Telomeres sit at the end of DNA strands and shorten with each cell replication. Shorter telomeres are associated with aging and an increase in multiple medical and psychiatric disorders. New research draws connections between the production of mitochondrial DNA, telomere length, the experience of childhood adversity, and mental illness.
Researcher Audrey Tyrka and colleagues divided 290 healthy adults into four categories based on whether or not they had experienced adversity in childhood and whether they had been diagnosed with a mental illness in their lifetime, including depression, anxiety, and substance abuse. The researchers also analyzed the participants’ telomere lengths and the copy number of their mitochondrial DNA. Both stressful events in childhood (such as maltreatment or the loss of a parent) and a history of mental illnesses (depression and anxiety) were associated with shorter telomeres and higher mitochondrial DNA copy numbers, a measure of cellular aging. Substance abuse was associated with higher mitochondrial DNA copy numbers.
Editor’s Note: This research replicates earlier findings that adversity is associated with shortening telomeres. The finding that mitochondrial DNA could play a role in the long-term effects of early life adversity and mental illnesses is new.
At the 2014 meeting of the International College of Neuropsychopharmacology, researcher Rieva et al. reported that 60% of bipolar patients with comorbid alcohol abuse have attempted suicide, and 48% of bipolar patients with cocaine abuse have attempted suicide. Thus, both of these comorbidities deserve specific attention and treatment. Unfortunately there are currently no Federal Drug Administration–approved drugs for bipolar patients with these comorbidities. The most promising treatments, based on data in patients with primary addictions, are the nutritional supplement N-acetylcysteine and topiramate, which have both performed better than placebo in studies of alcohol and cocaine abuse disorders.
Colleen Hanlon, a researcher at the Medical University of South Carolina, has found that biofeedback can be used to decrease cocaine craving in people with substance abuse problems. In her research, patients were given real time feedback from functional magnetic resonance imaging (fMRI) and learned to decrease the activation of a part of the brain called the anterior cingulate when exposed to cocaine cues (reminders of their desire for cocaine). They were able to decrease drug craving as well as heart rate and skin conduction, which often accompany it.
In adults with bipolar disorder, adversity in childhood has been associated with an earlier onset of bipolar disorder compared to those who did not experience some form of adversity such as verbal abuse, physical abuse, sexual abuse, loss of a parent, abandonment, or neglect. At the 2013 meeting of the Society of Biological Psychiatry, Nancy Low et al. reported that the number of these stressful life events a child experienced was associated with the number of their anxiety symptoms, psychiatric disorders, and lifetime substance abuse. Having experienced 3 or more adversities was associated with a 3.5-fold increased risk for developing a mood disorder and a 3-fold increase in anxiety disorders and alcohol or drug abuse.
While the study has not yet been published in a peer-reviewed journal, the abstract (#194) may be found in the meeting supplement, Volume 73, Number 9S of the journal Biological Psychiatry.
Editor’s Note: Low’s study is the first to report that childhood adversity is a risk factor for the onset of bipolar disorder in the general population.
Given the increasing evidence for the persistence of epigenetic marks on DNA and histones (which can’t change the sequence of genes but can change their structure) in those who have experienced such stressors in childhood, this could provide a mechanism for the long-term vulnerability of these children to the development of mood disorders and a variety of physical illnesses.
Synthetic marijuana, otherwise known as spice, skank, or K2, is not only vastly more potent than the tetrahydrocannabinol (THC) in marijuana plants, but it also lacks cannabidiol (CBD), the calming, antipsychotic substance also present in the plants. This makes spice much more likely to induce major psychiatric effects.
New evidence links use of spice during pregnancy to a tragic birth defect, anencephaly, or absence of the cerebral cortex. It can also lead to the later development of attention-deficit hyperactivity disorder, learning disabilities, memory impairment, depression, and aggression.
Effects of THC on gestation may occur as early as two weeks after conception, meaning by the time a woman realizes she is pregnant, the fetus may have been harmed by exposure to the drug.
