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.”

HPA hormone dysregulation in pediatric disorders of learning, behavior and neurodevelopment

Posted on September 25, 2010 by Dr. Jonathan

There is a large body of evidence that compels us not to overlook hormonal dysregulation in ADHD and other disorders of learning, behavior and brain development. A paper published not long ago in the journal European Neuropsychopharmacology addresses the broad topic of neurosteroids. The authors state in regard to the steroid hormones active in the nervous system:

“Neurosteroids play a significant role in neurodevelopment and are involved in a wide variety of psychopathological processes…there is increasing evidence for their critical role from the early stages of brain development until adolescence.“

They proceed to review the involvement of neurosteroids in neurodevelopment and mental disorders in children and adolescents, noting in particular:

“Adequate physiological levels protect the developing neural system from insult and contribute to the regulation of brain organization and function. Neurosteroids may be involved in the pathophysiology and pharmacotherapy of a variety of disorders in children and adolescents, including schizophrenia, depression, eating disorders, aggressive behavior and attention deficit.”

A paper published in the journal Neuropediatrics examines the association of hypothalamo-pituitary-adrenal (HPA) axis dysfunction and intelligence performance:

“The aim of the present study was to examine the effects of hypothalamo-pituitary-adrenal (HPA) axis reactivity on intelligence test performance in subjects with attention-deficit/hyperactivity disorder (ADHD). We investigated the extent to which an increase or decrease in cortisol after stress was associated with the intelligence test performance in 68 clinic-referred children with ADHD.”

They administered a battery of tests for both assessment and stressor applications, plus…

“A saliva sample was collected from each subject before and after psychological testing in order to measure the level of cortisol in the saliva.”

Salivary cortisol is the most reliable and necessarily non-invasive way to measure functional cortisol levels as we know here from extensive clinical experience. Their data painted a striking picture:

“Decreases in the level of cortisol after the test were correlated with poor intelligence performance and the decrease of cortisol in respect to baseline significantly affected the verbal, performance and total IQ in subjects who showed blunted responses to stress.”

A fine study published recently in the Chinese Journal of Contemporary Pediatrics further investigates…

“…the function of the hypothalamus-pituitary-adrenal (HPA) axis in children with attention deficit hyperactivity disorder (ADHD).”

128 boys with ADHD at ages of 6 to 14 years were diagnosed and grouped according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV): ADHD-predominantly inattention type, ADHD-predominantly hyperactive impulsive type and ADHD-combined type. 30 healthy boys served as the control group. They tested cortisol and assessed intelligence level with Raven′s standard progressive matrices. What did the data show?

“The mean plasma cortisol level in the ADHD group was significantly lower than that in the control group. The three ADHD subgroups showed significantly decreased plasma cortisol level compared with the control group. The plasma level of cortisol was the lowest in the ADHD-HI group, followed by the ADHD-I group and the ADHD-C group.”

Their conclusion should be borne in mind by both clinicians and parents:

“In the non-stress state, the HPA axis may be dysfunctional in children with ADHD, which may be attributed to the under reactivity of the HPA axis. Lower plasma cortisol…may closely be related to attention deficit, hyperactivity and impulsive behaviors.“

More valuable research was published in the Yonsei Medical Journal (Korea) in which the authors state:

“Children with attention-deficit/hyperactivity disorder (ADHD) often perform poorly during cognitive tests. We sought to evaluate cortisol as potential moderator of performance in mentally challenging tasks in children with ADHD.”

They measured salivary cortisol in 90 children with ADHD before and after administration of a continuous performance test (CPT). Their data adds evidence that cortisol dysregulation in association with poorer performance can be either abnormally high or low:

“Children whose cortisol level increased after testing displayed a significantly longer response time and increased response time variability scores as compared to children who did not display increase of cortisol after the CPT test.”

Since activation of α1 adrenergic receptor mediates both cortisol level increase and attention impairment, they also conclude that in association with cortisol:

“The result of the current study suggests that stress-induced high norepinephrine (NE) release may accompany poorer attention performance in patients with ADHD.”

