More evidence for an immune/inflammatory imbalance in both bipolar disorder and teenage suicide

Posted on December 19, 2011 by Dr. Jonathan

Summary: Neuroinflammatory signaling molecules are elevated in bipolar disorder patients compared to controls. Marked increases in proinflammatory cytokines are also observed in the brains of teen suicide victims. Brain inflammation, immune system dysregulation and the loss of self-tolerance are key factors in the management of BP and major depression.

A paper just published in the Journal of Psychiatric Research offers further evidence for the role of neuroinflammation resulting from immune system dysregulation in bipolar disorder. The authors state:

“Bipolar disorder (BD) is associated with considerable higher chronic medical comorbidities, overweight and obesity. Adipokines are adipocyte-derived secretory factors which have functions in immune response and seem to be associated with both BD and overweight. The aim of this study was to evaluate the plasma levels of adipokines (adiponectin, resistin and leptin) and TNF-α and its receptors (sTNFR1 and sTNFR2) in BD overweight patients in comparison with overweight controls.”

The authors measured plasma levels of adiponectin, resistin, leptin, TNF-α and TNF-α soluble receptors in thirty bipolar patients along with thirty controls matched by age, gender and body-mass index (BMI). The subjects were also assessed by Mini-International Neuropsychiatric Interview, Young Mania and Hamilton Depression rating scales. What did the data show?

“BD patients presented increased plasma levels of adiponectin, leptin and sTNFR1.”

This is but one drop in a sea of emerging evidence for the role of brain inflammation and immune dysregulation in neuropsychiatric disorders that clinicians should consider in comprehensive case management. The authors conclude:

“This study provides further support to the hypothesis of the immune/inflammatory imbalance in BD.”

Another study in the same journal documents a marked increase in proinflammatory cytokines in the frontal lobes of teenagers attempting suicide. The authors observe:

“”Proinflammatory cytokines play an important role in stress and in the pathophysiology of depression—two major risk factors for suicide. Cytokines are increased in the serum of patients with depression and suicidal behavior; however, it is not clear if similar abnormality in cytokines occurs in brains of suicide victims.”

So they evaluated 24 teenage suicide victims and 24 matched normal control subjects for gene and protein expression levels of the proinflammatory cytokines interleukin (IL)-1β, IL-6, and tissue necrosis factor (TNF)-α in the prefrontal cortex (PFC). Again we see the markers for brain inflammation:

“Our results show that the mRNA and protein expression levels of IL-1β, IL-6, and TNF-α were significantly increased in Brodmann area 10 (BA-10) of suicide victims compared with normal control subjects.”

This is the deepest biological expression of the loss of self-tolerance in these disorders. Autoimmune inflammatory conditions require evaluation of all the known underlying causal factors that may contribute to the loss of self and chemical tolerance in order to design the most helpful treatment plan. The authors conclude:

“These results suggest an important role for IL-1β, IL-6, and TNF-α in the pathophysiology of suicidal behavior and that proinflammatory cytokines may be an appropriate target for developing therapeutic agents.”

SSRI antidepressant use during pregnancy may increase the risk of autism

Posted on December 17, 2011 by Dr. Jonathan

Summary: The use of selective serotonin reuptake inhibitors (SSRIs, such as Prozac®, Celexa®, Lexapro®, Luvox® and Paxil®) taken during pregnancy—especially the first trimester—appears to increase the risk of autism spectrum disorders. There are evidence-based alternatives to SSRIs that support brain health without putting the fetus at risk.

A study recently published in the journal Archives of General Psychiatry draws attention to a risk of autism spectrum disorders (ASDs) born to mothers who took SSRI antidepressants during their pregnancy. The authors observe:

“The prevalence of autism spectrum disorders (ASDs) has increased over recent years. Use of antidepressant medications during pregnancy also shows a secular increase in recent decades, prompting concerns that prenatal exposure may contribute to increased risk of ASD.”

Therefore they set out to…

“…systematically evaluate whether prenatal exposure to antidepressant medications is associated with increased risk of ASD.”

