​Conclusions:  Our study supports the potential causal association between mtDNA-CN [Mitochondrial DNA Copy Number] and the risk of ASD [Autism Spectrum Disorder], suggesting that mtDNA-CN could serve as a promising biomarker for early screening of ASD.

​In conclusion, sensory processing difficulties can be considered as a non-specific transdiagnostic phenotype associated with a broad spectrum of psychiatric conditions.

Further research into the relevance and role of sensory processing difficulties in psychiatric disorders may improve long-term prognosis and treatment.

​Results: The research indicates that PTSD is marked by significant imbalances in pro-inflammatory and anti-inflammatory cytokines across various biological fluids, including blood, saliva, and cerebrospinal fluid.

Abnormal immune cell activation and elevated levels of soluble adhesion molecules, chemokines, and markers of inflammation were frequently observed in PTSD patients.

These inflammatory responses are accompanied by aberrant activity in central immune cells, suggesting that inflammation may play a key role in the pathogenesis of PTSD.

​In addition, neuroinflammatory processes were linked to cognitive and emotional disturbances commonly seen in individuals with PTSD.

​Given that behavioral addictions are prevalent, frequently co-occur with psychiatric disorders, may often go undiagnosed and untreated, and have been linked to poorer treatment outcomes, active screening and treatment are indicated.

Public health considerations should be expanded, and impacts of modern technologies should be investigated more intensively.

Treatment optimization involving pharmacotherapy, psychotherapy, neuromodulation, and their combination warrants additional investigation

​This study provides genetic proof supporting a causal relationship between various inflammatory factors and addiction phenotypes.

Abstract

​Beyond their role in immune signalling, cytokines have emerged as key neuromodulators influencing processes including neurotransmitter function, neuronal excitability, synaptic plasticity, neurogenesis, myelination, and cortical sleep-state.

These roles are observed in both the healthy brain and during infections when they reorient motivational, cognitive, and emotional responses.

Experimental evidence from human and non-human primate immune challenge studies has been pivotal to understanding these effects.

By showing that elevated cytokines readily induce transdiagnostic symptoms, including anhedonia, social withdrawal, psychomotor slowing, and cognitive impairment, they have also helped demonstrate that inflammation contributes to the shared neural dysfunction observed across psychiatric and neurological disorders.

Cytokines modulate glutamatergic and GABAergic neurotransmission, impair dopaminergic and serotonergic signalling, and regulate homeostatic synaptic scaling, leading to altered network connectivity and behavioural deficits.

While research has often focused on single cytokines in isolation, neuroimmune signalling occurs through combinatorial cytokine codes, requiring systems-level approaches to understand their interactive effects.

Advances in neuroimaging, molecular neuroscience, and biophysical modelling offer opportunities to link cellular cytokine action with macroscale network dysfunction, enabling mechanistic insights into cytokine-mediated neuromodulation.

Clinically, cytokine-targeting therapies hold promise for treating inflammation-driven cognitive and mood disorders, but their long-term impact on neuroplasticity remains uncertain.

Future research should characterize:
* immune signatures predictive of neuropsychiatric symptoms,
*identify cell-type-specific cytokine effects, and
*integrate multiscale modelling to refine understanding of neuroimmune interactions.

Reconceptualising cytokines as fundamental regulators of neural function rather than merely inflammatory mediators is crucial for developing precision medicine to mitigate immune-driven brain dysfunction and improve mental health outcomes.

Abstract
​
For 80 years there has been a link between autism and immune activation.

Studies point to dysfunction in immune responses in peripheral blood, gut mucosa, and brain.

Human postmortem brain studies in autism show increased differential expression of inflammatory immune genes, increased pro-inflammatory cytokine levels, and glial activation.

Immune cells in the brain are comprised of both tissue-resident cells and those recruited from the blood.

This includes regulatory T cells (Tregs) that foster immune tolerance and tissue repair.

