Attention-deficit hyperactivity disorder -- bipolar comorbidity in children and adolescents

OBJECTIVE: A substantial portion of juvenile bipolar disorder (BD) has a comorbid attention-deficit hyperactivity disorder (ADHD). The aim of our study was to analyze the cross-sectional and longitudinal implications of such comorbidity in children and adolescents with BD. METHODS: Ninety-eight refereed patients (mean age 13.7 +/- 3.0 years) with a diagnosis of BD by the Schedule for Affective Disorders and Schizophrenia for School-Age Children, Present and Lifetime version (K-SADS-PL) were followed for 6 months. RESULTS: Thirty-seven BD patients (37.8%) presented a lifetime diagnosis of comorbid ADHD. The mean age of onset of ADHD was 3.7 +/- 1.1 years, and the mean age of onset of BD was 10.0 +/- 3.2 years. Bipolar subjects with comorbid ADHD were predominantly male, younger, and had an earlier onset of BD (8.1 +/- 2.8 versus 11.1 +/- 2.9 years). Bipolar-ADHD patients presented more frequently a chronic rather than an episodic course of BD, with an irritable rather than an elated mood. They showed higher rates of oppositional defiant disorder/conduct disorder, lower rates of panic disorder, and less frequently received antidepressant medications. Finally, ADHD comorbidity was associated with a greater psychosocial impairment. CONCLUSIONS: ADHD comorbidity is frequent in juvenile BD and can influence age of onset, phenomenology, comorbidity, and course of BD. A timely diagnosis should improve our efforts regarding the outcome of these subjects.     

Risk factors associated with childbearing-related episodes in women with bipolar disorder

OBJECTIVE: For the onset of illness and possible recurrence during the childbearing period, women with bipolar disorder (BD) are at a higher risk. The aim of this study was to evaluate the impact of clinical and psychosocial factors associated with pregnancy and the postpartum period on the course of BD. METHODS: The childbearing and illness history of 72 women with BD were assessed to determine mood episodes related to the childbearing period. Data was analyzed to evaluate the risk factors (clinical, obstetric and psychosocial factors) related with mood episodes during pregnancy and the postpartum period. RESULTS: Data of 252 pregnancies and childbirths of 72 women with BD were included in the analysis. Twenty-three (32%) women with BD reported at least one mood episode during pregnancy or within 1 month after childbirth (childbearing-related episode, CBRE). Subjects with CBREs mean age at onset of illness and mean age at the time of assessment were significantly younger than subjects with N-CBRE. A lower number of women who experienced a postpartum episode after the birth of the first child chose to have the second one. Psychosocial factors during pregnancy and the postpartum period and method of delivery did not predict the first postpartum episode. Onset of illness at an early age, experiencing episode during the first pregnancy and experiencing physical problems during pregnancy predicted a mood episode during the first postpartum period. CONCLUSIONS: Interpretation of the results of the study is limited with the retrospective nature of data collection. Within the limitations, we may suggest that psychosocial factors do not play a significant role in the genesis of CBREs in women with BD.     

Concurrent tracking of alcohol use and bipolar disorder symptoms

OBJECTIVES: Alcohol use disorders (AUDs) are common co-occurring conditions in patients with bipolar disorder (BD), but it is unclear whether or not AUD and BD symptoms are temporally correlated. The primary aim of this analysis was to examine concurrent symptom tracking and how the relative onsets of AUD and BD influence the concurrent tracking of symptoms. METHODS: Participants met DSM-IV criteria for bipolar I disorder, manic or mixed, with no prior hospitalizations and minimal treatment. Patients were rated for alcohol use and bipolar symptom severity on a weekly basis for up to 7 years. For analysis purposes, patients were placed into groups with no AUD (BD Only; n = 21), onset of AUD either concurrent with or after the onset of bipolar symptoms (BD First; n = 32), and onset of AUD at least 1 year before the onset of bipolar symptoms (AUD First; n = 18). RESULTS: None of the patient groups demonstrate consistent positive or negative temporal correlations between alcohol use and affective symptoms. However, there were significant between-group differences on the relationship of symptom tracking and age of BD onset. For the AUD First group, the correlation between age of BD onset and symptom tracking was positive 0.41. However, for the BD First and BD Only groups the correlations were negative (-0.32 and -0.41, respectively). Moreover, for patients whose BD onset was < or =18 years old, the correlation between age of onset and tracking was -0.47. CONCLUSIONS: These findings suggest that although there is no direct temporal correlation of AUD and BD symptoms in subgroups of BD patients, age at illness onset contributes to the complex relationship between BD and AUD. For younger patients there may be a greater likelihood that alcohol use and bipolar symptoms increase or decrease in unison.     

