WARM Project

Children of parents diagnosed with psychosis and other complex mental health problems including schizophrenia, bipolar disorder and depression, are at increased risk of developing mental health problems compared to the general population. Having one parent with schizophrenia results in a 7% lifetime risk of schizophrenia (Gottesman, Laursen, Bertelsen, & Mortensen, 2010) and 55% risk of developing any psychiatric condition (Rasic, Hajek, Alda & Uher, 2013). Children of parents with schizophrenia also display motor-cognitive delay (Welham, Isohanni, Jones, & McGrath, 2009), more emotional problems preschool, and difficulties of attention and social adjustment at school age (Niemi, Suvisaari, Haukka, & Lönnqvist, 2005). Having one parent with bipolar disorder results in a 6% risk of bipolar disorder and a 60% risk of any psychiatric condition, whereas for offspring of depression the risk for depression are 26% and for any psychiatric condition 57% (Rasic, Hajek, Alda & Uher, 2013).  Thus the lifetime personal, familial, societal and financial costs associated with elevated risk indicate a significant global mental health burden (Knapp, Mangalore, & Simon, 2004).The parent-infant relationship is an important context for identifying very early risk/resilience factors and targets for the development of preventative interventions. Three concepts are explored in the present study: a) attachment as an important risk factor for suboptimal development, b) caregiving as a mediator of the inter-generational transmission of attachment, and c) stress-sensitivity (S-S) as a possible common developmental risk process involved in diverse offspring psychopathological outcomes.

Attachment

Early risk in schizophrenia has generally been investigated from a biological perspective and the role of specific environmental risk factors is under researched. However, many of these children grow up with their biological parents. Thus, in addition to any potential genetic vulnerability, their development is influenced by risk factors associated with growing up with a mentally ill parent. One of these risk factors is the early parent-child attachment relationship. The parent-child attachment relationship is vital in understanding child development with a  key role in children’s social, emotional and cognitive development (Thompson, 2008). Through this unique relationship with caregivers during the first year of life, the infant forms inner working models that are templates for relationships and patterns of emotion regulation throughout life. Attachment is classified in three organized patterns - one secure and two insecure. Secure attachment is characterized by using the caregiver as a reference point for increasing explorative behaviour and curiosity (secure base) and as a source of safeness and soothing when faced with a stressor (safe haven). In infants, insecure attachment is classified as avoidant or ambivalent. Avoidant attachment is linked to deactivated expression of distress and reduced utilization of the caregiver as a source of support. In contrast, ambivalent attachment is linked to reduced exploratory behaviour, increased hyper-activating expression of distress and lack of responsiveness to soothing. An additional category of disorganized attachment describes a breakdown in organized forms of attachment. Insecure attachment types are considered less optimal than secure attachment, but only disorganized attachment predicts later psychopathology (Sroufe, Egeland, Carlson, & Collins, 2005). High risk studies show early unstable family rearing conditions predict offspring diagnosis of schizophrenia (Cannon & Mednick, 1993,Wahlberg et al., 1997), but little is known about early parent-infant relationship characteristics in schizophrenia and their impact on infant development.  Maternal attachment classification is an important predictor of offspring attachment at 12 months (Behrens, Hesse, & Main, 2007; Bus & van Ijzendoorn, 1992; Fonagy, Steele, & Steele, 1991) and longitudinal studies show adult dismissing attachment may be an outcome of both infant avoidant and disorganized attachments (Liotti & Gumley, 2010; Main, Hesse, & Kaplan, 2005; Waters, Hamilton, & Weinfield, 2000). Dismissing attachment patterns are overrepresented among adults with psychosis compared to other clinical and non-clinical groups (Macbeth, Gumley, Schwannauer, & Fisher, 2010). We do not know whether the attachment relationship contributes to increased developmental risk amongst infants of mothers with schizophrenia but mothers with schizophrenia and their infants may exhibit an attachment relationship that significantly increases infant’s risk of psychopathology (Liotti & Gumley, 2010).

In this study we ultimately seek to explore correspondence between maternal attachment states of mind and infants’ attachment security in a high-risk sample of mothers with a diagnosis of a serious mental illness (psychosis / schizophrenia, bipolar disorder and major depression), thus providing the basis of the development of a high-risk longitudinal cohort study. However, significant uncertainty remains regarding antecedents of attachment and mediators of intergenerational transfer. However, three potential mechanisms for transmission of attachment from mother to infant merit study: maternal caregiver representation, quality of mother-infant interaction, and maternal-infant stress sensitivity. Elucidation of these mechanisms would highlight opportunities to develop clinical interventions focused on improving the early parent-infant relationship.

