Nicholas W. Carrellas

How prevalent and morbid are subthreshold manifestations of major depression in adolescents? A literature review

INTRODUCTION Major Depressive Disorder (MDD) among youth is a public health concern. Our aim was to examine the current body of knowledge to better characterize the prevalence and morbidity associated with subthreshold forms of MDD among youth. Given that MDD tends to develop gradually over time, we hypothesized a high prevalence and considerable impairment associated with youth suffering from depressive symptoms that fall short of full, syndromic status. METHODS A literature search was conducted using PubMed exclusively to identify studies assessing the prevalence and clinical characteristics of subthreshold MDD in adolescents. RESULTS Six scientific papers that met our priori inclusion and exclusion criteria were identified. All papers sampled adolescents. The prevalence of subthreshold MDD ranged from 5% over the past year, to 29% over the two weeks prior to screening. These papers reported clinically significant morbidity associated with subthreshold MDD among adolescents, with evidence for elevated rates of psychiatric comorbidities, impaired functioning in social and familial domains, increased suicidality, and frequent mental health service utilization. LIMITATIONS Though we examined a sizeable and diverse sample, we only identified six cross-sectional informative studies for this review. Variability of subthreshold MDD and major outcome definitions across studies, likely limits the specificity of findings. CONCLUSIONS Subthreshold MDD is prevalent among youth, and is associated with emotional and social impairments that reach the level of obtaining clinical care. These findings could lead to early intervention efforts aimed at mitigating the adverse outcomes associated with subthreshold MDD as well as the progression to full syndrome MDD. Our review documents that regardless of whether progression to full diagnostic status occurs, this condition is morbid.

Nonmedical Stimulant Use in College Students: Association With Attention-Deficit/Hyperactivity Disorder and Other Disorders

Objective The nonmedical use of stimulants (misuse) in the college setting remains of utmost public health and clinical concern. The objective of this study was to evaluate comprehensively the characteristics of college students who misused stimulants, attending to rates of attention-deficit/hyperactivity disorder (ADHD), other psychopathology, and substance use disorders. Methods The data presented are from a cross-sectional study of college students who misused prescription stimulant medications (not including cocaine or methamphetamine) and controls (college students without stimulant misuse). Between May 2010 and May 2013, college students were assessed blindly for psychopathology and substance use disorder by way of Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Patient Edition (SCID-I/P) and completion of self-report questionnaires. Results The analysis included 198 controls (mean ± SD age = 20.7 ± 2.6 years) and 100 stimulant misusers (20.7 ± 1.7 years). Misusers, when compared to controls, were more likely to endorse alcohol, drug, alcohol + drug, and any substance use disorder (all P values < .01). When a subset of stimulant misusers (n = 58) was examined, 67% had a full or subthreshold prescription stimulant use disorder. Misusers also had higher rates of conduct disorder (10% vs 3%; P = .02) and ADHD (including subthreshold cases; 27% vs 16%; P = .02) in addition to lower Global Assessment of Functioning score (P < .01). Higher rates of misuse of immediate-release—relative to extended-release—stimulants were reported. Conclusions Our data suggest that, compared to controls, college students who misuse stimulant medications are more likely to have ADHD, conduct disorder, stimulant and other substance use disorder, and overall dysfunction.

Examining the association between attention deficit hyperactivity disorder and substance use disorders: A familial risk analysis

OBJECTIVE The main aim of this study was to use familial risk analysis to examine the association between attention deficit hyperactivity disorder (ADHD) and substance use disorders (SUDs) attending to sex effects and the specificity of alcohol and drug use disorder risks. METHODS Subjects were derived from two longitudinal case-control family studies of probands aged 6-17 years with and without DSM-III-R ADHD of both sexes and their first degree relatives followed from childhood onto young adult years. Cox proportional hazard models were used to estimate rates of ADHD and SUDs (any SUD, alcohol dependence, and drug dependence). Logistic regression was used to test both co-segregation and assortative mating. RESULTS Our sample included 404 probands (ADHD: 112 boys and 96 girls; Control: 105 boys and 91 girls) and their 1336 relatives. SUDs in probands increased the risk for SUDs in relatives irrespective of ADHD status. The risk for dependence to drug or alcohol in relatives was non-specific. There was evidence that even in the absence of a SUD in the proband, ADHD by itself increased the risk of SUDs in relatives. Proband sex did not moderate the familial relationship between ADHD and SUDs. There was evidence of co-segregation between ADHD and SUD. CONCLUSIONS Findings indicate that various independent pathways are involved in the transmission of SUD in ADHD and that these risks were not moderated by proband sex. ADHD children and siblings should benefit from preventive and early intervention strategies to decrease their elevated risk for developing a SUD.

