Adolescent Brain Particularly Susceptible to Decline in IQ from Marijuana Use
A decades-long study in New Zealand suggests that people who use marijuana persistently during adolescence lose 8 IQ points by adulthood compared to their peers who never use marijuana. Quitting or reducing cannabis use after adolescence did not restore the intellectual abilities in those who used it persistently in their youth. This is the first study of its kind that controlled for differences in functioning that existed before adolescence.
Participants took part in neuropsychological testing at the age of 13, prior to any cannabis use, and then were periodically interviewed about their use of the drug (at the ages of 18, 21, 26, 32, and 38). At age 38 they underwent IQ testing again.
Although persistent cannabis users tended to have fewer years of education, the lack of education was not responsible for the difference in adult IQ.
Those participants who only began using cannabis persistently in adulthood did not see a decline in IQ, suggesting that the adolescent brain is particularly susceptible to damage from cannabis use.
Synthetic Marijuana Comes with Serious Risks, Including Risks to Fetus
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.
Harsh Physical Punishment is Associated with Mood and Other Disorders
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.
Women with Bipolar Disorder at Higher Risk for Postpartum Depression
The risk of having a depressive episode during pregnancy compared to afterward have not often been studied. A 2011 review article by Viguera et al. in the American Journal of Psychiatry compared rates of affective episodes among women with bipolar I and II disorders and recurrent major depressive disorder, both during pregnancy and the postpartum period. Risks were higher for women with bipolar disorder.
Among women with bipolar disorder, 23% experienced mood episodes during the pregnancy, while 52% had an episode in the months after giving birth. Among women with unipolar depression, 4.6% had a mood episode during pregnancy, while 30% did during the postpartum period, which is about double the risk seen in the general population. Depression was the most common type of morbidity the women experienced before and after giving birth.
Risk factors associated with mood episodes during pregnancy included (in descending order): younger age at illness onset, previous postpartum episodes, fewer years of illness, bipolar disorder, fewer children, and not being married. Risk factors associated with postpartum episodes included: younger age at illness onset, illness during pregnancy, bipolar disorder, fewer children, and more education.
Editor’s Note: The risk of postpartum depression increases from 15% in the general population, to 30% among women with unipolar disorder, to 50% in women with bipolar disorder. Special precautions should be taken to monitor and treat depression during and after pregnancy, in all women but particularly in those with a prior history of unipolar or bipolar disorder.
Rats Exposed to Jet Fuel Pass Epigenetic Changes on to Third Generation
A recent study of rats showed that exposure to hydrocarbons (jet fuel JP-8) can bring about disease not just in the rats who were exposed, but also in subsequent generations. Epigenetics is the study of how environmental events or biochemical changes can affect the structure of DNA, e.g. by attaching extra methyl groups. (These kinds of “epimutations” are separate from the inherited genetic makeup we receive from our parents, but new evidence suggests that some can be passed on to future generations.)
When first generation female rats were exposed to jet fuel, third generation rats showed 33 different examples of DNA methylation as well as obesity.
Previous research has shown similar signs of transgenerational transmission of disease resulting from first generation exposure to chemicals such as bisphenol A, phthalates, dioxins, and pesticide mixtures.
Female Rodents Are More Sensitive to Defeat Stress and Its Cross-Sensitization to Cocaine
Among rodents, being subjected to defeat stress (when an intruder mouse is threatened by a larger mouse defending its territory) can make an animal more susceptible to cocaine. This is referred to as cross-sensitization.
Researcher Elizabeth Holly and colleagues have found that compared to males, female rodents are more sensitive to defeat stress and have greater reactions to cocaine and cocaine sensitization following this type of stress. This is probably related to a neuropeptide called corticotropin releasing factor (CRF), which is associated with cross-sensitization. When the mice were exposed to cocaine, there were increases in CRF in a part of the brain called the ventral tegmental area (VTA), which contains cell bodies of dopamine neurons that travel to the nucleus accumbens, the brain’s reward center. Blocking the CRF receptors in the VTA prevented the sensitization to cocaine from occurring in the mice.
Editor’s Note: These data in animals resemble clinical observations in humans that women are more sensitive to stress and are more prone to depression, and can have an exceedingly difficult time stopping cocaine use if they become addicted.
Folic Acid Supplementation Not Linked To Cancer
Folic acid is often recommended for patients with difficult-to-treat depression and for pregnant women. A recent study suggested that when taken before and in the first weeks of pregnancy, the vitamin supplement can reduce the risk of autism in the child. However, some concern was raised after a 2007 study that suggested a possible link between folic acid and cancer risk. New research indicates that cancer is not a risk of folic acid supplementation.
In a meta-analysis that analyzed data from 13 different trials of folic acid that included a total of over 49,000 patients, no increased risk of cancer was found in patients taking folic acid. The meta-analysis was published this year in the Lancet.
Editor’s Note: In addition to folic acid’s beneficial effects during pregnancy, it can also enhance the effects of antidepressants and mood stabilizers. The dose typically recommended for depression is 1mg for women and 2mg for men.
Fifteen percent of the population has an inefficient form of the enzyme methylenetetrahydrofolate reductase (MTHFR), which converts folate to methylfolate. For treatment of depression in these individuals, l-methylfolate should be used instead of regular folic acid.
