Harsh Physical Punishment is Associated with Mood and Other Disorders

April 11, 2013 · Posted in Risk Factors · Comment 

physical punishment

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

January 15, 2013 · Posted in Comorbidities, Risk Factors · Comment 

substance abuse

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.

How Illness Progresses In The Recurrent Affective Disorders

December 12, 2012 · Posted in Peer-Reviewed Published Data, Risk Factors · Comment 

depressed man with woman

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:

  1. The likely acceleration of repeated episodes as a function of the number of prior episodes (episode sensitization)
  2. The increased responsivity of the illness to repeated stressors (stress sensitization)
  3. 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

The Explosive Combination of Bipolar Disorder and Substance Abuse

June 25, 2012 · Posted in Comorbidities · Comment 

boy with pills

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

Bipolar Disorder and Its Comorbidities in Youth

April 25, 2012 · Posted in Risk Factors · Comment 

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.

ADHD

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.

teen drinking

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

Why Preventive Treatment Is Important

November 25, 2011 · Posted in Course of Illness, Risk Factors · Comment 

Episodic vs. Continuous Social Stress Result in Different Rates of Cocaine Use

July 11, 2010 · Posted in Neurochemistry · Comment 

In a study of rodents exposed to stress (by being forced to enter another rodent’s territory) and given the opportunity to self-administer cocaine, those exposed to a few brief episodes of stress increased their cocaine use and engaged in binge-like episodes, while those exposed to stress chronically showed suppressed cocaine use.

At the American College of Neuropsychopharmacology meeting in December 2009, Klaus Miczek and colleagues from Tufts University in Boston presented a fascinating study indicating that the temporal aspects of the experience of social stress may have dramatic impact not only on defeat stress behaviors and the associated biochemistry, but also on the likelihood that an animal adopts cocaine self-administration.  These investigators compared episodic versus chronic defeat stress in rodents.

Episodic social defeat stress consisted of four brief confrontations between an intruding animal and an aggressive resident rat over the course of a period of ten days. In contrast, chronic subordination stress involved the continuous exposure of the intruder rat to an aggressive resident over five weeks, during which time the intruder lived in a protective cage within the resident’s home cage.

The episodically defeated intruder rats showed increases in intravenous cocaine self-administration and prolonged binge-like episodes, along with increases in brain-derived neurotropic factor (BDNF), which is necessary for long-term learning and memory, in the midbrain ventral-tegmental area (VTA) and increased dopamine release in the nucleus accumbens, the reward area of the brain.  In contrast, the continuously subordinate rats showed the opposite pattern of suppressed cocaine intake, suppression of dopamine release in the n. accumbens, and reduced BDNF in the VTA.

Read more

The N-acetylcysteine Story: A New Potential Therapy for Bipolar Illness and Substance Abuse

April 29, 2010 · Posted in Potential Treatments · 2 Comments 

N-acetylcysteine (NAC), a readily available substance from health food stores, is able to reestablish glutamate homeostasis (regulation and balance) in the reward area of brain (the nucleus accumbens), reported Peter Kalivas of the University of South Carolina at the “Staging neuropsychiatric disorders: Implications for idiopathogenesis and treatment” meeting in Mojacar, Spain this past November. Kalivas reported that NAC appears to be effective across a spectrum of addictions, including cocaine, heroin, alcohol, cigarette smoking, and gambling.

N-acetylcysteine Restores Cortical Control and Glutamate Homeostasis

How NAC works in the brain

Even more remarkably, NAC also appears to have positive effects in placebo-controlled studies in the treatment of patients with bipolar illness, report Mike Berk and colleagues, who are studying the same substance in Australia. Compared with placebo, patients taking adjunctive NAC showed improvement in all outcome measures, especially depression, after 3 and 6 months. In another article, also published in Biological Psychiatry in 2008, Berk’s research group demonstrated that NAC improved some negative symptoms of schizophrenia. NAC has also shown positive effects in trichotillomania and on nail-biting, suggesting that it has a variety of potential clinical uses in conditions associated with pathological compulsive behavioral patterns.

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Anticonvulsant Zonisamide (Zonegran) May Treat Alcohol Abuse

April 29, 2010 · Posted in Potential Treatments · Comment 

Albert Arias and collaborators from the University of Connecticut Health Center presented a study of zonisamide in which the drug provided significant benefits over placebo in patients with primary alcoholism (i.e., not with comorbid bipolar illness).  Treatments began at 100 mg/day and increased to a maximum of 500 mg/day.

EDITOR’S NOTE:  If replicated, this study would place zonisamide in a category with topiramate (Topamax), which has also been shown to decrease alcohol intake and craving. Both drugs also share the ability to cause minor weight loss as a potentially positive side effect, and both drugs have also proven effective in double-blind studies in the treatment of bulimia.

However, four double-blind, placebo-controlled studies found that topiramate did not have acute antimanic efficacy. Zonisamide has not been studied in a systematic fashion, but open studies suggest its potential utility in mania and, to a lesser degree, in depression.


Since zonisamide may have positive effects on mood in patients with bipolar disorder, and there is now placebo-controlled documentation of its efficacy in primary alcohol abuse disorders, its ultimate potential utility in patients with bipolar disorder and comorbid alcoholism deserves consideration.

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