Clinical characteristics and psychiatric comorbidity in males with exhibitionism

BACKGROUND: This study was constructed to detail the demographic and phenomenological features of males with exhibitionism. METHOD: Male subjects with DSM-IV exhibitionism were administered a semistructured interview to elicit demographic data and information on the phenomenology, age at onset, and associated features of the disorder. Subjects also underwent structured clinical interviews to assess both Axis I and Axis II comorbidities. Data were collected from September 2003 to March 2005. RESULTS: Twenty-five males with exhibitionism (mean +/- SD age = 35.0 +/-13.1 years [range, 14-68 years]) were studied. The majority of subjects were single (60% [N = 15]) and heterosexual (80% [N = 20]). The mean +/- SD age at onset for exhibitionism was 23.4 +/-13.1 years. All subjects reported urges to expose themselves with little control over these urges. Exposing oneself while driving was the most common expression of the disorder. Twenty-three (92%) suffered from a current comorbid Axis I disorder (major depressive disorder, compulsive sexual behavior, and substance use disorders were most common), and 40% (N = 10) suffered from a personality disorder. Suicidal thoughts were common (52% [N = 13]), and many (36% [N = 9]) had been arrested for exhibitionism. CONCLUSION: Exhibitionism appears to be associated with high rates of psychiatric comorbidity and impairment. Research is needed to optimize patient care for men with this disorder.     

Community survey of bipolar disorder in Canada: lifetime prevalence and illness characteristics.

OBJECTIVE: This study reports on the lifetime prevalence and illness characteristics of bipolar disorder (BD) in a large, representative sample of Canadians. METHOD: Data were obtained from the Canadian Community Health Survey: Mental Health and Well-Being. This representative, cross-sectional survey, conducted by Statistics Canada in 2002, examines the mental health of Canadians aged 15 years and over. The national response rate was 77%. We determined the prevalence rate of BD, correlates of a bipolar diagnosis, and illness characteristics. RESULTS: The weighted lifetime prevalence rate of BD was 2.2% (95% confidence interval [CI], 1.94% to 2.37%). Younger age, low income adequacy, lifetime anxiety disorder, and presence of a substance use disorder in the past 12 months were each significantly associated with the presence of a BD diagnosis (P < 0.001 for each). The largest effect found was for the presence of an anxiety disorder (odds ratio 7.94; 95% CI, 6.35 to 9.92). A lifetime history of anxiety disorder was reported by 51.8% (955% CI, 47.1% to 56.5%) of the respondents with BD, with both panic disorder and agoraphobia each being more frequent among women, compared with men (P = 0.01 and P < 0.001, respectively). The mean age at onset of illness was 22.5 years, SD 12.0. CONCLUSIONS: According to the estimated lifetime prevalence of BD found in this study, over 500 000 Canadians likely suffer from this condition. Identifying those at highest risk for BD may assist in developing more effective community-based identification and intervention strategies.     

Epidemiologic study of 203 sibling pairs with Parkinson's disease: the GenePD study.