The authors of a paper published in European Child & Adolescent Psychiatry offer additional evidence that children with ADHD must be evaluated as individuals for varying patterns of cortisol dysregulation:

“The aim of this study was to investigate whether a different pattern of HPA axis activity is found between the inattentive (I) and combined (C) subtypes of ADHD, in comparison with healthy control children.”

They studied the effects of stress by comparing cortisol responses to a psychosocial stressor (a public speaking task). Their data revealed interesting differences:

“Children with ADHD-I showed an elevated cortisol response to the psychosocial stressor, in contrast to children with ADHD-C who showed a blunted cortisol response to the psychosocial stressor…hyperactivity symptoms were clearly related to a lower cortisol reactivity to stress. The results indicate that a low-cortisol responsivity to stress may be a neurobiological marker for children with ADHD-C, but not for those with ADHD-I.”

The authors of a paper published in the Journal of Attention Disorders draw our attention to the link between sensory hyperarousal and HPA axis dysregulation with their investigation of salivary cortisol levels:

“To determine if sensory overresponsivity (SOR) is a moderating condition impacting the activity of the Hypothalamic Pituitary Adrenal (HPA) Axis in children with ADHD.”

Children with ADHD and known SOR were compared with those with ADHD but without SOR and normal children, all of whom participated in a Sensory Challenge Protocol. Salivary cortisol was used as a measure of HPA activity with two prechallenge and seven postchallenge samples taken. Interestingly, their data showed…

“…a borderline significant difference found between the ADHDt [without SOR] and ADHDs [with SOR] group and a significant difference between ADHDt and the typical [normal] group.”

In other words, salivary cortisol measurements distinguished both ADHD groups from the normal group.

Clarification of the different patterns of HPA axis dysregulation in ADHD was reported in the Journal of Abnormal Child Psychology:

“Disruptions to hypothalamic-pituitary-adrenal (HPA) axis function have been associated with varying forms of psychopathology in children. Studies suggesting children with ADHD have blunted HPA function have been complicated by the prevalence of comorbid diagnoses and heterogeneity of ADHD. The goals of this research were to assess the relations between waking and stress–response salivary cortisol levels and comorbid disruptive behavior (DBD) and anxiety (AnxD) disorders and problems in boys with ADHD, and to examine whether cortisol levels varied across ADHD subtypes.”

The authors examined salivary cortisol on waking and in reaction to venipuncture (to determine stress-response levels), psychiatric symptoms and behavioral problems in 170 elementary school-age boys. The data left no doubt that there are dysfunctional subtypes of ADHD, emphasizing the importance of evaluating each child as an individual:

“Boys’ comorbid AnxD and anxiety problems were associated with greater cortisol reactivity, whereas boys’ comorbid DBD and oppositional problems predicted diminished adrenocortical activity. Reactive cortisol increases were greatest in boys with ADHD and comorbid AnxD, but without DBD…comorbid DBD predicted decreased cortisol reactivity in boys with inattentive and hyperactive subtypes of ADHD, but not in boys with combined subtype of ADHD. The results clarify previous patterns of distinct and divergent dysregulations of HPA function associated with boys’ varying kinds of psychopathology.”

By the way, note that venipuncture (drawing blood) was used elicit a cortisol-modifying stress response. This is one reason why we use saliva instead of blood tests for cortisol.

We can add to this a study published in the journal Child Psychiatry & Human Development that further examines HPA axis dysregulation in a specific subtype of ADHD. The authors set out…

“To investigate the hypothalamic pituitary adrenal (HPA) axis response to a stressor in adolescents with inattentive type attention-deficit hyperactivity disorder symptoms (ADHD-I).”

They too used salivary cortisol measurements as a metric in response to a social/cognitive stressor for threshold inattentive (TI), moderately inattentive (MI) and no symptom groups of healthy adolescents. A distinction was present in this study as well:

“The TI group displayed a significant decrease in cortisol post stressor whereas both the MI and comparison groups showed an increase in cortisol.”

