Heredity in comorbid bipolar disorder and obsessive-compulsive disorder patients.

Partly due to the overlap of symptom groupings in DSM, psychiatric comorbidity is extremely common. One of the most common and difficult to manage comorbid conditions is the co-occurrence of bipolar disorder (BD) and obsessive compulsive disorder (OCD). However, the key nosological question about this condition - whether they are two distinct disorders or a subtype of one of the disorders - remains unresolved. In order to help address this unanswered question, we updated our recent systematic review, searching the electronic databases MEDLINE, Embase, and PsycINFO to specifically investigate the heredity in BD-OCD patients. We identified a total of 8 relevant papers, the majority of which found that, compared to non-BD-OCD patients, BD-OCD patients were more likely to have a family history for mood disorders and less likely to have a family history for OCD. These results support the view that the majority of cases of comorbid BD-OCD are, in fact, BD cases. If confirmed in larger, more focused studies, this conclusion would have important nosological and clinical implications.

Introduction

In 1970 the famous epidemiologist Alvan R. Feinstein defined comorbidity in relation to a specific index condition as, “any distinct additional entity that has existed or may occur during the clinical course of a patient who has the index disease under study”.[1] In Feinstein’s formulation, the implication was that a completely different and independent disease occurred at the same time as another disease.

In contrast to this approach, the Diagnostic and Statistical Manual of Mental Disorders (DSM) explicitly produces overlapping clinical criteria for many diagnoses, especially mood and anxiety disorders, guaranteeing comorbidity in quite a different sense than in the medical meaning of the term as co-occurrence of independent diseases.[1]

Psychiatric comorbidity is extremely common in bipolar disorder (BD). More than half of BD patients have an additional diagnosis, one of the most difficult to manage being obsessive-compulsive disorder (OCD).[2]

BD-OCD comorbidity has important nosological and clinical implications. The nosological question is whether this common “comorbidity” represents two diseases, or multiple symptoms of one disease. The clinical question is whether and how to treat the comorbidity since the main treatment for one disease can worsen the other diseases. Serotonin reuptake inhibitors (SSRIs) for OCD can cause mania and/or more mood episodes in BD.[3]

Although recent studies have investigated the cooccurrence of anxiety and bipolar disorders, the topic is insufficiently studied and the relationship between BD and OCD remains unclear.[4] In order to address this unanswered question, we updated our recent systematic review[5] to specifically investigate the heredity in BD-OCD patients.

Updated systematic review

Studies published in English through 31 October 2015 were identified by searching MEDLINE, Embase, and PsycINFO. We combined the search strategy of free text terms and exploded MESH headings for the topics of bipolar disorder, obsessive-compulsive disorder, and treatment combined as following: (((((((((“Bipolar Disorder”[Mesh]) OR Bipolar disorder) OR BD) OR Bipolar) OR Manic depressive disorder) OR Manic depressive) OR Manic)) AND ((((“Obsessive-Compulsive Disorder”[Mesh]) OR OCD) OR Obsessive-compulsive) OR Obsessive compulsive disorder))).

The eight studies shown in Table 1 were selected. No studies were found that examined familial transmission of comorbid BD-OCD. Seven studies[7, 8, 9, 10, 12, 13, 14] assessed family history for OCD or BD in comorbid BD-OCD probands using semi-structured or unstructured clinical interviews and clinical records. Five studies[8, 10, 12, 13, 14] reported that compared to non- BD-OCD patients, BD-OCD patients were more likely to have a family history for mood disorders and less likely to have a family history for OCD; one study[9] reported the opposite. The sole population-based study[7] found no statistically significant differences in the prevalence of a family history for OCD, depression, or mania between OCD patients with or without BD comorbidity. In one study, [11] a family history for mood disorders was reported to be more frequent in patients with episodic OCD than in those with continuous or chronic OCD symptoms.

