Medicine and Pharmacology

Abstract: Background: Early diagnosis in Bipolar Disorder Type I (BDI) is essential for a better outcome. Endophenotypes are an important subtype of biomarkers but to date very few have been discovered in psychiatry. Some previous studies show anxiety-trait as a possible Bipolar Disorder Type I endophenotype, but there is a lack of replication in another populations. Objective: Our study evaluate the presence of anxiety-trait and bipolarity risk in Bipolar Disorder Type I first-degree relatives (FDR). Methods: We evaluated 219 participants (119 healthy controls, 68 healthy FDR and 32 affective unipolar FDR) including socio-demographic data, psychiatric history, Spielberg's State and Trait Anxiety Inventory (STAI), General Health Questionnaire, Beck Depression Scale, and Mood Disorder Questionnaire (MDQ) scores as a measure of bipolarity risk. Results: In our sample, affective unipolar BDI's first degree relatives showed highest scores in STAI anxiety-trait compared to healthy controls and BDI's healthy first degree relatives. STAI-Trait only correlated significantly with bipolarity risk (MDQ) in the unipolar affective first degree relatives subgroup. Conclusion: Unless further investigation is needed, anxiety trait could be a possible BDI's endophenotype candidate since it seems to have high heritability and would confer higher lifetime risk to develop unipolar affective disorder and tendency to bipolarity.

Abstract: Objectives: Paramedics are at elevated risk for adverse mental health outcomes due to occupational exposures including trauma, workplace violence, and chronic operational stress. Community Paramedicine (CP) represents an evolving model of care in which paramedics provide scheduled, non-urgent clinical and psychosocial support, potentially altering exposure profiles and the associated mental health risks. Our objective was to estimate the prevalence of mental health concerns among community paramedics and compare their risk of adverse mental health outcomes with paramedics working in 9-1-1 emergency response roles. Methods: We conducted a cross-sectional survey of paramedics from two Ontario services during compulsory in-person continuing medical education sessions from September to December 2024. Participants completed validated self-report screening tools for posttraumatic stress disorder, major depressive disorder, generalized anxiety disorder, insomnia, alcohol use, and burnout. We used logistic regression models adjusted for demographic variables to assess the association between CP role and mental health outcomes. Results: A total of 995 paramedics participated (96% of eligible), including 63 (6%) assigned to CP roles. Overall, 12% screened positive for PTSD, 25% for major depressive disorder, 23% for generalized anxiety disorder, 30% for insomnia, and 36% for at least moderate burnout. CPs had significantly lower adjusted risk of major depressive disorder compared to paramedics in 9-1-1 response roles (adjusted odds ratio [aOR] 0.45, 95% confidence interval [CI] 0.20-0.98). For other outcomes, our point estimates favored lower risk among CPs but did not reach statistical significance, including a composite outcome of PTSD, major depressive disorder, or generalized anxiety disorder (aOR 0.81, 95% CI 0.46-1.45). Conclusions: Community paramedics demonstrated a lower adjusted risk of major depressive disorder and a consistent, though non-significant, pattern toward lower risk across multiple mental health outcomes compared to paramedics in 9-1-1 response roles. These findings suggest a potentially different occupational risk profile associated with CP practice environments. Further longitudinal and mixed-methods research is warranted.

Abstract: Pediatric acute-onset neuropsychiatric presentations occurring in the context of prior streptococcal exposure remain clinically important but diagnostically inconclusive, particularly at the interface between PANS and PANDAS. This observational cohort study examined whether serological, psychometric, and electroencephalographic findings converged within a clinically selected pediatric psychiatric sample. Children and adolescents presenting with acute-onset or abruptly worsened neuropsychiatric symptoms and a history suggestive of prior streptococcal exposure were recruited over a 12-month period through inpatient and outpatient child psychiatric services. Of 154 screened cases, 96 with analyzable baseline data were retained and stratified by ASO status. Symptom burden was quantified using the Pediatric Acute-onset Neuropsychiatric Syndrome 31-Item Symptom Rating Scale (PANS-31) and examined in relation to ASO titers, time since the last reported streptococcal infection, EEG findings, and selected developmental and clinical-history variables. Higher ASO values were strongly associated with greater PANS-31 symptom burden, whereas a shorter interval since the last reported streptococcal infection was associated with both higher ASO titers and higher symptom scores. PANS-31 showed good total-scale internal consistency and meaningful domain-level convergence with age-appropriate CSI-4 and ASI-4 domains. These findings do not support a disease-specific biomarker model, but suggest that higher antistreptococcal serology, more recent streptococcal exposure, and greater neuropsychiatric burden may cluster within a more clearly expressed clinical phenotype in a real-world psychiatric environment.

