Jeanette M. Johnstone

Nutrient supplementation approaches in the treatment of ADHD

Attention-deficit/hyperactivity disorder (ADHD) is a chronic, debilitating psychiatric illness that often co-occurs with other common psychiatric problems. Although empirical evidence supports pharmacological and behavioral treatments, side effects, concerns regarding safety and fears about long-term use all contribute to families searching for alternative methods of treating the symptoms of ADHD. This review presents the published evidence on supplementation, including single ingredients (e.g., minerals, vitamins, amino acids and essential fatty acids), botanicals and multi-ingredient formulas in the treatment of ADHD symptoms. In most cases, evidence is sparse, mixed and lacking information. Of those supplements where we found published studies, the evidence is best for zinc (two positive randomized, controlled trials); there is mixed evidence for carnitine, pycnogenol and essential fatty acids, and more research is needed before drawing conclusions about vitamins, magnesium, iron, SAM-e, tryptophan and Ginkgo biloba with ginseng. To date, there is no evidence to support the use of St John’s wort, tyrosine or phenylalanine in the treatment of ADHD symptoms. Multi-ingredient approaches are an intriguing yet under-researched area; we discuss the benefits of this approach considering the heterogeneous nature of ADHD.

Childhood neglect and abuse as predictors of antidepressant response in adult depression

Background: Childhood neglect and abuse are recognized as risk factors for depression, but are not often studied as predictors of treatment response in depression. Methods: Clinically depressed outpatients (n=195) were asked about childhood experiences before beginning a randomized antidepressant trial with either fluoxetine or nortriptyline. Three treatment outcomes were measured: Adequate trial, six‐week response and two months sustained recovery. Results: Patients reporting low paternal care (paternal neglect), as measured by the Parental Bonding Instrument (PBI), were less likely to complete an adequate six‐week trial of medication. Patients who reported high maternal protection (maternal overprotection) on the PBI had poorer treatment response in the short‐term at six weeks, and longer term, for two months of sustained recovery. However, abuse, whether sexual, physical, or psychological in nature, did not predict treatment response. Conclusions: The experience of having a neglectful father or an overprotective mother was more predictive of response to treatment for depression than abuse, suggesting that the quality of ongoing intra‐familial relationships has a greater impact on treatment outcomes for depression than experiences of discrete abuse in childhood. Depression and Anxiety, 2009.

Attention-deficit/hyperactivity disorder (ADHD) and being overweight/obesity: New data and meta-analysis

BACKGROUND Literature has suggested that ADHD may be associated with increased risk of obesity. If so, this would have important clinical implications. OBJECTIVE To clarify the size of the association between ADHD and obesity and to evaluate key moderators of the association including medication, gender, age, and psychiatric comorbidity. METHOD Two preliminary studies are presented to supply critical additional data for the meta-analysis: a two-year longitudinal study of an ADHD case-control sample of 313 children aged 7-11, and a national survey study of 45,309 families in the United States using the 2012 National Survey of Childrens Health. Formal meta-analysis was then conducted. The identification procedure yielded 43 studies, reporting 225 comparisons or effect sizes, studying 703,937 participants An overall effect size was estimated with a random effects model (after pooling within study using a modified fixed effects model). Effect size was then examined in relation to medication, gender, age, and psychiatric comorbidity. RESULTS The new study of children revealed no reliable association of ADHD and body mass index at any age or time point. In the national survey, ADHD was associated with obesity only in adolescent girls but not in children or boys; this effect was statistically accounted for by covarying of depression and conduct disorder. In the meta-analysis, the composite effect size was OR=1.22 (95% CI=1.11-1.34); 22 studies provided effects with medication controlled, yielding a composite effect size of OR=1.30 (95% CI=1.12-1.50). Pooled across age the association without covariates was reliable in females (OR=1.19 [1.01-1.41]) but not males (OR=1.10 [0.95-1.23]) although males and females did not statistically differ. Pooled across gender, the association was significantly larger in adults (>18years) (OR=1.37 [1.19-1.58]) than in youth (OR=1.13 [1.00-1.27]), p=.04. CONCLUSIONS ADHD has a small overall association with obesity, but this effect is moderate in adults. The effect is likely to be of no clinical significance in children, possible clinical significance in adolescent girls with comorbid disorders, and of clinical relevance by adulthood.

