Silvia Bernardi

The lifetime impact of attention deficit hyperactivity disorder: results from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC)

BACKGROUNDnThe aim of the study was to present nationally representative data on the lifetime independent association between attention deficit hyperactivity disorder (ADHD) and psychiatric co-morbidity, correlates, quality of life and treatment seeking in the USA.nnnMETHODnData were derived from a large national sample of the US population. Face-to-face surveys of more than 34 000 adults aged 18 years and older residing in households were conducted during the 2004-2005 period. Diagnoses of ADHD, Axis I and II disorders were based on the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV version.nnnRESULTSnADHD was associated independently of the effects of other psychiatric co-morbidity with increased risk of bipolar disorder, generalized anxiety disorder, post-traumatic stress disorder, specific phobia, and narcissistic, histrionic, borderline, antisocial and schizotypal personality disorders. A lifetime history of ADHD was also associated with increased risk of engaging in behaviors reflecting lack of planning and deficient inhibitory control, with high rates of adverse events, lower perceived health, social support and higher perceived stress. Fewer than half of individuals with ADHD had ever sought treatment, and about one-quarter had ever received medication. The average age of first treatment contact was 18.40 years.nnnCONCLUSIONSnADHD is common and associated with a broad range of psychiatric disorders, impulsive behaviors, greater number of traumas, lower quality of life, perceived social support and social functioning, even after adjusting for additional co-morbidity. When treatment is sought, it is often in late adolescence or early adulthood, suggesting the need to improve diagnosis and treatment of ADHD.

Impulsivity in the general population: A national study

OBJECTIVEnThe construct of impulsivity is an important determinant of personality differences, psychiatric disorders, and associated risk-taking behaviors. Most existing knowledge about impulsivity comes from clinical samples. To date, no study has estimated the prevalence of impulsivity and examined its correlates in the general population.nnnMETHODnWe analyzed data from a large national sample of the United States population. Face-to-face surveys of 34xa0653 adults aged 18 years and older residing in households were conducted during the 2004-2005 period. Diagnoses of mood, anxiety, and drug disorders as well as personality disorders were based on the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV Version.nnnRESULTSnImpulsivity was common (17% of the sample), particularly among males and younger individuals, and associated with a broad range of axis I and II disorders, particularly drug dependence, cluster B, dependent and schizotypal personality disorders, bipolar disorder and ADHD. It was associated with behavioral disinhibition, attention deficits, and lack of planning. Individuals with impulsivity were more likely to engage in behaviors that could be dangerous to themselves or others, including driving recklessly, starting fights, shoplifting, perpetrating domestic violence and trying to hurt or kill themselves. They were exposed to higher risk of lifetime trauma and to substantial physical and psychosocial impairment.nnnCONCLUSIONnGiven the association of impulsivity with psychiatric disorders and multiple adverse events, there is a need to target impulsivity in prevention and treatment efforts.

Unilateral low frequency versus sequential bilateral repetitive transcranial magnetic stimulation: is simpler better for treatment of resistant depression?

Repetitive transcranial magnetic stimulation (rTMS) efficacy in the treatment of major depression has been shown in both low frequency right-sided and high frequency left-sided stimulation over the dorsolateral prefrontal cortex (DLPFC). The aim of the present investigation was to evaluate the hypothesis of an additive effect of bilateral stimulation compare to sequential to unilateral stimulation. Sixty patients with treatment-resistant depression were assigned to receive either low-frequency rTMS over the right DLPFC (140 s x 1 Hz) followed by controlateral sham (unilateral group, n=20), low frequency right DLPFC rTMS followed by left DLPFC high frequency rTMS (5 s x 10 Hz) (bilateral group, n=20), or bilateral sham (sham group, n=20) in a 3 weeks double-blind, randomized trial. The primary outcome variable was the score on Hamilton Depression Scale (HAM-D). Low frequency right-sided and sequential bilateral stimulation showed different antidepressant efficacy at 3 weeks and across the full duration of the study, only the unilateral method appearing significantly more effective than sham at the end of the trial, and correlated to the higher percent of remitters (30% of the group vs. 10% -bilateral- and 5% -sham). Unilateral stimulation, but not bilateral, showed higher antidepressant efficacy compared to sham stimulation. The data suggest that right-sided low frequency stimulation may be a first line treatment alternative in resistant depression. To confirm and extend these findings further studies require a longer follow-up period, supported by biological observation and replication.

Serotonin dysfunction in pathological gamblers: increased prolactin response to oral m-CPP versus placebo.