Abstract: Autism spectrum disorder (ASD) is a neurological condition with an increasingly high incidence rate due to more effective diagnostic tools. The symptoms of ASD vary widely, making it difficult to detect. It represents a spectrum of alterations ranging from mild indications to severe impairments. Given this clinical presentation, each patient should be treated on an individual basis. Nevertheless, certain neuropathological changes are common, although the background of this disorder remains still unknown. Therefore, some research aimed at better understanding the pathology of the neurological alterations in ASD, as well as the possibilities for early diagnosis and treatment of this disorder, is urgently needed. This study presents the results of the studies on some selected proteins such as Tau protein, NFL, BDNF as well as IGF-1 that appear to be the best protein candidates for better understanding the causes of autism, as well as for use as fluid biomarkers in diagnosis and monitoring of ASD.

Abstract: Background: Borderline Personality Disorder (BPD) lacks approved pharmacological treatments despite a high symptom burden. Artificial intelligence (AI) offers new opportunities to accelerate drug discovery and model therapeutic effects. Objective: This study will outline an AI‑enabled framework for identifying and modelling a novel pharmacological agent for BPD, designed to meet five therapeutic goals: (1) reduce depression without increasing impulsivity and suicidality, (2) reduce suicidality without sedation, (3) limit side effects and weight gain, (4) reduce polypharmacy, and (5) provide combined antidepressant, anti-suicidal, mood‑stabilising, and antipsychotic effects.Methods: Three AI‑driven approaches will be piloted: (1) deep‑learning‑based compound generation, (2) natural‑language‑processing (NLP) evidence synthesis, and (3) predictive modelling of symptom trajectories. These methods will be used to design and characterise a hypothetical multimodal compound, BPD‑AI‑01, including its predicted 3D molecular structure and receptor binding profile. All analyses will use publicly available data and in silico simulations.Results: AI‑guided modelling will generate BPD‑AI‑01, a candidate molecule predicted to act as a partial agonist at 5‑HT1A receptors, a modulator at NMDA‑associated sites, and a weak antagonist at 5‑HT2A/D2 receptors, with low affinity for histaminergic and muscarinic receptors. Its 3D structure will be optimised to balance CNS penetration with reduced metabolic burden. Simulated trajectories will suggest potential antidepressant, anti-suicidal, mood‑stabilising, and antipsychotic‑like effects without marked sedation or weight gain. Conclusions: AI‑enabled pharmacological research may support the design of next‑generation medications for BPD that address multiple symptom domains within a single molecule. Empirical validation will be required before any clinical application.

Abstract: Major depressive disorder remains a leading cause of disability, and decades of monoam-ine-centered pharmacology have yielded delayed and often incomplete relief. Rapid-acting antidepressants reshaped the field by linking swift symptom improvement to glu-tamatergic plasticity, yet durable benefit depends on how newly reconfigured circuits are stabilized and tuned. This review synthesizes evidence that antidepressant efficacy arises from the coordinated engagement of synaptic plasticity, spanning induction and consoli-dation, and intrinsic excitability, which provides gain control, and proposes an integrated framework to guide future discovery. It first outlines induction through N-methyl-D-aspartate receptors (NMDARs) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), exemplified by ketamine and esketamine, followed by consoli-dation mediated by tropomyosin receptor kinase B (TrkB) signaling, translational disinhi-bition via eukaryotic elongation factor 2 kinase (eEF2K), and presynaptic stabilization in-dexed by synaptic vesicle glycoprotein 2A (SV2A); together, these processes transform transient potentiation into persistent network change. It then highlights intrinsic excitabil-ity, emphasizing voltage-gated potassium channel subfamily Q (Kv7), hyperpolarization-activated cyclic nucleotide-gated (HCN), and G protein-gated inwardly rectifying potassi-um (GIRK) channels as circuit-level governors that normalize firing and limit relapse-prone hyperexcitability. Finally, it presents a phase-aware Induction–Consolidation–Maintenance (ICM) roadmap, supported by SV2A positron emission tomography (PET) and electroencephalography (EEG)/functional magnetic resonance imaging (fMRI) bi-omarkers, to personalize treatment timing and combinations. This dual-target strategy re-frames antidepressants as network reprogrammers and suggests broader relevance for circuit repair across neurology and psychiatry.