OBJECTIVE: To examine patterns of familial aggregation and factors influencing onset age in a sample of siblings with PD. METHODS: Sibling pairs (n = 203) with PD were collected as part of the GenePD study. Standardized family history, medical history, and risk factor data were collected and analyzed. RESULTS: The mean age at onset was 61.4 years and did not differ according to sex, exposure to coffee, alcohol, or pesticides. Head trauma was associated with younger onset (p = 0.03) and multivitamin use with later onset (p = 0.007). Age at onset correlation between sibling pairs was significant (r = 0.56, p = 0.001) and was larger than the correlation in year of onset (r = 0.29). The mean difference in onset age between siblings was 8.7 years (range, 0 to 30 years). Female sex was associated with increased frequency of relatives with PD. The frequency of affected parents (7.0%) and siblings (5.1%) was increased when compared with frequency in spouses (2.0%). CONCLUSIONS: The greater similarity for age at onset than for year of onset in sibling pairs with PD, together with increased risk for biological relatives over spouses of cases, supports a genetic component for PD. Risk to siblings in this series is increased over that seen in random series of PD cases; however, patients in this sample have similar ages at onset and sex distribution as seen for PD generally. These analyses suggest that factors influencing penetrance are critical to the understanding of this disease.     

Birth‐cohort and dual diagnosis effects on age‐at‐onset in Brazilian patients with bipolar I disorder

Objective: Substance use disorders and birth‐cohort have been associated with an earlier onset in bipolar disorder (BD). This study aimed at evaluating the inter‐relations of these factors in age‐at‐onset in bipolar illness. Method: Two‐hundred and thirty patients with bipolar I disorder were cross‐sectionally evaluated. Patients were categorized into four age groups for analysis. Lifetime comorbidity and age‐at‐onset were derived from the Structured Clinical Interview for DSM‐IV. Results: There was a strong linear association between age group and age‐at‐onset. Lifetime alcohol and drug use disorders were also associated with age‐at‐onset. Illicit drug and alcohol use disorders and age group remained significant in the multivariate model. No interactions appeared. Conclusion: Both age group and dual diagnoses had strong and independent impacts on age‐at‐onset in out‐patients with BD. Substance abuse may be partly accountable for earlier symptom onset, but other features of BD in younger generations are still in need to be accounted for.     

Psychiatric and cognitive difficulties as indicators of juvenile huntington disease onset in 29 patients

BACKGROUND: Juvenile Huntington disease (JHD) is a rare clinical entity characterized by an age at onset younger than 20 years. Patients usually have an expansion of more than 60 CAG repeats in the Huntington disease (HD) gene, and the disease is usually inherited from the father. In general, precise age at onset is difficult to assess in HD because of insidious onset and anosognosia. Onset of motor difficulty signs is usually used to define age at onset. OBJECTIVES: To evaluate diagnosis delay in patients with JHD and to analyze the clinical and genetic features of JHD. DESIGN: Retrospective clinical and genetic review. SETTING: Referral center for HD at Salpêtrière Hospital, Paris, France. PATIENTS: Twenty-nine patients with HD with onset before or at age 20 years who carried an abnormal CAG repeat expansion in the HD gene. RESULTS: The mean +/- SD delay before diagnosis was 9 +/- 6 years (range, 0-21 years). The most remarkable signs at onset were severe psychiatric and cognitive disturbances (19 of 29 [65.5%]); rigidity was absent. Unusual signs at onset included myoclonic head tremor in 3 patients, severe isolated drug or alcohol addiction in 2, psychotic disorder in 1, and difficulty writing in 1. One patient had progressive cerebellar signs associated with cerebellar atrophy on cerebral magnetic resonance imaging before signs suggestive of HD appeared. During the course of the disease, psychiatric disturbances were severe, with at least 1 suicide attempt in 7 of 29 patients. Transmission was maternal in 25% of patients. Forty-six percent of patients with JHD had fewer than 60 CAG repeats; 6 of these patients inherited the disease from their father. Anticipation (mean +/- SD, 18 +/- 9 vs 25 +/- 11 years; P = .27) and age at onset (mean +/- SD, 17.14 +/- 2.2 vs 13.29 +/- 5.5 years; P = .09) was similar in patients with maternal compared with paternal transmission, respectively. CONCLUSIONS: Patients with JHD started showing disease symptoms through nonspecific features, mostly psychiatric and cognitive difficulties. This led to misdiagnosis or diagnosis delay, especially in cases without a familial history of HD. Maternal transmissions and expansions of fewer than 60 CAG repeats were unexpectedly frequent in this series and should not be considered exceptional.     

