria associated with schizophrenia. METHOD: Twelve affected-unaffected sibling pairs from families multiply affected with schizophrenia were studied. Bilateral measurement of the gyrification index, the ratio of the inner and outer surface contours, was performed on three different slices of the prefrontal region. RESULTS: The mean gyrification index on the right side was significantly higher in siblings with schizophrenia or schizoaffective disorder than in the unaffected siblings. CONCLUSIONS: In this family cohort study, the postmortem finding of right-sided hypergyria in subjects with schizophrenia was replicated in vivo with magnetic resonance imaging. This observation provides further support for a neurodevelopmental mechanism in the pathogenesis of schizophrenia.

Disturbed gyrification of the prefrontal region in male schizophrenic patients: A morphometric postmortem study.

OBJECTIVE: The goal was to test the hypothesis that abnormalities of gyrification are present in the prefrontal region of postmortem brains from schizophrenic patients. METHOD: The authors compared the prefrontal regions in brains from 24 schizophrenic patients and 24 normal comparison subjects. The gyrification index, the ratio of inner and outer surface contours, was measured bilaterally in three different slices from each brain. Area measurements of gray and white matter were studied separately by planimetric analysis in the same sections. In addition, a gray-to-white-matter ratio and an asymmetry coefficient were computed. RESULTS: The mean gyrification index on the right side was significantly higher in the male schizophrenic patients than in the comparison men. The gyrification index of the female patients was not significantly different from that of the female comparison subjects. Analysis of area measurements revealed no significant differences. CONCLUSIONS: As gyrification is an ontogenetic stable feature unaffected by atrophic processes during aging, the gyrification abnormalities of the prefrontal region provide further evidence of the importance of a neurodevelopmental mechanism in the etiology of schizophrenia, at least in males.

neu mutations and loss of normal allele in schwannomas induced by N-ethyl-N-nitrosourea in rats.

The mutational activation of the neu proto-oncogene was analyzed in schwannomas of the peripheral nervous system transplacentally induced by N-ethyl-N-nitrosourea (ENU) in rats. All nine primary schwannomas investigated contained a T-->A transversion mutation at nucleotide 2012 of the neu gene, leading to the substitution of valine to glutamic acid in the transmembrane domain. Loss of the wild-type allele occurred in five of nine (56%) primary schwannomas. All four ENU-induced schwannomas transplanted in syngenic hosts (2-14 passages) showed the T-->A transversion mutation and loss of the wild-type allele. These data suggest that mutation of one allele together with loss of the wild-type allele constitutes two critical steps in the progression of rat schwannomas. Since c-erbB-2, the human counterpart of the rat neu gene is frequently involved by amplification in the development of human gastric cancer [30], we screened 12 rat gastric carcinomas induced by N-methyl-N-nitrosourea (MNU) for mutations in the neu gene. However, none of these tumors contained mutations.