In order to do so they compared the data for 298 children with ASD to 1507 randomly selected control children, along with the data for both their mothers. Their findings support a cautionary approach to the prenatal use of SSRIs:

“Prenatal exposure to antidepressant medications was reported for 20 case children (6.7%) and 50 control children (3.3%). In adjusted logistic regression models, we found a 2-fold increased risk of ASD associated with treatment with selective serotonin reuptake inhibitors by the mother during the year before delivery (adjusted odds ratio, 2.2), with the strongest effect associated with treatment during the first trimester (adjusted odds ratio, 3.8).”

In other words, the increase in risk for the whole year before delivery was 220%, but limiting the investigation to the first trimester it was 380%. Interestingly…

“No increase in risk was found for mothers with a history of mental health treatment in the absence of prenatal exposure to selective serotonin reuptake inhibitors.”

Meaning that it wasn’t a history of mental health treatment the year before delivery but specifically the use of SSRIs that accounted for the increased risk of ASDs. The authors conclude:

“Although the number of children exposed prenatally to selective serotonin reuptake inhibitors in this population was low, results suggest that exposure, especially during the first trimester, may modestly increase the risk of ASD. The potential risk associated with exposure must be balanced with the risk to the mother or fetus of untreated mental health disorders.”

This would be a troubling dilemma were it not for the fact that therapies supporting brain health are available to treat depression. Serotonin production and signaling, when indicated, can be supported in a physiological and sustainable manner that promotes the brain health of mother and fetus. A categorization and description of key resources that applies to adults as well as children is available in the Parents’ Guide To Brain Health.

Depression as a dysfunction of the immune system

Posted on December 7, 2011 by Dr. Jonathan

Summary: chronic inflammation due to immune system dysregulation, with or without a diagnosed autoimmune disease, plays a fundamental role in chronic depression. This offers sustainable and evidence-based treatments for depression and brain health.

The authors of an important paper published in Current Immunology Reviews state:

…current antidepressants do not effectively target all of the pathological processes that are responsible for the major symptoms of depression…However, in recent years greater attention has been directed to the inter-relationship between the brain and peripheral organs (the” body-mind” connection) in which changes in the endocrine and immune systems play a major role in the pathological changes that occur in depression. Thus inflammation is beginning to emerge as a major contributing factor not only to depression and other major psychiatric disorders…”

Two major ways that immune dysfunction promotes depression are emphasized: the direct effect of inflammation on the brain, and the brain effects of the hormonal response to inflammation. Regarding the former:

“…in the past 30 years or so that clinical and experimental evidence has been obtained clearly demonstrating that aspects of both cellular and humoral immunity were dysfunctional in major depression…in particular the pro- and anti-inflammatory cytokines…Such clinical observations suggest that proinflammatory cytokines contribute to the major symptoms of depression and now forms the basis of the inflammation, cytokine or inflammatory response hypothesis of depression.”

It’s now known that peripherally derived inflammatory cytokines have access to the brain, including areas involved in depression…

“Once in the brain, the proinflammatory cytokines activated both neuronal and non-neuronal (for example, the microglia, astrocytes and oligodendroglia) cells via the nuclear factor-kappa-beta (NF-kB) cascade in a similar manner to that occurring in the peripheral inflammatory response…

Also, the production of serotonin and dopamine is adversely affected by inflammation:

“Recently much attention has been paid to the activation of the tryptophan-kynurenine pathway by these cytokines whereby tryptophan is shunted from the synthesis of serotonin to that of kynurenine…clearly this is an important mechanism whereby serotonergic function is decreased in depression. The activity of the dopaminergic system is also reduced in response to inflammation. For example, IFN reduces the synthesis of dopamine by decreasing the concentration of the co-factor tetrahydrobiopterin (BH4)…As IFN increases the synthesis of nitric oxide by activating the BH4 dependent enzyme nitric oxide synthase in the microglia it seems likely that the reduction in dopaminergic function is linked to the increase in nitric oxide. This gaseous neurotransmitter is known to activate the glutamatergic system which, when this exceeds physiologically limits, enhances apoptosis and neurodegeneration.”

