Characterizing major depression phenotypes by presence and type of psychomotor disturbance in adolescents and young adults

Abstract

Major depressive disorder (MDD) is phenomenologically heterogeneous, which has prompted investigation of intermediate MDD phenotypes based on specific key symptoms. Presence and type of psychomotor disturbance may be an important psychopathologic feature that differentiates clinically distinct forms of juvenile MDD. This study examined the phenotypic status of three putative MDD phenotypes in a community sample of 941 youths: (1) agitated depression (MDD with psychomotor agitation), (2) retarded depression (MDD with psychomotor retardation), and (3) agitated-retarded depression (MDD with psychomotor agitation and retardation within an episode). Hasler et al.'s [2004: Neuropsychopharmacology 29:1765-1781] criteria of specificity (degree of association with relevant symptoms and conditions related to the disease of interest versus other psychiatric conditions), stability (degree of stability over time), and heritability (degree of familial aggregation with relevant conditions) were used to evaluate the phenotypic significance of these subtypes. Results were suggestive that agitated depression was a relatively specific phenotypic syndrome characterized by irritability, arousal, physical complaints, and vulnerability to anxiety disorders and alcohol dependence; low stability across depressive episodes; and low heritability. Agitated-retarded depression was relatively specific and characterized by increased severity, recurrence, vegetative symptoms, suicidal ideation, social impairment, endogeneity, and vulnerability to anxiety disorders and bulimia; low stability across episodes; and modest heritability. Although retarded depression was associated with some specific distinguishing characteristics, most associations were explained by the increased severity of this phenotype. Retarded depression evidenced little stability or heritability. These findings offer partial support of the phenotypic status of agitated and agitated-retarded depression in youths.

Agitated depression in substance dependence

“…Although this approach does not account for fluctuations in symptom expression across MDEs, prior research suggests that categorizing individuals on the basis of symptoms experienced during most severe episode can yield valid depressive phenotypes that associate with substance dependence (Leventhal et al, 2008b; Marmorstein, in press). …”

“…We also created an “other drug” dependence category, which included dependence on any of the following substances: phencyclidine, hallucinogens, inhalants, solvents, or a combination of opioids and cocaine (i.e., “speedballs”). Substance abuse was not analyzed, given that PMA has been more strongly and consistently associated with dependence than abuse (Leventhal et al, 2008b; Marmorstein, in press). …”

“…Relationships between PMA and alcohol dependence have also been reported, but are less consistent across samples and analyses (Leventhal et al, 2008b; Leventhal and Zimmerman, 2010; Marmorstein, in press). Some of these associations extend across current and lifetime diagnoses and are robust even after controlling for demographics, comorbid psychiatric disorders, and depression severity, chronicity, and recurrence (Leventhal et al, 2008a; Leventhal et al, 2008b; Leventhal and Zimmerman, 2010; Marmorstein, in press). Although PMA is a diagnostic criterion for a manic episode (APA, 1994), evidence suggests that PMA and bipolar disorder have unique, non-overlapping relationships to substance dependence (Leventhal and Zimmerman, 2010).…”

“…PMA can be manifested as purposeless and stereotyped movements, such as fidgeting, pacing, and hand-wringing (APA, 1994; Parker et al, 1993). It is a marker of the melancholic subtype of depression (Leventhal et al, 2005) and may represent a unique psychopathologic depressive phenotype (Hasler et al, 2004; Leventhal et al, 2008b). Accordingly, there has been interest in exploring whether individuals with depression characterized by PMA (“agitated depression”) exhibit increased or decreased prevalence of substance dependence than those with non-agitated depression.…”

“…Extant research in epidemiologic and clinical samples indicates that depression with PMA is associated with higher rates of drug dependence, polysubstance use, and substance dependence (more broadly defined) than depression without PMA (Balázs et al, 2006; Leventhal et al, 2008a; Leventhal et al, 2008b; Leventhal et al, 2010; Maremmani et al, 2007; Marmorstein, in press). Relationships between PMA and alcohol dependence have also been reported, but are less consistent across samples and analyses (Leventhal et al, 2008b; Leventhal and Zimmerman, 2010; Marmorstein, in press).…”