Paternal heroin self-administration in rats increases drug-seeking behavior in male offspring via miR-19b downregulation in the nucleus accumbens
Wenjing Gao et al reported in Neuropsychopharmacology (2025) that “paternal heroin self-administration in rats results in increased heroin-seeking behavior in F1 male offspring. This effect was replicated by zygotic microinjection of sperm RNAs from heroin self-administration-experienced rats, but not from yoked infusion pairs, highlighting the role of sperm non-coding RNAs changes induced by paternal drug-seeking behavior (and not by just passive receipt of heroin.) Analysis of non-coding RNA changes in the NAc [nucleus accumbens] and sperm of the F0 generation revealed a significant correlation in miRNA expression profiles, particularly the downregulation of miR-19b in both tissues, which was linked to the observed phenotype. The heightened heroin-seeking behavior in the male F1 generation could be reversed by supplementing synthetic miR-19b in F0 sperm RNA or introducing miR-19b into the NAc of F1 offspring. These findings suggest that sperm miRNAs like miR-19b mirror changes in brain miRNAs, participate in epigenetic transmission of acquired traits from F0 to F1, as well as in regulating heroin SA behavior of offspring.”
Editor’s Note: These data suggest that dad rats self administering heroin transmit a vulnerability to self administering heroin to their offspring. It does not occur if the dad rats merely get heroin passively. It is likely that these data could be extrapolated to humans. If so, there is a question of whether taking opiates for pain (administered by a nurse as opposed to self administrated) would transmit vulnerability to the offspring. In any event, it may be that a heroin addict who self administers the drug not only puts himself at risk but also his male offspring. This makes clear that methods of producing primary protection in offspring for opiate addiction deserve exploration
Review: Reconsideration of bipolar disorder as a developmental disorder
Reconsideration of bipolar disorder as a developmental disorder: Importance of the time of onset
Pierre Alexis Geoffroy et al, J Physiology Paris, 2013
Eight admixture studies have demonstrated three homogeneous subgroups of patients with bipolar disorder, identi?ed by their age at onset (early, intermediate and late age at onset), with two cutoff points, at 21 and 34 years.
The early onset group had more: Suicide attempts, rapid cycling, drug and alcohol abuse, psychotic symptoms, panic disorder, OCD, and a positive family history for affective disorder. Early onset illness should be recognized and treated earlier.
Influence of Childhood Maltreatment on Morphometry and Brain Network Architecture in Bipolar Disorder
Martin Teicher of McLean Hospital, Harvard Medical School, reported on the influence of childhood maltreatment on morphometry and brain network architecture in Bipolar Disorder.
“Childhood maltreatment (MAL) is common in individuals with bipolar disorder (BP) and is associated with earlier onset, more severe course, and more comorbidities.” They found that reduced hippocampal volume and white matter alterations were present in those with a history of childhood maltreatment. They concluded that “MAL may act as a sensitizer promoting the emergence of bipolar symptoms in individuals with less severe network abnormalities” than in BP patients with no MAL.
Lithium Is Unparalleled in It Range of Efficacy in the Mood Disorders
Most clinicians are aware of lithium’s superiority over other mood stabilizers in bipolar illness prophylaxis. New data suggests this might also apply to the atypical antipsychotics.
Lithium is also not only an effective adjunct to antidepressant in unipolar depression, but has some of the best data for its use in long term prevention. In bipolar disorder prophylaxis it is particularly effective in those with classical presentations of discrete episodes of euphoric mania, treatment early in the course of illness, lack of anxiety and substance comorbidities, and a positive history of mood disorder in first-degree relatives.
New data indicates that it is also effective in childhood onset mania, and open long term follow ups indicate that it is more effective than other mood stabilizers or atypical antipsychotics.
Despite the compelling effectiveness data and many ancillary benefits, survey data indicates very low levels of current lithium use in both adult and child bipolar disorder. The conventional view, shared by most patients and many clinicians, underestimates its range of effectiveness and potential benefits while overestimating it is side effects. A more balanced view is needed as neglect of wider use of lithium is detrimental to the long term outcome of immense numbers of patients.