Neuropsychological functioning in college students who misuse prescription stimulants

BACKGROUND AND OBJECTIVES Relatively little is known about the neuropsychological profiles of college students who misuse prescription stimulant medications. METHODS Data presented are from college students aged 18-28 years who misused prescription stimulants prescribed for attention-deficit/hyperactivity disorder and controls (no prescription stimulant misuse). Students were assessed neuropsychologically using the self-report Behavioral Rating Inventory of Executive Functioning (BRIEF-A), the Cambridge Automated Neuropsychological Test and Battery (CANTAB), and other tests of cognitive functioning. The analyses included 198 controls (age 20.7 ± 2.6 years) and 100 prescription stimulant misusers (age 20.7 ± 1.7 years). RESULTS On the BRIEF-A, misusers were more likely than controls to endorse greater dysfunction on 8 of 12 measures including Inhibition, Self Monitor, Initiation, Working Memory, and Plan/Organize, when adjusting for race and sex (all ps < .05). Similarly, when dichotomizing the BRIEF-A as abnormal (T score ≥ 65), misusers had more abnormalities on five of nine subscales, as well as all major indices (ps < .05). Misusers also performed worse on several subtests of the CANTAB and standardized cognitive battery (ps < .05). A proxy of prescription stimulant misuse frequency was positively correlated with greater executive dysfunction on the BRIEF-A. DISCUSSION AND CONCLUSIONS These data demonstrate elevated risk for neuropsychological dysfunction among students who misuse prescription stimulants compared to non-misusing peers. The presence of ADHD contributed significantly to these cognitive findings. Students who misuse prescription stimulants should be screened for neuropsychological dysfunction. SCIENTIFIC SIGNIFICANCE These data may better elucidate the neuropsychological profile of college-aged prescription stimulant misusers. (Am J Addict 2017;26:379-387).

Similar familial underpinnings for full and subsyndromal pediatric bipolar disorder: A familial risk analysis

To examine the validity of subthreshold pediatric bipolar I disorder (BP‐I), we compared the familial risk for BP‐I in the child probands who had either full BP‐I, subthreshold BP‐I, ADHD, or were controls that neither had ADHD nor bipolar disorder.

Can subsyndromal manifestations of major depression be identified in children at risk

Children of parents with major depression are at significantly increased risk for developing major depression themselves; however, not all children at genetic risk will develop major depressive disorder (MDD). We investigated the utility of subsyndromal scores on the Child Behavior Checklist (CBCL) Anxiety/Depression scale in identifying children at the highest risk for pediatric MDD from among the pool of children of parents with MDD or bipolar disorder.

Subsyndromal Manifestations of Depression in Children Predict the Development of Major Depression

Objective To evaluate the utility of assessing subsyndromal symptoms of major depressive disorder in childhood, indexed through the Child Behavior Checklist (CBCL) anxiety/depression scale, in predicting risk of developing major depressive disorder in adolescent and young adult years. Study design The sample consisted of 537 children, 6‐17 years of age, originally ascertained for a longitudinal family genetic study of youth with and without attention‐deficit hyperactivity disorder and their first‐degree relatives who were followed prospectively and blindly for 10 years from childhood into young adult years. Children with full diagnosis major depressive disorder at baseline were excluded. For analysis, the sample was stratified into 4 groups based on the presence or absence of parental mood disorders and by the presence or absence of subsyndromal scores on the CBCL anxiety/depression scale at baseline assessment in childhood. Results Children of parents with mood disorders plus subsyndromal scores on the CBCL anxiety/depression scale at baseline (n = 22) had the highest risk for developing major depressive disorder and anxiety disorders at the 10‐year follow‐up when compared with the other groups. Children with either subsyndromal scores on the CBCL anxiety/depression scale at baseline alone (n = 22) or parental mood disorders alone (n = 172) had intermediate outcomes. Conclusion The CBCL anxiety/depression scale was useful in identifying children at high risk for the development of major depressive disorder and anxiety disorders at the 10‐year prospective follow‐up. Furthermore, our results emphasized the importance of familial psychiatric history in youth with subthreshold symptoms of depression. Parental mood disorder and subthreshold anxiety/depressive symptoms were predictive of developing depression.

Risk Factors for Overdose in Treatment-Seeking Youth With Substance Use Disorders

OBJECTIVE Overdoses (ODs) are among the leading causes of death in youth with substance use disorders (SUDs). Our aim was to identify the prevalence of OD and characteristics associated with a history of OD in youth presenting for SUD outpatient care. METHODS A systematic retrospective medical record review was conducted of consecutive psychiatric and SUD evaluations for patients aged 16 to 26 years with DSM-IV-TR criteria SUD at entry into an outpatient SUD treatment program for youth between January 2012 and June 2013. Unintentional OD was defined as substance use without intention of self-harm that was associated with a significant impairment in level of consciousness. Intentional OD was defined as ingestion of a substance that was reported as a suicide attempt. T tests, Pearson χ² tests, and Fisher exact tests were performed to evaluate characteristics associated with a history of OD. RESULTS We examined the medical records of 200 patients (157 males and 43 females) with a mean ± SD age of 20.2 ± 2.8 years. At intake, 58 patients (29%) had a history of OD, and 62% of those patients had a history of unintentional OD only (n = 36). Youth with ≥ 2 SUDs were 3 times more likely to have a history of OD compared to youth with 1 SUD (all P < .05). Compared to those without a history of OD, those with an OD were more likely to be female and have lifetime histories of alcohol, cocaine, amphetamine, anxiety, depressive, and/or eating disorders (all P < .05). CONCLUSIONS High rates of OD exist in treatment-seeking youth with SUD. OD was associated with more SUDs and psychiatric comorbidity.