Somatic and cognitive symptoms as indicators of potential endophenotypes in bipolar spectrum disorders: an exploratory and proof-of-concept study comparing bipolar II disorder with recurrent brief depression and healthy controls.

BACKGROUND: We examined whether somatic symptoms reported by patients with bipolar spectrum disorder (BSD), in this study defined as bipolar II (BD-2) or recurrent brief depression with (RBD-H) or without (RBD-O) a history of hypomanic symptoms might point to the possible underlying disease markers (endophenotypes). We hypothesized that somatic symptoms that are possible indirect indicators of endophenotypes should be more prevalent among patients than among healthy controls; should not correlate with neuroticism; should not correlate with the severity of current mental status (e.g., anxiety, depression); and should not correlate with the use of psychotropic drugs including antiepileptics or be explained by co-morbid medical diseases. METHODS: Sixty-one patients (BD-2: n=21; RBD-H: n=19; RBD-O: n=21) were compared with 21 healthy controls. Assessments included a 123-item somatic symptom checklist; assessments for neuroticism, anxiety and depression. Candidate somatic symptoms were selected using a 4-step inclusion/exclusion procedure. RESULTS: Seven symptoms survived in all three groups: general (fatigue, feeling exhausted); sensory (leaden sensation in legs, pain in the body, impaired sense of smell); cognitive (loss of memory) and autonomic (excessive perspiration). In addition 15 symptoms survived in one or two groups (examples: impaired hearing, hypersensitivity to sound, inability to find words). LIMITATIONS: Possible selection bias and small sample size precludes firm conclusions with regards to specific symptoms. CONCLUSION: Our approach identified symptoms for which an association with BSDs has been suggested previously, as well as symptoms not commonly associated with BSDs. The findings support the feasibility and validity of using assessment of somatic symptoms as an approach to identify potential endophenotypes in BSDs.

International prescribing patterns for mood illness: the International Mood Network (IMN).

OBJECTIVE: To show the feasibility of creating an international network that will build a common database for mood disorders research, and to present initial data on prescribing patterns worldwide. METHODS: An international research database was organized with clinicians and researchers actively treating mood disorders. Participating sites were asked to provide data on 10-50 subjects initially. This work was conducted under the auspices of a committee with representatives from North and South America, Europe, and Asia. Data was pooled from multiple sites using a centralized online system and then analyzed. Each site received IRB approval for its participation in the IMN and the Tufts Medical Center IRB provided approval for the entire project. LIMITATIONS: More than half of the population came from one country (United States) and there is the possibility of cultural bias. RESULTS: Among the 186 subjects enrolled in the IMN, a majority of subjects were prescribed mood stabilizers including lithium (64%), lamotrigine (37%), valproate (31%), and carbamazepine (3%). 79% had a diagnosis of bipolar disorder type I, II or NOS and 21% had a diagnosis of MDD. 81% of subjects used antidepressants at some point. 25% experienced antidepressant-induced mania and 26% had antidepressant-related rapid cycling. Mood stabilizers were prescribed more in Europe (86%), neuroleptics in South America (70%), and antidepressants in Asia (58%). CONCLUSIONS: The results confirm the diversity and feasibility of an international mood disorders database. Important regional differences in psychotropic drug treatment of mood illnesses were observed, with more mood stabilizer use in Europe and South America, and more antidepressant use in non-European populations.

Temperament and character in patients with bipolar II disorder and recurrent brief depression.

OBJECTIVES: We compared the temperament and character profiles of 21 patients with bipolar II disorder, 40 patients with recurrent brief depression (RBD; at least monthly depressive episodes meeting the diagnostic criteria for major depressive episode except for duration that is less than 2 weeks, typically 2-3 days, without fixed relation to menstrual cycle) of which 21 had no history of hypomania and 19 had experienced hypomanic episodes, and 21 age- and sex-matched controls. METHODS: Assessments included the Montgomery-Åsberg Depression Rating Scale, Hypomania Checklist, and Temperament and Character Inventory-125. Patients with cluster A and B personality disorders were excluded. RESULTS: Bipolar II and RBD patients had higher harm avoidance (HA) and lower self-directedness (SD) compared with controls. Excluding panic disorder comorbidity effaced this difference in HA and SD (bipolar II only) and harm avoidance. No other differences were found. CONCLUSIONS: In this first study comparing personality profiles of patients with bipolar II vs RBD, when controlling for confounders, neither bipolar II nor RBD patients differed significantly from healthy controls. The lower SD scores among RBD patients may reflect sampling bias (a higher rate of Axis 2 cluster C disorders).

The phenomenology of recurrent brief depression with and without hypomanic features.

BACKGROUND: The nosologic status of recurrent brief depression (RBD) is debated. We studied the phenomenology of RBD in a clinical sample of outpatients. METHODS: Forty patients (mean age 33; 73% females) and 21 age- and gender-matched mentally healthy controls were examined (clinical interview, M.I.N.I. neuropsychiatric interview, MADRS, Stanley Foundation Network Entry Questionnaire). Exclusion criteria were bipolar I or II disorders, a history of psychosis, concurrent major depressive episode, organic brain or personality disorders (clusters A and B). RESULTS: The mean age of onset of RBD was 20 years with a mean of 14 episodes/year with brief (mean 3 days) severe depressive episodes. Nineteen (47%) reported additional short episodes of brief hypomania (>1 day duration; RBD-H) of which nine (23%) never had experienced a major depression. Twenty-one (53%) patients reported RBD only (RBD-O) with or without (n=12) past history of major depression or dysthymia. During the last depressive episode, 76% of the RBD-O and 90% of the RBD-H patients had a melancholic depression. Seventy-one % of the RBD-O and 79% of the RBD-H reported at least two out of three atypical symptoms. Nineteen (48%) of the patients reported anger attacks and panic disorder, the latter being more prevalent in the RBD-H subgroup (68% versus 29%, p=0.012). LIMITATIONS: Cross-sectional study of self-referrals or patients referred by primary care physicians or psychiatrists. CONCLUSIONS: The study supports the validity of RBD as a disorder separate from bipolar II, cyclothymia and recurrent major depression. A brief episode of hypomanic symptoms is a severity marker of RBD.