Abstract: Anxiety disorders represent one of the most prevalent challenges in contemporary mental health, characterized by a hyperactivation of fear circuits. Although conventional pharmacotherapy (benzodiazepines and SSRIs) is effective, it often entails significant adverse effects and a risk of dependence. This article explores the scientific evidence and the functional neuroanatomy underlying clinical phytotherapy as an adjunctive strategy. The pharmacodynamics of key species such as Piper methysticum, Passiflora incarnata, Lavandula angustifolia, and Crocus sativus are analyzed, highlighting their structural interaction with the amygdaloid complex, the hippocampus, and the prefrontal cortex, as well as the modulation of GABAergic receptors and voltage-dependent calcium channels. It is concluded that the integration of standardized extracts offers a neurobiologically viable therapeutic alternative under rigorous professional supervision.

Abstract: Background/Objectives: Treatment-resistant depression (TRD) remains one of the most urgent unmet needs in psychiatry, while its therapeutic pipeline is evolving rapidly. To characterize current development trajectories, we conducted a registry-anchored mapping of interventional trials in adults with major depressive disorder and treatment resistance (MDD-TRD), with the aim of defining the distribution of intervention types, endpoint choices, and key design features across the active trial landscape. Methods: We sys-tematically searched ClinicalTrials.gov, the EU Clinical Trials Information System, and ISRCTN for interventional MDD-TRD trials registered up to September 18, 2025. After data cleaning and cross-registry deduplication, 237 unique trials were retained. Inter-ventions were categorized as pharmacological, device-based, biologic/novel, or digi-tal-combined. Primary endpoints were flagged as standard when they explicitly refer-enced the Montgomery–Åsberg Depression Rating Scale or Hamilton Depression Rating Scale. We also examined developmental phase, sample size, and recurrent methodo-logical features. Results: Digital or hybrid programs accounted for most trials (73.8%), followed by device-based neuromodulation studies (23.6%), pharmacological interven-tions (2.1%), and biologic/novel approaches (0.4%). Standard clinician-rated primary endpoints were used in 63.3% of studies. Trial development was concentrated in mid-phase designs, whereas sample sizes were generally modest (median 49; inter-quartile range, 19-87). Overall, the registered landscape suggested a shift away from novel molecules and toward digital-somatic hybrid models and precision neuromodu-lation. Across modalities, increasing attention was directed to durability of response, functioning, and patient-reported outcomes, with adaptive and enrichment-based designs appearing with greater frequency. Conclusions: The contemporary TRD trial ecosystem appears to be reorganizing around stratified, biomarker-informed, and multimodal care rather than conventional drug development alone. This registry-based mapping provides a near-real-time overview of the field and may support future harmonization of trial endpoints and design standards.

Abstract: Psychedelic drugs are serotonergic hallucinogens that can be divided into two types: naturally occurring (psilocybin, psilocin, and N,N-dimethyltryptamine) and synthetic (LSD, MDMA, 2,5-dimethoxy-4-iodoamphetamine, and ketamine). Psychedelics generally work on 5-hydroxytryptamine receptors and might be useful in cognitive enhancement, brain connectivity, neuroplasticity, and neuronal regeneration. These properties could be used in the pharmacological treatment of selected mental disorders. Autism spectrum disorders include a group of developmental disorders characterized by social communication issues, the presence of restricted interests as well as repetitive behaviors that impact the quality of life of patients and their caregivers. Currently, there are no authorized drugs for the treatment of the symptomatic features of ASD, but drugs are used for comorbid psychopathological aspects, but the efficacy and tolerability of such treatments are often questionable. Here, studies demonstrating the therapeutic utility of using psychedelic substances in autism are reported. These findings suggest a therapeutic potential of psychedelics for some aspects of symptoms associated with autism spectrum disorder.

