Genetic load on amygdala hypofunction during sadness in nonaffected brothers of schizophrenia patients.

OBJECTIVE In a previous study, the authors reported that patients with schizophrenia show subcortical-limbic hypoactivity during sadness. In this study, they capitalized on those findings in order to assess the genetic influence of negative mood experience in schizophrenia patients. Brain activity was measured during mood induction in patients with schizophrenia and their first-degree nonaffected relatives. METHOD Functional magnetic resonance imaging was used to investigate 13 male patients with schizophrenia, their nonaffected brothers (N=13), and a group of 26 individually matched healthy subjects unrelated to the siblings during induction of sad and happy moods as well as during a cognitive control task. A regional analysis was applied to investigate a possible subcortical-limbic dysfunction in relatives. RESULTS Mood induction was successful in all groups according to subjective ratings. During sadness induction, the patients and their nonaffected siblings demonstrated less activity in the amygdala compared with the healthy group of nonrelatives. Other regions of interest, such as the left orbitofrontal cortex, the left superior temporal cortex, and the left precuneus/posterior cingulate revealed significant group differences only between patients and nonrelated healthy subjects. During positive mood induction, no group differences could be found in the amygdala. CONCLUSIONS Following induction of sad mood, both patients with schizophrenia and their nonaffected brothers displayed reduced brain activity in the amygdala. Such hypoactivity is likely to represent a genetic influence and indicates that efficient compensatory mechanisms capable of preventing the onset of the illness must exist in nonaffected relatives.

[1]  S. Dollfus,et al.  Executive/attentional cognitive functions in schizophrenic patients and their parents: a preliminary study , 2002, Schizophrenia Research.

[2]  N. Sadato,et al.  Attention to emotion modulates fMRI activity in human right superior temporal sulcus. , 2001, Brain research. Cognitive brain research.

[3]  Eve C Johnstone,et al.  Magnetic resonance imaging of brain in people at high risk of developing schizophrenia , 1999, The Lancet.

[4]  Evelyn C. Ferstl,et al.  The Anterior Frontomedian Cortex and Evaluative Judgment: An fMRI Study , 2002, NeuroImage.

[5]  S. Lawrie,et al.  Brain structure, genetic liability, and psychotic symptoms in subjects at high risk of developing schizophrenia , 2001, Biological Psychiatry.

[6]  Ivanei E. Bramati,et al.  The Neural Correlates of Moral Sensitivity: A Functional Magnetic Resonance Imaging Investigation of Basic and Moral Emotions , 2002, The Journal of Neuroscience.

[7]  J. Cohen,et al.  Relation of prefrontal cortex dysfunction to working memory and symptoms in schizophrenia. , 2001, The American journal of psychiatry.

[8]  P. Eslinger,et al.  Frontopolar and anterior temporal cortex activation in a moral judgment task: preliminary functional MRI results in normal subjects. , 2001, Arquivos de neuro-psiquiatria.

[9]  J. Price,et al.  Limbic connections of the orbital and medial prefrontal cortex in macaque monkeys , 1995, The Journal of comparative neurology.

[10]  Robin M. Chan,et al.  An fMRI study of facial emotion processing in patients with schizophrenia. , 2002, The American journal of psychiatry.

[11]  Klaus P. Ebmeier,et al.  Altered cerebral perfusion measured by SPECT in relatives of patients with schizophrenia , 1999, British Journal of Psychiatry.

[12]  R. Gur,et al.  Mood effects on limbic blood flow correlate with emotional self-rating: A PET study with oxygen-15 labeled water , 1995, Psychiatry Research: Neuroimaging.

[13]  Nikos Makris,et al.  Thalamic and amygdala–hippocampal volume reductions in first-degree relatives of patients with schizophrenia: an MRI-based morphometric analysis , 1999, Biological Psychiatry.

[14]  S. Taylor,et al.  A functional anatomic study of emotion in schizophrenia , 2002, Schizophrenia Research.