Studies that met inclusion/exclusion criteria for systematic review about comorbid BD-OCD

reference	study design	country	study population	diagnostic method; criteria	results	study qualitya
BD, bipolar disorder			DSM, Diagnostic and Statistical Manual of Mental Disorders
OCD, obsessive-compulsive disorder			SCID, Structured Clinical Interview
MDE, major depressive disorder			NS, Not specified
			aaChecklist for measuring study quality developed by Downs and Black[6]
Angst 2005[7]	prospective cohort	Switzerland	591 subjects recruited at age 19 or 20 and assessed over 20 years: OCD (n=30), BD (n=93) OCD-BD (n=44)	Broad definition for BD and OCD; DSM-IV	No statistically significant differences in family history for OCD, depression, or mania in OCD patients with or without BD comorbidity	26/31
Berutti 2014[8]	cross sectional	Brazil	BD (n=488) age>18	SCID; DSM-IV	BD patients with a family history of mood disorders presented with significantly higher lifetime prevalence of OCD	24/31
Koyuncu 2010[9]	case control	Turkey	BD (n=214) mean age=34.8 (10.3) BD-OCD (n=35) mean age=36.2 (15.9)	SCID; DSM-IV	Higher prevalence of OCD in firstdegree relatives of BD-OCD patients versus that in relatives of non-BD-OCD patients (45.7% vs. 5.7%); no statistically significant differences in family history for BD	20/31
Mahasuar 2011[10]	case control	India	OCD (n=91) mean age=29.4 (8.3), BD-OCD (n=34) mean age=28.4 (7.1)	SCID; DSM-IV	Statistically non-significant trends of higher prevalence of family history for mood disorders in BD-OCD patients and lower prevalence of family history for OCD versus those in non-BD-OCD patients	19/31
Perugi 1998[11]	case control	Italy	OCD (n=135) mean age=38.4 (13.3)	NS; DSM-III-R	Positive correlation between episodic OCD and family history for mood disorders compared with patients with continuous OCD (54.1% vs. 34.7%)	21/31
Perugi 2002[12]	case control	Italy	OCD-MDE (n=68) mean age=34.2 (12.5) BD-OCD (n=38) mean age=35.9 (12.2)	SCID; DSM-IV	Statistically non-significant trends of higher prevalence of family history for mood disorders and lower prevalence of family history for OCD in BD-OCD patients versus those in non-BD-OCD patients	20/31
Shashidhara 2015[13]	cross sectional	India	BD-I (n=396, age>18)	SCID; DSM-IV	Higher prevalence of family history for mood disorders in BD-OCD patients compared to family history in OCD patients (33.3% vs. 6.7%)	23/31
Zutshi 2007[14]	case control	India	OCD (n=106) mean age=26.5 (7.4) BD-OCD (n=28) mean age=27.9 (6.7)	SCID; DSM-IV	Compared to non-BD-OCD patients, BD-OCD patients have higher prevalence of family history for mood disorder (36% vs. 6%) and lower prevalence of family history for OCD (0.0% vs. 21%)	20/31

Conclusions

Results from this review support the view that the majority of cases of comorbid BD-OCD are, in fact, BD cases. Considering course of illness as a key diagnostic validator, the majority of comorbid OCD cases appeared to be related to mood episodes. OC symptoms in comorbid patients appeared more often - and sometimes exclusively - during depressive episodes, and comorbid BD and OCD cycled together, with OC symptoms often remitting during manic/hypomanic episodes.[5]

From a therapeutic perspective, Osler’s view that medicine should focus on the treatment of diseases, not on the treatment of symptoms, is consistent with the recommended approach for treating comorbid BDOCD. Mood stabilization should be the first objective in treating apparent BD-OCD patients, not immediate treatment with selective serotonin reuptake inhibitors (SSRIs) In a minority of BD patients with refractory OCD, addition of low doses of antidepressants might also be considered while strictly monitoring emerging symptoms of mania and hypomania.[3]