Psychosocial therapeutic approaches for high-functioning autistic adults.

Autism spectrum disorder (ASD) is characterized by impaired social interaction and communication skills, repetitive behaviors, restricted interests, and specific sensory processing. Particularly, adults with high-functioning ASD often remain unrecognized, presumably due to their high compensatory skills, but at the cost of high stress, which is often linked to anxiety and depression. This may further explain the significantly high suicide rates and reduced life expectancy among individuals with ASD. Thus, providing support to high-functioning autistic adults in managing core symptoms, as well as co-occurring anxiety and depression, appears essential. To date, only a limited number of evidence-based psychosocial therapeutic options are available, and very few of them have undergone rigorous evaluation in a clinical context. To obtain a comprehensive understanding, a systematic literature search was conducted according to the PRISMA checklist, and only studies demonstrating robust methodological quality were included and discussed in this review article. Although promising initial key factors and methods have been identified, additional evidence-based studies are imperative to ascertain the optimal treatment and evaluate the long-term outcomes for adults with high-functioning ASD.

Prospective Prediction of Depression and Anxiety by Integrating Negative Emotionality and Cognitive Vulnerabilities in Children and Adolescents.

Negative emotionality (NE) and multiple cognitive vulnerabilities (CVs) (negative inferential style, brooding, self-criticism, dependency, dysfunctional attitudes) independently predict internalizing outcomes. The present study examined whether NE and CVs could be structurally integrated into a common factor reflecting shared variance across risks, and specific factors reflecting unique variance in risks. We evaluated the validity and utility of this integrated model via prospective prediction of future depression and anxiety compared to alternative models (NE and CVs individually, a correlated factor model). Youth from a large community sample (N = 571; M = 13.58 years old; 55% girls, 44% boys) reported on NE and CVs. Depression and anxiety symptoms based on youth report, and disorder onset based on youth and caregiver diagnostic interviews were assessed over a 1½ years follow-up. Results supported a structural model including a general NE-CV dimension and specific dimensions for NE, common cognitive risk, negative inferential style, and brooding; model invariance was obtained from late childhood through late adolescence and for girls and boys. The integrated general NE-CV factor more consistently and strongly predicted future depressive (ß = 0.58) and anxiety (ß = 0.56) symptoms, and onsets of depression (OR = 1.81) and anxiety (OR = 2.23) relative to NE and CV risk dimensions across alternative models (ps < .01). The general NE-CV dimension represents an important means to efficiently represent transdiagnostic risk for internalizing outcomes among youth.

The Interplay of Chronic Interpersonal Stress and Rumination on Nonsuicidal Self-Injury in Youth.

Nonsuicidal self-injury (NSSI) describes deliberate self-destructive behaviors without the intention to die. Little is known about what factors contribute to NSSI especially among youth. The current study tested two conceptual models for how chronic interpersonal stress and rumination may contribute to NSSI engagement across 18 months in a community sample of youth: (1) a mediation pathway based on the Emotional Cascade Model (i.e., stress contributes to rumination and then to subsequent NSSI), and (2) a moderation model based on the cognitive vulnerability-stress framework (i.e., rumination moderates the relation between stress and NSSI). 516 youth aged 7-16 (Mage = 12.0; 56% female; 90% Non-Hispanic or Non-Latinx) reported on ongoing interpersonal stress occurring between T1-T2 (every 6 months from T1 to 12 months) via the Youth Life Stress Interview, rumination via the Children's Response Styles Questionnaire (at T1 and 18 months later, T2), and NSSI engagement every six months from 18 to 36 months (T2-T3) via the Self-Injurious Thoughts and Behaviors Interview. Interpersonal stress predicted later rumination (b = .43, p < .01), rumination forecasted later NSSI occurrence (OR = 1.06, p < .01), and mediation was supported via a significant indirect effect of interpersonal stress on NSSI through rumination (b = .03, 95% CI = .01, .07). Rumination did not significantly moderate the relation between stress and NSSI. The prospective relation between chronic interpersonal stress and NSSI engagement was partly explained by rumination, aligning with the Emotional Cascade Model's prediction that rumination contributes to NSSI. Youth may conduct NSSI to interrupt rumination elicited by chronic interpersonal stress.