In other words, an increase in inflammatory cytokines derails the production of serotonin and dopamine, and activates the excitatory (glutamatergic) system to the point of cell death.

Additionally, proinflammatory cytokines activate the HPA (hypothalamo-pituitary-adrenal) axis causing excessive cortisol production which is lethal to brain cells at high levels…

“In addition to the modulation of neurotransmitter function, proinflammatory cytokines contribute to the major symptoms of depression by activating the HPA axis by increasing the release of CRF, thereby contributing to hypercortisolaemia, a feature of major depression. The mechanism whereby the cytokines induce hypercortisolaemia involves a decreased sensitivity of the glucocorticoid receptors thereby leading to glucocorticoid resistance…”

The inflammation model also sheds light on the role of stress in depression:

“…as major depression is often accompanied by inflammatory diseases (such as irritable bowel syndrome, type 2 diabetes, arthritis and autoimmune disorders) that can activate the peripheral and central inflammatory response, it is possible that such inflammatory disorders initiate the inflammatory changes that precipitate depression….[But] it is evident that inflammation also occurs in depressed patients who are not suffering from concurrent inflammatory disorders. Thus the increased vulnerability of depressed patients to psychosocial stress is probably the key factor that leads to the activation of the immune and endocrine axes in depression. It is known, for example, that even the relatively mild acute stress of public speaking causes an increase in NF-kB activity, a key element in the induction of the inflammatory cascade. In this regard, it is also known that patients with major depression frequently show an enhanced responsiveness of IL-6 and NF-kB to an antigen challenge…such changes appear to be associated with activation of the microglia thereby suggestion that the inflammatory changes are also occurring in the brain.”

In other words, patients with major depression have a more pronounced inflammatory response to substances to which they are sensitized or allergic to (antigens). This is in addition to an increased immune and hormonal response to psychosocial stress.

Of special significance for the use of heart rate variability analysis for evaluation of the autonomic nervous system and therapies that increase parasympathetic tone…

“The mechanism whereby psychological stress influences both the peripheral and central inflammatory cascade is co-ordinated by the autonomic nervous system. Thus the release of noradrenaline and adrenaline following the activation of the sympathetic system results in the activation of both alpha and beta adrenoceptors on immune cells thereby initiating the release of proinflammatory cytokines, via the activation of the NF-kB cascade, particularly on macrophages and monocytes in peripheral blood…Conversely stimulation of the parasympathetic system has the opposite effect on the stress induced inflammatory response…It is possible that the anti-depressant-like action of vagal nerve stimulation, occasionally used to treat resistant depression, is associated with such an anti-inflammatory action.”

Brain inflammation associated with depression actually causes the death of brain cells (apoptosis):

“Thus in major depression, the prolonged activation of the inflammatory network in the brain results in a decrease in neurotrophins, leading to reduced neuronal repair, a decrease in neurogenesis, and an increased activation of the glutamatergic pathway that contributes to neuronal apoptosis, oxidative stress and the induction of apoptosis in astrocytes and oligodendrocytes.”

On top of all this, inflammation causes the biochemical pathway that produces serotonin from tryptophan to converted to the production of neurotoxins instead through the tryptophan-kynurenine pathway and the production of quinolinic acid.

“As both the cytokines and cortisol are raised in major depression, it is not surprising to find that the tryptophan-kynurenine pathway is increased….Kynurenine hydroxylase metabolises kynurenine first to 3-hydroxykynurenine and then to 3-hydroxyanthranilic acid and quinolinic acid. This pathway is increased in depression and dementia…In chronic depression…the activated microglia produce an excess of the neurotoxin…Furthermore quinolinic acid can cause apoptosis of the astrocytes. This results in a reduction in the metabolic and physical buffer to the neurons that is usually provided by the astrocytes and thereby further exposes the neurons to the neurodegenerative actions of quinolinic acid.”