We can also appreciate a study published in the journal Psychiatry Research that looks specifically at aggressive behavior and cortisol. The authors state:

“We examined the relationship between the cortisol response to stress and aggression in patients with attention deficit hyperactivity disorder (ADHD). Based on a report stating that only some of the patients with ADHD retain their hypothalamic-pituitary-adrenal axis reactivity to stress, we separately analyzed the relationship between aggression and the cortisol response to stress in two groups according to their reactivity to stress.”

Their data included psychological testing as a stress indicator with salivary cortisol measurements made before and after psychological test administration. Behavioral problems and aggression were assessed with the local (Korean) version of the Child Behavior Checklist. Their findings also showed the connection:

“The increase of the cortisol level was inversely correlated with aggression in patients who retained their reactivity to stress. The absolute value of the decrease was negatively correlated with the attention score of the CBCL for the patients who showed decreases in cortisol after stress. For the patients who showed increases in their concentration of cortisol in reaction to stress, cortisol may play a protective role against aggression.”

In other words, when cortisol went down aggression went up and attention scored worse. As we can see, there is a large body of evidence showing that we must consider the possibility of hypothalamic-pituitary-adrenal dysregulation in pediatric disorders of learning and behavior. This is best assessed by the functional approach that encompasses the multiple factors such as blood sugar dysregulation, inflammation from allergy or autoimmunity, etc. that can be contributing causes to HPA axis dysfunction, along with experienced assessment of salivary cortisol levels together with associated laboratory findings.

Nutritional and metabolic requirements for pediatric brain health

Posted on September 15, 2010 by Dr. Jonathan

Numerous micro and macronutrients are required to grow and sustain a human brain in both structure and function. A paper published in the Journal of Nutrition, Health & Aging presents evidence for some of the key micronutrients:

“…most micronutrients (vitamins and trace-elements) have been directly evaluated in the setting of cerebral functioning. For instance, to produce energy, the use of glucose by nervous tissue implies the presence of vitamin B1; this vitamin modulates cognitive performance…Vitamins B6 and B12, among others, are directly involved in the synthesis of some neurotransmitters…Supplementation with cobalamin…frequently improves the functioning of factors related to the frontal lobe, as well as the language function of those with cognitive disorders. Adolescents who have a borderline level of vitamin B12 develop signs of cognitive changes.“

Revisiting the importance of iron for the brain:

“Iron is necessary to ensure oxygenation and to produce energy in the cerebral parenchyma (via cytochrome oxidase), and for the synthesis of neurotransmitters and myelin; iron deficiency is found in children with attention-deficit/hyperactivity disorder. Iron concentrations in the umbilical artery are critical during the development of the foetus, and in relation with the IQ in the child; infantile anaemia with its associated iron deficiency is linked to perturbation of the development of cognitive functions.“

Moreover, even subclinical deficiencies of micronutrients can have profound effects:

“…the full genetic potential of the child for physical growth and mental development may be compromised due to deficiency (even subclinical) of micronutrients.”

Macronutrients for the brain are addressed by the same author in an accompanying paper, starting with another look at fats:

“DHA (docosahexaenoic acid) is one for the major building structures of membrane phospholipids of brain and absolutely necessary for neuronal function…ALA acid deficiency alters the course of brain development…the nature of polyunsaturated fatty acids (in particular omega-3, ALA and DHA) present in formula milks for infants (premature and term) conditions the visual, neurological and cerebral abilities, including intellectual…Low fat diet may have adverse effects on mood.“

Regarding protein:

“The nature of the amino acid composition of dietary proteins contributes to cerebral function; taking into account that tryptophan plays a special role. In fact, some indispensable amino acids present in dietary proteins participate to elaborate neurotransmitters (and neuromodulators).”

The importance of blood sugar stability cannot be overstated:

“The regulation of glycaemia (thanks to the ingestion of food with a low glycaemic index ensuring a low insulin level) improves the quality and duration of intellectual performance, if only because at rest the brain consumes more than 50% of dietary carbohydrates, approximately 80% of which are used only for energy purpose. In infants, adults and aged, as well as in diabetes, poorer glycaemic control is associated with lower performances, for instance on tests of memory. At all ages…some cognitive functions appear sensitive to short term variations in glucose availability.”