Diagnosing Organic Causes of Schizophrenia Spectrum Disorders: Findings from a One-Year Cohort of the Freiburg Diagnostic Protocol in Psychosis (FDPP).

Introduction: Secondary schizophrenia spectrum disorders (SSDs) have clearly identifiable causes. The Department for Psychiatry and Psychotherapy at the University Hospital Freiburg has continued to expand its screening practices to clarify the organic causes of SSDs. This retrospective analysis was carried out to analyze whether a comprehensive organic diagnostic procedure could be informative in patients with SSDs. Methods and Participants: The "Freiburg Diagnostic Protocol in Psychosis" (FDPP) included basic laboratory analyses (e.g., thyroid hormones), metabolic markers, pathogens, vitamin status, different serological autoantibodies, rheumatic/immunological markers (e.g., complement factors), cerebrospinal fluid (CSF) basic and antineuronal antibody analyses, as well as cranial magnetic resonance imaging (cMRI) and electroencephalography (EEG). The findings of 76 consecutive patients with SSDs (55 with paranoid-hallucinatory; 14 with schizoaffective; 4 with hebephrenic; and 1 each with catatonic, acute polymorphic psychotic, and substance-induced psychotic syndromes) were analyzed. Results: Overall, vitamin and trace element deficiency was identified in 92%. Complement factor analyses detected reduced C3 levels in 11%. Immunological laboratory alterations were detected in 76%. CSF analysis revealed general alterations in 54% of the patients, mostly with signs of blood-brain barrier dysfunction. cMRI analyses showed chronic inflammatory lesions in 4%. Combination of EEG, cMRI, and CSF revealed alterations in 76% of the patients. In three patients, autoimmune psychosis was suspected (4%). Discussion: On the basis of these findings, we conclude that a comprehensive diagnostic procedure according to the FDPP in patients with SSD is worthwhile, considering the detection of secondary, organic forms of SSDs, as well as alterations in "modulating factors" of the disease course, such as vitamin deficiency. Larger studies using comprehensive diagnostic protocols are warranted to further validate this approach.

Novel Antineuronal Autoantibodies With Somatodendritic Staining Pattern in a Patient With Autoimmune Psychosis.

BACKGROUND: Autoimmune encephalitis, such as anti-NMDA-receptor encephalitis, typically presenting with subacute onset of neuropsychiatric symptoms, can be detected by antineuronal autoantibodies or inflammatory changes in the cerebrospinal fluid (CSF), as well as pathological alterations in electroencephalography (EEG), magnetic resonance imaging (MRI), or [18F]fluorodeoxyglucose positron emission tomography (FDG PET). For patients with predominant psychotic symptoms, the term autoimmune psychosis was proposed. Here, the authors present the case of a patient with probable autoimmune psychosis associated with unknown antineuronal antibodies. CASE PRESENTATION: A 18-year-old male patient with preexisting autism spectrum disorder developed a severe catatonic syndrome over 2.5 years. The MRI showed normal findings, the EEG depicted intermittent slowing, and the independent component analyses showed additional sharp spikes. However, FDG PET, the basic laboratory analysis and testing of the serum/CSF for well-characterized antineuronal autoantibodies were unsuspicious. The serum and CSF "tissue-based assay" using indirect immunofluorescence on unfixed murine brain tissue revealed antineuronal autoantibodies against an unknown epitope in granule cells in the cerebellum and to neurites of hippocampal interneurons with a somatodendritic staining pattern. The immunosuppressive treatment with high-dose glucocorticoids, plasma exchange, and rituximab led to partial improvement. CONCLUSION: The patient probably suffered from autoantibody-associated autoimmune psychosis. The special features of the case were that the patient (1) presented with mostly inconspicuous basic diagnostics, except for the altered EEG in combination with the detection of CSF autoantibodies directed against a currently unknown epitope, (2) experienced an isolated and long-lasting psychotic course, and (3) had pre-existing autism spectrum disorder. The detection of a probable autoimmune pathophysiology in such cases seems important, as it offers new and more causal immunosuppressive treatment alternatives.

Psychiatric Manifestation of Anti-LGI1 Encephalitis.