Inflammation in the brain over the long term causes neurodegeneration that appear as brain shrinkage:

“The structural changes observed in the brain of patients with chronic depression lends support to the neurodegenerative hypothesis of depression. It is known that there is a shrinkage of the hippocampus in patients with major depression and a decrease in the number of astrocytes and a neuronal loss in the prefrontal cortex and in the striatum. Such changes could be the consequence of chronic low grade inflammation in which the proinflammatory cytokines, nitric oxide, prostaglandin E2 and other inflammatory mediators play key roles; the cytokines are known to induce the cyclo-oxygenase and nitric oxide sythase pathways in the brain and thereby increase the inflammatory insult. The inhibition of neurotrophin synthesis in the brain by glucocorticoids, and the neurotoxic action of quinolinic acid, add further to the impact of the inflammatory changes.”

There are indications that patients who respond poorly to neurotransmitter-manipulating medications have markers for increased inflammation:

“Further evidence for the relationship between inflammation and depression is provided by the observation that depressed patients with a history of partial or lack of response to antidepressant treatments have elevated plasma concentrations of IL-6 and acute phase proteins that persist despite antidepressant treatment. It has been suggested that patients who are resistant to conventional antidepressant treatment possess abnormal alleles of the IL-1 and TNF genes, and possibly for T-cell function.”

Moreover, even when there is some relief from a depressed mood or anxiety with these medications…

“…there is abundant clinical evidence that the available antidepressants…are far less effective in treating the memory and cognitive dysfunction (fatigue, psychomotor retardation) that commonly affect middle aged and elderly depressed patients.”

There is mounting evidence that modulating inflammation can improve the inflammatory response:

“There are already indications from the clinical literature that TNF antagonists…reduce the symptoms of depression in a variety of patients with autoimmune diseases…the mood state of the patients improving before the signs of improvement of the autoimmune disorder…IL-10, and insulin-like growth factor that has prominent anti-inflammatory activity, have been shown to attenuate the depressive-like behaviour in rodents induced by an inflammatory challenge.”

IL-10 is increased by correcting suboptimal levels of vitamin D.

“Perhaps the most obvious step to the reduction of inflammation both centrally and peripherally is to reduce the activity of the prostenoid pathway and thereby reduce the synthesis of inflammatory prostaglandins such as PGE2.”

This is exactly what is accomplished by correcting an omega-3 fatty acid deficiency with a low 3:6 ratio.

The best chance for a sustainable program for helping depression by treating the inflammation is to determine with the appropriate tests why the excessive inflammation is happening in the first place. Then physiological and sustainable treatments can address those underlying causes properly. That brings up the very large topic of the functional management of autoimmune disease and chronic inflammation, a subject of many posts here and deserving of a weighty textbook. See posts forthcoming in the next week on the role of gastrointestinal inflammation as a contributing cause and treatment target for depression and the effectiveness of the omega-3 fatty acid EPA as a PGE2 reducer for depression.

Gluten sensitivity can increase suicide risk

Posted on September 6, 2011 by Dr. Jonathan

“When the gut is inflamed, the brain is inflamed” is a guideline that clinicians should bear in mind, and depression is one possible expression of brain inflammation. A study just published in the journal Digestive and Liver Disease offers evidence that inflammatory reactions to gluten can increase the risk for suicide. The authors state:

“Individuals with coeliac disease have increased risk of depression and death from external causes, but conclusive studies on death from suicide are missing. We examined the risk of suicide in coeliac disease and amongst individuals where the small intestinal biopsy showed no villous atrophy.”

The authors collected biopsy data on 29,083 individuals (from all 28 clinical pathology departments in Sweden) 1969–2007 who had celiac disease with villous atrophy (eroded gut lining), and another 13,263 who had non-celiac gluten sensitivity (inflammation but without villous atrophy), and 3719 subjects with positive coeliac disease lab results but normal mucosa. They the calculated Hazard ratios for suicide as recorded in the Swedish Cause of Death Register. What did their data show?

“The risk for suicide was higher in patients with coeliac disease compared to general population controls (HR = 1.55; based on 54 completed suicides). Whilst suicide was also more common amongst individuals with inflammation (HR = 1.96), no such increase was seen amongst individuals with a normal mucosa but positive coeliac disease serology.”