The author concludes:

“[A] number of findings show that dietary factors play major roles in determining whether the brain ages successfully or experiences neurodegenerative disorders.”

Research recently presented in Psychosomatic Medicine (Journal of Biobehavioral Medicine) investigates:

“……the association between dietary folate, riboflavin, vitamin B-6, and vitamin B-12 and depressive symptoms in a group of adolescents.“

The authors correlated data on dietary intake with scores for depressive symptoms in 3,067 boys and 3,450 girls aged 12 to 15 years as defined by the Center of Epidemiologic Studies Depression Scale. What were the results?

“The prevalence of depressive symptoms was 22.5% for boys and 31.2% for girls. Folate intake was inversely associated with depressive symptoms in both boys and girls. Vitamin B-6 intake was inversely associated with depressive symptoms in both boys and girls. Riboflavin intake was inversely associated with depressive symptoms in girls, but not in boys. No clear association was seen between vitamin B-12 intake and depressive symptoms in either sex.”

Other studies have show an association between low vitamin B12 and depression in adults. We can speculate that this may be due to declining gastric digestive and absorptive capacity with age.

The authors conclude:

“This study suggests that higher intake of dietary B vitamins, particularly folate and vitamin B-6, is independently associated with a lower prevalence of depressive symptoms in early adolescence.“

There is interesting evidence for the importance of zinc in the clinical management of ADHD in a paper published in the journal Progress in Neuro-Psychopharmacology and Biological Psychiatry. The authors state:

“Some studies suggest that deficiency of zinc play a substantial role in the aetiopathogenesis of ADHD. Therefore, to assess the efficacy of zinc sulfate we conducted treatment trial.”

They examined the effect of double-blind treatment with zinc sulfate or placebo on 72 girls and 328 boys with a diagnosis of ADHD. Efficacy was assessed with a triad of rating scales. What did the data show?

“Zinc sulfate was statistically superior to placebo in reducing both hyperactive, impulsive and impaired socialization symptoms, but not in reducing attention deficiency symptoms, as assessed by ADHDS. However, full therapeutic response rates of the zinc and placebo groups remained 28.7% and 20%, respectively. It was determined that the hyperactivity, impulsivity and socialization scores displayed significant decrease in patients of older age and high BMI score with low zinc and free fatty acids (FFA) levels.“

The benefit of carnitine has been investigated for ADHD in boys and presented in a paper published in the journal Prostaglandins, Leukotrienes and Essential Fatty Acids:

“The ADHD behavior was observed by parents completing the Child Behavior Checklist (CBCL) and by teachers completing the Conners teacher-rating score, in a randomized, double-blind, placebo-controlled double-crossover trial.”

Significant improvements in behavior at home and at school were documented:

“Before treatment, the CBCL total and sub-scores were significantly different from those of normal Dutch boys. Responders showed a significant improvement of the CBCL total scores compared to baseline…responders showed higher levels of plasma-free carnitine and acetylcarnitine.“

The authors state in their conclusion:

“Treatment with carnitine significantly decreased the attention problems and aggressive behavior in boys with ADHD.“

An important paper also published in Progress in Neuro-Psychopharmacology and Biological Psychiatry disruption of the metabolism of tryptophan by inflammation can contribute to major depressive disorder (MDD) in adolescents. For background the authors state:

“Cytokine induction of the enzyme indoleamine 2,3-dioxygenase (IDO) has been implicated in the development of major depressive disorder (MDD). IDO metabolizes tryptophan (TRP) into kynurenine (KYN), thereby decreasing TRP availability to the brain. KYN is further metabolized into several neurotoxins…The aims of this pilot were to examine possible relationships between plasma TRP, KYN, and 3-hydroxyanthranilic acid (3-HAA, neurotoxic metabolite) and striatal total choline (tCho, cell membrane turnover biomarker) in adolescents with MDD. We hypothesized that MDD adolescents would exhibit: i) positive correlations between KYN and 3-HAA and striatal tCho and a negative correlation between TRP and striatal tCho…”

The authors employed high resolution proton magnetic resonance spectroscopic imaging to examine fourteen adolescents with MDD, seven of whom had melancholic features, and six healthy controls.

