Table 1.

Bipolar Disorder and Schizophrenia: More in Common Than Supposed (Common Features Between Bipolar Disorder and Schizophrenia)

Geneticsa	Individual genes: AKT1, DISC1/DISC 2, Dysbindin, NOS1, GRM4, G30/G72, NRG1, MIR137. 79,81–83
	Loci (GWAS): CACNA1C, ANK3, ITIH3-ITIH4 region.80,81 Linkage “hot-spots”: 18p11, 22q11, 13q32, 10p14, and 1q32.83
	CNVs are found in excess in schizophrenia, but not in BD.76
Developmental abnormalities	Rates of developmental abnormalities (language abnormalities such as articulation abnormalities, language delay, and receptive-expressive language dysfunctions, as well as motor impairments such as delayed motor milestones, clumsiness, and poor coordination) are not significantly different between schizophrenia and bipolar patients.50
	Some developmental problems such as reading or writing difficulties seem to be more common in early-onset cases of schizophrenia than bipolar disorder.29
	Between childhood and early adolescence, both schizophrenia and bipolar patients show a greater decline in academic adjustment than healthy controls, more specifically in adaptation to school.50 However, lifelong academic underachievement was greater and started earlier in an early-onset schizophrenia group than in an early-onset bipolar disorder group.29
Antioxidant status	First-episode early-onset psychosis patients have been shown to have low antioxidant status, with no differences between schizophrenia and bipolar patients; however, only those with schizophrenia have lower glutathione at baseline.74 Decreased glutathione levels during the first psychotic episode were related to greater loss of cortical gray matter 2 years later in patients with first-episode early-onset psychosis.84
Neuroimaging	Lateral ventricle volumes are enlarged in both schizophrenia and BD, although this is more pronounced in schizophrenia than in BD.63,64
	GM reductions are less marked in subjects with BD than in those with schizophrenia.61,64
	In general, cortical and limbic GM abnormalities (such as hippocampus volume) are more pronounced in schizophrenia.63,64
	However, there are notably overlapping abnormalities in the paralimbic regions.64
	Studies in children and adolescents with a first psychotic episode show that most volume abnormalities, including thinner frontal cortical thickness or increased intracranial CSF, are common to bipolar and schizophrenia patients, although they seem to be quantitatively larger in those developing schizophrenia vs bipolar type I.51,67,69,70
	In early-onset psychosis, progressive brain volume changes (mainly reduction in frontal GM volume) seem to be more marked in those who develop schizophrenia than in those who develop other diagnoses.52 However, it is not clear to what extent this larger reduction is a reflection of the different diagnosis or a severity marker.52
NS	NS are present in both schizophrenia and BD.30
Insight	Chronic impaired insight characterizes those patients with a diagnosis of schizophrenia but not so much those with BD.85
Environmental factors	Childhood adversity seems to increase the risk for both schizophrenia and affective psychosis.86
	Cannabis use has also been related to increased risk of schizophrenia and other psychoses87,88 or BD.89,90
	Schizophrenia has been related to prenatal infection, prenatal famine, prenatal micronutrient deficiency (eg, vitamin D, iron, folate), prenatal psychological stress, and other prenatal complications (antepartum hemorrhage, gestational diabetes, rhesus incompatibility, or preeclampsia).91 However, the association between BD and pre- and perinatal complications is controversial.92–94
	Migration has also been a replicated risk factor for schizophrenia,95 while its effect on BD is controversial.96
	Urbanicity has repeatedly been found to be a risk factor for schizophrenia, but could be a protective factor for affective psychosis.97
	Obstetric complications have also been a replicated risk factor for schizophrenia15 that does not seem to increase the risk for BD.94
Premorbid developmental impairments	Premorbid developmental impairments (language, reading, motor development) have been described both in adult-34 and childhood-onset schizophrenia.34,35 The relationship between premorbid adjustment and BD is more controversial in early-onset cases, although there seems to be an association between poor premorbid functioning and severe forms of the disorder.47–49
Cognitive function	Neuropsychological impairment may be considered an intermediate phenotype, which is present and familial in schizophrenia and BD, but more severe in schizophrenia than in bipolar patients.98
	Cognitive impairment seems to remain similar during the first 2 years after the first psychotic episode in both bipolar and schizophrenia patients.23

Note: BD, bipolar disorder; CSF, cerebrospinal fluid; CNVs, copy number variants; GM, gray matter; GWAS, genome-wide association studies; NS, neurological signs (abnormalities in sensory and motor performance).

^aData on genetics show only some common genes as examples of genetic overlapping between schizophrenia and bipolar disorder.^79–82