Transmission mechanism 1: Caregiving representation

George and Solomon (George & Solomon, 2008; Solomon & George, 1996) have proposed the mediating link between the mother’s attachment status and that of her child is her symbolic representation of her relationship with her child i.e. her caregiving representation. There is a strong correspondence between maternal caregiving representation, maternal adult attachment classification and the infant’s attachment classification (Benoit, Parker, & Zeanah, 1997,George & Solomon, 1989, Zeanah, Benoit, Hirschberg, & Barton, 1994). During the first 12 months of the child’s life maternal caregiving representations are consolidated via maternal caregiving behaviours, in parallel to the development of the infant’s attachment behaviour.  The mother must internally shift her sense of self towards seeing herself as the child’s attachment figure and protector, facilitating coherent, appropriate organization of caregiving to the child.  The caregiving representation reflects the mothers’ own attachment experiences, her current level of social support and the actual relationship experience with the individual child.  Caregiving helplessness representations are assigned to mothers who experience themselves as struggling but failing to manage or control both the child and their own negative emotions and is associated with infant disorganized attachment (Solomon & George, 2011).

Transmission mechanism 2: Quality of mother-infant interaction

Discovery of infant disorganized attachment has led to identification of possible atypical parent-infant interaction patterns. Main and Hesse (1990) proposed that frequent interactions with a helplessly frightened, hostile and frightening, or confused caregiver create a relational trap: the infant’s defence system motivates them to flee from the frightened and/or frightening caregivers, while at the same time their attachment system motivates them, influenced by separation fear, to approach them (Madigan, Hawkins, Goldberg, & Benoit, 2006). Thus, the disorganized infant experiences “fright without solution” (Cassidy & Mohr, 2001; Main & Hesse, 1990, p.163). Early relational trauma such as this adversely influences development of the stress-coping system in the infant’s brain (Schore, 2003). Caregiving behaviours including role-confusion, disorientation and withdrawal have been found to predict infant disorganized attachment (Lyons-Ruth & Jacobvitz, 2008).

Transmission mechanism 3: Stress-sensitivity (S-S)

It is accepted that stress is an important factor in the development of psychosis and that individuals diagnosed with psychosis display increased vulnerability/sensitivity to stress. Empirical evidence supports the view that S-S may not be psychosis specific, but represents a general vulnerability for psychopathology (Myin-Germeys & van Os, 2007). Thus a developmental psychopathology approach to psychosis has been proposed (Harder et al., 2008). It is therefore apt to explore to what extent S-S is transmitted from mother to infant in schizophrenia, as this may be a common developmental risk process involved in offspring psychopathological outcomes. S-S can be assessed via psychophysiological studies of cortisol levels and release patterns following stressors.  Cortisol is a hormone involved in the human stress response.  Persons with psychosis and at risk of psychosis have higher baseline cortisol levels and exhibit a non-normative cortisol release pattern following stressful events (Myin-Germeys & van Os, 2007; Walker et al., 2011), suggesting increased S-S in schizophrenia. Studies also support an association between severe maternal mental illness, e.g. depression, and higher infant cortisol levels (Luijk et al., 2010). The infant-parent relationship is an infant’s most important emotion regulation system in the first 12 months. Early experiences thus shape attachment, thereby influencing regulation of behavioural and physiological responses.  Studies of parental care and attachment have identified associations between caregiving environment, attachment classification and infant physiological response to stressors.  Mothers whose interactions with their infants are most disrupted exhibit most deviation in cortisol levels (Lyons-Ruth, 2012 ). Infants with insecure and disorganized attachment classification have elevated cortisol levels during separation in the Strange Situation Procedure (SSP) and disorganized infants showed greatest elevation and slowest return to baseline cortisol levels after SST (Hertsgaard, Gunnar, Erickson, & Nachmias, 1995; Spangler & Grossmann, 1993). Research (Luijk et al., 2010) found that “D” infants differed from non-disorganized infants in diurnal cortisol rhythm, displaying a more flattened daily curve. These findings suggest links between mother-infant interaction, attachment classification and biological cortisol patterns, supporting exploration of the role of mother-infant interaction and attachment classification as possible correlates of stress-sensitivity transmission (cortisol reactivity) from mothers with schizophrenia to their infants.

