psychiatric disorders

Can Neuroimaging Reveal the Roots of Psychiatric Disorders? Not Just Yet

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Summary: While neuroimaging holds great potential in helping researchers link specific patterns of brain activity to mental health disorders, a new study finds there is still a way to go to effectively link neuroimaging results to specific mental health disorders.

Source: Yale

Neuroimaging technology has been shown to hold great promise in helping clinicians link specific symptoms of mental health disorders to abnormal patterns of brain activity. But a new Yale-led study shows there are still kinks to be ironed out before doctors can translate images of the brain to psychiatric disorders such as post-traumatic stress disorder (PTSD).

Their findings are published Jan. 11 in the American Journal of Psychiatry.

Several years ago, The National Institutes of Mental Health launched a multi-billion-dollar research effort to locate biomarkers of brain activity that point to the biological roots of a host of mental health diseases, which today are typically identified by clinical evaluation of a constellation of often overlapping symptoms reported by patients.

“The idea is to forget classification of disease by symptoms and find underlying biological causes,” said Yale’s Ilan Harpaz-Rotem, professor of psychiatry and psychology and senior author of the study.

For the new study, the Yale-led team attempted to replicate the findings of an earlier nationwide neuroimaging study, in which Emory and Harvard scientists linked clusters of brain activity to a variety of outcomes among patients who had arrived at U.S. emergency departments following traumatic events.

Specifically, when researchers measured patients’ brain activity during the performance of simple tasks — including ones that probe responses to threats and rewards — they detected a cluster of brain activity that showed high reactivity to both threat and reward signals and seemed to predict more severe symptoms of PTSD later on.

This shows a brain and a question mark

While they did identify the different clusters of brain activity observed in the earlier study, they found no association with prospective PTSD symptoms. Image is in the public domain

However, when Yale researchers analyzed similar neuroimaging data collected from recent trauma survivors in Israel, they were not able to replicate these findings. While they did identify the different clusters of brain activity observed in the earlier study, they found no association with prospective PTSD symptoms.

“That is not to say one set of data is right and the other is wrong, just that there is a lot of fundamental work that needs to be done to develop reliable models that could generalize across different studies,” said Yale’s Ziv Ben-Zion, a postdoctoral associate at Yale School of Medicine and the corresponding author of the study.

In fact, Yale researchers are currently working with the investigators of the original Emory-Harvard study to merge datasets “to search for common underlying patterns of brain activity associated with different responses to trauma,” Ben-Zion said.

“It took about 100 years to come up with current classifications of mental illness, but we’ve only been exploring refining psychiatric diagnoses using biomarkers for the last 10 years,” said Harpaz-Rotem. “We still have a long way to go.”

Brain Activity During Sleep Differs in Young People With Genetic Risk of Psychiatric Disorders

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Summary: Young people with 22q11.2 Deletion Syndrome have distinct and marked EEG differences in brain activity during sleep, which could influence psychiatric symptoms.

Source: eLife

The brain activity patterns during sleep shed light on the neurobiology behind a genetic condition called 22q11.2 Deletion Syndrome (22q11.2DS) and could be used as a biomarker to detect the onset of neuropsychiatric disorders in people with 22q11.2DS.

22q11.2DS is caused by a gene deletion of around 30 genes on chromosome 22 and occurs in 1 in 3000 births. It increases the risk of intellectual disability, autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD) and epileptic seizures. It is also one of the largest biological risk factors for schizophrenia.

However, the biological mechanisms underlying psychiatric symptoms in 22q11.2DS are unclear.

“We have recently shown that the majority of young people with 22q11.2DS have sleep problems, particularly insomnia and sleep fragmentation, that are linked with psychiatric disorders,” says co-senior author Marianne van den Bree, Professor of Psychological Medicine at Cardiff University, UK.

“However, our previous analysis was based on parents reporting on sleep quality of their children, and the neurophysiology – what’s happening to brain activity – has not yet been explored.”

An established way of measuring brain activity during sleep is an electroencephalogram (EEG). This measures electrical activity during sleep and features patterns called spindles and slow-wave (SW) oscillations.

These features are hallmarks of non-rapid eye movement (NREM) sleep and are thought to aid memory consolidation and brain development.