BACKGROUND: Anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis is typically characterized by limbic encephalitis, faciobrachial dystonic seizures and hyponatremia. The frequency with which milder forms of anti-LGI1 encephalitis mimic isolated psychiatric syndromes, such as psychoses, or may lead to dementia if untreated, is largely unknown. CASE PRESENTATION: Here, the authors present a 50-year-old patient who had suffered from neurocognitive deficits and predominant delusions for over one and a half years. He reported a pronounced feeling of thirst, although he was drinking 10-20 liters of water each day, and he was absolutely convinced that he would die of thirst. Due to insomnia in the last five years, the patient took Z-drugs; later, he also abused alcohol. Two years prior to admission, he developed a status epilepticus which had been interpreted as a withdrawal seizure. In his serum, anti-LGI1 antibodies were repeatedly detected by different independent laboratories. Cerebrospinal fluid analyses revealed slightly increased white blood cell counts and evidence for blood-brain-barrier dysfunction. Magnetic resonance imaging showed hyperintensities mesio-temporally and in the right amygdala. In addition, there was a slight grey-white matter blurring. A cerebral [18F] fluorodeoxyglucose positron emission tomography (FDG-PET) examination of his brain showed moderate hypometabolism of the bilateral rostral mesial to medial frontal cortices. Treatment attempts with various psychotropic drugs remained unsuccessful in terms of symptom relief. After the diagnosis of probable chronified anti-LGI1 encephalitis was made, two glucocorticoid pulse treatments were performed, which led to a slight improvement of mood and neurocognitive deficits. Further therapy was not desired by the patient and his legally authorized parents. CONCLUSION: This case study describes a patient with anti-LGI1 encephalitis in the chronified stage and a predominant long-lasting psychiatric course with atypical symptoms of psychosis and typical neurocognitive deficits. The patient's poor response to anti-inflammatory drugs was probably due to the delayed start of treatment. This delay in diagnosis and treatment may also have led to the FDG-PET findings, which were compatible with frontotemporal dementia ("state of damage"). In similar future cases, newly occurring epileptic seizures associated with psychiatric symptoms should trigger investigations for possible autoimmune encephalitis, even in patients with addiction or other pre-existing psychiatric conditions. This should in turn result in rapid organic clarification and-in positive cases-to anti-inflammatory treatment. Early treatment of anti-LGI1 encephalitis during the "inflammatory activity state" is crucial for overall prognosis and may avoid the development of dementia in some cases. Based on this case, the authors advocate the concept-long established in many chronic inflammatory diseases in rheumatology-of distinguishing between an "acute inflammatory state" and a "state of organ damage" in autoimmune psychosis resembling neurodegenerative mechanisms.

Anti-N-Methyl-D-Aspartate-Receptor Encephalitis: A 10-Year Follow-Up.

BACKGROUND: Anti-N-methyl-D-aspartate-receptor (NMDA-R) encephalitis is an autoimmune disease of the brain first described in 2007. The aim of this paper is to present a 10-year follow-up case history. CASE PRESENTATION: The authors present the case of a 39-year-old female patient who developed an anti-NMDA-R encephalitis in 2009 with predominant severe catatonic symptoms. Anti-inflammatory therapy led to the disappearance of catatonic symptoms and was discontinued during the course of the disease. After acute therapy, the patient achieved an almost full recovery presenting with ongoing discrete symptoms of sensory overload, subtle cognitive deficits, and fatigue/reduced energy levels. The follow-up investigation in 2019 showed inconspicuous findings in laboratory diagnostics and magnetic resonance imaging. Electroencephalography (EEG) analysis using independent component analysis detected left hemispherical spike-wave complexes and intermittent slowing. Regarding the sensory overload and reduced energy level, the patient benefited from low-dose neuroleptics (risperidone, amisulpride). In terms of sensory overload associated with experiences of panic, cognitive deficits and coping with the disease, she improved with cognitive behavioral therapy (CBT). CONCLUSION: Anti-inflammatory treatment led to almost full recovery with persistent disappearance of catatonic symptoms; however, a dysexecutive syndrome led to ongoing relevant problems with good response to low-dose atypical neuroleptics and CBT. The patient had persistent EEG alterations that indicated continuing neuronal network instability. Therefore, the case demonstrates the importance of multidisciplinary outpatient treatment following acute therapy for anti-NMDA-R encephalitis in patients with ongoing psychiatric deficits. For the symptomatic treatment of executive dysfunctions, "classical" psychiatric treatment may be helpful in the course of the disease.

