Opening new vistas on obsessive-compulsive disorder with the observing response task.

Obsessive-compulsive disorder (OCD), a highly prevalent and debilitating disorder, is incompletely understood in terms of underpinning behavioural, psychological, and neural mechanisms. This is attributable to high symptomatic heterogeneity; cardinal features comprise obsessions and compulsions, including clinical subcategories. While obsessive and intrusive thoughts are arguably unique to humans, dysfunctional behaviours analogous to those seen in clinical OCD have been examined in nonhuman animals. Genetic, ethological, pharmacological, and neurobehavioural approaches all contribute to understanding the emergence and persistence of compulsive behaviour. One behaviour of particular interest is maladaptive checking, whereby human patients excessively perform checking rituals despite these serving no purpose. Dysfunctional and excessive checking is the most common symptom associated with OCD and can be readily operationalised in rodents. This review considers animal models of OCD, the neural circuitries associated with impairments in habit-based and goal-directed behaviour, and how these may link to the compulsions observed in OCD. We further review the Observing Response Task (ORT), an appetitive instrumental learning procedure that distinguishes between functional and dysfunctional checking, with translational application in humans and rodents. By shedding light on the psychological and neural bases of compulsive-like checking, the ORT has potential to offer translational insights into the underlying mechanisms of OCD, in addition to being a platform for testing psychological and neurochemical treatment approaches.

Effectiveness of teleneuropsychological rehabilitation: Systematic review of randomized controlled trials.

OBJECTIVE: The effectiveness of neuropsychological rehabilitation is supported by the evidence found in previous reviews, but there is a lack of research regarding the effectiveness of remotely conducted neuropsychological rehabilitation. This review aimed to identify and evaluate the results of studies investigating the effectiveness of teleneuropsychological rehabilitation. METHODS: Relevant articles were extracted from electronic databases and filtered to include studies published in 2016 or later to focus on recent practices. Data were synthesized narratively. RESULTS: A total of 14 randomized controlled studies were included in the synthesis (9 for children/adolescents, 5 for adults). The most common type of intervention was computerized cognitive training with regular remote contact with the therapist (seven studies). Regarding children and adolescents, the evidence for the effectiveness was found only for these types of interventions with improvements in cognitive outcomes. The results regarding the family-centered interventions were mixed with improvements only found in psychosocial outcomes. No support was found for the effectiveness of interventions combining cognitive and motor training. Regarding adults, all included studies offered support for the effectiveness, at least to some extent. There were improvements particularly in trained cognitive functions. Long-term effects of the interventions with generalization to global functioning remained somewhat unclear. CONCLUSION: Remote interventions focused on computerized cognitive training are promising methods within teleneuropsychological rehabilitation. However, their impact on long-term meaningful, everyday functioning remained unclear. More research is needed to reliably assess the effectiveness of teleneuropsychological interventions, especially with more comprehensive approaches.

A digital teleneuropsychology platform for the diagnosis of mild cognitive impairment: from concept to certification as a medical device.

BACKGROUND: Innovative digital solutions are shaping a new concept of dementia care, opening additional venues for prevention, diagnosis, monitoring and treatment. Hereby, we report the development of a tablet-based teleneuropsychology platform (Tenèpsia®), from concept to certification as Medical Device (MD) Class IIA, as per new MD regulation 745/2017. METHODS: The platform was designed for the remote cognitive evaluation and created thanks to the effort of a collaborative working group including experts from three Italian scientific societies and Biogen Italia S.r.l. (hereafter "Biogen"), and developers from Xenia Reply and Inside AI. The development strategy was guided by converting traditional paper-and-pencil tests into digital versions while maintaining comparable neuropsychological features and optimizing patient accessibility and user experience. The experts focused on the choice and adaptation of traditional neuropsychology measures for a 45-min teleneuropsychology assessment. RESULTS: The developers created a web and a mobile interface, respectively, for the professional (neuropsychologist) and non-professional (patient and caregiver) use. Recording of voice, drawing and typing information was enabled. Instant dashboards provide a quick overview of the patient's condition. Simulation activities were performed to obtain MD certification, valid across Europe. CONCLUSION: Neuropsychology services will benefit from the implementation in clinics of harmonized digital tools with adequate scientific and technological standards. The use of digital cognitive testing for the diagnosis of mild cognitive impairment is expected to enhance patient and clinician outcomes through simplified, digital objective data collection, sparing of time and resources, with a positive impact on healthcare costs and access to treatments, reducing inequalities and delays in diagnosis and cure.