“Positive correlations were found only in the melancholic group, between KYN and 3-HAA and tCho in the right caudate and the left putamen, respectively…These preliminary findings suggest a possible role of the KYN pathway in adolescent melancholic MDD.“

In other words, the authors’ evidence shows that for the melancholic subset of adolescents with major depressive disorder, pro-inflammatory cytokines are disrupting the metabolism of tryptophan into serotonin. This brings into focus special considerations for the management of diet and nutritional precursor supplementation.

Environmental toxins also place a burden on brain metabolism that can disrupt neurodevelopment. A paper published in the journal Neurotoxicology describes the importance of the redox/methylation pathways in the brain. The authors state:

“Autistic children exhibit evidence of oxidative stress and impaired methylation, which may reflect effects of toxic exposure on sulfur metabolism. We review the metabolic relationship between oxidative stress and methylation, with particular emphasis on adaptive responses that limit activity of cobalamin and folate-dependent methionine synthase.”

Methionine synthase activity is required for the dopamine metabolic activity and dopamine receptor function that promotes neuronal synchronization and attention (synchrony is impaired in autism).

“Genetic polymorphisms adversely affecting sulfur metabolism, methylation, detoxification, dopamine signaling and the formation of neuronal networks occur more frequently in autistic subjects…oxidative stress, initiated by environment factors in genetically vulnerable individuals, [can lead] to impaired methylation and neurological deficits secondary to reductions in the capacity for synchronizing neural networks.”

Here we see the possibility of environment conditions demanding extraordinary metabolic support to prevent disruption of developing neural networks.

None of the research presented here implies that a specific nutritional or metabolic intervention is correct for any given individual. In all cases the parents and clinician should keep in mind the possibility that any of these factors may play a role. However, a “try this, try that” approach should be avoided in favor of objectively determining the needs of the individual with the appropriate laboratory tests. While the experienced clinician will have an abundant toolbox, the urinary assessment of organic acids is an indispensable resource.

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.

Gluten sensitivity without celiac disease in the elderly: is there a concern?

Posted on July 19, 2010 by Dr. Jonathan

Scandinavian Journal of Gastroenterology Often tests shows anti-gliadin antibodies (AGA; gliadin is the immunoreactive component of gluten) in the absence of celiac disease but with various autoimmune conditions representing the non-celiac manifestations of gluten sensitivity. The authors of a study just published in the Scandinavian Journal of Gastroenterology explore this issue for the elderly.

“…data suggest that AGA positivity [without celiac disease] might be related to distinct disease entities such as allergy and gluten ataxia (loss of muscular coordination with unsteady movements and gait). Our aim here is to explore the clinical relevance of positive AGA in the elderly population.”

The authors correlated positive lab tests for gluten sensitivity with the incidence of depression and rheumatoid arthritis in 2815 individuals aged 52–74 years. What did their data show?

“Rheumatoid arthritis and depression were found significantly more often in AGA-positives than controls. The significance remained even when tTGA-positive and known celiac disease cases were excluded.”

Don’t forget that anti-gliadin antibody tests are not an absolute screen for gluten (or any other food) sensitivity because there are a number of factors that can suppress the expression of antibodies at the time of specimen collection. However, this study shows that if an elderly person is suffering from depression or rheumatoid arthritis the possibility of gluten sensitivity should be investigated.

Gluten-free diet can improve depression and behavioral problems in adolescents

Posted on May 28, 2010 by Dr. Jonathan

As the authors of this study published in the journal BMC Psychiatry observe:

“Coeliac disease in adolescents has been associated with an increased prevalence of depressive and disruptive behavioural disorders, particularly in the phase before diet treatment.”

We are equally concerned with the ‘non-celiac’ aspects of gluten sensitivity. Gluten related inflammation in the brain can manifest as a host of cognitive, emotional and neurodegenerative disorders in the absence of intestinal manifestations. This is often referred to as “silent celiac disease”:

“Coeliac disease is an under-diagnosed autoimmune type of gastrointestinal disorder resulting from gluten ingestion in genetically susceptible individuals. Non-specific symptoms such as fatigue and dyspepsia are common, but the disease may also be clinically silent.”

