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Biomedical subjects

F Cassidy

Publications and source records attributed to F Cassidy.

At least 19 recordsLinked to original sources
PubMed2002

Thyroid function in mixed and pure manic episodes.

OBJECTIVES: Associations of both overt thyroid disease as well as subclinical thyroid abnormalities with affective disorders have been well established. Similar associations have been reported with mixed mania and rapid cycling bipolar disorder. We tested for differences in overt and subclinical thyroid disease and subclinical differences in a large series of bipolar patients examined during mixed or pure manic episodes. METHODS: Rates of previously diagnosed thyroid disease were compared by sex, race and manic subtype (mixed versus pure) in 443 patients. Serum thyroid stimulating hormone (TSH) and free thyroxine (FT4) concentrations obtained from patients with no clinical thyroid disease collected during manic and mixed bipolar episodes were compared using ANOVA statistics. Race was also included in the model and age was covaried. RESULTS: Rates of thyroid disease, in particular hypothyroidism, were higher in females and white people, and increased with advancing age. No differences were noted between subjects sampled during mixed or pure manic episodes. In patients with no history of thyroid disease, serum TSH and FT4 concentrations did not differ between manic subtypes or between sexes. TSH levels however, were significantly lower in African Americans. CONCLUSIONS: We did not confirm past reports of associations of overt or subclinical thyroid disease with mixed manic episodes. African Americans had significantly lower serum TSH concentrations than white people, while FT4 levels did not differ.

Adult↗
PubMed2001

MRI correlates of suicide attempt history in unipolar depression.

BACKGROUND: Suicide represents a major health problem in the United States, and prediction of suicide attempts is difficult. No structural neuroimaging studies have been done to specifically examine findings in patients who have attempted suicide. The objective of this study was to compare MRI findings in unipolar patients with and without a history of a suicide attempt. METHODS: In this post hoc analysis, 20 unipolar subjects with a history of a suicide attempt were matched by age and gender to unipolar subjects without a history of an attempt. Subjects were also matched on parameters such as cardiovascular history, electroconvulsive treatment history, and history of psychosis. Subjects with a history of any neurologic condition were excluded. There were no significant differences in age of onset of depression, number of episodes of depression, and Hamilton Depression scores between the two groups. T2-weighted magnetic resonance imaging (MRI) scans were rated using the Coffey and Boyko rating scales. RESULTS: Unipolar patients with a history of a suicide attempt demonstrated significantly more subcortical gray matter hyperintensities compared with patients without such a history. CONCLUSIONS: Patients with abnormal MRI findings may be at higher risk for mood disorders and suicide attempts because of disruption of critical neuroanatomic pathways. Gray matter hyperintensities in the basal ganglia may be especially associated with risk for suicide attempts.

Aged↗
PubMed2001

A prospective study of inter-episode consistency of manic and mixed subtypes of bipolar disorder.

BACKGROUND: Few studies have compared symptom presentations across manic or mixed episodes in manic-depressive patients. METHODS: In the current study we report on symptom presentations of 68 prospectively-evaluated subjects diagnosed with Bipolar Disorder during two discrete manic or mixed episodes. Each episode was categorized using DSM-IIIR criteria for Bipolar Disorder, manic or mixed, as well as a less restrictive definition for manic and mixed states derived from receiver operating characteristic (ROC) analysis of symptoms. RESULTS: The occurrence of mixed bipolar episodes was not random using either the DSM-IIIR or ROC-derived definitions of mixed episodes. LIMITATIONS: Subjects were not all fully medication-free at the time of evaluation which may have altered symptom presentation. The total duration of the study was limited, with the longest inter-episode interval under 6 years. CONCLUSIONS: Although there was variability in mixed symptomatology between episodes, the occurrence of mixed episodes was not random. Manic and mixed episodes tend to recur true to type.

Adolescent↗
PubMed2001

Frequencies of signs and symptoms in mixed and pure episodes of mania: implications for the study of manic episodes.