Other new finding associate use of spice with acute coronary syndrome and the kind of acute kidney injury that can lead to the organ shutting down.
Editor’s Note: It has now been found that synthetic marijuana, or spice, can lead to psychosis, delirium, acute coronary syndrome (heart attack) in young people, and now kidney dysfunction, in addition to causing birth defects if used by pregnant women. Not only is spice made up of more potent THC without the calming effects of CBD, but it is often laced with unknown contaminants, which are likely the cause of the heart and kidney damage.
Smoking regular marijuana is bad enough—it doubles the risk of psychosis and may precipitate the onset of schizophrenia. It may also cause long-lasting effects on cognitive function. Since many states are legalizing marijuana, it is important to know the risks. In any case the risks are much more serious with the synthetic product, and synthetic marijuana should be avoided at all costs.
Physical punishment of children has long been a controversial subject. A 2012 article by Afifi et al. in the journal Pediatrics suggests that having experienced harsh physical punishment during childhood is associated with mood disorders, anxiety disorders, substance abuse and dependence, and personality disorders in adulthood.
In this study harsh physical punishment included pushing, grabbing, shoving, slapping, or hitting. Participants who had experienced more severe maltreatment in childhood (including physical abuse, sexual abuse, emotional abuse, physical neglect, emotional neglect, and exposure to violence between intimate partners) were excluded from the study, and the results were adjusted for sociodemographic variables and family history of dysfunction, suggesting that physical punishment was the mediator of these effects.
Substance Use Among Canadian Adolescents with Bipolar Disorder: The Critical Need for Intervention and Prevention
At the 2012 meeting of the American Academy of Child and Adolescent Psychiatry (AACAP), Antoinette Scavone presented a poster on correlates of substance use disorders among Canadian adolescents with bipolar disorder. Participants were 62 adolescents aged 14 to 19 with bipolar disorder. Twenty-three participants (37.1%) had a substance abuse disorder.
Those with a comorbid substance use disorder were more likely to have a comorbid panic disorder or an oppositional defiant disorder. They also had higher rates of police contact or arrest, were more likely to have been involved in assault, and were more impulsive. In addition they had experienced more stressful life events.
Editor’s Note: These data from a Canadian sample replicate previous findings in the US and again indicate the critical importance of preventing the onset of substance abuse in adolescents at especially high risk because of their bipolar disorder.
This editor (RM Post) in collaboration with Jacqueline Fleming and Flavio Kapczinski published the article “Neurobiological mechanisms of illness progression in the recurrent affective disorders” in the Journal of Psychiatric Research this year. The article built on several themes about the progression of bipolar illness that had been explored in previous research.
These themes include:
- The likely acceleration of repeated episodes as a function of the number of prior episodes (episode sensitization)
- The increased responsivity of the illness to repeated stressors (stress sensitization)
- The increased behavioral reactivity to repeated use of psychomotor stimulants such as cocaine (stimulant-induced behavioral sensitization)
Not only are these observations well documented in the scientific literature, but recent observations also suggest that each type of sensitization can show cross-sensitization to the other two types. That is, individuals exposed to repeated stressors are more likely both to experience affective illness episodes and to adopt comorbid substance abuse. In a similar way, episodes of an affective disorder and stressors may also be associated with the relapse into drug administration in those who have been abstinent.
In addition to these mechanisms of illness progression in the recurrent affective disorders, the new article reviews the literature showing that the number of affective episodes or the duration of the illness appear to be associated with a variety of other clinical and neurobiological variables.
The number of affective episodes a patient experiences is associated with the degree of cognitive dysfunction present in their bipolar illness, and experiencing more than 4 episodes of unipolar or bipolar depression is a risk factor for dementia in late life. A relative lack of response to most treatments is also correlated with the number of prior episodes, and this holds true for response to naturalistic treatment in general. While most of these data are correlational and the direction of causality cannot be ascertained for certain, it is likely that the number of affective episodes and/or their duration could account for and drive difficulties with treatment and with cognitive function.