"Brain Fog" After COVID-19 Infection: How the Field of Neuropsychology Can Help Clear the Air.

The chapter explores the role of neuropsychology in understanding brain fog as a subjective complaint in the context of COVID-19. It discusses the historical and medical significance of the term "brain fog" and its psychological and neurological aspects. The chapter identifies the cognitive domains commonly affected by brain fog, such as attention, executive function, memory, and language. Additionally, it emphasizes the impact of societal changes during the COVID-19 pandemic on the general population as a crucial backdrop for understanding the issue. The chapter also highlights the important role of clinical and research neuropsychologists in gaining clarity on grouped data and individual patients' cognitive and emotional difficulties after COVID-19 infection. It discusses indications for neuropsychological rehabilitation and therapy and describes typical therapy phases and methods, including new approaches like telemedicine, virtual reality, and mobile app-based rehabilitation and self-tracking. The chapter underscores that experiences of brain fog can vary among COVID-19 patients and may change over time. It provides clinicians and interested parties with an in-depth understanding of brain fog and its manifestations, concomitant subtypes, and concrete strategies for addressing it. The chapter emphasizes the critical role of neuropsychology in scientifically examining brain fog and advocating for personalized approaches to cognitive rehabilitation.

Forensic neuropsychological assessment.

With its firm establishment as a neuropsychology subspecialty, forensic neuropsychological assessment is integral to many criminal and civil forensic evaluations. In addition to evaluating cognitive deficits, forensic neuropsychologists can provide reliable information regarding symptom magnification, malingering, and other neurocognitive and psychological issues that may impact the outcome of a particular legal case. This article is an overview and introduction to neuropsychological assessment in the forensic mental health context. Major issues impacting the current practice of forensic neuropsychology are summarized, and several examples from case law are highlighted.

Integrating Clinical Neuropsychology and Psychotic Spectrum Disorders: A Systematic Analysis of Cognitive Dynamics, Interventions, and Underlying Mechanisms.

Background and Objectives: The study aims to provide a comprehensive neuropsychological analysis of psychotic spectrum disorders, including schizophrenia, bipolar disorder, and depression. It focuses on the critical aspects of cognitive impairments, diagnostic tools, intervention efficacy, and the roles of genetic and environmental factors in these disorders. The paper emphasizes the diagnostic significance of neuropsychological tests in identifying cognitive deficiencies and their predictive value in the early management of psychosis. Materials and Methods: The study involved a systematic literature review following the PRISMA guidelines. The search was conducted in significant databases like Scopus, PsycINFO, PubMed, and Web of Science using keywords relevant to clinical neuropsychology and psychotic spectrum disorders. The inclusion criteria required articles to be in English, published between 2018 and 2023, and pertinent to clinical neuropsychology's application in these disorders. A total of 153 articles were identified, with 44 ultimately included for detailed analysis based on relevance and publication status after screening. Results: The review highlights several key findings, including the diagnostic and prognostic significance of mismatch negativity, neuroprogressive trajectories, cortical thinning in familial high-risk individuals, and distinct illness trajectories within psychosis subgroups. The studies evaluated underline the role of neuropsychological tests in diagnosing psychiatric disorders and emphasize early detection and the effectiveness of intervention strategies based on cognitive and neurobiological markers. Conclusions: The systematic review underscores the importance of investigating the neuropsychological components of psychotic spectrum disorders. It identifies significant cognitive impairments in attention, memory, and executive function, correlating with structural and functional brain abnormalities. The paper stresses the need for precise diagnoses and personalized treatment modalities, highlighting the complex interplay between genetic, environmental, and psychosocial factors. It calls for a deeper understanding of these neuropsychological processes to enhance diagnostic accuracy and therapeutic outcomes.