1. In a previous report the authors compared the frequency of 20 classical and mixed manic signs and symptoms in subjects meeting DSM-III-R criteria for Bipolar Disorder, manic or mixed. In that report, the authors commented that a possible limitation of the study was the diagnosis of mixed and pure mania using DSM-III-R criteria that may be too rigid The authors now address that issue, adopting a ROC-derived definition of mixed mania 2. Three hundred sixty-three subjects meeting DSM-III-R criteria for Bipolar Disorder, manic or mixed, were evaluated by rating 20 signs and symptoms of mania. The frequencies of these signs and symptoms were computed and compared for both mixed and pure subtypes, determined by the ROC-derived definition. 3. Mood lability, dysphoric mood, guilt, anxiety, and suicidality were more frequently observed in the mixed manic group In contrast, euphoria and grandiosity were more frequently observed in the pure manic group. Nonetheless, non-trivial rates of dysphoric mood, irritability and anxiety were still observed in the pure groups, despite the adoption of a less restrictive definition of mixed states. The current results are similar to the results obtained using DSM-III-R criteria for Bipolar Disorder, manic and mixed. Although rates of dysphoric mood, anxiety, lability, guilt and suicidality were lower in the manic group, each of these symptoms may be observed in pure manic episodes, underscoring the importance of recognition and evaluation of these features in formal studies of "pure" as well as mixed manic episodes.

Adult↗
PubMed2001

Subtypes of mania determined by grade of membership analysis.

Classical descriptions of mania subtypes extend back to Kraepelin; however, in marked contrast to the study of depression subtypes, validation of mania subtypes by multivariate statistical methods has seldom been attempted. We applied Grade of Membership (GOM) analysis to the rated clinical features of 327 inpatients with DSM-III-R mania diagnoses. GOM is a type of latent structure multivariate analysis, which differs from others of this type in making no a priori distributional assumptions about groupings. We obtained 5 GOM Pure Types with good face validity. The major Kraepelinian forms of "hypomania," "acute mania," "delusional mania," and "depressive or anxious mania" were validated. The major new finding is of two mixed mania presentations, each with marked lability of mood. The first of these displayed a dominant mood of severe depression with labile periods of pressured, irritable hostility and paranoia, and the complete absence of euphoria or humor. The second mixed mania Pure Type displayed a true, incongruous mixture of affects: periods of classical manic symptoms with euphoria, elation, humor, grandiosity, psychosis, and psychomotor activation, switching frequently to moderately depressed mood with pressured anxiety and irritability. This multivariate analysis validated classical clinical descriptions of the major subtypes of mania. Two distinct forms of mixed manic episodes were identified. DSM-III-R criteria did not reliably identify either of these two natural groups of mixed bipolar patients. As occurs in depression, this clinical heterogeneity of mania may influence response to drug treatments.

Adolescent↗
PubMed2001

The clinical epidemiology of pure and mixed manic episodes.

INTRODUCTION: Few large clinical epidemiological studies have been undertaken comparing subjects meeting criteria for mixed and pure states of bipolar disorder. In part, the difficulty comparing these states emanates from confusion in their diagnostic separation. In the current report, we use a definition derived from receiver operating characteristic (ROC) curve analysis as an alternative to the DSM-IIIR/IV definition, and we compare the two subtypes of manic episodes. METHODS: Three hundred and sixty-six patients meeting DSM-IIIR criteria for bipolar disorder, manic or mixed, were categorized using newly described criteria for mixed states. The two subtypes were compared on demographic variables and clinical history variables, using multiple analysis of variance with post hoc univariate F tests. The same analyses were conducted using the DSM-IIIR-defined subtypes. RESULTS: Using the ROC criteria, 79 subjects (21.6%) were characterized as mixed, in contrast to 51 subjects (13.9%) using DSM-IIIR criteria for bipolar disorder, mixed. The ROC-defined mixed manic group comprised more Caucasians and more females. Age of first psychiatric hospitalization was earlier and duration of illness longer in the mixed group. First episodes were unlikely to be categorized as mixed (< 5%). When the DSM-IIIR definition was employed, differences were not demonstrated. CONCLUSIONS: An earlier age of first psychiatric hospitalization and increased duration of illness, as well as a lower frequency of mixed subtype of manic episode during first hospitalization, are compatible with the view that mixed manic episodes occur more frequently later in the course of bipolar disorder. Moreover, differences in race, sex, and clinical histories of subjects in mixed episodes tend to support the separation of mixed mania as a diagnostic subtype of bipolar disorder.

Adolescent↗
PubMed2001

Corticotropin secretory dynamics in humans under low glucocorticoid feedback.