If this were the case, one would expect to see a variety of neurobiological correlates with the number of prior episodes or duration of illness, and in the article we summarize those that have been found in unipolar and bipolar disorder. Considerable data indicate that cortical volume and degrees of prefrontal cortical dysfunction can vary as a function of number of prior episodes. There is evidence that increased activity of the amygdala and the nucleus accumbens are also related to episodes or duration of illness. In those with unipolar depression, the volume of the hippocampus is decreased with longer duration of illness. Read more
At the 2012 annual meeting on pediatric bipolar disorder sponsored by the Ryan Licht Sang Foundation and Massachusetts General Hospital, Timothy E. Wilens gave a plenary talk on “The Explosive Combination of Bipolar and Substance Abuse.”
Wilens cited the statistic that 10% of adolescents in the general US population have at some time received a diagnosis of a substance abuse disorder. The age of onset of substance abuse peaks between ages 15 and 20.
Wilens said that in a recent survey about use in the past month, among participants in the general population aged 12 or higher with substance use, about 50% use marijuana and about 50% use prescription narcotics (often obtained from their parents’ medicine chest).
The rate of mortality from substance abuse has risen dramatically since 1993 and now approximates that from automobile accidents. According to Wilens, rates of emergency room visits and fatalities have increased recently, and this has been linked to opiate overdoses.
Adolescents with bipolar disorder are at greatly increased risk of substance abuse compared to the general population. Most substance abuse follows the onset of bipolar disorder, not vice versa.
Wilens cited the data of researcher Ben Goldstein that on 8-year follow up, 32% of bipolar adolescents developed a substance use disorder. Those treated with antimanic agents were much less likely to develop a substance use disorder. MORAL: Treat bipolar disorder psychopathology in adolescents well and help them avoid substance abuse.
Children with persistent emotion dysregulation were: 1) more likely to develop a substance use disorder; 2) more likely to begin using substances earlier; and 3) more likely to have a more severe form of combined (multiple) substance use disorders.
Treating Substance Use
Wilen suggested that a good interview is better than urine toxicology screens for assessing substance use. He suggested the following treatment paradigm: Read more
A symposium on bipolar disorder and its comorbidities in children and adolescents was held at the annual meeting of the American Academy of Child and Adolescent Psychiatry in 2011. The following findings were reported there.
Researcher Janet Wozniak discussed the relationship of bipolar illness and attention deficit hyperactivity disorder (ADHD). Based on interviews of family members of children with bipolar illness alone, bipolar illness plus ADHD, ADHD alone, and controls, she concluded that bipolar illness occurred more often in families of children with bipolar illness with or without ADHD. Similarly, she showed that there was more ADHD in relatives of children with either ADHD alone or ADHD comorbid with bipolar illness. She concluded that the comorbidity of bipolar illness and ADHD is a unique subtype of bipolar disorder and requires further study.
Emotional Dysregulation and Substance Abuse
In another presentation, Tim Wilens indicated that those with bipolar disorder and emotional dysregulation had an 8- to 20-fold increased risk of having a substance abuse comorbidity with their bipolar disorder.
Substance Abuse Comorbidity
In a third presentation, Ben Goldstein reported that the onset of bipolar illness predates the onset of substance abuse in 60 to 83% of instances of comorbid illness. He emphasized the dramatic negative impact of comorbid substance use in children with bipolar disorder in terms of increasing legal entanglements, pregnancy, academic failure, suicide, and decreased compliance with medications. He reported that in the multi-site, National Institute of Mental Health (NIMH)-funded Course and Outcome of Bipolar Illness in Youth (COBY) study, the largest longitudinal study to date of youth with bipolar disorder, the risk of new onset substance abuse over the course of 4 years of follow-up was 32%. These data taken with the 15% of children who already had substance abuse at intake indicates that in this study approximately half of the children with bipolar illness had or acquired a substance abuse problem near the beginning of their illness. Two-thirds of the children in the study had abused both alcohol and cannabis. Read more