Early intervention (EI) for patients with bipolar affective disorders (BPAD) is in its infancy. This is despite the fact that they constitute the second largest group of patients attending EI in psychosis (EIP) services [1]. There is a remarkable absence of research directed towards EI in BPAD and there are very few specific EI services for affective disorders. It is only when affective disorders are severe enough to be complicated by psychotic features that they fall into the remit of most EIP services. In some EIP services they are actually excluded, while in others they are simply subsumed within the larger non-affective group with no specific guidelines for managing their different needs. It is only very recently that a body of literature is emerging about the wider BPAD population attending Youth Mental Health services [2]. EI in affective disorders is very much the poor cousin. This is very surprising, given its high prevalence, morbidity, mortality, burden, social cost [3] and good potential for prevention [4].

Part of the reason for this emphasis on schizophrenia-spectrum disorders in EI is that schizophrenia has traditionally been viewed as the more serious and enduring condition, with long delays in accessing treatment, and a prognosis that is largely dependent on the initial course of the illness. BPAD is a rather more complicated condition, not least because it commonly presents with depressive episodes indistinguishable from unipolar depression, has divergent phases of illness, and may not be complicated by psychosis. Manic episodes are more acute in onset and shorter in duration, giving less opportunity for EI.

However, despite these shortcomings, interest in EI in BPAD is beginning to emerge and early evidence indicates that the rationale for EI in BPAD is just as compelling as that for psychotic disorders [4, 5].

The rationale for EI is that by investing resources into this early phase of illness, one not only can ameliorate and prevent unnecessary suffering but one can also maximize the chances of a full recovery and minimize the risk of relapse, thereby reducing the overall burden and costs for individuals, families and society [3]. In some individuals it may even be possible to prevent the onset of the illness altogether.

However, it is also clear that concepts that are central to EIP such as ‘at risk mental state’, duration of untreated psychosis (DUP) and the ‘critical period’ need re-evaluation when applied to BPAD. For example, estimates of the duration of untreated BPAD will vary widely depending on whether it is calculated from the onset of any mood change or is just limited to onset of mania [5]. Likewise interventions that might be quite appropriate in treating emerging schizophrenia may be very inappropriate in BPAD. However, the general EI principles of early detection, prevention and phase-specific interventions being maintained through a ‘critical period’ are very likely to hold true for BPAD as long as they are modified accordingly [4].

BPAD is a serious and potentially chronic condition that places a huge burden on society. BPAD is ranked sixth in a World Bank study of the global burden of diseases (ahead of Schizophrenia which was ranked eighth) [4] and ranked fourth among 10–24-year olds [7]. It is the disorder associated with the greatest loss of ‘human capital’ (i.e. the gap between individuals’ pre-morbid potential and their post onset functioning) [5]. McCrone et al. [3] estimated that compared to schizophrenia, BPAD affects 3 times as many individuals (1.4 vs. 0.5%), costs services in England nearly as much annually (£1.6 billion vs. £2.2 billion) and is a greater cost of lost employment (£5.2 vs. £4 billion) to the nation annually.

Similar to the field of psychosis, there is good evidence that a large proportion of patients presenting to services with BPAD for the first time have already had untreated episodes for several years. Several large studies have indicated that it is not unusual for people with bipolar disorder to experience a delay of over 10 years between the initial onset of symptoms, obtaining the correct diagnosis and receiving treatment [8]. Initial mood episodes typically develop in adolescence and have the potential to seriously disrupt the individuals’ capacity to establish their own independence and consolidate their emotional, social, educational and vocational trajectories. Delays in accessing treatment increase the risk of progression to severe stages of the illness with accompanying risk of hospitalisations, co-morbidity, poorer clinical outcomes and suicide [9]. Though symptomatic remission with treatment in the first episode is the norm (70–95%), functional recovery from the first episode is much poorer (35–56%) [5] and relapse rates (80%) are very high [10]. There is therefore a clear rationale for intervening earlier during this initial phase of the disorder.

Traditionally, BPAD is separated into two types: Bipolar Type I and II. Type I requires at least one manic episode while Type II requires only a hypomanic episode. Type II not uncommonly progresses later to Type I. The stability of the diagnosis is high (between 70 and 90%) and individuals commonly fall into one of two further categories of BPAD, the depressive polarity (60%) and the manic polarity (40%) [11]. Bipolar spectrum disorders encompass a broader category of mood states that include Cyclothymia.