[15]  R. Kikinis,et al.  Amygdala–hippocampal shape differences in schizophrenia: the application of 3D shape models to volumetric MR data , 2002, Psychiatry Research: Neuroimaging.

[16]  T. Schneider-Axmann,et al.  The temporal lobe in schizophrenia from uni- and multiply affected families , 2002, Neuroscience Letters.

[17]  J. Deakin,et al.  Familial and developmental abnormalities of frontal lobe function and neurochemistry in schizophrenia , 1997, Journal of psychopharmacology.

[18]  H. Whalley,et al.  Structural MRI of the brain in presumed carriers of genes for schizophrenia, their affected and unaffected siblings , 2002, Journal of neurology, neurosurgery, and psychiatry.

[19]  K. Kendler,et al.  Family characteristics of deficit and nondeficit schizophrenia in the Roscommon family study , 2000, Schizophrenia Research.

[20]  N C Andreasen,et al.  Remembering the past: two facets of episodic memory explored with positron emission tomography. , 1995, The American journal of psychiatry.

[21]  S. G. Cox,et al.  Functional MRI study of the cognitive generation of affect. , 1999, The American journal of psychiatry.

[22]  R. Lane,et al.  Neuroanatomical correlates of happiness, sadness, and disgust. , 1997, The American journal of psychiatry.

[23]  R. McCarley,et al.  A review of MRI findings in schizophrenia , 2001, Schizophrenia Research.

[24]  H. Tost,et al.  Sensory information processing in neuroleptic-naive first-episode schizophrenic patients: a functional magnetic resonance imaging study. , 2002, Archives of general psychiatry.

[25]  P. Michie,et al.  Phenotypic markers as risk factors in schizophrenia: neurocognitive functions. , 2000, The Australian and New Zealand journal of psychiatry.

[26]  S. Kay,et al.  The positive and negative syndrome scale (PANSS) for schizophrenia. , 1987, Schizophrenia bulletin.

[27]  U. Habel,et al.  Gender differences in regional cerebral activity during sadness , 2000, Human brain mapping.

[28]  P. Näätänen,et al.  Neuroanatomical substrata of amusement and sadness: a PET activation study using film stimuli , 2002 .

[29]  Ruben C. Gur,et al.  Standardized mood induction with happy and sad facial expressions , 1994, Psychiatry Research.

[30]  Wolfgang Grodd,et al.  Functional MRI reveals left amygdala activation during emotion , 1997, Psychiatry Research: Neuroimaging.

[31]  S. Paradiso,et al.  Cerebral blood flow changes associated with attribution of emotional valence to pleasant, unpleasant, and neutral visual stimuli in a PET study of normal subjects. , 1999, The American journal of psychiatry.

[32]  W. Grodd,et al.  Differential amygdala activation in schizophrenia during sadness , 1998, Schizophrenia Research.

[33]  D. Watson,et al.  Development and validation of brief measures of positive and negative affect: the PANAS scales. , 1988, Journal of personality and social psychology.

[34]  J. Talairach,et al.  Co-Planar Stereotaxic Atlas of the Human Brain: 3-Dimensional Proportional System: An Approach to Cerebral Imaging , 1988 .

[35]  Karl J. Friston,et al.  Functional anatomy of verbal fluency in people with schizophrenia and those at genetic risk , 2000, Schizophrenia Research.

[36]  I. Skre,et al.  "True" schizotypal personality disorder: a study of co-twins and relatives of schizophrenic probands. , 1993, The American journal of psychiatry.

[37]  Jim Mintz,et al.  The structure of schizotypy: relationships between neurocognitive and personality disorder features in relatives of schizophrenic patients in the UCLA Family Study , 2002, Schizophrenia Research.

[38]  Alan C. Evans,et al.  Amygdala–hippocampal volume and verbal memory in first-degree relatives of schizophrenic patients , 2001, Psychiatry Research: Neuroimaging.