Risk for Psychopathology High in Kids of Mentally Ill Parents

Pam Harrison

September 09, 2015

AMSTERDAM — Children born to parents with either schizophrenia or bipolar disorder are at high risk for a range of psychopathologies even at a young age, and even mild psychopathology in these children may a harbinger of future illness, a longitudinal study indicates.

The study was presented here during the 28th European College of Neuropsychopharmacology (ECNP) Congress.

"It's important to follow offspring of parents with schizophrenia or bipolar disorder because in the general population, both schizophrenia and bipolar disorder have a low prevalence of only about 1% to 2%, whereas in offspring, this prevalence increases tenfold, so it's 10% to 20% in offspring from parents with schizophrenia or bipolar disorder," Manon Hillegers, MD, PhD, University Medical Center Utrecht Brain Center Rodolf Magnus, the Netherlands, told Medscape Medical News.

"So we can identify children who are living in these families, and just by identifying their high-risk status, we have to acknowledge that even mild problems might be an early manifestation of an illness in development, and we have to treat these mild problems to prevent them from progressing further."

The Dutch Bipolar and Schizophrenia Offspring Study was initiated in an attempt to identify clinical and neuroimaging characteristics in offspring of patients with schizophrenia and bipolar disorder compared with healthy persons.

For the current analysis, the cohort included 35 offspring from parents with schizophrenia and 77 offspring from parents with bipolar disorder.

Clinical and neuroimaging parameters in the two groups at high risk were compared with those in 45 normal community-dwelling individuals, who served as a control group.

The mean age of all three groups was approximately 13 years. Fewer offspring of patients with schizophrenia (57%) were living with both biological parents than either offspring of patients with bipolar disorder (80%) or offspring in the control group (91%).

"We found that schizophrenia offspring had a very high lifetime prevalence of psychopathology in general, at around 70%, whereas the lifetime prevalence in bipolar disorder offspring was about 50% and between 15% and 18% in the general population," Dr Hillegers reported.

Psychopathology ranged from mild anxiety to major mood disorders, she noted.

The lifetime prevalence of children from either high-risk group having a DSM-IV axis I diagnosis for any mood disorder was approximately 25%.

The risk for major depression was much higher, at 15%, among offspring of schizophrenia patients compared with offspring of patients with bipolar disorder or control persons, she added.

Offspring of patients with schizophrenia were also much more likely to suffer from more severe major depressive disorder compared with offspring of patients with bipolar disorder and had higher levels of autism spectrum disorder.

Functional MRI

Investigators measured brain function using a reward task. As Dr Hillegers noted, the frontal subcortical network is very important in normal development during adolescence.

Importantly, however, subcortical regions normally mature at different rates compared with the frontal regions, and these differences are responsible for typical behavioral patterns manifested in adolescence, including irritability, mood swings, and risk taking.

"With this reward task, we were able to measure reward anticipation in the ventral striatum in the normal population, and we saw that ventral striatum activity levels increase with age," Dr Hillegers said.

There is also more frontal control over the same areas in the brain, meaning that typical adolescent behavior will disappear once these children reach adulthood, she added.

In contrast, schizophrenia offspring showed a decrease in ventral striatum activity during the same reward task. "This could mean a loss of frontal control in these patients," Dr Hillegers observed. "And we found high levels of activation in the ventral striatum in early adolescence and low levels of activation in late adolescence among schizophrenia offspring affected by a lifetime prevalence of axis I disorders."

They also observed increasing connectivity during normal development among control persons.

Again in contrast, schizophrenia offspring ― especially those with an axis I disorder ― showed reduced frontal subcortical connectivity in the resting state, although this was not observed in bipolar disorder offspring.

"This might indicate that there is already an imbalance in the important frontal subcortical network, so one of the questions that arises from this work is, Is there a wrong setpoint from early adolescence on?" he said.

Severe Mental Disorders

Asked by Medscape Medical News to comment on the study, Ralph Kupka, MD, PhD, professor of psychiatry, VU University Medical Center, Amsterdam, observed that schizophrenia and bipolar disorder are both severe mental disorders that often start in adolescence and thus may interfere with emotional, psychosocial, and occupational development of affected young people.

"Moreover, in a considerable number of cases, these are recurrent and potentially progressive disorders," Dr Kupka said in written correspondence. "And early detection and intervention may prevent further illness progression and improve prognosis."

Both disorders have a strong genetic etiology, he noted. "Detecting signals, either behavioral or neurobiological, that give an indication for developing psychiatric disorders in high-risk offspring is therefore particularly important," he said.

During the past 15 years, the Utrecht research group headed by Dr Hillegers, Willem Nolen, MD, and Rene Kahn, MD, has carried out several large offspring studies of patients with schizophrenia and bipolar disorder, he said.

"The skill and commitment of this research group has resulted in the successful recruitment of many patients and their offspring and has kept them engaged for long-term follow-up over the years," Dr Kupka said.

"Their research provides an ongoing and invaluable contribution to our knowledge of the risk factors and early signs of psychiatric disorders and opens the way to successful prevention and treatment."

The study was partially financed by a NARSAD independent investigator grant from the Brain and Behavior Research Foundation. Dr Hillegers and Dr Kupta have disclosed no relevant financial relationships.

28th European College of Neuropsychopharmacology (ECNP) Congress. Abstract S.22.01. Presented September 1, 2015.

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