They further note that:

“”Depressive symptoms and disorders are common among adult patients with coeliac disease, and depressive and disruptive behavioural disorders are highly common also among adolescents, particularly in the phase before diet treatment. Recently 73% of patients with untreated coeliac disease – but only 7% of patients adhering to a gluten-free diet – were reported to have cerebral blood flow abnormalities similar to those among patients with depressive disorders.”

Their data revealed abnormalities in tryptophan assimilation (tryptophan is the amino acid precursor to serotonin) and prolactin levels in adolescents with celiac disease and depression prior to treatment. Consequently…

“A significant decrease in psychiatric symptoms was found at 3 months on a gluten-free diet compared to patients’ baseline condition, coinciding with significantly decreased coeliac disease activity…”

They also make a fascinating observation that links gluten sensitivity, inflammation, and the serotonergic aspect of depression unrelated to malabsorption:

“…increased production of interferon-γ (IFN-γ), known to be the predominant cytokine produced by gluten-specific T-cells in active coeliac disease, can suppress serotonin function both directly and indirectly by enhancing tryptophan and serotonin turnover…even without malabsorption.”

To diagnose gluten sensitivity in the absence of celiac disease the gluten gene sensitivity test is the most reliable method for a number of reasons.

Vitamin D and depression in older men and women

Posted on May 16, 2010 by Dr. Jonathan

A study recently published in the Journal of Clinical Endocrinology & Metabolism adds more evidence to the importance of maintaining optimum vitamin D levels by investigating the link between suboptimal vitamin D and depression.

“We examined the relationship between 25-hydroxyvitamin D [25(OH)D] and depressive symptoms over a 6-yr follow-up in a sample of older adults.”

The authors measured 25(OH)D in 531 women and 423 men aged 65 and older while assessing them for depressive symptoms with the Center for Epidemiological Studies-Depression Scale (CES-D)over a 6 year period (and adjusted for relevant biomarkers and variables). When they crunched the numbers this is what emerged:

“Women with 25(OH)D less than 50 nmol/liter compared with those with higher levels experienced increases in CES-D scores [and]…significantly higher risk of developing depressive mood over the follow-up. In parallel models, men with 25(OH)D less than 50 nmol/liter compared with those with higher levels experienced increases in CES-D scores [and]…tended to have higher risk of developing depressed mood.”

There are a number of ways that suboptimal vitamin D can contribute to depression (some of which you can read about among these posts). The authors did not investigate the causal mechanisms but settled with this conclusion:

“Our findings suggest that hypovitaminosis D is a risk factor for the development of depressive symptoms in older persons.”

Iron supplementation can cause a zinc deficiency—implications for anger and depression

Posted on May 7, 2010 by Dr. Jonathan

Even borderline anemia due to mild iron deficiency has profound effects. But as this study recently published in the British Journal of Nutrition reveals, care must be taken to avoid creating a functional zinc deficiency even when iron supplementation is necessary. The authors begin by observing…

“Interventions to combat mild Fe deficiency in women of childbearing age may affect Zn nutriture.”

Three groups of subjects with low iron were randomly assigned to one of three groups: dietary advice, a daily iron supplement and placebo. Their data showed that serum zinc increased in the dietary advice group (who ate more meat) and the placebo group. In the iron supplement group zinc decreased, leading to their conclusion:

“Zn status was not improved compared with placebo by an Fe-based dietary intervention. However, a daily moderate-dose Fe supplement with meals appeared to lower Zn status in these young adult women.”

Among its many functions, zinc is involved in neurotransmitter production and the regulation of mood. This important study recently published in the European Journal of Clinical Nutrition begins with the observation…

“The relation of zinc (Zn) nutriture to brain development and function has been elucidated. The purpose of this study is to examine whether Zn supplementation improves mood states in young women.”

The authors used a double-blind, randomized and placebo-controlled procedure to correlate psychological measures, somatic symptoms and serum zinc in two groups who took either a multivitamin or a multivitamin with zinc daily for 10 weeks. What did their data reveal?