OBJECTIVEnAcute administration of the partial serotonin (5-HT) agonist meta-chlorophenylpiperazine (m-CPP), that is used also as a street drug, has been reported to induce a high and craving response in various impulsive and substance addiction disorders.nnnINTRODUCTIONnTo clarify altered 5-HT metabolism in pathological gamblers and to explore the specific role of serotonergic system in non-substance addictions, we assessed behavioral (high and craving) and neuroendocrine (prolactin and cortisol) responses to an oral single dose of m-CPP and placebo in pathological gamblers and matched controls. Moreover, the relationship between neuroendocrine outcome and clinical severity has been assessed.nnnMETHODnTwenty-six pathological gamblers and 26 healthy control subjects enter a double-blind, placebo-controlled-crossed administration of orally dose m-CPP 0.5 mg/kg. Outcome measures included prolactin and cortisol levels, gambling severity, mood, craving and high scales.nnnRESULTSnPathological gamblers had significantly increased prolactin response compared to controls at 180 minutes and at 210 minutes post-administration. Greater pathological gamblers severity correlated with increased neuroendocrine responsiveness to m-CCP, suggesting greater 5-HT dysregulation. Pathological gambling patients had a significantly increased high sensation after m-CPP administration compared with control.nnnCONCLUSIONnThese results provide additional evidence for 5-HT disturbance in pathological gamblers and they support the hypotheses that the role of the 5-HT dysfunction related to the experience of high might represent the pathway that leads to dyscontrolled behavior in pathological gamblers. Furthermore, the high feeling induced by m-CPP in pathological subjects may represent a marker of vulnerability to both behavioral and substance addictions.

Noradrenergic function in pathological gambling: blunted growth hormone response to clonidine.

The noradrenergic system has been linked to impulsive behaviour in animals and humans, yet little data on noradrenergic system exist in specific impulse control disorders. To explore the role of the noradrenergic system in pathological gamblers (PG), we assessed neuroendocrine growth hormone (GH) response to the α2-adrenergic receptor agonist clonidine and placebo in PG and controls. The net effects of clonidine are a decrease in neurotransmission by depressing locus coeruleus activity and stimulation of GH secretion through activation of post-synaptic α2-adrenergic receptors in the hypothalamus. Twenty-nine PG subjects, free of other comorbid conditions, and 27 healthy controls received a double-blinded, placebo-controlled, single dose of oral clonidine (0.15 mg/kg). Data observed included GH, clonidine levels and levels of the main noradrenergic metabolite, 3-methoxy-4-hydroxy-phenylglycol (MHPG). The area under the curve for GH response to clonidine was significantly lower (separate variance t with 44.3 df = 2.626, P = 0.012, d = 0.58) in the PG group (199.6) than in the control group (426.3). PG had significantly blunted GH responses compared with controls at 120 and 150 min post-clonidine. These results are consistent with the idea that the subsensitivity of post-synaptic α-2 receptors is possibly attributable to higher-than-normal noradrenergic secretion in PG. This peripheral noradrenergic dysfunction could be consistent with attenuated cortico-frontal noradrenergic function as shown in positron emission tomography (PET) studies of PG.

Serotonin function in pathological gambling: blunted growth hormone response to Sumatriptan

Pathological gambling is a disruptive behaviour and an important public health concern that is classified as an impulse control disorder, and is also conceptualized as a prototype of behavioural addiction’. Its phenomenology cannot be reduced to a single neurobiological dysfunction; instead, it has been conceived as a complex chain of events in which the serotonergic system (5-HT) has often been suggested as one of the most prominent involved. Acute administration of Sumatriptan, a selective 5-HT1B/1D agonist, has been used to investigate the functional responsivity of 5-HT1B/1D receptors in alcoholics, resulting in a blunted growth hormone response. These findings have been interpreted as being due to the down-regulation of these receptors. However, previous studies could not rule out the possibility that the changes in receptor function were induced by chronic substance exposure. Twenty-two pathological gamblers and 19 healthy control subjects were evaluated in response to double-blind administration of both a single dose of oral Sumatriptan (100 mg) and of placebo in a crossover design. All participants were screened to ensure that they were negative for lifetime alcohol and drug addiction, and had been free of substance abuse for at least 6 months. Outcome measures included growth hormone, prolactin, gambling severity, mood, craving and high’ change scales. A blunted growth hormone response was observed in pathological gamblers compared with healthy controls after Sumatriptan administration. No statistically significant differences were found for prolactin or behavioural measures, except for an increase in anxiety over time in pathological gamblers. These results, together with those obtained in our previous serotoninergic challenge study, document the presence of a serotonergic dysfunction in pathological gamblers similar to that reported in alcoholics.