In other words, their data showed a 96% increase in risk for suicide among those with gluten sensitivity who had gut inflammation. These findings are in keeping with the extensive evidence for brain inflammation as a factor in depression and the linked between microinflammati0n in the gut and destructive glial activity in the brain. The authors conclude with an exhortation to practitioners:

“We found a moderately increased risk of suicide amongst patients with coeliac disease. This merits increased attention amongst physicians treating these patients.”

Note: Many diagnoses are missed due to inadequate laboratory resources. Only Cyrex Labs currently offers a complete gluten sensitivity test panel.

Omega-3 fatty acids and depression in adolescents

Posted on August 20, 2011 by Dr. Jonathan

Imbalances or deficiencies in essential fatty acids which are critical brain components can contribute to depression and neurological disorders. A study just published online in the journal Acta Pædiatrica delineates the decisive difference they make in adolescents. The authors set out to…

“…study the relationship between polyunsaturated fatty acids (PUFA) status and depression in adolescents with eating disorders (ED) and weight loss.”

They measured essential fatty acids (FA) in the red blood cell membranes of 217 adolescents with eating disorders. As the clinicians reading this know, erythrocyte fatty acids also reflect the fatty acid status of the brain. The study subjects were also examined for depression by clinical interviews and psychological self-report instruments. A clear-cut picture emerged from the data:

“Adolescents with ED and depression did not differ from those with ED only in terms of age, BMI, weight loss and duration of disease. In their FA profile depressed adolescents had lower proportions of eicosapentanoic acid (EPA) and docosahexanoic acid (DHA), the end products of the ω3 PUFA series. The ratio of long chain (>18 carbons) ω6/ω3 PUFA was therefore higher in depressed adolescents. Indices of desaturase activites did not differ between depressed and not depressed adolescents.”

In other words, the only difference among the factors examined in this study between the adolescents with and without depression was their essential fatty acid status. Thus the authors conclude:

“Low ω3 status is related to depression in adolescents with ED. This cannot be explained by differences in weight (loss) and duration of disease, nor by differences in PUFA processing by desaturases. Data suggest a lower dietary intake of ω3 PUFA in those with depression. Further investigations should determine whether ω3 PUFA status improves by refeeding only or whether supplementation with PUFA is warranted.”

See also the Parents’ Guide To Brain Health for additional evidence of the role of fatty acids, along with information on the other important aspects.

Bright light helps non-seasonal major depression in the elderly

Posted on May 16, 2011 by Dr. Jonathan

More evidence for the profound effects of light therapy is offered in a randomized placebo-controlled trial published recently in the Archives of General Psychiatry that documents the effectiveness of bright light therapy for relieving depression. The authors first observe:

“Major depressive disorder (MDD) in elderly individuals is prevalent and debilitating. It is accompanied by circadian rhythm disturbances associated with impaired functioning of the suprachiasmatic nucleus, the biological clock of the brain. Circadian rhythm disturbances are common in the elderly. Suprachiasmatic nucleus stimulation using bright light treatment (BLT) may, therefore, improve mood, sleep, and hormonal rhythms in elderly patients with MDD.”

They went about testing their assumption with a double-blind, placebo-controlled randomized clinical trial of bright light treatment (BLT) with 89 subjects age 60 or above living in the Amsterdam region who suffered from MDD. Treatment consisted of three weeks of 1-hour early-morning BLT (pale blue, approximately 7500 lux) vs placebo (dim red light, approximately 50 lux). They were assessed for the degree of depression at baseline (T0), after 3 weeks of treatment (T1), and 3 weeks after the end of treatment (T2) with the Hamilton Scale for Depression and cortisol and melatonin levels. As for the results:

“Intention-to-treat analysis showed Hamilton Scale for Depression scores to improve with BLT more than placebo from T0 to T1 (7%) and from T0 to T2 (21%). At T1 relative to T0, get-up time after final awakening in the BLT group advanced by 7%, sleep efficiency increased by 2%, and the steepness of the rise in evening melatonin levels increased by 81% compared with the placebo group. At T2 relative to T0, get-up time was still advanced by 3% and the 24-hour urinary free cortisol level was 37% lower compared with the placebo group. The evening salivary cortisol level had decreased by 34% in the BLT group compared with an increase of 7% in the placebo group.”