“Women who took MV and Zn showed a significant reduction in anger–hostility score and depression–dejection score in the Profile of Moods State (POMS) and a significant increase in serum Zn concentration, whereas women who took only MV did not.”

The authors summarized their findings by concluding:

“Our results suggest that Zn supplementation may be effective in reducing anger and depression.”

It’s easy to see the strong biological momentum to feeling angry and/or depressed around menstruation? Iron is a necessary co-factor for both serotonin and dopamine. Supplementing iron can reduce zinc status, also an important mood-regulating co-factor. Even without adding the hormonal component it’s clear why so many women need help with this.

Side effects of antidepressants are grossly underrecognized by psychiatrists

Posted on April 25, 2010 by Dr. Jonathan

A study just published in The Journal of Clinical Psychiatry brings to light the extent to which the side effects of common antidepressant medications are not recognized or reported by psychiatrists. The authors state:

“Despite the clinical importance of detecting side effects, few studies have examined the adequacy of their detection and documentation by clinicians.”

The authors set out to compare the side effects recorded in the charts of three hundred depressed outpatients undergoing treatment with their own report on a side effects checklist. These were rated according to frequency and the degree of trouble they caused. Their data described a stunning difference:

“The mean number of side effects reported by the patients on the TSES (Toronto Side Effects Scale) was 20 times higher than the number recorded by the psychiatrists.”

Their conclusion is disturbing:

“Psychiatrists may not be aware of most side effects experienced by psychiatric outpatients receiving ongoing pharmacologic treatment for depression.”

Friends, consider the functional medicine approach that objectively evaluates the underlying causal physiology of depression and applies evidence-based interventions on an individual basis that are free of side effects.

Neurotransmitter GABA important for major depression

Posted on April 5, 2010 by Dr. Jonathan

This paper just published in the journal Biological Psychiatry reports on valuable finding that is important for anyone suffering from or treating major depression needs to know: the neurotransmitter GABA can play a significant role in the biological component of major depression. GABA is the most abundant inhibitory neurotransmitter in our bodies. The authors note that

“Several lines of evidence suggest that major depressive disorder is associated with deficits in γ-aminobutyric acid (GABA) inhibitory neurotransmission.”

In their study they used transcranial magnetic stimulation to measure the integrity of GABA function in

“medicated patients with treatment resistant major depressive disorder (TRD), unmedicated patients with major depressive disorder, and medicated euthymic [normal mood] patients with a history of major depressive disorder and compare them with healthy subjects.”

Their compelling findings were that

“All major depressive disorder patient groups demonstrated significant cortical silent period deficits [GABA(B) receptor-mediated inhibitory neurotransmission] compared with healthy subjects.” Interestingly, “only TRD [treatment resistant depression] patients demonstrated significant deficits in short-interval cortical inhibition [GABA(A) receptor-mediated inhibitory neurotransmission] compared with healthy subjects, medicated euthymic major depressive disorder patients, and unmedicated major depressive disorder patients.”

I’m sure readers know that there is much more to the story of major depression than one neurotransmitter. But this is a welcome study for functional medicine practitioners who have seen empirically positive results since we have excellent resources for physiologically supporting improved GABA function. They also noted another finding important for functional medicine doctors and neurotherapists who treat additional biological causes of depression (metabolic, inflammatory, electrical, etc):

“TRD patients also demonstrated a significantly greater resting motor threshold compared with all other clinical subgroups and healthy subjects, suggesting that TRD was also associated with hypoexcitability of the frontal cortex.”

The authors state in conclusion:

“Our findings suggest that GABA(B) neurophysiological deficits are closely related to pathophysiology of major depressive disorder. Our findings also suggest that more severe illness is selectively associated with GABA(A) receptor-mediated inhibitory deficits.”

By the way, four years earlier to the day there was a paper published in the same journal that concluded:

“This study provides evidence of reduced GABAergic [GABA function] tone and motor threshold asymmetry in patients with major depression.”

For an easy reading description on how this investigative approach can help personalize the treatment of depression and more on why GABA is important see this article.