Deficits in naming pictures of objects are associated with glioma infiltration of the inferior longitudinal fasciculus: A study with diffusion MRI tractography, volumetric MRI, and neuropsychology.

It has been suggested that the inferior longitudinal fasciculus (ILF) may play an important role in several aspects of language processing such as visual object recognition, visual memory, lexical retrieval, reading, and specifically, in naming visual stimuli. In particular, the ILF appears to convey visual information from the occipital lobe to the anterior temporal lobe (ATL). However, direct evidence proving the essential role of the ILF in language and semantics remains limited and controversial. The first aim of this study was to prove that patients with a brain glioma damaging the left ILF would be selectively impaired in picture naming of objects; the second aim was to prove that patients with glioma infiltrating the ATL would not be impaired due to functional reorganization of the lexical retrieval network elicited by the tumor. We evaluated 48 right-handed patients with neuropsychological testing and magnetic resonance imaging (MRI) before and after surgery for resection of a glioma infiltrating aspects of the left temporal, occipital, and/or parietal lobes; diffusion tensor imaging (DTI) was acquired preoperatively in all patients. Damage to the ILF, inferior frontal occipital fasciculus (IFOF), uncinate fasciculus (UF), arcuate fasciculus (AF), and associated cortical regions was assessed by means of preoperative tractography and pre-/pos-toperative MRI volumetry. The association of fascicles damage with patients' performance in picture naming and three additional cognitive tasks, namely, verbal fluency (two verbal non-visual tasks) and the Trail Making Test (a visual attentional task), was evaluated. Nine patients were impaired in the naming test before surgery. ILF damage was demonstrated with tractography in six (67%) of these patients. The odds of having an ILF damage was 6.35 (95% CI: 1.27-34.92) times higher among patients with naming deficit than among those without it. The ILF was the only fascicle to be significantly associated with naming deficit when all the fascicles were considered together, achieving an adjusted odds ratio of 15.73 (95% CI: 2.30-178.16, p = .010). Tumor infiltration of temporal and occipital cortices did not contribute to increase the odd of having a naming deficit. ILF damage was found to be selectively associated with picture naming deficit and not with lexical retrieval assessed by means of verbal fluency. Early after surgery, 29 patients were impaired in naming objects. The association of naming deficit with percentage of ILF resection (assessed by 3D-MRI) was confirmed (beta = -56.78 ± 20.34, p = .008) through a robust multiple linear regression model; no significant association was found with damage of IFOF, UF or AF. Crucially, postoperative neuropsychological evaluation showed that naming scores of patients with tumor infiltration of the anterior temporal cortex were not significantly associated with the percentage of ILF damage (rho = .180, p > .999), while such association was significant in patients without ATL infiltration (rho = -.556, p = .004). The ILF is selectively involved in picture naming of objects; however, the naming deficits are less severe in patients with glioma infiltration of the ATL probably due to release of an alternative route that may involve the posterior segment of the AF. The left ILF, connecting the extrastriatal visual cortex to the anterior region of the temporal lobe, is crucial for lexical retrieval on visual stimulus, such as in picture naming. However, when the ATL is also damaged, an alternative route is released and the performance improves.

Neuropsychology assessment and outcomes in adult mucopolysaccharidosis - A systematic review as the first step to service development in a large tertiary Lysosomal Storage Disorders centre.