Daily Use,Especially of High-Potency Cannabis,Drives the Earlier Onset of Psychosis in Cannabis Users

Cannabis use is associated with an earlier age of onset of psychosis (AOP). However, the reasons for this remain debated. Methods: We applied a Cox proportional hazards model to 410 first-episode psychosis patients to investigate the association between gender, patterns of cannabis use, and AOP. Results: Patients with a history of cannabis use presented with their first episode of psychosis at a younger age (mean years = 28.2, SD = 8.0; median years = 27.1) than those who never used cannabis (mean years = 31.4, SD = 9.9; median years = 30.0; hazard ratio [HR] = 1.42; 95% CI: 1.16–1.74; P < .001). This association remained significant after controlling for gender (HR = 1.39; 95% CI: 1.11–1.68; P < .001). Those who had started cannabis at age 15 or younger had an earlier onset of psychosis (mean years = 27.0, SD = 6.2; median years = 26.9) than those who had started after 15 years (mean years = 29.1, SD = 8.5; median years = 27.8; HR = 1.40; 95% CI: 1.06–1.84; P = .050). Importantly, subjects who had been using high-potency cannabis (skunk-type) every day had the earliest onset (mean years = 25.2, SD = 6.3; median years = 24.6) compared to never users among all the groups tested (HR = 1.99; 95% CI: 1.50- 2.65; P < .0001); these daily users of high-potency cannabis had an onset an average of 6 years earlier than that of non-cannabis users. Conclusions: Daily use, especially of high-potency cannabis, drives the earlier onset of psychosis in cannabis users.Key words: psychotic disorders, age of onset, gender, cannabis, survival plots, drug use, high-potency cannabis     

Early onset bipolar disorder: possible linkage to chromosome 9q34

OBJECTIVES: Bipolar disorder (BD) is characterized by manic and depressive states that onset at various times in life. Research shows that early onset forms of BD are associated with a stronger genetic loading for the illness. We hypothesized that using age at onset to look at subsets of BD families in a genetic linkage analysis would prove useful in separating etiologically homogeneous BD sub-groups and subsequently identifying genetic susceptibility regions. METHODS: We used the wave-I National Institute of Mental Health (NIMH) Genetics Initiative BD sample, which includes 540 individuals from 97 families with BD, in an ordered-subsets linkage analysis with age at onset of mania as the subset-identifying covariate. This analysis was performed using GENEHUNTER-PLUS followed by the ordered-subsets analysis program. This program generates empirical p-values for the subset with the largest LOD score to determine whether this value was significantly higher than the baseline LOD score using all families. RESULTS: Three chromosomal regions resulted in LOD scores above 2.0: 2.21 (6q25), 3.21 (9q34), and 2.16 (20q11). The largest increase in LOD score was observed on chromosome 9q34 between markers D9S290 and D9S915 in the subset of 58 families that had mania onset before age 20. Families with a minimal mania onset less than 20 years had a significantly greater number of psychiatric comorbidities (p = 0.02) and a marginal increase in depressive symptoms (p = 0.10). CONCLUSIONS: Further investigation into chromosomal region 9q34 is necessary to determine whether this region may harbor a gene specific to families with a minimal age at onset of less than 20.     