Parkinsonian Syndrome with Frontal Lobe Involvement and Anti-Glycine Receptor Antibodies.

Background: Atypical Parkinsonian syndromes with prominent frontal lobe involvement can occur in the 4R-taupathies progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Secondary forms of movement disorders may occur in the context of autoimmune encephalitis with antineuronal antibodies, such as anti-glycine receptor (anti-GlyR) antibodies, which are typically associated with Stiff-Person spectrum syndrome, or progressive encephalomyelitis with rigidity and myoclonus. Overlaps between neurodegenerative and immunological mechanisms have been recently suggested in anti-IgLON5 disease. In this case study, the authors describe a patient with a Parkinsonian syndrome with frontal lobe involvement and anti-GlyR antibodies. Case presentation: The patient presented was a 63-year-old female. Her symptoms had begun with insomnia at the age of 60, after which, since the age of 61, increasing personality changes developed, leading to a diagnosis of depression with delusional symptoms. Severe cognitive deficits emerged, along with a left-side accentuated Parkinsonian syndrome with postural instability. The personality changes involved frontal systems. Magnetic resonance imaging (MRI) showed low-grade mesencephalon atrophy. [18F]fluorodeoxyglucose positron emission tomography (FDG PET) depicted a moderate hypometabolism bilateral frontal and of the midbrain, while [123I]FPCIT single-photon emission computed tomography (SPECT) revealed severely reduced dopamine transporter availability in both striata, indicating pronounced nigrostriatal degeneration. In addition, anti-GlyR antibodies were repeatedly found in the serum of the patient (max. titer of 1:640, reference: <1:20). Therefore, an anti-inflammatory treatment with steroids and azathioprine was administered; this resulted in a decrease of antibody titers (to 1:80) but no detectable clinical improvement. The cerebrospinal fluid (CSF) and electroencephalography diagnostics showed inconspicuous findings, and negative CSF anti-GlyR antibody results. Conclusion: The patient presented here was suffering from a complex Parkinsonian syndrome with frontal lobe involvement. Because of the high anti-GlyR antibody titers, the presence of an autoimmune cause of the disorder was discussed. However, since no typical signs of autoimmune anti-GlyR antibody syndrome (e.g., hyperexcitability, anti-GlyR antibodies in CSF, or other inflammatory CSF changes) were detected, the possibility that the anti-GlyR antibodies might have been an unrelated bystander should be considered. Alternatively, the anti-GlyR antibodies might have developed secondarily to neurodegeneration (most likely a 4-repeat tauopathy, PSP or CBD) without exerting overt clinical effects, as in cases of anti-IgLON5 encephalopathy. In this case, such antibodies might also potentially modify the clinical course of classical movement disorders. Further research on the role of antineuronal antibodies in Parkinsonian syndromes is needed.

The breadth and potency of transdiagnostic cognitive risks for psychopathology in youth.

OBJECTIVE: Multiple cognitive risks from different theoretical paradigms (dysfunctional attitudes, negative inferential style, self-criticism, dependency, brooding) predict depression, but may be transdiagnostic vulnerabilities for multiple psychopathologies. Risk factors can be identified as broadly transdiagnostic and relatively specific to psychopathological outcomes by organizing the common and specific aspects of each respective construct using latent bifactor models, and by examining links between dimensions of risk and psychopathology. This study evaluated (a) whether a bifactor model of cognitive vulnerabilities, including a general cognitive risk dimension (c factor) and several specific dimensions replicated in early adolescents (Mage = 13.50 years) and extended to younger and older youth, and (b) how the general and specific cognitive risk dimensions related to the general psychopathology (p factor) and internalizing- and externalizing-specific dimensions. METHOD: Community youth (N = 571; 55% female) reported on cognitive risks; youth and a caregiver reported on psychopathologies (depression, anxiety, aggression, conduct, attention problems). RESULTS: The cognitive risk bifactor model showed good fit and slight advantages over a correlated factors model. The bifactor model exhibited invariance across development and captured key associations that were identified when each individual cognitive risk was related to the bifactor model of psychopathology. The c factor strongly related to internalizing-specific, and moderately to the p factor and externalizing-specific dimensions. Specific cognitive risk dimensions (brooding, negative inferential style, dependency) related to all psychopathology dimensions. CONCLUSION: A general cognitive vulnerability (c factor) transdiagnostically associates with a breadth of psychopathologies and most potently to internalizing-specific among youth. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

A Reformulated Architecture of Cognitive Risks for Psychopathology: Common and Specific Dimensions and Links to Internalizing Outcomes in Adolescence.

