Depression and anxiety disorders in children and adolescents with velo-cardio-facial syndrome (VCFS)

Velo-cardio-facial syndrome (VCFS) is characterized by a high prevalence of depression and anxiety disorders in childhood and adolescence. These disorders are a source of great impairment in everyday functioning, as well as important risk factors for the emergence of later psychotic disorders. Impairment in daily and social functioning as well as loss of IQ throughout growth are also are well-established correlates of the VCFS. This study aimed to confirm the high prevalence of depression and anxiety disorders. The second objective was to ascertain the correlation between anxious and depressive symptoms and the decline in adaptive and cognitive functioning. A total of 73 children and adolescents with VCFS (mean age 11.9years) underwent psychiatric evaluation. Subjects were further divided into four age groups: ages 6-9, 9-12, 12-15 and 15-18years. Assessments measuring intelligence, anxious and depressive symptoms, and adaptation skills reported by parents were submitted to a subsample of 62 children (mean age 12.2years); 62.2% of the sample showed an anxiety disorder, specific phobia being the most represented at all ages. Lifetime depression concerned 27% of the sample, peaking at age 12-15years. Anxious and depressive symptoms and low IQ were significantly associated with low adaptive functioning. Anxiety and depression are common disorders in children and adolescents with VCFS and have a great impact on adaptive functioning. Clinicians should pay great attention to diagnosis and treatmen

Adolescent Resting State Networks and Their Associations with Schizotypal Trait Expression

The rising interest in temporally coherent brain networks during baseline adult cerebral activity finds convergent evidence for an identifiable set of resting state networks (RSNs). To date, little is know concerning the earlier developmental stages of functional connectivity in RSNs. This study's main objective is to characterize the RSNs in a sample of adolescents. We further examine our data from a developmental psychopathology perspective of psychosis-proneness, by testing the hypothesis that early schizotypal symptoms are linked to disconnection in RSNs. In this perspective, this study examines the expression of adolescent schizotypal traits and their potential associations to dysfunctional RSNs. Thirty-nine adolescents aged between 12 and 20 years old underwent an 8-min functional magnetic resonance imaging (fMRI) “resting state” session. In order to explore schizotypal trait manifestations, the entire population was assessed by the Schizotypal Personality Questionnaire (SPQ). After conventional processing of the fMRI data, we applied group-level independent component analysis (ICA). Twenty ICA maps and associated time courses were obtained, among which there were RSNs that are consistent with findings in the literature. We applied a regression analysis at group level between the energy of RSN-associated time courses in different temporal frequency bins and the clinical measures (3 in total). Our results highlight the engagement of six relevant RSNs; (1) a default-mode network (DMN); (2) a dorso-lateral attention network; (3) a visual network (VN); (4) an auditory network (AN); (5) a sensory motor network (SMN); (6) a self-referential network (SRN). The regression analysis reveals a statistically significant correlation between the clinical measures and some of the RSNs, specifically the visual and the AN. In particular, a positive correlation is obtained for the VN in the low frequency range (0.05 Hz) with SPQ measures, while the AN correlates negatively in the high frequency range (0.16–0.19 Hz). Trend-like significance for the SRN may hint to its implication in disorganized thoughts and behaviors during adolescence. Unlike DMN activity in schizophrenic patients, adolescent DMN was unrelated to schizotypal trait expression. This suggests that relationships between the DMN and schizotypy may be modified in later developmental stages of both functional connectivity and psychotic expression. These results are discussed in light of RSNs literature involving children, adults, and individuals with schizophrenia

Developing Psychosis and Its Risk States Through the Lens of Schizotypy

Starting from the early descriptions of Kraepelin and Bleuler, the construct of schizotypy was developed from observations of aberrations in nonpsychotic family members of schizophrenia patients. In contemporary diagnostic manuals, the positive symptoms of schizotypal personality disorder were included in the ultra high-risk (UHR) criteria 20 years ago, and nowadays are broadly employed in clinical early detection of psychosis. The schizotypy construct, now dissociated from strict familial risk, also informed research on the liability to develop any psychotic disorder, and in particular schizophrenia-spectrum disorders, even outside clinical settings. Against the historical background of schizotypy it is surprising that evidence from longitudinal studies linking schizotypy, UHR, and conversion to psychosis has only recently emerged; and it still remains unclear how schizotypy may be positioned in high-risk research. Following a comprehensive literature search, we review 18 prospective studies on 15 samples examining the evidence for a link between trait schizotypy and conversion to psychosis in 4 different types of samples: general population, clinical risk samples according to UHR and/or basic symptom criteria, genetic (familial) risk, and clinical samples at-risk for a nonpsychotic schizophrenia-spectrum diagnosis. These prospective studies underline the value of schizotypy in high-risk research, but also point to the lack of evidence needed to better define the position of the construct of schizotypy within a developmental psychopathology perspective of emerging psychosis and schizophrenia-spectrum disorder