“Because sleep EEG is known to be altered in many neurodevelopmental disorders, the properties and coordination of these alterations can be used as biomarkers for psychiatric dysfunction” explained lead author Nick Donnelly, Clinical Lecturer in General Adult Psychiatry at the University of Bristol, UK

To explore this in 22q11.2DS, the team recorded sleep EEG over one night in 28 young people aged 6-20 years old with the chromosome deletion and in 17 unaffected siblings, recruited as part of the Cardiff University Experiences of Children with copy number variants (ECHO) study, led by Prof. van den Bree. They measured correlations between sleep EEG patterns and psychiatric symptoms, as well as performance in a recall test the next morning. 

They found that the group with 22q11.2DS had significant alterations in sleep patterns including a greater proportion of N3 NREM sleep (slow-wave sleep) and lower proportions of N1 (the first and lightest sleep stage) and rapid eye movement (REM) sleep, compared with their siblings.

Those carrying the chromosome deletion also had increased EEG power for both slow-wave oscillations and spindles. There was also an increase in the frequency and density of spindle patterns and stronger coupling between the spindle and slow-wave EEG features in the 22q112.DS group.

These changes may reflect alterations in the connections within and between areas of the brain that generate these oscillations, the cortex and the thalamus.

Participants also took part in a 2D object location task before sleep, where they had to remember where matching cards were on a screen. They were tested again on the same task in the morning, and the team found that in those with 22q11.2DS, higher spindle and SW amplitudes were associated with lower accuracy.

This shows a young girl sleeping
They found that the group with 22q11.2DS had significant alterations in sleep patterns including a greater proportion of N3 NREM sleep (slow-wave sleep) and lower proportions of N1 (the first and lightest sleep stage) and rapid eye movement (REM) sleep, compared with their siblings. Image is in the public domain

By contrast, in participants without the chromosome deletion, higher amplitudes were linked to higher accuracy in the morning recall test. 

Finally, the team estimated the impact of the differences in sleep patterns on psychiatric symptoms in the two groups using a statistical method called mediation.

They calculated the total effect of genotype on psychiatric measures and IQ, the indirect (mediated) effect of EEG measures, and then the proportion of the total effect that may be mediated by EEG patterns.

They found that the effects on anxiety, ADHD and ASD driven by the 22q11.2 deletion were partially mediated by sleep EEG differences.  

“Our EEG findings together suggest a complex picture of sleep neurophysiology in 22q11.2DS and highlight differences that could serve as potential biomarkers for 22q11.2DS-associated neurodevelopmental syndromes,” concluded co-senior author Matt Jones, Professorial Research Fellow in Neuroscience, University of Bristol, UK.

Abstract

Sleep EEG in young people with 22q11.2 deletion syndrome: a cross-sectional study of slow-waves, spindles and correlations with memory and neurodevelopmental symptoms

Background: Young people living with 22q11.2 Deletion Syndrome (22q11.2DS) are at increased risk of schizophrenia, intellectual disability, attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). In common with these conditions, 22q11.2DS is also associated with sleep problems. We investigated whether abnormal sleep or sleep-dependent network activity in 22q11.2DS reflects convergent, early signatures of neural circuit disruption also evident in associated neurodevelopmental conditions.

Methods: In a cross-sectional design, we recorded high-density sleep EEG in young people (6-20 years) with 22q11.2DS (n=28) and their unaffected siblings (n=17), quantifying associations between sleep architecture, EEG oscillations (spindles and slow waves) and psychiatric symptoms. We also measured performance on a memory task before and after sleep.

Results: 22q11.2DS was associated with significant alterations in sleep architecture, including a greater proportion of N3 sleep and lower proportions of N1 and REM sleep than in siblings. During sleep, deletion carriers showed broadband increases in EEG power with increased slow-wave and spindle amplitudes, increased spindle frequency and density, and stronger coupling between spindles and slow-waves. Spindle and slow-wave amplitudes correlated positively with overnight memory in controls, but negatively in 22q11.2DS. Mediation analyses indicated that genotype effects on anxiety, ADHD and ASD were partially mediated by sleep EEG measures.