Reminder: Multiple Risks for Fetus in Mothers Treated with Valproate
In pregnant women, exposure of the fetus to the anticonvulsant valproate (VPA or Depakote) is associated with a variety of serious problems that include congenital malformations, developmental delay, and autism.
The major congenital malformations that can result from valproate exposure include spina bifida, which results in lifelong paralysis of the child’s lower limbs.
Developmental delay resulting from valproate exposure can cause an average loss of 9 IQ points compared to children exposed to other anticonvulsant drugs in utero. The effects appear to be in part dose-related and dependent on the intensity of combination treatment with other agents. These deficits were originally seen in children at 3 years of age and were shown to persist in six-year-olds according to an article by Meador et al. this year in Lancet Neurology.
Now in addition, fetal exposure to valproate has been liked to autism and related disorders in an 11-year longitudinal study published this year in the Journal of Neurology, Neurosurgery and Psychiatry. A diagnosis of a developmental disorder occurred in 17% of children whose mothers were on valproate as opposed to 2% whose mothers were on carbamazepine and 7% whose mothers were on lamotrigine.
Neurologists are increasingly recommending that all women of childbearing age who are on a treatment regimen including valproate be treated with folic acid and vitamins B6 and B12, in the hopes that these might mitigate valproate’s effects on the fetus in the case of an unplanned pregnancy. The effectiveness of these vitamins has not been directly demonstrated. However, the study by Meador et al. did show that children of mothers who took prenatal folic acid supplements had IQs on average 7 point higher than children whose mothers did not. The benefit was seen only when mothers were already taking folic acid when they became pregnant and was not observed in children of mothers who began taking it after the first trimester.
Women of childbearing age should avoid valproate and if this is not possible, they should carefully protect themselves against an unwanted pregnancy. Women with bipolar disorder are 3.9 times more likely to have unplanned pregnancies than women of similar age in the general population. These data suggest the importance of careful education about birth control in patients with bipolar illness so that pregnancies can be planned for periods of good health and so that appropriate pharmacological measures can be taken.
Preterm Birth Is a Risk Factor for Bipolar Disorder
A study published in the Archives of General Psychiatry in 2012 sampled over one million births in Sweden and suggested that preterm birth (from 32 to 36 weeks) doubled the risk that a child would develop bipolar disorder later in life. Those born even earlier had a sevenfold increased risk for bipolar disorder.
Editor’s Note: A robust research literature indicates that schizophrenia is related to obstetrical and other pre- and perinatal medical problems. Now it seems bipolar disorder may be as well, with some caveats. Low Apgar score (which indicates difficulties at birth) and delayed growth were not found to relate to bipolar risk. Thus something about the shortened preterm development seems to convey the risk. The authors suggest that there may be different types of factors that predispose a person to develop bipolar disorder, and that in some people the illness may have development origins.
These data also fit with observations that only about 50% of patients with bipolar disorder have a positive family history of the illness. Thus, while bipolar disorder does run in families and has a strong genetic basis in many instances, there are many people who develop the illness without having this genetic/familial risk. Very preterm birth appears to be one other contributing risk factor, presumably among many others. Understanding the neurobiological mechanisms occurring before birth that mediate this risk may lead to direct preventive measures to lessen the risk. In the meantime, traditional measures supporting good maternal and fetal health are a good place to start. These include regular prenatal checkups, good nutrition, and prenatal vitamins that include high doses of folic acid.
Study of Twins Sheds Light on Epigenetic Mechanisms Implicated In Bipolar Disorder
At the 5th Biennial Conference of the International Society for Bipolar Disorders, H. Sugawara and colleagues reported on a particular example of epigenetics, an emerging field that studies ways that events and substances in the environment affect the structure of DNA. Often methyl or acetyl groups attach to DNA, making it easier or more difficult to transcribe. Sugawara’s group discussed hypermethylation of the serotonin transporter gene in bipolar disorder in an analysis of monozygotic twins discordant for bipolar disorder.
Monozygotic (identical) twins are highly concordant for bipolar disorder, meaning if one has the illness the other is likely to, but this does not occur 100% of the time. Thus, environmental or epigenetic mechanisms could account for the lack of genetic transmission of the illness in the odd cases in which one twin does not develop the illness.
Sugawara’s research group found that DNA hypermethylation of the allele encoding the serotonin transporter occurred in the twins with bipolar illness but not in those without. Once the expression of this particular gene had been identified as a difference between twins with and without bipolar disorder, the researchers examined the gene in non-twin patients with bipolar disorder compared to healthy controls and confirmed that people with bipolar disorder were more likely to have the hypermethylated allele.
The researchers believed that carrying a short form of the serotonin transporter was associated with DNA hypermethylation, and they went on to study the expression of mRNA for the transporter in bipolar patients carrying the short form of the allele. They found that DNA methylation was also higher at the serotonin transporter site in postmortem brains of bipolar patients.
Editor’s Note: This study provides one of the first insights into possible environmental mechanisms that explain why some people at risk for bipolar disorder develop the illness and others do not. Another possible mechanism for differential expression of the illness has been suggested by E.F. Torrey and colleagues, who believe that a viral infection may enter an individual’s genome and directly alter DNA sequences. The current data from Sugawara’s research group suggest the importance of further study of the serotonin transporter site in bipolar disorder and the mechanistic reasons for the DNA hypermethylation that occurs there.