Abstract: Behavioral addiction in digital environments is an increasingly relevant neurobehavioral phenomenon characterized by persistent engagement with high-frequency, algorithmically optimized reward stimuli. Although neural correlates of addictive behaviors have been widely studied, current models only partly explain how modern reinforcement environments reorganize behavior at the systems level. This review introduces Reward Instability Theory, a conceptual dynamical systems framework proposing that behavioral addiction may emerge as an attractor-like state within distorted reward landscapes shaped by high-density and high-variance reinforcement signals. The model shifts focus from static behavioral descriptions toward a systems account of motivation involving reinforcement learning, salience attribution, executive control, and environmental reward structure. We propose that digital environments may increase reinforcement density and reward variance, promoting dominant reward peaks and reducing behavioral diversity. To formalize these dynamics, we outline the Behavioral Reward Instability Index (BRII) as a heuristic systems construct integrating individual reward sensitivity, environmental reinforcement structure, and behavioral variability. The framework also situates established addiction models—including incentive sensitization, habit formation, and allostatic regulation—within a shared dynamical architecture. In addition, digital phenotyping is discussed as a potential empirical strategy for testing reward instability, while acknowledging limitations related to signal noise, ecological validity, bias, and privacy.

Abstract: Introduction: The clinical relationship between sexual violence and paraphilia is complex, with research indicating several risk factors; however, having paraphilia does not automatically mean an individual will commit sexual violence. Children are considered more vulnerable than able-bodied adults. This is why investigating the subjective psychopathological profile of paraphilia is important, both for prevention and punishment. The use of the term "paraphilia" refers to an intense and persistent psychophysical state of sexual interest in activities or objects that by conventional nature do not have that specific connotation or use. In literature, there is a clear difference between paraphilia and paraphilic disorder. The current validation study aims to introduce the “Perrotta Paraphilic Global Spectrum of Gradation”, which is the basis of a questionnaire that considers both intensity and frequency of the symptoms described by the patient and therefore can distinguish between the functional condition and the disorder, distinguishing between paraphilic interest, paraphilia and paraphilic disorder, in particular for the protection of minors and vulnerable minorities. Method: A validation study with 198 participants was set up, with statistical analysis of the data relating to the population sample. Results: In the case of content validity, all items obtained a CVR score greater than the cut-off value, with a minimum score of 0.902. Therefore, all items of the scale were considered essential. Also, regarding the relevance of the items in exploring the constructs investigated, optimal values of I-CVI (1.000) and scale (0.918) were obtained. Cronbach's alpha is 0.901 and McDonald’s Omega is 0.871. Therefore, all items were rated as relevant. Using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) we achieve construct validity and therefore the validity of the 9 clinical elements. Conclusion: The paraphilic manifestation has clinical relevance and the instrumental proposal that distinguishes the high-functioning forms from the low-functioning ones is suggestive for use on a larger scale.

Abstract: Background/Objectives: Intermittent fasting (IF) has been widely investigated for its metabolic effects, including improvements in insulin sensitivity, lipid metabolism, and inflammatory markers. However, its psychological and experiential dimensions remain comparatively underexplored. The present narrative review examines IF within a psychobiological framework, integrating evidence from metabolic science, neuroendocrinology, and affective neuroscience to explore its potential impact on emotional regulation and interoceptive processes. Methods: A structured narrative literature search was conducted across PubMed, Scopus, and Google Scholar, focusing on studies published between 2000 and 2025. Eligible studies included human and relevant animal research addressing metabolic, hormonal, interoceptive, and psychological responses to IF. Evidence was synthesized thematically to identify convergent mechanisms linking metabolic adaptations to emotional and regulatory outcomes. Results: The available literature indicates that IF induces a metabolic shift toward lipid utilization, characterized by increased lipolysis, elevated circulating free fatty acids, and enhanced ketone body production, particularly β-hydroxybutyrate. These metabolic changes are accompanied by modulation of neuroendocrine pathways, including transient activation followed by adaptive recalibration of the hypothalamic–pituitary–adrenal axis, as well as alterations in insulin, leptin, and ghrelin signaling. Emerging evidence suggests that these physiological adaptations may influence central nervous system functioning through mechanisms involving neuroinflammation, mitochondrial efficiency, and synaptic plasticity. At the psychological level, IF appears to modulate interoceptive signaling, with heterogeneous emotional outcomes: structured fasting protocols have been associated with modest improvements in depressive symptoms and perceived stress in metabolically healthy individuals, whereas increased irritability, anxiety, or behavioral rigidity may occur in the presence of psychological vulnerability. Individual variability appears to be associated with differences in interoceptive sensitivity, stress reactivity, and traits related to anxiety, perfectionism, and eating-related pathology. Conclusions: Overall, IF may be conceptualized as a context-dependent psychobiological stressor whose effects extend beyond metabolic regulation to include interoceptive and emotional processes. These effects appear bidirectional, potentially promoting psychological resilience in some individuals while increasing the risk of affective destabilization or maladaptive behaviors in others. Current evidence remains limited by a lack of integrative and longitudinal studies combining metabolic and psychological measures. Future research adopting multidisciplinary approaches is needed to clarify the mechanisms underlying individual variability and to better define the potential benefits and risks of IF in both clinical and non-clinical populations.