Successful duloxetine treatment of a binge eating disorder: a case report

We report the successful treatment of a case of refractory binge eating disorder (BED) with duloxetine, a combined serotonin and norepinephrine reuptake inhibitor, resulting in complete remission of the patient’s bingeing behaviours. This case is discussed in the context of the existing literature on the psychopharmacology of BED. Results demonstrate that inhibition of 5-HT and noradrenaline reuptake by duloxetine markedly reduces food intake, suggesting that this may be a novel approach for the treatment of obesity.

Prevalence and Correlates of Anger in the Community: Results from a National Survey

INTRODUCTIONnLittle is known about the prevalence and correlates of anger in the community.nnnMETHODSnWe used data derived from a large national sample of the U.S. population, which included more than 34,000 adults ages 18 years and older. We defined inappropriate, intense, or poorly controlled anger by means of self-report of the following: (1) anger that was triggered by small things or that was difficult to control, (2) frequent temper outbursts or anger that lead to loss of control, or (3) hitting people or throwing objects in anger.nnnRESULTSnThe overall prevalence of inappropriate, intense, or poorly controlled anger in the U.S. population was 7.8%. Anger was especially common among men and younger adults, and was associated with decreased psychosocial functioning. Significant and positive associations were evident between anger and parental factors, childhood, and adulthood adverse events. There were strong associations between anger and bipolar disorder, drug dependence, psychotic disorder, borderline, and schizotypal personality disorders. There was a dose-response relationship between anger and a broad range of psychopathology.nnnCONCLUSIONSnA rationale exists for developing screening tools and early intervention strategies, especially for young adults, to identify and help reduce anger.

Gender Differences in Adult Attention-Deficit/Hyperactivity Disorder: Results From the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC)

BACKGROUNDnGaining insight into possible gender differences in the clinical presentation of adults with attention-deficit/hyperactivity disorder (ADHD) is of relevance in order to conduct appropriate screening and treatment interventions in both genders.nnnMETHODnThe analyses compared (1) prevalence and sociodemographic correlates, (2) frequency of ADHD core symptoms, (3) rates of subtypes, (4) prevalence of comorbid mental health conditions, and (5) rates of risky/impulsive behaviors, as well as health and social correlates, in men and women with ADHD in a nationally representative, US population-based sample. Face-to-face psychiatric interviews were conducted according to DSM-IV criteria in 34,653 adults from the US National Epidemiologic Survey on Alcohol and Related Conditions (Wave 2, 2004-2005).nnnRESULTSnWhile the prevalence of lifetime ADHD was significantly higher in men than in women (OR = 1.46, 95% CI = 1.22-1.76), the rate of persistent ADHD did not significantly differ across genders (OR = 1.23, 95% CI = 0.96-1.58). Compared to men with persistent ADHD, women with persistent ADHD, despite having lower rates of hyperactive symptoms, presented with similar ADHD subtypes profile and rates of risky behaviors (except for reckless driving), as well as with significantly more anxiety and perceived mental health impairment (P = .032). Results were similar when considering lifetime ADHD.nnnCONCLUSIONSnOur findings show that, despite different symptom profiles and comorbidities, men and women have similar rates of current ADHD and of risky behaviors associated with the disorder. Women with ADHD should receive as much attention as their male counterparts.

Obsessive compulsive disorder comorbidity in DBA

Diamond-Blackfan Anemia (DBA) is a congenital erythroid aplasia characterized as a normochromic macrocytic anemia with a selective deficiency in red blood cell precursors in otherwise normocelullar bone marrow. DBA is known to be associated with mental retardation and learning disabilities. Although comorbidities with other psychiatric conditions have not been reported in the existing literature, we report in this paper a case of a DBA patient with previously undiagnosed comorbidity of obsessive compulsive disorder (OCD), successfully treated with sertaline 200 mg/day and valproic acid 600 mg/day. This case of comorbid presentation has clinical, therapeutic and pathophysiological implications. Given the difficulty of distinguishing among mental retardation, learning disabilities and OCD and the importance of precocious diagnosis in treating OCD especially since there are treatment methods interfering with anemia symptoms, physicians should adapt an adequate screening tool treating a child with DBA and comorbid mental disorder.