Strange-Face-in-the-Mirror Illusion and Schizotypy During Adolescence

Patients with schizophrenia can sometimes report strange face illusions when staring at themselves in the mirror; such experiences have been conceptualized as anomalous self-experiences that can be experienced with a varying degree of depersonalization. During adolescence, anomalous self-experiences can also be indicative of increased risk to develop schizophrenia-spectrum disorders. To date however, the Mirror-Gazing test (MGT), an experimentally validated experiment to evaluate the propensity of strange face illusions in nonclinical and clinical adults, has yet to be investigated in an adolescent sample. The first goal of the present study was to examine experimentally induced self-face illusions in a nonclinical sample of adolescents, using the MGT. The second goal was to investigate whether dimensions of adolescent trait schizotypy were differentially related to phenomena arising during the MGT. One hundred and ten community adolescents (59 male) aged from 12 to 19 years (mean age = 16.31, SD age = 1.77) completed the MGT and Schizotypal Personality Questionnaire. The results yielded 4 types of strange face illusions; 2 types of illusions (slight change of light/color [20%] and own face deformation [45.5%]) lacked depersonalization-like phenomena (no identity change), while 2 other types (vision of other identity [27.3%], and vision of non-human identity [7.3%]) contained clear depersonalization-like phenomena. Furthermore, the disorganization dimension of schizotypy associated negatively with time of first illusion (first press), and positively with frequency of illusions during the MGT. Statistically significant differences on positive and disorganized schizotypy were found when comparing groups on the basis of degree of depersonalization-like phenomena (from slight color changes to non-human visions). Similarly to experimentally induced self-face illusions in patients with schizophrenia, such illusions in a group of nonclinical adolescents present significant associations to schizotypy dimension

Clinical and cognitive risk factors for psychotic symptoms in 22q11.2 deletion syndrome: a transversal and longitudinal approach

22q11.2 deletion syndrome (22q11DS) is associated with increased risk for schizophrenia. Better identifying risk factors for the emergence of psychotic symptoms in this population is needed to improve clinical assessment and early interventions. Schizophrenia spectrum disorders, hallucinations and delusions were characterized in an original sample of 104 individuals with 22q11DS. Further analysis of positive and negative symptoms was performed in a subsample of 59 individuals. Finally, longitudinal data available in 56 patients were used to explore the developmental trajectories of psychotic symptoms as well as the associations between psychotic symptoms and cognitive functioning. Schizophrenia spectrum disorders and psychotic symptoms were frequent in adolescent and adults with 22q11DS. The severity of hallucinations and non-persecutory delusional ideas discriminated patients at ultra-high risk for conversion to psychosis. Whereas approximately one-third of patients experienced an emergence of psychotic symptoms during a 4-year interval, 20% displayed transient symptoms. Individuals with psychotic symptoms were characterized by a lower cognitive functioning in the context of the 22q11DS. The present study adds important data on the characteristics and developmental trajectory of psychotic symptoms in this population. This information may ultimately help clinicians dealing with these patients to reduce the duration of untreated psychosis and improve outcome

Hippocampal volume and declarative memory function in combat-related PTSD

The proposition that declarative memory deficits are systematically related to smaller hippocampal volume was tested in a relatively large sample (n = 95) of U.S. military veterans with and without combat-related posttraumatic stress disorder. This correlative analysis was extended by including multiple measures of verbal and visual declarative memory and multiple memory-relevant regional brain volumes that had been shown to exhibit main effects of PTSD in prior work. Small-to-moderate effects were observed on verbal declarative memory in line with a recent meta-analysis; nevertheless, little or no evidence of systematic linear covariation between memory measures and brain volumes was observed. (JINS, 2009, 15, 830-839.