Abstract: Background: A significant percentage of patients with major depressive disorder (MDD) fail to achieve remission with antidepressant monotherapy and frequently experience residual mood and cognitive symptoms that impair their functional recovery. Thus, an augmentation with vortioxetine, a multimodal antidepressant with reported cognitive benefits, might be a useful strategy for such patients. Methods: We conducted a 12-week naturalistic, prospective observational study in a Malaysian university hospital. 40 adults with MDD and inadequate response to at least eight weeks of antidepressant therapy received either adjunctive vortioxetine or optimization of their existing antidepressant as part of treatment-as-usual care. Depressive symptoms were assessed using the Montgomery–Åsberg Depression Rating Scale (MADRS), cognitive symptoms using the Perceived Deficits Questionnaire-5 (PDQ-D5), and global improvement using the Clinical Global Impressions–Improvement (CGI-I) scale. Results: Both groups demonstrated significant improvements in MADRS and PDQ-D5 scores over 12 weeks (p < 0.001). Remission rates at Week 12 were high in both groups (93.8% adjunctive vortioxetine vs 86.7% control). While between-group differences were not statistically significant, patients receiving vortioxetine showed earlier improvement in several core depressive symptoms, including apparent sadness, suicidal ideation, and appetite disturbance. Greater clinician-rated global improvement was observed in the vortioxetine group at Week 12 (87.5% vs 40.0%, p < 0.001). Conclusions: In this outpatient clinical setting, adjunctive vortioxetine was associated with earlier improvement of core depressive symptoms and greater global clinical improvement compared with optimization of existing antidepressant therapy. Collectively, these findings suggest adjunctive vortioxetine as a clinically relevant option for patients with MDD who show an inadequate response to antidepressant monotherapy.

Abstract: Background: Subthreshold depression is a prevalent condition among the elderly and often remains untreated due to limited efficacy and poor tolerability of standard antidepressants. Choline alfoscerate, a cholinergic precursor, is indicated for the treatment of a condition, pseudodepression in the elderly, that is currently clinically classified as subthreshold depression in older adults. Also, choline alphoscerate has shown neuroprotective and antidepressant-like effects. Objective: This pilot study aims to evaluate the efficacy and safety of choline alfoscerate in elderly patients with subthreshold depressive symptoms, using the most recent diagnostic assessments of the clinical condition and the treatment outcomes. Methods: Seventeen patients aged ≥65 years were enrolled in an open-label, single-arm study and received 1,200 mg/day of choline alfoscerate for 8 weeks. Clinical and neuropsychological assessments were performed at baseline, after 4 weeks and at study end. Results: A statistically significant improvement was observed in depressive symptoms as reflected by reductions in HAMD-17 (p < 0.001) and GDS-15 scores (p < 0.05), as well as in overall clinical severity assessed by the Clinical Global Impression–Severity scale (CGI-S, p < 0.05). No significant changes were noted in cognitive performance (MOCA) or apathy (AES-I). The treatment was well tolerated. Conclusion: Choline alfoscerate represents an effective and safe option for subthreshold depression in older adults. Further controlled and long-term studies are warranted to confirm its efficacy not only on depressive symptoms but also on cognitive function and other relevant clinical outcomes, such as global functioning in elderly patients with subthreshold depression.