Such a broad categorisation makes defining the first episode of BPAD a challenge. It is also complicated by the multidimensional nature of episodes, which are the presence of depression, mania, psychosis and their cyclical nature. Strictly speaking, BPAD should not be diagnosed until an individual has experienced two distinct episodes of mood disorder, one of which needs to be a manic, hypomanic or mixed manic episode (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision—ICD-10, World Health Organisation). If an individual has already been diagnosed with ‘unipolar’ depressive episodes prior to developing a manic, hypomanic or mixed episode, then technically the first depressive episode would in hindsight constitute the initial episode of BPAD. If an individual experiences their first acute mania/hypo/mixed mania with no history of depression, then according to ICD-10 one should reserve judgement until the person develops a second episode of mania/hypomania/depression and classify the first episode as a manic/hypomanic episode (not BPAD). However, this seems an academic distinction that fails to take into account the longitudinal course of BPAD.

Aetiological factors are important to mention as they identify those most at risk of developing BPAD and reveal opportunities for prevention. In reality, there are many different pathways that ultimately lead to the onset of BPAD and the factors along the way are complex, varied and dynamic. Genetics has been estimated to account for 59% of BPAD [14]. So far a myriad of genes have been implicated but as yet none has proven specific for BPAD. Early developmental factors such as Winter/Spring birth, obstetric complications, early brain injuries, delayed milestones, childhood adjustment and behavioural problems carry a higher risk [15]. Structural brain changes have been a relatively consistent but nonspecific finding in patients with BPAD. Neurochemical findings suggest abnormalities in the Opioid neuropeptide, Purinergic, Glutamatergic, Tachykinin Neuropeptide and Cholinergic systems, as well as the intracellular signalling pathways and oxidative stress [16]. Drugs and medications that act on the Serotonergic and Dopaminergic systems such as ecstasy, amphetamines, cocaine, methylphenidate, antidepressants and L-Dopa can trigger a first episode or aggravate further episodes in those susceptible to BPAD. Similarly, medications such as steroids that act on the Adrenocortical Axis can trigger episodes of BPAD. ACTH is more likely to induce mania while Prednisolone is more likely to induce depression. Other triggers particularly in the elderly are operative procedures under GA and physical illnesses such as stokes in the non-dominant cerebral hemisphere. Organic brain conditions are rare in younger patients and I present the most common, including HIV, SLE, and MS. Psychological factors such as perfectionism [17], negative self-esteem [18], need for approval [19] and coping styles that avoid negative emotion [20] are more prevalent in people with a diagnosis of BPAD. Social factors such as childhood adversity, stressful life events, sexual abuse and migration are also more common in people who develop BPAD [4]. Finally, sleep deprivation has been reported as an immediate precipitant in the onset of many cases of mania [21], and seasonal factors also affect mood with mania more likely to occur in Spring while depression in the autumn [22].

While each of these above factors carry risks across the general population, at the individual level each person carries his or her own unique constellation of risks (and protective factors) for developing BPAD. Like most other common illnesses, it is likely that a sizeable proportion of the general population carries a relatively high risk for BPAD but is fortunate to never actually develop the condition as they are not exposed to the lifestyle/environmental factors that trigger the onset or progression of the condition.

Genetic vulnerability is one of the most important predisposing factors for BPAD [14]. First degree relatives of affected cases carry a 10–15% risk of developing BPAD and this risk increases with the degree of familial loading, for example, having two affected parent carries a 25% risk while a monozygotic twin carries a 45% risk. In reality, only 20% of bipolar patients have an affected relative. Complicating this is that relatives of patients with other disorders also carry a high risk of BPAD, for example offspring of patients with schizophrenia carry 5 times the average population risk of BPAD.

It is likely that only a small fraction of those carrying a high genetic risk actually ever develop the condition and do so only in response to the interaction of developmental and environmental factors mentioned above [41]. Identifying who is most at risk and under what circumstances is a challenge. Falsely attributing risk would be common. This is an important consideration as more genetic/biomarkers become available [42] as their detection may produce unwanted iatrogenic effects stigmatising individuals, particularly if preventative measures are not readily available. A number of centres are already developing biobanks for genomic medical research, for example the Bipolar Biobank set up in 2008 at the Mayo Clinic with the aim of early identification and medical intervention for individuals at risk.