Duration of untreated bipolar disorder: missed opportunities on the long road to optimal treatment

Objective: Duration of untreated illness represents a potentially modifiable component of any diagnosis‐treatment pathway. In bipolar disorder (BD), this concept has rarely been systematically defined or not been applied to large clinically representative samples. Method: In a well‐characterized sample of 501 patients with BD, we estimated the duration of untreated bipolar disorder (DUB: the interval between the first major mood episode and first treatment with a mood stabilizer). Associations between DUB and clinical onset and the temporal sequence of key clinical milestones were examined. Results: The mean DUB was 9.6 years (SD 9.7; median 6). The median DUB for those with a hypomanic onset (14.5 years) exceeded that for depressive (13 years) and manic onset (8 years). Early onset BD cases have the longest DUB (P < 0.0001). An extended DUB was associated with more mood episodes (P < 0.0001), more suicidal behaviour (P = 0.0003) and a trend towards greater lifetime mood instability (e.g. rapid cycling, possible antidepressant‐induced mania). Conclusion: Duration of untreated bipolar disorder (DUB) will only be significantly reduced by more aggressive case finding strategies. Reliable diagnosis (especially for BD‐II) and/or instigation of recommended treatments is currently delayed by insufficient awareness of the early, polymorphous presentations of BD, lack of systematic screening and/or failure to follow established guidelines.     

A pilot study of antidepressant-induced mania in pediatric bipolar disorder: Characteristics, risk factors, and the serotonin transporter gene.

BACKGROUND: Antidepressant-induced mania (AIM) has been described in bipolar disorder (BD) and has been associated with the short-allele of the serotonin transporter gene (5-HTT). We wished to investigate the frequency of and risk factors for AIM in pediatric patients with or at high risk for BD. METHODS: Fifty-two children and adolescents (30 with BD and 22 with subthreshold manic symptoms, 15.1 +/- 3.4 years old), all with a parent with BD, were interviewed with their parents for manic/depressive symptoms occurring before and after past antidepressant treatment. The 47 subjects with serotonin reuptake inhibitor (SSRI) exposure were genotyped for the 5-HTT polymorphism. RESULTS: Fifty percent of subjects were AIM+ and 25.5% had new onset of suicidal ideation. The AIM+ and AIM- groups did not differ significantly in relation to allele (p = .36) or genotype (p = .53) frequencies of the 5-HTT polymorphism. The AIM+ subjects were more likely to have more comorbidities (3.2 vs. 2.4; p = .02) and be BD type I (p = .04) than AIM- subjects. CONCLUSIONS: Youth with or at high risk for BD may be particularly vulnerable to SSRI AIM and thus should be monitored if given SSRIs. In this preliminary study, we did not find that the 5-HTT polymorphism significantly influenced vulnerability to AIM.     

Regional gray matter changes in bipolar disorder: a voxel-based morphometric study

OBJECTIVE: To investigate structural abnormalities in bipolar disorder (BD) using optimized voxel-based morphometry (VBM) in closely matched patients and controls, and to examine the relationship of clinical features with regional gray matter (GM) volumes. METHODS: Twenty-four patients (six male) aged 19-59 years (mean=38.21 years, SD=11.04 years) with DSM-IV bipolar I disorder were compared with 25 control subjects, matched on age, sex, and years of education. VBM analyses were conducted on high-resolution T1-weighted brain magnetic resonance imaging to detect regional GM volume differences between groups, ensuring statistical correlation for age, sex and total intracranial volumes. Within the patient groups, regional GM changes were also investigated. RESULTS: Compared to controls, BD patients had increased GM volume in left parahippocampal gyrus and decreased GM volume in left middle temporal gyrus. Family history, psychotic symptoms and lithium status were associated with regional GM abnormalities in BD patients. CONCLUSIONS: This study presents evidence of gray matter volume abnormalities in adults with bipolar I disorder. Regional variation in relation to clinical factors suggests a neurobiological basis for clinical heterogeneity and posits the possibility of trait deficits.     