Abstract: Gambling disorder (GD) is associated with severe psychosocial impairment, impulsive dyscontrol, affective instability, and increased suicidal risk. Pharmacological options remain limited, particularly for patients whose presentation is dominated by transdi-agnostic dimensions such as impulsivity, emotional dysregulation, and suicidal vul-nerability. Lithium may be relevant because of its anti-suicidal properties and potential effects on affective instability and behavioral dyscontrol. We describe a 40-year-old man with sports-betting-related GD who presented after a suicidal crisis in the context of fi-nancial collapse and marital conflict. He entered a structured multimodal program in-cluding psychiatric care, lithium carbonate, individual psychotherapy, psychoeduca-tional and self-help groups, family intervention, and social support. After lithium initi-ation and titration to 600 mg/day, the patient showed progressive affective stabilization, remission of suicidal ideation, reduced gambling urges, and sustained abstinence, with one brief lapse that was rapidly contained. Psychometric reassessment paralleled the clinical course, showing reduced functional impairment, near-complete resolution of gambling-related cognitive distortions, and a shift from a highly impulsive/dysregulated gambling profile toward an emotionally vulnerable pattern. Although causal inference is limited by the single-case design and multimodal treatment context, this case supports the hypothesis that lithium may help stabilize core vulnerability dimensions in selected GD presentations, particularly impulsivity, affective dysregulation, and suicidality.

Abstract: Substance use disorders (SUD) arising during neurobiologically sensitive developmental windows may constitute a structurally distinct diagnostic category, fundamentally different from SUD with adult onset. This concept paper proposes the term Complex Addiction-Developmental Disorder (CADD) to name and frame this clinical entity. The argument draws an analogy with the distinction between PTSD and Complex PTSD (C-PTSD): just as repeated developmental trauma does not produce the same disorder as adult trauma, repeated substance use during childhood or adolescence does not produce the same disorder as adult addiction. What it produces instead is a structurally different psychopathology — one with its own risk profiles, longitudinal characteristics, and treatment logic. The core of CADD is the constitution of substance-bound self- and identity-components through repeated pharmacological exposure during active neuroplastic phases of personality development. This gives rise to three defining clinical features: a relationship to the substance that functions like attachment rather than hedonic craving; an abstinence phenomenology resembling identity rupture rather than withdrawal; and a therapeutic priority of identity integration over detoxification. The concept has not yet been empirically validated and is offered here as a hypothesis for scientific discussion.

Abstract: Speech in autism spectrum disorder (ASD) carries distinctive acoustic signatures that can offer valuable insight into the nature of autistic communication and its identification. Among these, vowel production remains insufficiently understood, despite its central role in speech intelligibility. This study investigates whether ASD is associated with systematic differences in vowel production. Eighteen Cypriot Greek adults with ASD and 18 peers with neurotypical development (ND), comparable in age, gender, education, nonverbal IQ, and verbal fluency, completed a controlled reading task. Participants produced disyllabic pseudowords embedding the five Greek vowels across four stress-syllable contexts. Acoustic analyses measured vowel-space organization, static spectral properties (F0, F1, F2, F3), dynamic trajectories (ΔF0, ΔF1, ΔF2, ΔF3), duration, and voice-quality indices (jitter, shimmer, harmonic-to-noise ratio [HNR], intensity). Bayesian models were used to evaluate group and vowel-specific differences. The results revealed a larger vowel-space area and greater vowel-space dispersion in the ASD group relative to the ND group, indicating a more expanded and dispersed acoustic vowel system. Group differences in individual acoustic measures were mostly selective rather than global: the clearest effects emerged in vowel-specific patterns of pitch, formants, and some dynamic formant measures. By contrast, duration, jitter, shimmer, and intensity did not show robust vowel-specific group differences. Among voice-quality measures, HNR showed the most consistent group difference, with ASD speakers showing higher HNR across all vowels. These findings challenge the notion of a single, uniform autistic voice, instead demonstrating that autism-related speech differences are multidimensional, vowel-specific, and language-sensitive. They therefore underscore the critical importance of segment-focused, cross-linguistically grounded approaches for advancing theory, assessment, and future speech-based identification in autism research.