Conclusions: This study provides a detailed description of sleep neurophysiology in 22q11.2DS, highlighting alterations in EEG signatures of sleep which have been previously linked to neurodevelopment, some of which were associated with psychiatric symptoms. Sleep EEG features may therefore reflect delayed or compromised neurodevelopmental processes in 22q11.2DS, which could inform our understanding of the neurobiology of this condition and be biomarkers for neuropsychiatric disorders.

Accumulating evidence suggests curcumin and turmeric can treat psychiatric disorders

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Living with a psychiatric disorder can be devastating for both sufferers and their loved ones. Unfortunately, many of the solutions offered by modern medicine do more harm than good while offering little in the way of relief. Thankfully, researchers have discovered that a compound in the popular Indian spice turmeric has the potential to effectively treat psychiatric disorders like bipolar disorder and depression.

You may have heard the fanfare about turmeric’s anti-inflammatory properties, which it gets from a compound within the spice known as curcumin. It has long been used in traditional Chinese medicine and has been gaining popularity in Western medicine in recent years. This polyphenol is being revered for its protective, anti-inflammatory and antioxidant properties, and is being used to help fight cancer and stop the cognitive decline of neurodegenerative disorders like Alzheimer’s. Non-toxic and affordable, it’s showing a lot of promise in helping deal with many of the health problems facing people today.

Image: Accumulating evidence suggests curcumin and turmeric can treat psychiatric disorders

The same anti-inflammatory qualities that make it so good at addressing issues like arthritis can also extend to mood disorders. Not only does it reduce levels of tumor necrosis factor alpha and inflammatory interleukin-1 beta, but it also reduces salivary cortisol concentrations while raising the levels of plasma brain-derived neurotrophic factor.

A study carried out by researchers at Australia’s Murdoch University found that curcumin extracts reduced people’s anxiety and depression scores. They noted that it was particularly effective at alleviating anxiety. Moreover, even low doses of the spice extract were effective in addressing depression. In addition, the researchers found it worked quite well on those with atypical depression, which is a marker of bipolar depression.

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Growing evidence of curcumin’s usefulness in addressing psychiatric disorders

Curcumin has been found in other studies to be just as effective as one of the most popular SSRI antidepressants on the market, Prozac, making it an excellent option for those who wish to avoid the negative side effects of this psychiatric medication. It works by raising levels of dopamine and serotonin, two vital neurotransmitters related to depression. In addition, because depression is believed to be caused by chronic inflammation, it makes sense that curcumin’s ability to reduce inflammation could alleviate depression.

Interestingly, studies have also found that when curcumin is taken either alone or with saffron, it reduces the symptoms of anxiety and depression in those suffering from major depressive disorder. When taken alongside the herb fenugreek, meanwhile, it can reduce fatigue, stress and anxiety in those with extreme occupational stress. Curcumin supplementation has also been shown to significantly improve compulsiveness and memory loss in those with obsessive-compulsive disorder.

It’s also worth noting that curcumin can be taken alongside antidepressants safely; studies have even shown taking the two together can enhance their effectiveness. However, it’s important to keep in mind that antidepressants carry a lot of risks, so it’s worth exploring whether curcumin alone could be enough to alleviate an individual’s depression.

The idea of curcumin helping with mood is supported by a study that was published in the American Journal of Geriatric Psychiatry earlier this year. In that study, researchers found that participants who took curcumin supplements noted mood improvements, and they plan to explore this connection in a study of patients with depression. The researchers expressed optimism that curcumin could be a safe way to provide people with cognitive benefits; they also discovered the spice can improve memory.

Now, researchers are looking for ways to increase curcumin’s bioavailability so that people can enjoy the benefits of this all-star natural treatment. In the meantime, be sure to add black pepper to your dishes when cooking with turmeric or look for curcumin supplements that contain piperine, a black pepper extract, as this boosts its bioavailability.

MAGNESIUM: THE SAFE FIRST LINE OF DEFENSE FOR CLINICAL DEPRESSION

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The science supporting the efficacy of magnesium for major depression and other psychiatric disorders, testing for magnesium deficiency, and which forms and dosages are most effective.