The M694V variant of the familial Mediterranean fever gene is associated with sporadic early-onset Alzheimer's disease in an Italian population sample

BACKGROUND: Inflammation is deemed to play a crucial role in the pathogenesis of Alzheimer's disease (AD). We sought to determine whether the proinflammatory M694V mutation of pyrin, the gene responsible for familial Mediterranean fever, could lead to an increased risk for AD. METHODS: We compared the M694V variant genotypes in 378 sporadic AD patients and 384 healthy control subjects of Italian descent. RESULTS: After adjustment for potential confounders, the M694V mutation was found to be associated with an increased risk for AD in subjects with an age at onset of 65 years or younger (multivariate-adjusted odds ratio, OR: 3.01, 95% confidence interval, CI: 1.24-6.72, p = 0.021), but not in patients with an age at onset older than 65 years (multivariate-adjusted OR: 0.81, 95% CI: 0.34-1.99, p = 0.847). Kaplan-Meier analysis indicated that AD patients bearing the M694V mutation presented with disease onset 7 years earlier than carriers of the wild-type genotype (log rank = 41.61, p < 0.001). CONCLUSION: Our data indicate that the M694V sequence variant in the pyrin gene might influence the age at onset of AD in the Italian population.     

Early age at onset of bipolar disorder is associated with more severe clinical features but delayed treatment seeking

OBJECTIVE: Our aim was to obtain a comprehensive view of differences between bipolar disorder (BD) patients with onset at early versus adult age in a representative study cohort. METHODS: In the Jorvi Bipolar Study (JoBS), 1,630 psychiatric in- and outpatients were systematically screened for BD using the Mood Disorder Questionnaire (MDQ). A total of 191 bipolar I and II patients with a current DSM-IV episode were interviewed to obtain information about age at onset of mood symptoms, clinical course, treatment, comorbidity, and functional status. The patients were classified as either early onset (<18 years) or adult onset. RESULTS: One-third of subjects with BD (58/191, 30%) had early onset. This was associated with female gender, more lifetime psychotic symptoms, greater overall comorbidity, and a greater length of time from first episode to treatment. CONCLUSIONS: Although BD patients with early age at onset have more severe clinical features and illness course, the delays from first episode to treatment and to correct diagnosis are longer than for those with adult onset disorder. To reduce morbidity rates related to the most severe forms of BD, the recognition and diagnosis of BD during adolescence needs to be improved.     

Demographic and clinical features of 131 adult pathological gamblers.

BACKGROUND: This study was constructed to detail the demographic and phenomenological features of pathological gamblers. METHOD: One hundred thirty-one subjects with DSM-IV pathological gambling were administered a semistructured interview to elicit demographic data and information on the phenomenology, age at onset, course, associated features, treatment history, and response to treatment of the disorder, followed by the Structured Clinical Interview for DSM-IV. RESULTS: Seventy-eight female (59.5%) and 53 male (40.5%) (mean +/- SD age = 47.7+/-11.0 years) pathological gamblers were studied. The majority of subjects (55.7%) were married. Subjects gambled a mean of 16 hours per week. Slot machines (65%), cards (33%), and blackjack (26%) were the most popular forms of gambling. The mean length of time between first gambling behavior and onset of pathological gambling was 6.3+/-8.9 years. Approximately one half (46%) of the subjects reported that television, radio, and billboard advertisements were a trigger to gamble. Most gamblers had severe financial, social, or legal problems. The majority of the subjects (58%) had at least 1 first-degree relative who also exhibited symptoms of problematic gambling behavior. CONCLUSION: Pathological gambling is a disabling disorder associated with high rates of social and legal difficulties.     

Status epilepticus in a population-based cohort with childhood-onset epilepsy in Finland

Little is known about the time course over which status epilepticus occurs in childhood-onset epilepsy and its impact on long-term prognosis. A population-based cohort of 150 children younger than age 16 years with new onset epilepsy between 1961 and 1964 residing in the catchment area of Turku University Hospital was observed prospectively until 1997. The occurrence of status epilepticus and recurrent status epilepticus, risk factors for status epilepticus, and the impact of status epilepticus on prognosis were examined. Of the 150 cases, 41 patients (27%) experienced an episode of status epilepticus of whom 22 patients (56%) had two or more episodes. The risk of status epilepticus was highest at the onset of the disorder with 30 (73%) cases occurring before (n = 12) or at (n = 18) onset and 37 (90%) cases within 2 years of onset. On multivariable analysis, risk factors for status epilepticus included remote symptomatic cause, age of onset 6 years or younger, and partial seizures. Specific epilepsy syndromes also were associated with a differential risk of status epilepticus. The occurrence of status epilepticus did not alter the mortality rates and had only a modest impact on the probability of attaining remission. In subjects with no other neurological handicap, social and educational outcomes were similar in those with status epilepticus and those with no history of status epilepticus. We conclude that status epilepticus is a common occurrence in childhood-onset epilepsy. When it does occur, it occurs early in the course of the disorder. The occurrence of status epilepticus does not appear to have significant adverse impact on long-term prognosis of childhood-onset epilepsy.     

