Gender Differences in ADHD

Dr. Philip Grossi
Saturday, 08 December 2012

ADHD, a major public health issue, affects 9% of all children with a sex ratio heretofore of male to female of 2:1. Diagnosis of ADHD has increased in recent years with the diagnosis in females increasing more rapidly than in males. Recent large epidemiological studies by Froehlich found 8.7% met criteria for ADHD of which 51% were boys and 48% were girls. Adult ADHD reveals a higher incidence in females than males suggesting a delayed onset which in turn suggests differential brain maturation rates in the two sexes. Girls show a more rapid neurobiological, cognitive, motor, and social development. During the onset of puberty increased estrogen and dopamine receptors may lead to increased symptoms in adolescence.

Barkley, RA have reported that those with ADHD are less likely to finish school, have few or no friends, exhibit more autistic social behavior, drive faster, have more accidents, have a higher rate of STDs, and are at increased risk for other psychiatric conditions in adulthood. Mick, E found that 16% of females with ADHD showed adequate social adjustment compared to 86% of females without ADHD. Females who met criteria for ADHD at 16 years of age showed a persistence of the condition into adulthood of 71% with deficits in executive function especially prominent. Earlier studies showed males as more impaired but they are likely in error because of failure to correct for ADHD subtypes. Current studies point to equal impairment in the two sexes.

The diagnosis of ADHD in girls is more complex and difficult than in boys because of the age of onset, more subtle clinical findings and problems problems associated with the criteria as set out in the DSM-IV as well as a variety of ratings which are tilted to the male presentation. Also, mental health professionals tend to have a bias toward more diagnosis in boys. In addition, boys have a delayed developmental maturity especially in self-control processes which likely contributes to over-diagnosis.

Males have brains that are 8-10% larger than females; however, female brains mature earlier and follow a different developmental course. Females are about three weeks ahead of males in physical maturation at birth and are often about one year more mature by the start of school at 5 years old. This is important because different maturations are associated with different patterns of cognitive skills. Total cortical volume is reached in females by 10.5 years and in boys by 14.5 years. This is also true for brain areas considered of importance in ADHD pathology. These areas include especially the frontal lobes and basal ganglia. 

To summarize, sexual dimorphism in human neurobiological development extends to patterns of behavior along the developmental course of ADHD.  Current research supports the equal prevalence in males and females.  Previous cross sectional research is flawed because comparable ages in males and females did not take into account the differential developmental trajectory of the two sexes. Future studies will undoubtedly nail down the differences more clearly. 

(Jump to a related post ADHD across the Lifecycle.)

Autism Spectrum Disorder (ASD)

Dr. Philip Grossi
Saturday, 08 December 2012

Autism spectrum disorders are a genetically heterogeneous array of syndromes which have as their core impairment social interactions, abnormal development of the social brain.  These syndromes have received increasing attention because of what appears to be an increasing incidence and high impact on families from an emotional as well as financial standpoint. All treatments including somatic ones have been ineffective in addressing the core pathology but have been somewhat effective in dealing with specific symptoms clusters.

The genetic underpinning has thus far been elusive but with newer technologies such as DNA microarrays (DNA chip) and exome sequencing ( a strategy to sequence the coding portions of the genome) that allow for detection of CNV (copy number variation in DNA which presents as an abnormal number of gene copies or portions of genes) and point mutations suggests that progress is likely at hand.  Point mutations have been discovered supporting the statistical conclusion that increased paternal age is a risk factor.

In the October 2012 issue of Science, Novarino use exome sequencing  in related families to discover an inborn metabolic error associated with epilepsy, autism, and intellectual disability. Their results suggest that the more serious autistic presentations offer the best chance to find a causative mutation. There is an overlap in the genetics of these severe autistic disorders and severe intellectual disability presentations.

Additional observations suggest that the same genotype can lead to a number of phenotypes (presentations) including autism, intellectual disability, schizophrenia, bipolar disorder, and epilepsy. There is a large number of genetic combinations present in any single patient which implies variability of genetic expression in those individuals who do not meet criteria for any disorder.

Novvarino identified a point mutation for the gene BCKDK which results in increased degradation of branched chained amino acids. This defect in mice can largely be reversed by feeding branched chained amino acids. This suggests that newborn screening for this error, which has not yet been developed, could lead to a straightforward treatment. It's only a hope now but should it be proven effective, it would be a very big development.

Caution: Bath Salts

Dr. Philip Grossi
Tuesday, 06 November 2012

Drug abuse is constantly changing and presents evolving therapeutic challenges to psychiatrists and other treating providers. In about the last eighteen months especially, "bath salts" or "plant food", have burst on the scene aided by the electronic marketplace, the internet, and the rapid movement of information. They are named for their white crystalline-pellet appearance and are the latest abusable substances. They are synthetic derivatives of cathinone, a naturally occuring psychostimulant found in the khat plant.  Natives of East Africa and the Arabian peninsula (mostly unmarried men in their 20s) have chewed the leaves of this plant for centuries to experience stimulation and relaxation.The most prevalent active ingredients are mephedrone, methylone, and methylenedioxypyrovalerone. They have amphetamine-like properties and will increase alertness, increase musical sensations, heighten libido and sexuality, euphoria, and relaxation. These are caused by the rapid release and reuptake blockade of dopamine, serotonin, and norepinephrine. The drug can be ingested, injected, smoked, or inhaled and they produce their effect in less than one hour.

Bath salt intoxication is a medical and psychiatric emergency. Auditory and visual hallucinations, delusions, paranoid thinking, agitation, and disorientation are common psychiatric symptoms.  Physical symptoms can include hypertension, hyperthermia, diaphoresis, tremors, hypereflexia, clonus, ocular clonus, flushed skin, and muscle breakdown which can cause kidney damage. The physical signs sound like serotonin toxicity as described in the blog, MAOI and Drugs.That fits the data as mephedrone can cause a tenfold increase in serotonin level. The psychotic signs are likely related to a sudden rise in dopamine and the neurovegetative signs are serotonin and norepinephrine related.

In short, bath salts are extraordinarily dangerous and could even be fatal. Do not use under any circumstances.