In this article the emerging biological overlaps of CNS disorders and psychiatric conditions are reviewed. Recent work has highlighted how immune-inflammatory processes and their interactions with oxidative and nitrosative stress, couple to drive changes in neuroregulatory tryptophan catabolites, with consequences for serotonin availability, including as a precursor for the melatonergic pathways. Subsequent alterations in the regulation of local melatonin synthesis are likely to have direct impacts on the reactivity of immune cells, both centrally and systemically. These inflammatory processes also lead to the activation of wider immune processes. Such wider processes can include the production of immunoglobulin (Ig)A and IgM antibody responses, including to tryptophan catabolites, emphasizing the importance of immune responses, and their interactions with inflammatory processes, in the etiology and course of an array of medical conditions, including CNS disorders and psychiatric conditions. Such work poses questions as to the validity and utility of current, non-biologically based classification systems for psychiatric and CNS disorders. In this article, the biological underpinnings of CNS disorders and psychiatric conditions are reviewed in the context of how recent data, in reconceptualizing key processes in these classically-conceived brain-associated disorders, provides scope for novel, and hopefully more clinically useful, treatments. These processes are looked at in detail in Alzheimer's disease and major depressive disorder. One important treatment target is the gut. Alterations in the gut, including gut permeability and the composition of the microbiome, have now become an important target for treatment across an array of medical conditions, emphasizing the importance of targeting regulators of the immune system in developing novel treatments that are based on a more comprehensive and 'wholistic' understanding of currently poorly managed medical conditions, particularly psychiatric and CNS disorders.
Background Increasing data suggest emergent affective symptoms during the COVID-19 pandemic. Objectives To study the impact of the COVID-19 pandemic on affective symptoms and suicidal ideation in Thai adults. Methods The Collaborative Outcomes Study on Health and Functioning during Infection Times uses non-probability sampling (chain referring and voluntary response sampling) and stratified probability sampling to identify risk factors of mental health problems and potential treatment targets to improve mental health outcomes during pandemics. Findings Analysing 14 271 adult survey participants across all four waves of the COVID-19 pandemic in Thailand, covering all 77 provinces from 1 June 2020 to 30 April 2022, affective symptoms and suicidality increased during COVID-19 pandemic. Affective symptoms were strongly predicted by pandemic (feelings of isolation, fear of COVID-19, loss of social support, financial loss, lack of protective devices) and non-pandemic (female sex, non-binary individuals, adverse childhood experiences (ACEs), negative life events, student status, multiple mental health and medical conditions, physical pain) risk factors. ACEs, prior mental health conditions and physical pain were the top three risk factors associated with both increased affective symptoms and suicidal ideation during the COVID-19 pandemic. Partial least squares analysis showed that ACEs were the most important risk factor as they impacted most pandemic and non-pandemic risk factors. Clinical implications Rational policymaking during a pandemic should aim to identify the groups at highest risk (those with ACEs, psychiatric and medical disease, women, non-binary individuals) and implement both immediate and long-term strategies to mitigate the impact of ACEs, while effectively addressing associated psychiatric and medical conditions.
Diabetes, dopamine, attachment style disorders, and hypomania share complex interrelations involving neuroinflammation, dysfunction in brain networks (DMN, CEN, SAL), and emotional regulation. Both Type 1 and Type 2 diabetes induce cognitive and structural changes in the brain through mechanisms such as hyperglycemia, insulin resistance, and chronic inflammation. These processes can affect the dopaminergic system, which plays a pivotal role in motivation, emotional regulation, and the manifestation of hypomania. Dopamine is directly linked to attachment styles, with disturbances in this system increasing vulnerability to emotional disorders, including bipolar disorder and schizophrenia. Hypomania, a hallmark of the bipolar spectrum, is associated with dopaminergic imbalances, often observed in diabetes.
Abstract Maes et al. (2008) published the first paper demonstrating that major depressive disorder (MDD) is accompanied by abnormalities in the microbiota-gut-brain axis, as evidenced by elevated serum IgM/IgA to lipopolysaccharides (LPS) of Gram-negative bacteria, such as Morganella morganii and Klebsiella Pneumoniae . The latter aberrations, which point to increased gut permeability (leaky gut), are linked to activated neuro-immune and oxidative pathways in MDD. To delineate the profile and composition of the gut microbiome in Thai patients with MDD, we examined fecal samples of 32 MDD patients and 37 controls using 16S rDNA sequencing and analyzed α-(Chao and Shannon indices) and β-diversity (Bray-Curtis dissimilarity) and conducted Linear discriminant analysis (LDA) Effect Size (LEfSe) analysis. Neither α-nor β-diversity differed significantly between MDD and controls. Rhodospirillaceae, Hungatella, Clostridium bolteae, Hungatella hathewayi , and Clostridium propionicum were significantly enriched in MDD, while Gracillibacteraceae family, Lutispora, and Ruminococcus genus, Ruminococcus callidus, Desulfovibrio piger, Coprococcus comes , and Gemmiger , were enriched in controls. Contradictory results have been reported for all these taxa, with the exception of Ruminococcus which is depleted in 6 different MDD studies (one study showed increased abundance), many medical disorders that show comorbidities with MDD, and animal MDD models. Our results may suggest a specific profile of compositional gut dysbiosis in Thai MDD patients with increases in some pathobionts and depletion of some beneficial microbiota. The results suggest that depletion of Ruminococcus may be a more universal biomarker of MDD that maybe contributes to increased enteral LPS load, LPS translocation, and gut-brain axis abnormalities.
Summary A patient is presented showing an altered oddball response while suffering from auditory hallucinations. The nontarget stimulus evokes a compound negative potential encompassing a normal early N 1 component and an additional negativity within the categorization N 2 range. These findings are discussed in reference to impaired mismatch processes and the deranged monitoring of inner speech theory, proposed in schizophrenia.
To investigate whether violent and nonviolent suicide and homicide are related to atmospheric or geomagnetic activity, we investigated the relationships between weekly number of suicides or homicides for all Belgium for the period 1979–1987, and ambient temperature, relative humidity, air pressure, hours of sunlight and precipitation per day, wind speed and geomagnetic index. The occurrence of violent suicide was significantly and positively related to ambient temperature, sunlight duration, an increase in temperature over the few past weeks, and negatively to relative humidity. Higher ambient temperature and an increase in air temperature over the few past weeks were the most significant climatic predictors of violent suicide rate. A highly significant common annual rhythm with a common acrophase of 190° was detected in violent suicide rate, ambient temperature and sunlight duration. No significant time‐relationships between nonviolent suicide or homicide and any of the weather variables were found. It is concluded that i) violent suicide may be related to short‐term fluctuations in the weather and in particular to temperature; and ii) the annual rhythm in violent suicide may be synchronized by the annual rhythms in ambient temperature and light‐dark span.