Identifying 22q11.2 Deletion Syndrome and Psychosis Using Resting-State Connectivity Patterns

The clinical picture associated with 22q11.2 deletion syndrome (22q11DS) includes mild mental retardation and an increased risk of schizophrenia. While the clinical phenotype has been related to structural brain network alterations, there is only scarce information about functional connectivity in 22q11DS. However, such studies could lead to a better comprehension of the disease and reveal potential biomarkers for psychosis. A connectivity decoding approach was used to discriminate between 42 patients with 22q11DS and 41 controls using resting-state connectivity. The same method was then applied within the 22q11DS group to identify brain connectivity patterns specifically related to the presence of psychotic symptoms. An accuracy of 84% was achieved in differentiating patients with 22q11DS from controls. The discriminative connections were widespread, but predominantly located in the bilateral frontal and right temporal lobes, and were significantly correlated to IQ. An 88% accuracy was obtained for identification of existing psychotic symptoms within the patients group. The regions containing most discriminative connections included the anterior cingulate cortex (ACC), the left superior temporal and the right inferior frontal gyri. Functional connectivity alterations in 22q11DS affect mostly frontal and right temporal lobes and are related to the syndrome's mild mental retardation. These results also provide evidence that resting-state connectivity can potentially become a biomarker for psychosis and that ACC plays an important role in the development of psychotic symptoms

Altered structural network architecture is predictive of the presence of psychotic symptoms in patients with 22q11.2 deletion syndrome

22q11.2 deletion syndrome (22q11DS) represents a homogeneous model of schizophrenia particularly suitable for the search of neural biomarkers of psychosis. Impairments in structural connectivity related to the presence of psychotic symptoms have been reported in patients with 22q11DS. However, the relationships between connectivity changes in patients with different symptomatic profiles are still largely unknown and warrant further investigations. In this study, we used structural connectivity to discriminate patients with 22q11DS with (N = 31) and without (N = 31) attenuated positive psychotic symptoms. Different structural connectivity measures were used, including the number of streamlines connecting pairs of brain regions, graph theoretical measures, and diffusion measures. We used univariate group comparisons as well as predictive multivariate approaches. The univariate comparison of connectivity measures between patients with or without attenuated positive psychotic symptoms did not give significant results. However, the multivariate prediction revealed that altered structural network architecture discriminates patient subtypes (accuracy = 67.7%). Among the regions contributing to the classification we found the anterior cingulate cortex, which is known to be associated to the presence of psychotic symptoms in patients with 22q11DS. Furthermore, a significant discrimination (accuracy = 64%) was obtained with fractional anisotropy and radial diffusivity in the left inferior longitudinal fasciculus and the right cingulate gyrus. Our results point to alterations in structural network architecture and white matter microstructure in patients with 22q11DS with attenuated positive symptoms, mainly involving connections of the limbic system. These alterations may therefore represent a potential biomarker for an increased risk of psychosis that should be further tested in longitudinal studies

Oscillatory neural signatures of visual perception across developmental stages in individuals with 22q11.2 deletion syndrome

Background: Numerous behavioral studies have highlighted the contribution of visual perceptual deficits to the nonverbal cognitive profile of individuals with 22q11.2 deletion syndrome. However, the neurobiological processes underlying these widespread behavioral alterations are yet to be fully understood. Thus, in this paper, we investigated the role of neural oscillations toward visuoperceptual deficits to elucidate the neurobiology of sensory impairments in deletion carriers. Methods: We acquired 125 high-density electroencephalography recordings during a visual grating task in a group of 62 deletion carriers and 63 control subjects. Stimulus-elicited oscillatory responses were analyzed with 1) time-frequency analysis using wavelets decomposition at sensor and source level, 2) intertrial phase coherence, and 3) Granger causality connectivity in source space. Additional analyses examined the development of neural oscillations across age bins. Results: Deletion carriers had decreased theta-band (4–8 Hz) and gamma-band (58–68 Hz) spectral power compared with control subjects in response to the visual stimuli, with an absence of age-related increase of theta- and gamma-band responses. Moreover, adult deletion carriers had decreased gamma- and theta-band responses but increased alpha/beta desynchronization (10–25 Hz) that correlated with behavioral performance. Granger causality estimates reflected an increased frontal-occipital connectivity in the beta range (22–40 Hz). Conclusions: Deletion carriers exhibited decreased theta- and gamma-band responses to visual stimuli, while alpha/beta desynchronization was preserved. Overall, the lack of age-related changes in deletion carriers implicates developmental impairments in circuit mechanisms underlying neural oscillations. The dissociation between the maturation of theta/gamma- and alpha/beta-band responses may indicate a selective impairment in supragranular cortical layers, leading to compensatory top-down connectivity