To explore the mechanisms of homeostatic adaptation of the hypothalamo-pituitary-adrenal axis to an experimental low-feedback condition, we quantitated pulsatile (ultradian), entropic (pattern-sensitive), and 24-h rhythmic (circadian) ACTH secretion during high-dose metyrapone blockade (2 g orally every 2 h for 12 h, and then 1 g every 2 h for 12 h). Plasma ACTH and cortisol concentrations were sampled concurrently every 10 min for 24 h in nine adults. The metyrapone regimen reduced the amplitude of nyctohemeral cortisol rhythm by 45% (P = 0.0013) and delayed the time of the cortisol maximum (acrophase) by 7.1 h (P = 0.0002). Attenuated cortisol negative feedback stimulated a 7-fold increase in the mean (24-h) plasma ACTH concentration, which rose from 24 +/- 1.6 to 169 +/- 31 pg/ml (ng/liter) (P < 0.0001). Augmented ACTH output was driven by a 12-fold amplification of ACTH secretory burst mass (integral of the underlying secretory pulse) (21 +/- 3.1 to 255 +/- 64 pg/ml; P < 0.0001), yielding a higher percentage of ACTH secreted in pulses (53 +/- 3.5 vs. 92 +/- 1.3%; P < 0.0001). There were minimal elevations in basal (nonpulsatile) ACTH secretion (by 50%; P = 0.0049) and ACTH secretory burst frequency (by 36%; P = 0.031). The estimated half-life of ACTH (median, 22 min) and the calculated ACTH secretory burst half-duration (pulse event duration at half-maximal amplitude) (median, 23 min) did not change. Hypocortisolemia evoked remarkably more orderly subordinate patterns of serial ACTH release, as quantitated by the approximate entropy statistic (P = 0.003). This finding was explained by enhanced regularity of successive ACTH secretory pulse mass values (P = 0.032). In contrast, there was no alteration in serial ACTH interpulse-interval (waiting-time) regularity. At the level of 24-h ACTH rhythmicity, cortisol withdrawal enhanced the daily rhythm in ACTH secretory burst mass by 29-fold, elevated the mesor by 16-fold, and delayed the acrophase by 3.4 h from 0831 h to 1154 h (each P < 10(-3)). In summary, short-term glucocorticoid feedback deprivation primarily (>97% of effect) amplifies pulsatile ACTH secretory burst mass, while minimally elevating basal/nonpulsatile ACTH secretion and ACTH pulse frequency. Reduced cortisol feedback paradoxically elicits more orderly (less entropic) patterns of ACTH release due to emergence of more regular ACTH pulse mass sequences. Cortisol withdrawal concurrently heightens the amplitude and mesor of 24-h rhythmic ACTH release and delays the timing of the ACTH acrophase. In contrast, the duration of underlying ACTH secretory episodes is not affected, which indicates that normal pulse termination may be programmed centrally rather than imposed by rapid negative feedback. Accordingly, we hypothesize that adrenal glucocorticoid negative feedback controls hypothalamo-pituitary-adrenal axis dynamics via the 3-fold distinct mechanisms of repressing the mass of ACTH secretory bursts, reducing the orderliness of the corticotrope release process, and modulating the intrinsic diurnal rhythmicity of the hypothalamo-corticotrope unit.

Adrenocorticotropic Hormone↗
PubMed2001

Substance abuse in bipolar disorder.

BACKGROUND: High rates of substance abuse have been reported in the general population, with males more often affected than females. Although high rates of substance abuse have also been reported in bipolar patients, the relationship between substance abuse and bipolar disorder has not been well characterized. METHODS: Substance abuse histories were obtained in 392 patients hospitalized for manic or mixed episodes of bipolar disorder and rates of current and lifetime abuse calculated. Analyses comparing sex, subtype (manic vs. mixed) and clinical history variables were conducted. RESULTS: Rates of lifetime substance abuse were high for both alcohol (48.5%) and drugs (43.9%). Nearly 60% of the cohort had a history of some lifetime substance abuse. Males had higher rates of abuse than females, but no differences in substance abuse were observed between subjects in manic and mixed bipolar states. Rates of active substance abuse were lower in older age cohorts. Subjects with a comorbid diagnosis of lifetime substance abuse had more psychiatric hospitalizations. CONCLUSIONS: Substance abuse is a major comorbidity in bipolar patients. Although rates decrease in older age groups, substance abuse is still present at clinically important rates in the elderly. Bipolar patients with comorbid substance abuse may have a more severe course. These data underscore the significance of recognition and treatment of substance abuse in bipolar disorder patients.