Remember, this is not seasonal affective disorder (SAD) but non-seasonal major depression. It’s also noteworthy that beneficial effects could still be measured three weeks after the end of treatment. The authors conclude:

“In elderly patients with MDD, BLT improved mood, enhanced sleep efficiency, and increased the upslope melatonin level gradient. In addition, BLT produced continuing improvement in mood and an attenuation of cortisol hyperexcretion after discontinuation of treatment.“

Exercise scores as well as Zoloft for major depression

Posted on October 28, 2010 by Dr. Jonathan

Another outcome study to add to the massive body of evidence that the psychopharmaceutical model for treating depression is seriously flawed was published in the journal Psychosomatic Medicine. The authors pitted sertraline (Zoloft, an SSRI) against exercise and placebo as they set out to…

“…assess whether patients receiving aerobic exercisetraining performed either at home or in a supervised group settingachieve reductions in depression comparable to standard antidepressantmedication (sertraline) and greater reductions in depressioncompared to placebo controls.”

They randomly assigned 202 adults diagnosed with major depression were to either supervised exercise in a group setting; home-based exercise; antidepressant medication (sertraline, 50–200 mg daily); or placebo pill for 16 weeks. This was followed by a structured clinical interview for depression and completed the Hamilton Depression Rating Scale (HAM-D). Typically, the data showed little difference between the placebo and Zoloft, and virtually no difference between the medication and exercise:

“After 4 months of treatment, 41% of the participants achieved remission, defined as no longer meeting the criteria for major depressive disorder (MDD) and a HAM-D score of <8. Patients receiving active treatments tended to have higher remission rates than the placebo controls: supervised exercise = 45%; home-based exercise = 40%; medication = 47%; placebo = 31%. All treatment groups had lower HAM-D scores after treatment; scores for the active treatment groups were not significantly different from the placebo group.”

There is an enormous amount of science showing that this class of medications profoundly perturbs the brain in such a way that attempting to stop taking them after 6 weeks or continuing them long-term can result in the dismal trap of a brain sensitized to depression. This study would have been even more striking had they compared the unmedicated exercise group to those who were medicated after attempting to stop. As it is, the authors conclude:

“The efficacy of exercise in patients seems generally comparable with patients receiving antidepressant medication and both tend to be better than the placebo in patients with MDD. Placebo response rates were high, suggesting that a considerable portion of the therapeutic response is determined by patient expectations, ongoing symptom monitoring, attention, and other nonspecific factors.”

Historically, before the age of psychopharmaceuticals most cases of major depression tended to be self-limiting. For an objective, meticulous, articulate and gripping scientific and historical narrative on how anti-depressants, tranquilizers and anti-psychotic medications have promoted the skyrocketing levels of mental disability, I suggest Anatomy of an Epidemic by Robert Whitaker. Anyone considering taking or prescribing these medications should be aware of the science reviewed comprehensively in this text.

Laser acupuncture lights up the brain for depression

Posted on September 27, 2010 by Dr. Jonathan

A fascinating study published in PLoS One (the Public Library of Science) documents the increase in metabolic activity in specific brain regions related to depression elicited by the application of laser light to acupuncture points (one of the methods for peripheral sensory-based neuromodulation of the brain that we routinely use). The authors state their intent:

“As laser acupuncture is being increasingly used to treat mental disorders, we sought to determine whether it has a biologically plausible effect by using functional magnetic resonance imaging (fMRI) to investigate the cerebral activation patterns from laser stimulation of relevant acupoints.”

They stimulated 4 acupoints (LR14, CV14, LR8 and HT7—indicated for depression in TCM) and a sham point with a fiber-optic infrared laser, alternating the stimulation with a fake laser. The measured the effect on the whole brain by recording changes in the blood oxygenation level-dependent (BOLD) fMRI response with a 3T scanner (and resolved changes in localized metabolic activity—brain cells ‘working’). What did the data show?