Micronutrients reduce stress and anxiety in adults with Attention-Deficit/Hyperactivity Disorder following a 7.1 earthquake

The role of good nutrition for resilience in the face of stress is a topic of interest, but difficult to study. A 7.1 earthquake took place in the midst of research on a micronutrient treatment for Attention-Deficit/Hyperactivity Disorder (ADHD), providing a unique opportunity to examine whether individuals with ADHD taking micronutrients demonstrated more emotional resilience post-earthquake than individuals with ADHD not taking micronutrients. Thirty-three adults with ADHD were assessed twice following the earthquake using a measure of depression, anxiety and stress also completed at some point pre-earthquake (baseline). Seventeen were not taking micronutrients at the time of the earthquake (control group), 16 were (micronutrient group). While there were no between-group differences one week post-quake (Time 1), at two weeks post-quake (Time 2), the micronutrient group reported significantly less anxiety and stress than the controls (effect size 0.69). These between group differences could not be explained by other variables, such as pre-earthquake measures of emotions, demographics, psychiatric status, and personal loss or damage following the earthquake. The results suggest that micronutrients may increase resilience to ongoing stress and anxiety associated with a highly stressful event in individuals with ADHD and are consistent with controlled studies showing benefit of micronutrients for mental health.

Moderators of treatment response in adults with ADHD treated with a vitamin-mineral supplement☆

BACKGROUND To date there has been no research investigating moderators of response to micronutrient treatment of mental illness, specifically baseline nutrient levels. METHOD We conducted analyses of data from a randomized placebo-controlled trial (RCT) of 80 adults (≥16years) with Attention-Deficit/Hyperactivity Disorder (ADHD), whereby participants were treated acutely (8weeks) with micronutrients or placebo followed by an open-label (OL) phase of 8weeks whereby all participants received micronutrients. To ensure that all participants had been exposed to the micronutrients for 8weeks, only those 64 who had adhered to the treatment protocol and completed 8weeks on nutrients were included in the data analysis: 34 from the group that had been randomized to the micronutrient arm, and 30 from the group that had been randomized to the placebo group and hence had only received nutrients in the OL phase. Six outcomes were examined: change in ADHD symptoms (self/clinician), ADHD responder, Clinical Global Impression-Improvement (CGI-I), change in mood, and change in Global Assessment of Functioning (GAF). Demographic, developmental and psychiatric history, current clinical characteristics, and baseline nutrient levels were all considered as putative predictors. RESULTS There were significant changes in all outcome variables after 8weeks exposure to the micronutrients. Among the nutrients recorded at baseline, substantial deficiencies (27%) were only observed for vitamin D. However, other than an association showing that higher iron at baseline was correlated with higher baseline depression scores, baseline nutrient levels were not correlated with baseline psychiatric variables/current clinical characteristics. Regression analyses revealed that higher baseline ferritin and lower baseline copper and vitamin D levels were associated with a better response to treatment for some but not all outcomes. None of the other nutrient levels was found to be associated with outcome, including zinc, vitamin B12, iron, and folate. There were no childhood risk factors, demographic variables or clinical correlates that contraindicated micronutrient treatment; more severe symptoms at baseline and greater number of developmental risk factors predicted greater treatment response. CONCLUSIONS Further research looking at nutrients more broadly is required to confirm these initial observations about ferritin, vitamin D and copper; however, the results suggest that serum nutrient levels have limited value for identifying who will respond to treatment.

Magic bullet thinking--why do we continue to perpetuate this fallacy?