Tregs reduce microglial reactivity, assist in regenerative and reparative processes, and promote differentiation of myelin-producing oligodendrocytes in the brain, thus modulating white matter development.

Neuroinflammation may be a universal autism phenotype independent of the underlying etiology that can be controlled by Tregs promoting homeostasis, microglia and oligodendrocyte function, and white matter development.

​Background:  Post-traumatic stress disorder (PTSD) is a debilitating psychological disorder that also presents with neuroimmune irregularities.

Patients display elevated sympathetic tone and are at an increased risk of developing secondary autoimmune diseases.

​Conclusions: Our data depict a novel role for β1/2 adrenergic and cAMP signaling in the balance of TH17/Treg lymphocytes.

​These findings provide a new target for pharmacological therapy in both psychiatric and autoimmune diseases associated with IL-17A-related pathology.

Abstract

Recent research has shed light on the intricate relationship between mood disorders, such as major depressive disorder (MDD) and bipolar disorder (BD), and inflammation.

This chapter explores the complex interplay involving immune and metabolic dysfunction in the pathophysiology of these disorders, emphasizing their association with:
* autoimmunity/inflammatory conditions,
* chronic low-grade systemic inflammation,
*T cell overactivation, and
*immunosenescence [the Aging  of the Immune System]

This perspective underscores the notion that MDD [Major Depressive Disorder]and BD [Bipolar Disorder] are not solely brain disorders, highlighting their nature as multi-system conditions.

​Immune abnormalities including an insufficiency of regulatory T cells (Treg) and increased blood-based inflammatory markers have been observed in bipolar disorders (BD), particularly during depression.

​As Tregs are pivotal to control inflammation, Treg stimulation by low-dose IL-2 (IL-2LD) could have a therapeutic impact on bipolar depression.

​Conclusions: These hypothesis-generating findings highlight T cell dysfunction in AGA+ positive SRD  [Schizophrenia Related Disorders], suggesting Tregs protecting against negative symptom severity but also an unidentified other T cell population to possibly be driving negative symptom severity.

​Strong causal relationships existed between immune cells, circulating inflammatory factors, and NDDs. Inflammatory factors mediated the pathways between immune cells and NDDs [Neurodevelopmental Disorders].

​A case study of a 9-year-old girl diagnosed with seronegative autoimmune encephalitis, who displayed severe obsessive-compulsive disorder (OCD) and aggressive behavior, exemplifies the complexities involved in treatment.

Promising interventions, including CAR-T-cell therapy and nanomedicine, are under development for various autoimmune diseases, such as vitiligo and refractory autoimmune rheumatic diseases (ARDs).

​Furthermore, emerging therapies, including CAR-T-cell therapy, mRNA-based strategies, and microbiome modulation, are being explored alongside advancements in personalized medicine and early diagnostic techniques to improve patient outcomes for individuals affected by autoimmune diseases.

​Since most brain diseases are either incurable or irreversible, they place a considerable burden on both society and the economy, highlighting the essential role of primary prevention in preserving brain health (Lazar et al., 2021).

​Modifiable lifestyle factors—behaviors that can be changed without professional intervention, such as smoking, alcohol consumption, and physical activity—are important targets for these prevention efforts.

​Our results demonstrate that changes in repetitive-like and social behaviors that are induced by MIA [Maternal Immune Activation] in male mice are not exacerbated by subsequent inflammatory challenge and highlights the importance of considering the timing of stressors in the appearance of developmental pathology.

Highlights

• 
  Maternal immune activation (MIA) may act as a disease primer for neurodevelopmental pathology.
• 
  Here we investigated if MIA synergized with postnatal inflammation to exacerbate pathology.
• 
  MIA decreases sociability and increases repetitive-like behaviors in males.
• 
  CD8 + T cells are impacted by MIA in a sex-dependent manner.
• 
  Postnatal immune inflammation did not exacerbate ASD-like pathology in either sex.