“Many of the acupoint laser stimulation conditions resulted in different patterns of neural activity. Regions with significantly increased activation included the limbic cortex (cingulate) and the frontal lobe (middle and superior frontal gyrus). Laser acupuncture tended to be associated with ipsilateral brain activation and contralateral deactivation that therefore cannot be simply attributed to somatosensory stimulation.”

A simple way to think of depression is a failure of the frontal lobes to ‘fire’ adequately. This research adds to the body of evidence that peripheral sensory-based modalities—stimulating sensory nerve endings such as acupoints and trigger points by various methods elicits a brain response. As we have found, this has practical significance in the treatment of depression. The note in their conclusion:

“We found that laser stimulation of acupoints lead to activation of frontal-limbic-striatal brain regions, with the pattern of neural activity somewhat different for each acupuncture point…Differing activity patterns depending on the acupoint site were demonstrated, suggesting that neurological effects vary with the site of stimulation.”

Inflammation, mitochondrial dysfunction and neurodegeneration in major depression

Posted on August 21, 2010 by Dr. Jonathan

Is depression mainly a disorder of serotonin regulation? A paper just published in Progress in Neuro-Psychopharmacology and Biological Psychiatry reminds us that, of course, it is not. The authors state:

“For many years, a deficiency of monoamines including serotonin has been the prevailing hypothesis on depression, yet research has failed to confirm consistent relations between brain serotonin and depression.“

They observe that there is a relationship between depression a number of other conditions with a common set of underlying causes:

“…depression is one of a family of related conditions sometimes referred to as the “affective spectrum disorders”, and variably including migraine, irritable bowel syndrome, chronic fatigue syndrome, fibromyalgia and generalized anxiety disorder, among many others.”

What do these disorders have in common?

“…we present data from many different experimental modalities that strongly suggest components of mitochondrial dysfunction and inflammation in the pathogenesis of depression and other affective spectrum disorders. The three concepts of monoamines, energy metabolism and inflammatory pathways are inter-related in many complex manners. For example, the major categories of drugs used to treat depression have been demonstrated to exert effects on mitochondria and inflammation, as well as on monoamines. Furthermore, commonly-used mitochondrial-targeted treatments exert effects on mitochondria and inflammation, and are increasingly being shown to demonstrate efficacy in the affective spectrum disorders.”

In the functional approach, the evaluation and treatment of depression is not complete without addressing the factors that contribute to neuroinflammation, neurodegeneration and mitochondrial dysfunction with the appropriate tests and physiological interventions.

Bipolar disorder and brain inflammation

Posted on July 16, 2010 by Dr. Jonathan

Neuroinflammation is being recognized as a fundamental cause for a range of psychiatric disorders. A paper recently published in the journal European Archives of Psychiatry and Clinical Neuroscience is a reminder that treatment for bipolar disorder is incomplete with addressing inflammation in the brain. The authors state:

“Bipolar disorder (BD) has been associated with a proinflammatory state in which TNF-α seems to play a relevant role. The aim of the present study was to evaluate the plasma levels of TNF-α and its soluble receptors (sTNFR1 and sTNFR2) in BD patients in mania and euthymia in comparison with control subjects.”

(TNF-α is a major proinflammatory cytokine.) As the data emerged they saw that:

“…higher sTNFR1 levels were found in BD patients. Of note, BD patients in mania had higher sTNFR1 levels than BD patients in euthymia and controls. The sTNFR1 and sTNFR2 levels correlated with BD duration, and sTNFR2 levels correlated with age of patients.”

The authors announce in their conclusion that:

“Our data indicate a proinflammatory status in BD patients during mania and further suggest that inflammatory mechanisms may be involved with the physiopathology of BD.”

The functional approach to BD, major depressive disorder, OCD, schizophrenia, and many more brain-based diagnoses must include a careful evaluation of each case for neuroinflammation and its causes.