Depression, a life-threatening psychiatric disorder, lies at the confluence of biochemical, hormonal, immunological, and neurodegenerative variables, which intersect to generate the pro-inflammatory state with which depression is associated. A major public health issue, depression is estimated to become one of the top three contributors to the global burden of diseases within a few years. Not only does depression consume a sizable portion of health care expenditures, but it is considered to be an independent risk factor for metabolic, cardiovascular, and neuropsychiatric disorders (1).

Current treatments are predicated upon a misguided serotonin theory of depression, and are accompanied by a laundry list of deleterious side effects ranging from sexual dysfunction to homicidality (2, 3, 4). Antidepressant medications likewise significantly increase the risk of all-cause mortality, or death from any cause, as well as heart disease, leading researchers to deem this class of pharmaceuticals as harmful to the general population (5). This, in combination with data indicating that antidepressants are clinically equivalent to placebo, render them an unfavorable option (6), especially considering that they offer little in the way of resolving the root cause.

Magnesium: The Miracle Mineral

Rather than resorting to psychotropic drugs, it would be prudent to explore whether magnesium (Mg) supplementation improves depression, since this essential mineral is implicated in the pathophysiology of this disorder. Magnesium may be indeed branded as miraculous given its essentiality as a cofactor to over three hundred enzymatic reactions (7). It is second only to potassium in terms of the predominant intracellular cations, or ions residing in cells that harbor a positive charge (7).

 Magnesium is fundamentally involved in protein production, synthesis of nucleic acids, cell growth and division, and maintenance of the delicate electrolyte composition of our cells (7). It also imparts stability to the membranes of the energy factories of our cells called mitochondria (7). As articulated by researchers, “The physiological consequences of these biochemical activities include Mg’s central roles in the control of neuronal activity, cardiac excitability, neuromuscular transmission, muscular contraction, vasomotor tone, and blood pressure” (7).

The biological effects of magnesium are widespread. When deficient, magnesium is correlated with systemic inflammation. Not only does magnesium sufficiency promote cardiovascular health, relaxing the smooth muscles that comprise blood vessels and preventing high levels of vascular resistance that cause hypertension, but it also plays a role in musculoskeletal health and prevents sarcopenia, osteoporosis, and fractures (8). Magnesium is essential to regulation of sleep (9) and vitamin D metabolism (10) as well as neural plasticity and cognitive function.

However, food processing and industrial agriculture, including monoculture crop practices and the use of magnesium-devoid fertilizers, have led to soil erosion and depletion of magnesium content in our food (7). Magnesium is likewise removed from most drinking water supplies, rendering magnesium deficiency an inevitability (11). As such, our daily intake of magnesium has steadily declined from 500 milligrams (mg) per day to 175 mg per day (7). The nutrient-poor, energy-dense dietary patterns which have come to dominate the industrialized landscape are also insufficient in the fiber-rich fruits and vegetables which contain magnesium.

Animal Studies Propose a Role for Magnesium in Depression

Preliminary animal studies pointed to a role of magnesium in depression, as depletion of magnesium in the diet of mice lead to enhanced depression- and anxiety-related behavior such as increased immobility time in the forced swim test (12). In the forced swim test, a common assay for examining depression-like behavior in rodents, the animal is confined to a container filled with water and observed as it attempts to escape. The time in which the animal exhibits immobility is used as a barometer of despair, indicating that the animal has succumbed to a fate of drowning (1).

This model is confirmed by studies showing that administering substances with antidepressant properties such as Hypericum perforatum, also known as St. John’s Wort, can significantly decrease the time the animal spends without locomotor activity (12). In addition, the time the animal spends immobilized is influenced by many of the factors that are changed as a consequence of depression in humans, such as drug-withdrawal-induced anhedonia, impaired sleep, and altered food consumption (1).

Human Studies Confirm the Role of Magnesium in Depression

There is a paucity of research on the influence of specific micronutrients in depression and results are inconsistent, but several studies have revealed low serum magnesium in this mood disorder. It is well-documented, for example, that dietary magnesium deficiency in conjunction with stress can lead to neuropathologies and symptoms of psychiatric disorders. Researchers echo this sentiment, stating that, “Dietary deficiencies of magnesium, coupled with excess calcium and stress may cause many cases of other related symptoms including agitation, anxiety, irritability, confusion, asthenia, sleeplessness, headache, delirium, hallucinations and hyperexcitability” (11, p. 362).