Differences between prepubertal- versus adolescent- onset bipolar disorder in a Spanish clinical sample

Objective To examine patients attended and diagnosed with bipolar disorder (BD) at a child and adolescent psychiatry service; to record age of diagnosis and age of onset, and to study clinical differences between prepubertal and adolescent onset groups. Methods All patients currently attended for BD type I, type II or non specified BD were reviewed and divided into two age groups: prepubertal onset (beginning before age 13) and adolescent onset (beginning at or above age 13). Results The sample were 43 patients with BD. Fourteen (32.6%) with prepubertal onset and 29 (67.4%) with adolescent onset. Time between onset of symptoms and diagnosis was longer in the prepubertal onset group (1.2 years versus 0.8 years respectively, P = .05). Patients with prepubertal onset BD more frequently presented previous symptoms such as irritability and conduct problems and had a higher rate of comorbidity (more frequently attention-deficit/hyperactivity disorder–ADHD). The adolescent onset group more often presented psychotic symptoms. Conclusion The clinical characteristics of patients with bipolar disorder differ according to whether onset is prepubertal or adolescent.     

The motor phenotype of Parkinson's disease in relation to age at onset

Background: Parkinson's disease (PD) is heterogeneous and age at onset may define variation in clinical phenotype. Most previous studies have used various age cut‐offs and have been based on clinical case series. Methods: We have studied the association between clinical features and age of onset in 358 community‐based and regional patients with PD. Results: Tremor at presentation is twice as common in those with onset over 64 years as compared to those with onset under 45 (early onset PD ‐ EOPD) and becomes more common with increasing age at onset (p values for trend ≤ 0.004). Dystonia affects 60% of those with EOPD, shows a curvilinear relationship with age at onset (cubic versus linear p=0.01) with highest risk in patients whose disease began before 48 years. In this study age at onset was a strong predictor of the development of dyskinesias, with younger age associated with a higher risk of dyskinesias. Following multivariable analysis, allowing for possibly confounding factors (disease duration, L‐DOPA dosage, L‐DOPA treatment duration) younger age at onset, (less than 55 years) predicted the development of L‐DOPA induced dyskinesia (odds ratio <45 years 2.1, 95% CI 1.0, 4.8; odds ratio < 55 years 3.8, 95% CI 1.8, 8.0). Only 2/70 (2.9%) EOPD patients carried pathogenic parkin or PINK1 mutations and the clinical differences between early and late onset disease were not explained by the presence of mutations in these genes. Discussion: This study highlights the clinical differences between early and late onset PD, which have important implications for diagnosis and management. © 2011 Movement Disorder Society     

Comorbidity of attention deficit hyperactivity disorder with early- and late-onset bipolar disorder

OBJECTIVE: The relationship between attention deficit hyperactivity disorder (ADHD) and earlier age at onset of affective illness was examined in probands with a history of bipolar disorder. METHOD: The authors assessed 56 adult bipolar subjects. Those with a history of childhood ADHD (N=8) were age and sex matched with bipolar subjects without a history of childhood ADHD (N=8). RESULTS: The age at onset of the first affective episode was lower for the subjects with bipolar disorder and a history of childhood ADHD (mean=12.1 years, SD=4.6) than for those without a history of childhood ADHD (mean=20. 0 years, SD=11.3). CONCLUSIONS: ADHD in children of bipolar probands might identify children at highest risk for development of bipolar disorder.