We write in response to the editorial on dietary supplementation for the treatment of attention-deficit hyperactivity disorder (ADHD). Although Rajyaguru & Cooper adequately reviewed some of the literature,[1][1] they missed an opportunity to challenge current methodologies and they simultaneously

Childhood predictors of lifetime suicide attempts and non-suicidal self-injury in depressed adults

Objective: Adverse childhood experiences are well-recognized risk factors for a variety of mental health issues, including depression, suicide attempts and non-suicidal self-injury. However, less is known about whether childhood adversity, in the form of low parental care, overprotection and abuse, is associated with suicide attempt and non-suicidal self-injury within a sample of depressed adults. Method: The sample of outpatients (n = 372) was drawn from two randomized depression trials. Childhood adversity variables, depression severity, age of first depressive episode (major depression episode onset), lifetime suicide attempt and non-suicidal self-injury were recorded at baseline. The association between variables and outcome measures was examined using partial correlations, univariate and multivariate logistic regressions. Results: Low maternal care was significantly associated with suicide attempt; low paternal care was associated with non-suicidal self-injury; overprotection was not associated with either outcome. Other risk factors for suicide attempt were major depression episode onset and baseline depression severity. Major depression episode onset was also a risk factor for non-suicidal self-injury. Abuse, regardless of how it was measured, was not significantly associated with either behaviour after adjusting for its correlations with low maternal or paternal care. Conclusion: In this sample of depressed adults, the quality of ongoing, intra-familial relationships, as measured by levels of parental care, had a greater impact on suicide attempt and non-suicidal self-injury than abuse. As the findings were not a priori hypotheses, they require replication. Although the cross-sectional study design limits causal determination, the findings suggest different childhood risk factors for suicide attempt and non-suicidal self-injury and underscore the impact of low parental care on these two behaviours. These findings signal to clinicians the importance of asking specifically about suicide attempts, and non-suicidal self-injury, as well as levels of parental care in childhood. When endorsed, low parental care may be considered an important factor in contextualizing a patient’s depression and potential risk for suicide and non-suicidal self-injury.

Can Micronutrients Improve Neurocognitive Functioning in Adults with ADHD and Severe Mood Dysregulation? A Pilot Study

OBJECTIVES Little research has investigated how micronutrients (minerals and vitamins) affect cognitive functioning, despite preliminary studies showing they may improve psychiatric functioning. INTERVENTION This pilot study investigated the impact of a 36-ingredient micronutrient formula consisting mainly of vitamins and minerals on neurocognitive functioning in 14 adults with attention-deficit/hyperactivity disorder (ADHD) and severe mood dysregulation. DESIGN The formula was consumed in an open-label trial over an 8-week period. OUTCOME MEASURES The participants completed tests of memory (Wide Range Assessment of Memory and Learning) and executive functioning (Delis-Kaplan Executive Functioning System and Conners Continuous Performance Test) at baseline and at the end of the trial. A gender- and age-matched control group of 14 non-ADHD adults not taking the formula were assessed on the same tests 8 weeks apart in order to investigate the impact of practice on the results. RESULTS There were no group differences in ethnicity, socio-economic status and estimated IQ. Significant improvement was observed in the ADHD group, but not the control group, across a range of verbal abilities including verbal learning, verbal cognitive flexibility and fluency, and verbal inhibition. These neurocognitive improvements were large and consistent with improved psychiatric functioning. No changes were noted above a practice effect in visual-spatial memory and there were no improvements noted in reaction time, working memory, or rapid naming for either groups. CONCLUSIONS Although the pilot and open-label design of the study limits the generalizability of the results, it supports a growing body of literature recognizing the importance of nutrients for mental health and cognition. The results also provide evidence supporting the need for randomized clinical trials of micronutrients as well as other experimental studies in order to better assess whether improved neurocognitive functioning may contribute to improved psychiatric symptoms.

Evaluation of dietary intake in children and college students with and without attention-deficit/hyperactivity disorder