A systematic review of Randomised Controlled Trials in adult mucopolysaccharidoses (MPSs) was conducted to inform neuropsychology service development at a large tertiary Lysosomal Storage Diseases centre. Studies including psychological endpoints for cognition, mood, and quality of life were reviewed. Forty-eight studies met the inclusion criteria for full text review. Of the 48 studies, 44% (21/48) included adult participants, while psychological endpoints were used in 52% (25/48) for cognition, 11% (5/48) for mood, and 69% (33/48) for quality of life. Five studies included both adult participants and relevant psychological endpoints. Risk of bias ratings were 'high' for two studies, while two studies received a rating of 'some concerns', and the last study a 'low' risk of bias rating. The evidence base for psychological outcomes in adult MPS disorders is limited and insufficient for guiding neuropsychology service development. Data on the psychosocial effects of MPS across the lifespan will be crucial for planning service development and supporting the neuropsychological needs of adult patients and their families.

Cognitive issues in patients with IDH mutant gliomas: from neuroscience to clinical neuropsychology.

PURPOSE: The understanding of cognitive symptoms in patients with IDH-Mutant gliomas (IDH-Mut) is rapidly developing. In this article, we summarize the neuroscientific knowledge base regarding the influence of IDH-Mut tumors and their treatment on cognition and provide guidance regarding the management of these symptoms in patients. METHODS: We performed a review of peer reviewed publications relevant to IDH-Mut glioma and cognitive outcomes and provide an overview of the literature as well as a case example to clarify management strategies. RESULTS: At the time of presentation, patients with IDH-Mut gliomas have a favorable cognitive profile as compared with those with IDH-wild type (WT) tumors. The relatively low cognitive burden may reflect the slower growth rate of IDH-Mut tumors, which is less disruptive to both local and widespread neural networks. Human connectomic research using a variety of modalities has demonstrated relatively preserved network efficiency in patients with IDH-Mut gliomas as compared with IDH-WT tumors. Risk of cognitive decline from surgery can potentially be mitigated by careful integration of intra-operative mapping. Longer term cognitive risks of tumor treatment, including chemotherapy and radiation, are best managed by instituting neuropsychological assessment as part of the long-term care of patients with IDH-Mutant glioma. A specific timeline for such integrative care is provided. CONCLUSIONS: Given the relative recency of the IDH-mutation based classification of gliomas, as well as the long time course of this disease, a thoughtful and comprehensive strategy to studying patient outcomes and devising methods of cognitive risk reduction is required.

Historical trends in reporting effect sizes in clinical neuropsychology journals: A call to venture beyond the results section.

OBJECTIVE: For decades, quantitative psychologists have recommended that authors report effect sizes to convey the magnitude and potential clinical relevance of statistical associations. However, fewer than one-third of neuropsychology articles published in the early 2000s reported effect sizes. This study re-examines the frequency and extent of effect size reporting in neuropsychology journal articles by manuscript section and over time. METHODS: A sample of 326 empirical articles were drawn from 36 randomly selected issues of six neuropsychology journals at 5-year intervals between 1995 and 2020. Four raters used a novel, reliable coding system to quantify the extent to which effect sizes were included in the major sections of all 326 articles. RESULTS: Findings showed medium-to-large increases in effect size reporting in the Methods and Results sections of neuropsychology journal articles that plateaued in recent years; however, there were only very small and nonsignificant changes in effect size reporting in the Abstract, Introduction, and Discussion sections. CONCLUSIONS: Authors in neuropsychology journals have markedly improved their effect size reporting in the core Methods and Results sections, but are still unlikely to consider these valuable metrics when motivating their study hypotheses and interpreting the conceptual and clinical implications of their findings. Recommendations are provided to encourage more widespread integration of effect sizes in neuropsychological research.

Was the COVID-19 Pandemic Associated with Gender Disparities in Authorship of Manuscripts Submitted to Clinical Neuropsychology Journals?