Adult↗
PubMed2000

Dexamethasone metabolism in dexamethasone suppression test suppressors and nonsuppressors.

BACKGROUND: Variable dexamethasone kinetics is a possible confound in the dexamethasone suppression test. Modifications to include dexamethasone plasma levels and specific dexamethasone "windows" have been proposed. Our study aims to validate our proposed dexamethasone windows in an independent sample of 121 subjects. METHODS: We performed dexamethasone suppression tests in 162 subjects with mixed psychiatric diagnoses. Dexamethasone levels and beta-phase half-life of dexamethasone were computed for suppressors and nonsuppressors. RESULTS: Dexamethasone levels were lower in nonsuppressors than in suppressors. Dexamethasone levels correlated inversely with cortisol levels in the total sample, but were nonsignificant or weakly associated in those samples restricted to the windows. The beta-phase half-life of dexamethasone was shorter in nonsuppressors. The dexamethasone windows were validated at 3:00 PM and 10:00 PM. We propose 4.0 ng/mL as a revised upper limit of the 8:00 AM dexamethasone window. CONCLUSIONS: The plasma dexamethasone level is confirmed as a confound in the dexamethasone suppression test through more rapid dexamethasone clearance in nonsuppressors. Application of dexamethasone windows will reduce this source of test variance.

Adrenal Cortex Function Tests↗
PubMed2000

Diagnostic depressive symptoms of the mixed bipolar episode.

BACKGROUND: There is not yet consensus on the best diagnostic definition of mixed bipolar episodes. Many have suggested the DSM-III-R/-IV definition is too rigid. We propose alternative criteria using data from a large patient cohort. METHODS: We evaluated 237 manic in-patients using DSM-III-R criteria and the Scale for Manic States (SMS). A bimodally distributed factor of dysphoric mood has been reported from the SMS data. We used both the factor and the DSM-III-R classifications to identify candidate depressive symptoms and then developed three candidate depressive symptom sets. Using ROC analysis we determined the optimal threshold number of symptoms in each set and compared the three ROC solutions. The optimal solution was tested against the DSM-III-R classification for crossvalidation. RESULTS: The optimal ROC solution was a set, derived from both the DSM-III-R and the SMS, and the optimal threshold for diagnosis was two or more symptoms. Applying this set iteratively to the DSM-III-R classification produced the identical ROC solution. The prevalence of mixed episodes in the cohort was 13.9% by DSM-III-R, 20.2% by the dysphoria factor and 27.4% by the new ROC solution. CONCLUSIONS: A diagnostic set of six dysphoric symptoms (depressed mood, anhedonia, guilt, suicide, fatigue and anxiety), with a threshold of two symptoms, is proposed for a mixed episode. This new definition has a foundation in clinical data, in the proved diagnostic performance of the qualifying symptoms, and in ROC validation against two previous definitions that each have face validity.

Adolescent↗
PubMed2000

Effect of transjugular intrahepatic portosystemic shunt on thrombocytopenia associated with cirrhosis.

Thrombocytopenia is a frequent complication of cirrhosis. Its pathogenesis is not well known, but it has been suggested that splenic congestion induced by portal hypertension may be a major contributory factor. However, the available data regarding the effect of portal decompression either by surgical shunts or transjugular intrahepatic portosystemic shunt (TIPS) on peripheral platelet count in cirrhotics is conflicting. We studied the effects of TIPS on platelet count and mean platelet volume, following a successful TIPS placement. The platelet count had a tendency to decrease but was not statistically significant (120,100 +/- 72,100/mm3 before TIPS vs 99,800 +/- 51,400/mm3 after TIPS). The mean platelet volume remained essentially unchanged (9.8 +/- 1.5 fL before TIPS and 9.9 +/- 1.5 fL after TIPS). These results confirm that TIPS has an unpredictable effect on platelet count in cirrhotic patients with thrombocytopenia. The lack of a consistent increase in the peripheral mean platelet volume following TIPS placement suggests that TIPS is unable to significantly enhance the release of platelets sequestered in the splenic compartment in portal hypertension.