Objectives: To evaluate dietary intake among individuals with and without attention-deficit hyperactivity disorder (ADHD), to evaluate the likelihood that those with ADHD have inadequate intakes. Methods: Children, 7–12 years old, with (n = 23) and without (n = 22) ADHD, and college students, 18–25 years old, with (n = 21) and without (n = 30) ADHD comprised the samples. Children’s dietary intake was assessed by a registered dietitian using 24-hour recalls over 3 days. College students kept a detailed food record over three days. Dietary information for both groups was entered into the Nutrition Data Systems for Research database, and output was analyzed using SAS 9.4. Nutrient analyses included the Healthy Eating Index-2010, Micronutrient Index (as a measure of overall micronutrient intake), and individual amino acids necessary for neurotransmission. Logistic regression was used to model the association of nutrient intake with ADHD. Models were adjusted for age, sex, IQ (or GPA), and energy intake (or total protein intake) as appropriate. Significance was evaluated at P = 0.05, and using the Benjamini–Hochberg corrected P-value for multiple comparisons. Results: No evidence existed for reduced nutrient intake among those with ADHD compared to controls in either age group. Across both groups, inadequate intakes of vitamin D and potassium were reported in 95% of participants. Children largely met nutrient intake guidelines, while college students failed to meet these guidelines for nine nutrients. In regards to amino acid intake in children, an increased likelihood of having ADHD was associated with higher consumption of aspartate, OR = 12.61 (P = 0.01) and glycine OR = 11.60 (P = 0.05); and a reduced likelihood of ADHD with higher intakes of glutamate, OR = 0.34 (P = 0.03). Among young adults, none of the amino acids were significantly associated with ADHD, though glycine and tryptophan approached significance. Discussion: Results fail to support the hypothesis that ADHD is driven solely by dietary micronutrient inadequacy. However, amino acids associated with neurotransmission, specifically those affecting glutamatergic neurotransmission, differed by ADHD status in children. Amino acids did not reliably vary among college students. Future larger scale studies are needed to further examine whether or not dietary intake of amino acids may be a modulating factor in ADHD.

Psychosis Resulting From Herbs Rather Than Nutrients

To the Editor: The very useful case report by Wong et al1 illustrates the potential harm of psychosis resulting from concurrent administration of over 50 ingredients, including 18 unregulated herbal agents, 19 digestive enzymes, 6 probiotic strains, and other over-the-counter substances. This is a valuable cautionary message, but the title and abstract lead readers astray. Instead of using specific language to identify the offending agents as herbs, the authors use the general term dietary supplements, an erroneous rubric often used in marketing herbs. By publishing evidence for an adverse herbal interaction with the term dietary supplements, this article inadvertently leads readers (many of whom read only the title and abstract) to believe that this case demonstrates harm from consumption of nutrients fundamental for human health. Without careful reading of the full text and Table 1, readers will not recognize that only 4 of the > 50 ingredients this patient consumed were minerals or vitamins (chromium, vitamin B6, folate, vitamin B12). And, given that the patient’s B12 levels, when tested, were in the low normal range, resulting in treatment with cyanocobalamin 1,000 μg, there is good reason to suspect that even these few nutrients were not very bioavailable or had trivial physiologic impact. It is unlikely that the patient’s psychosis resulted from the direct or combined effects of minerals, vitamins, enzymes, or probiotics. Rather, it is most likely that the patient’s physical and mental impairments resulted from the concurrent use of 18 botanicals, each with its own complex, nonspecific, and largely unmapped pharmacologic actions. Humans have evolved to need dietary nutrients such as minerals and vitamins for the function of every mitochondrion (and hence every cell) of our brains and bodies. In contrast, there is no evidence of evolutionary need of herbs. In fact, physiologically active herbs could be more accurately described as crude drugs that have been misclassified as dietary supplements (eg, St John’s wort, tobacco, marijuana, coca leaf, and poppies are plant parts with psychoactive chemicals). The signatories to this letter have contributed to the rapidly growing empirical literature demonstrating mental health benefits from nutrients (not herbs)2–8 as well as establishing safety of these nutrients,9 even when multiple nutrients are used in combination. It concerns us that the nonspecific use of the term dietary supplements could prejudice interpretation of the scientifically valid studies on nutritional approaches to treating psychiatric conditions. In addition to our own work, there is a large literature supporting the association between dietary patterns and mental health in population studies,10 and a new international society of scientists has formed to study this area (International Society for Nutritional Psychiatry Research; ISNPR.org).11 If the title and abstract of the report had accurately specified that it was primarily about the risk of the concurrent use of multiple unregulated botanical substances, there would be no confusion. Given the present situation, we respectfully ask that a correction be issued.