Abstract: Dementia affects approximately 55 million people worldwide, yet the psychological experience of diagnosis and the determinants of post-diagnostic wellbeing remain underexplored relative to biomedical research priorities. The existing literature has been predominantly deficit-oriented, focusing on cognitive decline, neuropsychiatric symptoms, and carer burden, with limited attention to preserved psychological capacities and what supports flourishing following diagnosis. This narrative review applies a positive psychology framework to synthesise evidence on meaning, purpose, hope, and post-diagnostic adjustment in early-stage dementia. A central empirical observation motivating the review is the wellbeing paradox: the consistent finding that subjective wellbeing in early-to-moderate dementia is frequently higher than carers and clinicians predict, and is more strongly associated with psychosocial variables than with objective cognitive status. Evidence from the IDEAL cohort and related longitudinal research demonstrates that emotional responsiveness, need satisfaction, and capacity for meaning-making are preserved in early-stage dementia and constitute clinically relevant assets. Four positive psychology constructs are identified as evidence-based targets for intervention: hope, self-compassion, social identity, and meaningful engagement. Clinical implications include the integration of strengths-based assessment, meaning-centred group interventions, structured peer support, and validated positive outcome measures into post-diagnostic care pathways. Health equity considerations and research priorities are addressed, including the underrepresentation of minority ethnic communities and people with young-onset dementia in existing research. The review argues that meaningful progress requires deliberate reorientation of clinical, commissioning, and research priorities toward a positive psychology framework for dementia care.

Abstract: Background and Objectives: Bipolar disorder (BD) is associated with widespread neuroanatomical alterations, particularly within subcortical structures involved in emotional regulation. Conventional magnetic resonance imaging (MRI) approaches may fail to detect subtle microstructural changes. This study aimed to evaluate histogram-based texture characteristics of the putamen in patients with BD and to compare these findings with those of healthy controls. Materials and Methods: This retrospective cross-sectional study included 66 participants (33 BD patients, 33 controls). All subjects underwent standardized cranial MRI. Regions of interest corresponding to the putamen were manually delineated, and histogram-based texture parameters were extracted using custom-developed software. Group comparisons were performed using appropriate statistical tests based on data distribution. Results: The groups were comparable in age and sex (p &gt; 0.05). Significant differences were observed in multiple texture parameters, particularly in the left putamen. Mean and median values were significantly higher in BD patients compared to controls (511.19 ± 106.96 vs. 440.68 ± 102.21, p = 0.008; 511.92 ± 106.71 vs. 440.53 ± 102.74, p = 0.007). Minimum intensity values and root-sum-of-squares levels were also significantly increased (p &lt; 0.001). Skewness differed significantly (p = 0.004), indicating altered distribution asymmetry. Percentile analyses demonstrated consistent differences across nearly all levels, suggesting a shift in intensity distribution. Additionally, Katz fractal dimension was significantly lower in BD patients (p &lt; 0.001), indicating reduced structural complexity. Similar but less pronounced alterations were observed in the right putamen. Overall, findings suggest the presence of widespread alterations in intensity distribution and structural characteristics. Conclusions: Patients with BD exhibit significant alterations in putamen texture parameters, potentially reflecting alterations in intensity distribution and texture-derived structural characteristics. These changes are more prominent in the left hemisphere, suggesting potential lateralization. Histogram-based texture analysis may provide a sensitive, non-invasive approach for detecting subtle brain alterations in BD and may serve as a complementary neuroimaging biomarker.

Abstract: Background: Obsessive–compulsive disorder (OCD) frequently co-occurs with autism spectrum disorder (ASD), but the prevalence and clinical correlates of this comorbidity remain incompletely understood. Methods: We examined a clinical sample of 603 patients with a primary diagnosis of OCD, of whom 149 (24.7%) presented with comorbid ASD. Sociodemographic variables, clinical characteristics, comorbidities, and obsessive–compulsive symptom dimensions were compared between patients with and without ASD. Results: Patients with OCD+ASD were significantly younger at assessment and reported an earlier onset of both obsessive–compulsive symptoms and full-blown disorder. A family history of affective disorders was more frequent in this subgroup. While overall symptom severity (Y-BOCS, HAM-D, HAM-A) was comparable, OCD+ASD patients reported higher exposure to stressful and traumatic life events, including severe trauma. Severe traumatic events, in particular, were found to be a predictor of ASD in our OCD cohort. Comorbidities were also distinct: onychophagia (66.4% vs. 0.4%) and trichotillomania (8.7% vs. 0%) were markedly more prevalent in the OCD+ASD group, as were Cluster B personality disorders (18.1% vs. 11.4%). Phenomenologically, OCD+ASD patients more often exhibited religious and somatic obsessions, as well as checking and repetition compulsions. Conclusions: OCD with comorbid ASD represents a clinically distinct subgroup, characterized by greater vulnerability to trauma, earlier onset, unique symptom profiles, and specific comorbidities. Recognition of these features, and in particular severe traumatic experiences, is crucial for early detection of ASD in individuals with OCD, personalized treatment planning and improved outcomes.