Abstract

​The boundaries between neurodevelopmental disorders are often indistinct, even among specialists.

But do these boundaries exist, or do experts struggle to distinguish and categorize symptoms in order to arrive at a dominant diagnosis while comorbidity continually leaves questions about where each disorder ends and begins?

What should be reconsidered?

The introduction of the term ‘spectrum of neurodevelopmental disorders’ could pave the way for a re-appraisal of the clinical continuum of neurodevelopmental disorders.

This study aims to highlight the problems that emerge in the field of the differential diagnosis of neurodevelopmental disorders and propose a renegotiation of the distinctiveness criteria.

​These diseases encompass cortical alterations commonly associated with neuronal dysfunctions.

To map the expression patterns of these risk gene sets in the early fetal human brain, we performed expression-weighted cell type enrichment (EWCE) analysis on single-cell RNA-sequencing (RNA-seq) data from telencephalic regions spanning the first trimester44 .

Consistent with our previous findings in macaque brain and other studies, genes associated with NDDs  [Neuro-Developmental Disorders]  were enriched in both inhibitory and excitatory neuronal signatures.

Similarly, LIS, FCD, and dyslexia genes showed neuronal enrichment, while MIC- and HC-associated genes were enriched in RG cells and glioblasts, MIC-, POLYM-, and rare MCD-associated genes in intermediate progenitor cells (IPCs), and AD genes in immune cell signatures

​The prenatal period is a vulnerable phase for the offspring's development in utero and ex utero.   Accordingly, negative environmental influences such as chronic maternal stress pose a major risk factor for the offspring to develop a variety of mental and physical disorders later in life.

Many of these pathologies are accompanied by an over-reactive immune system and chronic low-grade inflammation, and prospective human and mechanistic animal studies strengthen the idea that an exaggerated immune (re)activity plays a causal role in their pathogenesis.

In line with the latter, we have shown in mice that repeated administrations with heat-inactivated preparations of different immunoregulatory nontuberculous mycobacteria (NTM), such as M. vaccae NCTC 11659 and the closely related strain M. vaccae ATCC 15483T promote immunoregulation and stress protection

.  .  .

​The protective effects of M. vaccae ATCC 15483T on female offspring are harder to interpret, as the latter were not as reliably affected by PS.

Collectively, our findings indicate that repeated i.g. administration of M. vaccae ATCC 15483T in an intergenerational manner is protective against the negative consequences of PS  [PRENATAL STRESS] on the immune and musculoskeletal system.

Mycobacterium vaccae ATCC 15483T administered to nulliparous C57BL/6N mice prior to mating

protects their male offspring against the negative consequences of prenatal stress  (2026)

​Conclusion and relevance: These findings highlight the extensive comorbidities between IED [Intermittent Explosive Disorder] and psychiatric, neurological, and somatic disorders, emphasizing the need for integrated diagnostic and treatment approaches addressing both psychological and physical health aspects of IED.

​ Limitations related to reliance on medical records and low diagnostic rates of IED caution the generalizability of these findings, underscoring the need for further validation in prospective studies and more accurate, inclusive diagnosis of IED in patients with mental disorders