Adult↗
PubMed1999

Elevated frequency of diabetes mellitus in hospitalized manic-depressive patients.

OBJECTIVE: Disturbance in glucose homeostasis in psychiatric populations has been suggested since the early part of this century. Increased comorbidity of diabetes mellitus in persons with major mood disorders has also been suggested. The goal of this study was to determine whether subjects diagnosed with bipolar disorder have an elevated rate of comorbid diabetes mellitus. METHOD: Three hundred forty-five hospitalized patients, aged 20-74 years, who met the DSM-III-R criteria for bipolar disorder, manic or mixed subtype, were evaluated for a comorbid diagnosis of diabetes mellitus. The frequency of diabetes mellitus in the study group was determined and compared with the expected frequency, calculated as a weighted average based on sex and age from national norms. Variables characterizing the course and severity of the affective disorder in the group of diabetic bipolar subjects and a group of nondiabetic age-matched bipolar subjects were compared. RESULTS: The prevalence of diabetes mellitus among these bipolar patients was 9.9%, significantly greater than expected from national norms (3.4%). The patients with comorbid diabetes mellitus had significantly more lifetime psychiatric hospitalizations than the nondiabetic subjects, but age at first hospitalization and duration of psychiatric disorder were similar in the two groups. CONCLUSIONS: The frequency of diabetes mellitus in hospitalized patients diagnosed with bipolar disorder is higher than in the general population. Manic-depressive patients with diabetes mellitus have a more severe course of illness, as indicated by a greater number of psychiatric hospitalizations. Possible reasons for this increased comorbidity include a genetic relationship between the disorders, a causal relationship in which hypercortisolemia induces diabetes or diabetic vascular lesions contribute to mania, an overlapping functional disturbance affecting similar regions of the brain, or the effect of psychotropic medications.

Adult↗
PubMed1998

Plasma dexamethasone concentration and cortisol response during manic episodes.

BACKGROUND: Despite the widespread study of the dexamethasone suppression test (DST) in patients diagnosed with major depression, it has been less well studied during manic and mixed states of bipolar disorder. METHODS: Cortisol response to the administration of 1 mg of dexamethasone was studied in 44 patients diagnosed bipolar disorder, manic (n = 37) or mixed (n = 7). Dexamethasone levels and cortisol responses were compared between these groups. Four patients initially meeting criteria for bipolar disorder, mixed, and 7 patients initially meeting criteria for bipolar disorder, manic, all of whom were characterized as DST nonsuppressors, were retested after remission. RESULTS: Dexamethasone levels were lower and cortisol levels higher in those patients diagnosed bipolar disorder, mixed. An inverse correlation was found between log-transformed dexamethasone levels and log-transformed cortisol levels at 3 PM (r = -.619, p < or = .001) and 10 PM (r = -.501, p < or = .001). In those subjects retested after remission, dexamethasone levels were higher and cortisol levels lower than during the manic and mixed states. CONCLUSIONS: Disturbances in the hypothalamic-pituitary-adrenal axis are observed frequently during mixed states of bipolar disorder, but are also not uncommon in purely manic episodes. These changes appear to be state dependent and revert with treatment.

Adolescent↗
PubMed1998

Tryptophan depletion in recently manic patients treated with lithium.

BACKGROUND: Serotonin has been repeatedly implicated in the mechanism of action of lithium against acute mania. Its role, however, has never been directly confirmed. METHODS: We studied recently manic patients successfully treated with lithium using a tryptophan depletion methodology. RESULTS: Patients remained euthymic despite a confirmed decrease in serum tryptophan levels. CONCLUSIONS: These data do not suggest that serotonin plays a critical role in the acute antimanic effect of lithium.

Adult↗
PubMed1998

A factor analysis of the signs and symptoms of mania.