Multiple cognitive risk products (dysfunctional attitudes [DA], negative inferential style [NIS], self-criticism, dependency, rumination) predict internalizing disorders; however, an optimal structure to assess these risks is unknown. We evaluated the fit, construct validity, and utility of a bifactor, single, and correlated factor model in a community sample of 382 adolescents (age 11-15 years; 59% female). The bifactor, hierarchical single, and correlated factor models all fit well. The bifactor model included a common factor (c), capturing covariance across all cognitive risk measures, and specific latent factors for DA, NIS, dependency and rumination. Construct validity of these factor structures was evaluated with external validators, including depression and anxious arousal (AA) symptoms, positive affect (PA) and negative affect (NA), and onset of depression diagnostic onset over 2 years. C was associated with higher depression, NA, and AA; lower PA; and predicted depressive episodes. Hierarchical single and correlated factor models also related to external validators.

Psychophysiological reactivity, coping behaviour and intrusive memories upon multisensory Virtual Reality and Script-Driven Imagery analogue trauma: A randomised controlled crossover study.

BACKGROUND: Peri- and post-traumatic factors predict the differential development of stress-associated mental disorders. Prospective designs assessing these risk factors in real-time under controlled experimental conditions can overcome limitations of retrospective designs. Therefore, we aimed to investigate multi-sensory, experimental analogues of a traumatic experience delivered in Virtual Reality (VR) or Script-Driven Imagery (SDI). METHODS: In a randomised controlled crossover design, differences in the induced analogue trauma symptoms between multi-sensory analogue trauma by either VR or SDI versus a neutral condition were assessed in 127 non-clinical participants. RESULTS: Analogue symptoms (psychophysiological responses, coping behaviour and intrusive memories of the experimental trauma) increased following analogue trauma in both VR and SDI, with more analogue symptoms for VR. Psychophysiological arousal was in general higher in VR. LIMITATIONS: The analogue trauma situation of a car park fire that was used may be infrequent in real life. CONCLUSIONS: Multisensory (vision, olfaction, hearing) analogue trauma in VR and SDI offers a useful tool for the induction and real-time assessment of peri- and post-traumatic risk factors for analogue stress-associated psychopathology. VR was more effective in inducing analogue symptoms than SDI, even though the latter might be more personalised. New experimental models for studying trauma exposure and responses may contribute to a better understanding of risk factors and help to identify and protect individuals at risk.

Developmental Origins of Rumination in Middle Childhood: The Roles of Early Temperament and Positive Parenting.

Rumination, a thinking style characterized by a repetitive inward focus on negative cognitions, has been linked to internalizing disorders, particularly depression. Moreover, research suggests that rumination may be a cognitive vulnerability that predisposes individuals to psychopathology. Surprisingly little is known, however, about the etiology and development of rumination. The present study examined the role of specific components of child temperamental negative emotionality (sadness, fear, anger) and effortful control (inhibition), as well as parenting behaviors during early childhood on the development of rumination in middle childhood. Early childhood (age 3) temperament and parenting behaviors were assessed observationally and rumination was self-reported in middle childhood (age 9) in a large community sample (N = 425; 47.1% female). Two significant interactions emerged. First, temperamental anger interacted with inhibitory control (IC) such that high anger and low IC predicted higher levels of rumination, whereas low anger and low IC predicted lower levels of rumination. Second, IC interacted with parenting such that children with low IC and positive parenting had lower levels of rumination. In contrast, children with high IC reported similar levels of rumination regardless of parenting quality. Overall, these findings highlight the interplay of early IC with temperamental anger and positive parenting in the development of ruminative tendencies in middle childhood.

The impact of pre-existing anxiety on affective and cognitive processing of a Virtual Reality analogue trauma.