OBJECTIVE: The COVID-19 pandemic exacerbated gender disparities in some academic disciplines. This study examined the association of the pandemic with gender authorship disparities in clinical neuropsychology (CN) journals. METHOD: Author bylines of 1,018 initial manuscript submissions to four major CN journals from March 15 through September 15 of both 2019 and 2020 were coded for binary gender. Additionally, authorship of 40 articles published on pandemic-related topics (COVID-19, teleneuropsychology) across nine CN journals were coded for binary gender. RESULTS: Initial submissions to these four CN journals increased during the pandemic (+27.2%), with comparable increases in total number of authors coded as either women (+23.0%) or men (+25.4%). Neither the average percentage of women on manuscript bylines nor the proportion of women who were lead and/or corresponding authors differed significantly across time. Moreover, the representation of women as authors of pandemic-related articles did not differ from expected frequencies in the field. CONCLUSIONS: Findings suggest that representation of women as authors of peer-reviewed manuscript submissions to some CN journals did not change during the initial months of the COVID-19 pandemic. Future studies might examine how risk and protective factors may have influenced individual differences in scientific productivity during the pandemic.

Performance on the African neuropsychology battery using the learning ratio in a sample of healthy Congolese.

OBJECTIVE: Using the African Neuropsychology Battery (ANB), we seek to develop normative data by examining the demographic effects for two learning process scores: initial learning (Trial One) and learning ratio (LR, the percentage of items learned relative of to-be-learned material following Trial 1). METHODS: Healthy participants from the Democratic Republic of Congo completed the four memory tests of the ANB: the African Story Memory Test (ASMT), African List Memory Test (ALMT), African Visuospatial Memory Test (AVMT), and African Contextual Visuospatial Memory Test (ACVMT). We developed indices of learning for each subtest, as well as aggregate learning indices for Trial 1 and LR, and composite indices examining verbal, visual, contextual, and noncontextual learning, and grand indices comprising all four subtests. RESULTS: Trial 1 and LR scores each demonstrated acceptable intercorrelations across memory tests. We present normative data for Trial 1 and LR by age and education. CONCLUSION: These data provide normative standards for evaluating learning in Sub-Saharan Africa.

Neurophysiology, Neuropsychology, Epilepsy, 2022: Hills We Have Climbed and the Hills Ahead. Cognition and Sensory Systems in Healthy and Diseased Subjects.

This article summarizes selected presentations from a session titled "Cognition and Sensory Systems in Healthy and Diseased Subjects", held to highlight and honor the work of Dr. Marilyn Jones-Gotman. The session was part of a two-day symposium, "Neurophysiology, Neuropsychology, Epilepsy, 2022: Hills We Have Climbed and the Hills Ahead". The session presented research on epilepsy and sensory systems by colleagues and former trainees of Dr. Jones-Gotman. The extended summaries provide an overview of historical and current work in the neuropsychology of epilepsy, neuropsychological and neuroimaging approaches to understanding brain organization, sex differences in brain mechanisms underlying neurological disorders, dietary influences on brain function and cognition, and expertise in olfactory training and language experiences and their implications for brain organization and structure.

Neurophysiology, Neuropsychology, and Epilepsy, in 2022: Hills We Have Climbed and Hills Ahead. Neurophysiology in epilepsy.

Since the discovery of the human electroencephalogram (EEG), neurophysiology techniques have become indispensable tools in our armamentarium to localize epileptic seizures. New signal analysis techniques and the prospects of artificial intelligence and big data will offer unprecedented opportunities to further advance the field in the near future, ultimately resulting in improved quality of life for many patients with drug-resistant epilepsy. This article summarizes selected presentations from Day 1 of the two-day symposium "Neurophysiology, Neuropsychology, Epilepsy, 2022: Hills We Have Climbed and the Hills Ahead". Day 1 was dedicated to highlighting and honoring the work of Dr. Jean Gotman, a pioneer in EEG, intracranial EEG, simultaneous EEG/ functional magnetic resonance imaging, and signal analysis of epilepsy. The program focused on two main research directions of Dr. Gotman, and was dedicated to "High-frequency oscillations, a new biomarker of epilepsy" and "Probing the epileptic focus from inside and outside". All talks were presented by colleagues and former trainees of Dr. Gotman. The extended summaries provide an overview of historical and current work in the neurophysiology of epilepsy with emphasis on novel EEG biomarkers of epilepsy and source imaging and concluded with an outlook on the future of epilepsy research, and what is needed to bring the field to the next level.