The Hordaland Health study in Western Norway illustrated an inverse association between standardized energy-adjusted magnesium intake and depression scores, meaning that people who consumed less magnesium had higher rates of depression (13). When the serum and cerebrospinal fluid of acutely depressed patients diagnosed with major depressive disorder or bipolar patients in a depressive episode were compared to healthy controls, the calcium to magnesium ratio was found to be elevated in the former (14). Calcium and magnesium are minerals which antagonize one another and compete for absorption, since each of these minerals is a divalent cation (a positive ion with a valence of two). Suicidality, one of the primary manifestations of severe depression, is accompanied by low cerebrospinal fluid levels of magnesium despite normal calcium levels, lending credence to the role of magnesium in positive emotionality (15).

Magnesium Effective in Bipolar Disorder, Fibromyalgia, PMS, and Chronic Fatigue Syndrome

A formulation of magnesium aspartate hydrochloride known as Magnesiocard has been shown to invoke mood-stabilizing effects in patients with severe rapid cycling bipolar disorder in one open study label (16). In half of the patients treated, this magnesium preparation had results equivalent to lithium, the standard of care for this patient population, such that the researchers suggested: “The possibility that Magnesiocard could replace or improve the efficacy of lithium as a preventive treatment of manic-depressive illness merits further clinical investigation” (16, p. 171). When used as an adjunctive therapy in severe, therapy-resistant mania, magnesium sulphate infusions significantly reduced the use of lithium, benzodiazepines and neuroleptics, so much so that the researchers concluded that it “may be a useful supplementary therapy for the clinical management of severe manic agitation” (17, p. 239).

In another randomized trial of elderly patients with type 2 diabetes and magnesium deficiency, elemental magnesium administered at 450 mg per day was found to have equivalent efficacy to 50 mg of the antidepressant drug Imipramine in treating depressive symptoms (18). Magnesium citrate taken at 300 mg per day has likewise been shown to decrease depression and other symptoms in patients with fibromyalgia as indicated by significant decreases in the fibromyalgia impact questionnaire (FIQ) and Beck depression scores (19).

Data also indicate that supplementation with 360 mg of magnesium administered to women with premenstrual syndrome (PMS) three times a day in the second half of the cycle is effective for so-called negative affect and other premenstrual-related mood symptoms (20). Lastly, intramuscular magnesium sulphate administered every week for six weeks has been proven to be effective in improving emotional state and other parameters in chronic fatigue syndrome (CFS) (21).

Mechanism of Action for Antidepressant Effects of Magnesium

According to researchers, “Biological systems discussed to be involved in the pathophysiology of affective disorders and the action of mood stabilizing drugs are affected by Mg, such as the activity of the hypothalamus–pituitary–adrenocortical (HPA) system, corticotropin releasing factor (CRF)-, GABA- and glutamatergic (via NMDA receptors) neurotransmission and several transduction pathways including protein kinase C” (12). Not only that, but magnesium elicits similar effects on nocturnal hormonal secretion and sleep brain waves to lithium salts, which are used as a treatment modality for bipolar disorder, supporting the role of magnesium as a mood stabilizer (22).

Magnesium operates as an agonist, or a stimulatory molecule, for γ-aminobutyric acid (GABA) receptors (22). GABA is the main inhibitory neurotransmitter in the central nervous system. By binding to the GABA receptor and replicating the effects of GABA, magnesium may alleviate anxiety. Magnesium may also elicit its antidepressant effects by acting as an inorganic antagonist of N-methyl-d-aspartic acid (NMDA) receptor function (Poleszak et al., 2007). Receptor antagonists are ligands, or substances, which bind to a receptor but inhibit its activity rather than activating it. NMDA receptors, which occur on the surface of nerve cells, are activated in part by glutamate, one of the excitatory amino acids in the brain.