Dysfunctional processing of traumatic events may be in particular related to high trait anxiety as a pre-traumatic risk factor for the development of post-traumatic stress disorder (PTSD). However, as this has rarely been investigated in prospective, experimental studies, we aimed to analyse the association between high trait anxiety and affective as well as cognitive processing of stress using a new prospective Virtual Reality analogue trauma paradigm to overcome limitations of retrospective or current analogue designs. Individuals with high and low trait anxiety (N = 80) were exposed to a multi-sensory Virtual Reality emergency scenario while psychophysiological stress response, emotion regulation and intrusive memories were assessed. Our results showed that high trait anxiety individuals display increased (i) subjective stress responses, (ii) emotion dysregulation and (iii) intrusive memories upon VR analogue trauma exposure. In particular, our sample of high trait anxiety individuals displayed limited access to different emotion regulation strategies as well as increased worry and rumination regarding perceived intrusive memories. Considering the complex interplay of multiple risk factors, our findings suggests that peri-traumatic affective processing seems to mediate high trait anxiety and post-traumatic intrusive memories thereby pointing out the central role of peri-traumatic processes for intrusion development. In addition, HA as a modulating pre-traumatic risk factor might further increase the risk of later dysfunctional processing of an analogue trauma by interacting with factors of affective processing during analogue trauma exposure. Implications of these findings which may contribute to a higher risk to develop PTSD are discussed.

Understanding comorbidity among internalizing problems: Integrating latent structural models of psychopathology and risk mechanisms.

It is well known that comorbidity is the rule, not the exception, for categorically defined psychiatric disorders, and this is also the case for internalizing disorders of depression and anxiety. This theoretical review paper addresses the ubiquity of comorbidity among internalizing disorders. Our central thesis is that progress in understanding this co-occurrence can be made by employing latent dimensional structural models that organize psychopathology as well as vulnerabilities and risk mechanisms and by connecting the multiple levels of risk and psychopathology outcomes together. Different vulnerabilities and risk mechanisms are hypothesized to predict different levels of the structural model of psychopathology. We review the present state of knowledge based on concurrent and developmental sequential comorbidity patterns among common discrete psychiatric disorders in youth, and then we advocate for the use of more recent bifactor dimensional models of psychopathology (e.g., p factor; Caspi et al., 2014) that can help to explain the co-occurrence among internalizing symptoms. In support of this relatively novel conceptual perspective, we review six exemplar vulnerabilities and risk mechanisms, including executive function, information processing biases, cognitive vulnerabilities, positive and negative affectivity aspects of temperament, and autonomic dysregulation, along with the developmental occurrence of stressors in different domains, to show how these vulnerabilities can predict the general latent psychopathology factor, a unique latent internalizing dimension, as well as specific symptom syndrome manifestations.

Who gets afraid in the MRI-scanner? Neurogenetics of state-anxiety changes during an fMRI experiment.

Experiments using functional magnetic resonance imaging (fMRI) play a fundamental role in affective neuroscience. When placed in an MR scanner, some volunteers feel safe and relaxed in this situation, while others experience uneasiness and fear. Little is known about the basis and consequences of such inter-individually different responses to the general experimental fMRI setting. In this study emotional stimuli were presented during fMRI and subjects' state-anxiety was assessed at the onset and end of the experiment while they were within the scanner. We show that Val/Val but neither Met/Met nor Val/Met carriers of the catechol-O-methyltransferase (COMT) Val(158)Met polymorphism-a prime candidate for anxiety vulnerability-became significantly more anxious during the fMRI experiment (N=97 females: 24 Val/Val, 51 Val/Met, and 22 Met/Met). Met carriers demonstrated brain responses with increased stability over time in the right parietal cortex and significantly better cognitive performances likely mediated by lower levels of anxiety. Val/Val, Val/Met and Met/Met did not significantly differ in state-anxiety at the beginning of the experiment. The exposure of a control group (N=56 females) to the same experiment outside the scanner did not cause a significant increase in state-anxiety, suggesting that the increase we observe in the fMRI experiment may be specific to the fMRI setting. Our findings reveal that genetics may play an important role in shaping inter-individual different emotional, cognitive and neuronal responses during fMRI experiments.