Remote testing in Abbiategrasso (RTA): results from a counterbalanced cross-over study on direct-to-home neuropsychology with older adults.

BACKGROUND: The SARS-CoV-2 pandemic forced to rethink teleneuropsychology, since neuropsychological assessments started to be performed by phone or videoconference, with personal devices and without direct assistance from the clinician, a practice called "Direct-To-Home NeuroPsychology" (DTH-NP). AIMS: The present study, employing a counterbalanced cross-over design, was aimed at evaluating (1) the feasibility and (2) the acceptability of DTH-NP in Italian older adults without previously diagnosed neurocognitive disorder, (3) the comparability between remote and face-to-face administration of selected neuropsychological tests. METHODS: Fifty-eight community-dwelling older adults (65-85 years) were randomly assigned to one of two groups performing a complete neuropsychological assessment remotely (via phone call and videoconference) and face-to-face, in a counterbalance order, 8 weeks apart. The study recruitment rate was calculated, and the number of uncompleted tests and acceptability questionnaire responses were compared between the two administration modalities. Comparability was defined as good reliability of DTH-NP (intraclass correlation coefficient) and agreement between remote and face-to-face scores (Bland-Altman plots). RESULTS: Recruitment rate was 81%, with a preference for telephonic contact (79%). The acceptability analysis did not reveal any issues related to the DTH-NP assessment, even if most participants would rather repeat it face-to-face. Tests assessing short-term memory, language, and reasoning showed good comparability. DISCUSSION AND CONCLUSION: Our results point out to a good recruitment rate in a DTH-NP study in an Italian population of older adults (mean age = 80), satisfying acceptability of DTH-NP and remote-face-to-face comparability of certain verbally mediated tests. Further studies including larger samples in videoconference modality, and outpatients, could better clarify its strengths and limits.

The ambivalence toward neuropsychology in dementia research, diagnosis, and drug development: Myths and misconceptions.

Clinical assessment remains the gold standard for diagnosing dementia, monitoring progression, and conducting clinical research. Biomarkers hold promise for targeted therapeutic approaches, selection of participants in clinical trials, and direct physiological efficacy readouts. However, the anchoring of biomarker research to clinical symptomatology is often based on short and insensitive cognitive screening. This gives the impression that cognitive symptoms occur relatively late and that their progression in the early stages of the disease is slow. A thorough cognitive assessment is a powerful tool and has a key role in the accurate and early diagnosis of dementia. It is very different from the cognitive testing usually seen in biomarker research and drug development. Yet the distinction between these approaches is unclear to many. This paper highlights the misconceptions around cognitive research in dementia and suggests a way forward to facilitate biomarker and drug development through the improved utility of cognitive assessment tools.

[Psychoses on the Schizophrenia Spectrum in Adolescence: A Cross-sectional Study of Factors Influencing Neuropsychology, Treatment Outcome, and Negative Symptoms]. / Psychosen aus dem schizophrenen Formenkreis im Jugendalter: Einflussfaktoren auf Neuropsychologie, Behandlungserfolg und Negativsymptomatik.