Robert M. Post, MD
Quotes from Kay Jamison, PhD, Professor of Psychiatry at the Johns Hopkins School of Medicine
“There’s this notion that mania and depression are uncommon or certainly that mania is uncommon, and that is not true. The bipolar illness spectrum is associated with a lot of very damaging things, most importantly suicide, but also alcohol and drug use and violence. It’s a very early onset illness, so unlike dementia or heart disease, which hit people much later in life, these hit people when they’re young. They have to cope with [bipolar disorder] when they’re young, and they don’t have the experience of life to help them out. That tends to be overlooked, what it does to people and their families, and how devastating it is. First and foremost, I would want people to know that it’s treatable, imperfectly treatable, but treatable, and it’s important to get it treated….It’s completely reasonable to extend hope to somebody who has bipolar illness but to also make it very clear that it’s hard. But draw upon what you know. Read, read, read. Learn about it. Badger your doctors. Why are they doing this? What’s the point of this drug rather than that drug? Always question what’s happening to you. “
Editor’s Note: One of the most important things that people with mood disorder can do, is to every night chart chart their mood, functioning, sleep, medications, and other symptoms so that this graphic longitudinal assessment can be shown to their physician/therapist at each visit. This will help most efficiently refining the treatment regimen for an optimal long term outcome. See www.bipolarnews.org (click on Personal Calendar or Life Chart) for a good format for doing these daily ratings.
Parents of children (age 2-12) with mood and behavioral disorders can each week rate the severity of their child’s symptoms of anxiety, depression, ADHD, oppositional behavior, and mania on a secure website. This can be printed out to assist physicians with the assessment of need for treatment and of how well treatment is working. Informed consent for this system is available at www.bipolarnews.org (click on Child Network).
Antidepressant Use and Risk of Manic Episodes in Children and Adolescents With Unipolar Depression
Suvi Virtanen, PhD; et al in JAMA Psychiatry. September 27, 2023. report a low risk of switching in youngsters with unipolar depression. However, the odds ratio for a switch were significantly elevated when there was concomitant use of anticonvulsants and antipsychotics, and there was a four fold increased risk if a parent had bipolar disorder. Thus one should be particularly careful about treating depression with antidepressants (AD) when there is a positive parental history of bipolar disorder and one should think of other options, such as lamotrigine, an atypical with good AD effects, or lithium.
Childhood Bullying and Maltreatment Yield A Worse Course of Bipolar Illness
Highlights from the International Society for Bipolar Disorders Conference Posters and Presentations, Chicago, June 22-25, 2023
Georgina Hosang of Bart’s & The London, Queen Mary’s School of Medicine reported that bullying and maltreatment together were associated with more suicidal behaviors than either childhood experience alone.
Intranasal Oxytocin for Internalizing Symptoms in Youth With Disruptive Behavior Disorders
Highlights from Posters Presented at the Society of Biological Psychiatry Meeting, April 27-29, 2023 in San Diego
E. Kendall reported that “Fifty-two youths with diagnoses of DBD [Disruptive Behavior Disorders] participated in [this] study, and twenty-five completed three weeks of treatment of intranasal OXT [oxytocin] and twenty-seven placebo (PBO)…. Youth who received OXT showed a significantly greater reduction of depression [ p=0.012] and anxiety [p=0.031] compared to the [placebo] group.”
They concluded that “Intranasal OXT can show efficacy in reducing internalizing symptoms in youth with DBD. This was accompanied by neural level changes implicated in emotion regulation (mPFC [medial prefrontal cortex] and ACC [anterior cingulate cortex]).”
Early Antidepressant Use is Associated with Rapid Cycling Bipolar Disorder
Highlights from Posters Presented at the Society of Biological Psychiatry Meeting, April 27-29, 2023 in San Diego
A.C. Courtes and Jair Soares reported that “Antidepressants were prescribed as the first psychiatry medication in 74/114 (65%) of BD patients.” This and alcohol use disorder were independent predictors of rapid cycling.
Familial Aggregation of Major Depression Predicts Risk of Major Depression
Gronemann et al reported in JAMA Psychiatry: “In this cohort study of 2,903,430 individuals, maternal, paternal, full sibling, or half-sibling with MD were associated with 2-fold higher risks of MD in men and women….(E)xposure to family MD during childhood and adolescence was associated with increased risk. The risk increased with number of affected family members; (however) individuals exposed when 30 years or older had markedly lower risk.”
Editors Note: Even depression in grandparents adds further to the risk of depression. When there is high familial loading for depression and other psychiatric illnesses, one should be alert to the possible onset of depression in young individuals and treat them early and well accordingly.