State of the art

To our knowledge no Danish research group has systematically investigated early mother-infant interaction in schizophrenia, despite high-risk research (Mednick & Schulsinger, 1968) and clinical initiatives in this population (Lier, 1997). We systematically reviewed the international literature investigating mother infant interaction amongst women with a diagnosis of Schizophrenia. We identified 25-studies of mother-infant interaction in schizophrenia from 10 cohorts which have been published (D’Angelo, 1986; Goodman, 1987; Hipwell & Kumar, 1996; McNeil, Kaij, Naslund, & Blennow, 1983; Pawlby et al., 2010; Riordan, Appleby, & Faragher, 1999; Sameroff & Zax, 1987; Schachter et al., 1977, Snellen, Mack, & Trauer, 1999; Wan, Warren, Salmon, & Abel, 2008). Only two cohorts (McNeil et al., 1983; A. Sameroff & Zax, 1987) had longitudinal follow up (to infant age of 4 and 6), allowing for predictive analyses. Infant attachment data were only available in two studies (D’Angelo, 1986; Näslund, Persson-Blennow, McNeil, Kaij, & Malmquist-Larsson, 1984). Both found overrepresentation of insecure attachment in infants of mothers with schizophrenia (index group), compared to clinical and non-clinical controls. Insecure attachment in index infants was predicted by less infant responsivity towards the mother, more crying and less social contact during play before 12 months (Persson-Blennow, Binett, & Mcneil, 1988). Attachment status of index infants was not explained by mother’s psychotic status during the infant’s first year, number of psychiatric hospitalizations or infant gender (Näslund, Persson-Blennow, Mcneil, Kaij, & Malmquist-Larsson, 1984).

These two studies had important methodological shortcomings: First, the Näslund study used a modified version of the Strange Situation Procedure (Ainsworth, Blehar, Waters, & Wall, 1978), which results in over classification of secure attachment. Second, disorganized attachment was not investigated, although assessment of  disorganized attachment is a crucial measurement construct for predicting early risk factors for later psychopathology (Main et al., 2005; Waters et al., 2000). Third, maternal attachment was not investigated, though less optimal maternal behaviour was identified in all but one previous study, compared to normal controls and other clinical groups (Goodman & Brumley, 1990; Hipwell & Kumar, 1996; Persson-Blennow, Näslund, McNeil, & Kaij, 1986; Riordan et al., 1999; Snellen et al., 1999; Wan, Penketh, Salmon, & Abel, 2008; Wan, Warren, et al., 2008). Interaction between mothers with schizophrenia and their infants showed less mutuality and synchronicity (Näslund, Persson-Blennow, McNeil, & Kaij, 1985; Snellen et al., 1999; Wan et al., 2007). Correlations between infant development and quality of mother-infant interaction were found in two studies (infant IQ/maternal emotional involvement and responsivity, Goodman & Brumley 1990  and avoidant infant behaviour/reduced maternal sensitivity and responsivity, Wan et al., 2007). Only one study explored cortisol levels in offspring, finding no difference in cortisol levels between healthy adult offspring of mothers with schizophrenia and healthy controls (Yang et al., 2012). Previous research demonstrates disturbances in the mother-infant relationship in schizophrenia indicating that interaction quality affects infant development. However, the field lacks specific, theoretically informed hypotheses regarding the role of the attachment-caregiver relationship in identifying offspring vulnerabilities. Patterns of attachment in both mother and infant have never been investigated in a schizophrenia sample. This is vital to understanding the role of disorganized attachment, maternal S-S and the emergence of affect dysregulation in the infant. Attachment research demonstrates that maternal attachment and disorganized caregiving are important in transmission of psychopathological risk. This suggests an important gap in our understanding of early vulnerabilities in offspring of a high-risk group of women with Schizophrenia.

Aims

The aim of the present study is to establish the feasibility of developing a cohort of pregnant women with a life time diagnosis of psychosis / schizophrenia and the following comparison groups: pregnant women with a life time diagnosis of bipolar disorder, pregnant women with a diagnosis of major depressive disorder at the time of assessment and a non-psychiatric pregnant women control group. Establishing this cohort will provide the basis for long-term follow-up and intervention development. We will evaluate factors in the parents, the infant, the social environment and their interaction over time in terms of evolution of very early indicators of developmental risk and resilience (infant attachment, stress sensitivity and cognitive-motor development).

• Mother–infant interaction in schizophrenia: transmitting risk or resilience? A systematic review of the literature
  By Kirstine Agnete Davidsen, Susanne Harder, Angus MacBeth, Jenna-Marie Lundy, and Andrew Gumley
• Mor-barn samspillet - når mor har alvorlige psykiske vanskeligheder
  By Katrine Røhder, Kirstine Agnete Davidsen, Christopher Høier Trier, Maja Nyström-Hansen, and Susanne Harder.
• Wellbeing and resilience: mechanisms of transmission of health and risk in parents with complex mental health problems and their offspring—The WARM Study
  By Susanne Harder, Kirstine Davidsen, Angus MacBeth, Theis Lange, Helen Minnis, Marianne Skovsager Andersen, Erik Simonsen, Jenna-Marie Lundy, Maja Nyström-Hansen, Christopher Høier Trier, Katrine Røhder and Andrew Gumley

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• Susanne Harder' research profile
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