Researchers state that, “Dysfunction of NMDA receptors seems to play a crucial role in the neurobiology of disorders such as Parkinson’s disease, Alzheimer’s disease, epilepsy, ischemic stroke, anxiety and depression,” such that, “ligands interacting with different sites of NMDA receptor complex are widely investigated as potential agents for the treatment of a variety of neuropsychiatric disorders” (22). In fact, drug inhibitors at the NMDA receptor complex, such as ketamine, demonstrate antidepressant effects (23, 24), but also induce such severe side effects that their clinical utility is limited (31). Magnesium, on the other hand, may have a similar mechanism of action by interfering with NMDA receptor activation without the adverse consequences of drug-induced NMDA receptor blockade (25).

Recent Study Proves Efficacy of Oral Magnesium for Depression

A recent open-label, randomized, cross-over trial was conducted in outpatient primary care clinics on 126 adults diagnosed with depression (26). During the intervention, 248 mg of elemental magnesium chloride per day, obtained from four 500 mg tablets, was administered for six weeks and compared to six weeks of no treatment, and subjects were evaluated for changes in depressive symptoms (26).

Magnesium administration results in clinically significant improvements in scores on both the Patient Health Questionnaire-9 (PHQ-9), a validated measure of the severity of depression and response to treatment, as well as the Generalized Anxiety Disorders-7 (GAD-7), a sensitive self-reported screening tool for severity of anxiety disorders (26). Impressively, results appeared in as little as two weeks, representing the dramatic improvement that nutrient restoration can facilitate (26). Impressively, however, magnesium exerted anti-depressant effects regardless of baseline magnesium level. It also exhibited efficacy independent of the gender, age, or baseline severity of depression of subjects, as well as their use of antidepressant medications (26). The authors of the study conclude, “Magnesium is effective for mild-to-moderate depression in adults. It works quickly and is well tolerated without the need for close monitoring for toxicity” (26).

Populations At Risk for Magnesium Deficiency

Half of the population of the United States was found to consume less than the recommended amount of magnesium when estimated a decade ago (27). Not only is magnesium lost with certain medical conditions, but this mineral is excreted as a consequence of biological activities such as sweating, urinating, and defecating as well as excess production of stress hormones (7, 11). In addition, because low magnesium has been correlated with various disease states, increasing magnesium status may mitigate risk of these diseases.

For instance, researchers note that, “Low magnesium intakes and blood levels have been associated with type 2 diabetes, metabolic syndrome, elevated C-reactive protein, hypertension, atherosclerotic vascular disease, sudden cardiac death, osteoporosis, migraine headache, asthma, and colon cancer” (27, p. 153). In addition, magnesium deficiency at a cellular level “elicits calcium-activated inflammatory cascades independent of injury or pathogens” (27, p. 153). Low magnesium is associated with systemic inflammation, and inflammation is at the root of most chronic and degenerative diseases.

Testing for Magnesium and Food Sources of Magnesium

While the first inclination of some physicians may be to test magnesium levels for an objective parameter of deficiency, the widely used serum or plasma magnesium does not accurately reflect magnesium levels stored in other tissues (28, 29). In addition, both this hematological index of magnesium status, referred to as total magnesium, and the erythrocyte magnesium level, indicative of the levels of magnesium inside red blood cells, are not negatively affected until severe magnesium deprivation has occurred (7). Therefore, these testing methodologies are not accurate enough to catch preliminary or subclinical magnesium deficiency.

Good food sources of magnesium include pumpkin and squash seed kernels, Brazil nuts, almonds, cashews, peanuts, pine nuts, quinoa, spinach, Swiss chard, beet greens, potatoes, artichoke hearts, dates, bananas, coconut milk, prickly pear, black beans, lima beans, soybeans, and seafood sources including halibut, abalone, anchovy, caviar, conch, crab, oyster, scallop, snail, and pollock. However, it is important to note that magnesium can be leeched from vegetables when food is boiled, and that fiber in excess can decrease magnesium absorption by increasing gastrointestinal motility (7).

Most Bioavailable Forms of Magnesium

As elucidated by the researchers, “Over-the-counter magnesium can be offered as an alternative therapy to those patients hesitant to begin antidepressant treatment and is easily accessible without a prescription” (26). Because the soil is no longer enriched in magnesium, supplementation may be warranted. Organic salts of magnesium, including the acetate, ascorbate, aspartate, bicitrate, gluconate, and lactate forms are more soluble and biologically active over the magnesium mineral salts such as magnesium oxide, magnesium carbonate, magnesium chloride, and magnesium sulfate (7).