BACKGROUND: No adequate factor analyses of signs and symptoms of mania have been reported. From limited past reports, the view has arisen that 2 main symptom clusters (euphoric-grandiose and paranoid-destructive) occur in patients with mania, along with so-called core symptoms of psychomotor pressure. In this view, dysphoric mania is associated with paranoid-destructive symptoms and with psychosis. METHODS: We rated 237 patients with DSM-III-R-defined bipolar disorder, manic (n = 204) or mixed (n = 33), on 15 classic features of mania and 5 features related to dysphoric mood. Principal components factor analysis was applied to the ratings. RESULTS: Five clearly interpretable and clinically relevant factors were identified. The first and strongest factor represented dysphoria in mania, with strong positive loadings for depressed mood, lability, guilt, anxiety, and suicidal thoughts and behaviors and a strong negative loading for euphoric mood. Factors 2 through 5 represented psychomotor acceleration, psychosis, increased hedonic function, and irritable aggression, respectively. The distribution of weighted scores on factor 1 was bimodal, whereas the corresponding distributions of factors 2 through 5 were unimodal. Contrary to all past reports, no general factor denoting overall severity of mania was found. Factors previously proposed by Beigel and Murphy were not confirmed. CONCLUSIONS: Five independent factors representing dysphoric mood, psychomotor pressure, psychosis, increased hedonic function, and irritable aggression were identified. The conventional view of symptom factors in mania was not confirmed. Dysphoric features are statistically salient in patients with mania, and the bimodal distribution of the dysphoria factor is consistent with the possibility that mixed bipolar disorder is a distinct state.

Adolescent↗
PubMed1998

Signs and symptoms of mania in pure and mixed episodes.

BACKGROUND: Debate continues about the diagnosis of mixed mania and the restrictiveness of the DSM-III-R and DSM-IV criteria for Bipolar Disorder, mixed. Although awareness of dysphoric features during mania continues to grow, standard mania rating instruments do not adequately assess mixed states and there is a striking disparity between the dysphoric signs and symptoms emphasized in research studies and the commonly employed DSM criteria. METHODS: Three hundred sixteen inpatients meeting DSM-III-R criteria for Bipolar Disorder, manic or mixed, were evaluated by rating 20 signs and symptoms. The frequencies of these signs and symptoms were computed for both diagnostic subtypes and compared using chi2 statistics and conditional probability parameters. RESULTS: The most frequently noted signs and symptoms in mania are motor activation, accelerated thought process, pressured speech and decreased sleep. Although euphoric mood was present in a large portion of the cohort, irritability, dysphoric mood and mood lability were also prominent in the entire cohort. Dysphoric mood, mood lability, anxiety, guilt, suicidality, and irritability were the only symptoms significantly more common in the mixed group. In contrast, grandiosity, euphoric mood, and pressured speech were significantly more often observed in the pure manic group. Contrary to popular belief, paranoia did not differ significantly between the two groups. Suicidality was present in a non-trivial 7% of the entire cohort, including some subjects who did not meet the criteria for mixed mania. LIMITATIONS: The comparison of mixed and manic episodes requires the appropriate definition of mixed states. In the current report we use the DSM-III-R definition of Bipolar Disorder, mixed, which may be too rigid. CONCLUSIONS: The data underscore that mania is not a purely euphoric state. Substantial rates of dysphoria, lability, anxiety and irritability were noted in the "pure" manic patients, as well as in those who meet the full DSM criteria for Bipolar Disorder, mixed, suggesting, that perhaps a less restrictive definition of mixed states would be more appropriate.

Adolescent↗
PubMed1998

Familial leukoencephalopathy in bipolar disorder.

OBJECTIVE: Imaging studies of patients with bipolar disorder demonstrate changes in deep white matter and subcortical gray nuclei that are seen as focal hyperintensities on T2-weighted magnetic resonance imaging (MRI). The objective of this study was to examine MRIs in a family with a strong history of bipolar disorder to look for possible MRI abnormalities in members with and without affective illness. METHOD: The authors obtained MRIs of 21 members of a family with a strong history of bipolar disorder. Eight of the family members studied had bipolar illness, one had symptoms of bipolar disorder but did not meet full DSM-III-R criteria, two had unipolar disorder, and 10 did not have bipolar disorder. RESULTS: Fifteen of the 21 family members had MRI findings, including six of 10 family members who had no affective disorder and all of those with bipolar disorder. Lesions of both white matter and subcortical gray nuclei were found. CONCLUSIONS: Although the clinical significance of these MRI findings is unknown, the high prevalence of MRI findings in both affected and unaffected family members suggests that MRI findings may potentially serve as a biological marker for bipolar disorder. Recent genetic studies have established a link between familial leukoencephalopathy and chromosome 19. If leukoencephalopathy appears to be related to bipolar disorder, it may allow clearer characterization of the genetics of the disorder.

Adolescent↗