Psychoses on the Schizophrenia Spectrum in Adolescence: A Cross-sectional Study of Factors Influencing Neuropsychology, Treatment Outcome, and Negative Symptoms Abstract: Objective: The present study evaluated the factors influencing the course of disease of children and adolescents in an inpatient rehabilitation suffering from psychosis within the schizophrenia spectrum. Methods: 33 patients (mean age 19.4 years, SD = 2.3), 12 of (36 %) were female, participated. They were assessed with clinical interviews (IRAOS, SANS/SAPS), neuropsychological tests (WAIS-IV, TMT), and questionnaires (FBB, BSCL). Results: The neuropsychological functioning level and the premorbid cognitive performance were correlated, as were treatment success from the patient's perspective with a good relationship with the therapist, and greater negative symptomatology with a longer duration of untreated psychosis (DUP) and a longer initial hospital stay. Conclusion: Possible approaches to improving the treatment of adolescents with psychosis of the schizophrenic spectrum include a shortening of the DUP and a good therapeutic relationship.

[Relevance of Neuropsychology When Assessing Fitness to Drive After Stroke]. / Relevanz der Neuropsychologie bei der Beurteilung der Fahreignung nach Schlaganfall.

Relevance of Neuropsychology When Assessing Fitness to Drive After Stroke Abstract: Under normal circumstances, the mobility of oneself is often taken for granted. After a brain injury the quality of life is different and getting back into society may be difficult. Observing the patient's remaining qualities, the doctor or guardian will present guidelines. Often the patient no longer thinks of his former life, but only thinks of his taken away freedom. The doctor or guardian is often blamed for this. The patient will either accept the circumstances or could become aggressive or resentful. It is important for all to come together and present future guidelines. For street safety it is important and a duty for both parties to look into and solve this problem.

Neurocognitive risk in sickle cell disease: Utilizing neuropsychology services to manage cognitive symptoms and functional limitations.

Sickle cell disease (SCD) is an inherited blood disorder that is associated with developmental delays and neurocognitive deficits. This review details key findings related to neurocognitive outcomes for children and adults with emphasis on the impact of neurological correlates and disease severity. Associations between neurocognition, demographic factors and social determinants of health are also reviewed. Emerging literature has reported on the neurocognitive impact of SCD in children and adolescents in Africa and Europe, including children from immigrant communities. Neurocognitive deficits are linked to poor functional outcomes, including transition from paediatric to adult care, medication adherence and unemployment. Integrating neuropsychology into multidisciplinary care for individuals with SCD can assist with identification and management of neurocognitive concerns, intervention development, individualized care plan development and continued multidisciplinary research.

The meaning of significant mean group differences for biomarker discovery.

Over the past decade, biomarker discovery has become a key goal in psychiatry to aid in the more reliable diagnosis and prognosis of heterogeneous psychiatric conditions and the development of tailored therapies. Nevertheless, the prevailing statistical approach is still the mean group comparison between "cases" and "controls," which tends to ignore within-group variability. In this educational article, we used empirical data simulations to investigate how effect size, sample size, and the shape of distributions impact the interpretation of mean group differences for biomarker discovery. We then applied these statistical criteria to evaluate biomarker discovery in one area of psychiatric research-autism research. Across the most influential areas of autism research, effect size estimates ranged from small (d = 0.21, anatomical structure) to medium (d = 0.36 electrophysiology, d = 0.5, eye-tracking) to large (d = 1.1 theory of mind). We show that in normal distributions, this translates to approximately 45% to 63% of cases performing within 1 standard deviation (SD) of the typical range, i.e., they do not have a deficit/atypicality in a statistical sense. For a measure to have diagnostic utility as defined by 80% sensitivity and 80% specificity, Cohen's d of 1.66 is required, with still 40% of cases falling within 1 SD. However, in both normal and nonnormal distributions, 1 (skewness) or 2 (platykurtic, bimodal) biologically plausible subgroups may exist despite small or even nonsignificant mean group differences. This conclusion drastically contrasts the way mean group differences are frequently reported. Over 95% of studies omitted the "on average" when summarising their findings in their abstracts ("autistic people have deficits in X"), which can be misleading as it implies that the group-level difference applies to all individuals in that group. We outline practical approaches and steps for researchers to explore mean group comparisons for the discovery of stratification biomarkers.