However, case studies have shown remarkably rapid recovery from major depression, in less than seven days, when magnesium glycinate and magnesium taurinate are administered at dosages of 125 to 300 mg with each meal and at bedtime (11). Magnesium threonate may also be explored as a therapeutic option, as it may have better penetrance of the blood brain barrier and restore neurological levels of magnesium. This form, which is delivered directly to the brain, may improve cerebral signaling pathways and synaptic connections between nerve cells as well as support learning and memory, although the studies have been conducted in animal models (30).

Researchers report that magnesium is usually effective for treating depression in general use, and that comorbid conditions occurring in these case studies, including “traumatic brain injury, headache, suicidal ideation, anxiety, irritability, insomnia, postpartum depression, cocaine, alcohol and tobacco abuse, hypersensitivity to calcium, short-term memory loss and IQ loss were also benefited” by magnesium supplementation (11, p. 362). Barring abnormal kidney function, the Institute of Medicine sets the upper tolerable limit for intake at 350 mg of elemental magnesium per day, but there are few adverse side effects documented unless consumed in inordinate doses (26).

Before changing your medication or nutraceutical regimen, always consult a functional or integrative medical doctor for contraindications. However, given the benign nature of magnesium supplementation and the ubiquity of magnesium insufficiency, depressedpatients should be offered this as a first line strategy alongside a holistic root-cause resolution approach to treating depression

Antidepressant Drugs Affect Neurotransmitters Differently, Sometimes Increasing Thoughts Of Suicide Among Young Adults

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The idea it gets worse before it gets better is applicable to certain antidepressants, according to a new paper published in the journal Trends in Cognitive Sciences.

depression

Selective serotonin reuptake inhibitors (SSRIs) are among the most prescribed drugs (or overprescribed depending on who you talk to) for psychiatric disorders, including depression, anxiety, and eating disorders. They work to increase the brain’s level of serotonin — a chemical that work as a neurotransmitter and is responsible for maintaining mood balance — while inhibiting its reuptake (absorption) into the brain’s presynaptic cell. Chemical synapses are what allow neurons to form circuits within the central nervous system, as well as help connect to and control other systems of the body.

While serotonin can increase up to hours after an SSRI is taken, it takes two weeks before patients notice a subside in symptoms. It’s during this delay researchers from Otto-von-Guericke University believe depression gets worse before it gets better. Specifically, this delay stems from the different ways SSRI affects serotonin and another brain chemical called glutamate, which are both released from the serotonin neuron. Glutamate is the brain’s main excitatory neurotransmitter, and it’s important for neural communication, memory formation, learning and regulation.

Researchers culled data from existing studies and found when taking an SSRI, serotonin is immediately amplified while glutamate is suppressed. This balance is only restored after several days of drug treatment, Adrian Fischer, lead study author, said in a press release. Fischer added the serotonin component has been linked to motivation, while the glutamate component has been linked to pleasure and learning.

Put it another way: An SSRI immediately boosts motivation in depressed patients, while at the same time it’s hampering hedonic components (pleasure) of the reward system. The answer isn’t a higher dose of SSRIs either. Instead, researchers found this combination, whatever the dose, “could lead to the facilitation of suicidal thoughts or behavior in the early weeks of SSRI administration,” especially in young adults.

Pharmacology experts refer to this as a “paradoxical reaction.” Medical Daily previously reported this type of reaction is not uncommon among depression sufferers. One study was on par with the current study’s findings: 42 10- to 17-year-olds were compelled to self-harm after taking Prozac, four of which were hospitalized.

Fischer and his team concluded their paper “offers a framework of directly testable predictions for a better understanding and interpretation of studies employing SSRI challenges.” It also opens potentials for new drugs aiming to delay onset of SSRIs in depression. As always, consult with your doctor on the medication that is best suited for your particular symptoms; antidepressant, and otherwise prescription drugs, aren’t one size fits all. And if patients are prescribed medication, be sure to read up on possible side effects.

Source: Fischer A, Jocham G, Ullsperger M. Dual serotonergic signals: a key to understanding paradoxical effects? Trends in Cognitive Sciences. 2014.