There is evidence that various mental disorders can also be triggered by viruses or by the immune response to viruses. This is probably neither the only nor the most common cause of mental symptoms, but should be considered as a possible cause.
Certain inflammatory values in the blood are elevated in depression, while other inflammatory values are altered in fatigue and schizophrenia. Stress shows a positive correlation between cortisol and IL-6 in depressed people, whereas in healthy people there is a positive correlation between ACTH and CRP. COX-2 inhibitors and TNF-α antagonists can be used to treat depression.
Fatigue shows a reduction in IL-6 and TNF-alpha under stress.
A mild chronic inflammation of the brain is suspected in schizophrenia. Autoimmune diseases increase the risk of schizophrenia. Neurotrophic infections in childhood and adolescence can increase the risk of later psychosis. Sleep fragmentation can lead to inflammatory reactions in body tissue that are regulated by the autonomic nervous system.
1.1. Basal blood levels of cytokines
Compared to healthy people, the basal blood values of severely depressed people are on average (i.e. not for everyone affected)
- Significantly increased:
IL-6 (16 studies, n = 892) (31 studies). Similarly, a recent single study in relation to subclinical depression symptoms found that basal IL-6, but not TNF-α blood levels correlated with the degree of acute (subclinical) depressive mood in remitted depressives as in healthy individuals
- Deviating: IL-6 and sIL-6R (following administration of interferon-alpha) did not correlate with increased depression levels after the MADRS. Changes in daily IL-6 levels had no effect on behavior.
CRP (20 studies)
- Tends to increase, large fluctuation in results:
- Increased (meta-analysis of 13 studies, n = 788)
- Increase doubtful due to the high heterogeneity and inconsistency of the subgroups
- No increase in a recent study in relation to subclinical depression symptoms
- The basal IL-6, but not the TNF-α blood levels correlated with the degree of acute (subclinical) depressive mood in remitted depressives as in healthy individuals.
- Without differences:
IFN-γ (4 studies)
IL-1β (9 studies)
IL-2 (5 studies)
Il-4 (5 studies)
IL-8 (4 studies)
IL-10 (6 studies), also a more recent study on subclinical depression symptoms.
1.2. Stress responses of cytokines in depression
In acutely depressed people (unlike healthy people), there was a positive correlation between the stress responses of cortisol and IL-6 and between the stress responses of adrenaline, TNF-α and CRP. Healthy individuals only showed a significant correlation between ACTH and CRP stress responses.
In contrast, no correlation was found between the stress responses of cortisol on the one hand and cytokines on the other (IL-6, TNF-α, IL-10) in both non-depressed and remitted (healthy former) depressives.
1.3. Individual treatment options for depression from an immunological perspective
In depression, a correlation is observed between increased IL-6 levels and the resulting reduction in serotonin synthesis. Furthermore, increased levels of lymphocytes, phagocytes, IL-1, IL-2, INF-α, INF-γ, TNF-α, positive acute-phase proteins, CRP and peripheral mononuclear cells as well as reduced levels of negative acute-phase proteins have been described. Initial studies also indicate an antidepressant effect of (augmentative) COX2 inhibitors in depression, which inhibit IL-1 and IL-6 and increase serotonin levels, among other things. Diclofenac is a COX2 inhibitor, which explains the high cardiovascular risk of diclofenac, while ibuprofen and naproxen inhibit COX1 more strongly than COX2.
TNF-α antagonists also appear to have an antidepressant effect. In addition, the levels of pro-inflammatory inflammatory markers decrease in conventionally successfully treated patients (e.g. with electroconvulsive therapy).
One study reported that elevated IL-1-α levels were inhibited by supplementation of EPA or DHA, while elevated IL-6 and TNF-α levels were reduced by EPA (only).
In fatigue, a reduction in IL-6 and TNF-alpha was found in response to stress, while healthy people showed an increase as a stress response. In fatigue, ACTH and salivary cortisol levels were also lower overall, while blood cortisol was only basally lower. This showed a negative correlation of the IL-6 and TNF-alpha stress response to the cortisol stress response in fatigue, compared to a positive correlation in healthy individuals.
In treatment-resistant schizophrenia, mild chronic encephalitis (inflammation of the brain) is considered. Indications for this are
- Activated monocytes
- Proteome changes in the blood
- Discrete cerebrospinal fluid pathologies in more than 60% of treatment-resistant schizophrenic psychoses
- Activated microglia
- Disconnectivity in imaging processes.
The detection of low-grade chronic inflammatory factors is a major problem.
For schizophrenia, benefits of augmentative treatment with type 1 cytokine-promoting and COX-2 inhibiting drugs have been described.
A large cohort study of almost 1.2 million children found slight indications that neurotrophic infections in childhood and adolescence are a risk factor for later psychosis:
- CMV infections (cytomegalovirus, a herpes virus) almost doubled the risk
- Mumps virus infections increased the risk
- Bacterial infections or urban living increased the risk very slightly
- Enteroviruses did not increase the risk (risk ratio 1.0).
In contrast, psychosis in one parent increased the risk more than 6-fold.
Autoimmune diseases increase the risk of later schizophrenia by 45%. Conversely, 9 autoimmune diseases are more common in schizophrenia sufferers than in non-affected people and 12 autoimmune diseases are more common in parents of schizophrenia sufferers than in parents of non-affected people. Another study also comes to the conclusion that autoimmune diseases increase the risk of schizophrenia.
5. Sleep problems
Both single and chronic sleep fragmentation increased the mRNA and protein levels of cytokines in the body tissue of mice. Changes in inflammatory responses reflected the activation of stress axes with increased corticosterone and noradrenaline. Treatment with 6-OHDA significantly reduced inflammation caused by sleep fragmentation. This indicates a regulation of sleep fragmentation-induced inflammation in body tissue by the autonomic nervous system (sympathetic/parasympathetic nervous system).
Chronic sleep fragmentation showed more severe consequences than single (acute) sleep fragmentation. A one-week recovery from sleep fragmentation sufficiently alleviated the peripheral inflammatory responses, but not the noradrenergic responses.